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HK1115125B - 3-ethylidenehydrazino substituted heterocyclic compounds as thrombopoietin receptor activators - Google Patents

3-ethylidenehydrazino substituted heterocyclic compounds as thrombopoietin receptor activators Download PDF

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Publication number
HK1115125B
HK1115125B HK08105161.4A HK08105161A HK1115125B HK 1115125 B HK1115125 B HK 1115125B HK 08105161 A HK08105161 A HK 08105161A HK 1115125 B HK1115125 B HK 1115125B
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Hong Kong
Prior art keywords
group
radical
alkyl
methyl
substituted
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HK08105161.4A
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Chinese (zh)
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HK1115125A1 (en
Inventor
宫地克明
繁田幸宏
中野智
岩本俊介
广川裕
太田博史
柳原一史
大和田真吾
石绵纪久
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日产化学工业株式会社
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Priority claimed from PCT/JP2005/022907 external-priority patent/WO2006062240A1/en
Publication of HK1115125A1 publication Critical patent/HK1115125A1/en
Publication of HK1115125B publication Critical patent/HK1115125B/en

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Description

3-ethylidenehydrazino substituted heterocyclic compounds as thrombopoietin receptor activators
Technical Field
The present invention relates to a preventive, therapeutic or ameliorating agent for diseases which have an affinity and an agonistic action to the thrombopoietin receptor and which can be effectively treated by activating the thrombopoietin receptor. Specifically, the present invention relates to a pharmaceutical composition comprising a compound which increases platelets by stimulating differentiation and proliferation of hematopoietic stem cells, megakaryocytic progenitor cells and megakaryocytes, or a compound which stimulates differentiation and proliferation of vascular endothelial cells and endothelial progenitor cells to treat angiogenesis or has an anti-arteriosclerotic effect.
Background
Thrombopoietin is a cytokine consisting of 332 amino acids, which increases platelet formation by stimulating differentiation and proliferation of hematopoietic stem cells, megakaryocyte progenitor cells and megakaryocytes mediated by its receptor, and thus it is promising as a drug for treating blood diseases. It has recently been reported that it stimulates differentiation and proliferation of vascular endothelial cells and endothelial progenitor cells, and is therefore expected to be useful for the treatment of angiogenesis, anti-arteriosclerosis and prevention of cardiovascular diseases (for example, non-patent document 1, non-patent document 2 and non-patent document 3).
In addition to thrombopoietin itself, it is known that bioactive substances capable of regulating thrombopoiesis via the thrombopoietin receptor include low molecular weight peptides having affinity for the thrombopoietin receptor (for example, patent document 1, patent document 2, patent document 3, and patent document 4).
As a result of studies on non-peptide low molecular weight compounds that can increase thrombopoietin receptor-mediated thrombopoiesis, some low molecular weight compounds having affinity for the thrombopoietin receptor have been reported (for example, patent documents 5 to 26).
1) 1, 4-benzodiazepines, filed by Hokuriku Seiyaku Co., Ltd (benzodiazepine) derivatives (patent documents 5 and 6)
2) International published patent applications filed by Shionogi & co., ltd. (patent documents 7 to 10)
3) International published patent application filed by SmithKline Beecham corporation (patent documents 11 to 19)
4) Japanese laid-open patent application (patent document 20) filed by Torii Pharmaceutical co., ltd
5) International published patent application filed by Roche Diagnostics GMBH (patent document 21)
6) International published patent applications filed by Yamanouchi Pharmaceutical co., ltd. (patent documents 22 and 23)
7) Japanese published patent application filed by Japan Tabacco Inc. (patent document 24)
8) Japanese published patent applications (patent documents 25 and 26) filed by Nissan Chemical industry, Ltd
Patent document 1JP-A-10-72492
Patent document 2WO96/40750
Patent document 3WO96/40189
Patent document 4WO98/25965
Patent document 5JP-A-11-1477
Patent document 6JP-A-11-152276
Patent document 7WO01/07423
Patent document 8WO01/53267
Patent document 9WO02/059099
Patent document 10WO02/059100
Patent document 11WO00/35446
Patent document 12WO00/66112
WO01/34585 patent document 13
Patent document 14WO01/17349
Patent document 15WO01/39773
Patent document 16WO01/21180
Patent document 17WO01/89457
Patent document 18WO02/49413
Patent document 19WO02/085343
Patent document 20JP-A-2001-
Patent document 21WO99/11262
Patent document 22WO02/062775
Patent document 23WO03/062233
Patent document 24JP-A-2003-238565
Patent document 25WO04/033433
Patent document 26WO04/108683
Non-patent document 1microvasc. res, 1999: 58. p.108-113
Non-patent document 2circ.res., 1999: 84. p.785-796
Non-patent document 3Blood 2001: 98. p.71a-72a
Disclosure of Invention
Thrombopoietin and low molecular weight peptides with affinity for the thrombopoietin receptor can be easily degraded in the gastrointestinal tract and are therefore often difficult to administer orally. The emergence of anti-thrombopoietin antibodies has been reported for thrombopoietin itself.
Furthermore, although it is presumably possible to orally administer non-peptide low molecular weight compounds, no actual drug has been put on the market.
Therefore, there is a need for orally administrable low molecular weight compounds having excellent affinity and agonistic action to thrombopoietin receptor as preventive, therapeutic or ameliorating agents for diseases which can be treated by effectively activating thrombopoietin receptor. More specifically, there is a need for low molecular weight compounds that can be used as platelet increasing agents or other blood cell increasing agents by stimulating differentiation and proliferation of hematopoietic stem cells, megakaryocyte progenitor cells, and megakaryocytes, or low molecular weight compounds that can be used for treating angiogenesis or as preventive and therapeutic agents for arteriosclerosis by stimulating endothelial cells and endothelial progenitor cells.
The present inventors have conducted extensive studies in order to find low molecular weight compounds having affinity and agonistic action to the thrombopoietin receptor, and as a result, have found that the compounds of the present invention have high affinity and agonistic action, which makes them exhibit an effect of effectively increasing platelets by stimulating differentiation and proliferation of megakaryocyte progenitor cells and megakaryocytes. The present invention has been accomplished on the basis of this finding.
Namely, the present invention relates to the following aspects:
1. a compound represented by formula (1), a tautomer, prodrug or pharmaceutically acceptable salt of said compound, or a solvate thereof,
wherein A is a nitrogen atom or CR4(wherein, R4Is a hydrogen atom, a hydroxyl group (the hydroxyl group may be substituted by C)2-6Alkenyl or C2-6Alkynyl-substituted), thiol groups (which may be substituted by C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl or C1-10Alkyl carbonyl substituted), amino (the aminoThe radicals being substituted by one or two C2-6Alkenyl or one or two C2-6Alkynyl-substituted), formyl, halogen, nitro, cyano, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkylcarbonylamino, mono-or di-C1-10Alkylamino radical, C1-10Alkoxy (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkylcarbonylamino, mono-or di-C 1-10Alkylamino and C1-10Alkoxy groups may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkylcarbonyloxy (carbonyloxy), C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or one or more halogen atoms), C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group), C2-14Aryloxy group (the C)2-14The aryloxy group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C 2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkyl radicalCarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy), SO2R5、SOR5Or COR5(wherein, R5Is hydroxy, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C2-9Heterocyclyl and C1-10Alkoxy groups may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C 1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group), C2-14Aryloxy group (the C)2-14The aryloxy group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxylRadical, nitro radical, cyano radical, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy) or NR6R7(wherein, R6And R7Each independently is a hydrogen atom, a hydroxyl group, a formyl group, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C 1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy) or R6And R7Together represent- (C)H2)m1-E-(CH2)n2(wherein E is an oxygen atom, a sulfur atom, CR26R27(wherein, R26And R27Each independently is a hydrogen atom, C1-10Alkyl radical, C2-14Aryl radical, C1-10Alkoxy radical, C2-14Aryloxy, hydroxy or protected hydroxy), or NR8(wherein, R8Is hydrogen atom, hydroxy, formyl, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C 1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted by one or more halogen atoms) or C2-14Aryl radical (the radical C)2-14The aryl group may be substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy)), m1 and m2 are each independently an integer from 0 to 5, provided that m1+ m2 are3. 4 or 5))),
b is an oxygen atom, a sulfur atom or NR9(wherein, R9Is hydrogen atom, hydroxy, formyl, C 1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C1-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy) or C 2-14Aryloxy group (the C)2-14The aryloxy group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyanoA halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy)) (provided that, when A is a nitrogen atom, B is not NH),
R1is C2-14Aryl radical (the radical C)2-14The aryl group may be substituted with one or more groups selected from the group consisting of: halogen atom, carboxyl group, nitro group, formyl group, cyano group, hydroxy group, protected hydroxy group, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl (the radical C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkylcarbonyloxy and C1-10Alkoxycarbonyl groups may be optionally substituted by one or more groups selected from the following group: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C 1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy), a thiol group and an amino group (the thiol group and the amino group may be optionally substituted with one or two groups selected from the group consisting of: formyl radical, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl and C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C 1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms))),
L1is a bond, CR10R11(wherein, R10And R11Each independently is a hydrogen atom or C1-6Alkyl (the C)1-6Alkyl groups may be substituted by one or more halogen atoms)), oxygen atoms, sulfur atoms or NR12(wherein, R12Is hydrogen atom, hydroxy, formyl, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl radicalCarbonyloxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C 2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy)),
x is OR13、SR13Or NR14R15(wherein, R13Is a hydrogen atom, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl or C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), R)14And R15Each independently is a hydrogen atomSon, formyl, C 1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy and C1-10The alkylcarbonyl group may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-5Alkyl groups may be substituted with one or more halogen atoms) or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy)),
R2is a hydrogen atom, a formyl group, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy, C1-10 alkylcarbonyl (this C) 1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy and C1-10The alkylcarbonyl group may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl radical、C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C21-1Aryl and C2-14An aryloxy group),
L2is a bond, CR34R35(wherein, R34And R35Each independently is a hydrogen atom or C1-6Alkyl (the C)1-6Alkyl groups may be substituted by one or more halogen atoms)), oxygen atoms, sulfur atoms or NR 16(wherein, R16Is hydrogen atom, hydroxy, formyl, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkyl ammoniaRadical, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C 2-14Aryl and C2-14Aryloxy)),
L3is a bond, CR17R18(wherein, R17And R18Each independently is a hydrogen atom, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy and C1-10The alkylcarbonyl group may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C 2-14Aryloxy group)), an oxygen atom, a sulfur atom or NR19(wherein, R19Is hydrogen atom, hydroxy, formyl, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkoxy and C1-10The alkylcarbonyl group may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di -C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy)),
y being an oxygen atom, a sulfur atom or NR23(wherein, R23Is hydrogen atom, hydroxy, formyl, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C2-14Aryl radical (the radical C)2-14The aryl group may be substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C 1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy)),
L4is a bond, CR20R21(wherein, R20And R21Each independently is a hydrogen atom, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy and C1-10The alkylcarbonyl group may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-8Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C 1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms)), an oxygen atom, a sulfur atom or an NR group)22(wherein, R22Is hydrogen atom, hydroxy, protected hydroxy, formyl, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C 2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms))), and
when L is4When is a bond, R3Is methyl (the methyl group may be optionally substituted with one or more groups selected from the group consisting of C1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl (thioalkyl), C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino (this C)1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyloxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonylamino group may optionally be substituted by one or more C 2-14Aryl substituted (the C)2-14Aryl may optionally be substituted with one or more groups independently represented by-W1(CW2W3)mW4Substituted with the substituents shown (wherein, W1Is (CR)24R25)n(wherein, R24And R25Each independently is a hydrogen atom or C1-6Alkyl (the C)1-6Alkyl groups may be substituted with one or more halogen atoms), or R24And R25Together with each other represent O or S, and n is 0, 1, 2 or 3), an oxygen atom, a sulfur atom or NR36(wherein, R36Is a hydrogen atom, C1-6Alkyl, formyl or C1-6Alkylcarbonyl), W2And W3Each independently is a hydrogen atom or C1-3Alkyl (the C)1-3Alkyl groups may be substituted by one or more halogen atoms), m is 0, 1, 2 or 3, W4Is hydroxy, protected hydroxy, thiol, amino, formyl, halogen, nitro, cyano, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkylcarbonylamino, mono-or di-C1-10Alkylamino radical (this C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkylcarbonylamino and mono-or di-C1-10The alkylamino group may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C 1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, thiol, phosphonic acid, sulfonic acid, tetrazolyl, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-10Alkyl substitution (of this C)1-10Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), SO2R28、SOR28、COR28(wherein, R28Is hydroxy, protected hydroxy, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C2-9Heterocyclyl and C 1-10Alkoxy groups may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy radicals may be substituted by oneA plurality of C1-6Alkyl (the C)1-6Alkyl groups may be substituted with one or more halogen atoms) or one or more halogen atoms), C2-14Aryl radical, C2-14Aryloxy group (the C)2-14Aryl and C2-14The aryloxy group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl (the C)1-6Alkyl groups may be substituted with one or more halogen atoms) or one or more halogen atoms), or NR29R30(wherein, R29And R 30Each independently is a hydrogen atom, a hydroxyl group, a protected hydroxyl group, a formyl group, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylsulfonyl radical, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylsulfonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14The aryloxy group may optionally be substitutedSubstituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, sulfonyl, sulfamoyl, sulfo, nitro, cyano, halogen atom, C1-10Alkoxy (the C)1-10Alkoxy groups which may be substituted by one or more halogen atoms), C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C 2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl (the C)1-6Alkyl groups may be substituted with one or more halogen atoms) or one or more halogen atoms)), or C (C) or2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl (the C)1-6Alkyl groups may be substituted with one or more halogen atoms) or one or more halogen atoms), or R29And R30Together represent- (CH)2)m3-G-(CH2)m4- (wherein G is an oxygen atom, a sulfur atom, CR31R32(wherein, R31And R32Each independently is a hydrogen atom, C1-10Alkyl radical, C2-14Aryl radical, C1-10Alkoxy radical, C2-14Aryloxy, hydroxy or protected hydroxy) or NR33(wherein, R33Is hydrogenAtom, hydroxy group, formyl group, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C 1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl (the C)1-6Alkyl groups may be substituted with one or more halogen atoms) or one or more halogen atoms), or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl (the C)1-6Alkyl groups may be substituted by one or more halogen atoms) or by one or more halogen atoms)), m3 and m4 are each independently an integer from 0 to 5, provided that m3+ m4 are 3, 4 or 5))), tetrazolyl or phosphonic acid groups), or by one or more groups consisting of-W 5(CW6W7)m10W8Substituted with the substituents shown (wherein, W5、W6、W7And m10 is independently from W1、W2、W3Same as m, W1、W2、W3And m is as defined above, W8Is hydroxy, protected hydroxy, thiol, amino, formyl, halogen, nitro, cyano, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkylcarbonylamino, mono-or di-C1-10Alkylamino radical (this C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkylcarbonylamino and mono-or di-C1-10The alkylamino group may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), SO2R28a、SOR28a、COR28a(wherein, R28aAnd R28Same as R28Same as defined above), tetrazolyl or phosphonic acid groups)), and independently by-W9(CW10W11)m11W12A substituent of (wherein, W) 9、W10、W11、W12And m11 is independently from W1、W2、W3、W8Same as m, W1、W2、W3、W8And m is the same as defined above)), C2-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl or C2-9Heterocyclic group (the C)2-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl and C2-9The heterocyclyl group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylsulfonyl radical, C1-10Alkylaminocarbonyl radical, C1-10Alkylsulfamoyl, C1-10Dialkylaminocarbonyl group, C1-10Alkylcarbonylamino (this C)1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic radical, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylsulfonyl radical, C1-10Alkylaminocarbonyl radical, C1-10Alkylsulfamoyl radical, said C1-10Dialkylaminocarbonyl and C1-10The alkylcarbonylamino group may optionally be substituted by one or more C2-14Aryl substituted (the C)2-14Aryl is optionally substituted by one or more independently by-W1(CW2W3)mW4Substituted with the substituents shown (wherein, W1、W2、W3、W4And m is the same as defined above)) or by one or more groups of-W5(CW6W7)m10W8Substituted with the substituents shown (wherein, W5、W6、W7、W8And m10 is the same as defined above)), independently by W 9(CW10W11)m11W12A substituent of (wherein, W)9、W10、W11、W12And m11 is as defined above) and C2-14Aryl radical (the radical C)2-14Aryl may optionally be substituted with one or more groups independently represented by-W13(CW14W15)m12W16Of the representationSubstituent (wherein, W13、W14、W15、W16And m12 is independently from W1、W2、W3、W4Is the same as m, and W1、W2、W3、W4And m is as defined above)) or when L is present4Is CR20R21(wherein, R20And R21Each independently is a hydrogen atom, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy and C1-10The alkylcarbonyl group may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl (the C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C 1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl (the C)1-6Alkyl groups may be substituted with one or more halogen atoms) or one or more halogen atoms))), oxy groups, and (C) and (D) groups, and (C) groups, and (D) groupsA sulfur atom or NR22(wherein, R22Is hydrogen atom, hydroxy, protected hydroxy, formyl, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl (the C)1-6Alkyl groups may be substituted with one or more halogen atoms) or one or more halogen atoms), or C 2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl (the C)1-6Alkyl groups may be substituted with one or more halogen atoms) or one or more halogen atoms)))3Is C1-10Alkyl radical, C2-14Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl or C1-10Alkylcarbonylamino (this C)1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonylamino group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C 1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino (this C)1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyloxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonylamino group may optionally be substituted by one or more C2-14Aryl substituted (the C)2-14Aryl may optionally be substituted with one or more groups independently represented by-W1(CW2W3)mW4Substituted with the substituents shown (wherein, W1、W2、W3And W4And m is as defined above)) or by one or more independently-W5(CW6W7)m10W8Substituted with the substituents shown (wherein, W5、W6、W7、W8And m10 is as defined above)), independently by-W9(CW10W11)m11W12A substituent of (wherein, W)9、W10、W11、W12And m11 is as defined above) and C2-14Aryl radicals(the C)2-14Aryl may optionally be substituted by one or more independently by-W13(CW14W15)m12W16Substituted with the substituents shown (wherein, W13、W14、W15、W16And m12 is the same as defined above))).
2. The compound of claim 1, a tautomer, prodrug or pharmaceutically acceptable salt of said compound, or a solvate thereof, wherein L4Is a bond, R3Is methyl (the methyl group may be optionally substituted with one or more groups selected from the group consisting of C1-10Alkyl radical, C2-10Alkenyl radical, C 2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino (this C)1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonylamino group may optionally be substituted by one or more C2-14Aryl substituted (the C)2-14Aryl may optionally be substituted with one or more groups independently represented by-W1(CW2W3)mW4Substituted with the substituents shown (wherein, W1Is (CR)24R25)n(wherein, R24And R25Each independently is a hydrogen atom or C1-6Alkyl (the C)1-6Alkyl groups may be substituted with one or more halogen atoms), or R24And R25Together with each other represent O or S, n is 0, 1, 2 or 3), an oxygen atom, a sulfur atom or NR36(wherein, R36Is a hydrogen atom, C1-6Alkyl, formyl or C1-6Alkylcarbonyl), W2And W3Each independently is a hydrogen atom or C1-3Alkyl (the C)1-3The alkyl radical may be substituted by oneOr substituted by more halogen atoms), m is 0, 1, 2 or 3, and W4Is hydroxy, protected hydroxy, thiol, amino, formyl, halogen, nitro, cyano, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C2-9Heterocyclic group, C 1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkylcarbonylamino, mono-or di-C1-10Alkylamino radical (this C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkylcarbonylamino and mono-or di-C1-10The alkylamino group may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, thiol, phosphonic acid, sulfonic acid, tetrazolyl, C 2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-10Alkyl substitution (of this C)1-10Alkyl groups which may be substituted by one or more halogen atoms) or by oneOr substituted with more than one halogen atom)), SO2R28、SOR28、COR28(wherein, R28Is hydroxy, protected hydroxy, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C2-9Heterocyclyl and C1-10Alkoxy groups may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), C2-14Aryl radical, C2-14Aryloxy group (the C)2-14Aryl and C2-14The aryloxy group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C 1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted by one or more halogen atoms) or NR29R30(wherein, R29And R30Each independently is a hydrogen atom, a hydroxyl group, a protected hydroxyl group, a formyl group, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylsulfonyl radical, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, the C1-10Alkylsulfonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14The aryloxy group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C 2-6Alkenyl radical, C2-6Alkynyl, carboxyl, sulfonyl, sulfamoyl, sulfo, nitro, cyano, halogen atom, C1-10Alkoxy (the C)1-10Alkoxy groups which may be substituted by one or more halogen atoms), C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms))), or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), or R 29And R30Together represent- (CH)2)m3-G-(CH2)m4- (wherein G is an oxygen atom, a sulfur atom, CR31R32(wherein, R31And R32Each independently is a hydrogen atom, C1-10Alkyl radical, C2-14Aryl radical, C1-10Alkoxy radical, C2-14Aryloxy, hydroxy or protected hydroxy) or NR33(wherein, R33Is hydrogen atom, hydroxy, formyl, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted by one or more halogen atoms) or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10The alkyl radical may be substituted by oneOr substituted by more than one halogen atom), C 2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms)), m3 and m4 are each independently an integer from 0 to 5, provided that m3+ m4 are 3, 4 or 5))), tetrazolyl or phosphonic acid groups), or by one or more groups independently substituted with-W5(CW6W7)m10W8Substituted with the substituents shown (wherein, W5、W6、W7And m10 is independently from W1、W2、W3Same as m, W1、W2、W3And m is as defined above, and W8Is hydroxy, protected hydroxy, thiol, amino, formyl, halogen, nitro, cyano, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkylcarbonylamino, mono-or di-C1-10Alkylamino radical (this C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkylcarbonylamino and mono-or di-C1-10The alkylamino group may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C 1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), SO2R28a、SOR28a、COR28a(wherein, R28aAnd R28Same as R28Same as defined above), tetrazolyl or phosphonic acid groups)) and independently of-W9(CW10W11)m11W12A substituent of (wherein, W)9、W10、W11、W12And m11Respectively with W1、W2、W3、W8Same as m, W1、W2、W3、W8And m is as defined above)), C2-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl or C2-9Heterocyclic group (the C)2-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl and C2-9The heterocyclyl group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylaminocarbonyl radical, C1-10Dialkylaminocarbonyl group, C1-10Alkylcarbonylamino (this C)1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C 1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylaminocarbonyl radical, C1-10Dialkylaminocarbonyl and C1-10The alkylcarbonylamino group may optionally be substituted by one or more C2-14Aryl substituted (the C)2-14Aryl groups may optionally be substituted by one or more independently-W1(CW2W3)mW4Substituted by the substituents shown(wherein, W1、W2、W3、W4And m is as defined above)), or by one or more independently of-W5(CW6W7)m10W8Substituted with the substituents shown (wherein, W5、W6、W7、W8And m10 is as defined above)), independently by W9(CW10W11)m11W12A substituent of (wherein, W)9、W10、W11、W12And m11 is as defined above) and C2-14Aryl radical (the radical C)2-14Aryl may optionally be substituted by one or more independently by-W13(CW14W15)m12W16Substituted with the substituents shown (wherein, W13、W14、W15、W16And m12 is independently from W1、W2、W3、W4Same as m, W1、W2、W3、W4And m is as defined above))).
3. The compound of claim 1, a tautomer, prodrug or pharmaceutically acceptable salt of said compound, or a solvate thereof, wherein L4Is CR20R21(wherein, R20And R21Each independently is a hydrogen atom, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy and C1-10The alkylcarbonyl group may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C 1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms)), an oxygen atom, a sulfur atom or an NR group)22(wherein, R22Is hydrogen atom, hydroxy, protected hydroxy, formyl, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C 1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C) 1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms)))3Is C1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl or C1-10Alkylcarbonylamino (this C)1-10Alkyl radical, C2-14Alkenyl radical, C2-14Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonylamino group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl radical, C2-14Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino (this C)1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkyl carbonylMono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonylamino group may optionally be substituted by one or more C2-14Aryl substituted (the C)2-14Aryl may optionally be substituted by one or more independently by-W1(CW2W3)mW4Substituted with the substituents shown (wherein, W 1Is (CR)24R25)n(wherein, R24And R25Each independently is a hydrogen atom or C1-6Alkyl (the C)1-6Alkyl groups may be substituted by one or more halogen atoms), or R24And R25Together with each other represent O or S, n is 0, 1, 2 or 3), an oxygen atom, a sulfur atom or NR36(wherein, R36Is a hydrogen atom, C1-6Alkyl, formyl or C1-6Alkylcarbonyl), W2And W3Each independently is a hydrogen atom or C1-3Alkyl (the C)1-3Alkyl groups may be substituted by one or more halogen atoms), m is 0, 1, 2 or 3, and W is4Is hydroxy, protected hydroxy, thiol, amino, formyl, halogen, nitro, cyano, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkylcarbonylamino, mono-or di-C1-10Alkylamino radical (this C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkylcarbonylamino and mono-or di-C1-10The alkylamino group may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C 2-14Aryloxy group (the C)2-14Aryl and C2-14The aryloxy group may be substituted by one or moreA C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, thiol, phosphonic acid, sulfonic acid, tetrazolyl, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-10Alkyl substitution (of this C)1-10Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), SO2R28、SOR28、COR28(wherein, R28Is hydroxy, protected hydroxy, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C2-9Heterocyclyl and C1-10Alkoxy groups may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C 1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), C2-14Aryl radical, C2-14Aryloxy group (the C)2-14Aryl and C2-14The aryloxy group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted by one or more halogen atoms) or by one or more halogen atoms), or NR29R30(wherein, R29And R30Each independently is a hydrogen atom, a hydroxyl group, a protected hydroxyl group, a formyl group, C1-10Alkyl radical, C2-6Alkenyl radical, C 2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylsulfonyl radical, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylsulfonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), or C2-14Aryl radical (the radical C)2-14Aryl may be optionally substituted by oneOr substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C 2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), or R29And R30Together represent- (CH)2)m3-G-(CH2)m4- (wherein G is an oxygen atom, a sulfur atom, CR31R32(wherein, R31And R32Each independently is a hydrogen atom, C1-10Alkyl radical, C2-14Aryl radical, C1-10Alkoxy radical, C2-14Aryloxy, hydroxy or protected hydroxy) or NR33(wherein, R33Is hydrogen atom, hydroxy, formyl, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy radicals may be substituted by oneOr a plurality of C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C 2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted by one or more halogen atoms) or by one or more halogen atoms)), m3 and m4 are each independently an integer from 0 to 5, provided that m3+ m4 are 3, 4 or 5))), tetrazolyl or phosphonic acid groups), or by one or more groups independently substituted by-W5(CW6W7)m10W8Substituted with the substituents shown (wherein, W5、W6、W7And m10Respectively with W1、W2、W3Same as m, W1、W2、W3And m is as defined above, and W8Is hydroxy, protected hydroxy, thiol, amino, formyl, halogen, nitro, cyano, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkylcarbonylamino, mono-or di-C1-10Alkylamino radical (this C)1-10Alkyl radical, C2-6Alkenyl radical, C 2-6Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkylcarbonylamino and mono-or di-C1-10The alkylamino group may be optionally substituted with one or more groups selected from the group consisting of: carboxy, nitro, cyanoA halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), SO2R28a、SOR28a、 COR28a(wherein, R28aAnd R28Same as R28Same as defined above), tetrazolyl or phosphonic acid group)), independently-W9(CW10W11)m11W12A substituent of (wherein, W)9、W10、W11、W12And m11 is independently from W1、W2、W3、W8Same as m, W1、W2、W3、W8And m is as defined above) and C2-14Aryl radical (the radical C)2-14Aryl may optionally be substituted by one or more independently by-W13(CW14W15)m12W16Substituted with the substituents shown (wherein, W13、W14、W15、W16And m12 is independently from W1、W2、W3、W4Same as m, W1、W2、W3、W4And m is as defined above))).
4. A compound according to any one of claims 1 to 3, a tautomer, prodrug or pharmaceutically acceptable salt of said compound, or a solvate thereof, wherein a is a nitrogen atom and B is a sulfur atom.
5. A compound according to any one of claims 1 to 3, a tautomer, prodrug or pharmaceutically acceptable salt of said compound, or a solvate thereof, wherein a is a nitrogen atom and B is an oxygen atom.
6. The method according to any one of claims 1 to 3A compound, a tautomer, prodrug or pharmaceutically acceptable salt of said compound, or a solvate thereof, wherein a is a nitrogen atom and B is NR other than NH9(wherein, R9Is hydrogen atom, hydroxy, formyl, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more groups selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), C 2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy) or C2-14Aryloxy group (the C)2-14The aryloxy group may be optionally substituted with one or more groups selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy)).
7. The compound, tautomer, prodrug or pharmaceutically acceptable salt of the compound, or solvate thereof, of any one of claims 1-3, wherein A is CR4(wherein, R4Is a hydrogen atom, a hydroxyl group (the hydroxyl group may be substituted by C)2-6Alkenyl or C2-6Alkynyl-substituted), a thiol group (the thiol group may be C) 1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl or C1-10Alkylcarbonyl), amino (which amino may be substituted by one or two C)2-6Alkenyl or one or two C2-6Alkynyl-substituted), formyl, halogen, nitro, cyano, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkylcarbonylamino, mono-or di-C1-10Alkylamino radical, C1-10Alkoxy (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkylcarbonylamino, mono-or di-C1-10Alkylamino and C1-10Alkoxy may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of:C1-10alkyl (the C)1-10Alkyl groups may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C 1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group), C2-14Aryloxy group (the C)2-14The aryloxy group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy), SO2R5、SOR5Or COR5(wherein, R5Is hydroxy, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C2-9Heterocyclyl and C1-10Alkoxy groups may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C 1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group), C2-14Aryloxy group (the C)2-14The aryloxy group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy) or NR6R7(wherein, R6And R7Each independently is a hydrogen atom, a hydroxyl group, a formyl group, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkyl carbonyl oxy, C 1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy) or R6And R7Together represent- (CH)2)m1-E-(CH2)m2- (wherein E is an oxygen atom, a sulfur atom, CR 26R27(wherein, R26And R27Each independently is a hydrogen atom, C1-10Alkyl radical, C2-14Aryl radical, C1-10Alkoxy radical, C2-14Aryloxy, hydroxy or protected hydroxy) or NR8(wherein, R8Is hydrogen atom, hydroxy, formyl, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C 1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy)), m1 and m2 are each independently an integer from 0 to 5, provided that m1+ m2 is 3, 4 or 5))), and B is an oxygen atom.
8. The compound, tautomer, prodrug or pharmaceutically acceptable salt of the compound, or solvate thereof, of any one of claims 1-3, wherein A is CR4(wherein, R4Is a hydrogen atom, a hydroxyl group (the hydroxyl group may be substituted by C)2-6Alkenyl or C2-6Alkynyl-substituted), a thiol group (the thiol group may be C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl or C1-10Alkylcarbonyl), amino (which amino may be substituted by one or two C)2-6Substituted by alkenyl radicals or by one or two C2-6Alkynyl-substituted), formyl, halogen, nitro, cyano, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkylcarbonylamino, mono-or di-C1-10Alkylamino radical, C1-10Alkoxy (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkylcarbonylamino, mono-or di-C1-10Alkylamino and C1-10Alkoxy groups may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C 1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxygen radical、C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group), C2-14Aryloxy group (the C)2-14The aryloxy group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C 1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy), SO2R5、SOR5Or COR5(wherein, R5Is hydroxy, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C2-9Heterocyclyl and C1-10Alkoxy groups may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom,C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C 2-14Aryl and C2-14Aryloxy group), C2-14Aryloxy group (the C)1-14The aryloxy group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy) or NR6R7(wherein, R6And R7Each independently is a hydrogen atom, a hydroxyl group, a formyl group, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, alkynyl,C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C 2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy) or R6And R7Together represent- (CH)2)m1E-(CH2)m2- (wherein E is an oxygen atom, a sulfur atom, CR26R27(wherein, R26And R27Each independently is a hydrogen atom, C1-10Alkyl radical, C2-14Aryl radical, C1-10Alkoxy radical, C2-14Aryloxy, hydroxy or protected hydroxy) or NR8(wherein, R8Is hydrogen atom, hydroxy, formyl, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radicalBase, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C 1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy)), m1 and m2 are each independently an integer from 0 to 5, provided that m1+ m2 is 3, 4 or 5))), and B is a sulfur atom.
9. The compound, tautomer, prodrug or pharmaceutically acceptable salt of the compound, or solvate thereof, of any one of claims 1-3, wherein A is CR4(wherein, R4Is a hydrogen atom, a hydroxyl group (the hydroxyl group may be substituted by C)2-6Alkenyl or C2-6Alkynyl-substituted), a thiol group (the thiol group may be C)1-10Alkyl radical, C2-6Alkenyl radical, C 2-6Alkynyl or C1-10Alkylcarbonyl), amino (which amino may be substituted by one or two C)2-6Alkenyl or one or two C2-6Alkynyl-substituted), formyl, halogen, nitro, cyano, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkylcarbonylamino, mono-or di-C1-10Alkylamino radical, C1-10Alkoxy (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkylcarbonylamino, mono-or di-C1-10Alkylamino and C1-10Alkoxy groups may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C 1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group), C2-14Aryloxy group (the C)2-14The aryloxy group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protectedHydroxy, C2-14Aryl and C2-14Aryloxy), SO2R5、SOR5Or COR5(wherein, R5Is hydroxy, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C2-9Heterocyclyl and C1-10Alkoxy groups may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C1-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C 1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group), C2-14Aryloxy group (the C)2-14The aryloxy group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy) or NR6R7(wherein, R6And R7Each independently is a hydrogen atom, a hydroxyl group, a formyl group, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C 1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy) or R6And R7Together represent- (CH)2)m1-E-(CH2)m2- (wherein E is an oxygen atom, a sulfur atom, CR26R27(wherein, R 26And R27Each independently is a hydrogen atom, C1-10Alkyl radical, C2-14Aryl radical, C1-10Alkoxy radical, C2-14Aryloxy, hydroxy or protected hydroxy) or NR8(wherein, R8Is hydrogen atom, hydroxy, formyl, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C 1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy)), m1 and m2 are each independently an integer from 0 to 5, with the proviso that m1+ m2 are 3, 4 or 5))), and B is NR9(wherein, R9Is hydrogen atom, hydroxy, formyl, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be substituted, if desired, with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy radicals may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c 1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy) or C2-14Aryloxy group (the C)2-14The aryloxy group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy)).
10. A compound according to any one of the above 1-9, a tautomer, prodrug or pharmaceutically acceptable salt of said compound, or a solvate thereof, wherein, L1Is a bond.
11. The compound of any one of claims 1-10, a tautomer, prodrug or pharmaceutically acceptable salt of said compound, or a solvate thereof, wherein L2Is a bond.
12. The compound of any one of claims 1-11, a tautomer, prodrug or pharmaceutically acceptable salt of said compound, or a solvate thereof, wherein L 3Is NR19(wherein, R19Is hydrogen atom, hydroxy, formyl, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkoxy and C1-10The alkylcarbonyl group may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxylNitro group, cyano group, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C 1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy)).
13. The compound of any one of claims 1-11, a tautomer, prodrug or pharmaceutically acceptable salt of said compound, or a solvate thereof, wherein L3Is NH.
14. The compound of any one of claims 3-11, a tautomer, prodrug or pharmaceutically acceptable salt of said compound, or a solvate thereof, wherein L3As defined above for 12, L4Is NR22(wherein, R22Is hydrogen atom, hydroxy, formyl, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C 2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10The alkyl radical maySubstituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy)).
15. The compound of any one of claims 3-11, a tautomer, prodrug or pharmaceutically acceptable salt of said compound, or a solvate thereof, wherein L3As defined for 13, L4Is NR22(wherein, R22Is hydrogen atom, hydroxy, formyl, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C 1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy)).
16. The compound, tautomer, prodrug or pharmaceutically acceptable salt of said compound, or solvate thereof according to claim 14 or 15, wherein L4Is NH.
17. The compound of any one of claims 2 and 4-11, a tautomer, prodrug, or pharmaceutically acceptable salt of said compound, or a solvate thereof, wherein L3As defined in 12, L4Is a bond.
18. The compound of any one of claims 2 and 4-11, a tautomer, prodrug, or pharmaceutically acceptable salt of said compound, or a solvate thereof, wherein L 3As defined for 13, L4Is a bond.
19. The compound of any one of claims 14-18, a tautomer, prodrug or pharmaceutically acceptable salt of said compound, or a solvate thereof, wherein Y is an oxygen atom.
20. The compound of any one of claims 14-18, a tautomer, prodrug or pharmaceutically acceptable salt of said compound, or a solvate thereof, wherein Y is a sulfur atom.
21. The compound, tautomer, prodrug or pharmaceutically acceptable salt of said compound, or solvate thereof, of claim 19 or 20 wherein X is hydroxy.
22. The compound of any one of claims 19-21, a tautomer, prodrug or pharmaceutically acceptable salt of said compound, or a solvate thereof, wherein R is3Is C2-9Heterocyclic group (the C)2-9The heterocyclic group may be optionally substituted with one or more substituents selected from the group consisting of: hydroxy, amino, carboxyl, phosphonic acid, sulfonic acid, aminomethylAcyl, sulfamoyl, tetrazolyl, C1-10Alkoxycarbonyl group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkylcarbonylamino and mono-or di-C1-10Alkylamino).
23. The compound of any one of claims 19-21, a tautomer, prodrug or pharmaceutically acceptable salt of said compound, or a solvate thereof, wherein R is 3Is C2-9Heterocyclic group (the C)2-9The heterocyclic group is substituted with one substituent selected from the group consisting of: hydroxy, amino, carboxy, phosphonic acid, sulfonic acid, carbamoyl, sulfamoyl, tetrazolyl and C1-10Alkoxycarbonyl, and substituted with one substituent selected from the group consisting of: hydroxy, amino, carboxy, phosphonic acid, sulfonic acid, carbamoyl, sulfamoyl, tetrazolyl, C1-10Alkoxycarbonyl group, nitro group, cyano group, halogen atom, C1-10Alkyl, C substituted by one or more fluorine atoms1-10Alkyl radical, C1-10Sulfamoyl substituted by C1-10Alkyl-substituted carbamoyl and C1-10Alkylcarbonylamino).
24. The compound of any one of claims 19-21, a tautomer, prodrug or pharmaceutically acceptable salt of said compound, or a solvate thereof, wherein R is3Is C1-10Alkyl or C2-10Alkenyl (the C)1-10Alkyl and C2-10The alkenyl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl radical, C2-10Alkenyl radical, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino (this C)1-10Alkyl radical, C2-10Alkenyl radical, C1-10Alkoxy radical, C1-10Thioalkyl, C 1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonylamino group may be optionally substituted with one or more substituents selected from the group consisting of: hydroxy, amino, carboxy, phosphonic acid, sulfonic acid, carbamoyl, sulfamoyl, tetrazolyl, C1-10Alkoxycarbonyl group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkylcarbonylamino and mono-or di-C1-10Alkylamino), nitro, halogen, hydroxyl, amino, carboxyl, phosphonic acid, sulfonic acid, carbamoyl, sulfamoyl, and tetrazolyl).
25. The compound of any one of claims 19-21, a tautomer, prodrug or pharmaceutically acceptable salt of said compound, or a solvate thereof, wherein R is3Is C1-10Alkyl or C2-10Alkenyl (the C)1-10Alkyl and C2-10The alkenyl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl radical, C2-6Alkenyl radical, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino (this C)1-10Alkyl radical, C2-6Alkenyl radical, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C 1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonylamino group may be optionally substituted with one or more substituents selected from the group consisting of: hydroxyl group, amino group, carboxyl group, phosphonic acid group, sulfonic acid group, carbamoyl group, sulfamoyl group, and tetrazolyl group), a halogen atom, nitro group, hydroxyl group, amino group, carboxyl group, phosphonic acid group, sulfonic acid group, carbamoyl group, sulfamoyl group, and tetrazolyl group).
26. The compound of any one of claims 19-21, a tautomer, prodrug or pharmaceutically acceptable salt of said compound, or a solvate thereof, wherein R is3Is C2-9Heterocyclic group (the C)2-9The heterocyclic group is substituted with one or more substituents selected from the group consisting of: hydroxy, amino, halogen, carboxy, sulfonic acid, carbamoyl, hydroxycarbamoyl, cyanocarbamoyl, sulfamoyl, hydroxysulfamoyl, cyanosulfamoyl, thiocarbamoyl, -CH2COOH、-OCH2COOH、-NHCH2COOH、-CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH、-(C＝O)COOH、-CH2(C＝O)COOH、-NH(C＝O)COOH、-NHSO2NH2、C1-10Alkyl radical, C1-10Alkylsulfonyl radical, C1-10Alkylsulfamoyl, C1-10Alkylcarbonyl group, C1-10Alkylaminocarbonyl and C1-10Dialkylaminocarbonyl (this C)1-10Alkyl radical, C1-10Alkylsulfonyl radical, C1-10Alkylsulfamoyl, C1-10Alkylcarbonyl group, C1-10Alkylaminocarbonyl and C1-10The dialkylaminocarbonyl group may be substituted with one or more substituents selected from the group consisting of: phenyl, thienyl, furyl, pyridyl, nitro, cyano, hydroxyl, amino, carboxyl, phosphonic acid, sulfonic acid, carbamoyl, sulfamoyl, and tetrazolyl)).
27. A thrombopoietin receptor activator according to any one of claims 1-26.
28. A prophylactic, therapeutic or ameliorating agent for a disease which can be effectively treated by activating a thrombopoietin receptor, comprising the thrombopoietin receptor activator, its tautomer, prodrug or pharmaceutically acceptable salt, or a solvate thereof as described in 27 as an active ingredient.
29. A thrombopoietin receptor activator, a tautomer, prodrug, or pharmaceutically acceptable salt of the activator, or a solvate thereof, according to 27, as an active ingredient.
30. A medicament containing a compound, a tautomer, prodrug, or pharmaceutically acceptable salt of the compound, or a solvate thereof, according to any one of claims 1 to 26, as an active ingredient.
The present invention provides a pharmaceutical composition comprising a compound which increases platelets by stimulating differentiation and proliferation of hematopoietic stem cells, megakaryocytic progenitor cells and megakaryocytes, or a compound which stimulates differentiation and proliferation of vascular endothelial cells and endothelial progenitor cells to treat angiogenesis or has an anti-arteriosclerotic effect.
Brief Description of Drawings
FIG. 1 shows the proliferation of UT7/EPO-mpl cells when stimulated with a compound of the present invention (synthetic example 4).
FIG. 2 shows the proliferation of UT7/EPO cells when stimulated with a compound of the invention (synthetic example 4).
Best Mode for Carrying Out The Invention
The present invention will now be described in detail.
In the present invention, "n" represents "n", "i" represents "iso", "s" represents "secondary", "t" represents "tertiary", "c" represents "ring", "o" represents "ortho", "m" represents "meta", "p" represents "para", "Ph" represents phenyl "," Py "represents pyridyl", "naphyl" represents Naphthyl "," Me "represents methyl", "Et" represents ethyl "," Pr "represents propyl", "Bu" represents butyl, and "Ac" represents acetyl.
First, R will be explained1-R36The terms appearing in the respective substituents.
The halogen atom is a fluorine atom, a chlorine atom, a bromine atom or an iodine atom. C1-3The alkyl group may be linear, branched or C3Cycloalkyl groups include methyl, ethyl, n-propyl, i-propyl, and c-propyl, among others.
C1-6The alkyl group may be linear, branched or C3-6Cycloalkyl radicals, other than the above-mentioned radicalsThe method also comprises the following steps: n-butyl, i-butyl, s-butyl, t-butyl, c-butyl, 1-methyl-c-propyl, 2-methyl-c-propyl, n-pentyl, 1-methyl-n-butyl, 2-methyl-n-butyl, 3-methyl-n-butyl, 1-dimethyl-n-propyl, 1, 2-dimethyl-n-propyl, 2-dimethyl-n-propyl, 1-ethyl-n-propyl, c-pentyl, 1-methyl-c-butyl, 2-methyl-c-butyl, 3-methyl-c-butyl, 1, 2-dimethyl-c-propyl, n-butyl, n-pentyl, n-butyl, 2, 3-dimethyl-c-propyl, 1-ethyl-c-propyl, 2-ethyl-c-propyl, n-hexyl, 1-methyl-n-pentyl, 2-methyl-n-pentyl, 3-methyl-n-pentyl, 4-methyl-n-pentyl, 1-dimethyl-n-butyl, 1, 2-dimethyl-n-butyl, 1, 3-dimethyl-n-butyl, 2-dimethyl-n-butyl, 2, 3-dimethyl-n-butyl, 3-dimethyl-n-butyl, 1-ethyl-n-butyl, 2-ethyl-n-butyl, n-pentyl, n-hexyl, n-pentyl, 1-methyl-n-pentyl, 1-dimethyl-n-butyl, 2-dimethyl-n-butyl, 2, 3, 1, 1, 2-trimethyl-n-propyl, 1, 2, 2-trimethyl-n-propyl, 1-ethyl-1-methyl-n-propyl, 1-ethyl-2-methyl-n-propyl, c-hexyl, 1-methyl-c-pentyl, 2-methyl-c-pentyl, 3-methyl-c-pentyl, 1-ethyl-c-butyl, 2-ethyl-c-butyl, 3-ethyl-c-butyl, 1, 2-dimethyl-c-butyl, 1, 3-dimethyl-c-butyl, 2, 2-dimethyl-c-butyl, 2, 3-dimethyl-c-butyl, 2, 4-dimethyl-c-butyl, 3-dimethyl-c-butyl, 1-n-propyl-c-propyl, 2-n-propyl-c-propyl, 1-i-propyl-c-propyl, 2-i-propyl-c-propyl, 1, 2, 2-trimethyl-c-propyl, 1, 2, 3-trimethyl-c-propyl, 2, 3-trimethyl-c-propyl, 1-ethyl-2-methyl-c-propyl, 2-ethyl-1-methyl-c-propyl, 2-ethyl-2-methyl-c-propyl, 2-ethyl-3-methyl-c-propyl and the like.
C1-10The alkyl group may be linear, branched or C3-10Cycloalkyl groups, in addition to the above groups, include: 1-methyl-1-ethyl-n-pentyl, 1-heptyl, 2-heptyl, 1-ethyl-1, 2-dimethyl-n-propyl, 1-ethyl-2, 2-dimethyl-n-propyl, 1-octyl, 3-octyl, 4-methyl-3-n-heptyl, 6-methyl-2-n-heptyl, 2-propyl-1-n-heptyl, 2, 4, 4-trimethyl-1-n-pentyl, 1-nonyl, 2, 6-dimethyl-4-n-heptyl, 3-ethyl-2, 2-dimethyl-3-n-pentyl, 2-heptyl, 2-octyl, 3-methyl-2-n-heptyl, and mixtures thereof, 3, 5, 5-trimethyl-1-n-hexyl, 1-decyl, 2-decyl, 4-decyl, 3, 7-dimethyl-1-n-octyl, 3, 7-dimethyl-3-n-octyl, c-heptyl, c-octyl, 1-methyl-c-hexyl, 2-methyl-c-hexyl, 3-methyl-c-hexyl, 1, 2-dimethyl-c-hexyl, 1-ethyl-c-hexyl, 1-methyl-c-pentyl, 2-methyl-c-pentyl, 3-methyl-c-pentyl, etc.
C2-10The alkyl group may be linear, branched or C3-10Cycloalkyl radicals including the above pair C1-10Alkyl groups are those groups described, except for methyl.
C2-6Alkynyl groups may include: ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-methyl-2-butynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-1-butynyl, 1-dimethyl-2-propynyl, 2-ethyl-2-propynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 1-methyl-4-pentynyl, 2-methyl-3-pentynyl, 2-methyl-4-pentynyl, 3-methyl-1-pentynyl, 3-methyl-4-pentynyl, 4-methyl-1-pentynyl, 4-methyl-2-pentynyl, 1-dimethyl-2-butynyl, 1-dimethyl-3-butynyl, 1, 2-dimethyl-3-butynyl, 2-dimethyl-3-butynyl, 3-dimethyl-1-butynyl, 1-ethyl-2-butynyl, 1-ethyl-3-butynyl, 1-n-propyl-2-propynyl, 2-methyl-3-pentynyl, 2-methyl-4-pentynyl, 3-methyl-1-butynyl, 1-dimethyl-3-butynyl, 1-ethyl-2-butynyl, 1-, 2-ethyl-3-butynyl, 1-methyl-1-ethyl-2-propynyl, 1-i-propyl-2-propynyl, etc.
C2-10Alkynyl groups may be straight or branched chain and include, in addition to those groups recited above: 1-methyl-n-hexynyl, 1, 2-dimethyl-n-hexynyl, 1-ethyl-n-hexynyl, 1-n-heptynyl, 2-n-heptynyl, 3-n-heptynyl, 4-n-heptynyl, 1-n-octynyl, 2-n-octynyl, 3-n-octynyl and the like.
C2-6The alkenyl group may be linear, branched or C3-6Cycloalkenyl group, including: vinyl, 1-propenyl, 2-propenyl, 1-methyl-1-vinyl, 1-butenyl, 2-butenyl, 3-butenyl, 2-methyl-1-propenyl, 2-methyl-2-propenyl, 1-ethylvinyl, 1-methyl-1-propenyl, 1-methyl-2-propenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-n-propylvinyl, 1-methyl-1-butenyl, 1-methyl-2-butenyl, 1-methyl-3-butenyl, 2-ethyl-2-propenyl, 2-methyl-1-butenyl, 2-methyl-2-butenyl, 2-methyl-3-butenyl, 3-methyl-1-butenyl, 3-methyl-2-butenyl, 2-methyl-3-butenyl, 1-methyl-2-butenyl, 1-pentenyl, 2-pentenyl, 4-pentenyl, 1-n-propylvinyl, 1-methyl-1, 3-methyl-3-butenyl, 1-dimethyl-2-propenyl, 1-i-propylvinyl, 1, 2-dimethyl-1-propenyl, 1, 2-dimethyl-2-propenyl, 1-c-pentenyl, 2-c-pentenyl, 3-c-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-1-pentenyl, 1-methyl-2-pentenyl, 1-methyl-3-pentenyl, 1-methyl-4-pentenyl, 1-n-butylvinyl, 2-methyl-1-pentenyl, 1-methyl-2-pentenyl, 1-n-pentenyl, 1-methyl-pentenyl, 2-methyl-1-pentenyl, 1-methyl-pentenyl, 1-C-penten, 2-methyl-2-pentenyl, 2-methyl-3-pentenyl, 2-methyl-4-pentenyl, 2-n-propyl-2-propenyl, 3-methyl-1-pentenyl, 3-methyl-2-pentenyl, 3-methyl-3-pentenyl, 3-methyl-4-pentenyl, 3-ethyl-3-butenyl, 4-methyl-1-pentenyl, 4-methyl-2-pentenyl, 4-methyl-3-pentenyl, 4-methyl-4-pentenyl, 1-dimethyl-2-butenyl, 1-dimethyl-3-butenyl, 2-methyl-4-pentenyl, 3-n-propyl-2-propenyl, 3-methyl-3-pentenyl, 4-methyl-4-pentenyl, 1-dimethyl, 1, 2-dimethyl-1-butenyl, 1, 2-dimethyl-2-butenyl, 1, 2-dimethyl-3-butenyl, 1-methyl-2-ethyl-2-propenyl, 1-s-butylvinyl, 1, 3-dimethyl-1-butenyl, 1, 3-dimethyl-2-butenyl, 1, 3-dimethyl-3-butenyl, 1-i-butylvinyl, 2-dimethyl-3-butenyl, 2, 3-dimethyl-1-butenyl, 2, 3-dimethyl-2-butenyl, 2, 3-dimethyl-3-butenyl, 2-i-propyl-2-propenyl, 2-methyl-2-butenyl, 2, 3-dimethyl-3-butenyl, 2-i-propyl-2-propenyl, and the like, 3, 3-dimethyl-1-butenyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 1-n-propyl-1-propenyl, 1-n-propyl-2-propenyl, 2-ethyl-1-butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl, 1, 2-trimethyl-2-propenyl, 1-t-butylvinyl, 1-methyl-1-ethyl-2-propenyl, 1-ethyl-2-methyl-1-propenyl, 1-ethyl-2-methyl-2-propenyl, 1-ethyl, 1-i-propyl-1-propenyl group, 1-i-propyl-2-propenyl group, 1-methyl-2-c-pentenyl group, 1-methyl-3-c-pentenyl group, 2-methyl-1-c-pentenyl group, 2-methyl-2- c-pentenyl, 2-methyl-3-c-pentenyl, 2-methyl-4-c-pentenyl, 2-methyl-5-c-pentenyl, 2-methylene-c-pentyl, 3-methyl-1-c-pentenyl, 3-methyl-2-c-pentenyl, 3-methyl-3-c-pentenyl, 3-methyl-4-c-pentenyl, 3-methyl-5-c-pentenyl, 3-methylene-c-pentyl, 1-c-hexenyl, 2-c-hexenyl, 3-c-hexenyl, and the like.
C2-10The alkenyl group may be linear, branched or C3-10Cycloalkenyl radicals, in addition to those mentioned above, include: 1-methyl-n-hexenyl, 1, 2-dimethyl-n-hexenyl, 1-ethyl-n-hexenyl, 1-n-heptenyl, 2-n-heptenyl, 3-n-heptenyl, 4-n-heptenyl, 1-n-octenyl, 2-n-octenyl, 3-n-octenyl, 1-methyl-c-hexenyl, 1, 2-dimethyl-c-hexenyl, 1-ethyl-c-hexenyl, 1-c-heptenyl, 2-c-heptenyl, 3-c-heptenyl, 4-c-heptenyl, 1-c-octenyl, 2-c-octenyl, 3-c-octenyl, 4-c-octenyl, and the like.
C2-9The heterocyclic group may be a mono-heterocyclic group or a condensed bi-heterocyclic group containing at least one hetero atom optionally selected from a nitrogen atom, an oxygen atom and a sulfur atom, and 2 to 9 carbon atoms, and specifically has the following structure.
C2-14The aryl group may be C containing no hetero atom as a ring-constituting atom 6-14Aryl being either C2-9Aromatic heterocyclic group, C2-9The aromatic heterocyclic group may be a 5-to 7-membered C group containing 1 to 3 oxygen atoms, nitrogen atoms or sulfur atoms, alone or in combination2-6Monoheterocyclyl or 8-to 10-membered C5-9A fused bis-heterocyclyl.
C free of hetero atoms6-14Aryl groups include: phenyl, 1-indenyl, 2-indenyl, 3-indenyl, 4-indenyl, 5-indenyl, 6-indenyl, 7-indenyl, alpha-naphthyl, beta-naphthyl, 1-tetrahydronaphthyl, 2-tetrahydronaphthyl, 5-tetrahydronaphthyl, 6-tetrahydronaphthyl,o-biphenyl, m-biphenyl, p-biphenyl, 1-anthryl, 2-anthryl, 9-anthryl, 1-phenanthryl, 2-phenanthryl, 3-phenanthryl, 4-phenanthryl, 9-phenanthryl, and the like.
5-to 7-membered C2-6The monocyclic heterocyclic group may be 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyranyl, 3-pyranyl, 4-pyranyl, 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 1-imidazolyl, 2-imidazolyl, 4-imidazolyl, 1-pyrazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, 2-1, 3, 4-oxadiazolyl, 2-1, 3, 4-thiadiazolyl, 3-1, 2, 4-oxadiazolyl, 5-1, 2, 4-oxadiazolyl, 3-1, 2, 4-thiadiazolyl, 5-1, 2, 4-thiadiazolyl, 3-1, 2, 5-oxadiazolyl, 3-1, 2, 5-thiadiazolyl, and the like.
8-to 10-membered C5-9The fused heterocyclic group may be 2-benzofuranyl, 3-benzofuranyl, 4-benzofuranyl, 5-benzofuranyl, 6-benzofuranyl, 7-benzofuranyl, 1-isobenzofuranyl, 4-isobenzofuranyl, 5-isobenzofuranyl, 2-benzothienyl, 3-benzothienyl, 4-benzothienyl, 5-benzothienyl, 6-benzothienyl, 7-benzothienyl, 1-isobenzothienyl, 4-isobenzothienyl, 5-isobenzothienyl, 2-benzopyranyl, 3-benzopyranyl, 4-benzopyranyl, 5-benzopyranyl, 6-benzopyranyl, 7-benzopyranyl, 8-benzopyranyl, 1-indolizinyl, 2-indolizinyl, 3-indolizinyl, 5-indolizinyl, 6-indolizinyl, 7-indolizinyl, 8-indolizinyl, 1-isoindolyl, 2-isoindolyl, 4-isoindolyl, 5-isoindolyl, 1-indolyl, 2-indolyl, 3-indolyl, 4-indolyl, 5-indolyl, 6-indolyl, 7-indolyl, 1-indazolyl, 2-indazolyl, 3-indazolyl, 4-indazolyl, 5-indazolyl, 6-indazolyl, 7-purinyl (purinyl), 2-purinyl, 2-indolizinyl, 5-indolizinyl, 2-A purinyl group, a 3-purinyl group, a 6-purinyl group, a 7-purinyl group, an 8-purinyl group, a 2-quinolyl group, a 3-quinolyl group, a 4-quinolyl group, a 5-quinolyl group, a 6-quinolyl group, a 7-quinolyl group, a 8-quinolyl group, a 1-isoquinolyl group, a 3-isoquinolyl group, a 4-isoquinolyl group, a 5-isoquinolyl group, a 6-isoquinolyl group, a 7-isoquinolyl group, a 8-isoquinolyl group, a 1-2, 3-naphthyridinyl group, a 5-2, 3-naphthyridinyl group, a 6-2, 3-naphthyridinyl group, a 1-2, 7-naphthyridinyl group, a 4-2, 7-naphthyridinyl group, a, 1-2, 6-naphthyridinyl, 3-2, 6-naphthyridinyl, 4-2, 6-naphthyridinyl, 2-1, 8-naphthyridinyl, 3-1, 8-naphthyridinyl, 4-1, 8-naphthyridinyl, 2-1, 7-naphthyridinyl, 3-1, 7-naphthyridinyl, 4-1, 7-naphthyridinyl, 5-1, 7-naphthyridinyl, 6-1, 7-naphthyridinyl, 8-1, 7-naphthyridinyl, 2-1, 6-naphthyridinyl, 3-1, 6-naphthyridinyl, 4-1, 6-naphthyridinyl, 5-1, 6-naphthyridinyl, 7-1, 6-naphthyridinyl group, 8-1, 6-naphthyridinyl group, 2-1, 5-naphthyridinyl group, 3-1, 5-naphthyridinyl group, 4-1, 5-naphthyridinyl group, 6-1, 5-naphthyridinyl group, 7-1, 5-naphthyridinyl group, 8-1, 5-naphthyridinyl group, 2-quinoxalinyl group, 5-quinoxalinyl group, 6-quinoxalinyl group, 2-quinazolinyl group, 4-quinazolinyl group, 5-quinazolinyl group, 6-quinazolinyl group, 7-quinazolinyl group, 8-quinazolinyl group, 3-cinnolinyl group, 4-cinnolinyl group, 5-cinnolinyl group, 6-cinnolinyl group, 7-cinnolinyl group, 8-cinnolinyl group, 2-pteridinyl group, 4-pteridinyl, 6-pteridinyl, 7-pteridinyl and the like.
C2-14The aryloxy group may be C containing no hetero atom as a ring-forming atom6-14Aryloxy radical or is C2-9Aromatic heterocyclic oxy radical, C2-9The aromatic heterocyclic oxy group may be a 5-to 7-membered C containing 1 to 3 oxygen atoms, nitrogen atoms or sulfur atoms, alone or in combination2-6Mono-heterocyclic oxy or 8-to 10-membered C5-9A fused bis-heterocyclyloxy group.
C free of hetero atoms6-14Aryloxy groups include: phenoxy group, 1-indenoxy group, 2-indenoxy group, 3-indenoxy group, 4-indenoxy group, 5-indenoxy group, 6-indenoxy group, 7-indenoxy group, alpha-naphthoxy group, beta-naphthoxy groupOxy, 1-tetrahydronaphthyloxy, 2-tetrahydronaphthyloxy, 5-tetrahydronaphthyloxy, 6-tetrahydronaphthyloxy, o-biphenyloxy, m-biphenyloxy, p-biphenyloxy, 1-anthracenyloxy, 2-anthracenyloxy, 9-anthracenyloxy, 1-phenanthrenyloxy, 2-phenanthrenyloxy, 3-phenanthrenyloxy, 4-phenanthrenyloxy, 9-phenanthrenyloxy and the like.
5-to 7-membered C2-6The mono-heterocyclic oxy group may be 2-thiophenyloxy, 3-thiophenyloxy, 2-furanoxy, 3-furanoxy, 2-pyranyloxy, 3-pyranyloxy, 4-pyranyloxy, 1-pyrrolyloxy, 2-pyrrolyloxy, 3-pyrrolyloxy, 1-imidazolyloxy, 2-imidazolyloxy, 4-imidazolyloxy, 1-pyrazolyloxy, 3-pyrazolyloxy, 4-pyrazolyloxy, 2-thiazolyloxy, 4-thiazolyloxy, 5-thiazolyloxy, 3-isothiazolyloxy, 4-isothiazolyloxy, 5-isothiazolyloxy, 2-oxazolyloxy, 4-oxazolyloxy, 5-oxazolyloxy, 3-isoxazolyloxy, 4-isoxazolyloxy, 5-isoxazolyloxy, 2-isoxazolyloxy, 3-oxazolyloxy, 3-isothiazolyloxy, 3-isoxazolyloxy, 2, 2-pyridyloxy, 3-pyridyloxy, 4-pyridyloxy, 2-pyrazinyloxy, 2-pyrimidyloxy, 4-pyrimidyloxy, 5-pyrimidyloxy, 3-pyridazinyloxy, 4-pyridazinyloxy, 2-1, 3, 4-oxadiazoyloxy, 2-1, 3, 4-thiadiazolyloxy, 3-1, 2, 4-oxadiazoyloxy, 5-1, 2, 4-oxadiazoyloxy, 3-1, 2, 4-thiadiazolyloxy, 5-1, 2, 4-thiadiazolyloxy, 3-1, 2, 5-oxadiazoyloxy, 3-1, 2, 5-thiadiazolyloxy, etc.
8-to 10-membered C5-9The fused bis-heterocyclic oxy group may be 2-benzofuranyloxy, 3-benzofuranyloxy, 4-benzofuranyloxy, 5-benzofuranyloxy, 6-benzofuranyloxy, 7-benzofuranyloxy, 1-isobenzofuranyloxy, 4-isobenzofuranyloxy, 5-isobenzofuranyloxy, 2-benzothienyloxy, 3-benzothienyloxy, 4-benzothienyloxy, 5-benzothienyloxy, 6-benzothienyloxy, 7-benzothienyloxy, 1-isobenzothiophenyloxy, 4-isobenzothiophenyloxy, 5-isobenzothiophenyloxy, 2-benzopyrenyloxy, 3-benzopyrenyloxy, 4-benzopyrenyloxy, 5-benzopyrenyloxy, 2-benzopyrenyloxy, 3-benzopyrenyloxy, 4-benzofuranyloxy, 5-benzofuranyloxy, 6-benzopyranyloxy, 7-benzopyranyloxy, 8-benzopyranyloxy, 1-indolizinyloxy (indolizinyloxy), 2-indolizinyloxy, 3-indolizinyloxy, 5-indolizinyloxyOxy, 6-indolizinyloxy, 7-indolizinyloxy, 8-indolizinyloxy, 1-isoindolyloxy, 2-isoindolyloxy, 4-isoindolyloxy, 5-isoindolyloxy, 1-indoyloxy, 2-indoyloxy, 3-indoyloxy, 4-indoyloxy, 5-indoyloxy, 6-indoyloxy, 7-indoyloxy, 1-indazolyloxy, 2-indazolyloxy, 3-indazolyloxy, 4-indazolyloxy, 5-indazolyloxy, 6-indazolyloxy, 7-indazolyloxy, 1-purinyloxy, 2-purinyloxy, 3-purinyloxy, 6-purinyloxy, 7-purinyloxy, 8-purinyloxy, 2-quinolinyloxy, di-or-quinolinyloxy, 3-quinolinyloxy, 4-quinolinyloxy, 5-quinolinyloxy, 6-quinolinyloxy, 7-quinolinyloxy, 8-quinolinyloxy, 1-isoquinolinyloxy, 3-isoquinolinyloxy, 4-isoquinolinyloxy, 5-isoquinolinyloxy, 6-isoquinolinyloxy, 7-isoquinolinyloxy, 8-isoquinolinyloxy, 1-2, 3-naphthyryloxy (phthalaz-inoxy), 5-2, 3-naphthyryloxy, 6-2, 3-naphthyryloxy, 1-2, 7-naphthyryloxy, 3-2, 7-naphthyryloxy, 4-2, 7-naphthyryloxy, 1-2, 6-naphthyryloxy, 3-2, 6-naphthyryloxy, 4-2, 6-naphthyridinyloxy, 2-1, 8-naphthyryloxy, 3-1, 8-naphthyryloxy, 4-1, 8-naphthyryloxy, 2-1, 7-naphthyryloxy, 3-1, 7-naphthyryloxy, 4-1, 7-naphthyryloxy, 5-1, 7-naphthyryloxy, 6-1, 7-naphthyryloxy, 8-1, 7-naphthyryloxy, 2-1, 6-naphthyryloxy, 3-1, 6-naphthyryloxy, 4-1, 6-naphthyryloxy, 5-1, 6-naphthyryloxy, 7-1, 6-naphthyryloxy, 8-1, 6-naphthyryloxy, 2-1, 5-naphthyryloxy, 3-1, 5-naphthyryloxy, 4-1, 5-naphthyryloxy, 6-1, 5-naphthyryloxy, 7-1, 5-naphthyryloxy, 8-1, 5-naphthyryloxy, 2-quinoxalyloxy, 5-quinoxalyloxy, 6-quinoxalyloxy, 2-quinazolinyloxy, 4-quinazolinyloxy, 5-quinazolinyloxy, 6-quinazolinyloxy, 7-quinazolinyloxy, 8-quinazolinyloxy, 3-cinnolinyloxy, 4-cinnolinyloxy, 5-cinnolinyloxy, 6-cinnolinyloxy, 7-cinnolinyloxy, 8-cinnolinyloxy, 2-pteridinyloxy, 4-pteridinyloxy, 6-pteridinyloxy, 7-pteridinyloxy, and the like.
C1-6The alkylcarbonyl group may be linear, branched or C3-6Cycloalkylcarbonyl, which may include methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, i-propylcarbonyl, c-propylcarbonyl, n-butylcarbonyl, i-butylcarbonyl, s-butylcarbonyl, t-butylcarbonyl, c-butylcarbonyl, 1-methyl-c-propylcarbonyl, 2-methyl-c-propylcarbonyl, n-pentylcarbonyl, 1-methyl-n-butylcarbonyl, 2-methyl-n-butylcarbonyl, 3-methyl-n-butylcarbonyl, 1-dimethyl-n-propylcarbonyl, 1, 2-dimethyl-n-propylcarbonyl, 2-dimethyl-n-propylcarbonyl, 1-ethyl-n-propylcarbonyl, n-propylcarbonyl, c-pentylcarbonyl, 1-methyl-c-butylcarbonyl, 2-methyl-c-butylcarbonyl, 3-methyl-c-butylcarbonyl, 1, 2-dimethyl-c-propylcarbonyl, 2, 3-dimethyl-c-propylcarbonyl, 1-ethyl-c-propylcarbonyl, 2-ethyl-c-propylcarbonyl, n-hexylcarbonyl, 1-methyl-n-pentylcarbonyl, 2-methyl-n-pentylcarbonyl, 3-methyl-n-pentylcarbonyl, 4-methyl-n-pentylcarbonyl, 1-dimethyl-n-butylcarbonyl, 1, 2-dimethyl-n-butylcarbonyl, 1, 3-dimethyl-n-butylcarbonyl, 2, 2-dimethyl-n-butylcarbonyl, 2, 3-dimethyl-n-butylcarbonyl, 3-dimethyl-n-butylcarbonyl, 1-ethyl-n-butylcarbonyl, 2-ethyl-n-butylcarbonyl, 1, 2-trimethyl-n-propylcarbonyl, 1, 2, 2-trimethyl-n-propylcarbonyl, 1-ethyl-1-methyl-n-propylcarbonyl, 1-ethyl-2-methyl-n-propylcarbonyl, c-hexylcarbonyl, 1-methyl-c-pentylcarbonyl, 2-methyl-c-pentylcarbonyl, 3-methyl-c-pentylcarbonyl, 1-ethyl-c-butylcarbonyl, 2-ethyl-c-butylcarbonyl, 3-ethyl-c-butylcarbonyl, 1, 2-dimethyl-c-butylcarbonyl, 1, 3-dimethyl-c-butylcarbonyl, 2-dimethyl-c-butylcarbonyl, 2, 3-dimethyl-c-butylcarbonyl, 2, 4-dimethyl-c-butylcarbonyl, 3-dimethyl-c-butylcarbonyl, 1-n-propyl-c-propylcarbonyl, 2-n-propyl-c-propylcarbonyl, 1-i-propyl-c-propylcarbonyl, 2-i-propyl-c-propylcarbonyl, 1, 2, 2-trimethyl-c-propylcarbonyl, 1, 2, 3-trimethyl-c-propylcarbonyl, 2, 2, 3-trimethyl-c-propylcarbonyl, 1-ethyl-2-methyl-c-propylcarbonyl, 2-ethyl-1-methyl-c-propylcarbonyl, 2-ethyl-2-methyl-c-propylcarbonyl, 2-ethyl-3-methyl-c-propylcarbonyl, and the like.
C1-0The alkylcarbonyl group may be linear, branched or C3-10Cycloalkylcarbonyl, in addition to those groups described above, may include: 1-methyl-1-ethyl-n-pentylcarbonyl, 1-heptylcarbonyl, 2-heptylcarbonyl, 1-ethyl-1, 2-dimethyl-n-propylcarbonyl, 1-ethyl-2, 2-dimethyl-n-propylcarbonyl, 1-octylcarbonyl, 3-octylcarbonyl, 4-methyl-3-n-heptylcarbonyl, 6-methyl-2-n-heptylcarbonyl, 2-propyl-1-n-heptylcarbonyl, 2, 4, 4-trimethyl-1-n-pentylcarbonyl, 1-nonylcarbonyl, 2, 6-dimethyl-4-n-heptylcarbonyl, 2-methyl-1-n-propylcarbonyl, 3-ethyl-2, 2-dimethyl-3-n-pentylcarbonyl, 3, 5, 5-trimethyl-1-n-hexylcarbonyl, 1-decylcarbonyl, 2-decylcarbonyl, 4-decylcarbonyl, 3, 7-dimethyl-1-n-octylcarbonyl, 3, 7-dimethyl-3-n-octylcarbonyl, and the like.
C1-6The alkylsulfamoyl group may be linear, branched or C3-6A cycloalkylsulfamoyl group, comprising: methylsulfamoyl, ethylsulfamoyl, n-propylsulfamoyl, i-propylsulfamoyl, c-propylsulfamoyl, n-butylsulfamoyl, i-butylsulfamoyl, s-butylsulfamoyl, t-butylsulfamoyl, c-butylsulfamoyl, 1-methyl-c-propylsulfamoyl, 2-methyl-c-propylsulfamoyl, n-pentylsulfamoyl, 1-methyl-n-butylsulfamoyl, 2-methyl-n-butylsulfamoyl, 3-methyl-n-butylsulfamoyl, 1-dimethyl-n-propylsulfamoyl, 1, 2-dimethyl-n-propylsulfamoyl, 2, 2-dimethyl-n-propylsulfamoyl, 1-ethyl-n-propylsulfamoyl, c-pentylsulfamoyl, 1-methyl-c-butylsulfamoyl, 2-methyl-c-butylsulfamoyl, 3-methyl-c-butylsulfamoyl, 1, 2-dimethyl-c-propylsulfamoyl, 2, 3-dimethyl-c-propylsulfamoyl, 1-ethyl-c-propylsulfamoyl, 2-ethyl-c-propylsulfamoyl, n-hexylsulfamoyl, 1-methyl-n-pentylsulfamoyl, 2-methyl-n-pentylsulfamoyl, 3-methyl-n-pentylsulfamoyl, 1-methyl-n-pentylsulfamoyl, 2-methyl-c-butylsulfamoyl, 3-ethyl-c-butylsulfamoyl, 3-methyl-c-propylsulfamoyl, 4-methyl-n-pentylsulfamoyl, 1-dimethyl-n-butylsulfamoyl, 1, 2-dimethyl-n-butylsulfamoyl, 1, 3-dimethyl-n-butylsulfamoyl, 2-dimethyl-n-butylsulfamoyl Acyl, 2, 3-dimethyl-n-butylsulfamoyl, 3-dimethyl-n-butylsulfamoyl, 1-ethyl-n-butylsulfamoyl, 2-ethyl-n-butylsulfamoyl, 1, 2-trimethyl-n-propylsulfamoyl, 1, 2, 2-trimethyl-n-propylsulfamoyl, 1-ethyl-1-methyl-n-propylsulfamoyl, 1-ethyl-2-methyl-n-propylsulfamoyl, c-hexylsulfamoyl, 1-methyl-c-pentylsulfamoyl, 2-methyl-c-pentylsulfamoyl, 3-methyl-c-pentylsulfamoyl, N-butylsulfamoyl, N-ethylsulfamoyl, N-butylsulfamoyl, N-propylsulfamoyl, N-hexyl, 1-ethyl-c-butylsulfamoyl, 2-ethyl-c-butylsulfamoyl, 3-ethyl-c-butylsulfamoyl, 1, 2-dimethyl-c-butylsulfamoyl, 1, 3-dimethyl-c-butylsulfamoyl, 2-dimethyl-c-butylsulfamoyl, 2, 3-dimethyl-c-butylsulfamoyl, 2, 4-dimethyl-c-butylsulfamoyl, 3-dimethyl-c-butylsulfamoyl, 1-n-propyl-c-propylsulfamoyl, 2-n-propyl-c-propylsulfamoyl, 1-i-propyl-c-propylsulfamoyl, tert-butylsulfamoyl, tert-butyl, 2-i-propyl-c-propylsulfamoyl, 1, 2, 2-trimethyl-c-propylsulfamoyl, 1, 2, 3-trimethyl-c-propylsulfamoyl, 2, 2, 3-trimethyl-c-propylsulfamoyl, 1-ethyl-2-methyl-c-propylsulfamoyl, 2-ethyl-1-methyl-c-propylsulfamoyl, 2-ethyl-2-methyl-c-propylsulfamoyl, 2-ethyl-3-methyl-c-propylsulfamoyl, and the like.
C1-10The alkylsulfamoyl group may be linear, branched or C3-10Cycloalkylsulfonylamino groups, in addition to those groups described above, may include: 1-methyl-1-ethyl-n-pentylsulfamoyl, 1-heptylsulfamoyl, 2-heptylsulfamoyl, 1-ethyl-1, 2-dimethyl-n-propylsulfamoyl, 1-ethyl-2, 2-dimethyl-n-propylsulfamoyl, 1-octylsulfamoyl, 3-octylsulfamoyl, 4-methyl-3-n-heptylsulfamoyl, 6-methyl-2-n-heptylsulfamoyl, 2-propyl-1-n-heptylsulfamoyl, 2, 4, 4-trimethyl-1-n-pentylsulfamoyl, 1-nonylsulfamoyl, 2-nonylsulfamoyl, N-propylsulfamoyl, N-octylsulfamoyl, N-ethylsulfamoyl, N-propylsulfamoyl, N-, 2, 6-dimethyl-4-n-heptylsulfamoyl group, 3-ethyl-2, 2-dimethyl-3-n-pentylsulfamoyl group, 3, 5, 5-trimethyl-1-n-hexylsulfamoyl group, 1-decylsulfamoyl group, 2-decylsulfamoyl group, 4-decylsulfamoyl group3, 7-dimethyl-1-n-octylsulfamoyl group, 3, 7-dimethyl-3-n-octylsulfamoyl group, c-heptylsulfamoyl group, c-octylsulfamoyl group, 1-methyl-c-hexylsulfamoyl group, 2-methyl-c-hexylsulfamoyl group, 3-methyl-c-hexylsulfamoyl group, 1, 2-dimethyl-c-hexylsulfamoyl group, 1-ethyl-c-hexylsulfamoyl group, 1-methyl-c-pentylsulfamoyl group, 2-methyl-c-pentylsulfamoyl group, 3-methyl-c-pentylsulfamoyl group, and the like.
C1-6The alkylsulfonyl group may be linear, branched or C3-6Cycloalkylsulfonyl groups, which may include: methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, i-propylsulfonyl, c-propylsulfonyl, n-butylsulfonyl, i-butylsulfonyl, s-butylsulfonyl, t-butylsulfonyl, c-butylsulfonyl, 1-methyl-c-propylsulfonyl, 2-methyl-c-propylsulfonyl, n-pentylsulfonyl, 1-methyl-n-butylsulfonyl, 2-methyl-n-butylsulfonyl, 3-methyl-n-butylsulfonyl, 1-dimethyl-n-propylsulfonyl, 1, 2-dimethyl-n-propylsulfonyl, 2-dimethyl-n-propylsulfonyl, 1-ethyl-n-propylsulfonyl, c-pentylsulfonyl, 1-methyl-c-butylsulfonyl, 2-methyl-c-butylsulfonyl, 3-methyl-c-butylsulfonyl, 1, 2-dimethyl-c-propylsulfonyl, 2, 3-dimethyl-c-propylsulfonyl, 1-ethyl-c-propylsulfonyl, 2-ethyl-c-propylsulfonyl, n-hexylsulfonyl, 1-methyl-n-pentylsulfonyl, 2-methyl-n-pentylsulfonyl, 3-methyl-n-pentylsulfonyl, 4-methyl-n-pentylsulfonyl, 1-dimethyl-n-butylsulfonyl, n, 1, 2-dimethyl-n-butylsulfonyl group, 1, 3-dimethyl-n-butylsulfonyl group, 2, 2-dimethyl-n-butylsulfonyl group, 2, 3-dimethyl-n-butylsulfonyl group, 3-dimethyl-n-butylsulfonyl group, 1-ethyl-n-butylsulfonyl group, 2-ethyl-n-butylsulfonyl group, 1, 2-trimethyl-n-propylsulfonyl group, 1, 2, 2-trimethyl-n-propylsulfonyl group, 1-ethyl-1-methyl-n-propylsulfonyl group, 1-ethyl-2-methyl-n-propylsulfonyl group, c-hexylsulfonyl group, c-butylsulfonyl group, n-butylsulfonyl group, c-butylsulfonyl group, n-butyl, 1-methyl-c-pentylsulfonyl, 2-methyl-c-pentylsulfonyl, 3-methyl-c-pentylsulfonyl, 1-ethyl-c-butylsulfonyl, 2-ethyl-c-butylsulfonyl, 3-ethyl-c -butylsulfonyl, 1, 2-dimethyl-c-butylsulfonyl, 1, 3-dimethyl-c-butylsulfonyl, 2, 2-dimethyl-c-butylsulfonyl, 2, 3-dimethyl-c-butylsulfonyl, 2, 4-dimethyl-c-butylsulfonyl, 3-dimethyl-c-butylsulfonyl, 1-n-propyl-c-propylsulfonyl, 2-n-propyl-c-propylsulfonyl, 1-i-propyl-c-propylsulfonyl, 2-i-propyl-c-propylsulfonyl, 1, 2, 2-trimethyl-c-propylsulfonyl, n-butylsulfonyl, n, 1, 2, 3-trimethyl-c-propylsulfonyl, 2, 3-trimethyl-c-propylsulfonyl, 1-ethyl-2-methyl-c-propylsulfonyl, 2-ethyl-1-methyl-c-propylsulfonyl, 2-ethyl-2-methyl-c-propylsulfonyl, 2-ethyl-3-methyl-c-propylsulfonyl and the like.
C1-10The alkylsulfonyl group may be linear, branched or C3-10Cycloalkylsulfonyl groups, in addition to those groups described above, include: 1-methyl-1-ethyl-n-pentylsulfonyl, 1-heptylsulfonyl, 2-heptylsulfonyl, 1-ethyl-1, 2-dimethyl-n-propylsulfonyl, 1-ethyl-2, 2-dimethyl-n-propylsulfonyl, 1-octylsulfonyl, 3-octylsulfonyl, 4-methyl-3-n-heptylsulfonyl, 6-methyl-2-n-heptylsulfonyl, 2-propyl-1-n-heptylsulfonyl, 2, 4, 4-trimethyl-1-n-pentylsulfonyl, 1-nonylsulfonyl, 2, 6-dimethyl-4-n-heptylsulfonyl, methyl-ethyl-1-n-propylsulfonyl, 1-octylsulfonyl, 3-octylsulfonyl, 4-methyl-3-n-heptylsulfonyl, 2-methyl-2-n-heptylsulf, 3-ethyl-2, 2-dimethyl-3-n-pentylsulfonyl, 3, 5, 5-trimethyl-1-n-hexylsulfonyl, 1-decylsulfonyl, 2-decylsulfonyl, 4-decylsulfonyl, 3, 7-dimethyl-1-n-octylsulfonyl, 3, 7-dimethyl-3-n-octylsulfonyl, c-heptylsulfonyl, c-octylsulfonyl, 1-methyl-c-hexylsulfonyl, 2-methyl-c-hexylsulfonyl, 3-methyl-c-hexylsulfonyl, 1, 2-dimethyl-c-hexylsulfonyl, 1-ethyl-c-hexylsulfonyl, 1-decylsulfonyl, 2-decylsulfonyl, 3-methyl-c-hexylsulfonyl, 1, 2-dimethyl, 1-methyl-c-pentylsulfonyl, 2-methyl-c-pentylsulfonyl, 3-methyl-c-pentylsulfonyl, and the like.
C1-10The alkoxy group may be linear, branched or C3-10Cycloalkoxy groups, which may include: methoxy, ethoxy, n-propoxy, i-propoxy, c-propoxy, n-butoxy, i-butoxy, s-butoxy,t-butoxy, c-butoxy, 1-methyl-c-propoxy, 2-methyl-c-propoxy, n-pentyloxy, 1-methyl-n-butoxy, 2-methyl-n-butoxy, 3-methyl-n-butoxy, 1-dimethyl-n-propoxy, 1, 2-dimethyl-n-propoxy, 2-dimethyl-n-propoxy, 1-ethyl-n-propoxy, c-pentyloxy, 1-methyl-c-butoxy, 2-methyl-c-butoxy, 3-methyl-c-butoxy, 1, 2-dimethyl-c-propoxy, 2, 3-dimethyl-c-propoxy, 1-ethyl-c-propoxy, 2-ethyl-c-propoxy, n-hexyloxy, 1-methyl-n-pentyloxy, 2-methyl-n-pentyloxy, 3-methyl-n-pentyloxy, 4-methyl-n-pentyloxy, 1-dimethyl-n-butoxy, 1, 2-dimethyl-n-butoxy, 1, 3-dimethyl-n-butoxy, 2-dimethyl-n-butoxy, 2, 3-dimethyl-n-butoxy, 3-dimethyl-n-butoxy, 1-ethyl-n-butoxy, n-propyloxy, n-hexyloxy, 1-methyl-n-pentyloxy, 2-methyl-n-pentyloxy, 4-methyl-n-pentyloxy, 1-, 2-ethyl-n-butoxy, 1, 2-trimethyl-n-propoxy, 1, 2, 2-trimethyl-n-propoxy, 1-ethyl-1-methyl-n-propoxy, 1-ethyl-2-methyl-n-propoxy, c-hexyloxy, 1-methyl-c-pentyloxy, 2-methyl-c-pentyloxy, 3-methyl-c-pentyloxy, 1-ethyl-c-butoxy, 2-ethyl-c-butoxy, 3-ethyl-c-butoxy, 1, 2-dimethyl-c-butoxy, 1, 3-dimethyl-c-butoxy, 1, 2-dimethyl-c-butoxy, 1-methyl-c-butoxy, 1-ethyl-c-propoxy, 1-ethyl-n-propoxy, 1, 2-trimethyl-n-propoxy, 1, 2, 2-trimethyl, 2, 2-dimethyl-c-butoxy, 2, 3-dimethyl-c-butoxy, 2, 4-dimethyl-c-butoxy, 3-dimethyl-c-butoxy, 1-n-propyl-c-propoxy, 2-n-propyl-c-propoxy, 1-i-propyl-c-propoxy, 2-i-propyl-c-propoxy, 1, 2, 2-trimethyl-c-propoxy, 1, 2, 3-trimethyl-c-propoxy, 2, 2, 3-trimethyl-c-propoxy, 1-ethyl-2-methyl-c-propoxy, 2-ethyl-1-methyl-c-propoxy, 2-ethyl-c-propoxy, 2-n-propyl-c, 2-ethyl-2-methyl-c-propoxy, 2-ethyl-3-methyl-c-propoxy, 1-methyl-1-ethyl-n-pentyloxy, 1-heptyloxy, 2-heptyloxy, 1-ethyl-1, 2-dimethyl-n-propoxy, 1-ethyl-2, 2-dimethyl-n-propoxy, 1-octyloxy, 3-octyloxy, 4-methyl-3-n-heptyloxy, 6-methyl-2-n-heptyloxy, 2-propyl-1-n-heptyloxy, 2, 4, 4-trimethyl-1-n-pentyloxy, n-hexyloxy, n, 1-nonyloxy, 2, 6-dimethyl-4-n-heptyloxy, 3-ethyl-2, 2-dimethyl-3-n-pentyloxy, 3, 5, 5-trimethyl-1-n-hexyloxy, 1-decyloxy, 2-decyloxy, 4-decyloxy, 3, 7-decyloxy -dimethyl-1-n-octyloxy group, 3, 7-dimethyl-3-n-octyloxy group and the like.
C1-10The thioalkyl group may be linear, branched or C3-10Thiocycloalkyl groups, which may include: methylthio, ethylthio, n-propylthio, i-propylthio, c-propylthio, n-butylthio, i-butylthio, s-butylthio, t-butylthio, c-butylthio, 1-methyl-c-propylthio, 2-methyl-c-propylthio, n-pentylthio, 1-methyl-n-butylthio, 2-methyl-n-butylthio, 3-methyl-n-butylthio, 1-dimethyl-n-propylthio, 1, 2-dimethyl-n-propylthio, 2-dimethyl-n-propylthio, 1-ethyl-n-propylthio, c-pentylthio, 1-methyl-c-butylthio, 2-methyl-c-butylthio, 3-methyl-c-butylthio, 1, 2-dimethyl-c-propylthio, 2, 3-dimethyl-c-propylthio, 1-ethyl-c-propylthio, 2-ethyl-c-propylthio, n-hexylthio, 1-methyl-n-pentylthio, 2-methyl-n-pentylthio, 3-methyl-n-pentylthio, 4-methyl-n-pentylthio, 1-dimethyl-n-butylthio, 1, 2-dimethyl-n-butylthio, 1, 3-dimethyl-n-butylthio, 2-dimethyl-n-butylthio, n-propylthio, n-hexylthio, n-pentylthio, 1-methyl-n-pentylthio, 3-methyl-n-pentyl, 2, 3-dimethyl-n-butylthio, 3-dimethyl-n-butylthio, 1-ethyl-n-butylthio, 2-ethyl-n-butylthio, 1, 2-trimethyl-n-propylthio, 1, 2, 2-trimethyl-n-propylthio, 1-ethyl-1-methyl-n-propylthio, 1-ethyl-2-methyl-n-propylthio, c-hexylthio, 1-methyl-c-pentylthio, 2-methyl-c-pentylthio, 3-methyl-c-pentylthio, 1-ethyl-c-butylthio, 2-ethyl-c-butylthio, 3-dimethyl-n-butylthio, 1-ethyl-n-butylthio, 1, 2-trimethyl-n-propylthio, 1, 2, 2-trimethyl-c-pentylthio, 1-methyl-c-pentylthio, 3-ethyl-c-butylthio, 1, 2-dimethyl-c-butylthio, 1, 3-dimethyl-c-butylthio, 2, 2-dimethyl-c-butylthio, 2, 3-dimethyl-c-butylthio, 2, 4-dimethyl-c-butylthio, 3-dimethyl-c-butylthio, 1-n-propyl-c-propylthio, 2-n-propyl-c-propylthio, 1-i-propyl-c-propylthio, 2-i-propyl-c-propylthio, 1, 2, 2-trimethyl-c-propylthio, 1, 2, 3-trimethyl-c-propylthio, methyl-ethyl-butyl-thio, methyl-ethyl-c-butylthio, methyl-butyl-thio, methyl-butyl-ethyl-2, 2-dimethyl-c-butylthio, 2, 2, 2, 3-trimethyl-c-propylthio, 1-ethyl-2-methyl-c-propylthio, 2-ethyl-1-methyl-c-propylthio, 2-ethyl-2-methyl-c-propylthio, 2-ethyl-3-methyl-c-propylthio, 1-methyl-1-ethyl-n-pentylthio, 1-heptylthio, 2-heptylthio, 1-ethyl-1, 2-dimethyl-n-propylthio, 1-ethyl-2, 2-dimethyl-n-propylthio N-propylthio, 1-octylthio, 3-octylthio, 4-methyl-3-n-heptylthio, 6-methyl-2-n-heptylthio, 2-propyl-1-n-heptylthio, 2, 4, 4-trimethyl-1-n-pentylthio, 1-nonylthio, 2, 6-dimethyl-4-n-heptylthio, 3-ethyl-2, 2-dimethyl-3-n-pentylthio, 3, 5, 5-trimethyl-1-n-hexylthio, 1-decylthio, 2-decylthio, 4-decylthio, 3, 7-dimethyl-1-n-octylthio, 3-methyl-3-n-heptylthio, 3-methyl-1-n-pentylthio, 1-nonylthio, 2-dimethyl-, 3, 7-dimethyl-3-n-octylthio, and the like.
C1-6The alkoxycarbonyl group can be linear, branched or C3-6Cycloalkoxycarbonyl groups, which may include: methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, i-propoxycarbonyl, c-propoxycarbonyl, n-butoxycarbonyl, i-butoxycarbonyl, s-butoxycarbonyl, t-butoxycarbonyl, c-butoxycarbonyl, 1-methyl-c-propoxycarbonyl, 2-methyl-c-propoxycarbonyl, n-pentoxycarbonyl, 1-methyl-n-butoxycarbonyl, 2-methyl-n-butoxycarbonyl, 3-methyl-n-butoxycarbonyl, 1-dimethyl-n-propoxycarbonyl, 1, 2-dimethyl-n-propoxycarbonyl, 2-dimethyl-n-propoxycarbonyl, 1-ethyl-n-propoxycarbonyl, c-pentoxycarbonyl, 1-methyl-c-butoxycarbonyl, 2-methyl-c-butoxycarbonyl, 3-methyl-c-butoxycarbonyl, 1, 2-dimethyl-c-propoxycarbonyl, 2, 3-dimethyl-c-propoxycarbonyl, 1-ethyl-c-propoxycarbonyl, 2-ethyl-c-propoxycarbonyl, n-hexyloxycarbonyl, 1-methyl-n-pentoxycarbonyl, 2-methyl-n-pentoxycarbonyl, 3-methyl-n-pentoxycarbonyl, 4-methyl-n-pentoxycarbonyl, 1-dimethyl-n-butoxycarbonyl, 1, 2-dimethyl-n-butoxycarbonyl, 1, 3-dimethyl-n-butoxycarbonyl, 2, 2-dimethyl-n-butoxycarbonyl, 2, 3-dimethyl-n-butoxycarbonyl, 3-dimethyl-n-butoxycarbonyl, 1-ethyl-n-butoxycarbonyl, 2-ethyl-n-butoxycarbonyl, 1, 2-trimethyl-n-propoxycarbonyl, 1, 2, 2-trimethyl-n-propoxycarbonyl, 1-ethyl-1-methyl-n-propoxycarbonyl, 1-ethyl-2-methyl-n-propoxycarbonyl, c-hexyloxycarbonyl, n-butyloxycarbonyl, 1-methyl-c-pentyloxycarbonyl, 2-methyl-c-pentyloxycarbonyl, 3-methyl-c-pentyloxycarbonyl, 1-ethyl-c-butoxycarbonyl, 2-ethyl-c-butoxycarbonyl, 3-ethyloxycarbonyl The radical-c-butoxycarbonyl, 1, 2-dimethyl-c-butoxycarbonyl, 1, 3-dimethyl-c-butoxycarbonyl, 2, 2-dimethyl-c-butoxycarbonyl, 2, 3-dimethyl-c-butoxycarbonyl, 2, 4-dimethyl-c-butoxycarbonyl, 3-dimethyl-c-butoxycarbonyl, 1-n-propyl-c-propoxycarbonyl, 2-n-propyl-c-propoxycarbonyl, 1-i-propyl-c-propoxycarbonyl, 2-i-propyl-c-propoxycarbonyl, 1, 2, 2-trimethyl-c-propoxycarbonyl, 1, 2, 3-trimethyl-c-propoxycarbonyl, 2, 3-trimethyl-c-propoxycarbonyl, 1-ethyl-2-methyl-c-propoxycarbonyl, 2-ethyl-1-methyl-c-propoxycarbonyl, 2-ethyl-2-methyl-c-propoxycarbonyl, 2-ethyl-3-methyl-c-propoxycarbonyl, and the like.
C1-10The alkoxycarbonyl group can be linear, branched or C3-10Cycloalkoxycarbonyl, which may include, in addition to those groups described above: 1-methyl-1-ethyl-n-pentyloxycarbonyl, 1-heptyloxycarbonyl, 2-heptyloxycarbonyl, 1-ethyl-1, 2-dimethyl-n-propoxycarbonyl, 1-ethyl-2, 2-dimethyl-n-propoxycarbonyl, 1-octyloxycarbonyl, 3-octyloxycarbonyl, 4-methyl-3-n-heptyloxycarbonyl, 6-methyl-2-n-heptyloxycarbonyl, 2-propyl-1-n-heptyloxycarbonyl, 2, 4, 4-trimethyl-1-n-pentyloxycarbonyl, 1-nonyloxycarbonyl, 2, 6-dimethyl-4-n-heptyloxycarbonyl, n-hexyloxycarbonyl, n, 3-ethyl-2, 2-dimethyl-3-n-pentyloxycarbonyl, 3, 5, 5-trimethyl-1-n-hexyloxycarbonyl, 1-decyloxycarbonyl, 2-decyloxycarbonyl, 4-decyloxycarbonyl, 3, 7-dimethyl-1-n-octyloxycarbonyl, 3, 7-dimethyl-3-n-octyloxycarbonyl and the like.
C1-10The alkylcarbonyloxy group may be linear, branched or C3-10Cycloalkylcarbonyloxy, which may include: methylcarbonyloxy, ethylcarbonyloxy, n-propylcarbonyloxy, i-propylcarbonyloxy, c-propylcarbonyloxy, n-butylcarbonyloxy, i-butylcarbonyloxy, s-butylcarbonyloxy, t-butylcarbonyloxy, c-butylcarbonyloxy, 1-methyl-c-propylcarbonyloxy, 2-methyl-c-propylcarbonyloxy, n-pentylcarbonyloxy, 1-methyl-n-butylcarbonyloxy, 2-methyl-n-butylcarbonyloxy, 3-methyl-n-butylcarbonyloxy, 1,1-dimethyl-n-propylcarbonyloxy, 1, 2-dimethyl-n-propylcarbonyloxy, 2-dimethyl-n-propylcarbonyloxy, 1-ethyl-n-propylcarbonyloxy, c-pentylcarbonyloxy, 1-methyl-c-butylcarbonyloxy, 2-methyl-c-butylcarbonyloxy, 3-methyl-c-butylcarbonyloxy, 1, 2-dimethyl-c-propylcarbonyloxy, 2, 3-dimethyl-c-propylcarbonyloxy, 1-ethyl-c-propylcarbonyloxy, 2-ethyl-c-propylcarbonyloxy, n-hexylcarbonyloxy, 1-methyl-n-pentylcarbonyloxy, m-ethylcarbonyloxy, n-butylcarbonyloxy, n-ethyl, 2-methyl-n-pentylcarbonyloxy, 3-methyl-n-pentylcarbonyloxy, 4-methyl-n-pentylcarbonyloxy, 1-dimethyl-n-butylcarbonyloxy, 1, 2-dimethyl-n-butylcarbonyloxy, 1, 3-dimethyl-n-butylcarbonyloxy, 2, 2-dimethyl-n-butylcarbonyloxy, 2, 3-dimethyl-n-butylcarbonyloxy, 3-dimethyl-n-butylcarbonyloxy, 1-ethyl-n-butylcarbonyloxy, 2-ethyl-n-butylcarbonyloxy, 1, 2-trimethyl-n-propylcarbonyloxy, 1, 2, 2-trimethyl-n-propylcarbonyloxy, 2-methyl-n-pentylcarbonyloxy, 4-methyl-n-pentylcarbonyloxy, 1-dimethyl-n-butylcarbonyloxy, 1, 2-dimethyl-n-butylcarbonyloxy, 1, 3-dimethyl-n, 1-ethyl-1-methyl-n-propylcarbonyloxy, 1-ethyl-2-methyl-n-propylcarbonyloxy, c-hexylcarbonyloxy, 1-methyl-c-pentylcarbonyloxy, 2-methyl-c-pentylcarbonyloxy, 3-methyl-c-pentylcarbonyloxy, 1-ethyl-c-butylcarbonyloxy, 2-ethyl-c-butylcarbonyloxy, 3-ethyl-c-butylcarbonyloxy, 1, 2-dimethyl-c-butylcarbonyloxy, 1, 3-dimethyl-c-butylcarbonyloxy, 2-dimethyl-c-butylcarbonyloxy, 2, 3-dimethyl-c-butylcarbonyloxy, 2, 4-dimethyl-c-butylcarbonyloxy, 3-dimethyl-c-butylcarbonyloxy, 1-n-propyl-c-propylcarbonyloxy, 2-n-propyl-c-propylcarbonyloxy, 1-i-propyl-c-propylcarbonyloxy, 2-i-propyl-c-propylcarbonyloxy, 1, 2, 2-trimethyl-c-propylcarbonyloxy, 1, 2, 3-trimethyl-c-propylcarbonyloxy, 2, 2, 3-trimethyl-c-propylcarbonyloxy, 1-ethyl-2-methyl-c-propylcarbonyloxy, 2-ethyl-1-methyl-c-propylcarbonyloxy, 2-dimethyl-c-butylcarbonyloxy, 1-n-propyl-c-propylcarbonyloxy, 2-n-propyl-butylcarbonyloxy, 2-ethyl-c-propyl, 2-ethyl-2-methyl-c-propylcarbonyloxy, 2-ethyl-3-methyl-c-propylcarbonyloxy, 1-methyl-1-ethyl-n-pentylcarbonyloxy, 1-heptylcarbonyloxy, 2-heptylcarbonyloxy, 1-ethyl-1, 2-dimethyl-n-propylcarbonyloxy, 1-ethyl-2, 2-dimethyl-n-propylcarbonyloxy, 1-octylcarbonyloxy, 3-octylcarbonyloxy, 4-methyl-3-n-heptylcarbonyloxy, 6-methyl-2-n-heptylcarbonyloxy, 2-propyl-1-n-heptylcarbonyloxy, 2, 4, 4-trimethyl-1-n-pentylcarbonyloxy, 1-nonylcarbonyloxy, 2, 6-dimethyl-4-n-heptylcarbonyloxy, 3-ethyl-2, 2-dimethyl-3-n-pentylcarbonyloxy, 3, 5, 5-trimethyl-1-n-hexylcarbonyloxy, 1-decylcarbonyloxy, 2-decylcarbonyloxy, 4-decylcarbonyloxy, 3, 7-dimethyl-1-n-octylcarbonyloxy, 3, 7-dimethyl-3-n-octylcarbonyloxy and the like.
C1-10The alkylcarbonylamino group may be linear, branched or C3-10Cycloalkylcarbonylamino groups which may be mentioned include methylcarbonylamino, ethylcarbonylamino, n-propylcarbonylamino, i-propylcarbonylamino, c-propylcarbonylamino, n-butylcarbonylamino, i-butylcarbonylamino, s-butylcarbonylamino, t-butylcarbonylamino, c-butylcarbonylamino, 1-methyl-c-propylcarbonylamino, 2-methyl-c-propylcarbonylamino, n-pentylcarbonylamino, 1-methyl-n-butylcarbonylamino, 2-methyl-n-butylcarbonylamino, 3-methyl-n-butylcarbonylamino, 1-dimethyl-n-propylcarbonylamino, 1, 2-dimethyl-n-propylcarbonylamino, t-butylcarbonylamino, 2, 2-dimethyl-n-propylcarbonylamino, 1-ethyl-n-propylcarbonylamino, c-pentylcarbonylamino, 1-methyl-c-butylcarbonylamino, 2-methyl-c-butylcarbonylamino, 3-methyl-c-butylcarbonylamino, 1, 2-dimethyl-c-propylcarbonylamino, 2, 3-dimethyl-c-propylcarbonylamino, 1-ethyl-c-propylcarbonylamino, 2-ethyl-c-propylcarbonylamino, n-hexylcarbonylamino, 1-methyl-n-pentylcarbonylamino, 2-methyl-n-pentylcarbonylamino, 3-methyl-n-pentylcarbonylamino, 2-methyl-c-butylcarbonylamino, 3, 4-methyl-n-pentylcarbonylamino, 1-dimethyl-n-butylcarbonylamino, 1, 2-dimethyl-n-butylcarbonylamino, 1, 3-dimethyl-n-butylcarbonylamino, 2, 2-dimethyl-n-butylcarbonylamino, 2, 3-dimethyl-n-butylcarbonylamino, 3-dimethyl-n-butylcarbonylamino, 1-ethyl-n-butylcarbonylamino, 2-ethyl-n-butylcarbonylamino, 1, 2-trimethyl-n-propylcarbonylamino, 1, 2, 2-trimethyl-n-propylcarbonylamino, 1-ethyl-1-methyl-n-propylcarbonylamino, 1-dimethyl-n-butylcarbonylamino, 1, 2-dimethyl-n-butylcarbonylamino, 2, 3-dimethyl-n-butylcarbonylamino, 1, 3-ethyl-n-butylcarbonylamino, 2-ethyl, 1-ethyl-2-methyl-n-propylcarbonylamino, c-hexylcarbonylamino, 1-methyl-c-pentylcarbonylamino, 2-methyl-c-pentylcarbonylamino, 3-methyl The group-c-pentylcarbonylamino, 1-ethyl-c-butylcarbonylamino, 2-ethyl-c-butylcarbonylamino, 3-ethyl-c-butylcarbonylamino, 1, 2-dimethyl-c-butylcarbonylamino, 1, 3-dimethyl-c-butylcarbonylamino, 2-dimethyl-c-butylcarbonylamino, 2, 3-dimethyl-c-butylcarbonylamino, 2, 4-dimethyl-c-butylcarbonylamino, 3-dimethyl-c-butylcarbonylamino, 1-n-propyl-c-propylcarbonylamino, 2-n-propyl-c-propylcarbonylamino, 1-i-propyl-c-propylcarbonylamino, 2-i-propyl-c-propylcarbonylamino, 1, 2, 2-trimethyl-c-propyl-carbonylamino, 1, 2, 3-trimethyl-c-propylcarbonylamino, 2, 2, 3-trimethyl-c-propylcarbonylamino, 1-ethyl-2-methyl-c-propylcarbonylamino, 2-ethyl-1-methyl-c-propylcarbonylamino, 2-ethyl-2-methyl-c-propylcarbonylamino, 2-ethyl-3-methyl-c-propylcarbonylamino, 1-methyl-1-ethyl-n-pentylcarbonylamino, 2-methyl-c-propylcarbonylamino, 1-methyl-n-pentylcarbonylamino, 2, 1-heptylcarbonylamino, 2-heptylcarbonylamino, 1-ethyl-1, 2-dimethyl-n-propylcarbonylamino, 1-ethyl-2, 2-dimethyl-n-propylcarbonylamino, 1-octylcarbonylamino, 3-octylcarbonylamino, 4-methyl-3-n-heptylcarbonylamino, 6-methyl-2-n-heptylcarbonylamino, 2-propyl-1-n-heptylcarbonylamino, 2, 4, 4-trimethyl-1-n-pentylcarbonylamino, 1-nonylcarbonylamino, 2, 6-dimethyl-4-n-heptylcarbonylamino, 2-ethylcarbonylamino, 2, 3-ethyl-2, 2-dimethyl-3-n-pentylcarbonylamino, 3, 5, 5-trimethyl-1-n-hexylcarbonylamino, 1-decylcarbonylamino, 2-decylcarbonylamino, 4-decylcarbonylamino, 3, 7-dimethyl-1-n-octylcarbonylamino, 3, 7-dimethyl-3-n-octylcarbonylamino and the like.
C1-10The alkylaminocarbonyl radical may be C1-10Monoalkylaminocarbonyl or C1-10A dialkylaminocarbonyl group. C1-10The monoalkylaminocarbonyl group may be linear, branched or C3-10Cycloalkylaminocarbonyl groups, which may include: methylaminocarbonyl, ethylaminocarbonyl, n-propylaminocarbonyl, i-propylaminocarbonyl, c-propylaminocarbonyl, n-butylaminocarbonyl, i-butylaminocarbonyl, s-butylaminocarbonyl, t-butylaminocarbonyl, c-butylaminocarbonyl, 1-methyl-c-propylAlkylaminocarbonyl, 2-methyl-c-propylaminocarbonyl, n-pentylaminocarbonyl, 1-methyl-n-butylaminocarbonyl, 2-methyl-n-butylaminocarbonyl, 3-methyl-n-butylaminocarbonyl, 1-dimethyl-n-propylaminocarbonyl, 1, 2-dimethyl-n-propylaminocarbonyl, 2-dimethyl-n-propylaminocarbonyl, 1-ethyl-n-propylaminocarbonyl, c-pentylaminocarbonyl, 1-methyl-c-butylaminocarbonyl, 2-methyl-c-butylaminocarbonyl, 3-methyl-c-butylaminocarbonyl, 1, 2-dimethyl-c-propylaminocarbonyl, 2, 3-dimethyl-c-propylaminocarbonyl, 1-ethyl-c-propylaminocarbonyl, 2-ethyl-c-propylaminocarbonyl, n-hexylaminocarbonyl, 1-methyl-n-pentylaminocarbonyl, 2-methyl-n-pentylaminocarbonyl, 3-methyl-n-pentylaminocarbonyl, 4-methyl-n-pentylaminocarbonyl, 1-dimethyl-n-butylaminocarbonyl, 1, 2-dimethyl-n-butylaminocarbonyl, 1, 3-dimethyl-n-butylaminocarbonyl, 2-dimethyl-n-butylaminocarbonyl, 2, 3-dimethyl-n-butylaminocarbonyl, 3-dimethyl-n-butylaminocarbonyl, 1-ethyl-n-butylaminocarbonyl, 2-ethyl-n-butylaminocarbonyl, 1, 2-trimethyl-n-propylaminocarbonyl, 1, 2, 2-trimethyl-n-propylaminocarbonyl, 1-ethyl-1-methyl-n-propylaminocarbonyl, 1-ethyl-2-methyl-n-propylaminocarbonyl, c-hexylaminocarbonyl, 1-methyl-c-pentylaminocarbonyl, 2-methyl-c-pentylaminocarbonyl, 3-methyl-c-pentylaminocarbonyl, 1-ethyl-c-butylaminocarbonyl, 2-ethyl-c-butylaminocarbonyl, 3-ethyl-c-butylaminocarbonyl, 1, 2-dimethyl-c-butylaminocarbonyl, 1, 3-dimethyl-c-butylaminocarbonyl, 2-dimethyl-c-butylaminocarbonyl, 2, 3-dimethyl-c-butylaminocarbonyl, 2, 4-dimethyl-c-butylaminocarbonyl, 3-dimethyl-c-butylaminocarbonyl, 1-n-propyl-c-propylaminocarbonyl, 2-n-propyl-c-propylaminocarbonyl, 1-i-propyl-c-propylaminocarbonyl, methyl-ethyl-c-butylaminocarbonyl, 2-dimethyl-c-butylaminocarbonyl, 2, 3-dimethyl-c-butyla, 2-i-propyl-c-propylaminocarbonyl, 1, 2, 2-trimethyl-c-propylaminocarbonyl, 1, 2, 3-trimethyl-c-propylaminocarbonyl, 2, 2, 3-trimethyl-c-propylaminocarbonyl, 1-ethyl-2-methyl-c-propylaminocarbonyl, 2-ethyl-1-methyl-c-propylaminocarbonyl, 2-ethyl-2-methyl-c-propylaminocarbonyl, 2-ethyl-3-methyl-propyl-aminocarbonyl -c-propylaminocarbonyl, 1-methyl-1-ethyl-n-pentylaminocarbonyl, 1-heptylaminocarbonyl, 2-heptylaminocarbonyl, 1-ethyl-1, 2-dimethyl-n-propylaminocarbonyl, 1-ethyl-2, 2-dimethyl-n-propylaminocarbonyl, 1-octylaminocarbonyl, 3-octylaminocarbonyl, 4-methyl-3-n-heptylaminocarbonyl, 6-methyl-2-n-heptylaminocarbonyl, 2-propyl-1-n-heptylaminocarbonyl, 2, 4, 4-trimethyl-1-n-pentylaminocarbonyl, 1-nonylaminocarbonyl, methyl-1-n-pentylaminocarbonyl, methyl-1-2-n-pentylaminocarbonyl, methyl-1-n-, 2-nonylaminocarbonyl group, 2, 6-dimethyl-4-n-heptylaminocarbonyl group, 3-ethyl-2, 2-dimethyl-3-n-pentylaminocarbonyl group, 3, 5, 5-trimethyl-1-n-hexylaminocarbonyl group, 1-decylaminocarbonyl group, 2-decylaminocarbonyl group, 4-decylaminocarbonyl group, 3, 7-dimethyl-1-n-octylaminocarbonyl group, 3, 7-dimethyl-3-n-octylaminocarbonyl group and the like.
C1-10The dialkylaminocarbonyl groups can be symmetrical or asymmetrical. Symmetry C1-10The dialkylaminocarbonyl group may be linear, branched or C3-10Cycloalkylaminocarbonyl groups, which may include: dimethylaminocarbonyl, diethylaminocarbonyl, di-n-propylaminocarbonyl, di-i-propylaminocarbonyl, di-c-propylaminocarbonyl, di-n-butylaminocarbonyl, di-i-butylaminocarbonyl, di-s-butylaminocarbonyl, di-t-butylaminocarbonyl, di-c-butylaminocarbonyl, di- (1-methyl-c-propyl) aminocarbonyl, di- (2-methyl-c-propyl) aminocarbonyl, di-n-pentylaminocarbonyl, di- (1-methyl-n-butyl) aminocarbonyl, di- (2-methyl-n-butyl) aminocarbonyl, di- (3-methyl-n-butyl) aminocarbonyl, di-n-butylaminocarbonyl, di- (2, Bis- (1, 1-dimethyl-n-propyl) aminocarbonyl, bis- (1, 2-dimethyl-n-propyl) aminocarbonyl, bis- (2, 2-dimethyl-n-propyl) aminocarbonyl, bis- (1-ethyl-n-propyl) aminocarbonyl, bis-c-pentylaminocarbonyl, bis- (1-methyl-c-butyl) aminocarbonyl, bis- (2-methyl-c-butyl) aminocarbonyl, bis- (3-methyl-c-butyl) aminocarbonyl, bis- (1, 2-dimethyl-c-propyl) aminocarbonyl, bis- (2, 3-dimethyl-c-propyl) aminocarbonyl, Bis- (1-ethyl-c-propyl) aminocarbonyl, bis- (2-ethyl-c-propyl) aminocarbonyl, di-n-hexylaminocarbonyl, bis- (1-methyl-n-pentyl) aminocarbonyl, bis- (2-methyl-n-pentyl) aminocarbonyl -pentyl) aminocarbonyl, bis- (3-methyl-n-pentyl) aminocarbonyl, bis- (4-methyl-n-pentyl) aminocarbonyl, bis- (1, 1-dimethyl-n-butyl) aminocarbonyl, bis- (1, 2-dimethyl-n-butyl) aminocarbonyl, bis- (1, 3-dimethyl-n-butyl) aminocarbonyl, bis- (2, 2-dimethyl-n-butyl) aminocarbonyl, bis- (2, 3-dimethyl-n-butyl) aminocarbonyl, bis- (3, 3-dimethyl-n-butyl) aminocarbonyl, bis- (1-ethyl-n-butyl) aminocarbonyl, di- (1-methyl-n-butyl) aminocarbonyl, di- (2, 3-dimethyl-n-butyl) aminocarbonyl, di- (1-ethyl-n-butyl) aminocarbonyl, di- (2, 3-dimethyl-n-, Bis- (2-ethyl-n-butyl) aminocarbonyl, bis- (1, 1, 2-trimethyl-n-propyl) aminocarbonyl, bis- (1, 2, 2-trimethyl-n-propyl) aminocarbonyl, bis- (1-ethyl-1-methyl-n-propyl) aminocarbonyl, bis- (1-ethyl-2-methyl-n-propyl) aminocarbonyl, bis-c-hexylaminocarbonyl, bis- (1-methyl-c-pentyl) aminocarbonyl, bis- (2-methyl-c-pentyl) aminocarbonyl, bis- (3-methyl-c-pentyl) aminocarbonyl, bis- (1-ethyl-c-butyl) aminocarbonyl, di- (1-methyl-n-propyl) aminocarbonyl, Bis- (2-ethyl-c-butyl) aminocarbonyl, bis- (3-ethyl-c-butyl) aminocarbonyl, bis- (1, 2-dimethyl-c-butyl) aminocarbonyl, bis- (1, 3-dimethyl-c-butyl) aminocarbonyl, bis- (2, 2-dimethyl-c-butyl) aminocarbonyl, bis- (2, 3-dimethyl-c-butyl) aminocarbonyl, bis- (2, 4-dimethyl-c-butyl) aminocarbonyl, bis- (3, 3-dimethyl-c-butyl) aminocarbonyl, bis- (1-n-propyl-c-propyl) aminocarbonyl, bis- (2-n-propyl-c-propyl) aminocarbonyl, di- (3-dimethyl-c-butyl) aminocarbonyl, di- (2-n-propyl-c-, Bis- (1-i-propyl-c-propyl) aminocarbonyl, bis- (2-i-propyl-c-propyl) aminocarbonyl, bis- (1, 2, 2-trimethyl-c-propyl) aminocarbonyl, bis- (1, 2, 3-trimethyl-c-propyl) aminocarbonyl, bis- (2, 2, 3-trimethyl-c-propyl) aminocarbonyl, bis- (1-ethyl-2-methyl-c-propyl) aminocarbonyl, bis- (2-ethyl-1-methyl-c-propyl) aminocarbonyl, bis- (2-ethyl-2-methyl-c-propyl) aminocarbonyl, di- (2-, Bis- (2-ethyl-3-methyl-c-propyl) aminocarbonyl, bis- (1-methyl-1-ethyl-n-pentyl) aminocarbonyl, bis- (1-heptyl) aminocarbonyl, bis- (2-heptyl) aminocarbonyl, bis- (1-ethyl-1, 2-dimethyl-n-propyl) aminocarbonyl, bis- (1-ethyl-2, 2-dimethyl-n-propyl) aminocarbonyl, bis- (1-octyl) aminocarbonyl, bis- (3-octyl) aminocarbonyl, bis- (4-methyl-3-n-heptyl) aminocarbonyl, bis- (6-methyl-2-n-heptyl) aminocarbonyl, di- (2-methyl-n-heptyl) aminocarbonyl, di- (1-octyl) aminocarbonyl, di- (3-octyl) aminocarbonyl, di- (4-methyl-3-n-heptyl, Di- (2-propyl-1-n-heptyl) aminocarbonyl, Bis- (2, 4, 4-trimethyl-1-n-pentyl) aminocarbonyl, bis- (1-nonyl) aminocarbonyl, bis- (2, 6-dimethyl-4-n-heptyl) aminocarbonyl, bis- (3-ethyl-2, 2-dimethyl-3-n-pentyl) aminocarbonyl, bis- (3, 5, 5-trimethyl-1-n-hexyl) aminocarbonyl, bis- (1-decyl) aminocarbonyl, bis- (2-decyl) aminocarbonyl, bis- (4-decyl) aminocarbonyl, bis- (3, 7-dimethyl-1-n-octyl) aminocarbonyl, di- (2-nonyl) aminocarbonyl, di- (3-ethyl-2, 2-dimethyl-3-n-pentyl) aminocarbonyl, di- (3, 5, 5-trimethyl-1-n-hexyl) aminocarbonyl, di- (, Bis- (3, 7-dimethyl-3-n-octyl) aminocarbonyl, and the like.
Asymmetric C1-10The dialkylaminocarbonyl group may be linear, branched or C3-10Cycloalkylaminocarbonyl groups, which may include: (methyl, ethyl) aminocarbonyl, (methyl, n-propyl) aminocarbonyl, (methyl, i-propyl) aminocarbonyl, (methyl, c-propyl) aminocarbonyl, (methyl, n-butyl) aminocarbonyl, (methyl, i-butyl) aminocarbonyl, (methyl, s-butyl) aminocarbonyl, (methyl, t-butyl) aminocarbonyl, (methyl, n-pentyl) aminocarbonyl, (methyl, c-pentyl) aminocarbonyl, (methyl, n-hexyl) aminocarbonyl, (methyl, c-hexyl) aminocarbonyl, (ethyl, n-propyl) aminocarbonyl, (ethyl, i-propyl) aminocarbonyl, (ethyl, c-propyl) aminocarbonyl, (ethyl, n-butyl) aminocarbonyl, (ethyl, i-butyl) aminocarbonyl, methyl, n-butyl) aminocarbonyl, (ethyl, s-butyl) aminocarbonyl, (ethyl, t-butyl) aminocarbonyl, (ethyl, n-pentyl) aminocarbonyl, (ethyl, c-pentyl) aminocarbonyl, (ethyl, n-hexyl) aminocarbonyl, (ethyl, c-hexyl) aminocarbonyl, (n-propyl, i-propyl) aminocarbonyl, (n-propyl, c-propyl) aminocarbonyl, (n-propyl, n-butyl) aminocarbonyl, (n-propyl, i-butyl) aminocarbonyl, (n-propyl, s-butyl) aminocarbonyl, (n-propyl, t-butyl) aminocarbonyl, (n-propyl, n-pentyl) aminocarbonyl, (n-propyl, c-pentyl) aminocarbonyl, (n-propyl, n-hexyl) aminocarbonyl, (n-propyl, c-hexyl) aminocarbonyl, (i-propyl, c-propyl) aminocarbonyl, (i-propyl, n-butyl) aminocarbonyl, (i-propyl, i-butyl) aminocarbonyl, (i-propyl, s-butyl) aminocarbonyl, (i-propyl, t-butyl) aminocarbonyl, (i-propyl, n-pentyl) aminocarbonyl, (i-propyl, c-pentyl) aminocarbonyl, (i-propyl, n-hexyl) aminocarbonyl, (i-propyl, c-hexyl) aminocarbonyl, (c-propyl, n-butyl) aminocarbonyl, (c-propyl, i-butyl) aminocarbonyl, (c-propyl, s-butyl) aminocarbonyl, (c-propyl, t-butyl) aminocarbonyl, (c-propyl, n-pentyl) aminocarbonyl, (c-propyl, c-pentyl) aminocarbonyl, (c-propyl, n-hexyl) aminocarbonyl, (c-propyl, c-hexyl) aminocarbonyl, (n-butyl, i-butyl) aminocarbonyl, (n-butyl, s-butyl) aminocarbonyl, (n-butyl, t-butyl) aminocarbonyl, (n-butyl, n-pentyl) aminocarbonyl, (n-butyl, c-pentyl) aminocarbonyl, (n-butyl, n-hexyl) aminocarbonyl, (n-butyl, c-hexyl) aminocarbonyl, (i-butyl, s-butyl) aminocarbonyl, (i-butyl, t-butyl) aminocarbonyl, (i-butyl, n-pentyl) aminocarbonyl, (i-butyl, c-pentyl) aminocarbonyl, (i-butyl, n-hexyl) aminocarbonyl, (i-butyl, c-hexyl) aminocarbonyl, (s-butyl, t-butyl) aminocarbonyl, (s-butyl, n-pentyl) aminocarbonyl, (s-butyl, c-pentyl) aminocarbonyl, (s-butyl, n-hexyl) aminocarbonyl, (s-butyl, c-hexyl) aminocarbonyl, (t-butyl, n-pentyl) aminocarbonyl, (t-butyl, c-pentyl) aminocarbonyl, (t-butyl, n-hexyl) aminocarbonyl, (t-butyl, c-hexyl) aminocarbonyl, (n-pentyl, c-pentyl) aminocarbonyl, (n-pentyl, n-hexyl) aminocarbonyl, (n-pentyl, c-hexyl) aminocarbonyl, (c-pentyl, n-hexyl) aminocarbonyl, (c-pentyl, c-hexyl) aminocarbonyl, (n-hexyl, c-hexyl) aminocarbonyl, (methyl, n-heptyl) aminocarbonyl, (methyl, n-octyl) aminocarbonyl, n-hexyl) aminocarbonyl, (n-pentyl ) aminocarbonyl, n-pentyl, c-hexyl) aminocarbonyl, (methyl, n-nonyl) aminocarbonyl, (methyl, n-decyl) aminocarbonyl, (methyl, n-heptyl) aminocarbonyl, (ethyl, n-octyl) aminocarbonyl, (ethyl, n-nonyl) aminocarbonyl, (ethyl, n-decyl) aminocarbonyl, and the like.
C1-10The monoalkylamino group may be linear, branched or C3-10Cycloalkylamino groups, which may include: methylamino, ethylamino, n-propylamino, i-propylamino, c-propylamino, n-butylamino, i-butylamino, s-butylamino, t-butylamino, c-butylamino, 1-methyl-c-propylamino, 2-methyl-c-propylamino, n-pentylamino, 1-methylamino-n-butylamino, 2-methyl-n-butylamino, 3-methyl-n-butylamino, 1-dimethyl-n-propylamino, 1, 2-dimethyl-n-propylamino, 2-dimethyl-n-propylamino, 1-ethyl-n-propylamino, c-pentylamino, 1-methyl-c-butylamino, 2-methyl-c-butylamino, 3-methyl-c-butylamino, 1, 2-dimethyl-c-propylamino, 2, 3-dimethyl-c-propylamino, 1-ethyl-c-propylamino, 2-ethyl-c-propylamino, n-hexylamino group, 1-methyl-n-pentylamino group, 2-methyl-n-pentylamino group, 3-methyl-n-pentylamino group, 4-methyl-n-pentylamino group, 1-dimethyl-n-butylamino group, 1, 2-dimethyl-n-butylamino group, 1, 3-dimethyl-n-butylamino group, 2-dimethyl-n-butylamino group, 2, 3-dimethyl-n-butylamino group, 3-dimethyl-n-butylamino group, 1-ethyl-n-butylamino group, 2-ethyl-n-butylamino group, 1, 2-trimethyl-n-propylamino group, N-butylamino group, N, 1, 2, 2-trimethyl-n-propylamino, 1-ethyl-1-methyl-n-propylamino, 1-ethyl-2-methyl-n-propylamino, c-hexylamino, 1-methyl-c-pentylamino, 2-methyl-c-pentylamino, 3-methyl-c-pentylamino, 1-ethyl-c-butylamino, 2-ethyl-c-butylamino, 3-ethyl-c-butylamino, 1, 2-dimethyl-c-butylamino, 1, 3-dimethyl-c-butylamino, 2, 2-dimethyl-c-butylamino, N-methyl-n-propylamino, N-propyl-amino, N-methyl-c-pentylamino, N-pentyl-amino, N-pentyl, 2, 3-dimethyl-c-butylamino, 2, 4-dimethyl-c-butylamino, 3-dimethyl-c-butylamino, 1-n-propyl-c-propylamino, 2-n-propyl-c-propylamino, 1-i-propyl-c-propylamino, 2-i-propyl-c-propylamino, 1, 2, 2-trimethyl-c-propylamino, 1, 2, 3-trimethyl-c-propylamino, 2, 2, 3-trimethyl-c-propylamino, 1-ethyl-2-methyl-c-propylamino, 2-ethyl-1-methyl-c-propylamino, 2-ethyl-2-methyl-c-propylamino, 2-ethyl-3-methyl-c-propylamino, 1-methyl-1-ethyl-n-pentylamino, 1-heptylamino, 2-heptylamino, 1-ethyl-1, 2-dimethyl-n-propylamino, 1-ethyl-2, 2-dimethyl-n-propylamino, 1-octylamino, 3-octylamino, 4-methyl-3-n-heptylamino, 6-methyl-2-n-heptylamino, 2-propyl-1-n-heptylamino, 2, 4, 4-trimethyl-1-n-pentylamino, p-propylamino, p-methyl-1-n-propylamino, p-1-methyl-, 1-nonyl amino group, 2, 6-dimethyl-4-n-heptyl amino group, 3-ethyl-2 2-dimethyl-3-n-pentylamino group, 3, 5, 5-trimethyl-1-n-hexylamino group, 1-decylamino group, 2-decylamino group, 4-decylamino group, 3, 7-dimethyl-1-n-octylamino group, 3, 7-dimethyl-3-n-octylamino group and the like.
C1-10The dialkylamino group can be symmetric or asymmetric. Symmetry C1-10The dialkylamino group can be linear, branched or C3-10Cycloalkylamino groups, which may include: dimethylamino group, diethylamino group, di-n-propylamino group, di-i-propylamino group, di-c-propylamino group, di-n-butylamino group, di-i-butylamino group, di-s-butylamino group, di-t-butylamino group, di-c-butylamino group, di- (1-methyl-c-propyl) amino group, di- (2-methyl-c-propyl) amino group, di-n-pentylamino group, di- (1-methyl-n-butyl) amino group, di- (2-methyl-n-butyl) amino group, di- (3-methyl-n-butyl) amino group, di- (1, 1-dimethyl-n-propyl) amino group, di-n-propylamino group, di-c-propylamino group, di-n, Bis- (1, 2-dimethyl-n-propyl) amino, bis- (2, 2-dimethyl-n-propyl) amino, bis- (1-ethyl-n-propyl) amino, bis-c-pentylamino, bis- (1-methyl-c-butyl) amino, bis- (2-methyl-c-butyl) amino, bis- (3-methyl-c-butyl) amino, bis- (1, 2-dimethyl-c-propyl) amino, bis- (2, 3-dimethyl-c-propyl) amino, bis- (1-ethyl-c-propyl) amino, bis- (2-ethyl-c-propyl) amino, Di-n-hexylamino, di- (1-methyl-n-pentyl) amino, di- (2-methyl-n-pentyl) amino, di- (3-methyl-n-pentyl) amino, di- (4-methyl-n-pentyl) amino, di- (1, 1-dimethyl-n-butyl) amino, di- (1, 2-dimethyl-n-butyl) amino, di- (1, 3-dimethyl-n-butyl) amino, di- (2, 2-dimethyl-n-butyl) amino, di- (2, 3-dimethyl-n-butyl) amino, di- (3, 3-dimethyl-n-butyl) amino, di- (2-methyl-n-pentyl) amino, Bis- (1-ethyl-n-butyl) amino, bis- (2-ethyl-n-butyl) amino, bis- (1, 1, 2-trimethyl-n-propyl) amino, bis- (1, 2, 2-trimethyl-n-propyl) amino, bis- (1-ethyl-1-methyl-n-propyl) amino, bis- (1-ethyl-2-methyl-n-propyl) amino, bis-c-hexylamino, bis- (1-methyl-c-pentyl) amino, bis- (2-methyl-c-pentyl) amino, bis- (3-methyl-c-pentyl) amino, di-n-propyl-amino, di- (1-ethyl-2-methyl-n-propyl) amino, di-c-hexylamino, di- (1-methyl-c-pentyl) amino, di- (2-methyl-c-, Di- (1-ethyl-c-butyl) amino, di- (2-ethyl-c-butyl) amino, di- (3-ethyl) -c-butyl) amino, di- (1, 2-dimethyl-c-butyl) amino, di- (1, 3-dimethyl-c-butyl) amino, di- (2, 2-dimethyl-c-butyl) amino, di- (2, 3-dimethyl-c-butyl) amino, di- (2, 4-dimethyl-c-butyl) amino, di- (3, 3-dimethyl-c-butyl) amino, di- (1-n-propyl-c-propyl) amino, di- (2-n-propyl-c-propyl) amino, di- (1-i-propyl-c-propyl) amino, di- (2-n-propyl-c-butyl) amino, di- (2-n-butyl-c, Bis- (2-i-propyl-c-propyl) amino, bis- (1, 2, 2-trimethyl-c-propyl) amino, bis- (1, 2, 3-trimethyl-c-propyl) amino, bis- (2, 2, 3-trimethyl-c-propyl) amino, bis- (1-ethyl-2-methyl-c-propyl) amino, bis- (2-ethyl-1-methyl-c-propyl) amino, bis- (2-ethyl-2-methyl-c-propyl) amino, bis- (2-ethyl-3-methyl-c-propyl) amino, bis- (1-methyl-1-ethyl-n-pentyl) amino, di- (2-ethyl-3-methyl-c-propyl) amino, di- (1-methyl-1-ethyl-n-pentyl) amino, Bis- (1-heptyl) amino, bis- (2-heptyl) amino, bis- (1-ethyl-1, 2-dimethyl-n-propyl) amino, bis- (1-ethyl-2, 2-dimethyl-n-propyl) amino, bis- (1-octyl) amino, bis- (3-octyl) amino, bis- (4-methyl-3-n-heptyl) amino, bis- (6-methyl-2-n-heptyl) amino, bis- (2-propyl-1-n-heptyl) amino, bis- (2, 4, 4-trimethyl-1-n-pentyl) amino, bis- (1-nonyl) amino, di- (2-heptyl) amino, di- (1-octyl) amino, di- (4-methyl-3-n-heptyl) amino, di- (2-propyl-1-n-heptyl) amino, Di- (2-nonyl) amino, di- (2, 6-dimethyl-4-n-heptyl) amino, di- (3-ethyl-2, 2-dimethyl-3-n-pentyl) amino, di- (3, 5, 5-trimethyl-1-n-hexyl) amino, di- (1-decyl) amino, di- (2-decyl) amino, di- (4-decyl) amino, di- (3, 7-dimethyl-1-n-octyl) amino, di- (3, 7-dimethyl-3-n-octyl) amino, and the like.
Asymmetry C1-10The dialkylamino group can be linear, branched or C3-10Cycloalkylamino groups, which may include: (methyl, ethyl) amino, (methyl, n-propyl) amino, (methyl, i-propyl) amino, (methyl, c-propyl) amino, (methyl, n-butyl) amino, (methyl, i-butyl) amino, (methyl, s-butyl) amino, (methyl, t-butyl) amino, (methyl, n-pentyl) amino, (methyl, c-pentyl) amino, (methyl, n-hexyl) amino, (methyl, c-hexyl) amino, (ethyl, n-propyl) amino, (ethyl, i-propyl) amino, (ethyl, c-propyl) amino, (ethyl, n-butyl) amino, (ethyl, i-butyl) aminoA (ethyl, s-butyl) amino group, (ethyl, t-butyl) amino group, (ethyl, n-pentyl) amino group, (ethyl, c-pentyl) amino group, (ethyl, n-hexyl) amino group, (ethyl, c-hexyl) amino group, (n-propyl, i-propyl) amino group, (n-propyl, c-propyl) amino group, (n-propyl, n-butyl) amino group, (n-propyl, i-butyl) amino group, (n-propyl, s-butyl) amino group, (n-propyl, t-butyl) amino group, (n-propyl, n-pentyl) amino group, (n-propyl, c-pentyl) amino group, (n-propyl, n-hexyl) amino group, (n-propyl, c-hexyl) amino group, n-propyl, c-hexyl group, amino group, n-pentyl group, n-propyl, n-hexyl group, amino group, n-propyl, (i-propyl, c-propyl) amino, (i-propyl, n-butyl) amino, (i-propyl, i-butyl) amino, (i-propyl, s-butyl) amino, (i-propyl, t-butyl) amino, (i-propyl, n-pentyl) amino, (i-propyl, c-pentyl) amino, (i-propyl, n-hexyl) amino, (i-propyl, c-hexyl) amino, (c-propyl, n-butyl) amino, (c-propyl, i-butyl) amino, (c-propyl, s-butyl) amino, (c-propyl, t-butyl) amino, (c-propyl, n-pentyl) amino, (c-propyl, c-pentyl) amino, (c-propyl, n-hexyl) amino, (c-propyl, c-hexyl) amino, (n-butyl, i-butyl) amino, (n-butyl, s-butyl) amino, (n-butyl, t-butyl) amino, (n-butyl, n-pentyl) amino, (n-butyl, c-pentyl) amino, (n-butyl, n-hexyl) amino, (n-butyl, c-hexyl) amino, (i-butyl, s-butyl) amino, (i-butyl, t-butyl) amino, (i-butyl, n-pentyl) amino, (i-butyl, c-pentyl) amino, (i-butyl, n-hexyl) amino, (i-butyl, c-hexyl) amino, (s-butyl, t-butyl) amino, (s-butyl, n-pentyl) amino, (s-butyl, c-pentyl) amino, (s-butyl, n-hexyl) amino, (s-butyl, c-hexyl) amino, (t-butyl, n-pentyl) amino, (t-butyl, c-pentyl) amino, (t-butyl, n-hexyl) amino, (t-butyl, c-hexyl) amino, (n-pentyl, c-pentyl) amino, (n-pentyl, n-hexyl) amino, (n-pentyl, c-hexyl) amino, (c-pentyl, n-hexyl) amino, (c-pentyl, c-hexyl) amino, (n-hexyl, c-hexyl) amino, (methyl, n-heptyl) amino, (methyl, n-octyl) amino, (methyl, n-nonyl) amino, (methyl, n-decyl) amino, (methyl, n-heptyl) amino, (ethyl, n-octyl) amino, (ethyl, n-nonyl) amino, (ethyl, n-decyl) amino and the like 。
The protecting group in the protected hydroxy group may be C1-4Alkoxymethyl (e.g., MOM: methoxymethyl, MEM: 2-methoxyethoxymethyl, ethoxymethyl, n-propoxymethyl, i-propoxymethyl, n-butoxymethyl, iBM: isobutoxymethyl, BUM: t-butoxymethyl, POM: pivaloyloxymethyl, SEM: trimethylsilylethoxymethyl, etc., preferably C1-2Alkoxymethyl, etc.), aryloxymethyl (e.g., BOM: benzyloxymethyl, PMBM: p-methoxybenzyloxymethyl, p-AOM: p-anisoxymethyl, etc.), C1-4Alkylaminomethyl (e.g., dimethylaminomethyl), substituted acetamidomethyl (e.g., Acm: acetamidomethyl, Tacm: trimethylacetamidomethyl, etc.), substituted thiomethyl (e.g., MTM: methylthiomethyl, PTM: phenylthiomethyl, Btm: benzylthiomethyl, etc.), carboxy, C1-7Acyl (e.g., formyl, acetyl, fluoroacetyl, difluoroacetyl, trifluoroacetyl, chloroacetyl, dichloroacetyl, trichloroacetyl, propionyl, Pv: pivaloyl, tigloyl, etc.), arylcarbonyl (e.g., benzoyl, benzoylformyl, benzoylpropionyl, phenylpropionyl, etc.), C 1-4Alkoxycarbonyl (e.g., methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, i-propoxycarbonyl, n-butoxycarbonyl, i-butoxycarbonyl, BOC: t-butoxycarbonyl, AOC: t-pentoxycarbonyl, VOC: ethyleneoxycarbonyl, AOC: allyloxycarbonyl, Teoc: 2- (trimethylsilyl) ethoxycarbonyl, Troc: 2, 2, 2-trichloroethoxycarbonyl, etc., preferably BOC, etc.), aryloxycarbonyl (e.g., Z: benzyloxycarbonyl, p-nitrobenzyloxycarbonyl, MOZ: p-methoxybenzyloxycarbonyl, etc.), C-benzyloxycarbonyl1-4Alkylaminocarbonyl (e.g., methylcarbamoyl, Ec: ethylcarbamoyl, n-propylcarbamoyl, etc.), arylaminocarbonyl (e.g., phenylcarbamoyl, etc.), trialkylsilyl (e.g., TMS: trimethylsilyl, TES: triethylsilyl, TIPS: triisopropylsilyl, DEIPS: diethylisopropylsilyl, DMIPS: dimethylisopropylsilyl, DTBMS: di-t-butylmethylsilyl, IPDMS: isopropylbisMethylsilyl, TBDMS: t-butyldimethylsilyl group, TDS: t-hexyldimethylsilyl group and the like, preferably t-butyldimethylsilyl group and the like), trialkyyarylsilyl group (e.g., DPMS: diphenylmethylsilyl, TBDPS: t-butyldiphenylsilyl, TBMPS: t-butyldimethoxyphenylsilyl, TPS: triphenylsilyl, etc.), alkylsulfonyl (as Ms: methanesulfonyl, ethanesulfonyl, etc.) or arylsulfonyl (e.g., benzenesulfonyl, Ts: p-toluenesulfonyl, p-chlorobenzenesulfonyl, MBS: p-methoxybenzenesulfonyl, m-nitrobenzenesulfonyl, iMds: 2, 6-dimethoxy-4-methylbenzenesulfonyl, Mds: 2, 6-dimethyl-4-methoxybenzenesulfonyl, Mtb: 2, 4, 6-trimethoxybenzenesulfonyl group, Mte: 2, 3, 5, 6-tetramethyl-4-methoxybenzenesulfonyl, Mtr: 2, 3, 6-trimethyl-4-methoxybenzenesulfonyl, Mts: 2, 4, 6-trimethylbenzenesulfonyl group, Pme: pentamethylbenzenesulfonyl, and the like).
Substituent R1Preferred specific examples are phenyl, thienyl (2-thienyl and 3-thienyl), furyl (2-furyl and 3-furyl), pyridazinyl (3-pyridazinyl and 4-pyridazinyl), pyridyl (2-pyridyl, 3-pyridyl and 4-pyridyl), quinolyl (2-quinolyl, 3-quinolyl, 4-quinolyl, 5-quinolyl, 6-quinolyl, 7-quinolyl and 8-quinolyl) and isoquinolyl (1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl, 5-isoquinolyl, 6-isoquinolyl, 7-isoquinolyl and 8-isoquinolyl) which are optionally substituted by one or more of the following substituents.
Substituent(s): c1-10Alkyl, halogen atom, C substituted by one or more halogen atoms1-10Alkyl, C substituted by one or more halogen atoms1-10Alkoxy, nitro, amino, by one or two C1-10Amino substituted by alkyl, by C1-10Alkylcarbonyl-substituted amino, C1-10Alkyl-substituted thiol group, C1-10Alkyl carbonyl substituted thiol, hydroxyl, C1-6Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10An alkylcarbonyl group.
Substituent R1Particularly preferred examples of (a) are: phenyl, thienyl (2-thienyl and 3-thienyl), furyl (2-furyl and 3-furyl), pyridazinyl (3-pyridazinyl and 4-pyridazinyl), pyridyl (2-pyridyl, 3-pyridyl and 4-pyridyl), quinolyl (2-quinolyl, 3-quinolyl, 4-quinolyl, 5-quinolyl, 6-quinolyl, 7-quinolyl and 8-quinolyl) and isoquinolyl (1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl, 5-isoquinolyl, 6-isoquinolyl, 7-isoquinolyl and 8-isoquinolyl) optionally substituted by one or more of the following substituents.
Substituent(s): methyl group, t-butyl group, trifluoromethyl group, trifluoromethoxy group, chlorine atom, bromine atom, fluorine atom, methoxy group, methylamino group, dimethylamino group, t-butoxy group and t-butylamino group.
Preferred specific examples of such substituents are: 3-methyl-phenyl, 4-methyl-phenyl, 3, 4-dimethyl-phenyl, 3-t-butyl-phenyl, 4-t-butyl-phenyl, 3-trifluoromethyl-phenyl, 4-trifluoromethoxy-phenyl, 4-trifluoromethyl-phenyl, 3, 4-bistrifluoromethyl-phenyl, 3-chloro-phenyl, 4-bromo-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl, 3, 4-dichloro-phenyl, 4-methoxy-phenyl, 4-methylamino-phenyl, 3-methyl-thienyl, 4-methyl-thienyl, 3, 4-dimethyl-thienyl, 3-t-butyl-thienyl, 4-t-butyl-thienyl, 3-trifluoromethyl-thienyl, 4-trifluoromethyl-thienyl, 3, 4-bistrifluoromethyl-thienyl, 3-chloro-thienyl, 4-chloro-thienyl, 3-fluoro-thienyl, 4-fluoro-thienyl, 3, 4-dichloro-thienyl, 4-methoxy-thienyl, 4-methylamino-thienyl, 3-methyl-furyl, 4-methyl-furyl, 3, 4-dimethyl-furyl, 3-t-butyl-furyl, 4-t-butyl-furyl, 3-trifluoromethyl-furyl, etc, 4-trifluoromethyl-furyl, 3, 4-bistrifluoromethyl-furyl, 3-chloro-furyl, 4-chloro-furyl, 3-fluoro-furyl, 4-fluoro-furyl, 3, 4-dichloro-furyl, 4-methoxy-furyl, 4-methyl-furyl, 5-chloro-pyridazinyl, 5-methyl-pyridazinyl, 5-methoxy-pyridazinyl, 4-chloro-pyridazinyl, 4-methylpyridazinyl, 4-methoxy-pyridazinyl, 4-t-butoxy-pyridazinyl, and the like.
L1Preferred specific examples are: bond, CH2Oxygen atom, sulfur atom, NH, N-Me, N-CHO, CHMe, CMe2、N-CH2Ph, etc., particularly preferred examples are a bond, CH2Oxygen atom, sulfur atom, NH, NMe, etc.
Substituent R2Preferred specific examples are: hydrogen atom, methyl group, ethyl group, n-propyl group, i-propyl group, t-butyl group and phenyl group (the methyl group, ethyl group, n-propyl group, i-propyl group, t-butyl group and phenyl group may be optionally substituted by a group selected from the group consisting of amino group, monomethylamino group, dimethylamino group, monoethylamino group, diethylamino group, methoxy group, ethoxy group, methoxycarbonyl group, ethoxycarbonyl group, methylcarbonyloxy group, ethylcarbonyloxy group, methylcarbonylamino group or ethylcarbonylamino group, etc.), and particularly preferred examples are hydrogen atom, methyl group, ethyl group, n-propyl group, i-propyl group, t-butyl group, phenyl group, etc.
L2Examples of preferred groups are: bond, CH2Oxygen atom, sulfur atom, NH, N-Me, N-CHO, CHMe, CMe2、N-CH2Ph, etc., particularly preferred examples are a bond, CH2Oxygen atom, sulfur atom, NH, NMe, etc.
L3Examples of preferred groups are: bond, CH2Oxygen atom, sulfur atom, NH-OH, N-Me, N-CHO, CHMe, CMe2、N-CH2PH, etc., particularly preferred examples are: bond, CH 2Oxygen atom, sulfur atom, NH, NMe, etc.
Preferred examples of groups for X are: OH, SH, NH2、OMe、SMe、NHMe、NHEt、NH-CHO、NH-CH2Ph、OCH2Ph、SCH2Ph、OC(＝O)CH3、SC(＝O)CH3、NHC(＝O)CH3Etc., particularly preferred examples are OH, SH, NH2And the like.
Preferred examples of groups for Y are: oxygen atom, sulfur atom, NH, N-OH, N-CHO, N-Me, N-CH2Ph、N-OMe、N-OCH2Ph and the like, particularly preferred examples thereof are an oxygen atom, a sulfur atom, NH, N-OH and the like.
L4Examples of preferred groups of (a) are: bond, CH2Oxygen atom, sulfur atom, NH, N-Me, N-CHO, CHMe, CMe2、N-CH2Ph, etc., particularly preferred examples are a bond, CH2Oxygen atom, sulfur atom, NH, NMe, etc.
Substituent R3Examples of preferred groups of (a) are: methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, c-propyl, c-butyl, c-pentyl, c-hexyl, ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 4-pentynyl, 1-methyl-2-butynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-1-butynyl and the following heterocyclic groups, which are optionally substituted by one or more of the following substituents.
Heterocyclic radical
Substituent(s): hydrogen atom, hydroxyl group, amino group, halogen atom, nitro group, thiol group, carboxyl group, phosphonic acid group, sulfonic acid group, carbamoyl group, hydroxycarbamoyl group, cyanocarbamoyl group, sulfamoyl group, hydroxysulfamoyl group, cyanosulfamoyl group, tetrazolyl group, phenyl group, thienyl group, pyridyl group, furyl group, -CH 2CO2H、-OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H、-CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH、-(C＝O)CO2H、-CH2(C＝O)CO2H、-NH(C＝O)CO2H、-NH(＝O)2NH2、C1-10Alkyl (the C)1-10The alkyl group may be substituted with one or more substituents selected from the group consisting ofGeneration: hydroxy, carboxy, the following aryl, the following heterocyclic group and C1-10Alkylamino radical (this C)1-10Alkylamino may be substituted with one or more of the following aryl groups or one or more heterocyclic groups)), C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Thioalkyl, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkylaminocarbonyl radical, C1-10Dialkylaminocarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl, aminocarbonyl, C1-10Alkylcarbonylamino (this C)1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkylaminocarbonyl radical, C1-10Dialkylaminocarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl, aminocarbonyl and C1-10The alkylcarbonylamino group may be substituted with one or more substituents selected from the group consisting of: carboxyl group, carbamoyl group, sulfamoyl group, sulfo group, amino group, the following aryl groups and the following heterocyclic groups), the following aryl groups and the following heterocyclic groups.
Aryl: phenyl, thienyl (2-thienyl and 3-thienyl), furyl (2-furyl and 3-furyl), pyridazinyl (3-pyridazinyl and 4-pyridazinyl), pyridyl (2-pyridyl, 3-pyridyl and 4-pyridyl), pyrimidyl (2-pyrimidyl, 4-pyrimidyl and 5-pyrimidyl), quinolyl (2-quinolyl, 3-quinolyl, 4-quinolyl, 5-quinolyl, 6-quinolyl, 7-quinolyl and 8-quinolyl) and isoquinolyl (1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl, 5-isoquinolyl, 6-isoquinolyl, 7-isoquinolyl and 8-isoquinolyl).
Heterocyclic group: 1, 3, 4-oxadiazolyl, 1, 3, 4-thiadiazolyl, 1, 2, 4-oxadiazolyl, 1, 2, 4-thiadiazolyl, 1, 2, 5-oxadiazolyl, 1, 2, 5-thiadiazolyl, 1, 2-oxazolyl, and 1, 2-thiazolyl.
Substituent R3Other preferred specific examples of (a) are: optionally substituted by one or more substituents selected from group AA substituent and one or more substituents selected from the group consisting of substituent group B, methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, c-propyl, c-butyl, c-pentyl, c-hexyl, ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 4-pentynyl, 1-methyl-2-butynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-1-butynyl and the following heterocyclic groups.
Heterocyclic radical
Substituent group a group: hydroxy, amino, carboxy, phosphonate, sulfonate, carbamoyl, hydroxycarbamoyl, cyanocarbamoyl, sulfamoyl, hydroxysulfamoyl, cyanosulfamoyl, tetrazolyl, -CH2CO2H、-OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H and alkoxycarbonyl.
Substituent group B group: hydroxy group, amino group, carboxy group, phosphonic acid group, sulfonic acid group, carbamoyl group, hydroxycarbamoyl group, cyanocarbamoyl group, sulfamoyl group, nitro group, cyano group, halogen atom, C 1-10Alkyl, C substituted by one or more fluorine atoms1-10Alkyl radical, C1-10Alkyl-substituted sulfamoyl, C1-10Alkyl-substituted carbamoyl, C1-10Alkylcarbonylamino and C1-10Alkylaminocarbonyl radical (such C)1-10Alkylcarbonylamino and C1-10The alkylaminocarbonyl group may be substituted with one or more substituents selected from the group consisting of: phenyl, pyridyl, thienyl, and furyl).
The compounds of the present invention, which are preferred as a thrombopoietin receptor activator, prophylactic, therapeutic or ameliorating agent and thrombopoietin increasing agent for diseases effectively treatable by activating the thrombopoietin receptor, are as follows.
1) A compound represented by formula (1), a tautomer, prodrug or pharmaceutically acceptable salt of the compound, or a solvate thereof, wherein in formula (1), A is a nitrogen atom, and B is a sulfur atom.
2) A compound represented by formula (1), a tautomer, prodrug or pharmaceutically acceptable salt of the compound, or a solvate thereof, wherein in formula (1), A is a nitrogen atom and B is an oxygen atom.
3) A compound represented by the formula (1), a tautomer, prodrug or pharmaceutically acceptable salt of the compound, or a solvate thereof, wherein in the formula (1), A is a nitrogen atom, and B is NR other than NH9(wherein, R 9Is hydrogen atom, hydroxy, formyl, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogenSeed, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C 2-14Aryl and C2-14Aryloxy) or C2-14Aryloxy group (the C)2-14The aryloxy group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy)).
4) A compound represented by the formula (1), a tautomer, prodrug or pharmaceutically acceptable salt of the compound, or a solvate thereof, wherein A is CR in the formula (1)4(wherein R is4Is a hydrogen atom, a hydroxyl group (the hydroxyl group may be substituted by C)2-6Alkenyl or C2-6Alkynyl-substituted), a thiol group (the thiol group may be C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl or C1-10Alkylcarbonyl), amino (which amino may be substituted by one or two C)2-6Alkenyl or one or two C2-6Alkynyl-substituted), formyl, halogen, nitro, cyano, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkylcarbonylamino, mono-or di-C1-10Alkylamino radical, C1-10Alkoxy (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkylcarbonylamino, mono-or di-C1-10Alkylamino and C 1-10Alkoxy groups may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl radicalCarbonyloxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group), C2-14Aryloxy group (the C)2-14The aryloxy group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C 1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy), SO2R5、SOR5Or COR5(wherein, R5Is hydroxy, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl and C1-10Alkoxy groups may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C1-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C 1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group), C2-14Aryloxy group (the C)2-14The aryloxy group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy) or NR6R7(wherein, R6And R7Each independently is a hydrogen atom, a hydroxyl group, a formyl group, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C 2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy) or R6And R7Together represent- (CH)2)m1-E-(CH2)m2- (wherein E is an oxygen atom, a sulfur atom, CR26R27(wherein, R26And R27Each independently is a hydrogen atom, C1-10Alkyl radical, C2-14Aryl radical, C1-10Alkoxy radical, C2-14Aryloxy, hydroxy or protected hydroxy) or NR8(wherein, R8Is hydrogen atom, hydroxy, formyl, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C 1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy)), m1 and m2 are each independently an integer from 0 to 5, provided that m1+ m2 is 3, 4 or 5))), and B is an oxygen atom.
5) A compound represented by the formula (1), a tautomer, prodrug or pharmaceutically acceptable salt of the compound, or a solvate thereof, wherein A is CR in the formula (1)4(wherein, R4Is a hydrogen atom, a hydroxyl group (the hydroxyl group may be substituted by C)2-6Alkenyl or C2-6Alkynyl-substituted), a thiol group (the thiol group may be C) 1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl or C1-10Alkylcarbonyl), amino (which amino may be substituted by one or two C)2-6Alkenyl or one or two C2-6Alkynyl-substituted), formyl, halogen, nitro, cyano, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkylcarbonylamino, mono-or di-C1-10Alkylamino radical, C1-10Alkoxy (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkylcarbonylamino, mono-or di-C1-10Alkylamino and C1-10Alkoxy groups may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C 1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group), C2-14Aryloxy group (the C)2-14The aryloxy group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy radical)、SO2R5、SOR5Or COR5(wherein, R5Is hydroxy, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl and C1-10Alkoxy groups may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C 1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group), C2-14Aryloxy group (the C)2-14The aryloxy group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy) or NR6R7(wherein, R6And R7Each independently is a hydrogen atom, a hydroxyl group, a formyl group, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkyl carbonyl oxy, C 1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy) or R6And R7Together represent- (CH)2)m1-E-(CH2)m2- (wherein E is an oxygen atom, a sulfur atom, CR 26R27(wherein, R26And R27Each independently is a hydrogen atom, C1-10Alkyl radical, C2-14Aryl radical, C1-10Alkoxy radical, C2-14Aryloxy radicalHydroxy or protected hydroxy) or NR8(wherein, R8Is hydrogen atom, hydroxy, formyl, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C 1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy)), m1 and m2 are each independently an integer from 0 to 5, provided that m1+ m2 is 3, 4 or 5))), and B is a sulfur atom.
6) A compound represented by the formula (1), a tautomer, prodrug or pharmaceutically acceptable salt of the compound, or a solvate thereof, wherein A is CR in the formula (1)4(wherein, R4Is a hydrogen atom or a hydroxyl group (the hydroxyl group)Can be covered with C2-6Alkenyl or C2-6Alkynyl-substituted), a thiol group (the thiol group may be C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl or C1-10Alkylcarbonyl), amino (which amino may be substituted by one or two C)2-6Alkenyl or one or two C2-6Alkynyl-substituted), formyl, halogen, nitro, cyano, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkylcarbonylamino, mono-or di-C1-10Alkylamino radical, C1-10Alkoxy (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkylcarbonylamino, mono-or di-C1-10Alkylamino and C1-10Alkoxy groups may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C 1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group), C2-14Aryloxy group (the C)2-14The aryloxy group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl radical(the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C 1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy), SO2R5、SOR5Or COR5(wherein, R5Is hydroxy, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl and C1-10Alkoxy groups may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group), C 2-14Aryloxy group (the C)2-14The aryloxy group may be optionally substituted with one or more groups selected fromAnd (3) substituent: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy) or NR6R7(wherein, R6And R7Each independently is a hydrogen atom, a hydroxyl group, a formyl group, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more substituents selected from the group consisting of; carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C 2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of; c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy) or R6And R7Together represent- (CH)2)m1-E-(CH2)m2- (wherein E is an oxygen atom, a sulfur atom, CR26R27(wherein, R26And R27Each independently is a hydrogen atom, C1-10Alkyl radical, C2-14Aryl radical, C1-10Alkoxy radical, C2-14Aryloxy, hydroxy or protected hydroxy) or NR8(wherein, R8Is hydrogen atom, hydroxy, formyl, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C 1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy)), m1 and m2 are each independently an integer from 0 to 5, with the proviso that m1+ m2 are 3, 4 or 5))), and B is NR9(wherein, R9Is hydrogen atom, hydroxy, formyl, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C 1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), C2-14Aryl radical (the radical C)2-4The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy) or C2-14Aryloxy group (the C)2-14The aryloxy group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10The alkyl group may be substituted by one or more halogen atoms)、C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C 1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy)).
7) A compound represented by the formula (1) as described in 4), 5) or 6), a tautomer, prodrug or pharmaceutically acceptable salt of the compound, or a solvate thereof, wherein A is CR in the formula (1)37(wherein, R37Is a hydrogen atom, a hydroxyl group (the hydroxyl group may be substituted by C)2-6Alkenyl or C2-6Alkynyl-substituted), a thiol group (the thiol group may be C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl or C1-10Alkylcarbonyl), amino (which amino may be substituted by one or two C)2-6Alkenyl or one or two C2-6Alkynyl-substituted), formyl, halogen, nitro, cyano, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkylcarbonylamino, mono-or di-C1-10Alkylamino radical (this C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkylcarbonylamino and mono-or di-C1-10The alkylamino group may be substituted with one or more substituents selected from the group consisting of: halogen atom, carboxyl group, nitro group and cyano group), SO2R38、SOR38Or CO38(wherein, R38Is hydroxy, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl and C1-10The alkoxy group may be substituted with one or more substituents selected from the group consisting of: halogen atom, carboxyl group, nitro group and cyano group), C 2-14Aryl or C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms). At R37And R38The terms used in the respective substituents with R1-R36The terms used in the respective substituents have the same meaning.
8) The compound represented by the formula (1) as described in 3) or 6), a tautomer, prodrug or pharmaceutically acceptable salt of the compound, or a solvate thereof, wherein B is NR in the formula (1)39(wherein, R39Is hydrogen atom, hydroxy, formyl, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be substituted with one or more substituents selected from the group consisting of: carboxyl, halogen, nitro and cyano), C2-14Aryl or C2-14Aryloxy group (the C)2-14Aryl and C2-14The aryloxy group may be substituted with one or more substituents selected from the group consisting of: c1-6Alkyl (the C)1-6Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano and halogen atoms)). Substituent R 39The term as used in (1) with R1To R36The terms used in the respective substituents have the same meaning.
9) A compound represented by the formula (1) as described in 1), 2), 3), 4), 5), 6), 7) or 8), a tautomer, prodrug or pharmaceutically acceptable salt of the compound, or a solvate thereof, wherein, in the formula (1), L1Is a bond.
10) A compound represented by the formula (1) as described in 1), 2), 3), 4), 5), 6), 7), 8) or 9), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or a solvate thereof, wherein, in the formula (1), L2Is a bond.
11) A compound represented by the formula (1) as described in 1), 2), 3), 4), 5), 6), 7), 8), 9) or 10), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or a solvate thereof, wherein, in the formula (1), L3Is NR19(wherein, R19Is hydrogen atom, hydroxy, formyl, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C 1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy)).
12) A compound as described in 1), 2), 3), 4), 5), 6), 7), 8), 9) or 10), saidA tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein, L3Is NH.
13) A compound of 1), 2), 3), 4), 5), 6), 7), 8), 9) or 10), a tautomer, prodrug or pharmaceutically acceptable salt of the compound, or a solvate thereof, wherein L is 3Is CH2。
14) The compound of 11), 12) or 13), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein R is2Is a hydrogen atom, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl and C1-10Alkoxy groups may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), C2-14Aryl or C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms).
15) The compound of 11), 12) or 13), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein R is2Is a hydrogen atom, C 1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-3Alkoxy (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl and C1-3Alkoxy groups may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, phenyl and phenoxy (which phenyl and phenoxy groups may be substituted by one or more C's)1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted by one or more halogen atoms) or by one or more halogen atoms), phenyl or phenoxy groups (which phenyl and phenoxy groups may be substituted by one or more C's)1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms).
16) The compound of 11), 12) or 13), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein R is2Is a hydrogen atom, C1-10Alkyl radical, C2-6Alkenyl or C2-6Alkynyl (the C)1-10Alkyl radical, C2-6Alkenyl and C2-6The alkynyl group may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C 1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxyl, and protected hydroxyl).
17) The compound of 11), 12) or 13), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein R is2Is a hydrogen atom or C1-6Alkyl (the C)1-6The alkyl group may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxyl, and protected hydroxyl).
18) The compound of 11), 12) or 13), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein R is2Is a hydrogen atom or C1-3Alkyl (the C)1-3The alkyl group may be optionally substituted with one or more substituents selected from the group consisting of: halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxyl, and protected hydroxyl).
19) The compound of 14), 15), 16), 17) or 18), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein R is 1Is C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: halogen atom, carboxyl group, nitro group, formyl group, cyano group, hydroxy group, protected hydroxy group, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyloxy (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), C2-14Aryl radical, C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), thiol groups and amino groups (which may optionally be substituted with one or more substituents selected from the group consisting of: formyl radical, C 1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl and C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl and C1-10The alkylcarbonyl s may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms))).
20) The compound of 14), 15), 16), 17) or 18), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein R is1Is phenyl, thienyl, furyl, pyridazinyl, pyridyl, quinolyl or isoquinolyl (which phenyl, thienyl, furyl, pyridazinyl, pyridyl, quinolyl and isoquinolyl groups may be optionally substituted by one or more substituents selected from the group consisting of halogen atom, carboxyl, nitro, formyl, cyano, hydroxyl, protected hydroxyl, C1-10Alkyl radical, C2-6Alkenyl radical, C 2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyloxy (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkylcarbonyloxy and C1-10Alkoxycarbonyl can be optionally selectedSubstituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), thiol groups and amino groups (which may optionally be substituted with one or more substituents selected from the group consisting of: formyl radical, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl and C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C 1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms))).
21) The compound of 14), 15), 16), 17) or 18), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein R is1Is phenyl, thienyl, furyl, pyridazinyl, pyridyl, quinolyl or isoquinolyl (the phenyl, thienyl, furyl, pyridazinyl, pyridyl, quinolyl and isoquinolyl groups may be optionally substituted by one or more substituents selected from the group consisting of halogen atom, carboxyl, nitro, formyl, cyano, hydroxyl, protecting groupHydroxy group of (2), C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-40Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyloxy (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyloxy group may be optionally substituted with one or more substituents selected from the group consisting of: halogen atom, carboxyl group, nitro group and cyano group), C2-14Aryl radical, C2-14Aryloxy group (the C) 2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), thiol groups and amino groups (which may optionally be substituted with one or more substituents selected from the group consisting of: formyl radical, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl and C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more substituents selected from the group consisting of: halogen atom, carboxyl group, nitro group, cyano group, hydroxyl group, and protected hydroxyl group))).
22) The compound of 14), 15), 16), 17) or 18), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein R is1Is phenyl (which phenyl may be optionally substituted by one or more substituents selected from the group consisting of halogen atom, carboxyl group, nitro group, formyl group, cyano group, hydroxyl group, protected hydroxyl group, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyloxy (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyloxy group may be optionally substituted with one or more groups selected from the group consisting of The substituent (b): carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), thiol groups and amino groups (which may optionally be substituted with one or more substituents selected from the group consisting of: formyl radical, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl and C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl and C1-10The alkylcarbonyl s may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms))).
23) The compound of 14), 15), 16), 17) or 18), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein R is1Is phenyl (which phenyl may be optionally substituted by one or more substituents selected from the group consisting of halogen atom, carboxyl group, nitro group, formyl group, cyano group, hydroxyl group, protected hydroxyl group, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyloxy (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyloxy group may be optionally substituted with one or more substituents selected from the group consisting of: halogen atom, carboxyl group, nitro group and cyano group), C2-14Aryl radical, C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or with one or more halogen atoms), thiol groups and amino groups (which may optionally be substituted with one or more substituents selected from the group consisting of: formyl radical, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl and C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more substituents selected from the group consisting of: halogen atom, carboxyl group, nitro group, cyano group, hydroxyl group, and protected hydroxyl group))).
24) The compound of 19), 20), 21), 22) or 23), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein Y is an oxygen atom.
25) A compound as described in 19), 20), 21), 22) or 23), a tautomer, prodrug or pharmaceutically acceptable salt of said compound or solvate thereof, wherein Y is a sulfur atom.
26) The compound of 24) or 25), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein X is hydroxy.
27) The compound of 24), 25) or 26), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein L is4Is a bond, R3Is ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, c-propyl, c-butyl, c-pentyl, c-hexyl, ethynyl, 1-Propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 4-pentynyl, 1-methyl-2-butynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-1-butynyl or any of the following heterocyclic groups:
(the ethyl group, n-propyl group, i-propyl group, n-butyl group, s-butyl group, t-butyl group, c-propyl group, c-butyl group, c-pentyl group, c-hexyl group, ethynyl group, 1-propynyl group, 2-propynyl group, 1-butynyl group, 2-butynyl group, 3-butynyl group, 1-pentynyl group, 2-pentynyl group, 4-pentynyl group, 1-methyl-2-butynyl group, 1-methyl-3-butynyl group, 2-methyl-3-butynyl group, 3-methyl-1-butynyl group and the above heterocyclic group may be optionally substituted with one or more substituents selected from the group consisting of a hydroxyl group, an amino group, a thiol group, a carboxyl group, a phosphonic group, a sulfonic group, a carbamoyl group, a carboxyl group, a phosphonic group, a sulfonic group, Hydroxycarbamoyl, cyanocarbamoyl, sulphamoyl, hydroxysulphamoyl, cyanosulphamoyl, tetrazolyl, -CH 2CO2H、-OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H、-CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH、C1-10Alkoxycarbonyl group, C1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino and the following aryl and heterocyclyl radicals (C1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxygen radical、C1-10Alkoxycarbonyl group, C1-10The alkylcarbonylamino group and the following aryl and heterocyclyl groups may be optionally substituted with one or more substituents selected from the group consisting of: hydroxy, carboxy, carbamoyl, sulfonic acid, and sulfamoyl):
aryl: phenyl, thienyl (2-thienyl and 3-thienyl), furyl (2-furyl and 3-furyl), pyridazinyl (3-pyridazinyl and 4-pyridazinyl), pyridyl (2-pyridyl, 3-pyridyl and 4-pyridyl), pyrazinyl, pyrimidinyl (2-pyrimidinyl, 4-pyrimidinyl and 5-pyrimidinyl), quinolyl (2-quinolyl, 3-quinolyl group, 4-quinolyl group, 5-quinolyl group, 6-quinolyl group, 7-quinolyl group and 8-quinolyl group) and isoquinolyl group (1-isoquinolyl group, 3-isoquinolyl group, 4-isoquinolyl group, 5-isoquinolyl group, 6-isoquinolyl group, 7-isoquinolyl group and 8-isoquinolyl group);
Heterocyclic group: 1, 3, 4-oxadiazolyl, 1, 3, 4-thiadiazolyl, 1, 2, 4-oxadiazolyl, 1, 2, 4-thiadiazolyl, 1, 2, 5-oxadiazolyl, 1, 2, 5-thiadiazolyl, 1, 2-oxazolyl, 1, 2-thiazolyl, 1, 3-oxazolyl, 1, 3-thiazolyl, pyrrolyl, imidazolyl, and pyrazolyl).
28) The compound of 24), 25) or 26), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein L is4Is a bond, R3Is methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, c-propyl, c-butyl, c-pentyl, c-hexyl, ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 4-pentynyl, 1-methyl-2-butynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-1-butynyl or any of the following heterocyclic groups:
(the methyl group, ethyl group, n-propyl group, i-Propyl, n-butyl, s-butyl, t-butyl, c-propyl, c-butyl, c-pentyl, c-hexyl, ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 4-pentynyl, 1-methyl-2-butynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-1-butynyl and the above heterocyclic groups may optionally be substituted by one or more substituents selected from the following group: hydroxy, amino, thiol, carboxy, phosphonate, sulfonate, carbamoyl, hydroxycarbamoyl, cyanocarbamoyl, sulfamoyl, hydroxysulfamoyl, cyanosulfamoyl, tetrazolyl, -CH 2CO2H、-OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H、-CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH、C1-10Alkoxycarbonyl group, C1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylaminocarbonyl and C1-10Alkylcarbonylamino (this C)1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylaminocarbonyl and C1-10The alkylcarbonylamino group may be optionally substituted with one or more substituents selected from the group consisting of: c2-14Aryl, hydroxyl, carboxyl, carbamoyl, sulfonic acid, and sulfamoyl).
29) The compound of 24), 25) or 26), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein L is4Is a bond, R3Is methyl, ethyl, n-propyl, i-propyl, n-butyl, c-Propyl, c-hexyl, ethynyl, 1-propynyl, 2-propynyl or 1-butynyl (the methyl, ethyl, n-propyl, i-propyl, n-butyl, c-propyl, c-hexyl, ethynyl, 1-propynyl, 2-propynyl and 1-butynyl may be optionally substituted by one or more substituents selected from the group consisting of hydroxy, amino, thiol, carboxy, phosphonate, sulphonic acid, carbamoyl, hydroxycarbamoyl, cyanocarbamoyl, sulfamoyl, hydroxysulfamoyl, cyanosulfamoyl, tetrazolyl, -CH 2CO2H、-OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H、-CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH、C1-10Alkoxycarbonyl group, C1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10Alkylcarbonylamino (this C)1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonylamino group may be optionally substituted with one or more substituents selected from the group consisting of: hydroxyl, carboxyl, carbamoyl, sulfonic acid, and sulfamoyl)).
30) The compound of 24), 25) or 26), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein L is4Is a bond, R3Is methyl, ethyl, n-propyl, i-propyl, n-butyl, c-propyl, c-hexyl, ethynyl, 1-propynyl, 2-propynyl or 1-butynyl (the methyl, ethyl, n-propyl, i-propyl, n-butyl, c-propyl, c-hexyl, ethynyl, 1-propynyl, 2-propynyl and 1-butynyl may optionally be substituted by oneOr substituted with one or more substituents selected from the group consisting of: hydroxy, amino, thiol, carboxy, phosphonate, sulfonate, carbamoyl, hydroxycarbamoyl, cyanocarbamoyl, sulfamoyl, hydroxysulfamoyl, cyanosulfamoyl, tetrazolyl, -CH 2CO2H、-OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H、-CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH and C1-10Alkoxycarbonyl groups).
31) The compound of 24), 25) or 26), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein L is4Is a bond, R3Is any one of the following heterocyclic groups:
(the above heterocyclic group may be optionally substituted with one or more substituents selected from the group consisting of a hydrogen atom, a hydroxyl group, an amino group, a halogen atom, a nitro group, a thiol group, a carboxyl group, a phosphonic acid group, a sulfonic acid group, a carbamoyl group, a hydroxycarbamoyl group, a cyanocarbamoyl group, a sulfamoyl group, a hydroxysulfamoyl group, a cyanosulfamoyl group, a tetrazolyl group, a phenyl group, a thienyl group, a pyridyl group, a furyl group, a-CH2CO2H、-OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H、 -CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH、-(C＝O)CO2H、-CH2(C＝O)CO2H、-NH(C＝O)CO2H、-NH(＝O)2NH2、C1-10Alkoxycarbonyl group, C1-10Alkyl (the C)1-10The alkyl group may be substituted with one or more substituents selected from the group consisting of: hydroxy, carboxy, phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-pyridazinyl4-pyridazinyl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, pyrazinyl group, 2-pyrimidinyl group, 4-pyrimidinyl group, 5-pyrimidinyl group, 1, 3-oxazolyl group, 1, 3-thiazolyl group, pyrrolyl group, imidazolyl group, pyrazolyl group, 2-quinolyl group, 3-quinolyl group, 4-quinolyl group, 5-quinolyl group, 6-quinolyl group, 7-quinolyl group, 8-quinolyl group, 1-isoquinolyl group, 3-isoquinolyl group, 4-isoquinolyl group, 5-isoquinolyl group, 6-isoquinolyl group, 7-isoquinolyl group, 8-isoquinolyl group, 1, 3, 4-oxadiazolyl group, 1, 3, 4-thiadiazolyl group, 1, 2, 4-oxadiazolyl group, 1, 2, 4-thiadiazolyl group, 1-quinolyl group, 2-quinolyl group, 4-, 1, 2, 5-oxadiazolyl, 1, 2, 5-thiadiazolyl, 1, 2-oxazolyl, 1, 2-thiazolyl and C 1-10Alkylaminocarbonyl radical (such C)1-10The alkylaminocarbonyl group may be substituted with one or more substituents selected from the group consisting of: phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-pyridazinyl, 4-pyridazinyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-quinolyl, 3-quinolyl, 4-quinolyl, 5-quinolyl, 6-quinolyl, 7-quinolyl, 8-quinolyl, 1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl, 5-isoquinolyl, 6-isoquinolyl, 7-isoquinolyl, 8-isoquinolyl, 1, 3, 4-oxadiazolyl, 1, 3, 4-thiadiazolyl, 1, 2, 4-oxadiazolyl, 1, 2, 4-thiadiazolyl, 1, 2, 5-oxadiazolyl, 1-quinolyl, 1, 2, 5-thiadiazolyl, 1, 2-oxazolyl, 1, 2-thiazolyl, 1, 3-oxazolyl, 1, 3-thiazolyl, pyrrolyl, imidazolyl and pyrazolyl)), C2-10Alkenyl radical, C1-10Alkynyl, C2-9Heterocyclic group, C1-10Thioalkyl, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkylaminocarbonyl radical, C1-10Dialkylaminocarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino (this C)1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkylaminocarbonyl radical, C1-10Dialkylaminocarbonyl, mono-or di-C 1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonylamino group may be substituted with one or more substituents selected from the group consisting ofSubstituent group substitution: carboxyl group, carbamoyl group, sulfamoyl group, sulfo group, phenyl group, 2-thienyl group, 3-thienyl group, 2-furyl group, 3-pyridazinyl group, 4-pyridazinyl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, 2-quinolyl group, 3-quinolyl group, 4-quinolyl group, 5-quinolyl group, 6-quinolyl group, 7-quinolyl group, 8-quinolyl group, 1-isoquinolyl group, 3-isoquinolyl group, 4-isoquinolyl group, 5-isoquinolyl group, 6-isoquinolyl group, 7-isoquinolyl group, 8-isoquinolyl group, 1, 3, 4-oxadiazolyl group, 1, 3, 4-thiadiazolyl group, 1, 2, 4-oxadiazolyl group, 1, 2, 4-thiadiazolyl group, 1-thiadiazolyl group, 1, 2, 5-oxadiazolyl, 1, 2, 5-thiadiazolyl, 1, 2-oxazolyl, 1, 2-thiazolyl, 1, 3-oxazolyl, 1, 3-thiazolyl, pyrrolyl, imidazolyl and pyrazolyl), pyridylaminocarbonyl, phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-pyridazinyl, 4-pyridazinyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-quinolyl, 3-quinolyl, 4-quinolyl, 5-quinolyl, 6-quinolyl, 7-quinolyl, 8-quinolyl, 1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl, 5-isoquinolyl, 6-isoquinolyl, 1-isoquinolyl, 3-isoquinolyl, 5-isoquinolyl, 3-quinolyl, 4-quinolyl, 3-quinolyl, 1, 2, 5-thiadiazolyl, 1, 7-isoquinolinyl, 8-isoquinolinyl, 1, 3, 4-oxadiazolyl, 1, 3, 4-thiadiazolyl, 1, 2, 4-oxadiazolyl, 1, 2, 4-thiadiazolyl, 1, 2, 5-oxadiazolyl, 1, 2, 5-thiadiazolyl, 1, 2-oxazolyl, 1, 2-thiazolyl, 1, 3-oxazolyl, 1, 3-thiazolyl, pyrrolyl, imidazolyl and pyrazolyl).
32) The compound of 24), 25) or 26), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein L is4Is a bond, R3Is any one of the following heterocyclic groups:
(the above heterocyclic group may be optionally substituted with one or more substituents selected from the group consisting of a hydroxyl group, an amino group, a thiol group, a carboxyl group, a phosphonic acid group, a sulfonic acid group, a carbamoyl group, a hydroxycarbamoyl groupRadicals, cyanocarbamoyl, sulfamoyl, hydroxysulfamoyl, cyanosulfamoyl, tetrazolyl, -CH2CO2H、-OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H、-CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH、C1-10Alkoxycarbonyl group, C1-10Alkyl radical, C1-10Alkylcarbonyl group, C1-10Alkylsulfonyl radical, C1-10Alkylaminosulfonyl radical, C1-10Alkylaminocarbonyl and C1-10Dialkylaminocarbonyl (this C)1-10Alkyl radical, C1-10Alkylcarbonyl group, C1-10Alkylsulfonyl radical, C1-10Alkylaminosulfonyl radical, C1-10Alkylaminocarbonyl and C1-10The dialkylaminocarbonyl group may be substituted with one or more substituents selected from the group consisting of: phenyl, thienyl, furyl, pyridyl, nitro, cyano, hydroxyl, amino, carboxyl, phosphonate, sulfonate, carbamoyl, sulfamoyl, and tetrazolyl)).
33) The compound of 24), 25) or 26), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein L is 4Is a bond, R3Is any one of the following heterocyclic groups:
(the above heterocyclic group may be optionally substituted with one or more substituents selected from the group consisting of a hydroxyl group, an amino group, a thiol group, a carboxyl group, a phosphonic acid group, a sulfonic acid group, a carbamoyl group, a hydroxycarbamoyl group, a cyanocarbamoyl group, a sulfamoyl group, a hydroxysulfamoyl group, a cyanosulfamoyl group, a tetrazolyl group, -CH2CO2H、-OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H、-CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH、C1-10Alkoxycarbonyl group, C1-10Alkyl radical, C1-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10Alkylcarbonylamino (this C)1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonylamino group may be optionally substituted with one or more substituents selected from the group consisting of: hydroxyl, carboxyl, carbamoyl, sulfonic acid, and sulfamoyl)).
34) The compound of 24), 25) or 26), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein L is4Is a bond, R3Is any one of the following heterocyclic groups:
(the above heterocyclic group may be optionally substituted with one or more substituents selected from the group consisting of a hydroxyl group, an amino group, a thiol group, a carboxyl group, a phosphonic acid group, a sulfonic acid group, a carbamoyl group, a hydroxycarbamoyl group, a cyanocarbamoyl group, a sulfamoyl group, a hydroxysulfamoyl group, a cyanosulfamoyl group, a tetrazolyl group, -CH2CO2H、-OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H、-CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH、C1-10Alkoxycarbonyl, methyl, ethyl, n-propyl, i-propyl, methylcarbonylA group selected from the group consisting of a methyl group, an ethylcarbonyl group, an n-propylcarbonyl group, a methylsulfonyl group, an ethylsulfonyl group, an n-propylsulfonyl group, a methylaminosulfonyl group, an n-propylaminosulfonyl group, an i-propylaminosulfonyl group, a methylaminocarbonyl group, an ethylaminocarbonyl group, an n-propylaminocarbonyl group, an i-propylaminocarbonyl group, a c-propylaminocarbonyl group and an n-butylaminocarbonyl group (the methyl group, the ethyl group, the n-propyl group, the i-propyl group, the methylcarbonyl group, the ethylcarbonyl group, the ethylsulfonyl group, the n-propylsulfonyl group, the i-propylsulfonyl group, the methylaminosulfonyl group, the ethylaminosulfonyl group, the n-propylaminosulfonyl group, the i-propylaminosulfonyl, Methylaminocarbonyl, ethylaminocarbonyl, n-propylaminocarbonyl, i-propylaminocarbonyl, c-propylaminocarbonyl and n-butylaminocarbonyl may be substituted with one or more substituents selected from the following group: phenyl, thienyl, pyridyl, and furyl)).
35) The compound of 24), 25) or 26), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein L is4Is NR22(wherein, R22Is hydrogen atom, hydroxy, formyl, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkylcarbonyloxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C 1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy)), and R3Is ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, c-propyl, c-butyl, c-pentyl, c-hexyl, ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 4-pentynyl, 1-methyl-2-butynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-1-butynyl or any of the following heterocyclic groups:
(the ethyl group, n-propyl group, i-propyl group, n-butyl group, s-butyl group, t-butyl group, c-propyl group, c-butyl group, c-pentyl group, c-hexyl group, ethynyl group, 1-propynyl group, 2-propynyl group, 1-butynyl group, 2-butynyl group, 3-butynyl group, 1-pentynyl group, 2-pentynyl group, 4-pentynyl group, 1-methyl-2-butynyl group, 1-methyl-3-butynyl group, 2-methyl-3-butynyl group, 3-methyl-1-butynyl group and the above heterocyclic group may be optionally substituted with one or more substituents selected from the group consisting of a hydroxyl group, an amino group, a thiol group, a carboxyl group, a phosphonic group, a sulfonic group, a carbamoyl group, a carboxyl group, a phosphonic group, a sulfonic, Hydroxycarbamoyl, cyanocarbamoyl, sulphamoyl, hydroxysulphamoyl, cyanosulphamoyl, tetrazolyl, -CH 2CO2H、-OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H、-CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH、C1-10Alkoxycarbonyl group, C1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10Alkylcarbonylamino (this C)1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonylamino group may be optionally substituted with one or more substituents selected from the group consisting of: hydroxy, carboxy, carbamoyl, sulfonic acid, and sulfamoyl):
aryl: phenyl, thienyl (2-thienyl and 3-thienyl), furyl (2-furyl and 3-furyl), pyridazinyl (3-pyridazinyl and 4-pyridazinyl), pyridyl (2-pyridyl, 3-pyridyl and 4-pyridyl), quinolyl (2-quinolyl, 3-quinolyl, 4-quinolyl, 5-quinolyl, 6-quinolyl, 7-quinolyl and 8-quinolyl) and isoquinolyl (1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl, 5-isoquinolyl, 6-isoquinolyl, 7-isoquinolyl and 8-isoquinolyl);
heterocyclic group: 1, 3, 4-oxadiazolyl, 1, 3, 4-thiadiazolyl, 1, 2, 4-oxadiazolyl, 1, 2, 4-thiadiazolyl, 1, 2, 5-oxadiazolyl, 1, 2, 5-thiadiazolyl, 1, 2-oxazolyl, and 1, 2-thiazolyl).
36) The compound of 24), 25) or 26), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein L is4Is NR22(wherein, R22Is hydrogen atom, hydroxy, formyl, C1-10Alkyl, aryl, heteroaryl, and heteroaryl,C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C 1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy)), and R3Is methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, c-propyl, c-butyl, c-pentyl, c-hexyl, ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 4-pentynyl, 1-methyl-2-butynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-1-butynyl or any of the following heterocyclic groups:
(the methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, s-butyl group, t-butyl group, c-propyl group, c-butyl group, c-pentyl group, c-hexyl group, ethynyl group, 1-propynyl group, 2-propynyl group, 1-butynyl group, 2-butynyl group, 3-butynyl group, 1-pentynyl group, 2-pentynyl group, 4-pentynyl group, 1-methyl-2-butynyl group, 1-methyl-3-butynyl group, 2-methyl-3-butynyl group, 3-methyl-1-butynyl group and the above heterocyclic group may be optionally substituted with one or more substituents selected from the group consisting of a hydroxyl group, an amino group, a thiol group, a carboxyl group, a phosphonic group, a sulfonic group, a carbamoyl group, a, Hydroxycarbamoyl, cyanocarbamoyl, sulphamoyl, hydroxysulphamoyl, cyanosulphamoyl, tetrazolyl, -CH 2CO2H、-OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H、-CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH、C1-10Alkoxycarbonyl group, C1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10Alkylcarbonylamino (this C)1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonylamino group may be optionally substituted with one or more substituents selected from the group consisting of: hydroxyl, carboxyl, carbamoyl, sulfonic acid, and sulfamoyl)).
37) The compound of 24), 25) or 26), a tautomer, prodrug or pharmaceutically acceptable salt thereofA salt or solvate thereof, wherein L4Is NR22(wherein, R22Is hydrogen atom, hydroxy, formyl, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C 1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy)), and R3Is methyl, ethyl, n-propyl, i-propyl, n-butyl, c-propyl, c-hexyl, ethynyl, 1-propynyl, 2-propynyl or 1-butynyl (which methyl, ethyl, n-propyl, i-propyl, n-butyl, c-propyl, c-hexyl, ethynyl, 1-propynyl, 2-propynyl and 1-butynyl may optionally be substituted by one or more substituents selected from the group consisting of And (3) substitution: hydroxy, amino, thiol, carboxy, phosphonate, sulfonate, carbamoyl, hydroxycarbamoyl, cyanocarbamoyl, sulfamoyl, hydroxysulfamoyl, cyanosulfamoyl, tetrazolyl, -CH2CO2H、-OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H、-CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH、C1-10Alkoxycarbonyl group, C1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10Alkylcarbonylamino (this C)1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonylamino group may be optionally substituted with one or more substituents selected from the group consisting of: hydroxyl, carboxyl, carbamoyl, sulfonic acid, and sulfamoyl)).
38) The compound of 24), 25) or 26), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein L is4Is NR22(wherein, R22Is hydrogen atom, hydroxy, formyl, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C) 1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more substituents selected from the group consisting of: a carboxyl group,Nitro, cyano, halogen atoms, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy)), and R3Is methyl, ethyl, n-propyl, i-propyl, n-butyl, c-propyl, c-hexyl, ethynyl, 1-propynyl, 2-propynyl or 1-butynyl (which methyl, ethyl, n-propyl, i-propyl, n-butyl, c-propyl, c-hexyl, ethynyl, 1-propynyl, 2-propynyl and 1-butynyl may be optionally substituted by one or more substituents selected from the group consisting of hydroxy, amino, thiol, carboxy, phosphonate, sulphonic acid, carbamoyl, hydroxycarbamoyl, cyanocarbamoyl, sulphamoyl, tetrazolyl, -CH 2CO2H、-OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H、-CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH and C1-10Alkoxycarbonyl groups).
39) The compound of 24), 25) or 26), which isOr a pharmaceutically acceptable salt or solvate thereof, wherein L is4Is NR22(wherein, R22Is hydrogen atom, hydroxy, formyl, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C 2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy)), and R3Is any one of the following heterocyclic groups:
(the above heterocyclic group may be optionally substituted with one or more substituents selected from the group consisting of a hydroxyl group, an amino group, a thiol group, a carboxyl group, a phosphonic acid group, a sulfonic acid group, a carbamoyl group, a hydroxycarbamoyl group, a cyanocarbamoyl group, a sulfamoyl group, a hydroxysulfamoyl group, a cyanosulfamoyl group, a tetrazolyl group, -CH2CO2H、-OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H、-CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH、C1-10Alkoxycarbonyl group, C1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10Alkylcarbonylamino (this C)1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonylamino group may be optionally substituted with one or more substituents selected from the group consisting of: hydroxyl, carboxyl, carbamoyl, sulfonic acid, and sulfamoyl)).
40) The compound of 24), 25) or 26), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein L is4Is NR22(wherein, R22Is hydrogen atom, hydroxy, formyl, C1-10Alkyl radical, C1-1Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C 1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy)), and R3Is any one of the following heterocyclic groups:
(the above heterocyclic group may be optionally substituted with one or more substituents selected from the group consisting of a hydroxyl group, an amino group, a thiol group, a carboxyl group, a phosphonic acid group, a sulfonic acid group, a carbamoyl group, a hydroxycarbamoyl group, a cyanocarbamoyl group, a sulfamoyl group, a hydroxysulfamoyl group, a cyanosulfamoyl group, a tetrazolyl group, -CH2CO2H、-OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H、-CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH and C1-10Alkoxycarbonyl groups).
41) The compound of 24), 25) or 26), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein L is4Is NR22(wherein, R22Is hydrogen atom, hydroxy, formyl, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C 1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy)), and R3Is any one of the following heterocyclic groups:
(the above heterocyclic group may be optionally substituted with one or more substituents selected from the group consisting of a hydroxyl group, an amino group, a thiol group, a carboxyl group, a phosphonic acid group, a sulfonic acid group, a carbamoyl group, a hydroxycarbamoyl group, a cyanocarbamoyl group, a sulfamoyl group, a hydroxysulfamoyl group, a cyanosulfamoyl group, a tetrazolyl group, -CH 2CO2H、-OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H、-CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH、C1-10Alkoxycarbonyl group, C1-10Alkyl radical, C2-10Alkenyl radical, C22-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10Alkylcarbonylamino (this C)1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonylamino group may be optionally substituted with one or more substituents selected from the group consisting of: hydroxyl, carboxyl, carbamoyl, sulfonic acid, and sulfamoyl)).
42) The compound of 24), 25) or 26), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein L is4Is NR22(wherein, R22Is hydrogen atom, hydroxy, formyl, C1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonyl (the C)1-10Alkyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-10Alkoxy radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonyl group may be optionally substituted with one or more substituents selected from the group consisting of: carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C 1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy group (the C)2-14Aryl and C2-14Aryloxy groups may be substituted by one or more C1-6Alkyl substitution (of this C)1-6Alkyl groups may be substituted with one or more halogen atoms) or C2-14Aryl radical (the radical C)2-14The aryl group may be optionally substituted with one or more substituents selected from the group consisting of: c1-10Alkyl (the C)1-10Alkyl groups which may be substituted by one or more halogen atoms), C2-6Alkenyl radical, C2-6Alkynyl, carboxyl, nitro, cyano, halogen atom, C1-10Alkoxy radical, C1-10Alkylcarbonyl group, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino, amino, mono-or di-C1-10Alkylamino, hydroxy, protected hydroxy, C2-14Aryl and C2-14Aryloxy)), and R3Is any one of the following heterocyclic groups:
(the above heterocyclic group may be optionally substituted with one or more substituents selected from the group consisting of a hydroxyl group, an amino group, a thiol group, a carboxyl group, a phosphonic acid group, a sulfonic acid group, a carbamoyl group, a hydroxycarbamoyl group, a cyanocarbamoyl group, a sulfamoyl groupRadical, hydroxysulfamoyl, cyanosulfamoyl, tetrazolyl, -CH 2CO2H、-OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H、-CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH and C1-10Alkoxycarbonyl groups).
43) The compound of 24), 25) or 26), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein L is4Is NH, R3Is ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, c-propyl, c-butyl, c-pentyl, c-hexyl, ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 4-pentynyl, 1-methyl-2-butynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-1-butynyl or any of the following heterocyclic groups:
(the ethyl group, n-propyl group, i-propyl group, n-butyl group, s-butyl group, t-butyl group, c-propyl group, c-butyl group, c-pentyl group, c-hexyl group, ethynyl group, 1-propynyl group, 2-propynyl group, 1-butynyl group, 2-butynyl group, 3-butynyl group, 1-pentynyl group, 2-pentynyl group, 4-pentynyl group, 1-methyl-2-butynyl group, 1-methyl-3-butynyl group, 2-methyl-3-butynyl group, 3-methyl-1-butynyl group and the above heterocyclic group may be optionally substituted with one or more substituents selected from the group consisting of a hydroxyl group, an amino group, a thiol group, a carboxyl group, a phosphonic group, a sulfonic group, a carbamoyl group, a carboxyl group, a phosphonic group, a sulfonic, Hydroxycarbamoyl, cyanocarbamoyl, sulphamoyl, hydroxysulphamoyl, cyanosulphamoyl, tetrazolyl, -CH 2CO2H、-OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H、-CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH、C1-10Alkoxycarbonyl group, C1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino and the following aryl and heterocyclyl radicals (C1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10The alkylcarbonylamino group and the following aryl and heterocyclyl groups may be optionally substituted with one or more substituents selected from the group consisting of: hydroxy, carboxy, carbamoyl, sulfonic acid, and sulfamoyl):
aryl: phenyl, thienyl (2-thienyl and 3-thienyl), furyl (2-furyl and 3-furyl), pyridazinyl (3-pyridazinyl and 4-pyridazinyl), pyridyl (2-pyridyl, 3-pyridyl and 4-pyridyl), quinolyl (2-quinolyl, 3-quinolyl, 4-quinolyl, 5-quinolyl, 6-quinolyl, 7-quinolyl and 8-quinolyl) and isoquinolyl (1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl, 5-isoquinolyl, 6-isoquinolyl, 7-isoquinolyl and 8-isoquinolyl);
heterocyclic group: 1, 3, 4-oxadiazolyl, 1, 3, 4-thiadiazolyl, 1, 2, 4-oxadiazolyl, 1, 2, 4-thiadiazolyl, 1, 2, 5-oxadiazolyl, 1, 2, 5-thiadiazolyl, 1, 2-oxazolyl, and 1, 2-thiazolyl).
44) The compound of 24), 25) or 26), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein L is4Is NH, R3Is methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, c-propyl, c-butyl, c-pentyl, c-hexyl, ethynyl, 1-propynyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-pentyl, n-,2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 4-pentynyl, 1-methyl-2-butynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-1-butynyl or any of the following heterocyclic groups:
(the methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, s-butyl group, t-butyl group, c-propyl group, c-butyl group, c-pentyl group, c-hexyl group, ethynyl group, 1-propynyl group, 2-propynyl group, 1-butynyl group, 2-butynyl group, 3-butynyl group, 1-pentynyl group, 2-pentynyl group, 4-pentynyl group, 1-methyl-2-butynyl group, 1-methyl-3-butynyl group, 2-methyl-3-butynyl group, 3-methyl-1-butynyl group and the above heterocyclic group may be optionally substituted with one or more substituents selected from the group consisting of a hydroxyl group, an amino group, a thiol group, a carboxyl group, a phosphonic group, a sulfonic group, a carbamoyl group, a, Hydroxycarbamoyl, cyanocarbamoyl, sulphamoyl, hydroxysulphamoyl, cyanosulphamoyl, tetrazolyl, -CH 2CO2H、-OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H、-CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH、C1-10Alkoxycarbonyl group, C1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10Alkylcarbonylamino (this C)1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl radicalAnd C1-10The alkylcarbonylamino group may be optionally substituted with one or more substituents selected from the group consisting of: hydroxyl, carboxyl, carbamoyl, sulfonic acid, and sulfamoyl)).
45) The compound of 24), 25) or 26), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein L is4Is NH, R3Is methyl, ethyl, n-propyl, i-propyl, n-butyl, c-propyl, c-hexyl, ethynyl, 1-propynyl, 2-propynyl or 1-butynyl (which methyl, ethyl, n-propyl, i-propyl, n-butyl, c-propyl, c-hexyl, ethynyl, 1-propynyl, 2-propynyl and 1-butynyl may be optionally substituted by one or more substituents selected from the group consisting of hydroxy, amino, thiol, carboxy, phosphonate, sulphonic acid, carbamoyl, hydroxycarbamoyl, cyanocarbamoyl, sulphamoyl, tetrazolyl, -CH 2CO2H、 -OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H、-CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH、C1-10Alkoxycarbonyl group, C1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10Alkylcarbonylamino (this C)1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonylamino group may be optionally substituted with one or more substituents selected from the group consisting of: hydroxyl, carboxyl, carbamoyl, sulfonic acid, and sulfamoyl)).
46) The compound of 24), 25) or 26), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein L is4Is NH, R3Is methyl, ethyl, n-propyl, i-propyl, n-butyl, c-propyl, c-hexyl, ethynyl, 1-propynyl, 2-propynyl or 1-butynyl (which methyl, ethyl, n-propyl, i-propyl, n-butyl, c-propyl, c-hexyl, ethynyl, 1-propynyl, 2-propynyl and 1-butynyl may be optionally substituted by one or more substituents selected from the group consisting of hydroxy, amino, thiol, carboxy, phosphonate, sulphonic acid, carbamoyl, hydroxycarbamoyl, cyanocarbamoyl, sulphamoyl, tetrazolyl, -CH 2CO2H、-OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H、-CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH and C1-10Alkoxycarbonyl groups).
47) The compound of 24), 25) or 26), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein L is4Is NH, R3Is any one of the following heterocyclic groups:
(the above heterocyclic group may be optionally substituted with one or more substituents selected from the group consisting of a hydroxyl group, an amino group, a thiol group, a carboxyl group, a phosphonic acid group, a sulfonic acid group, a carbamoyl group, a hydroxycarbamoyl group, a cyanocarbamoyl group, a sulfamoyl group, a hydroxysulfamoyl group, a cyanosulfamoyl group, a tetrazolyl group, -CH2CO2H、-OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H、-CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH、C1-10Alkoxycarbonyl group, C1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10Alkylcarbonylamino (this C)1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonylamino group may be optionally substituted with one or more substituents selected from the group consisting of: hydroxyl, carboxyl, carbamoyl, sulfonic acid, and sulfamoyl)).
48) The compound of 24), 25) or 26), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein L is 4Is NH, R3Is any one of the following heterocyclic groups:
(the above heterocyclic group may be optionally substituted with one or more substituents selected from the group consisting of a hydroxyl group, an amino group, a thiol group, a carboxyl group, a phosphonic acid group, a sulfonic acid group, a carbamoyl group, a hydroxycarbamoyl group, a cyanocarbamoyl group, a sulfamoyl group, a hydroxysulfamoyl group, a cyanosulfamoyl group, a tetrazolyl group, -CH2CO2H、-OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H、-CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH and C1-10Alkoxycarbonyl groups).
49) As described in 24), 25) or 26)A compound, a tautomer, prodrug or pharmaceutically acceptable salt of said compound or a solvate thereof, wherein, L4Is NH, R3Is any one of the following heterocyclic groups:
(the above heterocyclic group may be optionally substituted with one or more substituents selected from the group consisting of a hydroxyl group, an amino group, a thiol group, a carboxyl group, a phosphonic acid group, a sulfonic acid group, a carbamoyl group, a hydroxycarbamoyl group, a cyanocarbamoyl group, a sulfamoyl group, a hydroxysulfamoyl group, a cyanosulfamoyl group, a tetrazolyl group, -CH2CO2H、-OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H、-CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH、C1-10Alkoxycarbonyl group, C1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10Alkylcarbonylamino (this C) 1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonylamino group may be optionally substituted with one or more substituents selected from the group consisting of: hydroxyl, carboxyl, carbamoyl, sulfonic acid, and sulfamoyl)).
50) The compound of 24), 25) or 26), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein L is4Is NH, R3Is any one of the following heterocyclic groups:
(the above heterocyclic group may be optionally substituted with one or more substituents selected from the group consisting of a hydroxyl group, an amino group, a thiol group, a carboxyl group, a phosphonic acid group, a sulfonic acid group, a carbamoyl group, a hydroxycarbamoyl group, a cyanocarbamoyl group, a sulfamoyl group, a hydroxysulfamoyl group, a cyanosulfamoyl group, a tetrazolyl group, -CH2CO2H、-OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H、-CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH and C1-10Alkoxycarbonyl groups).
51) The compound of 24), 25) or 26), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein L is4Is an oxygen or sulfur atom, R3Is ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, c-propyl, c-butyl, c-pentyl, c-hexyl, ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 4-pentynyl, 1-methyl-2-butynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-1-butynyl or any of the following heterocyclic groups:
(the ethyl group, n-propyl group, i-propyl group, n-butyl group, s-butyl group, t-butyl group, c-propyl group, c-butyl group, c-pentyl group, c-hexyl group, ethynyl group, 1-propynyl group, 2-propynyl group, 1-butynyl group, 2-butynyl group, 3-butynyl group, 1-pentynyl group, 2-pentynyl group, 4-pentynyl group, 1-methyl-2-butynyl groupThe group, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-1-butynyl and the above heterocyclic groups may be optionally substituted by one or more substituents selected from the group consisting of: hydroxy, amino, thiol, carboxy, phosphonate, sulfonate, carbamoyl, hydroxycarbamoyl, cyanocarbamoyl, sulfamoyl, hydroxysulfamoyl, cyanosulfamoyl, tetrazolyl, -CH2CO2H、-OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H、-CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH、C1-10Alkoxycarbonyl group, C1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10Alkylcarbonylamino and the following aryl and heterocyclyl radicals (C1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl group, C1-10The alkylcarbonylamino group and the following aryl and heterocyclyl groups may be optionally substituted with one or more substituents selected from the group consisting of: hydroxy, carboxy, carbamoyl, sulfonic acid, and sulfamoyl):
Aryl: phenyl, thienyl (2-thienyl and 3-thienyl), furyl (2-furyl and 3-furyl), pyridazinyl (3-pyridazinyl and 4-pyridazinyl), pyridyl (2-pyridyl, 3-pyridyl and 4-pyridyl), quinolyl (2-quinolyl, 3-quinolyl, 4-quinolyl, 5-quinolyl, 6-quinolyl, 7-quinolyl and 8-quinolyl) and isoquinolyl (1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl, 5-isoquinolyl, 6-isoquinolyl, 7-isoquinolyl and 8-isoquinolyl);
heterocyclic group: 1, 3, 4-oxadiazolyl, 1, 3, 4-thiadiazolyl, 1, 2, 4-oxadiazolyl, 1, 2, 4-thiadiazolyl, 1, 2, 5-oxadiazolyl, 1, 2, 5-thiadiazolyl, 1, 2-oxazolyl, and 1, 2-thiazolyl).
52) The compound of 24), 25) or 26), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein L is4Is an oxygen or sulfur atom, R3Is methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, c-propyl, c-butyl, c-pentyl, c-hexyl, ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 4-pentynyl, 1-methyl-2-butynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-1-butynyl or any of the following heterocyclic groups:
(the methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, s-butyl group, t-butyl group, c-propyl group, c-butyl group, c-pentyl group, c-hexyl group, ethynyl group, 1-propynyl group, 2-propynyl group, 1-butynyl group, 2-butynyl group, 3-butynyl group, 1-pentynyl group, 2-pentynyl group, 4-pentynyl group, 1-methyl-2-butynyl group, 1-methyl-3-butynyl group, 2-methyl-3-butynyl group, 3-methyl-1-butynyl group and the above heterocyclic group may be optionally substituted with one or more substituents selected from the group consisting of a hydroxyl group, an amino group, a thiol group, a carboxyl group, a phosphonic group, a sulfonic group, a carbamoyl group, a, Hydroxycarbamoyl, cyanocarbamoyl, sulphamoyl, hydroxysulphamoyl, cyanosulphamoyl, tetrazolyl, -CH2CO2H、-OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H、-CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH、C1-10Alkoxycarbonyl group, C1-10Alkyl radical, C2-10An alkenyl group,C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10Alkylcarbonylamino (this C)1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonylamino group may be optionally substituted with one or more substituents selected from the group consisting of: hydroxyl, carboxyl, carbamoyl, sulfonic acid, and sulfamoyl)).
53) The compound of 24), 25) or 26), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein L is4Is an oxygen or sulfur atom, R3Is methyl, ethyl, n-propyl, i-propyl, n-butyl, c-propyl, c-hexyl, ethynyl, 1-propynyl, 2-propynyl or 1-butynyl (which methyl, ethyl, n-propyl, i-propyl, n-butyl, c-propyl, c-hexyl, ethynyl, 1-propynyl, 2-propynyl and 1-butynyl may be optionally substituted by one or more substituents selected from the group consisting of hydroxy, amino, thiol, carboxy, phosphonate, sulphonic acid, carbamoyl, hydroxycarbamoyl, cyanocarbamoyl, sulphamoyl, tetrazolyl, -CH2CO2H、-OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H、-CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH、C1-10Alkoxycarbonyl group, C1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkylcarbonyloxy, C1-10Alkoxycarbonyl and C1-10Alkylcarbonylamino (this C)1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C 1-10Alkoxycarbonyl and C1-10The alkylcarbonylamino group may be optionally substituted with one or more substituents selected from the group consisting of: hydroxyl, carboxyl, carbamoyl, sulfonic acid, and sulfamoyl)).
54) The compound of 24), 25) or 26), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein L is4Is an oxygen or sulfur atom, R3Is methyl, ethyl, n-propyl, i-propyl, n-butyl, c-propyl, c-hexyl, ethynyl, 1-propynyl, 2-propynyl or 1-butynyl (which methyl, ethyl, n-propyl, i-propyl, n-butyl, c-propyl, c-hexyl, ethynyl, 1-propynyl, 2-propynyl and 1-butynyl may be optionally substituted by one or more substituents selected from the group consisting of hydroxy, amino, thiol, carboxy, phosphonate, sulphonic acid, carbamoyl, hydroxycarbamoyl, cyanocarbamoyl, sulphamoyl, tetrazolyl, -CH2CO2H、-OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H、-CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH and C1-10Alkoxycarbonyl groups).
55) The compound of 24), 25) or 26), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein L is4Is an oxygen or sulfur atom, R 3Any of the following heterocyclic groups of (a):
(the above heterocyclic group may be optionally substituted with one or more substituents selected from the group consisting of a hydroxyl group, an amino group, a thiol group, a carboxyl group, a phosphonic acid group, a sulfonic acid group, a carbamoyl group, a hydroxycarbamoyl group, a cyanocarbamoyl group, a sulfamoyl group, a hydroxysulfamoyl group, a cyanosulfamoyl group, a tetrazolyl group, -CH2CO2H、-OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H、-CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH、C1-10Alkoxycarbonyl group, C1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10Alkylcarbonylamino (this C)1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonylamino group may be optionally substituted with one or more substituents selected from the group consisting of: hydroxyl, carboxyl, carbamoyl, sulfonic acid, and sulfamoyl)).
56) The compound of 24), 25) or 26), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein L is4Is an oxygen or sulfur atom, R3Is any one of the following heterocyclic groups:
(the above heterocyclic group may be optionally substituted with one or more substituents selected from the group consisting of a hydroxyl group, an amino group, a thiol group, a carboxyl group, a phosphonic acid group, a sulfonic acid group, a carbamoyl group, a hydroxycarbamoyl group, a cyanocarbamoyl group, a sulfamoyl group, a hydroxysulfamoyl group, a cyanosulfamoyl group, a tetrazolyl group, -CH2CO2H、-OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H、-CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH and C1-10Alkoxycarbonyl groups).
57) The compound of 24), 25) or 26), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein L is4Is an oxygen or sulfur atom, R3Is any one of the following heterocyclic groups:
(the above heterocyclic group may be optionally substituted with one or more substituents selected from the group consisting of a hydroxyl group, an amino group, a thiol group, a carboxyl group, a phosphonic acid group, a sulfonic acid group, a carbamoyl group, a hydroxycarbamoyl group, a cyanocarbamoyl group, a sulfamoyl group, a hydroxysulfamoyl group, a cyanosulfamoyl group, a tetrazolyl group, -CH2CO2H、-OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H、-CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH、C1-10Alkoxycarbonyl group, C1-10Alkyl radical, C2-10Alkenyl radical, C2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10Alkylcarbonylamino (this C)1-10Alkyl radical, C2-10Alkenyl radical, C 2-10Alkynyl, C2-9Heterocyclic group, C1-10Alkoxy radical, C1-10Thioalkyl, C1-10Alkylcarbonyl, mono-or di-C1-10Alkylamino radical, C1-10Alkyl carbonyl oxy, C1-10Alkoxycarbonyl and C1-10The alkylcarbonylamino group may be optionally substituted with one or more substituents selected from the group consisting of: hydroxyl, carboxyl, carbamoyl, sulfonic acid, and sulfamoyl)).
58) The compound of 24), 25) or 26), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein L is4Is an oxygen or sulfur atom, R3Is any one of the following heterocyclic groups:
(the above heterocyclic group may be optionally substituted with one or more substituents selected from the group consisting of a hydroxyl group, an amino group, a thiol group, a carboxyl group, a phosphonic acid group, a sulfonic acid group, a carbamoyl group, a hydroxycarbamoyl group, a cyanocarbamoyl group, a sulfamoyl group, a hydroxysulfamoyl group, a cyanosulfamoyl group, a tetrazolyl group, -CH2CO2H、-OCH2CO2H、-NHCH2CO2H、-CH2CH2CO2H、-CH2OH、-OCH2OH、-NHCH2OH、-CH2CH2OH and C1-10Alkoxycarbonyl groups).
59) A compound, a tautomer, prodrug or pharmaceutically acceptable salt of said compound or a solvate thereof, wherein A, B, R1、L1、R2、L2、L3、Y、L4、R3And X is any combination shown in table 1 below. The symbols in table 1 represent the following substituents.
TABLE 1
60) Compound (I) wherein, A, B, R 1、L1、R2、L2、L3、Y、L4、R3And X is any combination shown in table 2, a tautomer, prodrug, or pharmaceutically acceptable salt of the compound or a solvate thereof. The symbols in Table 2 represent the following substitutionsAnd (4) a base.
TABLE 2
61) A compound of formula (I), wherein A, B, R1，L1，R2，L2，L2，Y，L4，R3And X is any combination shown in table 2, Q1a, Q1b, Q1c, Q1i, Q1j, T3a, T3b, T3c, T3d, T3e, Q3e, T3f, T3g, T3h, T3i and T3j in table 2 represent the following substituents, in the case of a tautomer, prodrug or pharmaceutically acceptable salt of the compound or a solvate thereof (provided that at 61). )
62) Compound (I) wherein, A, B, R1、L1、R2、L2、L3、Y、L4、R3And X is any combination shown in table 3, a tautomer, prodrug, or pharmaceutically acceptable salt of the compound or a solvate thereof. The symbols in table 3 represent the following substituents.
TABLE 3
63) Compound (I) wherein, A, B, R1、L1、R2、L2、L3、Y、L4、R3And X is any combination shown in table 3, Q1a, Q1b, and Q3a in table 3 represent the following substituents, in the case of a tautomer, prodrug, or pharmaceutically acceptable salt of the compound, or solvate thereof (provided at 63).
64) Compound (I) wherein, A, B, R1、L1、R2、L2、L3、Y、L4、R3And X is any combination shown in table 2, Q1a, Q1b, Q1c, Q1i, Q1j, T3a, T3b, T3c, T3d, T3e, Q3e, T3f, T3g, T3h, T3i, and T3j in table 2 represent the following substituents, in the case of a tautomer, prodrug, or pharmaceutically acceptable salt of the compound, or a solvate thereof (provided that at 64).
65) Compound (I) wherein, A, B, R1、L1、R2、L2、L3、Y、L4、R3And X is any combination shown in table 1, Q1a, Q1b, Q1c, Q1d, Q1e, Q1f, Q1g, Q1h, Q1i, Q1j, Q1k, Q1l, Q1m, Q1n, Q1k ', Q1 l', Q1m ', Q1 n', Q3a, Q3b, Q3c, Q3d, Q3e, Q3f, Q3g and Q3h in table 1 represent the following substituents.
66) Compound (I) wherein, A, B, R1、L1、R2、L2、L3、Y、L4、R3And X is any combination shown in table 1, Q1a, Q1b, Q1c, Q1d, Q1e, Q1f, Q1g, Q1h, Q1i, Q1j, Q1k, Q1l, Q1m, Q1n, Q1k ', Q1 l', Q1m ', Q1 n', Q3a, Q3b, Q3c, Q3d, Q3e, Q3f, Q3g and Q3h in table 1 represent the following substituents.
67) Compound (I) wherein, A, B, R1、L1、R2、L2、L3、Y、L4、R3And X is any combination shown in table 1, Q1a, Q1b, Q1c, Q1d, Q1e, Q1f, Q1g, Q1h, Q1i, Q1j, Q1k, Q1l, Q1m, Q1n, Q1k ', Q1 l', Q1m ', Q1 n', Q3a, Q3b, Q3c, Q3d, Q3e, Q3f, Q3g and Q3h in table 1 represent the following substituents.
68) Compound (I) wherein, A, B, R1、L1、R2、L2、L3、Y、L4、R3And X is any combination shown in table 1, Q1a, Q1b, Q1c, Q1d, Q1e, Q1f, Q1g, Q1h, Q1i, Q1j, Q1k, Q1l, Q1m, Q1n, Q1k ', Q1 l', Q1m ', Q1 n', Q3a, Q3b, Q3c, Q3d, Q3e, Q3f, Q3g and Q3h in table 1 represent the following substituents.
69) Compound (I) wherein, A, B, R1、L1、R2、L2、L3、Y、L4、R3And X is any combination shown in table 1, Q1a, Q1b, Q1c, Q1d, Q1e, Q1f, Q1g, Q1h, Q1i, Q1j, Q1k, Q1l, Q1m, Q1n, Q1k ', Q1 l', Q1m ', Q1 n', Q3a, Q3b, Q3c, Q3d, Q3e, Q3f, Q3g and Q3h in table 1 represent the following substituents.
70) Compound (I) wherein, A, B, R1、L1、R2、L2、L3、Y、L4、R3And X is any combination shown in table 1, Q1a, Q1b, Q1c, Q1d, Q1e, Q1f, Q1g, Q1h, Q1i, Q1j, Q1k, Q1l, Q1m, Q1n, Q1k ', Q1 l', Q1m ', Q1 n', Q3a, Q3b, Q3c, Q3d, Q3e, Q3f, Q3g and Q3h in table 1 represent the following substituents.
71) Compound (I) wherein, A, B, R1、L1、R2、L2、L3、Y、L4、R3And X is any combination shown in Table 1, a tautomer, prodrug or pharmaceutically acceptable salt of the compound or a solvent thereofIn the case of the compound (provided that 71), Q1a, Q1b, Q1c, Q1d, Q1e, Q1f, Q1g, Q1h, Q1i, Q1j, Q1k, Q1l, Q1m, Q1n, Q1k ', Q1 l', Q1m ', Q1 n', Q3a, Q3b, Q3c, Q3d, Q3e, Q3f, Q3g and Q3h in table 1 represent the following substituents.
72) Compound (I) wherein, A, B, R1、L1、R2、L2、L3、Y、L4、R3And X is any combination shown in table 1, Q1a, Q1b, Q1c, Q1d, Q1e, Q1f, Q1g, Q1h, Q1i, Q1j, Q1k, Q1l, Q1m, Q1n, Q1k ', Q1 l', Q1m ', Q1 n', Q3a, Q3b, Q3c, Q3d, Q3e, Q3f, Q3g and Q3h in table 1 represent the following substituents.
73) Compound (I) wherein, A, B, R1、L1、R2、L2、L3、Y、L4、R3And X is any combination shown in table 1, Q1a, Q1b, Q1c, Q1d, Q1e, Q1f, Q1g, Q1h, Q1i, Q1j, Q1k, Q1l, Q1m, Q1n, Q1k ', Q1 l', Q1m ', Q1 n', Q3a, Q3b, Q3c, Q3d, Q3e, Q3f, Q3g and Q3h in table 1 represent the following substituents.
74) Compound (I) wherein, A, B, R1、L1、R2、L2、L3、Y、L4、R3And X is any combination shown in table 1, Q1a, Q1b, Q1c, Q1d, Q1e, Q1f, Q1g, Q1h, Q1i, Q1j, Q1k, Q1l, Q1m, Q1n, Q1k ', Q1 l', Q1m ', Q1 n', Q3a, Q3b, Q3c, Q3d, Q3e, Q3f, Q3g and Q3h in table 1 represent the following substituents.
75) Compound (I) wherein, A, B, R1、L1、R2、L2、L3、Y、L4、R3And X is any combination shown in table 1, Q1a, Q1b, Q1c, Q1d, Q1e, Q1f, Q1g, Q1h, Q1i, Q1j, Q1k, Q1l, Q1m, Q1n, Q1k ', Q1 l', Q1m ', Q1 n', Q3a, Q3b, Q3c, Q3d, Q3e, Q3f, Q3g and Q3h in table 1 represent the following substituents.
76) Compound (I) wherein, A, B, R1、L1、R2、L2、L3、Y、L4、R3And X is any combination shown in table 1, a tautomer, prodrug, or pharmaceutically acceptable salt of the compound or solvate thereof (provided at 76) in table 1, Q1a, Q1b, Q1c, Q1d, Q1e, Q1f, Q1g, Q1h, Q1i, Q1j, Q1k, Q1l, Q1m, Q1n, Q1k ', Q1 l', Q1m ', Q1 n', Q3a, Q3b, Q3c, Q3d, or a solvate thereof, Q3e, Q3f, Q3g and Q3h represent the following substituents.
77) Compound (I) wherein, A, B, R1、L1、R2、L2、L3、Y、L4、R3And X is any combination shown in table 1, Q1a, Q1b, Q1c, Q1d, Q1e, Q1f, Q1g, Q1h, Q1i, Q1j, Q1k, Q1l, Q1m, Q1n, Q1k ', Q1 l', Q1m ', Q1 n', Q3a, Q3b, Q3c, Q3d, Q3e, Q3f, Q3g and Q3h in table 1 represent the following substituents.
78) Compound (I) wherein, A, B, R1、L1、R2、L2、L3、Y、L4、R3And X is any combination shown in table 1, Q1a, Q1b, Q1c, Q1d, Q1e, Q1f, Q1g, Q1h, Q1i, Q1j, Q1k, Q1l, Q1m, Q1n, Q1k ', Q1 l', Q1m ', Q1 n', Q3a, Q3b, Q3c, Q3d, Q3e, Q3f, Q3g and Q3h in table 1 represent the following substituents.
79) Compound (I) wherein, A, B, R1、L1、R2、L2、L3、Y、L4、R3And X isIn the case of any combination, prodrug or pharmaceutically acceptable salt of the compounds shown in table 1 or solvate thereof (provided at 79), Q1a, Q1b, Q1c, Q1d, Q1e, Q1f, Q1g, Q1h, Q1i, Q1j, Q1k, Q1l, Q1m, Q1n, Q1k ', Q1 l', Q1m ', Q1 n', Q3a, Q3b, Q3c, Q3d, Q3e, Q3f, Q3g and Q3h in table 1 represent the following substituents.
80) Compound (I) wherein, A, B, R1、L1、R2、L2、L3、Y、L4、R3And X is any combination shown in table 1, Q1a, Q1b, Q1c, Q1d, Q1e, Q1f, Q1g, Q1h, Q1i, Q1j, Q1k, Q1l, Q1m, Q1n, Q1k ', Q1 l', Q1m ', Q1 n', Q3a, Q3b, Q3c, Q3d, Q3e, Q3f, Q3g and Q3h in table 1 represent the following substituents.
81) Compound (I) wherein, A, B, R1、L1、R2、L2、L3、Y、L4、R3And X is any combination shown in table 1, Q1a, Q1b, Q1c, Q1d, Q1e, Q1f, Q1g, Q1h, Q1i, Q1j, Q1k, Q1l, Q1m, Q1n, Q1k ', Q1 l', Q1m ', Q1 n', Q3a, Q3b, Q3c, Q3d, Q3e, Q3f, Q3g and Q3h in table 1 represent the following substituents.
82) The compound represented by any one of 59) to 81) above, a tautomer, prodrug or pharmaceutically acceptable salt of the compound or a solvate thereof, wherein X is converted to SH.
83) The compound represented by any one of above 59) to 81), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or a solvate thereof, wherein X is changed to NH 2。
84) The compound represented by any one of 59) to 81) above, a tautomer, prodrug or pharmaceutically acceptable salt of the compound or solvate thereof, wherein X is converted to OAc.
85) A thrombopoietin receptor activator represented by any one of 1) to 84) above.
86) A prophylactic, therapeutic or ameliorating agent for a disease which can be effectively treated by activating a thrombopoietin receptor, which comprises the thrombopoietin receptor activator represented by the above 85) or formula (1), a tautomer, prodrug or pharmaceutically acceptable salt thereof, or a solvate of the same as an active ingredient.
87) A platelet increasing agent comprising a thrombopoietin receptor activator represented by the above 85) or formula (1), a tautomer, prodrug or pharmaceutically acceptable salt of the activator, or a solvate thereof, as an active ingredient.
88) A medicament containing a compound represented by any one of 1) to 84) or formula (1), a tautomer, prodrug or pharmaceutically acceptable salt of the compound, or a solvate thereof, as an active ingredient.
In the present invention, the compound represented by formula (1) of the present invention may exist in the following form: a tautomer or geometric isomer, a mixture of tautomers or geometric isomers, or a mixture thereof that undergoes endocyclic or exocyclic isomerization. When the compound of the present invention has an asymmetric center, whether the asymmetric center is generated by isomerization or not, the compound of the present invention may be in the form of a resolvable optical isomer or a mixture containing a certain proportion of optical isomers.
For example, the furan compounds, thiophene compounds and pyrrole compounds of the present invention may exist in the following forms: tetronic acid (4-hydroxy-2 (5H) -furanone) analogues, thiotetronic acid (4-hydroxy-2 (5H) -thiophenone) analogues and tetraminic acid (4-hydroxy-3-pyrrolin-2-one) analogues, mixtures thereof or mixtures of isomers thereof, represented by the following formulae (2), (3) and (4).
The compound represented by formula (1) of the present invention or a pharmaceutically acceptable salt thereof may be in the form of any crystal or any hydrate, depending on the production conditions. The present invention includes these crystals, hydrates and mixtures. They may be in the form of solvates with organic solvents such as acetone, ethanol and tetrahydrofuran, and the present invention includes any of these forms.
The compound represented by formula (1) of the present invention may be converted into a pharmaceutically acceptable salt or released from the resulting salt, if necessary. The pharmaceutically acceptable salts of the present invention may be, for example, salts with alkali metals (such as lithium, sodium and potassium), alkaline earth metals (such as magnesium and calcium), ammonium, organic bases and amino acids. They may be salts with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid and sulfuric acid and organic acids such as acetic acid, citric acid, maleic acid, fumaric acid, benzenesulfonic acid and p-toluenesulfonic acid.
The compounds which are prodrugs are derivatives of the present invention which have chemically or metabolically degradable groups to yield pharmaceutically active compounds of the present invention upon solvolysis or under physiological conditions in vivo. Selection or manufacture ofMethods of suitable prodrugs are described, for example, in Design of produgs (Elsevier, Amsterdam 1985). In the present invention, when a compound has a hydroxyl group, an acyloxy derivative obtained by, for example, reacting the compound with a suitable acid halide or a suitable acid anhydride may be referred to as a prodrug. Particularly preferred acyloxy groups as prodrugs include-OCOC2H5、-OCO(t-Bu)、-OCOC15H31、-OCO(m-CO2Na-Ph)、-OCOCH2CH2CO2Na、-OCOCH(NH2)CH3、-OCOCH2N(CH3)2And the like. When the compound of the present invention has an amino group, an amide derivative obtained by, for example, reacting the compound having an amino group with a suitable acid halide or a suitable mixed acid anhydride may be referred to as a prodrug. Particularly preferred amides as prodrugs include-NHCO (CH)2)2OOCH3、-NHCOCH(NH2)CH3And the like. When the compounds of the present invention contain a carboxyl group, a carboxylic acid ester of an aliphatic alcohol or a carboxylic acid ester obtained by reaction with an alcohol free hydroxyl group of a 1, 2-or 1, 3-diglyceride may be referred to as a prodrug. Particularly preferred prodrugs are methyl or ethyl esters.
A prophylactic, therapeutic or ameliorating agent for a disease which can be effectively treated by activating a thrombopoietin receptor, or a thrombopoietin comprising the thrombopoietin receptor activator, its tautomer, prodrug or pharmaceutically acceptable salt of the present invention or a solvate thereof as an active ingredient, which can be generally administered as an oral drug (such as tablet, capsule, powder, granule, pill and syrup), a rectal drug, a transdermal drug or an injection. The agents of the invention may be administered as a single therapeutic agent or as a mixture with other therapeutic agents. Although they may be administered as such, they may generally be administered in the form of a pharmaceutical composition. These pharmaceutical preparations can be obtained by conventional methods by adding pharmacologically or pharmaceutically acceptable additives. That is, for oral drugs, ordinary excipients, lubricants, binders, disintegrants, wetting agents, plasticizers, and coating agents may be used. Oral liquid preparations may be in the form of aqueous or oily suspensions, solutions, emulsions, slurries, or elixirs, or may be provided as a dry syrup for admixture with water or other suitable solvent prior to use. Such liquid preparations may contain conventional additives such as suspending agents, perfumes, diluents and emulsifiers. For rectal administration, they may be administered as suppositories. Suppositories may be used with suitable substances such as cocoa butter, lauryl ester (laurin tail), polyethylene glycol, glycerogelatin, Witepsol, sodium stearate and mixtures thereof as bases and, if desired, emulsifiers, suspending agents, preservatives and the like. For injection, pharmaceutical ingredients such as distilled water for injection, physiological saline, 5% dextrose solution, propylene glycol and other solvents or solubilizers, pH adjusting agents, isotonic agents (isotonizing agents), and stabilizers can be used to form aqueous dosage forms or dosage forms that require dissolution prior to use.
The dosage of the agent of the present invention for human administration is usually about 0.1 to 1000 mg/person/day when administered orally or rectally, and about 0.05 to 500 mg/person/day when injected, but this requirement depends on the age and symptoms of the patient. The above ranges are merely examples and the dosage should be determined by the symptoms of the patient.
The present invention is useful when improvement of pathological symptoms is expected using a compound having affinity for the thrombopoietin receptor and acting as an agonist of the thrombopoietin receptor. For example, hematological disorders accompanied by abnormal platelet counts are included. In particular, it is effective for treating or preventing a human or a mammal suffering from a disease caused by abnormal megakaryopoiesis (abnormal megakaryopoietisis), particularly a disease accompanied by thrombocytopenia. Examples of such diseases include thrombocytopenia accompanying cancer chemotherapy or radiotherapy, thrombocytopenia accompanying antiviral therapy for diseases such as hepatitis c, thrombocytopenia caused by bone marrow transplantation, surgery and severe infection or gastrointestinal bleeding, but the diseases are not limited thereto. Typical thrombocytopenias such as aplastic anemia, idiopathic thrombocytopenic purpura, myelodysplastic syndrome, liver disease, HIV infection, and thrombopoietin deficiency are also therapeutic targets of the agents of the present invention. The present invention can also be used as a peripheral stem cell activating agent, a promegakaryocyte or megakaryocyte leukemia cell differentiation inducer of a platelet donor, and a platelet increasing agent. In addition, potential uses include, but are not limited to, the prevention and treatment of arteriosclerosis, myocardial infarction, unstable angina, peripheral arterial occlusive disease, based on therapeutic angiogenesis of the differentiation and proliferation of vascular endothelial cells and endothelial progenitor cells.
The compound represented by the formula (1) is prepared by the method shown in the following formula (5).
Compound (I) and-NH2The compound (II) is reacted in a solvent, if necessary in the presence of a catalyst, heated and stirred to obtain the desired compound or a precursor thereof. If desired, the precursor may be hydrolyzed, deprotected, reduced or oxidized to the desired compound. The compounds of the invention can be purified, usually by column chromatography, thin layer chromatography, High Performance Liquid Chromatography (HPLC) or high performance liquid chromatography-mass spectrometry (LC-MS), if desired, by recrystallization or washing with a solvent to give a high purity product.
For the synthesis of intermediate (I), the following heterocyclic compounds can be preferably synthesized with reference to the following documents.
1) Pyrazole (formula (6))
Chem, soc, perkin, transi, page 81, (1985)
2) Isothiazole (formula (7))
Liebigs.Annalen.der.Chemie.，10，1534-1546(1979)
3) Isoxazoles (formula (8))
Synthesis，10，664-665(1975)
4) Thiophene (formula (9))
JP-A-48-026755
5) Furan (formula (10))
Chem., 21, 1492-1509(1956) and EP1253146
6) Pyrrole (formula (11))
Heterocyclic chem., 30, 1253(1993) and Tetrahedron, 50(26), 7849-56(1994)
7) Tetronic acid (4-hydroxy-2 (5H) -furanone) analogues (formula (12))
Synthesis, 7, 564-566(1988) and Yakugaku Zasshi, 96(4), 536-543(1976)
8) Tetraminic acid (4-hydroxy-3-pyrrolin-2-one) analogue (formula (13))
Synthesis, 2, 190-
For the synthesis of-NH2Compound (II), e.g. when L3When NH, reference is made to the following documents
1)L4Bond, Y ═ O
Synthetic Commun, 28(7), 1223-1231(1998), J.chem.Soc., 1225(1948) and J.chem.Soc., 2831(1952)
2)L4＝NH，Y＝O
Am, chem, soc, 46, 2813(1924) and j, chem, soc, 2654(1952)
3)L4＝NH，Y＝S
Can.J.Chem.，35，834(1957)
4)L4＝NR22Or N- (from R)22And R3Heterocyclic radicals formed)
J.Org.Chem.，53，2263(1988)
5)L4＝CH2，Y＝O
J.Org.Chem.，30，2487(1965)
6)L4＝O，Y＝O
Bul l.Soc.Chim.Belg.，68，409，(1959)
7)L4＝S，Y＝S
J.Med.Chem.，22，853(1979)
A compound represented by the formula (1) wherein L3Is NR19，L4NH and Y are O or S, and can be produced by the method represented by the following formula (14).
A compound represented by the formula (1) wherein L3Is NR19，L4Is a bond, and Y is O or S can be prepared by referring to the method represented by the following formula (15).
Compound (I) and NH2The compound (IV) is reacted in a solvent, if necessary in the presence of a catalyst, with heating and stirring to obtain the compound (III) as a desired product.
A compound represented by the formula (1) wherein L3Is NR19，L4Is NR22Or with R3Together form a heterocyclic group, and can be prepared by a method represented by the following formula (16).
Examples
Now, the present invention will be described in further detail with reference to synthesis examples, measurement examples and formulation examples. It should be understood, however, that the intention is not to limit the invention to the particular embodiments described.
1H-NMR analysis was carried out at 300MHz, and LC/MS was measured under the following conditions.
LC/MS Condition 1
Column: waters SunAire C18(3.5 μm, 4.6X 30mm)
Eluent: acetonitrile/0.1% aqueous formic acid (10/90 → 60/40)
LC/MS Condition 2
Column: waters SunAire C18(3.5 μm, 4.6X 30mm)
Eluent: acetonitrile/0.1% aqueous formic acid (10/90 → 85/15)
LC/MS Condition 3
Column: waters SunAire C18(3.5 μm, 4.6X 30mm)
Eluent: acetonitrile/0.1% aqueous formic acid (20/80 → 100/0)
LC/MS Condition 4
Column: waters Xterra MSC18(5 μm, 4.6X 50mm)
Eluent: acetonitrile/0.1% aqueous formic acid (10/90 → 60/40)
LC/MS Condition 5
Column: waters Xterra MSC18(3.5 μm, 2.1X 20mm)
Eluent: acetonitrile/0.2% aqueous formic acid (20/80 → 90/10)
Reference Synthesis example 1
Synthesis of 2- (3, 4-dichlorophenyl) -4- (1-hydrazono (hyorazano) ethyl) thiophen-3-ol
To a suspension of 2- (3, 4-dichlorophenyl) -3-hydroxy-4-methylcarbonylthiophene (300mg, 1.05mmol), prepared using the method disclosed in WO2004/108683, in isopropanol (20mL) was added hydrazine monohydrate (61. mu.L, 1.25 mmol). The reaction mixture was refluxed for 1.5 hours, stirred at room temperature for 0.5 hours, and stirred at 0 ℃ for 1 hour. The precipitated solid was collected by filtration and dried by a vacuum pump to obtain the desired product (yield 100%).
The form is as follows: pale yellow solid
1H-NMR(DMSO-d6)δ(ppm)：2.10(s，3H)，6.63(br s，2H)，7.58(s，2H)，7.61(s，1H)，7.98(s，1H)，12.88(s，1H)。
LC/MS: condition 4, Retention time 4.95 (minutes)
LC/MS(ESI+)m/z；301，303[M+1]+
LC/MS(ESI-)m/z；299，301[M-1]-
Reference Synthesis example 2
Synthesis of 1-hydrazinothiocarbonylpiperidine-4-carboxylic acid methyl ester
To a solution of methyl isopiperidinecarboxylate (1.0g, 7.0mmol) in tetrahydrofuran was added thiocarbonyldiimidazole (1.24g, 6.98mmol) at room temperature, and the reaction solution was stirred at room temperature for 1.5 hours and then stirred with hydrazine monohydrate (700mg, 14.0mmol) for 4 hours. After a saturated aqueous sodium chloride solution was added, the reaction solution was extracted with ethyl acetate and chloroform, and the extract was dried over anhydrous magnesium sulfate and concentrated to obtain the desired product (yield: 114%).
The form is as follows: pale yellow solid
LC/MS: condition 5, Retention time 0.52 (min)
LC/MS(ESI+)m/z；218，[M+1]+
Reference Synthesis example 3
Synthesis of 1-hydrazinothiocarbonylpiperidine-3-carboxylic acid ethyl ester
The synthesis was performed in the same manner as in reference synthesis example 2 using ethyl piperidinecarboxylate.
Reference Synthesis example 4
Synthesis of 1-hydrazinothiocarbonylpiperidine-4-carboxylic acid diethylamide
The synthesis was performed in the same manner as in reference synthesis example 2 using isopiperidine carboxylic acid diethylamide.
Reference Synthesis example 5
Synthesis of 1-hydrazinothiocarbonylpiperidin-4-ol (piperidin-4-ol)
A solution of methyl hydrazine carbothioate (1.0g, 8.2mmol) and piperidin-4-ol (1.24g, 12.3mmol) in ethanol (7mL) was heated at reflux for 2 days at 90 ℃. After addition of ethyl acetate, the reaction solution was washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated to obtain a crude desired product. The crude product can be used directly in the next reaction.
Reference Synthesis example 6
Synthesis of 1-hydrazinothiocarbonylpiperidin-3-ol
Synthesis was carried out in the same manner as in reference Synthesis example 5 using piperidin-3-ol.
Reference Synthesis example 7
Synthesis of 1-hydrazinothiocarbonylpiperidine-4-methanol
Synthesis was carried out in the same manner as in reference Synthesis example 5 using 4-piperidinemethanol.
Reference Synthesis example 8
Synthesis of methyl 2- [4- (tert-butoxycarbonyl) piperazin-1-yl ] acetate
A solution of 1- (tert-butoxycarbonyl) piperazine (1.38g, 7.41mmol) in acetonitrile (10mL) was stirred with triethylamine (2.07mL, 14.8mmol) and methyl 2-bromoacetate (1.02mL, 11.1mmol) at room temperature for 4 hours, then filtered. The filtrate was concentrated, and after adding a saturated aqueous ammonium chloride solution, extraction was performed with ethyl acetate. The organic phase was washed with a saturated aqueous solution of ammonium chloride and a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and concentrated to obtain the desired product (yield: 83%).
The form is as follows: light yellow liquid
1H-NMR(CDCl3)δ：1.46(s，9H)，2.53(t，J＝5.1Hz，4H)，3.24(s，2H)，3.49(t，J＝5.1Hz，4H)，3.73(s，3H)
Reference Synthesis example 9
Synthesis of ethyl 3- [4- (tert-butoxycarbonyl) piperazin-1-yl ] propionate
The synthesis was carried out in the same manner as in reference synthesis example 8 using ethyl 3-bromopropionate.
The form is as follows: colorless mixture of solid and liquid
1H-NMR(CDCl3)δ：1.26(t，J＝7.2Hz，3H)，1.46(s，9H)，2.41(t，J＝4.8Hz，4H)，2.50(t，J＝7.2Hz，2H)，2.71(t，J＝7.2Hz，2H)，3.42(t，J＝4.8Hz，4H)，4.14(q，J＝7.2Hz，2H)
Reference Synthesis example 10
Synthesis of methyl 2- [ 4-hydrazinothiocarbonylpiperazin-1-yl ] acetate
A solution of methyl 2- [4- (tert-butoxycarbonyl) piperazin-1-yl ] acetate in dioxane (9mL) prepared in reference synthesis example 8 was stirred with a 4N hydrogen chloride/dioxane solution (3.91mL, 15.7mmol) at 80 ℃ for 1.5 hours. The solution was allowed to cool and filtered. Tetrahydrofuran and triethylamine (0.88mL, 6.3mmol) were added to the filter cake, and the resulting solution was used to conduct the procedure of reference Synthesis example 2. The crude product produced can be used directly in the next reaction.
The form is as follows: pale yellow solid
Reference Synthesis example 11
Synthesis of ethyl 3- [ 4-hydrazinothiocarbonylpiperazin-1-yl ] propionate
Synthesis was carried out in the same manner as in reference Synthesis example 10 using ethyl 3- [4- (tert-butoxycarbonyl) piperazin-1-yl ] propionate prepared in reference Synthesis example 9.
The form is as follows: pale yellow solid
Synthesis example 1
Synthesis of 1- {1- [5- (3, 4-dichlorophenyl) -4-hydroxyphenylthio-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid methyl ester
Concentrated hydrochloric acid (9. mu.L, 0.1mmol) was added to a solution (600. mu.L) of 2- (3, 4-dichlorophenyl) -3-hydroxy-4-methylcarbonylthiophene (30mg, 0.10mmol) and methyl 1-hydrazinothiocarbonyl-piperidine-4-carboxylate (46mg, 0.20mmol) prepared in reference synthesis example 2 in dimethylformamide at room temperature, and the resultant solution was stirred at room temperature for 8 hours, then mixed with water and extracted with ethyl acetate. The extract was washed with 1M hydrochloric acid and saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated. The resultant residue was purified by silica gel column chromatography (hexane/ethyl acetate-1/1) and recrystallized from chloroform to obtain the desired product (yield: 55%).
The form is as follows: white solid
1H-NMR(DMSO-d6)δ：1.55-1.75(m，2H)，1.85-1.95(m，2H)，2.38(s，3H)，2.7-2.8(m，1H)，3.15-3.30(m，2H)，3.48(s，3H)，4.58(d，J＝13.5Hz，2H)，7.64(d，J＝8.4Hz，1H)，7.71(d，J＝8.4，2.1Hz，1H)，8.00(s，1H)，8.03(d，J＝2.1Hz，1H)，12.4(s，1H)
LC/MS: condition 5, Retention time 5.19 (minutes)
LC/MS(ESI+)m/z；486，488[M+1]+
LC/MS(ESI-)m/z；484；486[M-1]-
Synthesis example 2
Synthesis of 1- {1- [5- (3, 4-dichlorophenyl) -4-hydroxythiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid
To a suspension of 1- {1- [5- (3, 4-dichlorophenyl) -4-hydroxyphenylthio-3-yl ] -ethylidene-hydrazinocarbonyl } -piperidine-4-carboxylic acid methyl ester (10mg, 0.021mmol) in methanol (300. mu.L) was added 1M aqueous sodium hydroxide solution (250. mu.L) at room temperature, and the suspension was stirred at room temperature for 7 hours. After the reaction, 1M hydrochloric acid (250. mu.L) was added, and the formed crystals were collected by filtration to obtain the desired product (yield: 71%).
The form is as follows: grey solid
LC/MS: condition 5, Retention time 4.87 (min)
LC/MS(ESI+)m/z；472，474[M+1]+
LC/MS(ESI-)m/z；470，472[M-1]-
Synthesis example 3
Synthesis of methyl 2- [ (2- {1- [5- (3, 4-dichlorophenyl) -4-hydroxyphenylthio-3-yl ] -ethylidene } -hydrazinocarbo-thioyl) amino ] acetate
A solution of 2- (3, 4-dichlorophenyl) -4- (1-hydrazonoethyl) thiophen-3-ol (30mg, 0.10mmol) and methyl 2-isothiocyanatoacetate (20mg, 0.15mmol) prepared in reference Synthesis example 1 in dimethylformamide (300. mu.L) was stirred at room temperature for 2 hours at 40 ℃ and 50 ℃ respectively. After methanol-water was added, the solution was stirred at room temperature for 0.5 hour, and the formed crystals were collected by filtration as the desired product (yield: 72%).
The form is as follows: white solid
LC/MS: condition 5, Retention time 4.95 (minutes)
LC/MS(ESI+)m/z；432，434[M+1]+
LC/MS(ESI-)m/z；430，432[M-1]-
Synthesis example 4
Synthesis of 2- [ (2- {1- [5- (3, 4-dichlorophenyl) -4-hydroxyphenylthio-3-yl ] -ethylidene } -hydrazinothiocarbonyl) amino ] acetic acid
Synthesis was carried out in the same manner as in Synthesis example 2 using methyl 2- [ (2- {1- [5- (3, 4-dichlorophenyl) -4-hydroxyphenylthio-3-yl ] -ethylidene } -hydrazinothiocarbonyl) amino ] acetate prepared in Synthesis example 3 (yield: 39%).
The form is as follows: white solid
LC/MS: condition 5, Retention time 4.65 (min)
LC/MS(ESI+)m/z；418，420[M+1]+
LC/MS(ESI-)m/z；416，418[M-1]-
Synthesis example 5
Synthesis of methyl 3- [ (2- {1- [5- (3, 4-dichlorophenyl) -4-hydroxyphenylthio-3-yl ] -ethylidene } -hydrazinothiocarbonyl) amino ] propionate
Synthesis was carried out in the same manner as in Synthesis example 3 using methyl 3-isothiocyanatopropionate (yield: 78%).
The form is as follows: white solid
LC/MS: condition 5, Retention time 5.03 (min)
LC/MS(ESI+)m/z；446[M+1]+
LC/MS(ESI-)m/z；444，446[M-1]-
Synthesis example 6
Synthesis of 3- [ (2- {1- [5- (3, 4-dichlorophenyl) -4-hydroxyphenylthio-3-yl ] -ethylidene } -hydrazinothiocarbonyl) amino ] propionic acid
Synthesis was carried out in the same manner as in Synthesis example 2 using methyl 3- [ (2- {1- [5- (3, 4-dichlorophenyl) -4-hydroxyphenylthio-3-yl ] -ethylidene } -hydrazinothiocarbonyl) amino ] propionate prepared in Synthesis example 5 (yield: 41%).
The form is as follows: white solid
LC/MS: condition 5, Retention time 4.74 (minutes)
LC/MS(ESI+)m/z；432，434[M+1]+
LC/MS(ESI-)m/z；430，432[M-1]-
Synthesis example 7
Synthesis of 1- (2- {1- [5- (3, 4-dichlorophenyl) -4-hydroxyphenylthio-3-yl ] -ethylidene } -hydrazinothiocarbonyl) amino-2-methoxyethane
This was carried out in the same manner as in Synthesis example 3 using 2-methoxyethyl isothiocyanate (yield: 43%).
The form is as follows: pale yellow solid
LC/MS: condition 5, Retention time 5.05 (min)
LC/MS(ESI+)m/z；418，420[M+1]+
LC/MS(ESI-)m/z；416，418[M-1]-
Synthesis example 8
Synthesis of 1- {1- [5- (4-bromophenyl) -4-hydroxy-thiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid methyl ester
The synthesis was carried out in the same manner as in Synthesis example 1 using 1- [5- (4-bromophenyl) -4-hydroxy-thiophen-3-yl ] -ethanone (ethanone) (prepared by the method disclosed in WO 2004/108683) and methyl 1-hydrazinothiocarbonyl-piperidine-4-carboxylate prepared in reference Synthesis example 2 (yield: 64%).
The form is as follows: pale yellow solid
LC/MS: condition 2, Retention time 3.74 (minutes)
LC/MS(ESI+)m/z；496，498[M+1]+
LC/MS(ESI-)m/z；494，496[M-1]-
Synthesis example 9
Synthesis of 1- {1- [5- (4-bromophenyl) -4-hydroxy-thiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid
Synthesis was carried out in the same manner as in Synthesis example 2 using 1- {1- [5- (4-bromophenyl) -4-hydroxy-thiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid methyl ester prepared in Synthesis example 8 (yield: 87%).
The form is as follows: pale yellow solid
LC/MS: condition 2, Retention time 3.45 (minutes)
LC/MS(ESI+)m/z；482，484[M+1]+
LC/MS(ESI-)m/z；480，482[M-1]-
Synthesis example 10
Synthesis of 1- {1- [ 4-hydroxy-5- (4-trifluoromethylphenyl) -thiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid
1- {1- [ 4-hydroxy-5- (4-trifluoromethylphenyl) -thiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid methyl ester
The synthesis was carried out in the same manner as in Synthesis example 1 using 1- [ 4-hydroxy-5- (4-trifluoromethylphenyl) -thiophen-3-yl ] ethanone (prepared by the method disclosed in WO 2004/108683) and 1-hydrazinothiocarbonylpiperidine-4-carboxylate prepared in reference Synthesis example 2 (yield: 36%).
The form is as follows: pale yellow solid
LC/MS: condition 1, Retention time 4.54 (min)
LC/MS(ESI+)m/z；486[M+1]+
LC/MS(ESI-)m/z；484[M-1]-
1- {1- [ 4-hydroxy-5- (4-trifluoromethylphenyl) -thiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid
Synthesis was carried out in the same manner as in Synthesis example 2 using methyl 1- {1- [ 4-hydroxy-5- (4-trifluoromethylphenyl) -thiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylate prepared above (yield: 58%).
The form is as follows: white solid
LC/MS: condition 5, Retention time 4.88 (min)
LC/MS(ESI+)m/z；472[M+1]+
LC/MS(ESI-)m/z；470[M-1]-
Synthesis example 11
Synthesis of 1- {1- [5- (4-trifluoromethoxyphenyl) -4-hydroxythiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid
1- {1- [5- (4-trifluoromethoxyphenyl) -4-hydroxythiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid methyl ester
Synthesis was carried out in the same manner as in Synthesis example 1 using 1- [5- (4-trifluoromethoxyphenyl) -4-hydroxythiophen-3-yl ] ethanone (prepared according to the method disclosed in WO 2004/108683) and methyl 1-hydrazinothiocarbonylpiperidine-4-carboxylate prepared in reference Synthesis example 2 (yield: 53%).
The form is as follows: pale yellow solid
LC/MS: condition 2, Retention time 3.75 (minutes)
LC/MS(ESI+)m/z；502[M+1]+
LC/MS(ESI-)m/z；500[M-1]-
1- {1- [5- (4-trifluoromethoxyphenyl) -4-hydroxythiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid
Synthesis was carried out in the same manner as in Synthesis example 2 using methyl 1- {1- [5- (4-trifluoromethoxyphenyl) -4-hydroxyphenylthio-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylate prepared above (yield: 52%).
The form is as follows: pale yellow solid
LC/MS: condition 2, Retention time 3.49 (min)
LC/MS(ESI+)m/z；488[M+1]+
LC/MS(ESI-)m/z；486[M-1]-
Synthesis example 12
Synthesis of 1- {1- [5- (4-chlorophenyl) -4-hydroxy-thiophen-3-yl ] -ethylidene (ethilidene) -hydrazinothiocarbonyl } -piperidine-4-carboxylic acid
1- {1- [5- (4-chlorophenyl) -4-hydroxy-thiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid methyl ester
The synthesis was carried out in the same manner as in Synthesis example 1 using 1- [5- (4-chlorophenyl) -4-hydroxy-thiophen-3-yl ] ethanone (prepared by the method disclosed in WO 2004/108683) and methyl 1-hydrazinothiocarbonylpiperidine-4-carboxylate prepared in reference Synthesis example 2 (yield: 41%).
The form is as follows: pale yellow solid
LC/MS: condition 1, Retention time 4.50 (minutes)
LC/MS(ESI+)m/z；452，454[M+1]+
LC/MS(ESI-)m/z；450，452[M-1]-
1- {1- [5- (4-chlorophenyl) -4-hydroxy-thiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid
Synthesis was carried out in the same manner as in Synthesis example 2 using methyl 1- {1- [5- (4-chlorophenyl) -4-hydroxy-thiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylate prepared above (yield: 92%).
The form is as follows: yellow solid
LC/MS: condition 1, Retention time 4.14 (min)
LC/MS(ESI+)m/z；438，440[M+1]+
LC/MS(ESI-)m/z；436，438[M-1]-
Synthesis example 13
Synthesis of 1- {1- [5- (3, 4-dimethylphenyl) -4-hydroxy-thiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid
1- {1- [5- (3, 4-dimethylphenyl) -4-hydroxy-thiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid methyl ester
Synthesis was carried out in the same manner as in Synthesis example 1 using 1- [5- (3, 4-dimethylphenyl) -4-hydroxy-thiophen-3-yl ] -ethanone (prepared by the method disclosed in WO 2004/108683) and methyl 1-hydrazinothiocarbonylpiperidine-4-carboxylate prepared in reference Synthesis example 2 (yield: 28%).
The form is as follows: pale yellow solid
LC/MS: condition 2, Retention time 3.69 (minutes)
LC/MS(ESI+)m/z；446[M+1]+
LC/MS(ESI-)m/z；444[M-1]-
1- {1- [5- (3, 4-dimethylphenyl) -4-hydroxy-thiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid
Synthesis was carried out in the same manner as in Synthesis example 2 using 1- {1- [5- (3, 4-dimethylphenyl) -4-hydroxy-thiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid methyl ester prepared above (yield: 100%).
The form is as follows: light brown solid
LC/MS: condition 2, Retention time 3.38 (min)
LC/MS(ESI+)m/z；431.78[M+1]+
LC/MS(ESI-)m/z；429.89[M-1]-
Synthesis example 14
Synthesis of 1- {1- [5- (4-tert-butylphenyl) -4-hydroxy-thiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid
1- {1- [5- (4-tert-butylphenyl) -4-hydroxy-thiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid methyl ester
The synthesis was carried out in the same manner as in Synthesis example 1 using 2- (4-tert-butylphenyl) -3-hydroxy-4-methylcarbonylthiophene and methyl 1-hydrazinothiocarbonylpiperidine-4-carboxylate prepared in reference Synthesis example 2 (yield: 57%).
The form is as follows: light brown solid
LC/MS: condition 2, Retention time 3.87 (min)
LC/MS(ESI+)m/z；474[M+1]+
LC/MS(ESI-)m/z；472[M-1]-
1- {1- [5- (4-tert-butylphenyl) -4-hydroxy-thiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid
Synthesis was carried out in the same manner as in Synthesis example 2 using methyl 1- {1- [5- (4-tert-butylphenyl) -4-hydroxy-thiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylate prepared above (yield: 89%).
The form is as follows: dark brown solid
1H-NMR (ppm in DMSO-d)6Middle)
δ1.22(s，9H)，1.57-1.61(m，2H)，1.88-1.92(m，2H)，2.36(s，3H)，4.53-4.58(m，2H)，7.41(d，2H，J＝8.5Hz)，7.67(d，2H，J＝8.5Hz)，7.85(s，1H)，10.25(brs，1H)，11.98(brs，1H)
Synthesis example 15
Synthesis of 1- {1- [5- (3-chlorophenyl) -4-hydroxyphenylthio-3-yl ] -ethylidene-hydrazonothiocarbonyl } -piperidine-4-carboxylic acid
1- {1- [5- (3-chlorophenyl) -4-hydroxyphenylthio-3-yl ] -ethylidene-hydrazonothiocarbonyl } -piperidine-4-carboxylic acid methyl ester
Synthesis was carried out in the same manner as in Synthesis example 1 using 1- [5- (3-chlorophenyl) -4-hydroxy-3-phenylthio ] ethanone (prepared by the method disclosed in WO 2004/108683) and methyl 1-hydrazinothiocarbonylpiperidine-4-carboxylate prepared in reference Synthesis example 2 (yield: 63%).
The form is as follows: pale yellow solid
LC/MS: condition 2, Retention time 3.67 (minutes)
LC/MS(ESI+)m/z；452，454[M+1]+
LC/MS(ESI-)m/z；450，452[M-1]-
1- {1- [5- (3-chlorophenyl) -4-hydroxyphenylthio-3-yl ] -ethylidene-hydrazonothiocarbonyl } -piperidine-4-carboxylic acid
Synthesis was carried out in the same manner as in Synthesis example 2 using methyl 1- {1- [5- (3-chlorophenyl) -4-hydroxythiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylate prepared above (yield: 71%).
The form is as follows: pale yellow solid
LC/MS: condition 2, Retention time 3.38 (min)
LC/MS(ESI+)m/z；438，440[M+1]+
LC/MS(ESI-)m/z；436，438[M-1]-
Synthesis example 16
Synthesis of 1- {1- [ 4-hydroxy-1-methyl-5- (4-trifluoromethylphenyl) -1H-pyrazol-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid
1- {1- [ 4-hydroxy-1-methyl-5- (4-trifluoromethylphenyl) -1H-pyrazol-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid methyl ester
The synthesis was carried out in the same manner as in Synthesis example 1 using 1- [ 4-hydroxy-1-methyl-5- (4-trifluoromethylphenyl) -1H-pyrazol-3-yl ] ethanone (prepared by the method disclosed in WO 2004/108683) and methyl 1-hydrazinothiocarbonylpiperidine-4-carboxylate prepared in reference Synthesis example 2 (yield: 70%).
The form is as follows: yellow solid
LC/MS: condition 1, Retention time 4.12 (minutes)
LC/MS(ESI+)m/z；484[M+1]+
LC/MS(ESI-)m/z；482[M-1]-
1- {1- [ 4-hydroxy-1-methyl-5- (4-trifluoromethylphenyl) -1H-pyrazol-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid
Synthesis was carried out in the same manner as in Synthesis example 2 using methyl 1- {1- [ 4-hydroxy-1-methyl-5- (4-trifluoromethylphenyl) -1H-pyrazol-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylate prepared above (yield: 85%).
The form is as follows: pale yellow solid
LC/MS: condition 1, Retention time 3.69 (minutes)
LC/MS(ESI+)m/z；470[M+1]+
LC/MS(ESI-)m/z；468[M-1]-
Synthesis example 17
Synthesis of 1- {1- [5- (3, 4-dichlorophenyl) -4-hydroxy-1-methyl-1H-pyrazol-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid
1- {1- [5- (3, 4-dichlorophenyl) -4-hydroxy-1-methyl-1H-pyrazol-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid methyl ester
The synthesis was carried out in the same manner as in Synthesis example 1 using 1- [5- (3, 4-dichlorophenyl) -4-hydroxy-1-methyl-1H-pyrazol-3-yl ] ethanone (prepared by the method disclosed in WO 2004/108683) and methyl 1-hydrazinothiocarbonylpiperidine-4-carboxylate prepared in reference Synthesis example 2 (yield: 61%).
The form is as follows: pale pink solid
LC/MS: condition 1, Retention time 4.30 (minutes)
LC/MS(ESI+)m/z；484，486[M+1]+
LC/MS(ESI-)m/z；482，484[M-1]-
1- {1- [5- (3, 4-dichlorophenyl) -4-hydroxy-1-methyl-1H-pyrazol-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid
Synthesis was carried out in the same manner as in Synthesis example 2 using methyl 1- {1- [5- (3, 4-dichlorophenyl) -4-hydroxy-1-methyl-1H-pyrazol-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylate prepared above (yield: 89%).
The form is as follows: pale yellow solid
LC/MS: condition 1, Retention time 3.79 (minutes)
LC/MS(ESI+)m/z；470，472[M+1]+
LC/MS(ESI-)m/z；468，470[M-1]-
Synthesis example 18
Synthesis of 1- {1- [5- (3, 4-dichlorophenyl) -4-hydroxythiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-3-carboxylic acid
1- {1- [5- (3, 4-dichlorophenyl) -4-hydroxythiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-3-carboxylic acid ethyl ester
Synthesis was carried out in the same manner as in Synthesis example 1 using ethyl 1-hydrazino (hydraziono) thiocarbonylpiperidine-3-carboxylate prepared in reference Synthesis example 3 (yield: 52%).
The form is as follows: white solid
1- {1- [5- (3, 4-dichlorophenyl) -4-hydroxythiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-3-carboxylic acid
Synthesis was carried out in the same manner as in Synthesis example 2 using ethyl 1- {1- [5- (3, 4-dichlorophenyl) -4-hydroxyphenylthio-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-3-carboxylate prepared above (yield: 67%).
The form is as follows: white solid
LC/MS: condition 5, Retention time 4.98 (minutes)
LC/MS(ESI+)m/z；472[M+1]+
LC/MS(ESI-)m/z；470[M-1]-
Synthesis example 19
Synthesis of 1- {1- [5- (3, 4-dichlorophenyl) -4-hydroxythiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid diethylamide
The synthesis was carried out in the same manner as in Synthesis example 1 using 1-hydrazonothiocarbonylpiperidine-4-carboxylic acid diethylamide prepared in reference Synthesis example 4 (yield: 23%).
The form is as follows: white solid
LC/MS: condition 5, Retention time 3.80 (minutes)
LC/MS(ESI+)m/z；527[M+1]+
Synthesis example 20
Synthesis of 1- {1- [5- (3, 4-dichlorophenyl) -4-hydroxythiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidin-4-ol
The synthesis was carried out in the same manner as in Synthesis example 1 using 1-hydrazinothiocarbonylpiperidin-4-ol prepared in reference Synthesis example 5 (yield: 21%).
The form is as follows: white solid
LC/MS: condition 5, Retention time 4.88 (min)
LC/MS(ESI+)m/z；444[M+1]+
LC/MS(ESI-)m/z；442[M-1]-
Synthesis example 21
Synthesis of 1- {1- [5- (3, 4-dichlorophenyl) -4-hydroxythiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidin-3-ol
The synthesis was carried out in the same manner as in Synthesis example 1 using the crude 1-hydrazinothiocarbonylpiperidin-3-ol prepared in reference Synthesis example 6 (yield: 53%).
The form is as follows: pale yellow solid
LC/MS: condition 5, Retention time 4.92 (minutes)
LC/MS(ESI+)m/z；444[M+1]+
LC/MS(ESI-)m/z；442[M-1]-
Synthesis example 22
Synthesis of 1- {1- [5- (3, 4-dichlorophenyl) -4-hydroxythiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-methanol
The synthesis was carried out in the same manner as in Synthesis example 1 using the crude 1-hydrazinothiocarbonylpiperidine-4-methanol prepared in reference Synthesis example 7 (yield: 22%).
The form is as follows: white solid
LC/MS: condition 5, Retention time 4.98 (minutes)
LC/MS(ESI+)m/z；458[M+1]+
LC/MS(ESI-)m/z；456[M-1]-
Synthesis example 23
Synthesis of 1- (2- {1- [5- (3, 4-dichlorophenyl) -4-hydroxyphenylthio-3-yl ] -ethylidene } -hydrazinothiocarbonyl) amino-3-methoxypropane
Synthesis was carried out in the same manner as in Synthesis example 3 using 3-methoxypropyl isothiocyanate (yield: 19%).
The form is as follows: pale yellow solid
LC/MS: condition 5, Retention time 5.22 (minutes)
LC/MS(ESI+)m/z；432[M+1]+
LC/MS(ESI-)m/z；430[M-1]-
Synthesis example 24
Synthesis of 1- {1- [5- (4-bromophenyl) -4-hydroxythiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid 4-picolylamide
To 1- {1- [5- (4-bromophenyl) -4-hydroxythiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid (84mg, 0.17mmol) prepared in Synthesis example 9 were added dimethylformamide (2mL) and 1- [3- (dimethylamino) propyl ] -3-ethylcarbodiimide hydrochloride (66mg, 0.25mmol) and HOBt (47mg, 0.25mmol), followed by dimethylformamide (2.5mL) and diisopropylethylamine (91. mu.L, 0.52 mmol). The resulting solution was stirred at room temperature for 1 hour, then stirred with a solution of 4-pyridylmethylamine (47mg, 0.43mmol) in dimethylformamide (1.5mL) -for 24 hours. After addition of water, the reaction mixture was filtered, and the filter cake was dried and washed repeatedly with isopropanol to obtain the desired product (yield: 34%).
The form is as follows: pale yellow solid
LC/MS: condition 1, Retention time 3.05 (min)
LC/MS(ESI+)m/z；572，574[M+1]+
LC/MS(ESI-)m/z；570，572[M-1]-
Synthesis example 25
Synthesis of 1- {1- [5- (4-bromophenyl) -4-hydroxythiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid 2-pyridinecarboxamide
The synthesis was carried out in the same manner as in Synthesis example 24 using 2-pyridinemethylamine (yield: 22%).
The form is as follows: pale yellow solid
LC/MS: condition 1, Retention time 3.62 (min)
LC/MS(ESI+)m/z；572，574[M+1]+
LC/MS(ESI-)m/z；570，572[M-1]-
Synthesis example 26
Synthesis of 1- {1- [5- (4-bromophenyl) -4-hydroxythiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid 3-pyridinecarboxamide
The synthesis was carried out in the same manner as in Synthesis example 24 using 3-pyridinemethylamine (yield: 4%).
The form is as follows: yellow solid
LC/MS: condition 1, Retention time 3.25 (minutes)
LC/MS(ESI+)m/z；572，574[M+1]+
LC/MS(ESI-)m/z；570，572[M-1]-
Synthesis example 27
Synthesis of 2- [4- {1- [5- (3, 4-dichlorophenyl) -4-hydroxyphenylthio-3-yl ] -ethylidene-hydrazonothiocarbonyl } -piperazin-1-yl ] acetic acid
2- [4- {1- [5- (3, 4-dichlorophenyl) -4-hydroxyphenylthio-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperazin-1-yl ] acetic acid methyl ester
Methyl 2- [ 4-hydrazinothiocarbonylpiperazin-1-yl ] acetate (356mg, 1.52mmol) and 2- (3, 4-dichlorophenyl) -3-hydroxy-4-methylcarbonylthiophene (147mg, 0.512mmol) prepared in reference synthesis example 10 were stirred with dimethylformamide (4mL) and concentrated hydrochloric acid (42.6 μ L, 1.52mmol) at room temperature to 60 ℃ for 5 days. After addition of water, the reaction mixture was filtered and the filter cake was dried. The filter cake was mixed with chloroform, then filtered, and the filtrate was concentrated and then mixed with chloroform, isopropanol and n-hexane and filtered. The filter cake was dried to obtain the desired crude product (yield: 18%). The crude product can be used directly in the next reaction.
LC/MS: condition 1, Retention time 3.97 (min)
LC/MS(ESI+)m/z；501，503[M+1]+
LC/MS(ESI-)m/z；499，501[M-1]-
Synthesis of 2- [4- {1- [5- (3, 4-dichlorophenyl) -4-hydroxyphenylthio-3-yl ] -ethylidene-hydrazonothiocarbonyl } -piperazin-1-yl ] acetic acid
The desired crude product was obtained following the procedure of synthesis example 2 using methyl 2- [4- {1- [5- (3, 4-dichlorophenyl) -4-hydroxyphenylthio-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperazin-1-yl ] acetate. The crude product was washed with chloroform to obtain the desired product (yield: 11%).
The form is as follows: pale yellow solid
LC/MS: condition 1, Retention time 3.60 (minutes)
LC/MS(ESI+)m/z；487，489[M+1]+
LC/MS(ESI-)m/z；485，487[M-1]-
Synthesis example 28
Synthesis of 2- [4- {1- [5- (4-bromophenyl) -4-hydroxyphenylthio-3-yl ] -ethylidene-hydrazonothiocarbonyl } -piperazin-1-yl ] acetic acid
2- [4- {1- [5- (4-bromophenyl) -4-hydroxyphenylthio-3-yl ] -ethylidene-hydrazonothiocarbonyl } -piperazin-1-yl ] acetic acid methyl ester
According to the condensation procedure of Synthesis example 27, using 2- (4-bromophenyl) -3-hydroxy-4-methylcarbonylthiophene, the desired crude product was obtained (yield: 57%). The crude product can be used directly in the next reaction.
The form is as follows: pale yellow solid
2- [4- {1- [5- (4-bromophenyl) -4-hydroxyphenylthio-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperazin-1-yl ] acetic acid
According to the hydrolysis procedure of Synthesis example 27, methyl 2- [4- {1- [5- (4-bromophenyl) -4-hydroxyphenylthio-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperazin-1-yl ] acetate was used to obtain the desired product (yield: 43%).
The form is as follows: pale yellow solid
LC/MS: condition 1, Retention time 3.45 (minutes)
LC/MS(ESI+)m/z；497，499[M+1]+
LC/MS(ESI-)m/z；495，497[M-1]-
Synthesis example 29
Synthesis of 3- [4- {1- [5- (4-bromophenyl) -4-hydroxyphenylthio-3-yl ] -ethylidene-hydrazonothiocarbonyl } -piperazin-1-yl ] propionic acid
3- [4- {1- [5- (4-bromophenyl) -4-hydroxyphenylthio-3-yl ] -ethylidene-hydrazonothiocarbonyl } -piperazin-1-yl ] propionic acid methyl ester
According to the condensation procedure of Synthesis example 27, using ethyl 3- [ 4-hydrazinothiocarbonylpiperazin-1-yl ] propionate prepared in reference Synthesis example 11, the desired crude product was obtained (yield: 13%). The crude product can be used directly in the next reaction.
LC/MS: condition 1, Retention time 3.05 (min)
LC/MS(ESI+)m/z；539，541[M+1]+
LC/MS(ESI-)m/z；537，539[M-1]-
3- [4- {1- [5- (4-bromophenyl) -4-hydroxyphenylthio-3-yl ] -ethylidene-hydrazonothiocarbonyl } -piperazin-1-yl ] propionic acid
According to the hydrolysis procedure of Synthesis example 2, using methyl 3- [4- {1- [5- (4-bromophenyl) -4-hydroxyphenylthio-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperazin-1-yl ] propionate and ethanol as a solvent, the desired product was obtained (yield: 55%).
The form is as follows: pale yellow solid
LC/MS: condition 1, Retention time 3.07 (min)
LC/MS(ESI+)m/z；511，513[M+1]+
LC/MS(ESI-)m/z；509，511[M-1]-
The structural formula of the compound obtained in the synthesis example is as follows.
Measurement example 1
Stimulation of Thrombopoietin (TPO) dependent cell line (1) proliferation
The reactivity of the compound of synthetic example 4 of the present invention with Thrombopoietin (TPO) receptor was determined using the human leukemia cell line UT 7/EPO-mpl.
(1) Cells and cell culture
UT7/EPO-mpl is a stably transformed cell line obtained by introducing a vector inducing expression of the human TPO receptor (c-mpl) under the control of the cytomegalovirus immediate early promoter into the human leukemia cell line UT7/EPO using the method of Takatoku et al (J.biol.chem., 272: 7259-7263 (1997)). TPO stimulates the proliferation of this cell line, and its parent cell line UT7EPO did not respond to TPO. Using CO2Incubator (5% CO)237 ℃ C., in the presence of 10% fetal bovine serum (FBS; thermo Electron or Biowest) Iscove modified Dulbeco medium (IMDM; GIBCO) were subcultured.
(2) Cell proliferation assay
The above subcultured cells were washed twice with Phosphate Buffered Saline (PBS) and suspended in IMDM containing 10% FBS at a cell density of 6X 104Cells/ml. The cell suspension was transferred to 96 well tissue culture plates (CORNING) at 100- μ l per well. TPO (PeproTech EC) or the compound of synthetic example 4 dissolved in dimethyl sulfoxide (DMSO) was then diluted 83-fold with IMDM containing 10% FBS and added to the above cell suspension at 20- μ l per well. The resulting suspension is in CO 2Incubator (5% CO)2Cultured at 37 ℃ for 4 days. Cell proliferation was measured using WST-8 reagent (Kishida chemical Co., Ltd.) according to the manufacturer's instructions. 10- μ l of 5mM WST-8 test solution was added to each well of the tissue culture plate, and the plate was incubated at 37 ℃ for 4 hours. The formazan formed was detected by measuring the absorbance at 450nm with a 96-well microplate reader (Nihon Molecular Devices, Spectramax 190)A pigment. FIG. 1 shows the results of measurements on UT7/EPO-mpl cells, while FIG. 2 shows the data obtained with UT7/EPO cells that do not express the TPO receptor.
FIG. 1 demonstrates that the proliferation of UT7/EPO-mpl cells responding to TPO is stimulated in a concentration-dependent manner by the compound of Synthesis example 4, whereas no proliferative effect of this compound on UT7/EPO, the parent cell line, is observed, as shown in FIG. 2. These results indicate that the compound of synthetic example 4 of the present invention can selectively act as an activator for TPO receptor.
Measurement example 2
The compounds of the following synthesis examples were tested according to the method of assay example 1 to determine the presence of TPO (EC) corresponding to 10ng/ml50) The concentration of each compound at which the human leukemia cell line UT-7/EPO-mpl was observed to grow at a growth rate of 50%. The results are shown in Table 4.
TABLE 4
Formulation example 1
A granular product was prepared containing the following ingredients.
Composition (I)
10mg of the Compound represented by the formula (1)
Lactose 700mg
Corn starch 274mg
HPC-L 16mg
1000mg
The compound represented by formula (1) and lactose were sieved through a 60-mesh sieve. The corn starch was sieved through a 120 mesh sieve. They were mixed in a V blender. The powder mixture was kneaded with a low viscosity hydroxypropyl cellulose (HPC-L) aqueous solution, granulated (extrusion granulation, die size 0.5-1mm) and dried. The resulting dried granules were sieved through a vibrating sieve (12/60 mesh) to obtain a granular product.
Formulation example 2
A powder preparation for encapsulation containing the following ingredients was prepared.
Composition (I)
10mg of the Compound represented by the formula (1)
Lactose 79mg
Corn starch 10mg
Magnesium stearate 1mg
100mg
The compound represented by formula (1) and lactose were sieved through a 60-mesh sieve. The corn starch was sieved through a 120 mesh sieve. They were mixed with magnesium stearate in a V blender. 10% of the powder was filled into size 5 hard capsules, 100mg per capsule.
Formulation example 3
A granular product for encapsulation containing the following ingredients was prepared.
Composition (I)
15mg of the Compound represented by the formula (1)
Lactose 90mg
Corn starch 42mg
HPC-L 3mg
150mg
The compound represented by formula (1) and lactose were sieved through a 60-mesh sieve. The corn starch was sieved through a 120 mesh sieve. They were mixed in a V blender. The powder mixture was kneaded with an aqueous solution of low viscosity hydroxypropyl cellulose (HPC-L), granulated and dried. The resulting dried granules were sieved through a vibrating sieve (12/60 mesh) and filled into size 4 hard capsules, 150mg per capsule.
Formulation example 4
A tablet formulation was prepared containing the following ingredients.
Composition (I)
10mg of the Compound represented by the formula (1)
Lactose 90mg
Microcrystalline cellulose 30mg
Magnesium stearate 5mg
CMC-Na 15mg
150mg
The compound represented by formula (1), lactose, microcrystalline cellulose and CMC-Na (carboxymethyl cellulose sodium salt) were sieved through a 60-mesh sieve and mixed. The powder mixture is mixed with magnesium stearate to obtain a leavened powder mixture. The powder mixture was directly compressed into 150mg tablets.
Formulation example 5
The intravenous product was prepared according to the following formulation.
100mg of the Compound represented by the formula (1)
1000ml glycerides of saturated fatty acids
Solutions containing the above components can generally be administered intravenously to a patient at a rate of 1 ml per minute.
INDUSTRIAL APPLICABILITY
The compound having affinity for a thrombopoietin receptor and being useful as a thrombopoietin receptor agonist of the present invention is useful as a prophylactic, therapeutic or ameliorating agent for diseases which can be effectively treated by activating the thrombopoietin receptor, particularly as a drug for blood diseases accompanied by abnormality in platelet count, and as a drug for diseases which can be treated or prevented by stimulating differentiation and proliferation of vascular endothelial cells and endothelial progenitor cells, which are effective as drugs.

Claims (12)

1. A compound represented by the formula (1), a pharmaceutically acceptable salt of the compound,
wherein A is a nitrogen atom or CH,
when A is a nitrogen atom, B is NR9Wherein R is9Is C1-10Alkyl, when A is CH, B is a sulfur atom,
R1is phenyl substituted with one or more substituents selected from the group consisting of: halogen atom, C1-10Alkyl and C1-10Alkoxy radical, C1-10Alkyl and C1-10An alkoxy group is unsubstituted or substituted by one or more halogen atoms,
L1is a key of the series of keys,
x is an oxygen atom (OH),
R2is C1-10An alkyl group, a carboxyl group,
L2is a key of the series of keys,
L3is a radical of hydrogen (NH),
y is a sulfur atom,
L4is a bond or NH, and
when L is4When is a bond, R3Is piperidinyl, piperazinyl, wherein the piperidinyl and piperazinyl are substituted with substituents selected from the group consisting of: c1-10Alkoxycarbonyl, carboxyl, hydroxyl, C1-10Dialkylaminocarbonyl group, C1-10Alkylaminocarbonyl and C1-10Alkyl radical, wherein the C1-10Alkylaminocarbonyl and C1-10The alkyl group is substituted with a substituent selected from the group consisting of: pyridyl, hydroxy and carboxy, or when L4When is NH, R3Is C substituted by a substituent1-10Alkyl, wherein the substituents are selected from: c1-10Alkoxy radical, C1-10Alkoxycarbonyl or carboxyl.
2. The compound of claim 1, a pharmaceutically acceptable salt of said compound, wherein R is 2Is methyl, and
when L is4Is a bond, R3Is piperidinyl, piperazinyl, wherein the piperidinyl and piperazinyl are substituted with substituents selected from the group consisting of: methoxycarbonyl, carboxy, hydroxy, diethylaminocarbonyl, pyridylmethylaminocarbonyl, methyl and ethyl, wherein the methyl and ethyl are substituted by a substituent selected from the group consisting of: hydroxy and carboxy, or when L4When is NH, R3Is methyl, ethyl or n-propyl substituted with a substituent selected from: methoxy radicalMethoxycarbonyl and carboxyl.
3. The compound of claim 2, a pharmaceutically acceptable salt of said compound, wherein L is4Is a bond, R3Is piperidinyl substituted with carboxy.
4. A compound according to any one of claims 1 to 3, wherein a is CH and B is a sulfur atom, a pharmaceutically acceptable salt of the compound.
5. The compound of claim 4, a pharmaceutically acceptable salt of said compound, wherein R is1Is 3, 4-dichlorophenyl, 4-tert-butylphenyl, 3, 4-dimethylphenyl, 4-trifluoromethylphenyl, 4-chlorophenyl, 4-bromophenyl, 4-trifluoromethoxyphenyl or 3-chlorophenyl.
6. The compound of claim 3, a pharmaceutically acceptable salt of said compound, wherein a is a nitrogen atom and B is NR 9Wherein R is9Is methyl, and R2Is methyl.
7. The compound of claim 6, a pharmaceutically acceptable salt of said compound, wherein R is1Is 3, 4-dichlorophenyl or 4-trifluoromethylphenyl.
8. The compound of claim 1, selected from the group consisting of:
1- {1- [5- (3, 4-dichlorophenyl) -4-hydroxythiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid;
1- {1- [5- (4-bromophenyl) -4-hydroxy-thiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid;
1- {1- [ 4-hydroxy-5- (4-trifluoromethylphenyl) -thiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid;
1- {1- [5- (4-trifluoromethoxyphenyl) -4-hydroxythiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid;
1- {1- [5- (4-chlorophenyl) -4-hydroxy-thiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid;
1- {1- [5- (3, 4-dimethylphenyl) -4-hydroxy-thiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid;
1- {1- [5- (4-tert-butylphenyl) -4-hydroxy-thiophen-3-yl ] -ethylidene-hydrazinothiocarbonyl } -piperidine-4-carboxylic acid; and
1- {1- [5- (3-chlorophenyl) -4-hydroxyphenylthio-3-yl ] -ethylidene-hydrazonothiocarbonyl } -piperidine-4-carboxylic acid;
Or a pharmaceutically acceptable salt of said compound.
9. Use of a compound according to any one of claims 1 to 8 for the preparation of a thrombopoietin receptor activator.
10. A prophylactic, therapeutic or ameliorating agent for a disease which can be effectively treated by activating a thrombopoietin receptor, comprising a thrombopoietin receptor activator prepared from the compound according to any one of claims 1 to 8, a pharmaceutically acceptable salt of the activator as an active ingredient.
11. A thrombopoietin receptor activator prepared from the compound of any one of claims 1-8, the pharmaceutically acceptable salt of which is used as an active ingredient.
12. A pharmaceutical composition comprising the compound according to any one of claims 1 to 8, a pharmaceutically acceptable salt thereof, as an active ingredient.
HK08105161.4A 2004-12-08 2005-12-07 3-ethylidenehydrazino substituted heterocyclic compounds as thrombopoietin receptor activators HK1115125B (en)

Applications Claiming Priority (5)

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JP2004355195 2004-12-08
JP2004-355195 2004-12-08
JP2005-330891 2005-11-15
JP2005330891 2005-11-15
PCT/JP2005/022907 WO2006062240A1 (en) 2004-12-08 2005-12-07 3-ethylidenehydrazino substituted heterocyclic compounds as thrombopoietin receptor activators

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HK1115125A1 HK1115125A1 (en) 2008-11-21
HK1115125B true HK1115125B (en) 2013-02-08

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