RU2014147017A - Производное бензамида - Google Patents
Производное бензамида Download PDFInfo
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- RU2014147017A RU2014147017A RU2014147017A RU2014147017A RU2014147017A RU 2014147017 A RU2014147017 A RU 2014147017A RU 2014147017 A RU2014147017 A RU 2014147017A RU 2014147017 A RU2014147017 A RU 2014147017A RU 2014147017 A RU2014147017 A RU 2014147017A
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- 150000003936 benzamides Chemical class 0.000 title 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 39
- 125000005843 halogen group Chemical group 0.000 claims abstract 31
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract 29
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract 19
- 150000001875 compounds Chemical class 0.000 claims abstract 18
- 125000003545 alkoxy group Chemical group 0.000 claims abstract 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 13
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract 11
- 125000003277 amino group Chemical group 0.000 claims abstract 11
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract 9
- 125000000217 alkyl group Chemical group 0.000 claims abstract 7
- 125000003118 aryl group Chemical group 0.000 claims abstract 6
- 125000005144 cycloalkylsulfonyl group Chemical group 0.000 claims abstract 3
- 229910052760 oxygen Inorganic materials 0.000 claims abstract 3
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims abstract 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract 2
- 125000005149 cycloalkylsulfinyl group Chemical group 0.000 claims abstract 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 19
- 150000003839 salts Chemical class 0.000 claims 16
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 12
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 8
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical group C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims 6
- 206010028980 Neoplasm Diseases 0.000 claims 5
- 201000011510 cancer Diseases 0.000 claims 5
- GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims 5
- 239000008177 pharmaceutical agent Substances 0.000 claims 5
- 125000006592 (C2-C3) alkenyl group Chemical group 0.000 claims 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 4
- 206010016654 Fibrosis Diseases 0.000 claims 4
- 206010061218 Inflammation Diseases 0.000 claims 4
- 206010027476 Metastases Diseases 0.000 claims 4
- 230000004761 fibrosis Effects 0.000 claims 4
- 230000004054 inflammatory process Effects 0.000 claims 4
- 230000009401 metastasis Effects 0.000 claims 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims 3
- 230000009400 cancer invasion Effects 0.000 claims 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 2
- PIPWSBOFSUJCCO-UHFFFAOYSA-N 2,2-dimethylpiperazine Chemical group CC1(C)CNCCN1 PIPWSBOFSUJCCO-UHFFFAOYSA-N 0.000 claims 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims 2
- 229910003827 NRaRb Inorganic materials 0.000 claims 2
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims 2
- 125000003282 alkyl amino group Chemical group 0.000 claims 2
- 125000004414 alkyl thio group Chemical group 0.000 claims 2
- 229910052801 chlorine Inorganic materials 0.000 claims 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 claims 2
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims 1
- DJSMFIRHIXHJLY-UHFFFAOYSA-N 1,2,5-oxadiazepane Chemical compound C1CNOCCN1 DJSMFIRHIXHJLY-UHFFFAOYSA-N 0.000 claims 1
- NQPJDJVGBDHCAD-UHFFFAOYSA-N 1,3-diazinan-2-one Chemical compound OC1=NCCCN1 NQPJDJVGBDHCAD-UHFFFAOYSA-N 0.000 claims 1
- FVIVALCKMXCKQX-UHFFFAOYSA-N 1,8-diazaspiro[5.5]undecane Chemical compound N1CCCCC11CNCCC1 FVIVALCKMXCKQX-UHFFFAOYSA-N 0.000 claims 1
- YVHBSYTYLQYTOU-UHFFFAOYSA-N 3,6-diazabicyclo[3.1.1]heptane Chemical group C1NCC2CC1N2 YVHBSYTYLQYTOU-UHFFFAOYSA-N 0.000 claims 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 1
- UJHBTCNHHDVZIG-UHFFFAOYSA-N C1NCC11CNCCO1 Chemical compound C1NCC11CNCCO1 UJHBTCNHHDVZIG-UHFFFAOYSA-N 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 125000005163 aryl sulfanyl group Chemical group 0.000 claims 1
- 125000005135 aryl sulfinyl group Chemical group 0.000 claims 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims 1
- 125000005171 cycloalkylsulfanyl group Chemical group 0.000 claims 1
- 230000009545 invasion Effects 0.000 claims 1
- ONLRKTIYOMZEJM-UHFFFAOYSA-N n-methylmethanamine oxide Chemical compound C[NH+](C)[O-] ONLRKTIYOMZEJM-UHFFFAOYSA-N 0.000 claims 1
- 125000004193 piperazinyl group Chemical group 0.000 claims 1
- 229910052717 sulfur Inorganic materials 0.000 claims 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 abstract 3
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 abstract 1
- 125000002947 alkylene group Chemical group 0.000 abstract 1
- 125000004429 atom Chemical group 0.000 abstract 1
- 0 CC(**=NC(*)=O)=O Chemical compound CC(**=NC(*)=O)=O 0.000 description 2
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- C07C321/24—Thiols, sulfides, hydropolysulfides, or polysulfides having thio groups bound to carbon atoms of six-membered aromatic rings
- C07C321/28—Sulfides, hydropolysulfides, or polysulfides having thio groups bound to carbon atoms of six-membered aromatic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- C07C317/32—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/166—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
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- A—HUMAN NECESSITIES
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- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/18—Sulfonamides
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- C07C317/32—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
- C07C317/34—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having sulfone or sulfoxide groups and amino groups bound to carbon atoms of six-membered aromatic rings being part of the same non-condensed ring or of a condensed ring system containing that ring
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- C07C317/38—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having sulfone or sulfoxide groups and amino groups bound to carbon atoms of six-membered aromatic rings being part of the same non-condensed ring or of a condensed ring system containing that ring with the nitrogen atom of at least one amino group being part of any of the groups, X being a hetero atom, Y being any atom, e.g. N-acylaminosulfones
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- C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C323/39—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton at least one of the nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom
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- C07C323/46—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having at least one of the nitrogen atoms, not being part of nitro or nitroso groups, further bound to other hetero atoms
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- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
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- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
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Abstract
1. Соединение, представленное общей формулой (I), ниже:в которой Q обозначает СНили NH;кольцо А обозначает формулу (1) или (2), ниже:,в которых Аобозначает N или CR;Rобозначает атом галогена, цианогруппу, Cалкильную группу или Cалкоксигруппу, причем Cалкильная группа и Салкоксигруппа могут быть замещены 1-5 атомами галогена;Rможет быть атомом водорода, когда Аи/или Аобозначают N;Аобозначает N или CR;Rобозначает атом водорода, атом галогена, Cалкильную группу или Cалкоксигруппу, причем Cалкильная группа и Салкоксигруппа могут быть замещены 1-5 атомами галогена;Аобозначает N или CR;Rобозначает атом водорода, атом галогена, Cалкильную группу или Cалкоксигруппу, причем Cалкильная группа и Салкоксигруппа могут быть замещены 1-5 атомами галогена; иRобозначает Cалкилсульфонильную группу, Салкилсульфанильную группу, Cалкилсульфинильную группу, Сциклоалкилсульфонильную группу, Сциклоалкилсульфанильную группу, Сциклоалкилсульфинильную группу, Сарилсульфонильную группу, Сарилсульфанильную группу или Сарилсульфинильную группу; икольцо В обозначает любую из формул (3)-(9), ниже:в которых Вобозначает N или СН;Bобозначает N или CR;Rобозначает атом галогена, Cалкильную группу, Cалкоксигруппу, Салкенильную группу, цианогруппу, нитрогруппу, Сциклоалкильную группу, 4-10-членное ароматическое кольцо, 4-10-членный ароматический гетероцикл, 3-12-членный гетероцикл или Салкилсульфанильную группу, причем Cалкильная группа, Cалкоксигруппа, Салкенильная группа или Cалкилсульфанильная группа может быть замещена 1-5 атомами галогена;Bобозначает N или CR;Вобозначает О, S или NR;Rобозначает атом водорода, Cалкильную группу, в случае необходимости замещенную гидроксильной группой, атом галогена, аминогруппу, группу ОСОСН
Claims (18)
1. Соединение, представленное общей формулой (I), ниже:
в которой Q обозначает СН2 или NH;
кольцо А обозначает формулу (1) или (2), ниже:
в которых А1 обозначает N или CR1;
R1 обозначает атом галогена, цианогруппу, C1-3 алкильную группу или C1-3 алкоксигруппу, причем C1-3 алкильная группа и С1-3 алкоксигруппа могут быть замещены 1-5 атомами галогена;
R1 может быть атомом водорода, когда А2 и/или А3 обозначают N;
А2 обозначает N или CR2;
R2 обозначает атом водорода, атом галогена, C1-3 алкильную группу или C1-3 алкоксигруппу, причем C1-3 алкильная группа и С1-3 алкоксигруппа могут быть замещены 1-5 атомами галогена;
А3 обозначает N или CR3;
R3 обозначает атом водорода, атом галогена, C1-3 алкильную группу или C1-3 алкоксигруппу, причем C1-3 алкильная группа и С1-3 алкоксигруппа могут быть замещены 1-5 атомами галогена; и
R4 обозначает C1-6 алкилсульфонильную группу, С1-6 алкилсульфанильную группу, C1-6 алкилсульфинильную группу, С3-8 циклоалкилсульфонильную группу, С3-8 циклоалкилсульфанильную группу, С3-8 циклоалкилсульфинильную группу, С6-10 арилсульфонильную группу, С6-10 арилсульфанильную группу или С6-10 арилсульфинильную группу; и
кольцо В обозначает любую из формул (3)-(9), ниже:
в которых В1 обозначает N или СН;
B2 обозначает N или CR5;
R5 обозначает атом галогена, C1-6 алкильную группу, C1-6 алкоксигруппу, С2-6 алкенильную группу, цианогруппу, нитрогруппу, С3-8 циклоалкильную группу, 4-10-членное ароматическое кольцо, 4-10-членный ароматический гетероцикл, 3-12-членный гетероцикл или С1-6 алкилсульфанильную группу, причем C1-6 алкильная группа, C1-6 алкоксигруппа, С2-6 алкенильная группа или C1-6 алкилсульфанильная группа может быть замещена 1-5 атомами галогена;
B3 обозначает N или CR6;
В6 обозначает О, S или NR6;
R6 обозначает атом водорода, C1-3 алкильную группу, в случае необходимости замещенную гидроксильной группой, атом галогена, аминогруппу, группу ОСОСН3 или группу, представленную следующей формулой (i), ниже:
причем в формуле (i)
X обозначает -(CH2)n-, -NH- или -О-;
Y обозначает С3-8 циклоалкильную группу, 4-10-членное ароматическое кольцо, 3-12-членный гетероцикл, 4-10-членный ароматический гетероцикл или -(NH(СН2)q)r-, причем С3-8 циклоалкильная группа, 4-10-членное ароматическое кольцо, 3-12-членный гетероцикл или 4-10-членный ароматический гетероцикл может быть замещен (а) 1-5 C1-6 алкильными группами;
Z обозначает атом водорода, C1-6 алкильную группу, диметиламиноксид, -(СН2)mNRaRb, -NRiCOCH2Rc, -(СН2)mNRiCORc, -(СН2)mORd, -(СН2)mCORe, -(СН2)mNRjSO2Rk, -(CH2)mSO2Rk, -(CH2)mCONRlRm, C3-8 циклоалкильную группу, 4-10-членный ароматический гетероцикл или 3-12-членный гетероцикл, причем 4-10-членный ароматический гетероцикл или 3-12-членный гетероцикл может быть замещен 1-5 C1-6 алкильными группами;
n означает 0, 1, 2 или 3;
m означает 0, 1, 2 или 3;
q означает 0, 1, 2 или 3;
r означает 0, 1, 2 или 3;
Ra и Rb являются одинаковыми или разными, и каждый обозначает атом водорода, C1-6 алкильную группу, С2-6 алкинильную группу, С3-8 циклоалкильную группу, 3-12-членный гетероцикл или -SO2CH3, причем C1-6 алкильная группа, С3-8 циклоалкильная группа, 3-12-членный гетероцикл или С2-6 алкинильная группа может быть замещен(а) 1-5 атомами галогена, гидроксильными группами, C1-6 алкоксигруппами, аминогруппами, -CONH2, моно-C1-6 алкиламино группами, ди-С1-6 алкиламино группами, цианогруппами, OCH2Ph и/или 3-12-членными гетероциклами;
Rc обозначает C1-6 алкильную группу, C1-6 алкоксигруппу, С3-8 циклоалкильную группу, гидроксильную группу, цианогруппу, 3-12-членный гетероцикл, 4-10-членный ароматический гетероцикл или аминогруппу, причем С1-6 алкильная группа может быть независимо замещена 1-3 гидроксилами, амино, моно-C1-6 алкиламино и/или ди-C1-6 алкиламино группами;
Rd обозначает атом водорода или C1-6 алкильную группу, причем C1-6 алкильная группа может быть замещена 1-3 гидроксилами и/или аминогруппами;
Re обозначает C1-6 алкильную группу, гидроксильную группу, 3-12-членный гетероцикл или 4-10-членный ароматический гетероцикл, причем C1-6 алкильная группа может быть замещена 1-3 гидроксилами и/или аминогруппами;
Ri обозначает атом водорода или C1-6 алкильную группу, причем C1-6 алкильная группа может быть замещена 1-5 атомами галогена;
Rj обозначает атом водорода или C1-6 алкильную группу, причем C1-6 алкильная группа может быть замещена 1-5 атомами галогена;
Rk обозначает атом водорода, C1-6 алкильную группу, аминогруппу, моно-C1-6 алкиламино группу или ди-С1-6 алкиламино группу, причем C1-6 алкильная группа может быть замещена 1-3 гидроксилами, амино, моно-C1-6 алкиламино и/или ди-C1-6 алкиламино группами; и
Rl и Rm являются одинаковыми или разными, и каждый обозначает атом водорода, C1-6 алкильную группу или 3-12-членный гетероцикл, причем C1-6 алкильная группа может быть независимо замещена 1-3 амино, моно-C1-6 алкиламино и/или ди-С1-6 алкиламино группами;
B4 обозначает N или CR7;
R7 обозначает атом водорода, атом галогена, цианогруппу, C1-6 алкильную группу, C1-6 алкоксигруппу, С2-6 алкенильную группу или С3-8 циклоалкильную группу (причем C1-6 алкильная группа, C1-6 алкоксигруппа, С2-6 алкенильная группа или С3-8 циклоалкильная группа может быть замещена 1-5 атомами галогена), или группу, представленную формулой (ii), ниже:
в которой X2 обозначает -(СН2)p-;
р означает 0, 1, 2 или 3;
Y2 обозначает 4-10-членное ароматическое кольцо, 3-12-членный гетероцикл или 4-10-членный ароматический гетероцикл, причем 4-10-членное ароматическое кольцо, 3-12-членный гетероцикл или 4-10-членный ароматический гетероцикл может быть замещен 1-5 C1-6 алкильными группами;
Z2 обозначает атом водорода, C1-6 алкильную группу, гидроксильную группу, -NRfRg, 3-12-членный гетероцикл или 4-10-членный ароматический гетероцикл, причем С1-6 алкильная группа может быть замещена 1-5 атомами галогена, и 3-12-членный гетероцикл или 4-10-членный ароматический гетероцикл может быть замещен 1-5 C1-6 алкильными группами; и
Rf и Rg являются одинаковыми или разными, и каждый обозначает атом водорода, C1-6 алкильную группу, -СОСН3 или -SO2CH3;
B5 обозначает N или CR8; и
R8 обозначает атом водорода, C1-6 алкильную группу или атом галогена, причем C1-6 алкильная группа может быть замещена 1-5 атомами галогена,
или его фармацевтически приемлемая соль.
3. Соединение или его фармацевтически приемлемая соль по п. 1 или 2, в котором Q обозначает СН2.
4. Соединение или его фармацевтически приемлемая соль по п. 1 или 2, в котором R2 обозначает атом водорода или C1-3 алкильную группу, причем C1-3 алкильная группа может быть замещена 1-5 атомами галогена.
5. Соединение или его фармацевтически приемлемая соль по п. 1 или 2, в котором R3 обозначает атом водорода, атом хлора или C1-3 алкильную группу, причем C1-3 алкильная группа может быть замещена 1-5 атомами галогена.
6. Соединение или его фармацевтически приемлемая соль по п. 1 или 2, в котором R5 обозначает атом галогена, C1-3 алкильную группу, С2-3 алкенильную группу или C1-3 алкоксигруппу, причем C1-3 алкильная группа, С2-3 алкенильная группа или C1-3 алкоксигруппа может быть замещена 1-5 атомами галогена.
7. Соединение или его фармацевтически приемлемая соль по п. 1 или 2, в котором
R6 обозначает атом водорода или группу, представленную формулой (i), ниже:
в которой X обозначает СН2;
Y обозначает пиперазин, пирролидин, пиперидин, морфолин, 3,3-диметилпиперазин, 3,6-диазабицикло[3.1.1]гептан, азаспиро[2,4]гептан, 2-оксо-1,3-диазинан, 1,2,5-оксадиазепан, 2-оксопиперидин, азетидин, 5-окса-2,8-диазаспиро[3,5]нонан, 1,8-диазаспиро[5,5]ундекан, имидазол или бензол;
Ζ обозначает атом водорода, -(СН2)mNRaRb, -NHCOCH2Rc, -(СН2)mNHCORc, -(CH2)mORd, -(CH2)mCORe, -(CH2)mCONRlRm, пиперазин, пирролидин, пиперидин или тетрагидропиран;
m означает 0, 1, 2 или 3;
Ra и Rb являются одинаковыми или разными, и каждый обозначает атом водорода, C1-6 алкильную группу, С3-6 циклоалкильную группу или -SO2CH3, причем C1-6 алкильная группа или С3-6 циклоалкильная группа может быть замещена 1-5 атомами галогена, гидроксильными группами, C1-6 алкоксигруппами, аминогруппами, -CONH2, моно-C1-6 алкиламиногруппами, ди-С1-6 алкиламиногруппами или цианогруппами;
Rc обозначает С1-4 алкильную группу, C1-4 алкоксигруппу, 4-6-членный гетероцикл, 4-6-членный ароматический гетероцикл или аминогруппу, причем C1-4 алкильная группа может быть независимо замещена 1-2 амино, моно-C1-2 алкиламино и/или ди-С1-2 алкиламино группами;
Rd обозначает атом водорода или C1-2 алкильную группу, причем C1-2 алкильная группа может быть замещена аминогруппой или гидроксильной группой;
Re обозначает С1-2 алкильную группу или 4-6-членный гетероцикл, причем C1-2 алкильная группа может быть замещена аминогруппой или гидроксильной группой; и
Rl и Rm являются одинаковыми или разными, и каждый обозначает атом водорода, С1-3 алкильную группу или 4-6-членный гетероцикл, причем C1-3 алкильная группа независимо замещена 1-3 амино, моно-C1-3 алкиламино и/или ди-С1-3 алкиламино группами.
8. Соединение или его фармацевтически приемлемая соль по п. 1 или 2, в котором
В4 обозначает CR7, и
R7 обозначает атом хлора, атом брома, атом водорода, цианогруппу, C1-3 алкильную группу, C1-3 алкоксигруппу, С2-3 алкенильную группу, С3-6 циклоалкильную группу (причем C1-3 алкильная группа, C1-3 алкоксигруппа, С2-3 алкенильная группа или С3-6 циклоалкильная группа может быть замещена 1-3 атомами галогена) или группу, представленную формулой (ii), ниже:
в которой X2 обозначает -(СН2)p-, р обозначает 0 или 1;
Y2 обозначает пиперазин, пирролидин, пиперидин, морфолин или 3,3-диметилпиперазин;
Z2 обозначает атом водорода, C1-3 алкильную группу, -NRfRg, пирролидин, морфолин или тетрагидропиран, причем С1-3 алкильная группа может быть замещена 1-3 атомами галогена; и
Rf и Rg являются одинаковыми или разными, и каждый обозначает атом водорода, C1-3 алкильную группу, -СОСН3 или -SO2CH3.
9. Соединение или его фармацевтически приемлемая соль по п. 1 или 2, в котором R8 обозначает атом водорода.
10. Фармацевтические средства, включающие соединение или его фармацевтически приемлемую соль по любому из пп. 1-9 в качестве активного ингредиента.
11. Фармацевтические средства по п. 10, причем фармацевтические средства используются для лечения рака и/или инвазии/метастаза рака.
12. Фармацевтические средства по п. 10, причем фармацевтические средства используются для лечения фиброза и/или воспаления.
13. Способ лечения рака и/или инвазии/метастаза рака, включающий введение пациенту фармацевтически эффективного количества композиции, включающей соединение или его фармацевтически приемлемую соль по любому из пп. 1-9.
14. Способ лечения фиброза и/или воспаления, включающий введение пациенту фармацевтически эффективного количества композиции, включающей соединение или его фармацевтически приемлемую соль по любому из пп. 1-9.
15. Применение соединения или его фармацевтически приемлемой соли по любому из пп. 1-9 для получения средства для лечения рака и/или инвазии/метастаза рака.
16. Применение соединения или его фармацевтически приемлемой соли по любому из пп. 1-9 для получения средства для лечения фиброза и/или воспаления.
17. Соединение или его фармацевтически приемлемая соль по п. 1 или 2 для применения в лечении рака и/или инвазии/метастаза рака.
18. Соединение или его фармацевтически приемлемая соль по п. 1 или 2 для применения в лечении фиброза и/или воспаления.
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| JP2012-098953 | 2012-04-24 | ||
| PCT/JP2013/062003 WO2013161851A1 (ja) | 2012-04-24 | 2013-04-24 | ベンズアミド誘導体 |
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| EP (1) | EP2842939B1 (ru) |
| JP (1) | JP6177768B2 (ru) |
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| CN105829285A (zh) | 2013-10-23 | 2016-08-03 | 中外制药株式会社 | 喹唑啉酮和异喹啉酮衍生物 |
| MX2017006020A (es) * | 2014-11-07 | 2017-06-19 | Lonza Ag | Metodo de preparacion de compuestos fluoro, cloro y fluoro-cloro alquilados por catalisis homogenea. |
| EP3101009A1 (en) * | 2015-06-05 | 2016-12-07 | Lead Pharma Cel Models IP B.V. | Ror gamma (rory) modulators |
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| KR20180043199A (ko) | 2015-08-31 | 2018-04-27 | 도레이 카부시키가이샤 | 요소 유도체 및 그 용도 |
| EP3414247B1 (en) * | 2016-02-08 | 2021-04-21 | F. Hoffmann-La Roche AG | Spiroindolinones as ddr1 inhibitors |
| CN106397174B (zh) * | 2016-08-24 | 2018-12-21 | 河北诚信集团有限公司 | 一种制备3,6-二氯-2-甲氧基苯甲酸的方法 |
| KR102841700B1 (ko) * | 2019-02-22 | 2025-08-01 | 피아이 인더스트리스 엘티디. | 안트라닐산 디아미드 화합물 및 그의 중간체의 합성 방법 |
| CN115697485B (zh) | 2020-05-25 | 2025-03-14 | 奇斯药制品公司 | 作为ddr抑制剂的苄胺衍生物 |
| MX2024002016A (es) * | 2021-08-17 | 2024-05-10 | Kanaph Therapeutics Inc | Inhibidor de sos1 y uso del mismo. |
| WO2024059210A2 (en) * | 2022-09-15 | 2024-03-21 | Vanderbilt University | 6,5 western core compounds as mglu5 negative allosteric modulators and methods of making and using the same |
| KR20240127910A (ko) * | 2023-02-16 | 2024-08-23 | 주식회사 카나프테라퓨틱스 | Sos1 억제제 및 항암제를 포함하는 암 치료용 약학 조성물 |
| KR20240127909A (ko) * | 2023-02-16 | 2024-08-23 | (주) 사이러스테라퓨틱스 | Sos1 억제제로서의 아졸릴피리딘 피리다지논 아미드 |
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- 2013-04-24 KR KR1020147032532A patent/KR20150013563A/ko not_active Withdrawn
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Also Published As
| Publication number | Publication date |
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| US9695118B2 (en) | 2017-07-04 |
| WO2013161851A1 (ja) | 2013-10-31 |
| EP2842939A4 (en) | 2015-11-11 |
| HK1203926A1 (en) | 2015-11-06 |
| AR090836A1 (es) | 2014-12-10 |
| EP2842939B1 (en) | 2018-05-30 |
| JPWO2013161851A1 (ja) | 2015-12-24 |
| US20150152047A1 (en) | 2015-06-04 |
| TW201348187A (zh) | 2013-12-01 |
| SG11201406871UA (en) | 2014-11-27 |
| BR112014026266A2 (pt) | 2017-06-27 |
| JP6177768B2 (ja) | 2017-08-09 |
| AU2013253539A1 (en) | 2014-11-13 |
| CN104379560A (zh) | 2015-02-25 |
| KR20150013563A (ko) | 2015-02-05 |
| MX2014012991A (es) | 2015-08-14 |
| CA2871237A1 (en) | 2013-10-31 |
| EP2842939A1 (en) | 2015-03-04 |
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| AR034588A1 (es) | Derivados heterociclilalcoxi-, -alquiltio- y -alquilamino-benzazol como ligandos de 5-hidroxitriptamina-6, un proceso para su preparacion, intermediarios, composiciones farmaceuticas y el uso de dichos derivados para la manufactura de medicamentos |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FA91 | Application withdrawn (on applicant's request) |
Effective date: 20160804 |