SK212001A3 - Thiobenzimidazole derivatives - Google Patents

Thiobenzimidazole derivatives Download PDF

Info

Publication number: SK212001A3
Authority: SK; Slovakia
Prior art keywords: group; cooh; substituted; carbon atoms; unsubstituted
Prior art date: 1998-07-15

Application number

SK21-2001A

Other languages

English (en)

Slovak (sk)

Inventor

Yoshiyuki Matsumoto

Susumu Takeuchi

Naoki Hase

Original Assignee

Teijin Ltd

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1998-07-15

Filing date

1999-07-14

Publication date

2001-11-06

1999-07-14 Application filed by Teijin Ltd filed Critical Teijin Ltd

2001-11-06 Publication of SK212001A3 publication Critical patent/SK212001A3/sk

Links

KSAPYRIVHFAQGR-UHFFFAOYSA-N 1-sulfanylbenzimidazole Chemical class C1=CC=C2N(S)C=NC2=C1 KSAPYRIVHFAQGR-UHFFFAOYSA-N 0.000 title claims abstract description 36
150000003839 salts Chemical class 0.000 claims abstract description 32
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 17
201000010099 disease Diseases 0.000 claims abstract description 15
101000909983 Homo sapiens Chymase Proteins 0.000 claims abstract description 13
230000002401 inhibitory effect Effects 0.000 claims abstract description 8
230000003449 preventive effect Effects 0.000 claims abstract description 8
125000000896 monocarboxylic acid group Chemical group 0.000 claims description 922
125000004432 carbon atom Chemical group C* 0.000 claims description 112
-1 phenoxy, phenoxy Chemical group 0.000 claims description 54
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 52
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 29
229910052760 oxygen Inorganic materials 0.000 claims description 29
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 27
239000001301 oxygen Substances 0.000 claims description 27
229910052757 nitrogen Inorganic materials 0.000 claims description 26
125000000217 alkyl group Chemical group 0.000 claims description 24
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 23
125000001424 substituent group Chemical group 0.000 claims description 21
229910052736 halogen Inorganic materials 0.000 claims description 20
125000003118 aryl group Chemical group 0.000 claims description 18
125000005843 halogen group Chemical group 0.000 claims description 18
125000002947 alkylene group Chemical group 0.000 claims description 17
150000002367 halogens Chemical class 0.000 claims description 16
125000004953 trihalomethyl group Chemical group 0.000 claims description 16
125000001072 heteroaryl group Chemical group 0.000 claims description 15
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
125000000732 arylene group Chemical group 0.000 claims description 13
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
229910005965 SO 2 Inorganic materials 0.000 claims description 12
125000003545 alkoxy group Chemical group 0.000 claims description 12
125000005549 heteroarylene group Chemical group 0.000 claims description 11
229910052717 sulfur Inorganic materials 0.000 claims description 10
150000003536 tetrazoles Chemical class 0.000 claims description 10
125000004951 trihalomethoxy group Chemical group 0.000 claims description 10
125000004122 cyclic group Chemical group 0.000 claims description 9
239000011593 sulfur Substances 0.000 claims description 9
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 8
239000003814 drug Substances 0.000 claims description 8
229940124597 therapeutic agent Drugs 0.000 claims description 8
239000008194 pharmaceutical composition Substances 0.000 claims description 7
125000002252 acyl group Chemical group 0.000 claims description 6
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 6
125000004093 cyano group Chemical group *C#N 0.000 claims description 6
239000003937 drug carrier Substances 0.000 claims description 6
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
125000004043 oxo group Chemical group O=* 0.000 claims description 6
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 6
125000004434 sulfur atom Chemical group 0.000 claims description 6
125000004414 alkyl thio group Chemical group 0.000 claims description 5
208000026935 allergic disease Diseases 0.000 claims description 5
210000000988 bone and bone Anatomy 0.000 claims description 5
230000004097 bone metabolism Effects 0.000 claims description 5
230000008414 cartilage metabolism Effects 0.000 claims description 5
239000001257 hydrogen Substances 0.000 claims description 5
229910052739 hydrogen Inorganic materials 0.000 claims description 5
208000030159 metabolic disease Diseases 0.000 claims description 5
210000000056 organ Anatomy 0.000 claims description 5
125000004442 acylamino group Chemical group 0.000 claims description 4
150000003931 anilides Chemical group 0.000 claims description 4
229910052799 carbon Inorganic materials 0.000 claims description 4
208000027866 inflammatory disease Diseases 0.000 claims description 4
125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
PCJFEVUKVKQSSL-UHFFFAOYSA-N 2h-1,2,4-oxadiazol-5-one Chemical compound O=C1N=CNO1 PCJFEVUKVKQSSL-UHFFFAOYSA-N 0.000 claims description 3
IGAVZWMNOPFOCW-UHFFFAOYSA-N 2h-1,2,4-thiadiazol-5-one Chemical compound O=C1NC=NS1 IGAVZWMNOPFOCW-UHFFFAOYSA-N 0.000 claims description 3
125000004429 atom Chemical group 0.000 claims description 3
125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 2
125000004430 oxygen atom Chemical group O* 0.000 claims description 2
230000000241 respiratory effect Effects 0.000 claims description 2
125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims 1
125000003342 alkenyl group Chemical group 0.000 claims 1
230000002554 disease preventive effect Effects 0.000 claims 1
230000003389 potentiating effect Effects 0.000 abstract description 3
150000001875 compounds Chemical class 0.000 description 149
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 144
239000000460 chlorine Substances 0.000 description 71
239000000203 mixture Substances 0.000 description 63
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 51
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 45
239000000243 solution Substances 0.000 description 32
238000006243 chemical reaction Methods 0.000 description 29
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 28
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
239000002904 solvent Substances 0.000 description 26
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 25
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
238000002360 preparation method Methods 0.000 description 22
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
230000002829 reductive effect Effects 0.000 description 20
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 18
QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 16
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 15
150000001556 benzimidazoles Chemical class 0.000 description 14
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
238000010189 synthetic method Methods 0.000 description 13
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 12
238000010898 silica gel chromatography Methods 0.000 description 12
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 12
238000001035 drying Methods 0.000 description 11
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
238000000605 extraction Methods 0.000 description 11
HPJKCIUCZWXJDR-UHFFFAOYSA-N letrozole Chemical compound C1=CC(C#N)=CC=C1C(N1N=CN=C1)C1=CC=C(C#N)C=C1 HPJKCIUCZWXJDR-UHFFFAOYSA-N 0.000 description 11
229960003881 letrozole Drugs 0.000 description 11
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 10
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
230000000694 effects Effects 0.000 description 9
239000003889 eye drop Substances 0.000 description 9
229940012356 eye drops Drugs 0.000 description 9
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
239000005711 Benzoic acid Substances 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
229940058303 antinematodal benzimidazole derivative Drugs 0.000 description 8
235000010233 benzoic acid Nutrition 0.000 description 8
230000007062 hydrolysis Effects 0.000 description 8
238000006460 hydrolysis reaction Methods 0.000 description 8
229910000104 sodium hydride Inorganic materials 0.000 description 8
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
150000002148 esters Chemical class 0.000 description 7
239000010410 layer Substances 0.000 description 7
238000000034 method Methods 0.000 description 7
239000000843 powder Substances 0.000 description 7
238000010992 reflux Methods 0.000 description 7
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
108090000227 Chymases Proteins 0.000 description 6
102000003858 Chymases Human genes 0.000 description 6
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
238000009472 formulation Methods 0.000 description 6
239000012312 sodium hydride Substances 0.000 description 6
GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 5
DPJCXCZTLWNFOH-UHFFFAOYSA-N 2-nitroaniline Chemical class NC1=CC=CC=C1[N+]([O-])=O DPJCXCZTLWNFOH-UHFFFAOYSA-N 0.000 description 5
150000001412 amines Chemical class 0.000 description 5
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
239000008187 granular material Substances 0.000 description 5
210000003630 histaminocyte Anatomy 0.000 description 5
239000003112 inhibitor Substances 0.000 description 5
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
238000003756 stirring Methods 0.000 description 5
239000003826 tablet Substances 0.000 description 5
PHRABVHYUHIYGY-UHFFFAOYSA-N 1-methylnaphthalene Chemical group C1=CC=C2C([CH2])=CC=CC2=C1 PHRABVHYUHIYGY-UHFFFAOYSA-N 0.000 description 4
CKUXMYYDAQIJRQ-UHFFFAOYSA-N 5,6-dimethyl-1,3-dihydrobenzimidazole-2-thione Chemical compound C1=C(C)C(C)=CC2=C1NC(=S)N2 CKUXMYYDAQIJRQ-UHFFFAOYSA-N 0.000 description 4
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
101000909992 Papio hamadryas Chymase Proteins 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
239000002253 acid Substances 0.000 description 4
239000002585 base Substances 0.000 description 4
239000002775 capsule Substances 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
229910052801 chlorine Inorganic materials 0.000 description 4
239000013078 crystal Substances 0.000 description 4
239000002552 dosage form Substances 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
QKASDIPENBEWBU-UHFFFAOYSA-N methyl 2-(bromomethyl)benzoate Chemical compound COC(=O)C1=CC=CC=C1CBr QKASDIPENBEWBU-UHFFFAOYSA-N 0.000 description 4
239000003921 oil Substances 0.000 description 4
235000019198 oils Nutrition 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
125000006239 protecting group Chemical group 0.000 description 4
238000010791 quenching Methods 0.000 description 4
239000011780 sodium chloride Substances 0.000 description 4
239000000725 suspension Substances 0.000 description 4
XMWGTKZEDLCVIG-UHFFFAOYSA-N 1-(chloromethyl)naphthalene Chemical compound C1=CC=C2C(CCl)=CC=CC2=C1 XMWGTKZEDLCVIG-UHFFFAOYSA-N 0.000 description 3
MMPXKUSIQTTZCJ-UHFFFAOYSA-N 1-(naphthalen-1-ylmethyl)imidazole Chemical compound C=1C=CC2=CC=CC=C2C=1CN1C=CN=C1 MMPXKUSIQTTZCJ-UHFFFAOYSA-N 0.000 description 3
YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 3
IOHPVZBSOKLVMN-UHFFFAOYSA-N 2-(2-phenylethyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1CCC1=CC=CC=C1 IOHPVZBSOKLVMN-UHFFFAOYSA-N 0.000 description 3
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
230000004913 activation Effects 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
238000004440 column chromatography Methods 0.000 description 3
238000007796 conventional method Methods 0.000 description 3
238000001816 cooling Methods 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 3
239000007924 injection Substances 0.000 description 3
238000002347 injection Methods 0.000 description 3
239000007788 liquid Substances 0.000 description 3
229910052943 magnesium sulfate Inorganic materials 0.000 description 3
235000019341 magnesium sulphate Nutrition 0.000 description 3
DXPVKEHMQWTSTM-UHFFFAOYSA-N methyl 2-(1h-benzimidazol-2-ylsulfanylmethyl)benzoate Chemical compound COC(=O)C1=CC=CC=C1CSC1=NC2=CC=CC=C2N1 DXPVKEHMQWTSTM-UHFFFAOYSA-N 0.000 description 3
FLDMWRZKOSGMIS-UHFFFAOYSA-N methyl 2-[(5,6-dimethyl-1h-benzimidazol-2-yl)sulfanylmethyl]benzoate Chemical compound COC(=O)C1=CC=CC=C1CSC1=NC2=CC(C)=C(C)C=C2N1 FLDMWRZKOSGMIS-UHFFFAOYSA-N 0.000 description 3
125000001624 naphthyl group Chemical group 0.000 description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
239000000546 pharmaceutical excipient Substances 0.000 description 3
229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
239000001267 polyvinylpyrrolidone Substances 0.000 description 3
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
239000003755 preservative agent Substances 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
WHMDPDGBKYUEMW-UHFFFAOYSA-N pyridine-2-thiol Chemical compound SC1=CC=CC=N1 WHMDPDGBKYUEMW-UHFFFAOYSA-N 0.000 description 3
208000023504 respiratory system disease Diseases 0.000 description 3
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
YHMYGUUIMTVXNW-UHFFFAOYSA-N 1,3-dihydrobenzimidazole-2-thione Chemical compound C1=CC=C2NC(S)=NC2=C1 YHMYGUUIMTVXNW-UHFFFAOYSA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
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DLURHXYXQYMPLT-UHFFFAOYSA-N 2-nitro-p-toluidine Chemical compound CC1=CC=C(N)C([N+]([O-])=O)=C1 DLURHXYXQYMPLT-UHFFFAOYSA-N 0.000 description 2
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GGMOEAJLUSRQNN-UHFFFAOYSA-N 5-methyl-3-(naphthalen-1-ylmethyl)-1h-benzimidazole-2-thione Chemical compound C1=CC=C2C(CN3C(S)=NC4=CC=C(C=C43)C)=CC=CC2=C1 GGMOEAJLUSRQNN-UHFFFAOYSA-N 0.000 description 2
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206010012438 Dermatitis atopic Diseases 0.000 description 2
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MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
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239000004472 Lysine Substances 0.000 description 2
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
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MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 2
208000031481 Pathologic Constriction Diseases 0.000 description 2
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- A—HUMAN NECESSITIES
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D235/28—Sulfur atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems

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SK21-2001A 1998-07-15 1999-07-14 Thiobenzimidazole derivatives SK212001A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
JP20025098		1998-07-15
PCT/JP1999/003799 WO2000003997A1 (en)	1998-07-15	1999-07-14	Thiobenzimidazole derivatives

Publications (1)

Publication Number	Publication Date
SK212001A3 true SK212001A3 (en)	2001-11-06

Family

ID=16421274

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK21-2001A SK212001A3 (en)	1998-07-15	1999-07-14	Thiobenzimidazole derivatives

Country Status (22)

Country	Link
US (2)	US7268145B2 (pt)
EP (1)	EP1097926A4 (pt)
JP (1)	JP3923255B2 (pt)
KR (1)	KR100903531B1 (pt)
CN (1)	CN1187337C (pt)
AU (1)	AU758789B2 (pt)
BG (1)	BG65514B1 (pt)
BR (1)	BR9912098A (pt)
CA (1)	CA2336909C (pt)
EE (1)	EE04904B1 (pt)
HR (1)	HRP20010030A2 (pt)
HU (1)	HUP0103256A3 (pt)
ID (1)	ID26899A (pt)
IL (1)	IL140862A (pt)
IS (1)	IS5807A (pt)
NO (1)	NO318957B1 (pt)
NZ (1)	NZ509207A (pt)
PL (1)	PL203730B1 (pt)
RU (1)	RU2237663C2 (pt)
SK (1)	SK212001A3 (pt)
TR (1)	TR200100047T2 (pt)
WO (1)	WO2000003997A1 (pt)

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1999
- 1999-07-14 SK SK21-2001A patent/SK212001A3/sk unknown
- 1999-07-14 EP EP99929832A patent/EP1097926A4/en not_active Withdrawn
- 1999-07-14 EE EEP200100022A patent/EE04904B1/xx not_active IP Right Cessation
- 1999-07-14 PL PL345540A patent/PL203730B1/pl not_active IP Right Cessation
- 1999-07-14 ID IDW20010090A patent/ID26899A/id unknown
- 1999-07-14 HR HR20010030A patent/HRP20010030A2/hr not_active Application Discontinuation
- 1999-07-14 HU HU0103256A patent/HUP0103256A3/hu unknown
- 1999-07-14 IL IL14086299A patent/IL140862A/xx not_active IP Right Cessation
- 1999-07-14 WO PCT/JP1999/003799 patent/WO2000003997A1/ja not_active Ceased
- 1999-07-14 RU RU2001104339A patent/RU2237663C2/ru not_active IP Right Cessation
- 1999-07-14 BR BR9912098-4A patent/BR9912098A/pt not_active Application Discontinuation
- 1999-07-14 JP JP2000560104A patent/JP3923255B2/ja not_active Expired - Fee Related
- 1999-07-14 CA CA002336909A patent/CA2336909C/en not_active Expired - Fee Related
- 1999-07-14 CN CNB998108162A patent/CN1187337C/zh not_active Expired - Fee Related
- 1999-07-14 TR TR2001/00047T patent/TR200100047T2/xx unknown
- 1999-07-14 KR KR1020017000503A patent/KR100903531B1/ko not_active Expired - Fee Related
- 1999-07-14 AU AU46519/99A patent/AU758789B2/en not_active Ceased
- 1999-07-14 NZ NZ509207A patent/NZ509207A/xx not_active IP Right Cessation
2001
- 2001-01-12 IS IS5807A patent/IS5807A/is unknown
- 2001-01-12 NO NO20010193A patent/NO318957B1/no not_active IP Right Cessation
- 2001-01-15 BG BG105149A patent/BG65514B1/bg unknown
2004
- 2004-10-14 US US10/963,710 patent/US7268145B2/en not_active Expired - Fee Related
2007
- 2007-05-09 US US11/797,975 patent/US20070275995A1/en not_active Abandoned

Also Published As

Publication number	Publication date
EE200100022A (et)	2002-06-17
IL140862A (en)	2005-05-17
HRP20010030A2 (en)	2001-12-31
US20060040976A1 (en)	2006-02-23
PL203730B1 (pl)	2009-11-30
EE04904B1 (et)	2007-10-15
NO318957B1 (no)	2005-05-30
AU4651999A (en)	2000-02-07
BG105149A (en)	2001-08-31
RU2237663C2 (ru)	2004-10-10
KR20010079527A (ko)	2001-08-22
BR9912098A (pt)	2001-09-25
US20070275995A1 (en)	2007-11-29
NZ509207A (en)	2003-01-31
KR100903531B1 (ko)	2009-06-23
WO2000003997A1 (en)	2000-01-27
TR200100047T2 (tr)	2001-10-22
CN1187337C (zh)	2005-02-02
EP1097926A4 (en)	2004-06-30
ID26899A (id)	2001-02-15
NO20010193L (no)	2001-01-12
EP1097926A1 (en)	2001-05-09
IL140862A0 (en)	2002-02-10
CA2336909A1 (en)	2000-01-27
IS5807A (is)	2001-01-12
HUP0103256A2 (hu)	2002-04-29
AU758789B2 (en)	2003-03-27
PL345540A1 (en)	2001-12-17
NO20010193D0 (no)	2001-01-12
US7268145B2 (en)	2007-09-11
BG65514B1 (bg)	2008-10-31
HUP0103256A3 (en)	2002-05-28
CN1316998A (zh)	2001-10-10
CA2336909C (en)	2009-10-20
JP3923255B2 (ja)	2007-05-30

Publication	Publication Date	Title
SK212001A3 (en)	2001-11-06	Thiobenzimidazole derivatives
JPWO2000003997A1 (ja)	2001-09-18	チオベンズイミダゾール誘導体
AU777813B2 (en)	2004-11-04	Benzimidazole derivatives
AU783839B2 (en)	2005-12-15	Human chymase inhibitors
JPWO2001053291A1 (ja)	2003-06-17	ベンズイミダゾール誘導体
US7176320B2 (en)	2007-02-13	Benzimidazole derivative
US20050267148A1 (en)	2005-12-01	Benzimidazole derivative
CZ2001153A3 (cs)	2001-06-13	Thiobenzimidazolové deriváty
JP2001199968A (ja)	2001-07-24	アミノベンズイミダゾール誘導体
JP2001199983A (ja)	2001-07-24	ベンズイミダゾール誘導体
HK1037364A (en)	2002-02-08	Thiobenzimidazole derivatives
JP2007119478A (ja)	2007-05-17	チオベンズイミダゾール誘導体
MXPA01000011A (en)	2002-02-26	Thiobenzimidazole derivatives
AU2007234538B2 (en)	2008-09-04	Benzimidazole derivatives

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2010-10-07	FB9A	Suspension of patent application procedure