JP5260818B2 - 高親和性低分子C5a受容体調節物質 - Google Patents
高親和性低分子C5a受容体調節物質 Download PDFInfo
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- JP5260818B2 JP5260818B2 JP2002551496A JP2002551496A JP5260818B2 JP 5260818 B2 JP5260818 B2 JP 5260818B2 JP 2002551496 A JP2002551496 A JP 2002551496A JP 2002551496 A JP2002551496 A JP 2002551496A JP 5260818 B2 JP5260818 B2 JP 5260818B2
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- butyl
- phenyl
- alkyl
- amino
- phenylmethyl
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- 102000005590 Anaphylatoxin C5a Receptor Human genes 0.000 title abstract description 31
- 108010059426 Anaphylatoxin C5a Receptor Proteins 0.000 title abstract description 27
- 229940075993 receptor modulator Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 271
- -1 benzo [b] thiophen-5-ylmethyl Chemical group 0.000 claims description 690
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 221
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 215
- CRZDNISJUXVSKX-UHFFFAOYSA-N 1h-imidazol-2-ylmethanamine Chemical compound NCC1=NC=CN1 CRZDNISJUXVSKX-UHFFFAOYSA-N 0.000 claims description 134
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 47
- JPJMLQRVGZBWPD-UHFFFAOYSA-N 2-methyl-1h-imidazol-5-amine Chemical compound CC1=NC=C(N)N1 JPJMLQRVGZBWPD-UHFFFAOYSA-N 0.000 claims description 46
- 150000003839 salts Chemical class 0.000 claims description 31
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 16
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 14
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 10
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 9
- PQAMFDRRWURCFQ-UHFFFAOYSA-N 2-ethyl-1h-imidazole Chemical compound CCC1=NC=CN1 PQAMFDRRWURCFQ-UHFFFAOYSA-N 0.000 claims description 8
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 6
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 4
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000005605 benzo group Chemical group 0.000 claims description 3
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- ITACCRHKSPSKKL-UHFFFAOYSA-N 1-(1,3-benzodioxol-5-yl)-n-(1,3-benzodioxol-5-ylmethyl)-n-[(3-butyl-2,5-diphenylimidazol-4-yl)methyl]methanamine Chemical compound CCCCN1C(CN(CC=2C=C3OCOC3=CC=2)CC=2C=C3OCOC3=CC=2)=C(C=2C=CC=CC=2)N=C1C1=CC=CC=C1 ITACCRHKSPSKKL-UHFFFAOYSA-N 0.000 claims description 2
- DEURIUYJZZLADZ-UHFFFAOYSA-N 2-(1h-imidazol-2-yl)ethanamine Chemical compound NCCC1=NC=CN1 DEURIUYJZZLADZ-UHFFFAOYSA-N 0.000 claims description 2
- ZLZBGQFTBBMXPQ-UHFFFAOYSA-N 2-[[5-[[butyl-[(3-butyl-2,5-diphenylimidazol-4-yl)methyl]amino]methyl]pyridin-2-yl]amino]ethanol Chemical compound C=1C=C(NCCO)N=CC=1CN(CCCC)CC(N1CCCC)=C(C=2C=CC=CC=2)N=C1C1=CC=CC=C1 ZLZBGQFTBBMXPQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000004462 3,4-difluorophenylmethyl group Chemical group FC=1C=C(C=CC1F)C* 0.000 claims description 2
- FPQYWLZRMCVFGT-UHFFFAOYSA-N 3-[[benzyl-[(3-butyl-2,5-diphenylimidazol-4-yl)methyl]amino]methyl]phenol Chemical compound C=1C=CC=CC=1C=1N=C(C=2C=CC=CC=2)N(CCCC)C=1CN(CC=1C=C(O)C=CC=1)CC1=CC=CC=C1 FPQYWLZRMCVFGT-UHFFFAOYSA-N 0.000 claims description 2
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 2
- WGBSBGKWCNRTOJ-UHFFFAOYSA-N 4-[[(3-butyl-2,5-diphenylimidazol-4-yl)methyl-(cyclohexylmethyl)amino]methyl]-n,n-dimethylaniline Chemical compound C=1C=CC=CC=1C=1N=C(C=2C=CC=CC=2)N(CCCC)C=1CN(CC=1C=CC(=CC=1)N(C)C)CC1CCCCC1 WGBSBGKWCNRTOJ-UHFFFAOYSA-N 0.000 claims description 2
- YOZDLTJJRBIIKL-UHFFFAOYSA-N 4-[[(3-butyl-2,5-diphenylimidazol-4-yl)methyl-[(4-methoxyphenyl)methyl]amino]methyl]benzoic acid Chemical compound C=1C=CC=CC=1C=1N=C(C=2C=CC=CC=2)N(CCCC)C=1CN(CC=1C=CC(=CC=1)C(O)=O)CC1=CC=C(OC)C=C1 YOZDLTJJRBIIKL-UHFFFAOYSA-N 0.000 claims description 2
- WAWOOQYBGGKSDJ-UHFFFAOYSA-N 4-[[(3-butyl-2,5-diphenylimidazol-4-yl)methyl-[[4-(dimethylamino)phenyl]methyl]amino]methyl]benzoic acid Chemical compound C=1C=CC=CC=1C=1N=C(C=2C=CC=CC=2)N(CCCC)C=1CN(CC=1C=CC(=CC=1)C(O)=O)CC1=CC=C(N(C)C)C=C1 WAWOOQYBGGKSDJ-UHFFFAOYSA-N 0.000 claims description 2
- BXNSRMJBQLZZHK-UHFFFAOYSA-N 4-[[1-(3-butyl-2-phenylimidazol-4-yl)pentyl-(cyclohexylmethyl)amino]methyl]phenol Chemical compound C=1N=C(C=2C=CC=CC=2)N(CCCC)C=1C(CCCC)N(CC=1C=CC(O)=CC=1)CC1CCCCC1 BXNSRMJBQLZZHK-UHFFFAOYSA-N 0.000 claims description 2
- RIXQUHXIMCMAFG-UHFFFAOYSA-N 4-[[[3-butyl-5-(4-methoxyphenyl)-2-phenylimidazol-4-yl]methyl-(cyclohexylmethyl)amino]methyl]-2,6-dimethylphenol Chemical compound C=1C=C(OC)C=CC=1C=1N=C(C=2C=CC=CC=2)N(CCCC)C=1CN(CC=1C=C(C)C(O)=C(C)C=1)CC1CCCCC1 RIXQUHXIMCMAFG-UHFFFAOYSA-N 0.000 claims description 2
- RAKJIEVWOFZWRL-UHFFFAOYSA-N 4-[[benzyl-[(3-butyl-2,5-diphenylimidazol-4-yl)methyl]amino]methyl]-2,6-dimethylphenol Chemical compound C=1C=CC=CC=1C=1N=C(C=2C=CC=CC=2)N(CCCC)C=1CN(CC=1C=C(C)C(O)=C(C)C=1)CC1=CC=CC=C1 RAKJIEVWOFZWRL-UHFFFAOYSA-N 0.000 claims description 2
- AJXWVDXTQLBYIW-UHFFFAOYSA-N 4-[[benzyl-[(3-butyl-2,5-diphenylimidazol-4-yl)methyl]amino]methyl]-2-methylphenol Chemical compound C=1C=CC=CC=1C=1N=C(C=2C=CC=CC=2)N(CCCC)C=1CN(CC=1C=C(C)C(O)=CC=1)CC1=CC=CC=C1 AJXWVDXTQLBYIW-UHFFFAOYSA-N 0.000 claims description 2
- KBPBOTDHPCOXQS-UHFFFAOYSA-N 4-[[benzyl-[(3-butyl-2,5-diphenylimidazol-4-yl)methyl]amino]methyl]benzamide Chemical compound C=1C=CC=CC=1C=1N=C(C=2C=CC=CC=2)N(CCCC)C=1CN(CC=1C=CC(=CC=1)C(N)=O)CC1=CC=CC=C1 KBPBOTDHPCOXQS-UHFFFAOYSA-N 0.000 claims description 2
- ZEIXNOMGNPGGIK-UHFFFAOYSA-N 4-[[butyl-[(3-butyl-2,5-diphenylimidazol-4-yl)methyl]amino]methyl]benzamide Chemical compound C=1C=C(C(N)=O)C=CC=1CN(CCCC)CC(N1CCCC)=C(C=2C=CC=CC=2)N=C1C1=CC=CC=C1 ZEIXNOMGNPGGIK-UHFFFAOYSA-N 0.000 claims description 2
- LKRFPDPLBKCSCF-UHFFFAOYSA-N 4-[[butyl-[(3-butyl-5-tert-butyl-2-phenylimidazol-4-yl)methyl]amino]methyl]benzamide Chemical compound C=1C=C(C(N)=O)C=CC=1CN(CCCC)CC(N1CCCC)=C(C(C)(C)C)N=C1C1=CC=CC=C1 LKRFPDPLBKCSCF-UHFFFAOYSA-N 0.000 claims description 2
- XWSKSEYOCVTWCB-UHFFFAOYSA-N 4-[[butyl-[1-(3-butyl-2,5-diphenylimidazol-4-yl)ethyl]amino]methyl]-2,6-dimethylphenol Chemical compound C=1C=CC=CC=1C=1N=C(C=2C=CC=CC=2)N(CCCC)C=1C(C)N(CCCC)CC1=CC(C)=C(O)C(C)=C1 XWSKSEYOCVTWCB-UHFFFAOYSA-N 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- UOCJDOLVGGIYIQ-PBFPGSCMSA-N cefatrizine Chemical group S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)[C@H](N)C=2C=CC(O)=CC=2)CC=1CSC=1C=NNN=1 UOCJDOLVGGIYIQ-PBFPGSCMSA-N 0.000 claims description 2
- KIQWGWCWLLTSGO-UHFFFAOYSA-N n-(1,3-benzodioxol-5-ylmethyl)-n-[[3-butyl-2-(2-methoxyphenyl)-5-phenylimidazol-4-yl]methyl]-1-phenylmethanamine Chemical compound C=1C=CC=CC=1C=1N=C(C=2C(=CC=CC=2)OC)N(CCCC)C=1CN(CC=1C=C2OCOC2=CC=1)CC1=CC=CC=C1 KIQWGWCWLLTSGO-UHFFFAOYSA-N 0.000 claims description 2
- PPGSXXCVLXOGBR-UHFFFAOYSA-N n-(1,3-benzodioxol-5-ylmethyl)-n-[[3-butyl-2-(2-methoxyphenyl)-5-phenylimidazol-4-yl]methyl]butan-1-amine Chemical compound C=1C=C2OCOC2=CC=1CN(CCCC)CC(N1CCCC)=C(C=2C=CC=CC=2)N=C1C1=CC=CC=C1OC PPGSXXCVLXOGBR-UHFFFAOYSA-N 0.000 claims description 2
- TUFDVPSEZCCKDN-UHFFFAOYSA-N n-(1,3-benzodioxol-5-ylmethyl)-n-[[3-butyl-5-(4-fluorophenyl)-2-phenylimidazol-4-yl]methyl]-1-phenylmethanamine Chemical compound C=1C=C(F)C=CC=1C=1N=C(C=2C=CC=CC=2)N(CCCC)C=1CN(CC=1C=C2OCOC2=CC=1)CC1=CC=CC=C1 TUFDVPSEZCCKDN-UHFFFAOYSA-N 0.000 claims description 2
- YXXXDSZASRCEOG-UHFFFAOYSA-N n-(1,3-benzodioxol-5-ylmethyl)-n-benzyl-1-(3-butyl-2,5-diphenylimidazol-4-yl)ethanamine Chemical compound C=1C=CC=CC=1C=1N=C(C=2C=CC=CC=2)N(CCCC)C=1C(C)N(CC=1C=C2OCOC2=CC=1)CC1=CC=CC=C1 YXXXDSZASRCEOG-UHFFFAOYSA-N 0.000 claims description 2
- VNHDZVSNADXBDE-UHFFFAOYSA-N n-(1,3-benzodioxol-5-ylmethyl)-n-benzyl-1-(3-butyl-2,5-diphenylimidazol-4-yl)pentan-1-amine Chemical compound C=1C=CC=CC=1C=1N=C(C=2C=CC=CC=2)N(CCCC)C=1C(CCCC)N(CC=1C=C2OCOC2=CC=1)CC1=CC=CC=C1 VNHDZVSNADXBDE-UHFFFAOYSA-N 0.000 claims description 2
- LJIZTYVOEQIHAG-UHFFFAOYSA-N n-[(3-butyl-2,5-diphenylimidazol-4-yl)methyl]-n-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-1-phenylmethanamine Chemical compound C=1C=CC=CC=1C=1N=C(C=2C=CC=CC=2)N(CCCC)C=1CN(CC=1C=C2OCCOC2=CC=1)CC1=CC=CC=C1 LJIZTYVOEQIHAG-UHFFFAOYSA-N 0.000 claims description 2
- OWLXGDCKVMQTSM-UHFFFAOYSA-N n-[(3-butyl-2,5-diphenylimidazol-4-yl)methyl]-n-[(2,5-difluorophenyl)methyl]-1-(4-methoxyphenyl)methanamine Chemical compound C=1C=CC=CC=1C=1N=C(C=2C=CC=CC=2)N(CCCC)C=1CN(CC=1C(=CC=C(F)C=1)F)CC1=CC=C(OC)C=C1 OWLXGDCKVMQTSM-UHFFFAOYSA-N 0.000 claims description 2
- GAXFISLJYONFJB-UHFFFAOYSA-N n-[(3-butyl-2,5-diphenylimidazol-4-yl)methyl]-n-[(2,6-dichlorophenyl)methyl]-1-(4-methoxyphenyl)methanamine Chemical compound C=1C=CC=CC=1C=1N=C(C=2C=CC=CC=2)N(CCCC)C=1CN(CC=1C(=CC=CC=1Cl)Cl)CC1=CC=C(OC)C=C1 GAXFISLJYONFJB-UHFFFAOYSA-N 0.000 claims description 2
- DGPWKXMYCZOSOL-UHFFFAOYSA-N n-[(3-butyl-2,5-diphenylimidazol-4-yl)methyl]-n-[(2,6-difluorophenyl)methyl]-1-(4-methoxyphenyl)methanamine Chemical compound C=1C=CC=CC=1C=1N=C(C=2C=CC=CC=2)N(CCCC)C=1CN(CC=1C(=CC=CC=1F)F)CC1=CC=C(OC)C=C1 DGPWKXMYCZOSOL-UHFFFAOYSA-N 0.000 claims description 2
- 125000006514 pyridin-2-ylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 2
- PXSLWYWMPPHCTP-UHFFFAOYSA-N 4-[[benzyl-[1-(3-butyl-2,5-diphenylimidazol-4-yl)ethyl]amino]methyl]benzamide Chemical compound CCCCN1C(C=2C=CC=CC=2)=NC(C=2C=CC=CC=2)=C1C(C)N(CC=1C=CC(=CC=1)C(N)=O)CC1=CC=CC=C1 PXSLWYWMPPHCTP-UHFFFAOYSA-N 0.000 claims 1
- AIZKSRXBUUSBBY-UHFFFAOYSA-N 4-[[butyl-[(3-butyl-2,5-diphenylimidazol-4-yl)methyl]amino]methyl]-2,6-dimethylphenol Chemical compound C=1C(C)=C(O)C(C)=CC=1CN(CCCC)CC(N1CCCC)=C(C=2C=CC=CC=2)N=C1C1=CC=CC=C1 AIZKSRXBUUSBBY-UHFFFAOYSA-N 0.000 claims 1
- 125000001072 heteroaryl group Chemical group 0.000 abstract description 47
- 230000000694 effects Effects 0.000 abstract description 20
- 239000005557 antagonist Substances 0.000 abstract description 12
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 9
- 238000001727 in vivo Methods 0.000 abstract description 8
- 230000002757 inflammatory effect Effects 0.000 abstract description 8
- 230000011268 leukocyte chemotaxis Effects 0.000 abstract description 6
- 239000000556 agonist Substances 0.000 abstract description 5
- 108010078546 Complement C5a Proteins 0.000 abstract description 4
- 239000003446 ligand Substances 0.000 abstract description 4
- 208000026278 immune system disease Diseases 0.000 abstract description 3
- 208000027866 inflammatory disease Diseases 0.000 abstract description 3
- 125000000217 alkyl group Chemical group 0.000 description 324
- 229910052736 halogen Inorganic materials 0.000 description 296
- 150000002367 halogens Chemical class 0.000 description 296
- 125000001188 haloalkyl group Chemical group 0.000 description 259
- 125000004093 cyano group Chemical group *C#N 0.000 description 243
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 238
- 125000001424 substituent group Chemical group 0.000 description 214
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 201
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 196
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 172
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 170
- 229910052739 hydrogen Inorganic materials 0.000 description 169
- 239000001257 hydrogen Substances 0.000 description 169
- 125000003545 alkoxy group Chemical group 0.000 description 138
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 132
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 130
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 125
- 125000000753 cycloalkyl group Chemical group 0.000 description 107
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 77
- 125000004076 pyridyl group Chemical group 0.000 description 77
- 125000003342 alkenyl group Chemical group 0.000 description 76
- 125000000304 alkynyl group Chemical group 0.000 description 75
- 125000001544 thienyl group Chemical group 0.000 description 73
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 71
- 125000000714 pyrimidinyl group Chemical group 0.000 description 69
- 125000001041 indolyl group Chemical group 0.000 description 59
- 125000004663 dialkyl amino group Chemical group 0.000 description 58
- 229910052760 oxygen Inorganic materials 0.000 description 57
- 125000003373 pyrazinyl group Chemical group 0.000 description 57
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 56
- 239000001301 oxygen Substances 0.000 description 56
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 55
- 125000002619 bicyclic group Chemical group 0.000 description 54
- 125000001624 naphthyl group Chemical group 0.000 description 53
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 52
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 52
- 150000002148 esters Chemical class 0.000 description 50
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 49
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 44
- 125000000928 benzodioxinyl group Chemical group O1C(=COC2=C1C=CC=C2)* 0.000 description 43
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- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 41
- 125000002883 imidazolyl group Chemical group 0.000 description 40
- 125000000168 pyrrolyl group Chemical group 0.000 description 37
- 102100031506 Complement C5 Human genes 0.000 description 36
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 36
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 35
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- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 11
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- 150000003335 secondary amines Chemical class 0.000 description 11
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 7
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- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
- C07D217/04—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
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- C—CHEMISTRY; METALLURGY
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- 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
- C07D405/14—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 three or more hetero rings
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- C—CHEMISTRY; METALLURGY
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- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
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- 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
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- 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
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- C07D471/04—Ortho-condensed systems
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- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
- H01J1/00—Details of electrodes, of magnetic control means, of screens, or of the mounting or spacing thereof, common to two or more basic types of discharge tubes or lamps
- H01J1/02—Main electrodes
- H01J1/30—Cold cathodes, e.g. field-emissive cathode
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| PA8535601A1 (es) | 2000-12-21 | 2002-11-28 | Pfizer | Derivados benzimidazol y piridilimidazol como ligandos para gabaa |
| CA2479928A1 (en) * | 2002-03-28 | 2003-10-09 | Neurogen Corporation | Substituted biaryl amides as c5a receptor modulators |
| WO2003082828A1 (en) | 2002-03-28 | 2003-10-09 | Neurogen Corporation | Substituted tetrahydroisoquinolines as c5a receptor modulators |
| US6858637B2 (en) | 2002-03-28 | 2005-02-22 | Neurogen Corporation | Substituted biaryl amides as C5a receptor modulators |
| JP2005528368A (ja) * | 2002-03-29 | 2005-09-22 | ニューロジェン・コーポレーション | C5a受容体モジュレータである新規なアリールイミダゾール及び関連化合物。 |
| GB0214139D0 (en) * | 2002-06-19 | 2002-07-31 | Glaxo Group Ltd | Chemical compounds |
| US7169775B2 (en) | 2002-08-21 | 2007-01-30 | Neurogen Corporation | Amino methyl imidazoles as C5a receptor modulators |
| JP3714948B2 (ja) | 2002-09-11 | 2005-11-09 | 呉羽化学工業株式会社 | アミン化合物及びその用途 |
| ATE552253T1 (de) | 2002-11-08 | 2012-04-15 | Novartis Int Pharm Ltd | 3-substituierte-6-aryl- pyridin derivate als liganden für c5a-rezeptoren |
| US8329169B2 (en) | 2003-05-15 | 2012-12-11 | Genentech, Inc. | Methods and compositions for the prevention and treatment of sepsis |
| CA2558600C (en) | 2004-03-10 | 2013-07-09 | Kureha Corporation | A substituted-trialkyl amine compound with anti-viral activity based on antagonism against a chemokine receptor cxcr4 |
| EP1814576A2 (en) * | 2004-07-20 | 2007-08-08 | Critical Therapeutics, Inc. | Combination therapies of hmgb and complement inhibitors against inflammation |
| JP2007284352A (ja) * | 2004-08-05 | 2007-11-01 | Dai Ichi Seiyaku Co Ltd | ピラゾール誘導体 |
| EP1817030A2 (en) | 2004-12-01 | 2007-08-15 | Kalypsys, Inc. | Inducible nitric oxide synthase dimerization inhibitors |
| AR052674A1 (es) | 2005-02-17 | 2007-03-28 | Wyeth Corp | Derivados de indol, benzotiofeno, benzofurano e indeno cicloalquilcondensados |
| EP1739078A1 (de) | 2005-05-30 | 2007-01-03 | Jerini AG | C5a-Rezeptor-Antagonisten |
| RS54998B1 (sr) | 2008-12-22 | 2016-11-30 | Chemocentryx Inc | Antagonisti c5ar |
| HRP20171176T1 (hr) | 2010-06-24 | 2017-10-06 | Chemocentryx, Inc. | C5ar antagonisti |
| BR112015026847A2 (pt) * | 2013-04-22 | 2017-07-25 | Abbvie Inc | tiazóis e usos dos mesmos |
| CN106999481B (zh) | 2014-09-29 | 2021-04-16 | 凯莫森特里克斯股份有限公司 | 制备C5aR拮抗剂的方法和中间体 |
| EP3072891A1 (en) * | 2015-03-24 | 2016-09-28 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | New Toll-Like Receptor 9 Antagonists |
| TWI791423B (zh) | 2016-01-14 | 2023-02-11 | 美商卡默森屈有限公司 | C3腎絲球病變之治療方法 |
| MA44629A (fr) | 2016-04-04 | 2021-03-24 | Chemocentryx Inc | Antagonistes de c5ar solubles |
| MA48803A (fr) | 2017-05-31 | 2020-04-08 | Chemocentryx Inc | Cycles 6-5 fusionnés utilisés en tant qu'inhibiteurs de c5a |
| MA48800A (fr) | 2017-05-31 | 2020-04-08 | Chemocentryx Inc | Cycles 5-5 fusionnés utilisés en tant qu'inhibiteurs de c5a |
| EP3703687A4 (en) | 2017-10-30 | 2021-04-07 | ChemoCentryx, Inc. | DEUTERATED COMPOUNDS USED AS IMMUNOMODULATORS |
| CN111788185B (zh) | 2017-12-22 | 2024-12-13 | 凯莫森特里克斯股份有限公司 | 作为C5a抑制剂的二芳基取代的6,5稠合环化合物 |
| MA51327A (fr) | 2017-12-22 | 2021-05-26 | Chemocentryx Inc | Composés cycliques fusionnés en 5,5 à substitution diaryle, utilisés en tant qu'inhibiteurs du c5ar |
| MA52245A (fr) | 2018-04-02 | 2021-04-28 | Chemocentryx Inc | Promédicaments d'antagonistes de c5ar bicycliques fusionnés |
| CN114957165A (zh) * | 2021-02-26 | 2022-08-30 | 清华大学 | 一种抗病毒化合物及其制备方法和应用 |
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| JPS6157590A (ja) * | 1984-08-29 | 1986-03-24 | Asahi Shiyueebell Kk | シラン化合物およびその製造法 |
| US5159083A (en) * | 1990-12-28 | 1992-10-27 | Neurogen Corporation | Certain aminomethyl phenylimidazole derivatives; a class of dopamine receptor subtype specific ligands |
| US5681956A (en) * | 1990-12-28 | 1997-10-28 | Neurogen Corporation | 4-aryl substituted piperazinylmethyl phenylimidazole derivatives; a new class of dopamine receptor subtype specific ligands |
| MX9308025A (es) * | 1992-12-22 | 1994-08-31 | Lilly Co Eli | Compuestos inhibidores de la proteasa del virus dela inmunodeficiencia humana, procedimiento para supreparacion y formulacion farmaceutica que los contiene. |
| US5652237A (en) * | 1994-09-09 | 1997-07-29 | Warner-Lambert Company | 2-substituted-4H-3, 1-benzoxazin-4-ones and benzthiazin-4-ones as inhibitors of complement C1r protease for the treatment of inflammatory processes |
| BR9509760A (pt) * | 1994-11-23 | 1998-06-30 | Neurogen Corp | Composto |
| GB9426103D0 (en) * | 1994-12-23 | 1995-02-22 | Merck Sharp & Dohme | Therapeutic agents |
| WO1998002434A1 (en) * | 1996-07-13 | 1998-01-22 | Glaxo Group Limited | Fused heterocyclic compounds as protein tyrosine kinase inhibitors |
| EP1017382B1 (en) * | 1997-05-29 | 2006-03-01 | Merck & Co., Inc. (a New Jersey corp.) | Biarylalkanoic acids as cell adhesion inhibitors |
| MY153569A (en) * | 1998-01-20 | 2015-02-27 | Mitsubishi Tanabe Pharma Corp | Inhibitors of ?4 mediated cell adhesion |
| CN1181817C (zh) * | 1998-03-20 | 2004-12-29 | 第一三得利制药株式会社 | 以苯基甲苯醌为有效成分的NF-kB抑制剂 |
| ES2258331T3 (es) * | 1998-05-22 | 2006-08-16 | Scios Inc. | Compuestos heterociclicos y procedimientos de tratamiento de insuficiencia cardiaca y otros trastornos. |
| EP1097137A1 (en) * | 1998-07-10 | 2001-05-09 | AstraZeneca AB | N-substituted naphthalene carboxamides as neurokinin-receptor antagonists |
| US6423519B1 (en) * | 1998-07-15 | 2002-07-23 | Gpc Biotech Inc. | Compositions and methods for inhibiting fungal growth |
| AU743411B2 (en) * | 1998-08-21 | 2002-01-24 | Viropharma Incorporated | Compounds, compositions and methods for treating or preventing viral infections and associated diseases |
| US6437146B1 (en) * | 1998-09-25 | 2002-08-20 | Fujisawa Pharmaceutical Co., Ltd. | Oxazole compounds as prostaglandin e2 agonists or antagonists |
| EP1126843A4 (en) * | 1998-10-29 | 2005-06-15 | Bristol Myers Squibb Co | AMINO-CELL DERIVATIVE COMPOUNDS INHIBITORS OF ENZYME IMPDH |
| US6503905B1 (en) * | 1998-12-29 | 2003-01-07 | Pfizer Inc | 3,3-biarylpiperidine and 2,2-biarylmorpholine derivatives |
| PL350998A1 (en) * | 1999-03-24 | 2003-02-24 | Anormed Inc | Chemokine recpetor binding heterocyclic compounds |
| US6369226B1 (en) * | 1999-06-21 | 2002-04-09 | Agouron Pharmaceuticals, Inc. | Substituted benzamide inhibitors of rhinovirus 3C protease |
| ATE339406T1 (de) * | 1999-09-23 | 2006-10-15 | Astrazeneca Ab | Chinazoline verbindungen als heilmittel |
| DE60143457D1 (de) * | 2000-09-15 | 2010-12-23 | Anormed Inc | Chemokin Rezeptor bindende heterozyklische Verbindungen |
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| YU23503A (sh) | 2006-03-03 |
| NO20031370L (no) | 2003-05-30 |
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| BR0017338A (pt) | 2004-04-27 |
| EP1322309A4 (en) | 2004-10-13 |
| WO2002049993A3 (en) | 2003-02-20 |
| IL154993A0 (en) | 2003-10-31 |
| KR20030060887A (ko) | 2003-07-16 |
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