KR20010013954A - 엔도텔린 길항제로서의 피롤리딘 카복실산 유도체 - Google Patents

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Publication number

KR20010013954A

KR20010013954A KR1019997011980A KR19997011980A KR20010013954A KR 20010013954 A KR20010013954 A KR 20010013954A KR 1019997011980 A KR1019997011980 A KR 1019997011980A KR 19997011980 A KR19997011980 A KR 19997011980A KR 20010013954 A KR20010013954 A KR 20010013954A

Authority

KR

South Korea

Prior art keywords

phenyl

trans

fluoro

methoxyphenyl

fluorophenyl

Prior art date

1997-06-17

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• 108050009340 Endothelin Proteins 0.000 title claims abstract description 33
• 102000002045 Endothelin Human genes 0.000 title claims abstract description 33
• ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 title claims abstract description 32
• 239000005557 antagonist Substances 0.000 title description 3
• NYCVCXMSZNOGDH-UHFFFAOYSA-N pyrrolidine-1-carboxylic acid Chemical class OC(=O)N1CCCC1 NYCVCXMSZNOGDH-UHFFFAOYSA-N 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 200
• 238000000034 method Methods 0.000 claims abstract description 99
• 150000003839 salts Chemical class 0.000 claims abstract description 37
• 230000008485 antagonism Effects 0.000 claims abstract 3
• -1 4-ethoxyphenyl Chemical group 0.000 claims description 564
• 125000000217 alkyl group Chemical group 0.000 claims description 100
• 229910052739 hydrogen Inorganic materials 0.000 claims description 81
• 239000001257 hydrogen Substances 0.000 claims description 79
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 78
• 125000003545 alkoxy group Chemical group 0.000 claims description 74
• 125000002947 alkylene group Chemical group 0.000 claims description 69
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 62
• 125000003118 aryl group Chemical group 0.000 claims description 55
• 125000000623 heterocyclic group Chemical group 0.000 claims description 49
• 125000005871 1,3-benzodioxolyl group Chemical group 0.000 claims description 43
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 43
• 125000005877 1,4-benzodioxanyl group Chemical group 0.000 claims description 41
• 125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 claims description 41
• 125000001188 haloalkyl group Chemical group 0.000 claims description 37
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 32
• 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 27
• 125000001424 substituent group Chemical group 0.000 claims description 27
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 26
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 25
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 25
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 24
• 125000005111 carboxyalkoxy group Chemical group 0.000 claims description 24
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 24
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 23
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 22
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 22
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 22
• 125000001207 fluorophenyl group Chemical group 0.000 claims description 22
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
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• 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
• 125000005805 dimethoxy phenyl group Chemical group 0.000 claims description 20
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 19
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 19
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 19
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 19
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• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
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• 239000002253 acid Substances 0.000 claims description 14
• 125000004450 alkenylene group Chemical group 0.000 claims description 14
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• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
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• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 10
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 9
• 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 8
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• 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 8
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• 125000004076 pyridyl group Chemical group 0.000 claims description 8
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• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 7
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 6
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• 125000004689 alkyl amino carbonyl alkyl group Chemical group 0.000 claims description 6
• 125000005097 aminocarbonylalkyl group Chemical group 0.000 claims description 6
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• 125000005020 hydroxyalkenyl group Chemical group 0.000 claims description 6
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• 125000005415 substituted alkoxy group Chemical group 0.000 claims description 6
• IMCGHZIGRANKHV-AJNGGQMLSA-N tert-butyl (3s,5s)-2-oxo-5-[(2s,4s)-5-oxo-4-propan-2-yloxolan-2-yl]-3-propan-2-ylpyrrolidine-1-carboxylate Chemical compound O1C(=O)[C@H](C(C)C)C[C@H]1[C@H]1N(C(=O)OC(C)(C)C)C(=O)[C@H](C(C)C)C1 IMCGHZIGRANKHV-AJNGGQMLSA-N 0.000 claims description 6
• RNNCMVHNZGHSLY-ICTSCBFQSA-N (2r,3r,4s)-4-(1,3-benzodioxol-5-yl)-1-[2-(2,6-diethylanilino)-2-oxoethyl]-2-(4-ethoxyphenyl)pyrrolidine-3-carboxylic acid Chemical compound C1=CC(OCC)=CC=C1[C@@H]1N(CC(=O)NC=2C(=CC=CC=2CC)CC)C[C@H](C=2C=C3OCOC3=CC=2)[C@H]1C(O)=O RNNCMVHNZGHSLY-ICTSCBFQSA-N 0.000 claims description 5
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 5
• PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims description 5
• 229930105110 Cyclosporin A Natural products 0.000 claims description 5
• 108010036949 Cyclosporine Proteins 0.000 claims description 5
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• 125000005127 aryl alkoxy alkyl group Chemical group 0.000 claims description 5
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• 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 5
• NETOEYWNARBNQU-FLIPHLSNSA-N (2r,3r,4s)-4-(1,3-benzodioxol-5-yl)-1-[2-(2,6-diethylanilino)-2-oxoethyl]-2-[4-(2-ethoxyethoxy)phenyl]pyrrolidine-3-carboxylic acid Chemical compound C1=CC(OCCOCC)=CC=C1[C@@H]1N(CC(=O)NC=2C(=CC=CC=2CC)CC)C[C@H](C=2C=C3OCOC3=CC=2)[C@H]1C(O)=O NETOEYWNARBNQU-FLIPHLSNSA-N 0.000 claims description 4
• YPCZZHQNKFJAOP-FUKIBTTHSA-N (2r,3r,4s)-4-(1,3-benzodioxol-5-yl)-1-[2-(2,6-diethylanilino)-2-oxoethyl]-2-[4-(2-methoxyethoxy)phenyl]pyrrolidine-3-carboxylic acid Chemical compound CCC1=CC=CC(CC)=C1NC(=O)CN1[C@@H](C=2C=CC(OCCOC)=CC=2)[C@H](C(O)=O)[C@@H](C=2C=C3OCOC3=CC=2)C1 YPCZZHQNKFJAOP-FUKIBTTHSA-N 0.000 claims description 4
• WDCIAYCBGZOIRY-UHFFFAOYSA-N 1-[2-(2,6-diethylanilino)-2-oxoethyl]pyrrolidine-3-carboxylic acid Chemical compound CCC1=CC=CC(CC)=C1NC(=O)CN1CC(C(O)=O)CC1 WDCIAYCBGZOIRY-UHFFFAOYSA-N 0.000 claims description 4
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• JAEIBKXSIXOLOL-UHFFFAOYSA-N pyrrolidin-1-ium-3-carboxylate Chemical compound OC(=O)C1CCNC1 JAEIBKXSIXOLOL-UHFFFAOYSA-N 0.000 claims description 2
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