CA2297894A1 - Antagonistes d'endotheline - Google Patents
Antagonistes d'endotheline Download PDFInfo
- Publication number
- CA2297894A1 CA2297894A1 CA002297894A CA2297894A CA2297894A1 CA 2297894 A1 CA2297894 A1 CA 2297894A1 CA 002297894 A CA002297894 A CA 002297894A CA 2297894 A CA2297894 A CA 2297894A CA 2297894 A1 CA2297894 A1 CA 2297894A1
- Authority
- CA
- Canada
- Prior art keywords
- loweralkyl
- hydrogen
- aryl
- haloalkyl
- methoxyphenyl
- Prior art date
- Legal status (The legal status 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 status listed.)
- Abandoned
Links
- 108050009340 Endothelin Proteins 0.000 title claims abstract description 15
- 102000002045 Endothelin Human genes 0.000 title claims abstract description 15
- 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 15
- JAEIBKXSIXOLOL-UHFFFAOYSA-N pyrrolidin-1-ium-3-carboxylate Chemical class OC(=O)C1CCNC1 JAEIBKXSIXOLOL-UHFFFAOYSA-N 0.000 title claims description 44
- 239000005557 antagonist Substances 0.000 title description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 378
- 238000000034 method Methods 0.000 claims abstract description 168
- 150000003839 salts Chemical class 0.000 claims abstract description 33
- 230000008569 process Effects 0.000 claims abstract description 21
- 238000002360 preparation method Methods 0.000 claims abstract description 15
- 230000003042 antagnostic effect Effects 0.000 claims abstract description 12
- -1 loweralkyl Chemical group 0.000 claims description 481
- 229910052739 hydrogen Inorganic materials 0.000 claims description 198
- 239000001257 hydrogen Substances 0.000 claims description 174
- 125000003118 aryl group Chemical group 0.000 claims description 155
- 125000000623 heterocyclic group Chemical group 0.000 claims description 148
- 125000002947 alkylene group Chemical group 0.000 claims description 145
- 125000001188 haloalkyl group Chemical group 0.000 claims description 143
- 125000003545 alkoxy group Chemical group 0.000 claims description 124
- 239000000203 mixture Substances 0.000 claims description 118
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 117
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 106
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 104
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 95
- 125000000217 alkyl group Chemical group 0.000 claims description 94
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 83
- 125000003342 alkenyl group Chemical group 0.000 claims description 80
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 76
- 125000005877 1,4-benzodioxanyl group Chemical group 0.000 claims description 75
- 125000005871 1,3-benzodioxolyl group Chemical group 0.000 claims description 71
- 125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 claims description 69
- 125000001424 substituent group Chemical group 0.000 claims description 69
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 68
- 125000004994 halo alkoxy alkyl group Chemical group 0.000 claims description 62
- 239000002253 acid Substances 0.000 claims description 59
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 55
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 53
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 52
- 150000002148 esters Chemical class 0.000 claims description 49
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 47
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 45
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 44
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 43
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 42
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 42
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 41
- 125000004212 difluorophenyl group Chemical group 0.000 claims description 40
- 125000005805 dimethoxy phenyl group Chemical group 0.000 claims description 40
- 125000001207 fluorophenyl group Chemical group 0.000 claims description 37
- 125000005111 carboxyalkoxy group Chemical group 0.000 claims description 36
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 31
- 125000000304 alkynyl group Chemical group 0.000 claims description 30
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 29
- 150000002367 halogens Chemical class 0.000 claims description 29
- 125000005081 alkoxyalkoxyalkyl group Chemical group 0.000 claims description 27
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 26
- 229910052736 halogen Inorganic materials 0.000 claims description 26
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 24
- 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 claims description 24
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 24
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- 125000004450 alkenylene group Chemical group 0.000 claims description 24
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 24
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 23
- MALIONKMKPITBV-UHFFFAOYSA-N 2-(3-chloro-4-hydroxyphenyl)-n-[2-(4-sulfamoylphenyl)ethyl]acetamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1CCNC(=O)CC1=CC=C(O)C(Cl)=C1 MALIONKMKPITBV-UHFFFAOYSA-N 0.000 claims description 21
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 20
- 125000005127 aryl alkoxy alkyl group Chemical group 0.000 claims description 20
- 125000004689 alkyl amino carbonyl alkyl group Chemical group 0.000 claims description 19
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 19
- 125000005097 aminocarbonylalkyl group Chemical group 0.000 claims description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 19
- 125000003282 alkyl amino group Chemical group 0.000 claims description 18
- 239000003054 catalyst Substances 0.000 claims description 18
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 18
- 241000124008 Mammalia Species 0.000 claims description 17
- 125000005020 hydroxyalkenyl group Chemical group 0.000 claims description 17
- 125000004076 pyridyl group Chemical group 0.000 claims description 16
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 16
- 125000002541 furyl group Chemical group 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 13
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 13
- 206010002383 Angina Pectoris Diseases 0.000 claims description 11
- 208000019695 Migraine disease Diseases 0.000 claims description 11
- 208000027418 Wounds and injury Diseases 0.000 claims description 11
- 206010009887 colitis Diseases 0.000 claims description 11
- 230000006378 damage Effects 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- 208000014674 injury Diseases 0.000 claims description 11
- 206010027599 migraine Diseases 0.000 claims description 11
- 208000002815 pulmonary hypertension Diseases 0.000 claims description 11
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 10
- 239000007868 Raney catalyst Substances 0.000 claims description 9
- 229910000564 Raney nickel Inorganic materials 0.000 claims description 9
- 230000009471 action Effects 0.000 claims description 9
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 9
- 125000004104 aryloxy group Chemical group 0.000 claims description 9
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 9
- 238000005984 hydrogenation reaction Methods 0.000 claims description 8
- 229930105110 Cyclosporin A Natural products 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 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 6
- 108010036949 Cyclosporine Proteins 0.000 claims description 6
- 208000003782 Raynaud disease Diseases 0.000 claims description 6
- 208000012322 Raynaud phenomenon Diseases 0.000 claims description 6
- 229960001265 ciclosporin Drugs 0.000 claims description 6
- 229930182912 cyclosporin Natural products 0.000 claims description 6
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 6
- DQFUEDRYWCNOLS-UHFFFAOYSA-N 1-[2-(dibutylamino)-2-oxoethyl]pyrrolidine-3-carboxylic acid Chemical compound CCCCN(CCCC)C(=O)CN1CCC(C(O)=O)C1 DQFUEDRYWCNOLS-UHFFFAOYSA-N 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 230000000694 effects Effects 0.000 claims description 5
- 238000006345 epimerization reaction Methods 0.000 claims description 5
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical group [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 5
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 4
- 125000000262 haloalkenyl group Chemical group 0.000 claims description 4
- IWYDHOAUDWTVEP-ZETCQYMHSA-N (S)-mandelic acid Chemical compound OC(=O)[C@@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-ZETCQYMHSA-N 0.000 claims description 3
- 102000004506 Blood Proteins Human genes 0.000 claims description 3
- 108010017384 Blood Proteins Proteins 0.000 claims description 3
- 101150087654 chrnd gene Proteins 0.000 claims description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 3
- SYIZDRIGROMPEM-UNHDOIQYSA-N (2s,3r,4s)-4-(1,3-benzodioxol-5-yl)-1-[2-(dibutylamino)-2-oxoethyl]-2-[2-(2-methoxyphenyl)ethyl]pyrrolidine-3-carboxylic acid Chemical compound C([C@H]1[C@@H]([C@H](CN1CC(=O)N(CCCC)CCCC)C=1C=C2OCOC2=CC=1)C(O)=O)CC1=CC=CC=C1OC SYIZDRIGROMPEM-UNHDOIQYSA-N 0.000 claims description 2
- BIGMNZHMQYPRAI-UHFFFAOYSA-N 1-[2-[2-(2,2,3,3,3-pentafluoropropoxy)ethylsulfonyl-propylamino]ethyl]pyrrolidine-3-carboxylic acid Chemical compound C(CC)N(S(=O)(=O)CCOCC(C(F)(F)F)(F)F)CCN1CC(CC1)C(=O)O BIGMNZHMQYPRAI-UHFFFAOYSA-N 0.000 claims description 2
- ZKNHDJMXIUOHLX-UHFFFAOYSA-N 2-ethoxy-1,1,1-trifluoroethane Chemical compound CCOCC(F)(F)F ZKNHDJMXIUOHLX-UHFFFAOYSA-N 0.000 claims description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 2
- 238000001727 in vivo Methods 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 102000004169 proteins and genes Human genes 0.000 claims description 2
- 108090000623 proteins and genes Proteins 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims 29
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 16
- 230000001154 acute effect Effects 0.000 claims 10
- 208000035475 disorder Diseases 0.000 claims 10
- 229910018828 PO3H2 Inorganic materials 0.000 claims 9
- 125000001589 carboacyl group Chemical group 0.000 claims 9
- 201000001320 Atherosclerosis Diseases 0.000 claims 8
- 201000006474 Brain Ischemia Diseases 0.000 claims 8
- 206010007559 Cardiac failure congestive Diseases 0.000 claims 8
- 206010008120 Cerebral ischaemia Diseases 0.000 claims 8
- 206010019280 Heart failures Diseases 0.000 claims 8
- 206010020772 Hypertension Diseases 0.000 claims 8
- 230000002490 cerebral effect Effects 0.000 claims 8
- 206010008118 cerebral infarction Diseases 0.000 claims 8
- 208000031225 myocardial ischemia Diseases 0.000 claims 8
- OAEWNSKRLBVVBV-QSEAXJEQSA-N (2s,3r,4s)-1-[2-(dibutylamino)-2-oxoethyl]-2-(2,2-dimethylpentyl)-4-(7-methoxy-1,3-benzodioxol-5-yl)pyrrolidine-3-carboxylic acid Chemical compound OC(=O)[C@H]1[C@H](CC(C)(C)CCC)N(CC(=O)N(CCCC)CCCC)C[C@@H]1C(C=C1OC)=CC2=C1OCO2 OAEWNSKRLBVVBV-QSEAXJEQSA-N 0.000 claims 7
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims 7
- 208000004403 Prostatic Hyperplasia Diseases 0.000 claims 7
- 206010003162 Arterial injury Diseases 0.000 claims 6
- 208000037803 restenosis Diseases 0.000 claims 6
- 208000009304 Acute Kidney Injury Diseases 0.000 claims 5
- 206010048610 Cardiotoxicity Diseases 0.000 claims 5
- 102000000588 Interleukin-2 Human genes 0.000 claims 5
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- 102000004895 Lipoproteins Human genes 0.000 claims 5
- 108090001030 Lipoproteins Proteins 0.000 claims 5
- 206010028980 Neoplasm Diseases 0.000 claims 5
- 208000001647 Renal Insufficiency Diseases 0.000 claims 5
- 208000033626 Renal failure acute Diseases 0.000 claims 5
- 208000007536 Thrombosis Diseases 0.000 claims 5
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- 201000011040 acute kidney failure Diseases 0.000 claims 5
- 208000012998 acute renal failure Diseases 0.000 claims 5
- 208000006673 asthma Diseases 0.000 claims 5
- 201000011510 cancer Diseases 0.000 claims 5
- 231100000259 cardiotoxicity Toxicity 0.000 claims 5
- 230000001684 chronic effect Effects 0.000 claims 5
- 208000020832 chronic kidney disease Diseases 0.000 claims 5
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- 239000002158 endotoxin Substances 0.000 claims 5
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- 208000010110 spontaneous platelet aggregation Diseases 0.000 claims 5
- 231100000419 toxicity Toxicity 0.000 claims 5
- 230000001988 toxicity Effects 0.000 claims 5
- 230000036269 ulceration Effects 0.000 claims 5
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- 239000008194 pharmaceutical composition Substances 0.000 claims 4
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical group [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims 3
- 150000007513 acids Chemical class 0.000 claims 3
- 229940125692 cardiovascular agent Drugs 0.000 claims 3
- 239000002327 cardiovascular agent Substances 0.000 claims 3
- 231100000268 induced nephrotoxicity Toxicity 0.000 claims 3
- 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 3
- 230000003287 optical effect Effects 0.000 claims 2
- ONQFGCOKSYLREQ-QSEAXJEQSA-N (2s,3r,4s)-4-(1,3-benzodioxol-5-yl)-1-[2-(dibutylamino)-2-oxoethyl]-2-(2,2-dimethylpentyl)pyrrolidine-3-carboxylic acid Chemical compound OC(=O)[C@H]1[C@H](CC(C)(C)CCC)N(CC(=O)N(CCCC)CCCC)C[C@@H]1C1=CC=C(OCO2)C2=C1 ONQFGCOKSYLREQ-QSEAXJEQSA-N 0.000 claims 1
- MFQJKAWSOOEUKH-VDWGHMIBSA-N (2s,3r,4s)-4-(1,3-benzodioxol-5-yl)-1-[2-(dibutylamino)-2-oxoethyl]-2-[(2-methoxyphenoxy)methyl]pyrrolidine-3-carboxylic acid Chemical compound C([C@@H]1[C@@H]([C@H](CN1CC(=O)N(CCCC)CCCC)C=1C=C2OCOC2=CC=1)C(O)=O)OC1=CC=CC=C1OC MFQJKAWSOOEUKH-VDWGHMIBSA-N 0.000 claims 1
- IWEQMCSDVPZVMA-UMTXDNHDSA-N (2s,3r,4s)-4-(1,3-benzodioxol-5-yl)-1-[2-(dibutylamino)-2-oxoethyl]-2-[2-(2-oxopyrrolidin-1-yl)ethyl]pyrrolidine-3-carboxylic acid Chemical compound C([C@H]1[C@@H]([C@H](CN1CC(=O)N(CCCC)CCCC)C=1C=C2OCOC2=CC=1)C(O)=O)CN1CCCC1=O IWEQMCSDVPZVMA-UMTXDNHDSA-N 0.000 claims 1
- HPPJVFANSFCYQS-UHFFFAOYSA-N 1-[2-[3-chloropropylsulfonyl(propyl)amino]ethyl]pyrrolidine-3-carboxylic acid Chemical compound ClCCCS(=O)(=O)N(CCC)CCN1CCC(C(O)=O)C1 HPPJVFANSFCYQS-UHFFFAOYSA-N 0.000 claims 1
- 125000006213 aryl hydroxyalkyl group Chemical group 0.000 claims 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical class [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 150
- 238000005481 NMR spectroscopy Methods 0.000 description 132
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 40
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 32
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 30
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 29
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- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 29
- 239000012267 brine Substances 0.000 description 21
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 21
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 21
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- PBGGNZZGJIKBMJ-UHFFFAOYSA-N di(propan-2-yl)azanide Chemical compound CC(C)[N-]C(C)C PBGGNZZGJIKBMJ-UHFFFAOYSA-N 0.000 description 1
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- FHHZOYXKOICLGH-UHFFFAOYSA-N dichloromethane;ethanol Chemical compound CCO.ClCCl FHHZOYXKOICLGH-UHFFFAOYSA-N 0.000 description 1
- GRTGGSXWHGKRSB-UHFFFAOYSA-N dichloromethyl methyl ether Chemical compound COC(Cl)Cl GRTGGSXWHGKRSB-UHFFFAOYSA-N 0.000 description 1
- JXSJBGJIGXNWCI-UHFFFAOYSA-N diethyl 2-[(dimethoxyphosphorothioyl)thio]succinate Chemical compound CCOC(=O)CC(SP(=S)(OC)OC)C(=O)OCC JXSJBGJIGXNWCI-UHFFFAOYSA-N 0.000 description 1
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- 125000004598 dihydrobenzofuryl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 description 1
- 125000001070 dihydroindolyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- RQKYPMNUYSOMOD-UHFFFAOYSA-N dimethyl(methylsulfanyl)sulfanium Chemical compound CS[S+](C)C RQKYPMNUYSOMOD-UHFFFAOYSA-N 0.000 description 1
- WEHWNAOGRSTTBQ-UHFFFAOYSA-N dipropylamine Chemical compound CCCNCCC WEHWNAOGRSTTBQ-UHFFFAOYSA-N 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 1
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- 125000004185 ester group Chemical group 0.000 description 1
- 239000010696 ester oil Substances 0.000 description 1
- ZRSDQBKGDNPFLT-UHFFFAOYSA-N ethanol;oxolane Chemical compound CCO.C1CCOC1 ZRSDQBKGDNPFLT-UHFFFAOYSA-N 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- YZEWJYIDAAGEHA-UHFFFAOYSA-N ethyl 2-di(propan-2-yloxy)phosphorylacetate Chemical compound CCOC(=O)CP(=O)(OC(C)C)OC(C)C YZEWJYIDAAGEHA-UHFFFAOYSA-N 0.000 description 1
- JUEBDJQXUIBLAM-UHFFFAOYSA-N ethyl 3-[4-methoxy-2-(methoxymethoxy)phenyl]-3-oxopropanoate Chemical group CCOC(=O)CC(=O)C1=CC=C(OC)C=C1OCOC JUEBDJQXUIBLAM-UHFFFAOYSA-N 0.000 description 1
- UTXVCHVLDOLVPC-UHFFFAOYSA-N ethyl 3-methylbut-2-enoate Chemical compound CCOC(=O)C=C(C)C UTXVCHVLDOLVPC-UHFFFAOYSA-N 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
- WUDNUHPRLBTKOJ-UHFFFAOYSA-N ethyl isocyanate Chemical compound CCN=C=O WUDNUHPRLBTKOJ-UHFFFAOYSA-N 0.000 description 1
- 125000006260 ethylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 230000024924 glomerular filtration Effects 0.000 description 1
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- 125000005842 heteroatom Chemical group 0.000 description 1
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- 238000011905 homologation Methods 0.000 description 1
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- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
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- 239000012535 impurity Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
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- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
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- 208000012947 ischemia reperfusion injury Diseases 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
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- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
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- 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
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- 210000005053 lamin Anatomy 0.000 description 1
- FEWJPZIEWOKRBE-LWMBPPNESA-N levotartaric acid Chemical compound OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- LZWQNOHZMQIFBX-UHFFFAOYSA-N lithium;2-methylpropan-2-olate Chemical compound [Li+].CC(C)(C)[O-] LZWQNOHZMQIFBX-UHFFFAOYSA-N 0.000 description 1
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- UGVPKMAWLOMPRS-UHFFFAOYSA-M magnesium;propane;bromide Chemical compound [Mg+2].[Br-].CC[CH2-] UGVPKMAWLOMPRS-UHFFFAOYSA-M 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
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- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 description 1
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- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
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- 101150009274 nhr-1 gene Proteins 0.000 description 1
- 125000006502 nitrobenzyl group Chemical group 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
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- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 125000003232 p-nitrobenzoyl group Chemical group [N+](=O)([O-])C1=CC=C(C(=O)*)C=C1 0.000 description 1
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- 230000007310 pathophysiology Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 description 1
- 238000005897 peptide coupling reaction Methods 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 125000006678 phenoxycarbonyl group Chemical group 0.000 description 1
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- 238000006303 photolysis reaction Methods 0.000 description 1
- 230000015843 photosynthesis, light reaction Effects 0.000 description 1
- 125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- YQDKSZGVQJBJAH-UHFFFAOYSA-N piperidin-1-yl nitrite Chemical compound O=NON1CCCCC1 YQDKSZGVQJBJAH-UHFFFAOYSA-N 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- ZRLVQFQTCMUIRM-UHFFFAOYSA-N potassium;2-methylbutan-2-olate Chemical compound [K+].CCC(C)(C)[O-] ZRLVQFQTCMUIRM-UHFFFAOYSA-N 0.000 description 1
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- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910001923 silver oxide Inorganic materials 0.000 description 1
- CLDWGXZGFUNWKB-UHFFFAOYSA-M silver;benzoate Chemical compound [Ag+].[O-]C(=O)C1=CC=CC=C1 CLDWGXZGFUNWKB-UHFFFAOYSA-M 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
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- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
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- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 description 1
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- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
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- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—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
- C07D207/18—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 one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—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 one double bond between ring members or between a ring member and a non-ring member 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 to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
- C07D207/27—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—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
- C07D207/04—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
- C07D207/10—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 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 to ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- C07D403/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D405/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D405/14—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
-
- 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
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
- C07D417/14—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 three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Neurology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Diabetes (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Steroid Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyrrole Compounds (AREA)
Abstract
La présente invention concerne des composés représentés par la formule (I) ou un sel pharmaceutiquement acceptable de ceux-ci ainsi que des processus de fabrication desdits composés et des intermédiaires utilisés dans lesdits processus et un procédé permettant de bloquer l'activité d'une endothéline.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/905,913 | 1997-08-04 | ||
| US08/905,913 US6162927A (en) | 1994-08-19 | 1997-08-04 | Endothelin antagonists |
| US4895598A | 1998-03-27 | 1998-03-27 | |
| US09/048,955 | 1998-03-27 | ||
| PCT/US1998/015479 WO1999006397A2 (fr) | 1997-08-04 | 1998-07-27 | Antagonistes d'endotheline |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2297894A1 true CA2297894A1 (fr) | 1999-02-11 |
Family
ID=26726720
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002297894A Abandoned CA2297894A1 (fr) | 1997-08-04 | 1998-07-27 | Antagonistes d'endotheline |
Country Status (16)
| Country | Link |
|---|---|
| EP (1) | EP1003740A2 (fr) |
| JP (1) | JP2001512119A (fr) |
| CN (1) | CN1301264A (fr) |
| AU (1) | AU748469B2 (fr) |
| BG (1) | BG104216A (fr) |
| BR (1) | BR9815296A (fr) |
| CA (1) | CA2297894A1 (fr) |
| HU (1) | HUP0003484A3 (fr) |
| IL (1) | IL134175A0 (fr) |
| NO (1) | NO20000542L (fr) |
| NZ (1) | NZ502395A (fr) |
| PL (1) | PL342500A1 (fr) |
| SK (1) | SK1452000A3 (fr) |
| TR (4) | TR200000993T2 (fr) |
| TW (1) | TW552260B (fr) |
| WO (1) | WO1999006397A2 (fr) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1097236A4 (fr) * | 1998-07-15 | 2006-10-04 | Bristol Myers Squibb Co | Amination reductrice stereoselective de cetones |
| TWI306760B (en) | 2000-08-07 | 2009-03-01 | Abbott Lab | Use of an endothelin et-a receptor antagonist and orally delivered pharmaceutical composition comprising the same |
| JPWO2002051836A1 (ja) * | 2000-12-27 | 2004-04-22 | 協和醗酵工業株式会社 | ジペプチジルペプチダーゼ−iv阻害剤 |
| PE20021032A1 (es) * | 2001-04-11 | 2002-11-12 | Abbott Lab | Composicion farmaceutica para uso en la modulacion favorable de la calidad de vida relacionada con la salud y progresion temporal ajustada a la calidad relacionada con la salud de una enfermedad en pacientes con cancer de prostata |
| FR2874015B1 (fr) * | 2004-08-05 | 2006-09-15 | Sanofi Synthelabo | Derives de n-(1h-indolyl)-1h-indole-2-carboxamides, leur preparation et leur application en therapeutique |
| FR2880625B1 (fr) * | 2005-01-07 | 2007-03-09 | Sanofi Aventis Sa | Derives de n-(heteroaryl)-1h-indole-2-carboxamides, leur preparation et leur application en therapeutique |
| WO2007034406A1 (fr) * | 2005-09-22 | 2007-03-29 | Actelion Pharmaceuticals Ltd | Derives amides d'acide pyrrolidine-3-carboxylique utilises comme inhibiteurs de la renine |
| EP2545920A1 (fr) | 2007-08-22 | 2013-01-16 | Abbott GmbH & Co. KG | Thérapie pour complications du diabète |
| WO2011114103A1 (fr) | 2010-03-18 | 2011-09-22 | Biolipox Ab | Pyrimidinones pour usage médicamenteux |
| JO2998B1 (ar) | 2010-06-04 | 2016-09-05 | Amgen Inc | مشتقات بيبيريدينون كمثبطات mdm2 لعلاج السرطان |
| AU2012316055B2 (en) | 2011-09-27 | 2016-05-12 | Amgen Inc. | Heterocyclic compounds as MDM2 inhibitors for the treatment of cancer |
| WO2013082458A1 (fr) | 2011-12-02 | 2013-06-06 | The Regents Of The University Of California | Solution de protection de reperfusion et ses utilisations |
| US11407721B2 (en) | 2013-02-19 | 2022-08-09 | Amgen Inc. | CIS-morpholinone and other compounds as MDM2 inhibitors for the treatment of cancer |
| CA2902856C (fr) | 2013-02-28 | 2021-02-16 | Amgen Inc. | Inhibiteur mdm2 derive de l'acide benzoique pour le traitement du cancer |
| WO2014151863A1 (fr) | 2013-03-14 | 2014-09-25 | Amgen Inc. | Composés morpholinone d'acide hétéroaryle utilisés comme inhibiteurs de mdm2 pour le traitement du cancer |
| MA53572A1 (fr) | 2013-06-10 | 2021-10-29 | Amgen Inc | Procédés de production et formes cristallines d'un inhibiteur mdm2 |
| CN104262329A (zh) * | 2014-10-22 | 2015-01-07 | 南京友杰医药科技有限公司 | 反式阿曲生坦的制备 |
| GB2606804B (en) | 2019-07-17 | 2023-12-27 | 2692372 Ontario Inc | Benzenesulfonamide derivatives and uses thereof |
| TW202328111A (zh) * | 2021-09-03 | 2023-07-16 | 大陸商深圳信立泰藥業股份有限公司 | 內皮素a(eta)受體拮抗劑化合物、其藥物組合物及其用途 |
| EP4545520A4 (fr) * | 2022-07-25 | 2025-11-26 | Shenzhen Salubris Pharm Co Ltd | Sel de composé antagoniste du récepteur de l'endothéline a (eta), son procédé de préparation et son utilisation médicale |
| CN117447453B (zh) * | 2022-07-25 | 2025-09-30 | 深圳信立泰药业股份有限公司 | 一种内皮素a(eta)受体拮抗剂化合物可药用的盐晶型及其制备方法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5013842A (en) * | 1990-01-22 | 1991-05-07 | Monsanto Company | Synthesis of chiral pyrrolidine and piperidine glycosidase inhibitors |
| CA2517691A1 (fr) * | 1994-08-19 | 1996-02-29 | Abbott Laboratories | Antagonistes d'endotheline |
| PT888340E (pt) * | 1996-02-13 | 2002-12-31 | Abbott Lab | Derivados de acido 4-(benzo-1,3-dioxolil)pirrolidino-3-carboxilico como antagonistas de endotelina |
| US5618949A (en) * | 1996-07-12 | 1997-04-08 | Abbott Laboratories | Process for synthesis of chiral cis- and trans-3-amino-4-substituted pyrrolidine compounds |
-
1998
- 1998-07-27 TR TR2000/00993T patent/TR200000993T2/xx unknown
- 1998-07-27 CN CN98809462A patent/CN1301264A/zh active Pending
- 1998-07-27 WO PCT/US1998/015479 patent/WO1999006397A2/fr not_active Ceased
- 1998-07-27 TR TR2005/01137T patent/TR200501137T2/xx unknown
- 1998-07-27 CA CA002297894A patent/CA2297894A1/fr not_active Abandoned
- 1998-07-27 IL IL13417598A patent/IL134175A0/xx unknown
- 1998-07-27 TR TR2001/01233T patent/TR200101233T2/xx unknown
- 1998-07-27 HU HU0003484A patent/HUP0003484A3/hu unknown
- 1998-07-27 AU AU85921/98A patent/AU748469B2/en not_active Ceased
- 1998-07-27 EP EP98937139A patent/EP1003740A2/fr not_active Ceased
- 1998-07-27 PL PL98342500A patent/PL342500A1/xx not_active Application Discontinuation
- 1998-07-27 TR TR2001/01234T patent/TR200101234T2/xx unknown
- 1998-07-27 BR BR9815296-3A patent/BR9815296A/pt not_active Application Discontinuation
- 1998-07-27 JP JP2000505155A patent/JP2001512119A/ja active Pending
- 1998-07-27 NZ NZ502395A patent/NZ502395A/xx unknown
- 1998-07-27 SK SK145-2000A patent/SK1452000A3/sk unknown
- 1998-08-10 TW TW087112783A patent/TW552260B/zh not_active IP Right Cessation
-
2000
- 2000-02-02 NO NO20000542A patent/NO20000542L/no not_active Application Discontinuation
- 2000-03-02 BG BG104216A patent/BG104216A/bg unknown
Also Published As
| Publication number | Publication date |
|---|---|
| HUP0003484A3 (en) | 2002-02-28 |
| WO1999006397A3 (fr) | 1999-12-09 |
| NO20000542L (no) | 2000-04-04 |
| TR200501137T2 (tr) | 2005-12-21 |
| BG104216A (bg) | 2000-12-29 |
| EP1003740A2 (fr) | 2000-05-31 |
| IL134175A0 (en) | 2001-04-30 |
| JP2001512119A (ja) | 2001-08-21 |
| AU748469B2 (en) | 2002-06-06 |
| TR200000993T2 (tr) | 2000-12-21 |
| BR9815296A (pt) | 2001-11-20 |
| HUP0003484A2 (hu) | 2002-01-28 |
| PL342500A1 (en) | 2001-06-04 |
| CN1301264A (zh) | 2001-06-27 |
| TR200101234T2 (tr) | 2002-06-21 |
| TW552260B (en) | 2003-09-11 |
| TR200101233T2 (tr) | 2002-06-21 |
| NO20000542D0 (no) | 2000-02-02 |
| NZ502395A (en) | 2002-08-28 |
| SK1452000A3 (en) | 2001-05-10 |
| WO1999006397A2 (fr) | 1999-02-11 |
| AU8592198A (en) | 1999-02-22 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |