BRPI0610283A2 - composto, uso do mesmo na preparação de um medicamento para o tratamento ou prevenção de uma infecção por vìrus de hepatite c, composição farmacêutica e combinação farmacêutica - Google Patents

Info

Publication number

BRPI0610283A2

BRPI0610283A2 BRPI0610283-2A BRPI0610283A BRPI0610283A2 BR PI0610283 A2 BRPI0610283 A2 BR PI0610283A2 BR PI0610283 A BRPI0610283 A BR PI0610283A BR PI0610283 A2 BRPI0610283 A2 BR PI0610283A2

Authority

BR

Brazil

Prior art keywords

trans

amino

thiophene

carboxylic acid

methyl

Prior art date

2005-05-13

Links

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• 150000001875 compounds Chemical class 0.000 title claims abstract description 282
• 238000002360 preparation method Methods 0.000 title claims abstract description 32
• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 21
• 230000002265 prevention Effects 0.000 title claims abstract description 5
• 208000010710 hepatitis C virus infection Diseases 0.000 title claims abstract 4
• 239000003814 drug Substances 0.000 title claims description 9
• 150000003839 salts Chemical class 0.000 claims abstract description 25
• 239000012453 solvate Substances 0.000 claims abstract description 13
• -1 substituted Chemical class 0.000 claims description 479
• 125000000217 alkyl group Chemical group 0.000 claims description 145
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 111
• 125000000623 heterocyclic group Chemical group 0.000 claims description 107
• 125000001072 heteroaryl group Chemical group 0.000 claims description 95
• 239000002253 acid Substances 0.000 claims description 93
• 125000003342 alkenyl group Chemical group 0.000 claims description 80
• 125000000304 alkynyl group Chemical group 0.000 claims description 79
• 125000003118 aryl group Chemical group 0.000 claims description 77
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 76
• 229910052757 nitrogen Inorganic materials 0.000 claims description 65
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 49
• 229910052736 halogen Inorganic materials 0.000 claims description 45
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 43
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 43
• 150000002367 halogens Chemical class 0.000 claims description 42
• 125000004475 heteroaralkyl group Chemical group 0.000 claims description 42
• 125000003545 alkoxy group Chemical group 0.000 claims description 41
• 230000003612 virological effect Effects 0.000 claims description 38
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 33
• 239000003795 chemical substances by application Substances 0.000 claims description 32
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 32
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 30
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 30
• GQPLMRYTRLFLPF-UHFFFAOYSA-N nitrous oxide Inorganic materials [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 claims description 29
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 28
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 28
• 108010050904 Interferons Proteins 0.000 claims description 26
• 102000014150 Interferons Human genes 0.000 claims description 26
• 125000001424 substituent group Chemical group 0.000 claims description 26
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 24
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 23
• 125000005133 alkynyloxy group Chemical group 0.000 claims description 23
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 22
• 239000003112 inhibitor Substances 0.000 claims description 22
• QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 claims description 22
• 125000004043 oxo group Chemical group O=* 0.000 claims description 21
• 125000004104 aryloxy group Chemical group 0.000 claims description 20
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 20
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 19
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 18
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 18
• 125000003320 C2-C6 alkenyloxy group Chemical group 0.000 claims description 17
• 150000002923 oximes Chemical class 0.000 claims description 15
• 125000006652 (C3-C12) cycloalkyl group Chemical group 0.000 claims description 14
• 229910052760 oxygen Inorganic materials 0.000 claims description 14
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 13
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 13
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 12
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 12
• 239000001301 oxygen Substances 0.000 claims description 12
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
• 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 claims description 11
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 11
• 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 10
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 10
• 239000003001 serine protease inhibitor Substances 0.000 claims description 10
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 claims description 9
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 9
• 108060004795 Methyltransferase Proteins 0.000 claims description 8
• 230000002519 immonomodulatory effect Effects 0.000 claims description 8
• 229940079322 interferon Drugs 0.000 claims description 8
• 125000000522 cyclooctenyl group Chemical group C1(=CCCCCCC1)* 0.000 claims description 7
• 229910052739 hydrogen Inorganic materials 0.000 claims description 7
• 125000003386 piperidinyl group Chemical group 0.000 claims description 7
• 230000000692 anti-sense effect Effects 0.000 claims description 6
• 239000003963 antioxidant agent Substances 0.000 claims description 6
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
• 229910052717 sulfur Inorganic materials 0.000 claims description 6
• 125000005915 C6-C14 aryl group Chemical group 0.000 claims description 5
• 239000003242 anti bacterial agent Substances 0.000 claims description 5
• 239000003443 antiviral agent Substances 0.000 claims description 5
• 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 claims description 5
• 239000003937 drug carrier Substances 0.000 claims description 5
• 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 5
• 125000004193 piperazinyl group Chemical group 0.000 claims description 5
• 229910052705 radium Inorganic materials 0.000 claims description 5
• 229910052701 rubidium Inorganic materials 0.000 claims description 5
• LBFROQIFJOYWFA-HDRKRICHSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(Br)=C1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(Br)=C1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 LBFROQIFJOYWFA-HDRKRICHSA-N 0.000 claims description 4
• IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims description 4
• DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 claims description 4
• 229960003805 amantadine Drugs 0.000 claims description 4
• 125000005879 dioxolanyl group Chemical group 0.000 claims description 4
• 230000002443 hepatoprotective effect Effects 0.000 claims description 4
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
• 229940021747 therapeutic vaccine Drugs 0.000 claims description 4
• AMOXNTAMLUCWJT-UHFFFAOYSA-N 5-(4,4-dimethylcyclohexyl)-3-[(4-methoxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylic acid Chemical compound C1CC(OC)CCC1N(C1=C(SC(=C1)C1CCC(C)(C)CC1)C(O)=O)C(=O)C1CCC(C)CC1 AMOXNTAMLUCWJT-UHFFFAOYSA-N 0.000 claims description 3
• GVYKMIALDJEPRQ-CPONINCNSA-N C1=C(C=2CCC(C)CC=2)SC(C(O)=O)=C1N(C(C)C)C(=O)[C@H]1CC[C@H](C)CC1 Chemical compound C1=C(C=2CCC(C)CC=2)SC(C(O)=O)=C1N(C(C)C)C(=O)[C@H]1CC[C@H](C)CC1 GVYKMIALDJEPRQ-CPONINCNSA-N 0.000 claims description 3
• HZCUBYGLTQHCPR-JCNLHEQBSA-N C1=C(C=2CCCCC=2)SC(C(O)=O)=C1N(C(C)C)C(=O)[C@H]1CC[C@H](C)CC1 Chemical compound C1=C(C=2CCCCC=2)SC(C(O)=O)=C1N(C(C)C)C(=O)[C@H]1CC[C@H](C)CC1 HZCUBYGLTQHCPR-JCNLHEQBSA-N 0.000 claims description 3
• WJGGHFVZSJUBRZ-YSXIEMCBSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCC(C)(C)CC=1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCC(C)(C)CC=1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 WJGGHFVZSJUBRZ-YSXIEMCBSA-N 0.000 claims description 3
• QMKHTEOIBBSGKN-WHLIJDCNSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CC(C2)CCC2C1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CC(C2)CCC2C1 QMKHTEOIBBSGKN-WHLIJDCNSA-N 0.000 claims description 3
• CRLPSZXQCTYECG-KESTWPANSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CCC(C)(C)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CCC(C)(C)CC1 CRLPSZXQCTYECG-KESTWPANSA-N 0.000 claims description 3
• OUUFVRBISAEUNT-YSXIEMCBSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCCC=1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCCC=1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 OUUFVRBISAEUNT-YSXIEMCBSA-N 0.000 claims description 3
• BVXHTXRVCMTCJW-XBFADQFBSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)[C@@H]1CC[C@@H](C)CC1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)[C@@H]1CC[C@@H](C)CC1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 BVXHTXRVCMTCJW-XBFADQFBSA-N 0.000 claims description 3
• BVXHTXRVCMTCJW-GONJQHFYSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)[C@H]1CC[C@@H](C)CC1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)[C@H]1CC[C@@H](C)CC1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 BVXHTXRVCMTCJW-GONJQHFYSA-N 0.000 claims description 3
• XLJOUVDPWPSXDM-VYUAXZJKSA-N C1C[C@@H](C)CC[C@@H]1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 XLJOUVDPWPSXDM-VYUAXZJKSA-N 0.000 claims description 3
• XLJOUVDPWPSXDM-ICNBMTIMSA-N C1C[C@@H](C)CC[C@H]1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 Chemical compound C1C[C@@H](C)CC[C@H]1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 XLJOUVDPWPSXDM-ICNBMTIMSA-N 0.000 claims description 3
• QOIHGTCVBFQWJO-DRLVJGDXSA-N C1C[C@@H](OC)CC[C@@H]1N(C1=C(SC(=C1)C1CCC(CC1)C(F)(F)F)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 Chemical compound C1C[C@@H](OC)CC[C@@H]1N(C1=C(SC(=C1)C1CCC(CC1)C(F)(F)F)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 QOIHGTCVBFQWJO-DRLVJGDXSA-N 0.000 claims description 3
• JFUHFSBVZUPBIF-IKYFGSHTSA-N C1C[C@@H](OC)CC[C@@H]1N(C1=C(SC(=C1)C=1CCC(CC=1)C(F)(F)F)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 Chemical compound C1C[C@@H](OC)CC[C@@H]1N(C1=C(SC(=C1)C=1CCC(CC=1)C(F)(F)F)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 JFUHFSBVZUPBIF-IKYFGSHTSA-N 0.000 claims description 3
• 102000053642 Catalytic RNA Human genes 0.000 claims description 3
• 108090000994 Catalytic RNA Proteins 0.000 claims description 3
• 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 3
• 108010036949 Cyclosporine Proteins 0.000 claims description 3
• 102000013462 Interleukin-12 Human genes 0.000 claims description 3
• 108010065805 Interleukin-12 Proteins 0.000 claims description 3
• 244000272459 Silybum marianum Species 0.000 claims description 3
• 235000010841 Silybum marianum Nutrition 0.000 claims description 3
• 108010046075 Thymosin Proteins 0.000 claims description 3
• 102000007501 Thymosin Human genes 0.000 claims description 3
• 125000002393 azetidinyl group Chemical group 0.000 claims description 3
• 125000004069 aziridinyl group Chemical group 0.000 claims description 3
• 229960001265 ciclosporin Drugs 0.000 claims description 3
• 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 claims description 3
• 229930182912 cyclosporin Natural products 0.000 claims description 3
• ZSWFCLXCOIISFI-UHFFFAOYSA-N endo-cyclopentadiene Natural products C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 claims description 3
• 229940117681 interleukin-12 Drugs 0.000 claims description 3
• 229960000329 ribavirin Drugs 0.000 claims description 3
• HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 claims description 3
• 108091092562 ribozyme Proteins 0.000 claims description 3
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 3
• 150000003536 tetrazoles Chemical class 0.000 claims description 3
• LCJVIYPJPCBWKS-NXPQJCNCSA-N thymosin Chemical compound SC[C@@H](N)C(=O)N[C@H](CO)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CO)C(=O)N[C@H](CO)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@H]([C@H](C)O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@H](CCC(O)=O)C(O)=O LCJVIYPJPCBWKS-NXPQJCNCSA-N 0.000 claims description 3
• GJNZQSSHAVNWFW-UHFFFAOYSA-N 5-(cyclohexen-1-yl)-3-[(2,4-dichlorobenzoyl)-propan-2-ylamino]thiophene-2-carboxylic acid Chemical compound C1=C(C=2CCCCC=2)SC(C(O)=O)=C1N(C(C)C)C(=O)C1=CC=C(Cl)C=C1Cl GJNZQSSHAVNWFW-UHFFFAOYSA-N 0.000 claims description 2
• AHQGMPPSKUDUDL-UHFFFAOYSA-N 5-(cyclohexen-1-yl)-3-[(4-fluorocyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylic acid Chemical compound C1CC(C)CCC1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CCC(F)CC1 AHQGMPPSKUDUDL-UHFFFAOYSA-N 0.000 claims description 2
• CHSWOVCXLYDIIY-UHFFFAOYSA-N 5-(cyclopenten-1-yl)-3-[(2,4-dichlorobenzoyl)-propan-2-ylamino]thiophene-2-carboxylic acid Chemical compound C1=C(C=2CCCC=2)SC(C(O)=O)=C1N(C(C)C)C(=O)C1=CC=C(Cl)C=C1Cl CHSWOVCXLYDIIY-UHFFFAOYSA-N 0.000 claims description 2
• 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 2
• YBQKQVZAEDDNAU-CTYIDZIISA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C)C1=C(C(O)=O)SC(C=2CCCCC=2)=C1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C)C1=C(C(O)=O)SC(C=2CCCCC=2)=C1 YBQKQVZAEDDNAU-CTYIDZIISA-N 0.000 claims description 2
• URPYXASENBMACD-FORLXOICSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1CCC(C)(C)CC1)C(O)=O)[C@@H]1CC[C@H](N2N=CN=C2)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1CCC(C)(C)CC1)C(O)=O)[C@@H]1CC[C@H](N2N=CN=C2)CC1 URPYXASENBMACD-FORLXOICSA-N 0.000 claims description 2
• LMCDACUYZVUIFN-WXVWHJFISA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCC(C)(C)CC=1)C(O)=O)C1CCC2(C(N(C)C(=O)N2C)=O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCC(C)(C)CC=1)C(O)=O)C1CCC2(C(N(C)C(=O)N2C)=O)CC1 LMCDACUYZVUIFN-WXVWHJFISA-N 0.000 claims description 2
• FBOBFRVOSFIYOQ-XHPGVBHPSA-N C1C[C@@H](OC)CC[C@@H]1N(C1=C(SC(=C1)C=1CCC(C)(C)CC=1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 Chemical compound C1C[C@@H](OC)CC[C@@H]1N(C1=C(SC(=C1)C=1CCC(C)(C)CC=1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 FBOBFRVOSFIYOQ-XHPGVBHPSA-N 0.000 claims description 2
• ARGZTWUXBRUFQC-GUJRETQESA-N C1C[C@@H](OCOCC)CC[C@@H]1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 Chemical compound C1C[C@@H](OCOCC)CC[C@@H]1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 ARGZTWUXBRUFQC-GUJRETQESA-N 0.000 claims description 2
• 241000132536 Cirsium Species 0.000 claims description 2
• PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 claims description 2
• 229960004308 acetylcysteine Drugs 0.000 claims description 2
• 125000004188 dichlorophenyl group Chemical group 0.000 claims description 2
• 229910052731 fluorine Inorganic materials 0.000 claims description 2
• 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 2
• NRWYAVDHRVTITK-UPRSBDKSSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCC=1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCC=1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 NRWYAVDHRVTITK-UPRSBDKSSA-N 0.000 claims 2
• NKLCHDQGUHMCGL-UHFFFAOYSA-N cyclohexylidenemethanone Chemical group O=C=C1CCCCC1 NKLCHDQGUHMCGL-UHFFFAOYSA-N 0.000 claims 2
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• NTNUDYROPUKXNA-UHFFFAOYSA-N methyl 2-(triphenyl-$l^{5}-phosphanylidene)acetate Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OC)C1=CC=CC=C1 NTNUDYROPUKXNA-UHFFFAOYSA-N 0.000 description 1
• ZXCYYTFNTVJHLH-UHFFFAOYSA-N methyl 2-[8-(nitromethyl)-1,4-dioxaspiro[4.5]decan-8-yl]acetate Chemical compound C1CC(CC(=O)OC)(C[N+]([O-])=O)CCC21OCCO2 ZXCYYTFNTVJHLH-UHFFFAOYSA-N 0.000 description 1
• JEMOHNKXRFEUDT-UHFFFAOYSA-N methyl 3-[(2-methylpropan-2-yl)oxycarbonylamino]thiophene-2-carboxylate Chemical compound COC(=O)C=1SC=CC=1NC(=O)OC(C)(C)C JEMOHNKXRFEUDT-UHFFFAOYSA-N 0.000 description 1
• CKHQMNWVACYRCJ-UHFFFAOYSA-N methyl 3-[(4-azidocyclohexyl)-(4-methylcyclohexanecarbonyl)amino]-5-(4,4-dimethylcyclohexyl)thiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C2CCC(C)(C)CC2)=CC=1N(C(=O)C1CCC(C)CC1)C1CCC(N=[N+]=[N-])CC1 CKHQMNWVACYRCJ-UHFFFAOYSA-N 0.000 description 1
• FUFKLFUHAOZTRC-UHFFFAOYSA-N methyl 3-[(4-hydroxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound S1C=CC(N(C2CCC(O)CC2)C(=O)C2CCC(C)CC2)=C1C(=O)OC FUFKLFUHAOZTRC-UHFFFAOYSA-N 0.000 description 1
• YPQKLYKBVPUWAG-UHFFFAOYSA-N methyl 3-[1,3-bis[tri(propan-2-yl)silyloxy]propan-2-ylamino]-5-(4,4-dimethylcyclohexen-1-yl)thiophene-2-carboxylate Chemical compound CC(C)[Si](C(C)C)(C(C)C)OCC(CO[Si](C(C)C)(C(C)C)C(C)C)NC1=C(C(=O)OC)SC(C=2CCC(C)(C)CC=2)=C1 YPQKLYKBVPUWAG-UHFFFAOYSA-N 0.000 description 1
• JGHMTFPYGOMSIB-UHFFFAOYSA-N methyl 3-[1,4-dioxaspiro[4.5]decan-8-yl-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound S1C=CC(N(C2CCC3(CC2)OCCO3)C(=O)C2CCC(C)CC2)=C1C(=O)OC JGHMTFPYGOMSIB-UHFFFAOYSA-N 0.000 description 1
• BQQHXIZCAPCAQE-UHFFFAOYSA-N methyl 3-amino-5-(4,4-dimethylcyclohexen-1-yl)thiophene-2-carboxylate Chemical compound NC1=C(C(=O)OC)SC(C=2CCC(C)(C)CC=2)=C1 BQQHXIZCAPCAQE-UHFFFAOYSA-N 0.000 description 1
• NKMNDFXAMGNIMF-UHFFFAOYSA-N methyl 3-bromo-5-(4,4-dimethylcyclohexen-1-yl)thiophene-2-carboxylate Chemical compound BrC1=C(C(=O)OC)SC(C=2CCC(C)(C)CC=2)=C1 NKMNDFXAMGNIMF-UHFFFAOYSA-N 0.000 description 1
• PEGSJNCGPSIJOX-UHFFFAOYSA-N methyl 3-bromothiophene-2-carboxylate Chemical compound COC(=O)C=1SC=CC=1Br PEGSJNCGPSIJOX-UHFFFAOYSA-N 0.000 description 1
• RDMQJIFPUUUVAS-UHFFFAOYSA-N methyl 5-(1-hydroxycyclohexyl)-3-[(2-methylpropan-2-yl)oxycarbonylamino]thiophene-2-carboxylate Chemical compound CC(C)(C)OC(=O)NC1=C(C(=O)OC)SC(C2(O)CCCCC2)=C1 RDMQJIFPUUUVAS-UHFFFAOYSA-N 0.000 description 1
• DWPUQUYRFXVZMZ-UHFFFAOYSA-N methyl 5-(2,3-difluorocyclohexen-1-yl)-3-[(4-methoxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound C1CC(OC)CCC1N(C1=C(SC(=C1)C=1CCCC(F)C=1F)C(=O)OC)C(=O)C1CCC(C)CC1 DWPUQUYRFXVZMZ-UHFFFAOYSA-N 0.000 description 1
• TZUJJCSDLZTBCF-UHFFFAOYSA-N methyl 5-(4,4-dimethylcyclohexen-1-yl)-3-[[4-(1,2,4-triazol-1-yl)cyclohexyl]amino]thiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C=2CCC(C)(C)CC=2)=CC=1NC(CC1)CCC1N1C=NC=N1 TZUJJCSDLZTBCF-UHFFFAOYSA-N 0.000 description 1
• UDFZVRTZRTUZLH-UHFFFAOYSA-N methyl 5-(cyclohexen-1-yl)-3-[(3-oxo-2-azaspiro[4.5]decan-8-yl)amino]thiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C=2CCCCC=2)=CC=1NC(CC1)CCC21CNC(=O)C2 UDFZVRTZRTUZLH-UHFFFAOYSA-N 0.000 description 1
• MELBMXRSFAPHMC-UHFFFAOYSA-N methyl 5-(cyclohexen-1-yl)-3-[(4-fluorocyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C=2CCCCC=2)=CC=1N(C(=O)C1CCC(C)CC1)C1CCC(F)CC1 MELBMXRSFAPHMC-UHFFFAOYSA-N 0.000 description 1
• OSUVFWFEGCZXCD-UHFFFAOYSA-N methyl 5-(cyclohexen-1-yl)-3-[(4-methoxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound C1CC(OC)CCC1N(C1=C(SC(=C1)C=1CCCCC=1)C(=O)OC)C(=O)C1CCC(C)CC1 OSUVFWFEGCZXCD-UHFFFAOYSA-N 0.000 description 1
• UJPXPQITBKABOQ-UHFFFAOYSA-N methyl 5-(cyclohexen-1-yl)-3-[(4-methylcyclohexanecarbonyl)-[1-(2-methylpropanoyl)piperidin-4-yl]amino]thiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C=2CCCCC=2)=CC=1N(C(=O)C1CCC(C)CC1)C1CCN(C(=O)C(C)C)CC1 UJPXPQITBKABOQ-UHFFFAOYSA-N 0.000 description 1
• QFIKJRHQBUOWDD-UHFFFAOYSA-N methyl 5-(cyclohexen-1-yl)-3-[[4-(1,2,4-triazol-1-yl)cyclohexyl]amino]thiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C=2CCCCC=2)=CC=1NC(CC1)CCC1N1C=NC=N1 QFIKJRHQBUOWDD-UHFFFAOYSA-N 0.000 description 1
• CKAFQCCNBSOGEI-UHFFFAOYSA-N methyl 5-(cyclohexen-1-yl)-3-[[4-(methoxymethoxy)cyclohexyl]-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound C1CC(OCOC)CCC1N(C1=C(SC(=C1)C=1CCCCC=1)C(=O)OC)C(=O)C1CCC(C)CC1 CKAFQCCNBSOGEI-UHFFFAOYSA-N 0.000 description 1
• JWGYYGHNONYRSO-UHFFFAOYSA-N methyl 5-bromo-3-(1,4-dioxaspiro[4.5]decan-8-ylamino)thiophene-2-carboxylate Chemical compound S1C(Br)=CC(NC2CCC3(CC2)OCCO3)=C1C(=O)OC JWGYYGHNONYRSO-UHFFFAOYSA-N 0.000 description 1
• DNVFEPOGJHDYMJ-UHFFFAOYSA-N methyl 5-bromo-3-[(2,2-dimethyl-1,3-dioxan-5-yl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound S1C(Br)=CC(N(C2COC(C)(C)OC2)C(=O)C2CCC(C)CC2)=C1C(=O)OC DNVFEPOGJHDYMJ-UHFFFAOYSA-N 0.000 description 1
• PYTFYQSPFFVGMA-UHFFFAOYSA-N methyl 5-bromo-3-[(2,2-dimethyl-1,3-dioxan-5-yl)amino]thiophene-2-carboxylate Chemical compound S1C(Br)=CC(NC2COC(C)(C)OC2)=C1C(=O)OC PYTFYQSPFFVGMA-UHFFFAOYSA-N 0.000 description 1
• VONOFJWOVOTLIO-UHFFFAOYSA-N methyl 5-bromo-3-[(4-fluorocyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound S1C(Br)=CC(N(C2CCC(F)CC2)C(=O)C2CCC(C)CC2)=C1C(=O)OC VONOFJWOVOTLIO-UHFFFAOYSA-N 0.000 description 1
• IGJSQSPXSPMZLX-UHFFFAOYSA-N methyl 5-bromo-3-[1,3-dihydroxypropan-2-yl-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound S1C(Br)=CC(N(C(CO)CO)C(=O)C2CCC(C)CC2)=C1C(=O)OC IGJSQSPXSPMZLX-UHFFFAOYSA-N 0.000 description 1
• QRHBBGITAUTBKO-UHFFFAOYSA-N methyl 5-bromo-3-[1,3-dioxan-5-yl-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound S1C(Br)=CC(N(C2COCOC2)C(=O)C2CCC(C)CC2)=C1C(=O)OC QRHBBGITAUTBKO-UHFFFAOYSA-N 0.000 description 1
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