DE69908555T2 - Chinolinderivate als antibakterielles arzneimittel - Google Patents
Chinolinderivate als antibakterielles arzneimittel Download PDFInfo
- Publication number
- DE69908555T2 DE69908555T2 DE69908555T DE69908555T DE69908555T2 DE 69908555 T2 DE69908555 T2 DE 69908555T2 DE 69908555 T DE69908555 T DE 69908555T DE 69908555 T DE69908555 T DE 69908555T DE 69908555 T2 DE69908555 T2 DE 69908555T2
- Authority
- DE
- Germany
- Prior art keywords
- piperidine
- heptyl
- propyl
- methoxy
- quinolin
- 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.)
- Expired - Fee Related
Links
- 230000000844 anti-bacterial effect Effects 0.000 title description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical class N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 title description 3
- 229940126601 medicinal product Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 262
- -1 amino, piperidyl Chemical group 0.000 claims description 148
- 238000000034 method Methods 0.000 claims description 102
- 125000000217 alkyl group Chemical group 0.000 claims description 80
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical class O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 78
- 230000008569 process Effects 0.000 claims description 38
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 30
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 29
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 23
- 239000002253 acid Substances 0.000 claims description 19
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 18
- 125000003118 aryl group Chemical group 0.000 claims description 17
- 125000003342 alkenyl group Chemical group 0.000 claims description 16
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 15
- 238000002360 preparation method Methods 0.000 claims description 14
- 229910052717 sulfur Inorganic materials 0.000 claims description 13
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 12
- 125000002252 acyl group Chemical group 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 11
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 11
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 125000005090 alkenylcarbonyl group Chemical group 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 125000005092 alkenyloxycarbonyl group Chemical group 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- 125000000623 heterocyclic group Chemical group 0.000 claims description 8
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 239000012458 free base Substances 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 150000001204 N-oxides Chemical class 0.000 claims description 6
- 125000004423 acyloxy group Chemical group 0.000 claims description 6
- 125000003277 amino group Chemical group 0.000 claims description 6
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 6
- 150000002118 epoxides Chemical class 0.000 claims description 6
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims description 6
- 208000035143 Bacterial infection Diseases 0.000 claims description 5
- 241000124008 Mammalia Species 0.000 claims description 5
- 125000005137 alkenylsulfonyl group Chemical group 0.000 claims description 5
- 125000004414 alkyl thio group Chemical group 0.000 claims description 5
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- SCNDCEOTFBJOTD-MMZZDGEESA-N 1-[(3r,4r)-1-heptyl-4-[3-(6-methoxyquinolin-4-yl)propyl]piperidin-3-yl]ethanol Chemical compound CC(O)[C@H]1CN(CCCCCCC)CC[C@H]1CCCC1=CC=NC2=CC=C(OC)C=C12 SCNDCEOTFBJOTD-MMZZDGEESA-N 0.000 claims description 4
- MGPAAHBYOJOVQI-RSXGOPAZSA-N 2-[(3r,4r)-1-heptyl-4-[3-(6-methoxyquinolin-4-yl)propyl]piperidin-3-yl]ethyl acetate Chemical compound CC(=O)OCC[C@H]1CN(CCCCCCC)CC[C@H]1CCCC1=CC=NC2=CC=C(OC)C=C12 MGPAAHBYOJOVQI-RSXGOPAZSA-N 0.000 claims description 4
- 125000005035 acylthio group Chemical group 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 229910052796 boron Inorganic materials 0.000 claims description 4
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 125000001072 heteroaryl group Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 229910052720 vanadium Inorganic materials 0.000 claims description 4
- 229910052727 yttrium Inorganic materials 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
- DFHLBJKUZQIJGE-UHFFFAOYSA-N 4-[(1-heptylpiperidin-4-yl)methoxy]-6-methoxyquinoline Chemical compound C1CN(CCCCCCC)CCC1COC1=CC=NC2=CC=C(OC)C=C12 DFHLBJKUZQIJGE-UHFFFAOYSA-N 0.000 claims description 3
- OWPIVGMZBKGNCQ-FCHUYYIVSA-N 4-[2-[(3r,4r)-3-ethyl-1-heptylpiperidin-4-yl]ethyl]-6-methoxyquinoline Chemical compound CC[C@H]1CN(CCCCCCC)CC[C@H]1CCC1=CC=NC2=CC=C(OC)C=C12 OWPIVGMZBKGNCQ-FCHUYYIVSA-N 0.000 claims description 3
- QUTCTDGMSAMAQN-XZOQPEGZSA-N 4-[3-[(3r,4r)-3-ethenyl-1-(2-phenoxyethyl)piperidin-4-yl]propyl]-6-methoxyquinoline Chemical compound C([C@H]([C@H](C1)C=C)CCCC2=CC=NC3=CC=C(C=C32)OC)CN1CCOC1=CC=CC=C1 QUTCTDGMSAMAQN-XZOQPEGZSA-N 0.000 claims description 3
- ZLLZBIQCMMMRHB-WUFINQPMSA-N 4-[3-[(3r,4r)-3-ethyl-1-heptylpiperidin-4-yl]propyl]-6-(piperidin-4-ylmethoxy)quinoline Chemical compound CC[C@H]1CN(CCCCCCC)CC[C@H]1CCCC(C1=C2)=CC=NC1=CC=C2OCC1CCNCC1 ZLLZBIQCMMMRHB-WUFINQPMSA-N 0.000 claims description 3
- SAXSDOJOUGHKRK-YDUIRMPASA-N 4-[4-[(3r,4r)-3-ethyl-1-heptylpiperidin-4-yl]butan-2-yl]-6-methoxyquinoline Chemical compound CC[C@H]1CN(CCCCCCC)CC[C@H]1CCC(C)C1=CC=NC2=CC=C(OC)C=C12 SAXSDOJOUGHKRK-YDUIRMPASA-N 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 3
- 230000008707 rearrangement Effects 0.000 claims description 3
- MTMVVOSGPKURPD-FIXSFTCYSA-N (2s)-1-[(3r,4s)-3-ethyl-1-heptylpiperidin-4-yl]-3-(6-methoxyquinolin-4-yl)propan-2-ol Chemical compound CC[C@H]1CN(CCCCCCC)CC[C@H]1C[C@H](O)CC1=CC=NC2=CC=C(OC)C=C12 MTMVVOSGPKURPD-FIXSFTCYSA-N 0.000 claims description 2
- 125000004642 (C1-C12) alkoxy group Chemical group 0.000 claims description 2
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 2
- SYQXYPSSIFFSBO-UHFFFAOYSA-N 1-(1-heptylpiperidin-4-yl)-3-(6-methoxyquinolin-4-yl)propan-2-ol Chemical compound C1CN(CCCCCCC)CCC1CC(O)CC1=CC=NC2=CC=C(OC)C=C12 SYQXYPSSIFFSBO-UHFFFAOYSA-N 0.000 claims description 2
- WVTBUPSWLGBABS-IEDSLXKASA-N 1-(6-aminoquinolin-4-yl)-3-[(3r,4r)-3-ethyl-1-heptylpiperidin-4-yl]propan-1-ol Chemical compound CC[C@H]1CN(CCCCCCC)CC[C@H]1CCC(O)C1=CC=NC2=CC=C(N)C=C12 WVTBUPSWLGBABS-IEDSLXKASA-N 0.000 claims description 2
- XSFWZXPIJMLEKV-IEDSLXKASA-N 1-(6-azidoquinolin-4-yl)-3-[(3R,4R)-3-ethyl-1-heptylpiperidin-4-yl]propan-1-ol Chemical compound C(C)[C@H]1CN(CC[C@H]1CCC(C1=CC=NC2=CC=C(C=C12)N=[N+]=[N-])O)CCCCCCC XSFWZXPIJMLEKV-IEDSLXKASA-N 0.000 claims description 2
- RCADNRZCMMDLTE-OMQKAAQBSA-N 1-[(3r,4r)-1-heptyl-4-[3-(6-methoxyquinolin-4-yl)propyl]piperidin-3-yl]propan-2-ol Chemical compound CC(O)C[C@H]1CN(CCCCCCC)CC[C@H]1CCCC1=CC=NC2=CC=C(OC)C=C12 RCADNRZCMMDLTE-OMQKAAQBSA-N 0.000 claims description 2
- UEBNGCLREGPCDZ-ACKJMCFBSA-N 1-[6-(5-aminopentoxy)quinolin-4-yl]-3-[(3r,4r)-3-ethyl-1-heptylpiperidin-4-yl]propan-1-ol Chemical compound CC[C@H]1CN(CCCCCCC)CC[C@H]1CCC(O)C1=CC=NC2=CC=C(OCCCCCN)C=C12 UEBNGCLREGPCDZ-ACKJMCFBSA-N 0.000 claims description 2
- NOHZKHZGVCYPTI-UHFFFAOYSA-N 1-heptyl-n-(6-methoxyquinolin-4-yl)piperidine-4-carboxamide Chemical compound C1CN(CCCCCCC)CCC1C(=O)NC1=CC=NC2=CC=C(OC)C=C12 NOHZKHZGVCYPTI-UHFFFAOYSA-N 0.000 claims description 2
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims description 2
- AFNHEZHAFSXQMB-VWNXMTODSA-N 2-[(3r,4r)-1-heptyl-4-[3-(6-methoxyquinolin-4-yl)propyl]piperidin-3-yl]ethanol Chemical compound OCC[C@H]1CN(CCCCCCC)CC[C@H]1CCCC1=CC=NC2=CC=C(OC)C=C12 AFNHEZHAFSXQMB-VWNXMTODSA-N 0.000 claims description 2
- DGLWHNSPAQNLID-VWNXMTODSA-N 2-[(3r,4r)-1-heptyl-4-[3-(6-methoxyquinolin-4-yl)propyl]piperidin-3-yl]ethyl carbamate Chemical compound NC(=O)OCC[C@H]1CN(CCCCCCC)CC[C@H]1CCCC1=CC=NC2=CC=C(OC)C=C12 DGLWHNSPAQNLID-VWNXMTODSA-N 0.000 claims description 2
- IKQUYBYIZXYCBM-RSXGOPAZSA-N 2-[(3r,4r)-1-heptyl-4-[3-(6-methoxyquinolin-4-yl)propyl]piperidin-3-yl]ethyl n-ethylcarbamate Chemical compound CCNC(=O)OCC[C@H]1CN(CCCCCCC)CC[C@H]1CCCC1=CC=NC2=CC=C(OC)C=C12 IKQUYBYIZXYCBM-RSXGOPAZSA-N 0.000 claims description 2
- WCVPIIKWQGFVKT-IPEYFGQDSA-N 2-[(3r,4s)-3-ethenyl-1-heptylpiperidin-4-yl]-1-(6-methoxyquinolin-4-yl)ethanol Chemical compound C=C[C@H]1CN(CCCCCCC)CC[C@H]1CC(O)C1=CC=NC2=CC=C(OC)C=C12 WCVPIIKWQGFVKT-IPEYFGQDSA-N 0.000 claims description 2
- FGNWTBNQJHEIEF-LOSJGSFVSA-N 2-[3-[4-[3-[(3r,4r)-3-ethyl-1-heptylpiperidin-4-yl]propyl]quinolin-6-yl]oxypropyl]guanidine Chemical compound CC[C@H]1CN(CCCCCCC)CC[C@H]1CCCC1=CC=NC2=CC=C(OCCCN=C(N)N)C=C12 FGNWTBNQJHEIEF-LOSJGSFVSA-N 0.000 claims description 2
- UUGIVZNWPDJGDF-BJKOFHAPSA-N 2-[4-[3-[(3r,4r)-3-ethyl-1-heptylpiperidin-4-yl]propyl]quinolin-6-yl]oxyethanamine Chemical compound CC[C@H]1CN(CCCCCCC)CC[C@H]1CCCC1=CC=NC2=CC=C(OCCN)C=C12 UUGIVZNWPDJGDF-BJKOFHAPSA-N 0.000 claims description 2
- PLXLUAHBZPUHDR-BJKOFHAPSA-N 2-[4-[3-[(3r,4r)-3-ethyl-1-heptylpiperidin-4-yl]propyl]quinolin-6-yl]oxyethanol Chemical compound CC[C@H]1CN(CCCCCCC)CC[C@H]1CCCC1=CC=NC2=CC=C(OCCO)C=C12 PLXLUAHBZPUHDR-BJKOFHAPSA-N 0.000 claims description 2
- JLOPKNLHBOJOAN-FEMHNBHWSA-N 3-[(3R,4R)-3-ethyl-1-(3-phenylprop-2-enyl)piperidin-4-yl]-1-(6-methoxyquinolin-4-yl)propan-1-ol Chemical compound C(C)[C@H]1CN(CC[C@H]1CCC(C1=CC=NC2=CC=C(C=C12)OC)O)CC=CC1=CC=CC=C1 JLOPKNLHBOJOAN-FEMHNBHWSA-N 0.000 claims description 2
- KXTMVVOLTUHORR-BWOOIXMFSA-N 3-[(3r,4r)-1-decyl-3-ethylpiperidin-4-yl]-1-(6-methoxyquinolin-4-yl)propan-1-ol Chemical compound CC[C@H]1CN(CCCCCCCCCC)CC[C@H]1CCC(O)C1=CC=NC2=CC=C(OC)C=C12 KXTMVVOLTUHORR-BWOOIXMFSA-N 0.000 claims description 2
- HQMFEJWCGYLQKF-LOSJGSFVSA-N 3-[(3r,4r)-1-decyl-3-ethylpiperidin-4-yl]-1-(6-methoxyquinolin-4-yl)propan-1-one Chemical compound CC[C@H]1CN(CCCCCCCCCC)CC[C@H]1CCC(=O)C1=CC=NC2=CC=C(OC)C=C12 HQMFEJWCGYLQKF-LOSJGSFVSA-N 0.000 claims description 2
- JNZZZQCLAKXJTF-YEOOOGFDSA-N 3-[(3r,4r)-1-dodecyl-3-ethylpiperidin-4-yl]-1-(6-methoxyquinolin-4-yl)propan-1-ol Chemical compound CC[C@H]1CN(CCCCCCCCCCCC)CC[C@H]1CCC(O)C1=CC=NC2=CC=C(OC)C=C12 JNZZZQCLAKXJTF-YEOOOGFDSA-N 0.000 claims description 2
- PXDPKSBTBVJFLQ-RRPNLBNLSA-N 3-[(3r,4r)-1-dodecyl-3-ethylpiperidin-4-yl]-1-(6-methoxyquinolin-4-yl)propan-1-one Chemical compound CC[C@H]1CN(CCCCCCCCCCCC)CC[C@H]1CCC(=O)C1=CC=NC2=CC=C(OC)C=C12 PXDPKSBTBVJFLQ-RRPNLBNLSA-N 0.000 claims description 2
- RMQNNPGEGPCOET-OCTGXNKJSA-N 3-[(3r,4r)-1-heptyl-3-(2-hydroxyethyl)piperidin-4-yl]-1-(6-methoxyquinolin-4-yl)propan-1-ol Chemical compound OCC[C@H]1CN(CCCCCCC)CC[C@H]1CCC(O)C1=CC=NC2=CC=C(OC)C=C12 RMQNNPGEGPCOET-OCTGXNKJSA-N 0.000 claims description 2
- UTBHPELDVZYPKL-NOZRDPDXSA-N 3-[(3r,4r)-1-heptyl-4-[3-(6-methoxyquinolin-4-yl)propyl]piperidin-3-yl]propan-1-ol Chemical compound OCCC[C@H]1CN(CCCCCCC)CC[C@H]1CCCC1=CC=NC2=CC=C(OC)C=C12 UTBHPELDVZYPKL-NOZRDPDXSA-N 0.000 claims description 2
- AAHZJSGGQIDHES-QNWUEUMSSA-N 3-[(3r,4r)-3-ethenyl-1-heptylpiperidin-4-yl]-1-(6-methoxyquinolin-4-yl)propan-1-ol Chemical compound C=C[C@H]1CN(CCCCCCC)CC[C@H]1CCC(O)C1=CC=NC2=CC=C(OC)C=C12 AAHZJSGGQIDHES-QNWUEUMSSA-N 0.000 claims description 2
- ZYFTYUQUQNEEGK-SYDXZMBCSA-N 3-[(3r,4r)-3-ethyl-1-(2-phenylethyl)piperidin-4-yl]-1-(6-methoxyquinolin-4-yl)propan-1-ol Chemical compound C([C@@H]([C@@H](CC1)CCC(O)C=2C3=CC(OC)=CC=C3N=CC=2)CC)N1CCC1=CC=CC=C1 ZYFTYUQUQNEEGK-SYDXZMBCSA-N 0.000 claims description 2
- MBZUZSCPUDFFPZ-FEMHNBHWSA-N 3-[(3r,4r)-3-ethyl-1-(3-phenylpropyl)piperidin-4-yl]-1-(6-methoxyquinolin-4-yl)propan-1-ol Chemical compound C([C@@H]([C@@H](CC1)CCC(O)C=2C3=CC(OC)=CC=C3N=CC=2)CC)N1CCCC1=CC=CC=C1 MBZUZSCPUDFFPZ-FEMHNBHWSA-N 0.000 claims description 2
- FCAYEFXDXWWJKZ-SMWUWQHRSA-N 3-[(3r,4r)-3-ethyl-1-heptylpiperidin-4-yl]-1-(6-methoxyquinolin-4-yl)propan-1-amine Chemical compound CC[C@H]1CN(CCCCCCC)CC[C@H]1CCC(N)C1=CC=NC2=CC=C(OC)C=C12 FCAYEFXDXWWJKZ-SMWUWQHRSA-N 0.000 claims description 2
- GCXXQAWDVDJDTD-QNWUEUMSSA-N 3-[(3r,4r)-3-ethyl-1-heptylpiperidin-4-yl]-1-(6-methoxyquinolin-4-yl)propan-1-ol Chemical compound CC[C@H]1CN(CCCCCCC)CC[C@H]1CCC(O)C1=CC=NC2=CC=C(OC)C=C12 GCXXQAWDVDJDTD-QNWUEUMSSA-N 0.000 claims description 2
- RQSYUMQOOCUXON-FCHUYYIVSA-N 3-[(3r,4r)-3-ethyl-1-heptylpiperidin-4-yl]-1-(6-methoxyquinolin-4-yl)propan-1-one Chemical compound CC[C@H]1CN(CCCCCCC)CC[C@H]1CCC(=O)C1=CC=NC2=CC=C(OC)C=C12 RQSYUMQOOCUXON-FCHUYYIVSA-N 0.000 claims description 2
- XIOSYABBIYIWTR-IEDSLXKASA-N 3-[(3r,4r)-3-ethyl-1-hexylpiperidin-4-yl]-1-(6-methoxyquinolin-4-yl)propan-1-ol Chemical compound CC[C@H]1CN(CCCCCC)CC[C@H]1CCC(O)C1=CC=NC2=CC=C(OC)C=C12 XIOSYABBIYIWTR-IEDSLXKASA-N 0.000 claims description 2
- XLUQBTFHSJZSAV-LEWJYISDSA-N 3-[(3r,4r)-3-ethyl-1-hexylpiperidin-4-yl]-1-(6-methoxyquinolin-4-yl)propan-1-one Chemical compound CC[C@H]1CN(CCCCCC)CC[C@H]1CCC(=O)C1=CC=NC2=CC=C(OC)C=C12 XLUQBTFHSJZSAV-LEWJYISDSA-N 0.000 claims description 2
- WIULLPVKMWXFRE-SYDXZMBCSA-N 3-[(3r,4r)-3-ethyl-1-octylpiperidin-4-yl]-1-(6-methoxyquinolin-4-yl)propan-1-ol Chemical compound CC[C@H]1CN(CCCCCCCC)CC[C@H]1CCC(O)C1=CC=NC2=CC=C(OC)C=C12 WIULLPVKMWXFRE-SYDXZMBCSA-N 0.000 claims description 2
- AVVAFHIOFVUREY-XZOQPEGZSA-N 3-[(3r,4r)-3-ethyl-1-octylpiperidin-4-yl]-1-(6-methoxyquinolin-4-yl)propan-1-one Chemical compound CC[C@H]1CN(CCCCCCCC)CC[C@H]1CCC(=O)C1=CC=NC2=CC=C(OC)C=C12 AVVAFHIOFVUREY-XZOQPEGZSA-N 0.000 claims description 2
- FQYQJNKDYWBQLD-LOSJGSFVSA-N 3-[4-[3-[(3r,4r)-3-ethyl-1-heptylpiperidin-4-yl]propyl]quinolin-6-yl]oxypropan-1-amine Chemical compound CC[C@H]1CN(CCCCCCC)CC[C@H]1CCCC1=CC=NC2=CC=C(OCCCN)C=C12 FQYQJNKDYWBQLD-LOSJGSFVSA-N 0.000 claims description 2
- NSTMVRWATNHOBQ-YDNHHRFVSA-N 4-[(2s,3s)-3-[[(3r,4s)-3-ethenyl-1-heptylpiperidin-4-yl]methyl]oxiran-2-yl]-6-methoxyquinoline Chemical compound C=C[C@H]1CN(CCCCCCC)CC[C@H]1C[C@H]1[C@H](C=2C3=CC(OC)=CC=C3N=CC=2)O1 NSTMVRWATNHOBQ-YDNHHRFVSA-N 0.000 claims description 2
- BNOLGGLYOFCTDK-SYDXZMBCSA-N 4-[(3r,4r)-3-ethyl-1-heptylpiperidin-4-yl]-2-(6-methoxyquinolin-4-yl)butan-2-ol Chemical compound CC[C@H]1CN(CCCCCCC)CC[C@H]1CCC(C)(O)C1=CC=NC2=CC=C(OC)C=C12 BNOLGGLYOFCTDK-SYDXZMBCSA-N 0.000 claims description 2
- CQNDIWWWNPBUPJ-QNWUEUMSSA-N 4-[1-azido-3-[(3R,4R)-3-ethenyl-1-heptylpiperidin-4-yl]propyl]-6-methoxyquinoline Chemical compound C(=C)[C@H]1CN(CC[C@H]1CCC(C1=CC=NC2=CC=C(C=C12)OC)N=[N+]=[N-])CCCCCCC CQNDIWWWNPBUPJ-QNWUEUMSSA-N 0.000 claims description 2
- KGPTXDWZFCHYIZ-FCHUYYIVSA-N 4-[2-[(3r,4r)-3-ethenyl-1-heptylpiperidin-4-yl]ethyl]-6-methoxyquinoline Chemical compound C=C[C@H]1CN(CCCCCCC)CC[C@H]1CCC1=CC=NC2=CC=C(OC)C=C12 KGPTXDWZFCHYIZ-FCHUYYIVSA-N 0.000 claims description 2
- OQAJOUSJSWKJMV-VXKWHMMOSA-N 4-[2-[(3r,4s)-3-ethenyl-1-heptylpiperidin-4-yl]ethoxy]-6-methoxyquinoline Chemical compound C=C[C@H]1CN(CCCCCCC)CC[C@H]1CCOC1=CC=NC2=CC=C(OC)C=C12 OQAJOUSJSWKJMV-VXKWHMMOSA-N 0.000 claims description 2
- KGPTXDWZFCHYIZ-FGZHOGPDSA-N 4-[2-[(3s,4r)-3-ethenyl-1-heptylpiperidin-4-yl]ethyl]-6-methoxyquinoline Chemical compound C=C[C@@H]1CN(CCCCCCC)CC[C@H]1CCC1=CC=NC2=CC=C(OC)C=C12 KGPTXDWZFCHYIZ-FGZHOGPDSA-N 0.000 claims description 2
- GMCXHKKOCRFGAG-UHFFFAOYSA-N 4-[3-(1-heptylpiperidin-4-yl)prop-1-enyl]-6-methoxyquinoline Chemical compound C1CN(CCCCCCC)CCC1CC=CC1=CC=NC2=CC=C(OC)C=C12 GMCXHKKOCRFGAG-UHFFFAOYSA-N 0.000 claims description 2
- YZWUSZOVXNFSJZ-UHFFFAOYSA-N 4-[3-(1-heptylpiperidin-4-yl)propyl]-6-methoxyquinoline Chemical compound C1CN(CCCCCCC)CCC1CCCC1=CC=NC2=CC=C(OC)C=C12 YZWUSZOVXNFSJZ-UHFFFAOYSA-N 0.000 claims description 2
- TWNDOZNMWVTTLB-XZOQPEGZSA-N 4-[3-[(3r,4r)-3-ethenyl-1-heptylpiperidin-4-yl]propyl]-6-methoxyquinoline Chemical compound C=C[C@H]1CN(CCCCCCC)CC[C@H]1CCCC1=CC=NC2=CC=C(OC)C=C12 TWNDOZNMWVTTLB-XZOQPEGZSA-N 0.000 claims description 2
- UNFZAXNIOVMCKD-IEDSLXKASA-N 4-[3-[(3r,4r)-3-ethyl-1-heptylpiperidin-4-yl]-1-hydroxypropyl]quinolin-6-ol Chemical compound CC[C@H]1CN(CCCCCCC)CC[C@H]1CCC(O)C1=CC=NC2=CC=C(O)C=C12 UNFZAXNIOVMCKD-IEDSLXKASA-N 0.000 claims description 2
- NKOYNZFOVUKUMY-XZOQPEGZSA-N 4-[3-[(3r,4r)-3-ethyl-1-heptylpiperidin-4-yl]propyl]-6-methoxyquinoline Chemical compound CC[C@H]1CN(CCCCCCC)CC[C@H]1CCCC1=CC=NC2=CC=C(OC)C=C12 NKOYNZFOVUKUMY-XZOQPEGZSA-N 0.000 claims description 2
- YOUAPNABWNMSDF-LOSJGSFVSA-N 4-[3-[(3r,4r)-3-ethyl-1-heptylpiperidin-4-yl]propyl]-6-propoxyquinoline Chemical compound CC[C@H]1CN(CCCCCCC)CC[C@H]1CCCC1=CC=NC2=CC=C(OCCC)C=C12 YOUAPNABWNMSDF-LOSJGSFVSA-N 0.000 claims description 2
- OSBYHPROZMZLBS-FCHUYYIVSA-N 4-[3-[(3r,4r)-3-ethyl-1-heptylpiperidin-4-yl]propyl]quinolin-6-ol Chemical compound CC[C@H]1CN(CCCCCCC)CC[C@H]1CCCC1=CC=NC2=CC=C(O)C=C12 OSBYHPROZMZLBS-FCHUYYIVSA-N 0.000 claims description 2
- TWNDOZNMWVTTLB-DHIUTWEWSA-N 4-[3-[(3s,4r)-3-ethenyl-1-heptylpiperidin-4-yl]propyl]-6-methoxyquinoline Chemical compound C=C[C@@H]1CN(CCCCCCC)CC[C@H]1CCCC1=CC=NC2=CC=C(OC)C=C12 TWNDOZNMWVTTLB-DHIUTWEWSA-N 0.000 claims description 2
- HHBAYVJDZPKXOM-QZXCJWAESA-N 4-[3-[(3z,4r)-3-ethylidene-1-heptylpiperidin-4-yl]propyl]-6-methoxyquinoline Chemical compound C/C=C/1CN(CCCCCCC)CC[C@H]\1CCCC1=CC=NC2=CC=C(OC)C=C12 HHBAYVJDZPKXOM-QZXCJWAESA-N 0.000 claims description 2
- NDWDVDKLTKOBNE-IZZNHLLZSA-N 4-[4-[3-[(3r,4r)-3-ethyl-1-heptylpiperidin-4-yl]propyl]quinolin-6-yl]oxybutan-1-amine Chemical compound CC[C@H]1CN(CCCCCCC)CC[C@H]1CCCC1=CC=NC2=CC=C(OCCCCN)C=C12 NDWDVDKLTKOBNE-IZZNHLLZSA-N 0.000 claims description 2
- JVPWTRFRXSTJBV-VXKWHMMOSA-N 4-[[(3r,4r)-3-ethyl-1-heptylpiperidin-4-yl]methylsulfanylmethyl]-6-methoxyquinoline Chemical compound CC[C@H]1CN(CCCCCCC)CC[C@H]1CSCC1=CC=NC2=CC=C(OC)C=C12 JVPWTRFRXSTJBV-VXKWHMMOSA-N 0.000 claims description 2
- MHBAAZDMDVEJCF-RRPNLBNLSA-N 5-[4-[3-[(3r,4r)-3-ethyl-1-heptylpiperidin-4-yl]propyl]quinolin-6-yl]oxypentan-1-amine Chemical compound CC[C@H]1CN(CCCCCCC)CC[C@H]1CCCC1=CC=NC2=CC=C(OCCCCCN)C=C12 MHBAAZDMDVEJCF-RRPNLBNLSA-N 0.000 claims description 2
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 2
- XLLKSQQUSXSKIU-FYYLOGMGSA-N [(3r,4r)-1-heptyl-4-[3-(6-methoxyquinolin-4-yl)propyl]piperidin-3-yl]methanol Chemical compound OC[C@H]1CN(CCCCCCC)CC[C@H]1CCCC1=CC=NC2=CC=C(OC)C=C12 XLLKSQQUSXSKIU-FYYLOGMGSA-N 0.000 claims description 2
- UZPUDUHOISZXOQ-JTHBVZDNSA-N [(3r,4s)-1-heptyl-4-[3-(6-methoxyquinolin-4-yl)propyl]piperidin-3-yl]methyl carbamate Chemical compound NC(=O)OC[C@H]1CN(CCCCCCC)CC[C@@H]1CCCC1=CC=NC2=CC=C(OC)C=C12 UZPUDUHOISZXOQ-JTHBVZDNSA-N 0.000 claims description 2
- PGJANJHHABZLDH-QNWUEUMSSA-N [3-[(3r,4r)-3-ethenyl-1-heptylpiperidin-4-yl]-1-(6-methoxyquinolin-4-yl)propyl]urea Chemical compound C=C[C@H]1CN(CCCCCCC)CC[C@H]1CCC(NC(N)=O)C1=CC=NC2=CC=C(OC)C=C12 PGJANJHHABZLDH-QNWUEUMSSA-N 0.000 claims description 2
- 125000004442 acylamino group Chemical group 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 2
- 125000005360 alkyl sulfoxide group Chemical group 0.000 claims description 2
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 2
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 2
- 125000005361 aryl sulfoxide group Chemical group 0.000 claims description 2
- 125000005110 aryl thio group Chemical group 0.000 claims description 2
- 125000004104 aryloxy group Chemical group 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 239000004305 biphenyl Substances 0.000 claims description 2
- 235000010290 biphenyl Nutrition 0.000 claims description 2
- 125000006267 biphenyl group Chemical group 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 2
- 125000004468 heterocyclylthio group Chemical group 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- INXYGYDFRWCCMF-XZOQPEGZSA-N n-[2-[(3r,4s)-3-ethenyl-1-heptylpiperidin-4-yl]ethyl]-6-methoxy-n-methylquinolin-4-amine Chemical compound C=C[C@H]1CN(CCCCCCC)CC[C@H]1CCN(C)C1=CC=NC2=CC=C(OC)C=C12 INXYGYDFRWCCMF-XZOQPEGZSA-N 0.000 claims description 2
- UVHRGOSZOFSEDH-FEMHNBHWSA-N n-[3-[(3r,4r)-3-ethenyl-1-heptylpiperidin-4-yl]-1-(6-methoxyquinolin-4-yl)propyl]acetamide Chemical compound C=C[C@H]1CN(CCCCCCC)CC[C@H]1CCC(NC(C)=O)C1=CC=NC2=CC=C(OC)C=C12 UVHRGOSZOFSEDH-FEMHNBHWSA-N 0.000 claims description 2
- UOCHGRZSCFALNO-SFTDATJTSA-N n-[[(3r,4r)-3-ethenyl-1-heptylpiperidin-4-yl]methyl]-6-methoxyquinoline-4-carboxamide Chemical compound C=C[C@H]1CN(CCCCCCC)CC[C@H]1CNC(=O)C1=CC=NC2=CC=C(OC)C=C12 UOCHGRZSCFALNO-SFTDATJTSA-N 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 2
- 125000006413 ring segment Chemical group 0.000 claims description 2
- 239000011593 sulfur Substances 0.000 claims description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
- CLEPDZYETJYMRM-UHFFFAOYSA-N 2-(1-heptylpiperidin-4-yl)-1-(6-methoxyquinolin-4-yl)ethanol Chemical compound C1CN(CCCCCCC)CCC1CC(O)C1=CC=NC2=CC=C(OC)C=C12 CLEPDZYETJYMRM-UHFFFAOYSA-N 0.000 claims 1
- CTTNZICAQJZWBS-VWNXMTODSA-N 3-[(3r,4r)-1-heptyl-4-[3-(6-methoxyquinolin-4-yl)propyl]piperidin-3-yl]propanamide Chemical compound NC(=O)CC[C@H]1CN(CCCCCCC)CC[C@H]1CCCC1=CC=NC2=CC=C(OC)C=C12 CTTNZICAQJZWBS-VWNXMTODSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 229
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 220
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 165
- 239000000203 mixture Substances 0.000 description 138
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 102
- 239000000243 solution Substances 0.000 description 99
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 96
- 239000003921 oil Substances 0.000 description 95
- 235000019198 oils Nutrition 0.000 description 95
- 239000000047 product Substances 0.000 description 88
- 239000000741 silica gel Substances 0.000 description 82
- 229910002027 silica gel Inorganic materials 0.000 description 82
- 235000019439 ethyl acetate Nutrition 0.000 description 78
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 72
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 68
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 64
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 59
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 57
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 52
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 51
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 47
- 238000004440 column chromatography Methods 0.000 description 45
- 239000011541 reaction mixture Substances 0.000 description 45
- 238000006243 chemical reaction Methods 0.000 description 42
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 39
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 38
- 238000004587 chromatography analysis Methods 0.000 description 33
- 150000002500 ions Chemical class 0.000 description 32
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 31
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 30
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 29
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 28
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 26
- 239000000284 extract Substances 0.000 description 25
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 21
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- 150000003254 radicals Chemical class 0.000 description 21
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 20
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 19
- 235000011114 ammonium hydroxide Nutrition 0.000 description 19
- 239000012267 brine Substances 0.000 description 19
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 19
- 235000019341 magnesium sulphate Nutrition 0.000 description 19
- 239000012044 organic layer Substances 0.000 description 19
- 238000010992 reflux Methods 0.000 description 19
- 239000007787 solid Substances 0.000 description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- 238000003756 stirring Methods 0.000 description 18
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 17
- 239000012043 crude product Substances 0.000 description 15
- 229910000027 potassium carbonate Inorganic materials 0.000 description 15
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 14
- 229910052786 argon Inorganic materials 0.000 description 14
- 239000002585 base Substances 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 13
- 229910021529 ammonia Inorganic materials 0.000 description 13
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 13
- 239000006260 foam Substances 0.000 description 13
- 150000001412 amines Chemical class 0.000 description 12
- 229910052744 lithium Inorganic materials 0.000 description 12
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 12
- 239000011347 resin Substances 0.000 description 12
- 229920005989 resin Polymers 0.000 description 12
- 150000003839 salts Chemical class 0.000 description 12
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 11
- 238000001819 mass spectrum Methods 0.000 description 11
- 235000017557 sodium bicarbonate Nutrition 0.000 description 11
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 10
- 230000029936 alkylation Effects 0.000 description 10
- 238000005804 alkylation reaction Methods 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 9
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 9
- 239000008346 aqueous phase Substances 0.000 description 9
- 239000012280 lithium aluminium hydride Substances 0.000 description 9
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- 125000006239 protecting group Chemical group 0.000 description 8
- 230000009467 reduction Effects 0.000 description 8
- 229910000104 sodium hydride Inorganic materials 0.000 description 8
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 7
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
- LMHCYRULPLGEEZ-UHFFFAOYSA-N 1-iodoheptane Chemical compound CCCCCCCI LMHCYRULPLGEEZ-UHFFFAOYSA-N 0.000 description 6
- XXLFLUJXWKXUGS-UHFFFAOYSA-N 6-methoxyquinoline-4-carboxylic acid Chemical compound N1=CC=C(C(O)=O)C2=CC(OC)=CC=C21 XXLFLUJXWKXUGS-UHFFFAOYSA-N 0.000 description 6
- FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo(3.3.1)nonane Chemical compound C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 6
- 150000001408 amides Chemical class 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- 238000003776 cleavage reaction Methods 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 230000007017 scission Effects 0.000 description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 description 6
- 150000003573 thiols Chemical class 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- LSXKDWGTSHCFPP-UHFFFAOYSA-N 1-bromoheptane Chemical compound CCCCCCCBr LSXKDWGTSHCFPP-UHFFFAOYSA-N 0.000 description 5
- BEOVBLPXVFICSP-UHFFFAOYSA-N 4-chloro-6-methoxyquinoline Chemical compound N1=CC=C(Cl)C2=CC(OC)=CC=C21 BEOVBLPXVFICSP-UHFFFAOYSA-N 0.000 description 5
- PZASAAIJIFDWSB-CKPDSHCKSA-N 8-[(1S)-1-[8-(trifluoromethyl)-7-[4-(trifluoromethyl)cyclohexyl]oxynaphthalen-2-yl]ethyl]-8-azabicyclo[3.2.1]octane-3-carboxylic acid Chemical compound FC(F)(F)C=1C2=CC([C@@H](N3C4CCC3CC(C4)C(O)=O)C)=CC=C2C=CC=1OC1CCC(C(F)(F)F)CC1 PZASAAIJIFDWSB-CKPDSHCKSA-N 0.000 description 5
- 241000283690 Bos taurus Species 0.000 description 5
- 239000004593 Epoxy Substances 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- 239000000010 aprotic solvent Substances 0.000 description 5
- 239000003638 chemical reducing agent Substances 0.000 description 5
- 239000006071 cream Substances 0.000 description 5
- 150000002009 diols Chemical class 0.000 description 5
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 238000005984 hydrogenation reaction Methods 0.000 description 5
- HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 5
- 229910052763 palladium Inorganic materials 0.000 description 5
- 238000002953 preparative HPLC Methods 0.000 description 5
- 239000000377 silicon dioxide Substances 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 239000012279 sodium borohydride Substances 0.000 description 5
- 229910000033 sodium borohydride Inorganic materials 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 230000007704 transition Effects 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- 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 4
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 150000004703 alkoxides Chemical class 0.000 description 4
- UJVLJVVVVPBNKB-VBRLCVBGSA-N benzyl (3r,4r)-3-(1-hydroxyethyl)-4-[3-(6-methoxyquinolin-4-yl)propyl]piperidine-1-carboxylate Chemical compound C([C@H]([C@H](C1)C(C)O)CCCC2=CC=NC3=CC=C(C=C32)OC)CN1C(=O)OCC1=CC=CC=C1 UJVLJVVVVPBNKB-VBRLCVBGSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 4
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 238000011065 in-situ storage Methods 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 239000012948 isocyanate Substances 0.000 description 4
- 125000002524 organometallic group Chemical group 0.000 description 4
- 239000012285 osmium tetroxide Substances 0.000 description 4
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- LOUPRKONTZGTKE-LHHVKLHASA-N quinidine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@H]2[C@@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-LHHVKLHASA-N 0.000 description 4
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 4
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 4
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 4
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
- PHGNGVYUHOARGF-UHFFFAOYSA-N 6-methoxyquinolin-4-amine Chemical compound N1=CC=C(N)C2=CC(OC)=CC=C21 PHGNGVYUHOARGF-UHFFFAOYSA-N 0.000 description 3
- VAPXHQJBDLJPBV-VHHDRZGZSA-N C(C1=CC=CC=C1)OC(=O)N1C[C@@H]([C@@H](CC1)CCCC1=CC=NC2=CC=C(C=C12)OC)C1OC1 Chemical compound C(C1=CC=CC=C1)OC(=O)N1C[C@@H]([C@@H](CC1)CCCC1=CC=NC2=CC=C(C=C12)OC)C1OC1 VAPXHQJBDLJPBV-VHHDRZGZSA-N 0.000 description 3
- 238000006969 Curtius rearrangement reaction Methods 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 3
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 241001274216 Naso Species 0.000 description 3
- 235000019502 Orange oil Nutrition 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 150000001350 alkyl halides Chemical class 0.000 description 3
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 3
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 3
- 239000006196 drop Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000006735 epoxidation reaction Methods 0.000 description 3
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 150000002513 isocyanates Chemical class 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 229910052987 metal hydride Inorganic materials 0.000 description 3
- 150000004681 metal hydrides Chemical class 0.000 description 3
- SVMMKSXYADZNFW-DBMQZSJKSA-N methyl (3r,4r)-3-ethenyl-4-[1-methoxy-3-(6-methoxyquinolin-4-yl)-1,3-dioxopropan-2-yl]piperidine-1-carboxylate Chemical compound C=1C=NC2=CC=C(OC)C=C2C=1C(=O)C(C(=O)OC)[C@@H]1CCN(C(=O)OC)C[C@@H]1C=C SVMMKSXYADZNFW-DBMQZSJKSA-N 0.000 description 3
- 239000002808 molecular sieve Substances 0.000 description 3
- 239000010502 orange oil Substances 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 150000003053 piperidines Chemical class 0.000 description 3
- 125000003386 piperidinyl group Chemical group 0.000 description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 235000010356 sorbitol Nutrition 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- RWFNAZVDXYFIIG-OATREDKOSA-N tert-butyl (3r,4r)-3-ethenyl-4-[1-methoxy-3-(6-methoxyquinolin-4-yl)-1,3-dioxopropan-2-yl]piperidine-1-carboxylate Chemical compound C=1C=NC2=CC=C(OC)C=C2C=1C(=O)C(C(=O)OC)[C@@H]1CCN(C(=O)OC(C)(C)C)C[C@@H]1C=C RWFNAZVDXYFIIG-OATREDKOSA-N 0.000 description 3
- YLWWCGNFSIGQTB-UHFFFAOYSA-N (1-heptylpiperidin-4-yl)methanol Chemical compound CCCCCCCN1CCC(CO)CC1 YLWWCGNFSIGQTB-UHFFFAOYSA-N 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 2
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
- AUWIJOBQBVDDDA-JDQGPONISA-N 1-[(3r,4r)-4-[3-(6-methoxyquinolin-4-yl)propyl]piperidin-3-yl]ethanol Chemical compound C12=CC(OC)=CC=C2N=CC=C1CCC[C@@H]1CCNC[C@@H]1C(C)O AUWIJOBQBVDDDA-JDQGPONISA-N 0.000 description 2
- GRNOZCCBOFGDCL-UHFFFAOYSA-N 2,2,2-trichloroacetyl isocyanate Chemical compound ClC(Cl)(Cl)C(=O)N=C=O GRNOZCCBOFGDCL-UHFFFAOYSA-N 0.000 description 2
- VKJCJJYNVIYVQR-UHFFFAOYSA-N 2-(3-bromopropyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCCBr)C(=O)C2=C1 VKJCJJYNVIYVQR-UHFFFAOYSA-N 0.000 description 2
- ABFPKTQEQNICFT-UHFFFAOYSA-M 2-chloro-1-methylpyridin-1-ium;iodide Chemical compound [I-].C[N+]1=CC=CC=C1Cl ABFPKTQEQNICFT-UHFFFAOYSA-M 0.000 description 2
- ZNGINKJHQQQORD-UHFFFAOYSA-N 2-trimethylsilylethanol Chemical compound C[Si](C)(C)CCO ZNGINKJHQQQORD-UHFFFAOYSA-N 0.000 description 2
- RUROFEVDCUGKHD-UHFFFAOYSA-N 3-bromoprop-1-enylbenzene Chemical compound BrCC=CC1=CC=CC=C1 RUROFEVDCUGKHD-UHFFFAOYSA-N 0.000 description 2
- MCSXGCZMEPXKIW-UHFFFAOYSA-N 3-hydroxy-4-[(4-methyl-2-nitrophenyl)diazenyl]-N-(3-nitrophenyl)naphthalene-2-carboxamide Chemical compound Cc1ccc(N=Nc2c(O)c(cc3ccccc23)C(=O)Nc2cccc(c2)[N+]([O-])=O)c(c1)[N+]([O-])=O MCSXGCZMEPXKIW-UHFFFAOYSA-N 0.000 description 2
- HSBKMMSLWXJVGJ-UHFFFAOYSA-N 4-(chloromethyl)-6-methoxyquinoline Chemical compound N1=CC=C(CCl)C2=CC(OC)=CC=C21 HSBKMMSLWXJVGJ-UHFFFAOYSA-N 0.000 description 2
- SKLNYYGFABAGPC-OUGHWAIZSA-N 4-[3-[(3z,4r)-3-ethylidene-1-heptylpiperidin-4-yl]propyl]quinolin-6-ol Chemical compound C/C=C/1CN(CCCCCCC)CC[C@H]\1CCCC1=CC=NC2=CC=C(O)C=C12 SKLNYYGFABAGPC-OUGHWAIZSA-N 0.000 description 2
- MBVGYFIYXWVPQY-UHFFFAOYSA-N 6-methoxy-4-methylquinoline Chemical compound N1=CC=C(C)C2=CC(OC)=CC=C21 MBVGYFIYXWVPQY-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- XLLKSQQUSXSKIU-JTHBVZDNSA-N [(3R,4S)-1-heptyl-4-[3-(6-methoxyquinolin-4-yl)propyl]piperidin-3-yl]methanol Chemical compound C(CCCCCC)N1C[C@@H]([C@H](CC1)CCCC1=CC=NC2=CC=C(C=C12)OC)CO XLLKSQQUSXSKIU-JTHBVZDNSA-N 0.000 description 2
- RSWGJHLUYNHPMX-ONCXSQPRSA-N abietic acid Chemical compound C([C@@H]12)CC(C(C)C)=CC1=CC[C@@H]1[C@]2(C)CCC[C@@]1(C)C(O)=O RSWGJHLUYNHPMX-ONCXSQPRSA-N 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- OJHAHQJRQIOCFK-UHFFFAOYSA-N azane;chloroform;methanol Chemical compound N.OC.ClC(Cl)Cl OJHAHQJRQIOCFK-UHFFFAOYSA-N 0.000 description 2
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 2
- TUWZZXGAUMSUOB-UHFFFAOYSA-N benzyl piperidine-1-carboxylate Chemical compound C1CCCCN1C(=O)OCC1=CC=CC=C1 TUWZZXGAUMSUOB-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- XNNQFQFUQLJSQT-UHFFFAOYSA-N bromo(trichloro)methane Chemical compound ClC(Cl)(Cl)Br XNNQFQFUQLJSQT-UHFFFAOYSA-N 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 235000008504 concentrate Nutrition 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- XFKLQSGGOBPOQV-UHFFFAOYSA-N ethyl 1-heptylpiperidine-4-carboxylate Chemical compound CCCCCCCN1CCC(C(=O)OCC)CC1 XFKLQSGGOBPOQV-UHFFFAOYSA-N 0.000 description 2
- MHYCRLGKOZWVEF-UHFFFAOYSA-N ethyl acetate;hydrate Chemical compound O.CCOC(C)=O MHYCRLGKOZWVEF-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- FXHGMKSSBGDXIY-UHFFFAOYSA-N heptanal Chemical compound CCCCCCC=O FXHGMKSSBGDXIY-UHFFFAOYSA-N 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- 238000006197 hydroboration reaction Methods 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 150000005217 methyl ethers Chemical class 0.000 description 2
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 125000004043 oxo group Chemical group O=* 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- DTUQWGWMVIHBKE-UHFFFAOYSA-N phenylacetaldehyde Chemical compound O=CCC1=CC=CC=C1 DTUQWGWMVIHBKE-UHFFFAOYSA-N 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 2
- 229960001404 quinidine Drugs 0.000 description 2
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 2
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
- 235000010265 sodium sulphite Nutrition 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- OSBSFAARYOCBHB-UHFFFAOYSA-N tetrapropylammonium Chemical compound CCC[N+](CCC)(CCC)CCC OSBSFAARYOCBHB-UHFFFAOYSA-N 0.000 description 2
- DUYAAUVXQSMXQP-UHFFFAOYSA-M thioacetate Chemical compound CC([S-])=O DUYAAUVXQSMXQP-UHFFFAOYSA-M 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 2
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 2
- 239000008215 water for injection Substances 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- ZPBVSNLTCADQOD-UHFFFAOYSA-N (6-methoxyquinolin-4-yl)methanol Chemical compound N1=CC=C(CO)C2=CC(OC)=CC=C21 ZPBVSNLTCADQOD-UHFFFAOYSA-N 0.000 description 1
- ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 1
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- XBYRMPXUBGMOJC-UHFFFAOYSA-N 1,2-dihydropyrazol-3-one Chemical compound OC=1C=CNN=1 XBYRMPXUBGMOJC-UHFFFAOYSA-N 0.000 description 1
- BEFJUXMMFMXCHU-UHFFFAOYSA-N 1-(6-methoxyquinolin-4-yl)-2-piperidin-4-ylethanol Chemical compound C12=CC(OC)=CC=C2N=CC=C1C(O)CC1CCNCC1 BEFJUXMMFMXCHU-UHFFFAOYSA-N 0.000 description 1
- DPJQFIQFRZICNY-UHFFFAOYSA-N 1-(6-methoxyquinolin-4-yl)-2-piperidin-4-ylethanone Chemical compound C12=CC(OC)=CC=C2N=CC=C1C(=O)CC1CCNCC1 DPJQFIQFRZICNY-UHFFFAOYSA-N 0.000 description 1
- SHLMRTBDHWEPQA-UHFFFAOYSA-N 1-(6-methoxyquinolin-4-yl)-3-piperidin-4-ylpropan-2-ol Chemical compound C12=CC(OC)=CC=C2N=CC=C1CC(O)CC1CCNCC1 SHLMRTBDHWEPQA-UHFFFAOYSA-N 0.000 description 1
- FWWDPVVHPCDDFD-FCHUYYIVSA-N 1-[(3r,4r)-3-ethenyl-4-[3-(6-methoxyquinolin-4-yl)propyl]piperidin-1-yl]-2-phenoxyethanone Chemical compound C([C@H]([C@H](C1)C=C)CCCC2=CC=NC3=CC=C(C=C32)OC)CN1C(=O)COC1=CC=CC=C1 FWWDPVVHPCDDFD-FCHUYYIVSA-N 0.000 description 1
- XAOFMTDKQYEOES-UHFFFAOYSA-N 1-bromo-5-methylhexane Chemical compound CC(C)CCCCBr XAOFMTDKQYEOES-UHFFFAOYSA-N 0.000 description 1
- BFYPQDKZLOZOLQ-UHFFFAOYSA-N 1-bromo-6-methylheptane Chemical compound CC(C)CCCCCBr BFYPQDKZLOZOLQ-UHFFFAOYSA-N 0.000 description 1
- MYMSJFSOOQERIO-UHFFFAOYSA-N 1-bromodecane Chemical compound CCCCCCCCCCBr MYMSJFSOOQERIO-UHFFFAOYSA-N 0.000 description 1
- PBLNBZIONSLZBU-UHFFFAOYSA-N 1-bromododecane Chemical compound CCCCCCCCCCCCBr PBLNBZIONSLZBU-UHFFFAOYSA-N 0.000 description 1
- MNDIARAMWBIKFW-UHFFFAOYSA-N 1-bromohexane Chemical compound CCCCCCBr MNDIARAMWBIKFW-UHFFFAOYSA-N 0.000 description 1
- VMKOFRJSULQZRM-UHFFFAOYSA-N 1-bromooctane Chemical compound CCCCCCCCBr VMKOFRJSULQZRM-UHFFFAOYSA-N 0.000 description 1
- CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 1
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 1
- WSNFKVVZSAMWRX-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrochloride Chemical compound Cl.C1=CC=C2N(O)N=NC2=C1 WSNFKVVZSAMWRX-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 1
- JYWKEVKEKOTYEX-UHFFFAOYSA-N 2,6-dibromo-4-chloroiminocyclohexa-2,5-dien-1-one Chemical compound ClN=C1C=C(Br)C(=O)C(Br)=C1 JYWKEVKEKOTYEX-UHFFFAOYSA-N 0.000 description 1
- CHZXTOCAICMPQR-UHFFFAOYSA-N 2-(2-bromoethyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCBr)C(=O)C2=C1 CHZXTOCAICMPQR-UHFFFAOYSA-N 0.000 description 1
- QKVHAKICMNABGB-UHFFFAOYSA-N 2-(5-bromopentyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCCCCBr)C(=O)C2=C1 QKVHAKICMNABGB-UHFFFAOYSA-N 0.000 description 1
- VRPJIFMKZZEXLR-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid Chemical compound CC(C)(C)OC(=O)NCC(O)=O VRPJIFMKZZEXLR-UHFFFAOYSA-N 0.000 description 1
- QKCNBNQGBHHBMC-KSCSMHSMSA-N 2-[(3R,4S)-3-ethenyl-1-heptylpiperidin-4-yl]-2-(methylamino)acetic acid Chemical compound CCCCCCCN1CC[C@H](C(NC)C(O)=O)[C@@H](C=C)C1 QKCNBNQGBHHBMC-KSCSMHSMSA-N 0.000 description 1
- YCTPUFJIGWNRQR-SFTDATJTSA-N 2-[(3r,4s)-3-ethenyl-1-heptylpiperidin-4-yl]-1-(6-methoxyquinolin-4-yl)ethanone Chemical compound C=C[C@H]1CN(CCCCCCC)CC[C@H]1CC(=O)C1=CC=NC2=CC=C(OC)C=C12 YCTPUFJIGWNRQR-SFTDATJTSA-N 0.000 description 1
- XUCLXWHWUHUMKJ-IRXDYDNUSA-N 2-[(3r,4s)-3-ethenyl-1-heptylpiperidin-4-yl]-n-methylethanamine Chemical compound CCCCCCCN1CC[C@H](CCNC)[C@@H](C=C)C1 XUCLXWHWUHUMKJ-IRXDYDNUSA-N 0.000 description 1
- NVYJDNRWHWNUCO-HOTGVXAUSA-N 2-[(3r,4s)-3-ethenyl-1-heptylpiperidin-4-yl]ethanol Chemical compound CCCCCCCN1CC[C@@H](CCO)[C@@H](C=C)C1 NVYJDNRWHWNUCO-HOTGVXAUSA-N 0.000 description 1
- MBJTUSSLFXQAJQ-AXEKQOJOSA-N 2-[(3r,4s)-3-ethenylpiperidin-4-yl]-1-(6-methoxyquinolin-4-yl)ethanone;dihydrochloride Chemical compound Cl.Cl.C12=CC(OC)=CC=C2N=CC=C1C(=O)C[C@@H]1CCNC[C@@H]1C=C MBJTUSSLFXQAJQ-AXEKQOJOSA-N 0.000 description 1
- LLNBTHNJAWYSNQ-WZKMZYQSSA-N 2-[5-[4-[3-[(3r,4r)-3-ethyl-1-heptylpiperidin-4-yl]-1-hydroxypropyl]quinolin-6-yl]oxypentyl]isoindole-1,3-dione Chemical compound CC[C@H]1CN(CCCCCCC)CC[C@H]1CCC(O)C(C1=C2)=CC=NC1=CC=C2OCCCCCN1C(=O)C2=CC=CC=C2C1=O LLNBTHNJAWYSNQ-WZKMZYQSSA-N 0.000 description 1
- WTRIMJTZOOLIFZ-UHFFFAOYSA-N 2-bromo-2-methylpropanamide Chemical compound CC(C)(Br)C(N)=O WTRIMJTZOOLIFZ-UHFFFAOYSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- JTVBWGYLHDFBPW-NTEFNCDNSA-N 2-methoxy-1-[(3R,4R)-4-[3-(6-methoxyquinolin-4-yl)propyl]piperidin-3-yl]ethanol Chemical compound OC(COC)[C@H]1CNCC[C@H]1CCCC1=CC=NC2=CC=C(C=C12)OC JTVBWGYLHDFBPW-NTEFNCDNSA-N 0.000 description 1
- PKUPAJQAJXVUEK-UHFFFAOYSA-N 2-phenoxyacetyl chloride Chemical compound ClC(=O)COC1=CC=CC=C1 PKUPAJQAJXVUEK-UHFFFAOYSA-N 0.000 description 1
- JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 1
- PBVXLYZMXNTBOS-NOZRDPDXSA-N 3-[(3r,4r)-1-heptyl-4-[3-(6-methoxyquinolin-4-yl)propyl]piperidin-3-yl]propanenitrile Chemical compound N#CCC[C@H]1CN(CCCCCCC)CC[C@H]1CCCC1=CC=NC2=CC=C(OC)C=C12 PBVXLYZMXNTBOS-NOZRDPDXSA-N 0.000 description 1
- QVJFKLDDQFSFFS-NWDGAFQWSA-N 3-[(3r,4r)-3-ethenyl-1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]propanoic acid Chemical compound CC(C)(C)OC(=O)N1CC[C@@H](CCC(O)=O)[C@@H](C=C)C1 QVJFKLDDQFSFFS-NWDGAFQWSA-N 0.000 description 1
- NQCUGVKTWQTSJC-SMWUWQHRSA-N 3-[(3r,4r)-3-ethenyl-1-heptylpiperidin-4-yl]-1-(6-methoxyquinolin-4-yl)propan-1-amine Chemical compound C=C[C@H]1CN(CCCCCCC)CC[C@H]1CCC(N)C1=CC=NC2=CC=C(OC)C=C12 NQCUGVKTWQTSJC-SMWUWQHRSA-N 0.000 description 1
- NHVCPGIQKWXLDK-VKWYCSODSA-N 3-[(3r,4r)-3-ethenylpiperidin-4-yl]-1-(6-methoxyquinolin-4-yl)propan-1-ol Chemical compound C12=CC(OC)=CC=C2N=CC=C1C(O)CC[C@@H]1CCNC[C@@H]1C=C NHVCPGIQKWXLDK-VKWYCSODSA-N 0.000 description 1
- AAUYBNKTUTZDCH-VKWYCSODSA-N 3-[(3r,4r)-3-ethylpiperidin-4-yl]-1-(6-methoxyquinolin-4-yl)propan-1-ol Chemical compound CC[C@H]1CNCC[C@H]1CCC(O)C1=CC=NC2=CC=C(OC)C=C12 AAUYBNKTUTZDCH-VKWYCSODSA-N 0.000 description 1
- YRGQIEDLMKYPAB-LSDHHAIUSA-N 3-[(3r,4r)-3-ethylpiperidin-4-yl]-1-(6-methoxyquinolin-4-yl)propan-1-one Chemical compound CC[C@H]1CNCC[C@H]1CCC(=O)C1=CC=NC2=CC=C(OC)C=C12 YRGQIEDLMKYPAB-LSDHHAIUSA-N 0.000 description 1
- GAXILEMACJJMLK-AEFFLSMTSA-N 3-[(3r,4r)-4-[3-(6-methoxyquinolin-4-yl)propyl]piperidin-3-yl]propan-1-ol Chemical compound C12=CC(OC)=CC=C2N=CC=C1CCC[C@@H]1CCNC[C@@H]1CCCO GAXILEMACJJMLK-AEFFLSMTSA-N 0.000 description 1
- MVMHTGDHKJQJKG-AEFFLSMTSA-N 3-[(3r,4r)-4-[3-(6-methoxyquinolin-4-yl)propyl]piperidin-3-yl]propanenitrile Chemical compound C12=CC(OC)=CC=C2N=CC=C1CCC[C@@H]1CCNC[C@@H]1CCC#N MVMHTGDHKJQJKG-AEFFLSMTSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- ZYJSTSMEUKNCEV-UHFFFAOYSA-N 3-diazo-1-diazonioprop-1-en-2-olate Chemical compound [N-]=[N+]=CC(=O)C=[N+]=[N-] ZYJSTSMEUKNCEV-UHFFFAOYSA-N 0.000 description 1
- 125000006192 3-phenylprop-2-enyl group Chemical group [H]\C(=C(\[H])C([H])([H])*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- YGCZTXZTJXYWCO-UHFFFAOYSA-N 3-phenylpropanal Chemical compound O=CCCC1=CC=CC=C1 YGCZTXZTJXYWCO-UHFFFAOYSA-N 0.000 description 1
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- OMVZHYHZPBUNOM-LSDHHAIUSA-N 4-[2-[(3r,4r)-3-ethylpiperidin-4-yl]ethyl]-6-methoxyquinoline Chemical compound CC[C@H]1CNCC[C@H]1CCC1=CC=NC2=CC=C(OC)C=C12 OMVZHYHZPBUNOM-LSDHHAIUSA-N 0.000 description 1
- FHWBOWSHNLAZBG-HUUCEWRRSA-N 4-[2-[(3s,4r)-3-ethenylpiperidin-4-yl]ethyl]-6-methoxyquinoline Chemical compound C12=CC(OC)=CC=C2N=CC=C1CC[C@@H]1CCNC[C@H]1C=C FHWBOWSHNLAZBG-HUUCEWRRSA-N 0.000 description 1
- NVZVXLGGQCKMPP-JKSUJKDBSA-N 4-[3-[(3r,4r)-3-ethylpiperidin-4-yl]propyl]-6-methoxyquinoline Chemical compound CC[C@H]1CNCC[C@H]1CCCC1=CC=NC2=CC=C(OC)C=C12 NVZVXLGGQCKMPP-JKSUJKDBSA-N 0.000 description 1
- NQQGAEDSYKPAAI-LSDHHAIUSA-N 4-[3-[(3r,4r)-3-ethylpiperidin-4-yl]propyl]quinolin-6-ol Chemical compound CC[C@H]1CNCC[C@H]1CCCC1=CC=NC2=CC=C(O)C=C12 NQQGAEDSYKPAAI-LSDHHAIUSA-N 0.000 description 1
- YZAUOUVSPZNVEW-FOGCTLQKSA-N 4-[3-[(3z,4r)-3-ethylidenepiperidin-4-yl]propyl]quinolin-6-ol Chemical compound C\C=C1/CNCC[C@H]1CCCC1=CC=NC2=CC=C(O)C=C12 YZAUOUVSPZNVEW-FOGCTLQKSA-N 0.000 description 1
- JCPCYHJDKAIQNB-LRUHZDSUSA-N 4-[4-[(3r,4r)-3-ethylpiperidin-4-yl]butan-2-yl]-6-methoxyquinoline Chemical compound CC[C@H]1CNCC[C@H]1CCC(C)C1=CC=NC2=CC=C(OC)C=C12 JCPCYHJDKAIQNB-LRUHZDSUSA-N 0.000 description 1
- SOSBBTMOJYKVAG-GJZGRUSLSA-N 4-[[(3r,4r)-3-ethylpiperidin-4-yl]methylsulfanylmethyl]-6-methoxyquinoline Chemical compound CC[C@H]1CNCC[C@H]1CSCC1=CC=NC2=CC=C(OC)C=C12 SOSBBTMOJYKVAG-GJZGRUSLSA-N 0.000 description 1
- 150000005011 4-aminoquinolines Chemical class 0.000 description 1
- QISOBCMNUJQOJU-UHFFFAOYSA-N 4-bromo-1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1NN=CC=1Br QISOBCMNUJQOJU-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 1
- CKOZVEHVVHCMGD-UHFFFAOYSA-N 5-[(4-fluorophenyl)methyl]-n,n-dimethyltetrazole-1-carboxamide Chemical compound CN(C)C(=O)N1N=NN=C1CC1=CC=C(F)C=C1 CKOZVEHVVHCMGD-UHFFFAOYSA-N 0.000 description 1
- FUFZNHHSSMCXCZ-UHFFFAOYSA-N 5-piperidin-4-yl-3-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazole Chemical compound FC(F)(F)C1=CC=CC(C=2N=C(ON=2)C2CCNCC2)=C1 FUFZNHHSSMCXCZ-UHFFFAOYSA-N 0.000 description 1
- BWEGRKPOJXNZSK-UHFFFAOYSA-N 6-Methoxyquinoline N-oxide Chemical compound [O-][N+]1=CC=CC2=CC(OC)=CC=C21 BWEGRKPOJXNZSK-UHFFFAOYSA-N 0.000 description 1
- RVTLXJLNIDCHKT-UHFFFAOYSA-N 6-methoxy-1h-quinolin-4-one Chemical compound N1=CC=C(O)C2=CC(OC)=CC=C21 RVTLXJLNIDCHKT-UHFFFAOYSA-N 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 238000006237 Beckmann rearrangement reaction Methods 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 101150065749 Churc1 gene Proteins 0.000 description 1
- 235000001258 Cinchona calisaya Nutrition 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Natural products OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229910010082 LiAlH Inorganic materials 0.000 description 1
- 238000006751 Mitsunobu reaction Methods 0.000 description 1
- SMSKYSIBSAPCKG-SYDXZMBCSA-N N-[4-[3-[(3R,4R)-3-ethyl-1-heptylpiperidin-4-yl]-1-hydroxypropyl]quinolin-6-yl]-2-hydroxy-2-methylpropanamide Chemical compound C(C)[C@H]1CN(CC[C@H]1CCC(C1=CC=NC2=CC=C(C=C12)NC(C(C)(C)O)=O)O)CCCCCCC SMSKYSIBSAPCKG-SYDXZMBCSA-N 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 150000007930 O-acyl isoureas Chemical class 0.000 description 1
- PMFDUVOTACYLOB-NTEFNCDNSA-N OC(CSC)[C@H]1CNCC[C@H]1CCCC1=CC=NC2=CC=C(C=C12)OC Chemical compound OC(CSC)[C@H]1CNCC[C@H]1CCCC1=CC=NC2=CC=C(C=C12)OC PMFDUVOTACYLOB-NTEFNCDNSA-N 0.000 description 1
- RTWBSAKCFVMXHW-IDCZIQLBSA-N OC(C[C@H]1CNCC[C@H]1CCCC1=CC=NC2=CC=C(C=C12)OC)C Chemical compound OC(C[C@H]1CNCC[C@H]1CCCC1=CC=NC2=CC=C(C=C12)OC)C RTWBSAKCFVMXHW-IDCZIQLBSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 102100038239 Protein Churchill Human genes 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 229940122490 Sigma receptor antagonist Drugs 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 244000277583 Terminalia catappa Species 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 238000007239 Wittig reaction Methods 0.000 description 1
- ULZUIENXXPDBMV-GDBMZVCRSA-N [(3r,4r)-4-[3-(6-methoxyquinolin-4-yl)propyl]piperidin-3-yl]methanol Chemical compound C12=CC(OC)=CC=C2N=CC=C1CCC[C@@H]1CCNC[C@@H]1CO ULZUIENXXPDBMV-GDBMZVCRSA-N 0.000 description 1
- XDILZEPJCPEDLT-UHFFFAOYSA-N [Na].[O-][N+]1=CC=CC=C1S Chemical compound [Na].[O-][N+]1=CC=CC=C1S XDILZEPJCPEDLT-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 125000005103 alkyl silyl group Chemical group 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940063655 aluminum stearate Drugs 0.000 description 1
- 238000010640 amide synthesis reaction Methods 0.000 description 1
- 238000007098 aminolysis reaction Methods 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 230000000078 anti-malarial effect Effects 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- HYTACLVSJIFYBY-UHFFFAOYSA-N azane;dichloromethane;methanol Chemical compound N.OC.ClCCl HYTACLVSJIFYBY-UHFFFAOYSA-N 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- OKBTWQYZVRHYJP-JNBDQXKTSA-N benzyl (3R,4R)-3-(1-hydroxy-2-methoxyethyl)-4-[3-(6-methoxyquinolin-4-yl)propyl]piperidine-1-carboxylate Chemical compound C(C1=CC=CC=C1)OC(=O)N1C[C@@H]([C@@H](CC1)CCCC1=CC=NC2=CC=C(C=C12)OC)C(COC)O OKBTWQYZVRHYJP-JNBDQXKTSA-N 0.000 description 1
- HLOYTVAVFOTIHD-JNBDQXKTSA-N benzyl (3R,4R)-3-(1-hydroxy-2-methylsulfanylethyl)-4-[3-(6-methoxyquinolin-4-yl)propyl]piperidine-1-carboxylate Chemical compound C(C1=CC=CC=C1)OC(=O)N1C[C@@H]([C@@H](CC1)CCCC1=CC=NC2=CC=C(C=C12)OC)C(CSC)O HLOYTVAVFOTIHD-JNBDQXKTSA-N 0.000 description 1
- SCXRJISYRFCQRV-VWNXMTODSA-N benzyl (3r,4r)-3-(2-hydroxyethyl)-4-[3-(6-methoxyquinolin-4-yl)propyl]piperidine-1-carboxylate Chemical compound C([C@H]([C@H](C1)CCO)CCCC2=CC=NC3=CC=C(C=C32)OC)CN1C(=O)OCC1=CC=CC=C1 SCXRJISYRFCQRV-VWNXMTODSA-N 0.000 description 1
- VOYAGLIEUDLXRC-UXUFEPEVSA-N benzyl (3r,4r)-3-(2-hydroxypropyl)-4-[3-(6-methoxyquinolin-4-yl)propyl]piperidine-1-carboxylate Chemical compound C([C@H]([C@H](C1)CC(C)O)CCCC2=CC=NC3=CC=C(C=C32)OC)CN1C(=O)OCC1=CC=CC=C1 VOYAGLIEUDLXRC-UXUFEPEVSA-N 0.000 description 1
- SWBAZGVMFXGFKR-NOZRDPDXSA-N benzyl (3r,4r)-3-(3-hydroxypropyl)-4-[3-(6-methoxyquinolin-4-yl)propyl]piperidine-1-carboxylate Chemical compound C([C@H]([C@H](C1)CCCO)CCCC2=CC=NC3=CC=C(C=C32)OC)CN1C(=O)OCC1=CC=CC=C1 SWBAZGVMFXGFKR-NOZRDPDXSA-N 0.000 description 1
- LGXPYQHOKCVCBX-FYYLOGMGSA-N benzyl (3r,4r)-3-(hydroxymethyl)-4-[3-(6-methoxyquinolin-4-yl)propyl]piperidine-1-carboxylate Chemical compound C([C@H]([C@H](C1)CO)CCCC2=CC=NC3=CC=C(C=C32)OC)CN1C(=O)OCC1=CC=CC=C1 LGXPYQHOKCVCBX-FYYLOGMGSA-N 0.000 description 1
- YYZZGMIOYURCPX-FCHUYYIVSA-N benzyl (3r,4r)-3-ethenyl-4-[3-(6-methoxyquinolin-4-yl)-3-oxopropyl]piperidine-1-carboxylate Chemical compound C([C@H]([C@H](C1)C=C)CCC(=O)C2=CC=NC3=CC=C(C=C32)OC)CN1C(=O)OCC1=CC=CC=C1 YYZZGMIOYURCPX-FCHUYYIVSA-N 0.000 description 1
- AFVRMSFSXLLESR-XZOQPEGZSA-N benzyl (3r,4r)-3-ethenyl-4-[3-(6-methoxyquinolin-4-yl)propyl]piperidine-1-carboxylate Chemical compound C([C@H]([C@H](C1)C=C)CCCC2=CC=NC3=CC=C(C=C32)OC)CN1C(=O)OCC1=CC=CC=C1 AFVRMSFSXLLESR-XZOQPEGZSA-N 0.000 description 1
- IKOZGRADTBVFMP-FYYLOGMGSA-N benzyl (3r,4r)-3-formyl-4-[3-(6-methoxyquinolin-4-yl)propyl]piperidine-1-carboxylate Chemical compound C([C@H]([C@H](C1)C=O)CCCC2=CC=NC3=CC=C(C=C32)OC)CN1C(=O)OCC1=CC=CC=C1 IKOZGRADTBVFMP-FYYLOGMGSA-N 0.000 description 1
- RBGNUPWGTMNTQP-VWNXMTODSA-N benzyl (3r,4r)-4-[3-(6-methoxyquinolin-4-yl)propyl]-3-(2-oxoethyl)piperidine-1-carboxylate Chemical compound C([C@H]([C@H](C1)CC=O)CCCC2=CC=NC3=CC=C(C=C32)OC)CN1C(=O)OCC1=CC=CC=C1 RBGNUPWGTMNTQP-VWNXMTODSA-N 0.000 description 1
- MHCTZQXZAMUOBB-NOZRDPDXSA-N benzyl (3r,4r)-4-[3-(6-methoxyquinolin-4-yl)propyl]-3-prop-2-enylpiperidine-1-carboxylate Chemical compound C([C@H]([C@H](C1)CC=C)CCCC2=CC=NC3=CC=C(C=C32)OC)CN1C(=O)OCC1=CC=CC=C1 MHCTZQXZAMUOBB-NOZRDPDXSA-N 0.000 description 1
- JBXFXGZIMBAUIT-UHFFFAOYSA-N benzyl 4-(2-ethoxyacetyl)piperidine-1-carboxylate Chemical compound C1CC(C(=O)COCC)CCN1C(=O)OCC1=CC=CC=C1 JBXFXGZIMBAUIT-UHFFFAOYSA-N 0.000 description 1
- LINIORCIRVAZSM-UHFFFAOYSA-N benzyl 4-(hydroxymethyl)piperidine-1-carboxylate Chemical compound C1CC(CO)CCN1C(=O)OCC1=CC=CC=C1 LINIORCIRVAZSM-UHFFFAOYSA-N 0.000 description 1
- LOWFFKJGPLDVQR-UHFFFAOYSA-N benzyl 4-(iodomethyl)piperidine-1-carboxylate Chemical compound C1CC(CI)CCN1C(=O)OCC1=CC=CC=C1 LOWFFKJGPLDVQR-UHFFFAOYSA-N 0.000 description 1
- XZDQWUQAENQXST-UHFFFAOYSA-N benzyl 4-[2-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]piperidine-1-carboxylate Chemical compound C12=CC(OC)=CC=C2N=CC=C1CC(O)CC(CC1)CCN1C(=O)OCC1=CC=CC=C1 XZDQWUQAENQXST-UHFFFAOYSA-N 0.000 description 1
- DKOFUEHDTGPNQU-OIDHKYIRSA-N benzyl 4-[[4-[3-[(3R,4R)-3-ethyl-1-heptylpiperidin-4-yl]propyl]quinolin-6-yl]oxymethyl]piperidine-1-carboxylate Chemical compound C(C)[C@H]1CN(CC[C@H]1CCCC1=CC=NC2=CC=C(C=C12)OCC1CCN(CC1)C(=O)OCC1=CC=CC=C1)CCCCCCC DKOFUEHDTGPNQU-OIDHKYIRSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 239000003781 beta lactamase inhibitor Substances 0.000 description 1
- 229940126813 beta-lactamase inhibitor Drugs 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 125000006355 carbonyl methylene group Chemical group [H]C([H])([*:2])C([*:1])=O 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
- MYPYJXKWCTUITO-KIIOPKALSA-N chembl3301825 Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)C(O)[C@H](C)O1 MYPYJXKWCTUITO-KIIOPKALSA-N 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000544 cholinesterase inhibitor Substances 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- DKRSEIPLAZTSFD-UHFFFAOYSA-N d-quinotoxine Natural products C12=CC(OC)=CC=C2N=CC=C1C(=O)CCC1CCNCC1C=C DKRSEIPLAZTSFD-UHFFFAOYSA-N 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- XXTZHYXQVWRADW-UHFFFAOYSA-N diazomethanone Chemical compound [N]N=C=O XXTZHYXQVWRADW-UHFFFAOYSA-N 0.000 description 1
- FHHZOYXKOICLGH-UHFFFAOYSA-N dichloromethane;ethanol Chemical compound CCO.ClCCl FHHZOYXKOICLGH-UHFFFAOYSA-N 0.000 description 1
- MQYQOVYIJOLTNX-UHFFFAOYSA-N dichloromethane;n,n-dimethylformamide Chemical compound ClCCl.CN(C)C=O MQYQOVYIJOLTNX-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- HDRXZJPWHTXQRI-BHDTVMLSSA-N diltiazem hydrochloride Chemical compound [Cl-].C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CC[NH+](C)C)C2=CC=CC=C2S1 HDRXZJPWHTXQRI-BHDTVMLSSA-N 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003221 ear drop Substances 0.000 description 1
- 229940047652 ear drops Drugs 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 description 1
- 238000006266 etherification reaction Methods 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
- RUJPPJYDHHAEEK-UHFFFAOYSA-N ethyl piperidine-4-carboxylate Chemical compound CCOC(=O)C1CCNCC1 RUJPPJYDHHAEEK-UHFFFAOYSA-N 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 150000004820 halides Chemical group 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000007163 homologation reaction Methods 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- RCBVKBFIWMOMHF-UHFFFAOYSA-L hydroxy-(hydroxy(dioxo)chromio)oxy-dioxochromium;pyridine Chemical compound C1=CC=NC=C1.C1=CC=NC=C1.O[Cr](=O)(=O)O[Cr](O)(=O)=O RCBVKBFIWMOMHF-UHFFFAOYSA-L 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
- DBYQHFPBWKKZAT-UHFFFAOYSA-N lithium;benzene Chemical compound [Li+].C1=CC=[C-]C=C1 DBYQHFPBWKKZAT-UHFFFAOYSA-N 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- BRMYZIKAHFEUFJ-UHFFFAOYSA-L mercury diacetate Chemical compound CC(=O)O[Hg]OC(C)=O BRMYZIKAHFEUFJ-UHFFFAOYSA-L 0.000 description 1
- UXVFOFFVXPRWBZ-UHFFFAOYSA-N methyl 6-methoxyquinoline-4-carboxylate Chemical compound C1=C(OC)C=C2C(C(=O)OC)=CC=NC2=C1 UXVFOFFVXPRWBZ-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- LSEFCHWGJNHZNT-UHFFFAOYSA-M methyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 LSEFCHWGJNHZNT-UHFFFAOYSA-M 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- QIVWUIJKEZWHTD-KBPBESRZSA-N n-[[(3r,4r)-3-ethenylpiperidin-4-yl]methyl]-6-methoxyquinoline-4-carboxamide Chemical compound C12=CC(OC)=CC=C2N=CC=C1C(=O)NC[C@@H]1CCNC[C@@H]1C=C QIVWUIJKEZWHTD-KBPBESRZSA-N 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 description 1
- 229940055577 oleyl alcohol Drugs 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- WLCAJVVSNAVBSM-UHFFFAOYSA-N oxalic acid;piperidine Chemical compound C1CCNCC1.OC(=O)C(O)=O WLCAJVVSNAVBSM-UHFFFAOYSA-N 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical group [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- KRIOVPPHQSLHCZ-UHFFFAOYSA-N phenyl propionaldehyde Natural products CCC(=O)C1=CC=CC=C1 KRIOVPPHQSLHCZ-UHFFFAOYSA-N 0.000 description 1
- 229940100595 phenylacetaldehyde Drugs 0.000 description 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004344 phenylpropyl group Chemical group 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
- XBXHCBLBYQEYTI-UHFFFAOYSA-N piperidin-4-ylmethanol Chemical compound OCC1CCNCC1 XBXHCBLBYQEYTI-UHFFFAOYSA-N 0.000 description 1
- QTHXRDTZNWHMMO-UHFFFAOYSA-N piperidine;2,2,2-trifluoroacetic acid Chemical compound C1CCNCC1.OC(=O)C(F)(F)F.OC(=O)C(F)(F)F QTHXRDTZNWHMMO-UHFFFAOYSA-N 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 229960000948 quinine Drugs 0.000 description 1
- 229940114722 quinine and derivative for disorders of the musculo-skeletal system Drugs 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 238000000926 separation method Methods 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
- 239000010802 sludge Substances 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 125000005415 substituted alkoxy group Chemical group 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 150000003462 sulfoxides Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- BXWDGHCIFCFASL-CTNGQTDRSA-N tert-butyl (3r,4r)-3-(2-cyanoethyl)-4-[3-(6-methoxyquinolin-4-yl)propyl]piperidine-1-carboxylate Chemical compound C12=CC(OC)=CC=C2N=CC=C1CCC[C@@H]1CCN(C(=O)OC(C)(C)C)C[C@@H]1CCC#N BXWDGHCIFCFASL-CTNGQTDRSA-N 0.000 description 1
- JZSPBWCDZXBEQO-HOTGVXAUSA-N tert-butyl (3r,4r)-3-ethenyl-4-[(2-trimethylsilylethoxycarbonylamino)methyl]piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@@H](CNC(=O)OCC[Si](C)(C)C)[C@@H](C=C)C1 JZSPBWCDZXBEQO-HOTGVXAUSA-N 0.000 description 1
- BGMGXODQCUITKM-IRXDYDNUSA-N tert-butyl (3r,4r)-3-ethenyl-4-[[(6-methoxyquinoline-4-carbonyl)amino]methyl]piperidine-1-carboxylate Chemical compound C12=CC(OC)=CC=C2N=CC=C1C(=O)NC[C@@H]1CCN(C(=O)OC(C)(C)C)C[C@@H]1C=C BGMGXODQCUITKM-IRXDYDNUSA-N 0.000 description 1
- ZMYMNKYFQVVYPX-QWRGUYRKSA-N tert-butyl (3r,4r)-3-ethyl-4-(hydroxymethyl)piperidine-1-carboxylate Chemical compound CC[C@H]1CN(C(=O)OC(C)(C)C)CC[C@H]1CO ZMYMNKYFQVVYPX-QWRGUYRKSA-N 0.000 description 1
- SWLFYLJHEMTSME-ROUUACIJSA-N tert-butyl (3r,4r)-3-ethyl-4-[(6-methoxyquinolin-4-yl)methylsulfanylmethyl]piperidine-1-carboxylate Chemical compound CC[C@H]1CN(C(=O)OC(C)(C)C)CC[C@H]1CSCC1=CC=NC2=CC=C(OC)C=C12 SWLFYLJHEMTSME-ROUUACIJSA-N 0.000 description 1
- PBNBZDWHNRZZGB-STQMWFEESA-N tert-butyl (3r,4r)-4-(acetyloxymethyl)-3-ethylpiperidine-1-carboxylate Chemical compound CC[C@H]1CN(C(=O)OC(C)(C)C)CC[C@H]1COC(C)=O PBNBZDWHNRZZGB-STQMWFEESA-N 0.000 description 1
- KNGOWEHLTMIMCP-QWRGUYRKSA-N tert-butyl (3r,4r)-4-(bromomethyl)-3-ethylpiperidine-1-carboxylate Chemical compound CC[C@H]1CN(C(=O)OC(C)(C)C)CC[C@H]1CBr KNGOWEHLTMIMCP-QWRGUYRKSA-N 0.000 description 1
- ONEFUGJPKIYPSR-RSXGOPAZSA-N tert-butyl (3r,4r)-4-[3-(6-methoxyquinolin-4-yl)propyl]-3-[2-(4-methylphenyl)sulfonyloxyethyl]piperidine-1-carboxylate Chemical compound C([C@H]1CN(CC[C@H]1CCCC1=CC=NC2=CC=C(C=C21)OC)C(=O)OC(C)(C)C)COS(=O)(=O)C1=CC=C(C)C=C1 ONEFUGJPKIYPSR-RSXGOPAZSA-N 0.000 description 1
- DSVLZTRRVVHYMB-IZZNHLLZSA-N tert-butyl 2-[4-[3-[(3r,4r)-3-ethyl-1-heptylpiperidin-4-yl]propyl]quinolin-6-yl]oxyacetate Chemical compound CC[C@H]1CN(CCCCCCC)CC[C@H]1CCCC1=CC=NC2=CC=C(OCC(=O)OC(C)(C)C)C=C12 DSVLZTRRVVHYMB-IZZNHLLZSA-N 0.000 description 1
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
- RUDXNALMPUXCJY-UHFFFAOYSA-N tert-butyl N-carbamoyl-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamate Chemical compound C(C)(C)(C)OC(=O)N(C(=O)N)C(=O)OC(C)(C)C RUDXNALMPUXCJY-UHFFFAOYSA-N 0.000 description 1
- PRJVMUFHASYVLZ-UHFFFAOYSA-N tert-butyl [4-(2-hydroxyethyl)piperidin-1-yl] carbonate Chemical compound CC(C)(C)OC(=O)ON1CCC(CCO)CC1 PRJVMUFHASYVLZ-UHFFFAOYSA-N 0.000 description 1
- SJZZAAUAHSUVFW-LEWJYISDSA-N tert-butyl n-[2-[(3r,4r)-3-ethenyl-4-[3-(6-methoxyquinolin-4-yl)propyl]piperidin-1-yl]ethyl]carbamate Chemical compound C12=CC(OC)=CC=C2N=CC=C1CCC[C@@H]1CCN(CCNC(=O)OC(C)(C)C)C[C@@H]1C=C SJZZAAUAHSUVFW-LEWJYISDSA-N 0.000 description 1
- 150000003509 tertiary alcohols Chemical class 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000759 toxicological effect Toxicity 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- PGAJYUDRKAPMPA-UHFFFAOYSA-N trimethylsilyl n-ethylcarbamate Chemical compound CCNC(=O)O[Si](C)(C)C PGAJYUDRKAPMPA-UHFFFAOYSA-N 0.000 description 1
- ORGHESHFQPYLAO-UHFFFAOYSA-N vinyl radical Chemical compound C=[CH] ORGHESHFQPYLAO-UHFFFAOYSA-N 0.000 description 1
- XFXANHWIBFMEOY-JKSUJKDBSA-N viqualine Chemical compound C12=CC(OC)=CC=C2N=CC=C1CCC[C@@H]1CCNC[C@@H]1C=C XFXANHWIBFMEOY-JKSUJKDBSA-N 0.000 description 1
- DKRSEIPLAZTSFD-LSDHHAIUSA-N viquidil Chemical compound C12=CC(OC)=CC=C2N=CC=C1C(=O)CC[C@@H]1CCNC[C@@H]1C=C DKRSEIPLAZTSFD-LSDHHAIUSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 229940126085 β‑Lactamase Inhibitor Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9801630.6A GB9801630D0 (en) | 1998-01-26 | 1998-01-26 | Novel compounds |
| GB9801630 | 1998-01-26 | ||
| GBGB9821072.7A GB9821072D0 (en) | 1998-09-29 | 1998-09-29 | Medicaments |
| GB9821072 | 1998-09-29 | ||
| PCT/EP1999/000333 WO1999037635A1 (en) | 1998-01-26 | 1999-01-21 | Quinoline derivatives as antibacterials |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69908555D1 DE69908555D1 (de) | 2003-07-10 |
| DE69908555T2 true DE69908555T2 (de) | 2004-05-06 |
Family
ID=26313018
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69908555T Expired - Fee Related DE69908555T2 (de) | 1998-01-26 | 1999-01-21 | Chinolinderivate als antibakterielles arzneimittel |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP1051413B1 (enExample) |
| JP (1) | JP2002501061A (enExample) |
| AR (1) | AR018042A1 (enExample) |
| AU (1) | AU2717899A (enExample) |
| CA (1) | CA2318842A1 (enExample) |
| DE (1) | DE69908555T2 (enExample) |
| ES (1) | ES2201674T3 (enExample) |
| WO (1) | WO1999037635A1 (enExample) |
Families Citing this family (50)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9822450D0 (en) * | 1998-10-14 | 1998-12-09 | Smithkline Beecham Plc | Medicaments |
| GB9822440D0 (en) * | 1998-10-14 | 1998-12-09 | Smithkline Beecham Plc | Medicaments |
| AU2437900A (en) * | 1999-01-20 | 2000-08-07 | Smithkline Beecham Plc | Piperidinylquinolines as protein tyrosine kinase inhibitors |
| GB9914486D0 (en) | 1999-06-21 | 1999-08-18 | Smithkline Beecham Plc | Medicaments |
| GB9917408D0 (en) | 1999-07-23 | 1999-09-22 | Smithkline Beecham Plc | Compounds |
| GB9917406D0 (en) * | 1999-07-23 | 1999-09-22 | Smithkline Beecham Plc | Compounds |
| FR2798656B1 (fr) * | 1999-09-17 | 2004-12-17 | Aventis Pharma Sa | Derives de la quinolyl propyl piperidine, leur preparation et les compositions qui les contiennent |
| US6403610B1 (en) | 1999-09-17 | 2002-06-11 | Aventis Pharma S.A. | Quinolylpropylpiperidine derivatives, their preparation and the compositions which comprise them |
| US6803369B1 (en) | 2000-07-25 | 2004-10-12 | Smithkline Beecham Corporation | Compounds and methods for the treatment of neoplastic disease |
| EP1305308B1 (en) * | 2000-07-26 | 2006-12-20 | Smithkline Beecham Plc | Aminopiperidine quinolines and their azaisosteric analogues with antibacterial activity |
| FR2816618B1 (fr) * | 2000-11-15 | 2002-12-27 | Aventis Pharma Sa | Derives heterocyclylalcoyl piperidine, leur preparation et les compositions qui les contiennent |
| US6603005B2 (en) | 2000-11-15 | 2003-08-05 | Aventis Pharma S.A. | Heterocyclylalkylpiperidine derivatives, their preparation and compositions containing them |
| GB0031086D0 (en) * | 2000-12-20 | 2001-01-31 | Smithkline Beecham Plc | Medicaments |
| GB0031088D0 (en) * | 2000-12-20 | 2001-01-31 | Smithkline Beecham Plc | Medicaments |
| GB0101577D0 (en) | 2001-01-22 | 2001-03-07 | Smithkline Beecham Plc | Compounds |
| FR2822154B1 (fr) * | 2001-03-13 | 2005-10-21 | Aventis Pharma Sa | Derives de la quinolyl propyl piperidine, leur preparation et les compositions qui les contiennent |
| US6602884B2 (en) | 2001-03-13 | 2003-08-05 | Aventis Pharma S.A. | Quinolylpropylpiperidine derivatives, their preparation, and compositions containing them |
| GB0112834D0 (en) | 2001-05-25 | 2001-07-18 | Smithkline Beecham Plc | Medicaments |
| GB0112836D0 (en) | 2001-05-25 | 2001-07-18 | Smithkline Beecham Plc | Medicaments |
| AU2003239302A1 (en) * | 2002-01-29 | 2003-09-02 | Glaxo Group Limited | Aminopiperidine compounds, process for their preparation, and pharmaceutical compositions containing them |
| EP1470125A1 (en) | 2002-01-29 | 2004-10-27 | Glaxo Group Limited | Aminopiperidine derivatives |
| AR040335A1 (es) | 2002-06-26 | 2005-03-30 | Glaxo Group Ltd | Compuesto de ciclohexano o ciclohexeno, uso del mismo para preparar un medicamento, composicion farmaceutica que lo comprende, procedimiento y compuestos intermediarios de utilidad para preparar dicho compuesto |
| TW200409637A (en) | 2002-06-26 | 2004-06-16 | Glaxo Group Ltd | Compounds |
| FR2842807A1 (fr) | 2002-07-23 | 2004-01-30 | Aventis Pharma Sa | Derives de la quinolyl propyl piperidine, procede et intermediaires de preparation et compositions les renfermant |
| GB0217294D0 (en) * | 2002-07-25 | 2002-09-04 | Glaxo Group Ltd | Medicaments |
| NZ538391A (en) * | 2002-07-25 | 2005-10-28 | Janssen Pharmaceutica Nv | Quinoline derivatives and their use as mycobacterial inhibitors |
| ATE463494T1 (de) | 2002-10-10 | 2010-04-15 | Morphochem Ag Komb Chemie | Neue verbindungen mit antibakterieller aktivität |
| DE60331849D1 (de) | 2002-11-05 | 2010-05-06 | Glaxosmithkline Llc | Antibakterielle wirkstoffe |
| ES2350977T3 (es) | 2002-11-05 | 2011-01-28 | Glaxo Group Limited | Agentes antibacterianos. |
| US7491714B2 (en) | 2002-12-04 | 2009-02-17 | Glaxo Group Limited | Quinolines and nitrogenated derivatives thereof and their use as antibacterial agents |
| CN1795177A (zh) * | 2003-03-28 | 2006-06-28 | 辉瑞产品公司 | 作为治疗动脉粥样硬化和肥胖症的cetp抑制剂的 1 , 2 , 4 , －取代的1，2，3，4，－四氢－和1，2二氢－喹啉以及1， 2 , 3 ， 4－四氢－喹喔啉衍生物 |
| JP2007501854A (ja) * | 2003-05-27 | 2007-02-01 | ファイザー・プロダクツ・インク | 受容体型チロシンキナーゼ阻害薬としてのキナゾリン類およびピリド［３，４−ｄ］ピリミジン類 |
| US7348434B2 (en) | 2003-08-08 | 2008-03-25 | Antony Bigot | 4-substituted quinoline derivatives, method and intermediates for their preparation and pharmaceutical compositions containing them |
| FR2858619B1 (fr) * | 2003-08-08 | 2006-12-22 | Aventis Pharma Sa | Derives de quinoleines-4-substituees, leurs procede et intermediaires de preparation et les compositions pharmaceutiques qui les contiennent |
| AU2005210036B2 (en) * | 2004-01-29 | 2010-12-23 | Janssen Pharmaceutica N.V. | Quinoline derivatives for use as mycobacterial inhibitors |
| WO2006081178A2 (en) * | 2005-01-25 | 2006-08-03 | Glaxo Group Limited | Antibacterial agents |
| US7709472B2 (en) | 2005-01-25 | 2010-05-04 | Glaxo Group Limited | Antibacterial agents |
| JP2008528604A (ja) | 2005-01-25 | 2008-07-31 | グラクソ グループ リミテッド | 抗菌剤 |
| US7592334B2 (en) | 2005-01-25 | 2009-09-22 | Glaxo Group Limited | Antibacterial agents |
| WO2006081264A1 (en) | 2005-01-25 | 2006-08-03 | Glaxo Group Limited | Antibacterial agents |
| CA2528849C (en) | 2005-06-08 | 2014-01-14 | Janssen Pharmaceutica N.V. | Quinoline derivatives as antibacterial agents |
| EA010601B1 (ru) * | 2005-06-09 | 2008-10-30 | Янссен Фармацевтика Н.В. | Производные хинолина в качестве антибактериальных агентов |
| ES2376488T3 (es) | 2006-01-26 | 2012-03-14 | Actelion Pharmaceuticals Ltd. | Antibióticos de tetrahidropirano. |
| JP2009532504A (ja) | 2006-04-06 | 2009-09-10 | グラクソ グループ リミテッド | 抗菌薬 |
| EP2085383A4 (en) * | 2006-11-16 | 2010-09-22 | Astellas Pharma Inc | Piperidin derivatives or salts thereof |
| MX2009012117A (es) | 2007-05-09 | 2009-11-23 | Pfizer | Composiciones y derivados heterociclicos sustituidos y su uso farmaceutico como antibacterianos. |
| WO2016008381A1 (zh) * | 2014-07-14 | 2016-01-21 | 辰欣药业股份有限公司 | 吡啶衍生物及其作为抗分支杆菌的应用 |
| US10301254B2 (en) | 2015-04-23 | 2019-05-28 | Temple University—Of the Commonwealth System of Higher Education | Substituted polycationic multi-quaternary ammonium salts as antimicrobial agents |
| US11111216B2 (en) | 2016-10-26 | 2021-09-07 | Temple University-Of The Commonwealth System Of Higher Education | Polycationic amphiphiles as antimicrobial agents and methods using same |
| WO2020169593A1 (en) | 2019-02-19 | 2020-08-27 | Univerza V Ljubljani | Antibacterials based on monocyclic fragments coupled to aminopiperidine naphthyridine scaffold |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3362875A (en) * | 1965-06-04 | 1968-01-09 | Richardson Merrell Inc | N4, n4'-decamethylene-bis(4-amino)-quinaldine diacetate compositions for controllingtopical infections |
| FR2177511A1 (en) * | 1972-03-28 | 1973-11-09 | Omnium Chimique Sa | Quinolyl pipiridylethyl ketones - with vasodilatory and antispasmodic activity |
| GB1496371A (en) * | 1975-08-18 | 1977-12-30 | Serdex | 4-amino-quinoline derivatives process for their preparation and therapeutic applications thereof |
| NL7908031A (nl) * | 1979-11-01 | 1981-06-01 | Acf Chemiefarma Nv | Nieuwe chinolinederivaten en farmaceutische preparaten die een dergelijke verbinding bevatten, alsmede werk- wijze voor het bereiden van deze verbindingen. |
-
1999
- 1999-01-21 WO PCT/EP1999/000333 patent/WO1999037635A1/en not_active Ceased
- 1999-01-21 AU AU27178/99A patent/AU2717899A/en not_active Abandoned
- 1999-01-21 ES ES99907388T patent/ES2201674T3/es not_active Expired - Lifetime
- 1999-01-21 DE DE69908555T patent/DE69908555T2/de not_active Expired - Fee Related
- 1999-01-21 EP EP99907388A patent/EP1051413B1/en not_active Expired - Lifetime
- 1999-01-21 JP JP2000528558A patent/JP2002501061A/ja active Pending
- 1999-01-21 CA CA002318842A patent/CA2318842A1/en not_active Abandoned
- 1999-01-26 AR ARP990100304A patent/AR018042A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CA2318842A1 (en) | 1999-07-29 |
| DE69908555D1 (de) | 2003-07-10 |
| EP1051413A1 (en) | 2000-11-15 |
| WO1999037635A1 (en) | 1999-07-29 |
| ES2201674T3 (es) | 2004-03-16 |
| JP2002501061A (ja) | 2002-01-15 |
| AR018042A1 (es) | 2001-10-31 |
| AU2717899A (en) | 1999-08-09 |
| EP1051413B1 (en) | 2003-06-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69908555T2 (de) | Chinolinderivate als antibakterielles arzneimittel | |
| DE69925150T2 (de) | Naphthyridin-Verbindungen und ihre Azaisosteren Analoga als antibakterielle Mittel | |
| DE602004011767T2 (de) | Cyclohexylsulfone als gamma-sekretase-inhibitoren | |
| DE60022523T2 (de) | Aminopiperidinderivate als antibakterielles arzneimittel | |
| DE60006823T2 (de) | Quinolin-derivate und deren verwendung als antibakterielle wirkstoffe | |
| DE69232334T2 (de) | Substituierte 3-aminochinuclidine | |
| DE60112791T2 (de) | Piperidin mch antagonisten und ihre verwendung in der behandlung von obesität | |
| DE69928952T2 (de) | Chinolin-derivate und ihre verwendung als antibakterielle wirkstoffe | |
| DE69918296T2 (de) | N-substituierte aminotetraline als neuropeptid y y5 rezeptor-liganden und ihre anwendung zur behandlung von fettleibigkeit und anderen erkrankungen | |
| DE69637105T2 (de) | Tricyclische derivate anwendbar als g-protein inhibitoren und für die behandlung von proliferative erkrankungen | |
| DE69617701T2 (de) | 3-pyridyloxyalkyl heterozyklische ether-verbindungen, verwendbar zur steuerung von chemischer synaptischer transmission | |
| DE69625517T2 (de) | 3-spiro-indolin-2-onderivate als liganden der vasopressin und/oder der ocytocin rezeptoren | |
| DE60303954T2 (de) | Chinolylpropylpiperidin-derivate und deren verwendung als antimikrobielle wirkstoffe | |
| DE60211223T2 (de) | Piperidinderivate als Kalium-Kanal Blockers | |
| DE60012048T2 (de) | Phenoxypropanolamin-derivate, ihre herstellung und therapeutische verwendung | |
| DE69623745T2 (de) | Derivate von DC 107 | |
| DE60120138T2 (de) | Amid-verbindungen und deren verwendung | |
| DE69316068T2 (de) | 1-[2-(Arylsulfonylamino)-1-oxoethyl]piperidin-Derivate, ihre Herstellung und therapeutische Verwendung | |
| DE69427542T2 (de) | Tricyclische derivate und ihre anwendung als arzneimittel | |
| DE60213629T2 (de) | Piperidinverbindungen als muscarinantagonisten | |
| DE69400791T2 (de) | 5-Amino-8-methyl-7-pyrrolidinylchinolin-3-Carbonsäurederivat | |
| DE60223692T2 (de) | Cyclohexyl-sulphone | |
| EP1117652B1 (de) | Tan-1057 derivate | |
| DE69131428T2 (de) | Individuelle stereoisomere von 7-[3-(aminoalkyl)-1-pyrrolidinyl]-quinolone und naphthyridone als antibakterielle wirkstoffe | |
| DE60025348T2 (de) | Ethansulfonyl-piperidin-derivate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |