CA2448525A1 - Nitrogen-containing bicyclic heterocycles for use as antibacterials - Google Patents
Nitrogen-containing bicyclic heterocycles for use as antibacterials Download PDFInfo
- Publication number
- CA2448525A1 CA2448525A1 CA002448525A CA2448525A CA2448525A1 CA 2448525 A1 CA2448525 A1 CA 2448525A1 CA 002448525 A CA002448525 A CA 002448525A CA 2448525 A CA2448525 A CA 2448525A CA 2448525 A1 CA2448525 A1 CA 2448525A1
- Authority
- CA
- Canada
- Prior art keywords
- amino
- dihydro
- alkyl
- amide
- oxo
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 229940088710 antibiotic agent Drugs 0.000 title description 5
- 230000000844 anti-bacterial effect Effects 0.000 title description 3
- 238000000034 method Methods 0.000 claims abstract description 180
- 241000124008 Mammalia Species 0.000 claims abstract description 9
- 208000035143 Bacterial infection Diseases 0.000 claims abstract description 7
- 208000022362 bacterial infectious disease Diseases 0.000 claims abstract description 7
- -1 amino, piperidyl Chemical group 0.000 claims description 363
- 150000001875 compounds Chemical class 0.000 claims description 209
- 125000000217 alkyl group Chemical group 0.000 claims description 133
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 74
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 50
- 125000003118 aryl group Chemical group 0.000 claims description 49
- 125000003277 amino group Chemical group 0.000 claims description 44
- 229910052739 hydrogen Inorganic materials 0.000 claims description 44
- 125000005090 alkenylcarbonyl group Chemical group 0.000 claims description 42
- 230000008569 process Effects 0.000 claims description 41
- 125000005092 alkenyloxycarbonyl group Chemical group 0.000 claims description 39
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 39
- 239000001257 hydrogen Substances 0.000 claims description 39
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 38
- 125000003342 alkenyl group Chemical group 0.000 claims description 36
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 36
- VUHCPMIDSUGHNO-UHFFFAOYSA-N 6-methoxy-1,5-naphthyridin-4-amine Chemical compound N1=CC=C(N)C2=NC(OC)=CC=C21 VUHCPMIDSUGHNO-UHFFFAOYSA-N 0.000 claims description 35
- 239000002253 acid Substances 0.000 claims description 35
- 125000005843 halogen group Chemical group 0.000 claims description 35
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 34
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 32
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 32
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 29
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 28
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 27
- 125000000623 heterocyclic group Chemical group 0.000 claims description 24
- 150000001408 amides Chemical class 0.000 claims description 23
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 22
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 22
- 125000004414 alkyl thio group Chemical group 0.000 claims description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 21
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 20
- 229910052760 oxygen Inorganic materials 0.000 claims description 20
- 125000001424 substituent group Chemical group 0.000 claims description 19
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 18
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 125000004429 atom Chemical group 0.000 claims description 14
- 150000002367 halogens Chemical class 0.000 claims description 14
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 13
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 13
- 125000006574 non-aromatic ring group Chemical group 0.000 claims description 13
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 12
- 238000005984 hydrogenation reaction Methods 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 101150020251 NR13 gene Proteins 0.000 claims description 11
- 125000002252 acyl group Chemical group 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 125000004043 oxo group Chemical group O=* 0.000 claims description 11
- 125000005842 heteroatom Chemical group 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- RAHZWNYVWXNFOC-UHFFFAOYSA-N sulfur dioxide Inorganic materials O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 10
- 101100240517 Caenorhabditis elegans nhr-11 gene Proteins 0.000 claims description 9
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 9
- 150000002431 hydrogen Chemical group 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- 101000585507 Solanum tuberosum Cytochrome b-c1 complex subunit 7 Proteins 0.000 claims description 8
- 125000005605 benzo group Chemical group 0.000 claims description 8
- 125000001153 fluoro group Chemical group F* 0.000 claims description 8
- 125000004423 acyloxy group Chemical group 0.000 claims description 7
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 7
- 125000005647 linker group Chemical group 0.000 claims description 7
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims description 6
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 6
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 6
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 6
- PHGNGVYUHOARGF-UHFFFAOYSA-N 6-methoxyquinolin-4-amine Chemical compound N1=CC=C(N)C2=CC(OC)=CC=C21 PHGNGVYUHOARGF-UHFFFAOYSA-N 0.000 claims description 5
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 5
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 5
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 5
- 229910052727 yttrium Inorganic materials 0.000 claims description 5
- 125000001414 1,2,4-triazol-5-yl group Chemical group [H]N1N=C([H])N=C1[*] 0.000 claims description 4
- 125000005035 acylthio group Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 229910052721 tungsten Inorganic materials 0.000 claims description 4
- OJLZRYSTMRWWQM-UHFFFAOYSA-N 8-fluoro-6-methoxyquinolin-4-amine Chemical compound N1=CC=C(N)C2=CC(OC)=CC(F)=C21 OJLZRYSTMRWWQM-UHFFFAOYSA-N 0.000 claims description 3
- NZNMSOFKMUBTKW-UHFFFAOYSA-N Cyclohexanecarboxylic acid Natural products OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 claims description 3
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 125000006413 ring segment Chemical group 0.000 claims description 3
- 101100294102 Caenorhabditis elegans nhr-2 gene Proteins 0.000 claims description 2
- VOZMETOQQCEOLY-SHTZXODSSA-N S1CC(=O)NC2=CC(S(=O)(=O)N[C@H]3CC[C@@H](CC3)C(=O)NC3=CC=NC4=CC=C(N=C43)OC)=CC=C21 Chemical compound S1CC(=O)NC2=CC(S(=O)(=O)N[C@H]3CC[C@@H](CC3)C(=O)NC3=CC=NC4=CC=C(N=C43)OC)=CC=C21 VOZMETOQQCEOLY-SHTZXODSSA-N 0.000 claims description 2
- 125000004442 acylamino group Chemical group 0.000 claims description 2
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 2
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 2
- 125000004391 aryl sulfonyl 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
- 125000002527 bicyclic carbocyclic group Chemical group 0.000 claims description 2
- 150000003950 cyclic amides Chemical class 0.000 claims description 2
- VZFUCHSFHOYXIS-UHFFFAOYSA-N cycloheptane carboxylic acid Natural products OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000005223 heteroarylcarbonyl group 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
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical group O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
- OIBGVZXCQRBLSA-ZXYWRSMDSA-N (1r,3r,4r)-3-hydroxy-n-(6-methoxy-1,5-naphthyridin-4-yl)-4-[(2-oxo-1h-pyrido[3,4-b][1,4]thiazin-7-yl)methylamino]cyclohexane-1-carboxamide Chemical compound N1C(=O)CSC(C=N2)=C1C=C2CN[C@@H]([C@H](O)C1)CC[C@H]1C(=O)NC1=CC=NC2=CC=C(OC)N=C21 OIBGVZXCQRBLSA-ZXYWRSMDSA-N 0.000 claims 2
- OIBGVZXCQRBLSA-RFUYNDQBSA-N (1s,3s,4s)-3-hydroxy-n-(6-methoxy-1,5-naphthyridin-4-yl)-4-[(2-oxo-1h-pyrido[3,4-b][1,4]thiazin-7-yl)methylamino]cyclohexane-1-carboxamide Chemical compound N1C(=O)CSC(C=N2)=C1C=C2CN[C@H]([C@@H](O)C1)CC[C@@H]1C(=O)NC1=CC=NC2=CC=C(OC)N=C21 OIBGVZXCQRBLSA-RFUYNDQBSA-N 0.000 claims 2
- KLDOCEWRXGXRDS-YEWWUXTCSA-N (1s,3s,4s)-3-hydroxy-n-(6-methoxy-1,5-naphthyridin-4-yl)-4-[(3-oxo-4h-pyrido[3,2-b][1,4]thiazin-6-yl)methylamino]cyclohexane-1-carboxamide Chemical compound S1CC(=O)NC2=NC(CN[C@H]3CC[C@@H](C[C@@H]3O)C(=O)NC3=CC=NC4=CC=C(N=C43)OC)=CC=C21 KLDOCEWRXGXRDS-YEWWUXTCSA-N 0.000 claims 2
- BOPUCGGDXLOLLU-ZXYWRSMDSA-N (1r,3r,4r)-3-hydroxy-n-(6-methoxy-1,5-naphthyridin-4-yl)-4-[(2-oxo-1h-pyrido[3,4-b][1,4]oxazin-7-yl)methylamino]cyclohexane-1-carboxamide Chemical compound N1C(=O)COC(C=N2)=C1C=C2CN[C@@H]([C@H](O)C1)CC[C@H]1C(=O)NC1=CC=NC2=CC=C(OC)N=C21 BOPUCGGDXLOLLU-ZXYWRSMDSA-N 0.000 claims 1
- UQPMSQLUONKZOF-DDUZABMNSA-N (1r,3r,4r)-3-hydroxy-n-(6-methoxy-1,5-naphthyridin-4-yl)-4-[(3-oxo-4h-pyrido[3,2-b][1,4]oxazin-6-yl)methylamino]cyclohexane-1-carboxamide Chemical compound O1CC(=O)NC2=NC(CN[C@@H]3CC[C@H](C[C@H]3O)C(=O)NC3=CC=NC4=CC=C(N=C43)OC)=CC=C21 UQPMSQLUONKZOF-DDUZABMNSA-N 0.000 claims 1
- KLDOCEWRXGXRDS-DDUZABMNSA-N (1r,3r,4r)-3-hydroxy-n-(6-methoxy-1,5-naphthyridin-4-yl)-4-[(3-oxo-4h-pyrido[3,2-b][1,4]thiazin-6-yl)methylamino]cyclohexane-1-carboxamide Chemical compound S1CC(=O)NC2=NC(CN[C@@H]3CC[C@H](C[C@H]3O)C(=O)NC3=CC=NC4=CC=C(N=C43)OC)=CC=C21 KLDOCEWRXGXRDS-DDUZABMNSA-N 0.000 claims 1
- TVHALYRBKNFFTC-JXXFODFXSA-N (1r,3r,4r)-3-hydroxy-n-(6-methoxy-1,5-naphthyridin-4-yl)-4-[(7-methyl-3,4-dihydro-2h-pyrido[3,2-b][1,4]thiazin-6-yl)methylamino]cyclohexane-1-carboxamide Chemical compound N1CCSC(C=C2C)=C1N=C2CN[C@@H]([C@H](O)C1)CC[C@H]1C(=O)NC1=CC=NC2=CC=C(OC)N=C21 TVHALYRBKNFFTC-JXXFODFXSA-N 0.000 claims 1
- UFKFMBOQSFSOAP-RVZJWNSFSA-N (1r,3r,4r)-4-[(7-chloro-3-oxo-4h-pyrido[3,2-b][1,4]thiazin-6-yl)methylamino]-3-hydroxy-n-(6-methoxy-1,5-naphthyridin-4-yl)cyclohexane-1-carboxamide Chemical compound N1C(=O)CSC(C=C2Cl)=C1N=C2CN[C@@H]([C@H](O)C1)CC[C@H]1C(=O)NC1=CC=NC2=CC=C(OC)N=C21 UFKFMBOQSFSOAP-RVZJWNSFSA-N 0.000 claims 1
- CYHZYFWBZFKFHI-RVZJWNSFSA-N (1r,3r,4r)-4-[(7-fluoro-3-oxo-4h-pyrido[3,2-b][1,4]thiazin-6-yl)methylamino]-3-hydroxy-n-(6-methoxy-1,5-naphthyridin-4-yl)cyclohexane-1-carboxamide Chemical compound N1C(=O)CSC(C=C2F)=C1N=C2CN[C@@H]([C@H](O)C1)CC[C@H]1C(=O)NC1=CC=NC2=CC=C(OC)N=C21 CYHZYFWBZFKFHI-RVZJWNSFSA-N 0.000 claims 1
- JRCHTIOVCDZDOL-QQGDVQBRSA-N (1r,3r,4r)-n-(6,8-difluoroquinolin-4-yl)-3-hydroxy-4-[(3-oxo-4h-pyrido[3,2-b][1,4]thiazin-6-yl)methylamino]cyclohexane-1-carboxamide Chemical compound C1=C(F)C=C2C(NC(=O)[C@H]3C[C@H]([C@@H](CC3)NCC=3N=C4NC(=O)CSC4=CC=3)O)=CC=NC2=C1F JRCHTIOVCDZDOL-QQGDVQBRSA-N 0.000 claims 1
- BOPUCGGDXLOLLU-RFUYNDQBSA-N (1s,3s,4s)-3-hydroxy-n-(6-methoxy-1,5-naphthyridin-4-yl)-4-[(2-oxo-1h-pyrido[3,4-b][1,4]oxazin-7-yl)methylamino]cyclohexane-1-carboxamide Chemical compound N1C(=O)COC(C=N2)=C1C=C2CN[C@H]([C@@H](O)C1)CC[C@@H]1C(=O)NC1=CC=NC2=CC=C(OC)N=C21 BOPUCGGDXLOLLU-RFUYNDQBSA-N 0.000 claims 1
- DQAOVLVVHPRDAI-YEWDVWPNSA-N (1s,3s,4s)-3-hydroxy-n-(6-methoxy-1,5-naphthyridin-4-yl)-4-[(6-oxo-5h-pyridazino[3,4-b][1,4]thiazin-3-yl)methylamino]cyclohexane-1-carboxamide Chemical compound N1C(=O)CSC(N=N2)=C1C=C2CN[C@H]([C@@H](O)C1)CC[C@@H]1C(=O)NC1=CC=NC2=CC=C(OC)N=C21 DQAOVLVVHPRDAI-YEWDVWPNSA-N 0.000 claims 1
- TVHALYRBKNFFTC-FTRWYGJKSA-N (1s,3s,4s)-3-hydroxy-n-(6-methoxy-1,5-naphthyridin-4-yl)-4-[(7-methyl-3,4-dihydro-2h-pyrido[3,2-b][1,4]thiazin-6-yl)methylamino]cyclohexane-1-carboxamide Chemical compound N1CCSC(C=C2C)=C1N=C2CN[C@H]([C@@H](O)C1)CC[C@@H]1C(=O)NC1=CC=NC2=CC=C(OC)N=C21 TVHALYRBKNFFTC-FTRWYGJKSA-N 0.000 claims 1
- UFKFMBOQSFSOAP-YEWDVWPNSA-N (1s,3s,4s)-4-[(7-chloro-3-oxo-4h-pyrido[3,2-b][1,4]thiazin-6-yl)methylamino]-3-hydroxy-n-(6-methoxy-1,5-naphthyridin-4-yl)cyclohexane-1-carboxamide Chemical compound N1C(=O)CSC(C=C2Cl)=C1N=C2CN[C@H]([C@@H](O)C1)CC[C@@H]1C(=O)NC1=CC=NC2=CC=C(OC)N=C21 UFKFMBOQSFSOAP-YEWDVWPNSA-N 0.000 claims 1
- CYHZYFWBZFKFHI-YEWDVWPNSA-N (1s,3s,4s)-4-[(7-fluoro-3-oxo-4h-pyrido[3,2-b][1,4]thiazin-6-yl)methylamino]-3-hydroxy-n-(6-methoxy-1,5-naphthyridin-4-yl)cyclohexane-1-carboxamide Chemical compound N1C(=O)CSC(C=C2F)=C1N=C2CN[C@H]([C@@H](O)C1)CC[C@@H]1C(=O)NC1=CC=NC2=CC=C(OC)N=C21 CYHZYFWBZFKFHI-YEWDVWPNSA-N 0.000 claims 1
- JRCHTIOVCDZDOL-NXXSPTCGSA-N (1s,3s,4s)-n-(6,8-difluoroquinolin-4-yl)-3-hydroxy-4-[(3-oxo-4h-pyrido[3,2-b][1,4]thiazin-6-yl)methylamino]cyclohexane-1-carboxamide Chemical compound C1=C(F)C=C2C(NC(=O)[C@@H]3C[C@@H]([C@H](CC3)NCC=3N=C4NC(=O)CSC4=CC=3)O)=CC=NC2=C1F JRCHTIOVCDZDOL-NXXSPTCGSA-N 0.000 claims 1
- UDQAHFTWCBMBAL-UHFFFAOYSA-N 6,8-difluoroquinolin-4-amine Chemical compound C1=C(F)C=C2C(N)=CC=NC2=C1F UDQAHFTWCBMBAL-UHFFFAOYSA-N 0.000 claims 1
- XHJAYRSUYPCMGM-UHFFFAOYSA-N 6-(2-methoxyethoxy)-1,5-naphthyridin-4-amine Chemical compound N1=CC=C(N)C2=NC(OCCOC)=CC=C21 XHJAYRSUYPCMGM-UHFFFAOYSA-N 0.000 claims 1
- PMEDPIYDZJCMMZ-UHFFFAOYSA-N 6-[[[4-hydroxy-4-[2-(6-methoxy-1,5-naphthyridin-4-yl)ethyl]cyclohexyl]amino]methyl]-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound O1CC(=O)NC2=NC(CNC3CCC(CC3)(O)CCC3=CC=NC4=CC=C(N=C43)OC)=CC=C21 PMEDPIYDZJCMMZ-UHFFFAOYSA-N 0.000 claims 1
- KLSTXOBNGOBMHF-JCNLHEQBSA-N C1=CC(O)=C2C(=O)NC(CN[C@H]3CC[C@@H](CC3)C(=O)NC3=CC=NC4=CC=C(N=C43)OC)=CC2=C1 Chemical compound C1=CC(O)=C2C(=O)NC(CN[C@H]3CC[C@@H](CC3)C(=O)NC3=CC=NC4=CC=C(N=C43)OC)=CC2=C1 KLSTXOBNGOBMHF-JCNLHEQBSA-N 0.000 claims 1
- YAIJZMMUWSFXQD-QAQDUYKDSA-N C1=CC2=NSN=C2C=C1CN[C@H](CC1)CC[C@@H]1C(=O)NC1=CC=NC2=CC=C(OC)C=C21 Chemical compound C1=CC2=NSN=C2C=C1CN[C@H](CC1)CC[C@@H]1C(=O)NC1=CC=NC2=CC=C(OC)C=C21 YAIJZMMUWSFXQD-QAQDUYKDSA-N 0.000 claims 1
- WTLYHEBGJJAVMZ-WKILWMFISA-N C1=CC2=NSN=C2C=C1CN[C@H](CC1)CC[C@@H]1C(=O)NC1=CC=NC2=CC=C(OC)N=C21 Chemical compound C1=CC2=NSN=C2C=C1CN[C@H](CC1)CC[C@@H]1C(=O)NC1=CC=NC2=CC=C(OC)N=C21 WTLYHEBGJJAVMZ-WKILWMFISA-N 0.000 claims 1
- VSNSMACOFUVZJV-QAQDUYKDSA-N C1=CC=CC2=NC(CN[C@H]3CC[C@@H](CC3)C(=O)NC3=CC=NC4=CC=C(N=C43)OC)=CC(=O)N21 Chemical compound C1=CC=CC2=NC(CN[C@H]3CC[C@@H](CC3)C(=O)NC3=CC=NC4=CC=C(N=C43)OC)=CC(=O)N21 VSNSMACOFUVZJV-QAQDUYKDSA-N 0.000 claims 1
- CFBZHYHIGXNJHA-JCNLHEQBSA-N C1=CN=C2NC(CN[C@H]3CC[C@@H](CC3)C(=O)NC3=CC=NC4=CC=C(N=C43)OC)=CC2=C1 Chemical compound C1=CN=C2NC(CN[C@H]3CC[C@@H](CC3)C(=O)NC3=CC=NC4=CC=C(N=C43)OC)=CC2=C1 CFBZHYHIGXNJHA-JCNLHEQBSA-N 0.000 claims 1
- KMOIDLZGUMVZAI-HAQNSBGRSA-N C1C[C@@H](C(=O)O)CC[C@@H]1NCC1=CC=C(SC=N2)C2=C1 Chemical compound C1C[C@@H](C(=O)O)CC[C@@H]1NCC1=CC=C(SC=N2)C2=C1 KMOIDLZGUMVZAI-HAQNSBGRSA-N 0.000 claims 1
- RONNYFTVWCSTTR-WKILWMFISA-N COC=1N=C2C(=CC=NC2=CC1)NC(=O)[C@@H]1CC[C@H](CC1)NCC=1C=CC2=C(N=NS2)C1 Chemical compound COC=1N=C2C(=CC=NC2=CC1)NC(=O)[C@@H]1CC[C@H](CC1)NCC=1C=CC2=C(N=NS2)C1 RONNYFTVWCSTTR-WKILWMFISA-N 0.000 claims 1
- VUWIHBMHDCCKDK-KESTWPANSA-N COc1ccc2nccc(C(=O)C[C@H]3CC[C@@H](CC3)NCc3ccc4OCCOc4c3)c2c1 Chemical compound COc1ccc2nccc(C(=O)C[C@H]3CC[C@@H](CC3)NCc3ccc4OCCOc4c3)c2c1 VUWIHBMHDCCKDK-KESTWPANSA-N 0.000 claims 1
- KXTMYJBJTDOVIC-NUDRXGSASA-N COc1ccc2nccc(C(O)C[C@H]3CC[C@@H](CC3)NCc3ccc4OCCOc4c3)c2c1 Chemical compound COc1ccc2nccc(C(O)C[C@H]3CC[C@@H](CC3)NCc3ccc4OCCOc4c3)c2c1 KXTMYJBJTDOVIC-NUDRXGSASA-N 0.000 claims 1
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- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004551 isoquinolin-3-yl group Chemical group C1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- BEJNERDRQOWKJM-UHFFFAOYSA-N kojic acid Chemical compound OCC1=CC(=O)C(O)=CO1 BEJNERDRQOWKJM-UHFFFAOYSA-N 0.000 description 1
- 229960004705 kojic acid Drugs 0.000 description 1
- WZNJWVWKTVETCG-UHFFFAOYSA-N kojic acid Natural products OC(=O)C(N)CN1C=CC(=O)C(O)=C1 WZNJWVWKTVETCG-UHFFFAOYSA-N 0.000 description 1
- 125000000686 lactone group Chemical group 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000010410 layer 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
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- MHCFAGZWMAWTNR-UHFFFAOYSA-M lithium perchlorate Chemical compound [Li+].[O-]Cl(=O)(=O)=O MHCFAGZWMAWTNR-UHFFFAOYSA-M 0.000 description 1
- 229910001486 lithium perchlorate Inorganic materials 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- PPNAOCWZXJOHFK-UHFFFAOYSA-N manganese(2+);oxygen(2-) Chemical compound [O-2].[Mn+2] PPNAOCWZXJOHFK-UHFFFAOYSA-N 0.000 description 1
- VASIZKWUTCETSD-UHFFFAOYSA-N manganese(II) oxide Inorganic materials [Mn]=O VASIZKWUTCETSD-UHFFFAOYSA-N 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- HWOQCGSIDCQVRM-UHFFFAOYSA-N methyl 1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C1=CN=C2NC(C(=O)OC)=CC2=C1 HWOQCGSIDCQVRM-UHFFFAOYSA-N 0.000 description 1
- QABLOFMHHSOFRJ-UHFFFAOYSA-N methyl 2-chloroacetate Chemical compound COC(=O)CCl QABLOFMHHSOFRJ-UHFFFAOYSA-N 0.000 description 1
- NUYQDKMFCYCSAG-UHFFFAOYSA-N methyl 2-oxo-1h-pyrido[2,3-b][1,4]oxazine-7-carboxylate Chemical compound O1CC(=O)NC2=CC(C(=O)OC)=CN=C21 NUYQDKMFCYCSAG-UHFFFAOYSA-N 0.000 description 1
- HVFSNKWAUPKWPC-UHFFFAOYSA-N methyl 2-oxo-1h-pyrido[2,3-b][1,4]thiazine-7-carboxylate Chemical compound S1CC(=O)NC2=CC(C(=O)OC)=CN=C21 HVFSNKWAUPKWPC-UHFFFAOYSA-N 0.000 description 1
- UFSVRHNRNVVBJR-UHFFFAOYSA-N methyl 3-oxo-4h-1,4-benzothiazine-6-carboxylate Chemical compound S1CC(=O)NC2=CC(C(=O)OC)=CC=C21 UFSVRHNRNVVBJR-UHFFFAOYSA-N 0.000 description 1
- UIAHQILQYROVCF-UHFFFAOYSA-N methyl 3-oxo-4h-pyrido[3,2-b][1,4]thiazine-6-carboxylate Chemical compound S1CC(=O)NC2=NC(C(=O)OC)=CC=C21 UIAHQILQYROVCF-UHFFFAOYSA-N 0.000 description 1
- NGPXWAVPBFAMSB-UHFFFAOYSA-N methyl 6-(2-ethoxy-2-oxoethoxy)-5-nitropyridine-3-carboxylate Chemical compound CCOC(=O)COC1=NC=C(C(=O)OC)C=C1[N+]([O-])=O NGPXWAVPBFAMSB-UHFFFAOYSA-N 0.000 description 1
- YJUKTIBOUBUOJH-UHFFFAOYSA-N methyl 6-amino-3-bromopyridine-2-carboxylate Chemical compound COC(=O)C1=NC(N)=CC=C1Br YJUKTIBOUBUOJH-UHFFFAOYSA-N 0.000 description 1
- NQBKWYATWFBKLZ-UHFFFAOYSA-N methyl 6-amino-5-(3-ethoxy-3-oxopropyl)pyridine-2-carboxylate Chemical compound CCOC(=O)CCC1=CC=C(C(=O)OC)N=C1N NQBKWYATWFBKLZ-UHFFFAOYSA-N 0.000 description 1
- JPBDKSNTZAWJHR-FNORWQNLSA-N methyl 6-amino-5-[(e)-3-ethoxy-3-oxoprop-1-enyl]pyridine-2-carboxylate Chemical compound CCOC(=O)\C=C\C1=CC=C(C(=O)OC)N=C1N JPBDKSNTZAWJHR-FNORWQNLSA-N 0.000 description 1
- WRVXVTUGOFOAIW-UHFFFAOYSA-N methyl 6-amino-5-bromo-3-chloropyridine-2-carboxylate Chemical compound COC(=O)C1=NC(N)=C(Br)C=C1Cl WRVXVTUGOFOAIW-UHFFFAOYSA-N 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
- SYDZNYACMNJDDT-UHFFFAOYSA-N methyl 7-bromo-3-oxo-4h-pyrido[3,2-b][1,4]thiazine-6-carboxylate Chemical compound N1C(=O)CSC2=C1N=C(C(=O)OC)C(Br)=C2 SYDZNYACMNJDDT-UHFFFAOYSA-N 0.000 description 1
- AFIHSFFRLJYZAX-UHFFFAOYSA-N methyl 7-chloro-3-oxo-4h-pyrido[3,2-b][1,4]thiazine-6-carboxylate Chemical compound N1C(=O)CSC2=C1N=C(C(=O)OC)C(Cl)=C2 AFIHSFFRLJYZAX-UHFFFAOYSA-N 0.000 description 1
- YIMJWMNJTWDJJD-UHFFFAOYSA-N methyl [1,3]thiazolo[5,4-b]pyridine-6-carboxylate Chemical compound COC(=O)C1=CN=C2SC=NC2=C1 YIMJWMNJTWDJJD-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
- SGMGASBLEOSDMW-UHFFFAOYSA-N methyl thiadiazolo[5,4-b]pyridine-6-carboxylate Chemical compound COC(=O)C1=CN=C2SN=NC2=C1 SGMGASBLEOSDMW-UHFFFAOYSA-N 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- KGPQKNJSZNXOPV-UHFFFAOYSA-N moniliformin Chemical group OC1=CC(=O)C1=O KGPQKNJSZNXOPV-UHFFFAOYSA-N 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 1
- 239000012452 mother liquor Substances 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
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 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
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 150000005054 naphthyridines Chemical class 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 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
- 238000005580 one pot reaction Methods 0.000 description 1
- 229940006093 opthalmologic coloring agent diagnostic Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 239000012285 osmium tetroxide Substances 0.000 description 1
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 150000004893 oxazines Chemical class 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 238000005949 ozonolysis reaction Methods 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 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
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 125000005633 phthalidyl group Chemical group 0.000 description 1
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 1
- CUQOHAYJWVTKDE-UHFFFAOYSA-N potassium;butan-1-olate Chemical compound [K+].CCCC[O-] CUQOHAYJWVTKDE-UHFFFAOYSA-N 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 235000013772 propylene glycol 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
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 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
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000004526 pyridazin-2-yl group Chemical group N1N(C=CC=C1)* 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 125000004260 quinazolin-2-yl group Chemical group [H]C1=NC(*)=NC2=C1C([H])=C([H])C([H])=C2[H] 0.000 description 1
- 125000004159 quinolin-2-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C([H])C(*)=NC2=C1[H] 0.000 description 1
- 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 description 1
- GPPZVGNHXBJPRM-UHFFFAOYSA-N quinolin-4-one Chemical compound C1=CC=C2C(=O)C=C=NC2=C1 GPPZVGNHXBJPRM-UHFFFAOYSA-N 0.000 description 1
- 239000011369 resultant mixture Substances 0.000 description 1
- 229910052701 rubidium Inorganic materials 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 239000012363 selectfluor Substances 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229940048181 sodium sulfide nonahydrate Drugs 0.000 description 1
- WMDLZMCDBSJMTM-UHFFFAOYSA-M sodium;sulfanide;nonahydrate Chemical compound O.O.O.O.O.O.O.O.O.[Na+].[SH-] WMDLZMCDBSJMTM-UHFFFAOYSA-M 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 238000000638 solvent extraction Methods 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
- 241000894007 species Species 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
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- 230000000707 stereoselective effect Effects 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 150000003440 styrenes Chemical class 0.000 description 1
- 125000005415 substituted alkoxy group Chemical group 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 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
- 238000010189 synthetic method Methods 0.000 description 1
- 239000002278 tabletting lubricant Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- GOKOJYFPGZIEBM-UHFFFAOYSA-N tert-butyl n-[4-[(6-methoxy-1,5-naphthyridin-4-yl)carbamoyl]cyclohexyl]carbamate Chemical compound C12=NC(OC)=CC=C2N=CC=C1NC(=O)C1CCC(NC(=O)OC(C)(C)C)CC1 GOKOJYFPGZIEBM-UHFFFAOYSA-N 0.000 description 1
- 150000003509 tertiary alcohols Chemical class 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
- OSBSFAARYOCBHB-UHFFFAOYSA-N tetrapropylammonium Chemical compound CCC[N+](CCC)(CCC)CCC OSBSFAARYOCBHB-UHFFFAOYSA-N 0.000 description 1
- XJPANWOKBWZVHC-UHFFFAOYSA-N tetrazol-2-amine Chemical compound NN1N=CN=N1 XJPANWOKBWZVHC-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- LGXDAWAHSVHYCG-UHFFFAOYSA-N thiadiazolo[5,4-b]pyridine-6-carbaldehyde Chemical compound O=CC1=CN=C2SN=NC2=C1 LGXDAWAHSVHYCG-UHFFFAOYSA-N 0.000 description 1
- YFRBFGUUUDQBMZ-UHFFFAOYSA-N thiadiazolo[5,4-b]pyridine-6-carboxylic acid Chemical compound OC(=O)C1=CN=C2SN=NC2=C1 YFRBFGUUUDQBMZ-UHFFFAOYSA-N 0.000 description 1
- 150000004897 thiazines Chemical class 0.000 description 1
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000759 toxicological effect Toxicity 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 125000001425 triazolyl group Chemical group 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
- AHZJKOKFZJYCLG-UHFFFAOYSA-K trifluoromethanesulfonate;ytterbium(3+) Chemical compound [Yb+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F AHZJKOKFZJYCLG-UHFFFAOYSA-K 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- PGAJYUDRKAPMPA-UHFFFAOYSA-N trimethylsilyl n-ethylcarbamate Chemical compound CCNC(=O)O[Si](C)(C)C PGAJYUDRKAPMPA-UHFFFAOYSA-N 0.000 description 1
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
- VFJYIHQDILEQNR-UHFFFAOYSA-M trimethylsulfanium;iodide Chemical compound [I-].C[S+](C)C VFJYIHQDILEQNR-UHFFFAOYSA-M 0.000 description 1
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 150000003751 zinc Chemical class 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
- C07D401/12—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
-
- 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
-
- 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
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
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- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
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Applications Claiming Priority (3)
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| GB0112834.7 | 2001-05-25 | ||
| GBGB0112834.7A GB0112834D0 (en) | 2001-05-25 | 2001-05-25 | Medicaments |
| PCT/EP2002/005708 WO2003087098A1 (en) | 2001-05-25 | 2002-05-24 | Nitrogen-containing bicyclic heterocycles for use as antibacterials |
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| CA2448525A1 true CA2448525A1 (en) | 2003-10-23 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002448525A Abandoned CA2448525A1 (en) | 2001-05-25 | 2002-05-24 | Nitrogen-containing bicyclic heterocycles for use as antibacterials |
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| US7109213B2 (en) | 2002-01-29 | 2006-09-19 | Glaxo Group Limited | Aminopiperidine compounds, process for their preparation, and pharmaceutical compositions containing them |
| US6818772B2 (en) * | 2002-02-22 | 2004-11-16 | Abbott Laboratories | Antagonists of melanin concentrating hormone effects on the melanin concentrating hormone receptor |
| TW200406413A (en) * | 2002-06-26 | 2004-05-01 | Glaxo Group Ltd | Compounds |
| FR2844270B1 (fr) | 2002-09-11 | 2006-05-19 | Aventis Pharma Sa | Derives de la quinolyl propyl piperidine, leur procede et intermediaires de preparation et les compositions qui les contiennent |
| FR2844268B1 (fr) | 2002-09-11 | 2004-10-22 | Aventis Pharma Sa | Derives de la quinolyl propyl piperidine, leurs procedes et intermediaires de preparation et les compositions qui les contiennent |
| ATE463494T1 (de) | 2002-10-10 | 2010-04-15 | Morphochem Ag Komb Chemie | Neue verbindungen mit antibakterieller aktivität |
| TW200427688A (en) * | 2002-12-18 | 2004-12-16 | Glaxo Group Ltd | Antibacterial agents |
| DE10316081A1 (de) | 2003-04-08 | 2004-10-21 | Morphochem AG Aktiengesellschaft für kombinatorische Chemie | Neue Verbindungen mit antibakterieller Aktivität |
-
2001
- 2001-05-25 GB GBGB0112834.7A patent/GB0112834D0/en not_active Ceased
-
2002
- 2002-05-23 AR ARP020101914A patent/AR038172A1/es not_active Application Discontinuation
- 2002-05-23 TW TW091110839A patent/TWI232219B/zh not_active IP Right Cessation
- 2002-05-24 CA CA002448525A patent/CA2448525A1/en not_active Abandoned
- 2002-05-24 US US10/478,154 patent/US7141564B2/en not_active Expired - Fee Related
- 2002-05-24 CZ CZ20033202A patent/CZ20033202A3/cs unknown
- 2002-05-24 KR KR10-2003-7015379A patent/KR20040010654A/ko not_active Withdrawn
- 2002-05-24 WO PCT/EP2002/005708 patent/WO2003087098A1/en not_active Ceased
- 2002-05-24 ES ES02807202T patent/ES2298439T3/es not_active Expired - Lifetime
- 2002-05-24 DE DE60224039T patent/DE60224039T2/de not_active Expired - Lifetime
- 2002-05-24 EP EP02807202A patent/EP1399443B1/en not_active Expired - Lifetime
- 2002-05-24 CN CNA028146689A patent/CN1535272A/zh active Pending
- 2002-05-24 IL IL15886902A patent/IL158869A0/xx unknown
- 2002-05-24 AT AT02807202T patent/ATE380812T1/de not_active IP Right Cessation
- 2002-05-24 JP JP2003584054A patent/JP4463565B2/ja not_active Expired - Fee Related
- 2002-05-24 AU AU2002367697A patent/AU2002367697A1/en not_active Abandoned
- 2002-05-24 HU HU0400017A patent/HUP0400017A2/hu unknown
- 2002-05-24 PL PL02367079A patent/PL367079A1/xx not_active Application Discontinuation
- 2002-05-24 MX MXPA03010790A patent/MXPA03010790A/es unknown
- 2002-05-24 BR BR0210016-9A patent/BR0210016A/pt not_active IP Right Cessation
-
2003
- 2003-11-07 ZA ZA200308696A patent/ZA200308696B/en unknown
- 2003-11-18 CO CO03101671A patent/CO5540344A2/es not_active Application Discontinuation
- 2003-11-21 NO NO20035190A patent/NO20035190D0/no not_active Application Discontinuation
-
2006
- 2006-11-22 US US11/604,045 patent/US20070135422A1/en not_active Abandoned
-
2009
- 2009-11-13 JP JP2009259981A patent/JP2010031057A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| MXPA03010790A (es) | 2004-03-02 |
| US20040171620A1 (en) | 2004-09-02 |
| AR038172A1 (es) | 2005-01-05 |
| CN1535272A (zh) | 2004-10-06 |
| GB0112834D0 (en) | 2001-07-18 |
| CO5540344A2 (es) | 2005-07-29 |
| BR0210016A (pt) | 2004-06-15 |
| JP2010031057A (ja) | 2010-02-12 |
| TWI232219B (en) | 2005-05-11 |
| JP4463565B2 (ja) | 2010-05-19 |
| EP1399443B1 (en) | 2007-12-12 |
| ZA200308696B (en) | 2004-05-21 |
| ES2298439T3 (es) | 2008-05-16 |
| NO20035190D0 (no) | 2003-11-21 |
| AU2002367697A1 (en) | 2003-10-27 |
| JP2005519981A (ja) | 2005-07-07 |
| PL367079A1 (en) | 2005-02-21 |
| WO2003087098A1 (en) | 2003-10-23 |
| ATE380812T1 (de) | 2007-12-15 |
| CZ20033202A3 (cs) | 2004-08-18 |
| HUP0400017A2 (hu) | 2004-06-28 |
| EP1399443A1 (en) | 2004-03-24 |
| IL158869A0 (en) | 2004-05-12 |
| US20070135422A1 (en) | 2007-06-14 |
| DE60224039T2 (de) | 2008-11-27 |
| US7141564B2 (en) | 2006-11-28 |
| DE60224039D1 (de) | 2008-01-24 |
| KR20040010654A (ko) | 2004-01-31 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |