DE60221969T2 - Durch eine piperidin-enthaltende einheit an position 4 substituierte chinoline und deren stickstoff-enthaltende derivate und ihre verwendung als antibakterielle wirkstoffe - Google Patents

Info

Publication number

DE60221969T2

DE60221969T2 DE60221969T DE60221969T DE60221969T2 DE 60221969 T2 DE60221969 T2 DE 60221969T2 DE 60221969 T DE60221969 T DE 60221969T DE 60221969 T DE60221969 T DE 60221969T DE 60221969 T2 DE60221969 T2 DE 60221969T2

Authority

DE

Germany

Prior art keywords

alkyl

hydroxy

piperidin

optionally substituted

amino

Prior art date

2001-01-22

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 - Lifetime

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• 239000003242 anti bacterial agent Substances 0.000 title description 3
• 238000000034 method Methods 0.000 claims abstract description 130
• 241000124008 Mammalia Species 0.000 claims abstract description 6
• 208000035143 Bacterial infection Diseases 0.000 claims abstract description 5
• 208000022362 bacterial infectious disease Diseases 0.000 claims abstract description 5
• -1 amino, piperidyl Chemical group 0.000 claims description 217
• 150000001875 compounds Chemical class 0.000 claims description 176
• 125000000217 alkyl group Chemical group 0.000 claims description 151
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 109
• 229910052739 hydrogen Inorganic materials 0.000 claims description 53
• 230000008569 process Effects 0.000 claims description 43
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 40
• 239000001257 hydrogen Substances 0.000 claims description 37
• 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 36
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 36
• 125000003277 amino group Chemical group 0.000 claims description 34
• 150000003839 salts Chemical class 0.000 claims description 32
• 125000003118 aryl group Chemical group 0.000 claims description 31
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 31
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 31
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 28
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 28
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 28
• 150000003254 radicals Chemical class 0.000 claims description 28
• 125000005090 alkenylcarbonyl group Chemical group 0.000 claims description 27
• 125000005092 alkenyloxycarbonyl group Chemical group 0.000 claims description 26
• 229910052736 halogen Inorganic materials 0.000 claims description 26
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 26
• 150000002367 halogens Chemical class 0.000 claims description 25
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 21
• 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 21
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical group [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 19
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 19
• 125000000623 heterocyclic group Chemical group 0.000 claims description 19
• 125000004414 alkyl thio group Chemical group 0.000 claims description 18
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 18
• 229910052760 oxygen Inorganic materials 0.000 claims description 18
• 125000001424 substituent group Chemical group 0.000 claims description 18
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 17
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 16
• 125000005137 alkenylsulfonyl group Chemical group 0.000 claims description 16
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 16
• 125000002252 acyl group Chemical group 0.000 claims description 14
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
• 125000004429 atom Chemical group 0.000 claims description 12
• 229910002091 carbon monoxide Inorganic materials 0.000 claims description 12
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
• 238000002360 preparation method Methods 0.000 claims description 12
• 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 11
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 11
• 150000001204 N-oxides Chemical class 0.000 claims description 11
• 239000012453 solvate Substances 0.000 claims description 11
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
• IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims description 10
• RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 10
• 125000005843 halogen group Chemical group 0.000 claims description 10
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
• 229910052717 sulfur Inorganic materials 0.000 claims description 10
• 229910052727 yttrium Inorganic materials 0.000 claims description 10
• 229910052757 nitrogen Inorganic materials 0.000 claims description 9
• 229910052721 tungsten Inorganic materials 0.000 claims description 9
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 8
• 239000003814 drug Substances 0.000 claims description 8
• 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 8
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 7
• SZHYPQDQYNLZJP-UHFFFAOYSA-N 3-oxo-4h-pyrido[3,2-b][1,4]thiazine-6-carboxylic acid Chemical compound S1CC(=O)NC2=NC(C(=O)O)=CC=C21 SZHYPQDQYNLZJP-UHFFFAOYSA-N 0.000 claims description 7
• QLJMNDBZNCJZMV-UHFFFAOYSA-N 7-bromo-3-oxo-4h-pyrido[3,2-b][1,4]thiazine-6-carboxylic acid Chemical compound N1C(=O)CSC2=C1N=C(C(=O)O)C(Br)=C2 QLJMNDBZNCJZMV-UHFFFAOYSA-N 0.000 claims description 6
• 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 6
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 6
• 125000003396 thiol group Chemical class [H]S* 0.000 claims description 6
• 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 claims description 6
• 125000001414 1,2,4-triazol-5-yl group Chemical group [H]N1N=C([H])N=C1[*] 0.000 claims description 5
• 125000004423 acyloxy group Chemical group 0.000 claims description 5
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 5
• 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 5
• 229910052799 carbon Inorganic materials 0.000 claims description 5
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
• 239000001301 oxygen Substances 0.000 claims description 5
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 5
• 125000005035 acylthio group Chemical group 0.000 claims description 4
• 125000005842 heteroatom Chemical group 0.000 claims description 4
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 4
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 4
• FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 claims description 3
• QFSXNHZMFQOXHL-FQEVSTJZSA-N 7-[[[1-[(2r)-2-hydroxy-2-(6-methoxy-1,5-naphthyridin-4-yl)ethyl]piperidin-4-yl]amino]methyl]-1h-pyrido[3,4-b][1,4]thiazin-2-one Chemical compound N1C(=O)CSC(C=N2)=C1C=C2CNC(CC1)CCN1C[C@H](O)C1=CC=NC2=CC=C(OC)N=C21 QFSXNHZMFQOXHL-FQEVSTJZSA-N 0.000 claims description 3
• SHVJDPNOVPQBCL-IBGZPJMESA-N 7-bromo-6-[[[1-[(2r)-2-hydroxy-2-(6-methoxy-1,5-naphthyridin-4-yl)ethyl]piperidin-4-yl]amino]methyl]-4h-pyrido[3,2-b][1,4]thiazin-3-one Chemical compound N1C(=O)CSC(C=C2Br)=C1N=C2CNC(CC1)CCN1C[C@H](O)C1=CC=NC2=CC=C(OC)N=C21 SHVJDPNOVPQBCL-IBGZPJMESA-N 0.000 claims description 3
• 229940079593 drug Drugs 0.000 claims description 3
• 125000002883 imidazolyl group Chemical group 0.000 claims description 3
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
• LRKRSCBXNYHQPM-QFIPXVFZSA-N (1r)-1-(6-methoxy-1,5-naphthyridin-4-yl)-2-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-ylmethylamino)piperidin-1-yl]ethanol Chemical compound C1CCNC2=NC(CNC3CCN(CC3)C[C@H](O)C3=CC=NC4=CC=C(N=C43)OC)=CC=C21 LRKRSCBXNYHQPM-QFIPXVFZSA-N 0.000 claims description 2
• YXGCEBKQJZAGQL-QHCPKHFHSA-N (1r)-2-[4-(1,3-benzodioxol-5-ylmethylamino)piperidin-1-yl]-1-(6-methoxyquinolin-4-yl)ethanol Chemical compound C1=C2OCOC2=CC(CNC2CCN(CC2)C[C@H](O)C2=CC=NC3=CC=C(C=C32)OC)=C1 YXGCEBKQJZAGQL-QHCPKHFHSA-N 0.000 claims description 2
• WZCJTDWSEDVQNY-DEOSSOPVSA-N (1r)-2-[4-(2,3-dihydro-1,4-benzodioxin-6-ylmethylamino)piperidin-1-yl]-1-(6-methoxyquinolin-4-yl)ethanol Chemical compound O1CCOC2=CC(CNC3CCN(CC3)C[C@H](O)C3=CC=NC4=CC=C(C=C43)OC)=CC=C21 WZCJTDWSEDVQNY-DEOSSOPVSA-N 0.000 claims description 2
• SIUXHCYRZKHSTR-QHCPKHFHSA-N (1r)-2-[4-(3,4-dihydro-2h-pyrido[3,2-b][1,4]thiazin-6-ylmethylamino)piperidin-1-yl]-1-(6-methoxyquinolin-4-yl)ethanol Chemical compound S1CCNC2=NC(CNC3CCN(CC3)C[C@H](O)C3=CC=NC4=CC=C(C=C43)OC)=CC=C21 SIUXHCYRZKHSTR-QHCPKHFHSA-N 0.000 claims description 2
• OWQNDGWKMBNZOX-NRFANRHFSA-N (1r)-2-[4-[(6-fluoro-2,3-dihydro-1,4-benzodioxin-7-yl)methylamino]piperidin-1-yl]-1-(6-methoxy-1,5-naphthyridin-4-yl)ethanol Chemical compound O1CCOC(C=C2F)=C1C=C2CNC(CC1)CCN1C[C@H](O)C1=CC=NC2=CC=C(OC)N=C21 OWQNDGWKMBNZOX-NRFANRHFSA-N 0.000 claims description 2
• JECYNCQXXKQDJN-UHFFFAOYSA-N 2-(2-methylhexan-2-yloxymethyl)oxirane Chemical group CCCCC(C)(C)OCC1CO1 JECYNCQXXKQDJN-UHFFFAOYSA-N 0.000 claims description 2
• OHDMXSQSXYADHZ-NRFANRHFSA-N 6-[[[1-[(2r)-2-hydroxy-2-(6-methoxy-1,5-naphthyridin-4-yl)ethyl]piperidin-4-yl]amino]methyl]-4h-1,4-benzoxazin-3-one Chemical compound O1CC(=O)NC2=CC(CNC3CCN(CC3)C[C@H](O)C3=CC=NC4=CC=C(N=C43)OC)=CC=C21 OHDMXSQSXYADHZ-NRFANRHFSA-N 0.000 claims description 2
• UBMVVMILAXGUEA-IBGZPJMESA-N 6-[[[1-[(2r)-2-hydroxy-2-(6-methoxy-1,5-naphthyridin-4-yl)ethyl]piperidin-4-yl]amino]methyl]-4h-pyrido[3,2-b][1,4]thiazin-3-one Chemical compound S1CC(=O)NC2=NC(CNC3CCN(CC3)C[C@H](O)C3=CC=NC4=CC=C(N=C43)OC)=CC=C21 UBMVVMILAXGUEA-IBGZPJMESA-N 0.000 claims description 2
• JBXWVEMLTDXSCR-DEOSSOPVSA-N 6-[[[1-[(2r)-2-hydroxy-2-(6-methoxyquinolin-4-yl)ethyl]piperidin-4-yl]amino]methyl]-4h-1,4-benzothiazin-3-one Chemical compound S1CC(=O)NC2=CC(CNC3CCN(CC3)C[C@H](O)C3=CC=NC4=CC=C(C=C43)OC)=CC=C21 JBXWVEMLTDXSCR-DEOSSOPVSA-N 0.000 claims description 2
• ZSFFWCNXJDGECL-DEOSSOPVSA-N 6-[[[1-[(2r)-2-hydroxy-2-(6-methoxyquinolin-4-yl)ethyl]piperidin-4-yl]amino]methyl]-4h-1,4-benzoxazin-3-one Chemical compound O1CC(=O)NC2=CC(CNC3CCN(CC3)C[C@H](O)C3=CC=NC4=CC=C(C=C43)OC)=CC=C21 ZSFFWCNXJDGECL-DEOSSOPVSA-N 0.000 claims description 2
• HIXTTZIJAWUHCI-FQEVSTJZSA-N 7-[[[1-[(2r)-2-hydroxy-2-(6-methoxy-1,5-naphthyridin-4-yl)ethyl]piperidin-4-yl]amino]methyl]-1h-pyrido[2,3-b][1,4]thiazin-2-one Chemical compound S1CC(=O)NC2=CC(CNC3CCN(CC3)C[C@H](O)C3=CC=NC4=CC=C(N=C43)OC)=CN=C21 HIXTTZIJAWUHCI-FQEVSTJZSA-N 0.000 claims description 2
• JAJVSMJTXIDLRT-DEOSSOPVSA-N 7-fluoro-6-[[[1-[(2r)-2-hydroxy-2-(6-methoxyquinolin-4-yl)ethyl]piperidin-4-yl]amino]methyl]-4h-1,4-benzoxazin-3-one Chemical compound N1C(=O)COC(C=C2F)=C1C=C2CNC(CC1)CCN1C[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 JAJVSMJTXIDLRT-DEOSSOPVSA-N 0.000 claims description 2
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
• 125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 2
• 125000005360 alkyl sulfoxide group Chemical group 0.000 claims description 2
• 125000006615 aromatic heterocyclic 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
• 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
• 125000002527 bicyclic carbocyclic group Chemical group 0.000 claims description 2
• 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 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
• 125000001624 naphthyl group Chemical group 0.000 claims description 2
• 239000008194 pharmaceutical composition Substances 0.000 claims description 2
• 125000006413 ring segment Chemical group 0.000 claims description 2
• 125000003107 substituted aryl group Chemical group 0.000 claims description 2
• 239000011593 sulfur Substances 0.000 claims description 2
• RBBMMMJYPLTDJJ-VWLOTQADSA-N (1r)-1-(6-methoxyquinolin-4-yl)-2-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-ylmethylamino)piperidin-1-yl]ethanol Chemical compound C1CCNC2=NC(CNC3CCN(CC3)C[C@H](O)C3=CC=NC4=CC=C(C=C43)OC)=CC=C21 RBBMMMJYPLTDJJ-VWLOTQADSA-N 0.000 claims 1
• AKVZCTPKTKXUFZ-QHCPKHFHSA-N (1r)-1-(6-methoxyquinolin-4-yl)-2-[4-[(6-nitro-1,3-benzodioxol-5-yl)methylamino]piperidin-1-yl]ethanol Chemical compound C([C@H](O)C1=CC=NC2=CC=C(C=C21)OC)N(CC1)CCC1NCC(C(=C1)[N+]([O-])=O)=CC2=C1OCO2 AKVZCTPKTKXUFZ-QHCPKHFHSA-N 0.000 claims 1
• CIYIYWQDQTXPMR-DEOSSOPVSA-N (1r)-2-[4-(2,3-dihydro-1h-pyrido[2,3-b][1,4]thiazin-7-ylmethylamino)piperidin-1-yl]-1-(6-methoxyquinolin-4-yl)ethanol Chemical compound S1CCNC2=CC(CNC3CCN(CC3)C[C@H](O)C3=CC=NC4=CC=C(C=C43)OC)=CN=C21 CIYIYWQDQTXPMR-DEOSSOPVSA-N 0.000 claims 1
• IQTIWIZDWUXWDH-QHCPKHFHSA-N (1r)-2-[4-(2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-6-ylmethylamino)piperidin-1-yl]-1-(6-methoxyquinolin-4-yl)ethanol Chemical compound O1CCOC2=NC(CNC3CCN(CC3)C[C@H](O)C3=CC=NC4=CC=C(C=C43)OC)=CC=C21 IQTIWIZDWUXWDH-QHCPKHFHSA-N 0.000 claims 1
• UQKCHSYMXQWFMW-QHCPKHFHSA-N (1r)-2-[4-[(6-chloro-1,3-benzodioxol-5-yl)methylamino]piperidin-1-yl]-1-(6-methoxyquinolin-4-yl)ethanol Chemical compound C([C@H](O)C1=CC=NC2=CC=C(C=C21)OC)N(CC1)CCC1NCC(C(=C1)Cl)=CC2=C1OCO2 UQKCHSYMXQWFMW-QHCPKHFHSA-N 0.000 claims 1
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
• LAQYHRQFABOIFD-UHFFFAOYSA-N 2-methoxyhydroquinone Chemical compound COC1=CC(O)=CC=C1O LAQYHRQFABOIFD-UHFFFAOYSA-N 0.000 claims 1
• GAGAICHLGQDUTL-UHFFFAOYSA-N 4h-thiazin-3-one Chemical compound O=C1CC=CSN1 GAGAICHLGQDUTL-UHFFFAOYSA-N 0.000 claims 1
• WFPGYFRYIRNCNS-DEOSSOPVSA-N 5-fluoro-6-[[[1-[(2r)-2-hydroxy-2-(6-methoxyquinolin-4-yl)ethyl]piperidin-4-yl]amino]methyl]-3-methyl-1,3-benzoxazol-2-one Chemical compound C([C@H](O)C1=CC=NC2=CC=C(C=C21)OC)N(CC1)CCC1NCC(C(=C1)F)=CC2=C1N(C)C(=O)O2 WFPGYFRYIRNCNS-DEOSSOPVSA-N 0.000 claims 1
• OPAAZANXDHQVPI-NRFANRHFSA-N 6-[[[1-[(2r)-2-hydroxy-2-(6-methoxy-1,5-naphthyridin-4-yl)ethyl]piperidin-4-yl]amino]methyl]-4h-1,4-benzothiazin-3-one Chemical compound S1CC(=O)NC2=CC(CNC3CCN(CC3)C[C@H](O)C3=CC=NC4=CC=C(N=C43)OC)=CC=C21 OPAAZANXDHQVPI-NRFANRHFSA-N 0.000 claims 1
• JLAMMHGOVQRIBT-IBGZPJMESA-N 6-[[[1-[(2r)-2-hydroxy-2-(6-methoxy-1,5-naphthyridin-4-yl)ethyl]piperidin-4-yl]amino]methyl]-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound O1CC(=O)NC2=NC(CNC3CCN(CC3)C[C@H](O)C3=CC=NC4=CC=C(N=C43)OC)=CC=C21 JLAMMHGOVQRIBT-IBGZPJMESA-N 0.000 claims 1
• XOJAZZVOEWKCAZ-DEOSSOPVSA-N 6-[[[1-[(2r)-2-hydroxy-2-(6-methoxyquinolin-4-yl)ethyl]piperidin-4-yl]amino]methyl]-3-methyl-1,3-benzoxazol-2-one Chemical compound C1=C2N(C)C(=O)OC2=CC(CNC2CCN(CC2)C[C@H](O)C2=CC=NC3=CC=C(C=C32)OC)=C1 XOJAZZVOEWKCAZ-DEOSSOPVSA-N 0.000 claims 1
• GNWHDFGJPRKJTC-DEOSSOPVSA-N 6-[[[1-[(2r)-2-hydroxy-2-(6-methoxyquinolin-4-yl)ethyl]piperidin-4-yl]amino]methyl]-3-methyl-1,3-benzoxazole-2-thione Chemical compound C1=C2N(C)C(=S)OC2=CC(CNC2CCN(CC2)C[C@H](O)C2=CC=NC3=CC=C(C=C32)OC)=C1 GNWHDFGJPRKJTC-DEOSSOPVSA-N 0.000 claims 1
• QDTLTBXLSFBPEM-QFIPXVFZSA-N 6-[[[1-[(2r)-2-hydroxy-2-(6-methoxyquinolin-4-yl)ethyl]piperidin-4-yl]amino]methyl]-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound O1CC(=O)NC2=NC(CNC3CCN(CC3)C[C@H](O)C3=CC=NC4=CC=C(C=C43)OC)=CC=C21 QDTLTBXLSFBPEM-QFIPXVFZSA-N 0.000 claims 1
• ICNZKASFSKJTIH-DEOSSOPVSA-N 7-fluoro-6-[[[1-[(2r)-2-hydroxy-2-(6-methoxyquinolin-4-yl)ethyl]piperidin-4-yl]amino]methyl]-4h-1,4-benzothiazin-3-one Chemical compound N1C(=O)CSC(C=C2F)=C1C=C2CNC(CC1)CCN1C[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 ICNZKASFSKJTIH-DEOSSOPVSA-N 0.000 claims 1
• MWMMKZFAGJCOKL-NRFANRHFSA-N n-[1-[(2r)-2-hydroxy-2-(6-methoxy-1,5-naphthyridin-4-yl)ethyl]piperidin-4-yl]-4-oxo-3,5-dihydro-2h-1,5-benzothiazepine-7-sulfonamide Chemical compound S1CCC(=O)NC2=CC(S(=O)(=O)NC3CCN(CC3)C[C@H](O)C3=CC=NC4=CC=C(N=C43)OC)=CC=C21 MWMMKZFAGJCOKL-NRFANRHFSA-N 0.000 claims 1
• CBSYFDWHOUSOBP-QHCPKHFHSA-N n-[1-[(2r)-2-hydroxy-2-(6-methoxyquinolin-4-yl)ethyl]piperidin-4-yl]-2,3-dihydro-1,4-benzodioxine-6-carboxamide Chemical compound O1CCOC2=CC(C(=O)NC3CCN(CC3)C[C@H](O)C3=CC=NC4=CC=C(C=C43)OC)=CC=C21 CBSYFDWHOUSOBP-QHCPKHFHSA-N 0.000 claims 1
• UFMASMIVYIHNGW-QHCPKHFHSA-N n-[1-[(2r)-2-hydroxy-2-(6-methoxyquinolin-4-yl)ethyl]piperidin-4-yl]-3-oxo-4h-1,4-benzothiazine-6-sulfonamide Chemical compound S1CC(=O)NC2=CC(S(=O)(=O)NC3CCN(CC3)C[C@H](O)C3=CC=NC4=CC=C(C=C43)OC)=CC=C21 UFMASMIVYIHNGW-QHCPKHFHSA-N 0.000 claims 1
• AHPYIHIYYHWROA-NRFANRHFSA-N n-[1-[(2r)-2-hydroxy-2-(6-methoxyquinolin-4-yl)ethyl]piperidin-4-yl]-3-oxo-4h-pyrido[3,2-b][1,4]thiazine-6-carboxamide Chemical compound S1CC(=O)NC2=NC(C(=O)NC3CCN(CC3)C[C@H](O)C3=CC=NC4=CC=C(C=C43)OC)=CC=C21 AHPYIHIYYHWROA-NRFANRHFSA-N 0.000 claims 1
• 150000003053 piperidines Chemical class 0.000 abstract description 2
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 228
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 191
• 239000000243 solution Substances 0.000 description 189
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 184
• 239000007787 solid Substances 0.000 description 117
• 239000000203 mixture Substances 0.000 description 114
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