JP3959348B2 - 新規な非環式ヌクレオシドホスホネート誘導体、その塩および合成方法 - Google Patents

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Publication number

JP3959348B2

JP3959348B2 JP2002557964A JP2002557964A JP3959348B2 JP 3959348 B2 JP3959348 B2 JP 3959348B2 JP 2002557964 A JP2002557964 A JP 2002557964A JP 2002557964 A JP2002557964 A JP 2002557964A JP 3959348 B2 JP3959348 B2 JP 3959348B2

Authority

JP

Japan

Prior art keywords

methyl

compound

amino

oxy

purin

Prior art date

2001-01-19

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

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• 150000003839 salts Chemical class 0.000 title claims description 13
• VWFCHDSQECPREK-LURJTMIESA-N Cidofovir Chemical class NC=1C=CN(C[C@@H](CO)OCP(O)(O)=O)C(=O)N=1 VWFCHDSQECPREK-LURJTMIESA-N 0.000 title claims description 5
• 230000015572 biosynthetic process Effects 0.000 title description 87
• 238000003786 synthesis reaction Methods 0.000 title description 87
• 238000000034 method Methods 0.000 title description 15
• 150000001875 compounds Chemical class 0.000 claims description 403
• -1 hydroxy, amino Chemical group 0.000 claims description 209
• 238000004519 manufacturing process Methods 0.000 claims description 112
• YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 claims description 86
• 238000006243 chemical reaction Methods 0.000 claims description 72
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 44
• 229910052739 hydrogen Inorganic materials 0.000 claims description 41
• 239000001257 hydrogen Substances 0.000 claims description 41
• 125000003396 thiol group Chemical group [H]S* 0.000 claims description 32
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 23
• 150000002431 hydrogen Chemical class 0.000 claims description 22
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 19
• 229910052736 halogen Inorganic materials 0.000 claims description 16
• 150000002367 halogens Chemical class 0.000 claims description 16
• 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 15
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 13
• SHGVMNPGAPQLTG-UHFFFAOYSA-N 7-butylphosphanyl-2,2-dimethylheptanoic acid Chemical compound CCCCPCCCCCC(C)(C)C(O)=O SHGVMNPGAPQLTG-UHFFFAOYSA-N 0.000 claims description 12
• KDNSSKPZBDNJDF-UHFFFAOYSA-N [1-[(2-aminopurin-9-yl)methyl]cyclopropyl]oxymethylphosphonic acid Chemical compound C12=NC(N)=NC=C2N=CN1CC1(OCP(O)(O)=O)CC1 KDNSSKPZBDNJDF-UHFFFAOYSA-N 0.000 claims description 10
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 10
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
• 125000003545 alkoxy group Chemical group 0.000 claims description 8
• 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 claims description 8
• NNPIBIAFMRKGDS-UHFFFAOYSA-N 4-[[1-[(2-amino-6-oxo-1H-purin-9-yl)methyl]cyclopropyl]oxymethyl-(2,2-dimethylpropanoyloxymethoxy)phosphoryl]oxy-2,2-dimethylbutanoic acid Chemical compound C1=NC(C(N=C(N)N2)=O)=C2N1CC1(OCP(=O)(OCOC(=O)C(C)(C)C)OCCC(C)(C)C(O)=O)CC1 NNPIBIAFMRKGDS-UHFFFAOYSA-N 0.000 claims description 7
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 7
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 7
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 7
• 239000011737 fluorine Substances 0.000 claims description 7
• 229910052731 fluorine Inorganic materials 0.000 claims description 7
• NNQNNHMEFBBMJY-UHFFFAOYSA-N 2-[1-[(2-amino-6-oxo-3h-purin-9-yl)methyl]cyclopropyl]ethylphosphonic acid Chemical compound C12=NC(N)=NC(O)=C2N=CN1CC1(CCP(O)(O)=O)CC1 NNQNNHMEFBBMJY-UHFFFAOYSA-N 0.000 claims description 6
• HJGDZNIKQVIHLM-UHFFFAOYSA-N 2-[1-[(2-aminopurin-9-yl)methyl]cyclopropyl]propylphosphonic acid Chemical compound C1=NC2=CN=C(N)N=C2N1CC1(C(CP(O)(O)=O)C)CC1 HJGDZNIKQVIHLM-UHFFFAOYSA-N 0.000 claims description 6
• SOZWOLUYZONMNT-UHFFFAOYSA-N 2-[1-[(6-aminopurin-9-yl)methyl]cyclopropyl]ethylphosphonic acid Chemical compound C1=NC=2C(N)=NC=NC=2N1CC1(CCP(O)(O)=O)CC1 SOZWOLUYZONMNT-UHFFFAOYSA-N 0.000 claims description 6
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 6
• YCEKSNOJSIKTBV-UHFFFAOYSA-N 4-[[1-[(2-amino-6-chloropurin-9-yl)methyl]cyclopropyl]oxymethyl-(2,2-dimethylpropanoyloxymethoxy)phosphoryl]oxy-2,2-dimethylbutanoic acid Chemical compound C1=NC2=C(Cl)N=C(N)N=C2N1CC1(OCP(=O)(OCOC(=O)C(C)(C)C)OCCC(C)(C)C(O)=O)CC1 YCEKSNOJSIKTBV-UHFFFAOYSA-N 0.000 claims description 6
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
• 125000001424 substituent group Chemical group 0.000 claims description 6
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 5
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 5
• GFWRXBKJRHHOBQ-UHFFFAOYSA-N [[1-[(2-aminopurin-9-yl)methyl]cyclopropyl]oxymethyl-(2-methylpropanoyloxymethoxy)phosphoryl]oxymethyl 2-methylpropanoate Chemical compound C1=NC2=CN=C(N)N=C2N1CC1(OCP(=O)(OCOC(=O)C(C)C)OCOC(=O)C(C)C)CC1 GFWRXBKJRHHOBQ-UHFFFAOYSA-N 0.000 claims description 5
• YQQZFOTZFRQHRK-UHFFFAOYSA-N [[1-[(2-aminopurin-9-yl)methyl]cyclopropyl]oxymethyl-(piperidine-1-carbonyloxymethoxy)phosphoryl]oxymethyl piperidine-1-carboxylate Chemical compound C12=NC(N)=NC=C2N=CN1CC1(OCP(=O)(OCOC(=O)N2CCCCC2)OCOC(=O)N2CCCCC2)CC1 YQQZFOTZFRQHRK-UHFFFAOYSA-N 0.000 claims description 5
• LBMGUBIXYLAHIP-UHFFFAOYSA-N [[1-[(2-aminopurin-9-yl)methyl]cyclopropyl]oxymethyl-(pyrrolidine-1-carbonyloxymethoxy)phosphoryl]oxymethyl pyrrolidine-1-carboxylate Chemical compound C12=NC(N)=NC=C2N=CN1CC1(OCP(=O)(OCOC(=O)N2CCCC2)OCOC(=O)N2CCCC2)CC1 LBMGUBIXYLAHIP-UHFFFAOYSA-N 0.000 claims description 5
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
• 208000002672 hepatitis B Diseases 0.000 claims description 5
• 125000005842 heteroatom Chemical group 0.000 claims description 5
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
• 229910052757 nitrogen Inorganic materials 0.000 claims description 5
• 229910052760 oxygen Inorganic materials 0.000 claims description 5
• 239000001301 oxygen Substances 0.000 claims description 5
• NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 claims description 4
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 4
• VUDVGFWLOQIDAI-UHFFFAOYSA-N 2-[1-[(2-amino-6-oxo-3h-purin-9-yl)methyl]cyclopropyl]propylphosphonic acid Chemical compound C1=NC2=C(O)N=C(N)N=C2N1CC1(C(CP(O)(O)=O)C)CC1 VUDVGFWLOQIDAI-UHFFFAOYSA-N 0.000 claims description 4
• ARKBKBKWZNRBNM-UHFFFAOYSA-N 2-[1-[[2-amino-6-(4-methylphenyl)sulfanylpurin-9-yl]methyl]cyclopropyl]ethylphosphonic acid Chemical compound C1=CC(C)=CC=C1SC1=NC(N)=NC2=C1N=CN2CC1(CCP(O)(O)=O)CC1 ARKBKBKWZNRBNM-UHFFFAOYSA-N 0.000 claims description 4
• BDEVHGQJJNGNOV-UHFFFAOYSA-N 4-[[1-[(2-aminopurin-9-yl)methyl]-2-methylcyclopropyl]oxymethyl-(2,2-dimethylpropanoyloxymethoxy)phosphoryl]oxy-2,2-dimethylbutanoic acid Chemical compound CC1CC1(OCP(=O)(OCCC(C)(C)C(O)=O)OCOC(=O)C(C)(C)C)CN1C2=NC(N)=NC=C2N=C1 BDEVHGQJJNGNOV-UHFFFAOYSA-N 0.000 claims description 4
• UIMKOFHPSGUNNQ-UHFFFAOYSA-N 4-[[1-[(6-aminopurin-9-yl)methyl]-2-methylcyclopropyl]oxymethyl-(2,2-dimethylpropanoyloxymethoxy)phosphoryl]oxy-2,2-dimethylbutanoic acid Chemical compound CC1CC1(OCP(=O)(OCCC(C)(C)C(O)=O)OCOC(=O)C(C)(C)C)CN1C2=NC=NC(N)=C2N=C1 UIMKOFHPSGUNNQ-UHFFFAOYSA-N 0.000 claims description 4
• DHYIHVGXVTVVIK-UHFFFAOYSA-N 4-[[1-[[2-amino-6-(4-methoxyphenyl)sulfanylpurin-9-yl]methyl]-2-methylcyclopropyl]oxymethyl-(2,2-dimethylpropanoyloxymethoxy)phosphoryl]oxy-2,2-dimethylbutanoic acid Chemical compound C1=CC(OC)=CC=C1SC1=NC(N)=NC2=C1N=CN2CC1(OCP(=O)(OCCC(C)(C)C(O)=O)OCOC(=O)C(C)(C)C)C(C)C1 DHYIHVGXVTVVIK-UHFFFAOYSA-N 0.000 claims description 4
• HLSAOBJQLYKMFM-UHFFFAOYSA-N 4-[[1-[[2-amino-6-(4-methoxyphenyl)sulfanylpurin-9-yl]methyl]cyclopropyl]oxymethyl-(2,2-dimethylpropanoyloxymethoxy)phosphoryl]oxy-2,2-dimethylbutanoic acid Chemical compound CC(C)(C)C(=O)OCOP(=O)(COC1(CC1)CN2C=NC3=C2N=C(N=C3SC4=CC=C(C=C4)OC)N)OCCC(C)(C)C(=O)O HLSAOBJQLYKMFM-UHFFFAOYSA-N 0.000 claims description 4
• DJYANLQPSGKNDM-UHFFFAOYSA-N C1CCC(C1)C(=O)OCOP(=O)(COC2(CC2)CN3C=NC4=C(N=CN=C43)N)OCC5(CCCC5)C(=O)O Chemical compound C1CCC(C1)C(=O)OCOP(=O)(COC2(CC2)CN3C=NC4=C(N=CN=C43)N)OCC5(CCCC5)C(=O)O DJYANLQPSGKNDM-UHFFFAOYSA-N 0.000 claims description 4
• OAHDFPXZMPHLGP-UHFFFAOYSA-N CC1(CC1(CN2C=NC3=C2N=C(NC3=O)N)OCP(=O)(OCCC(C)(C)C(=O)O)OCOC(=O)C(C)(C)C)C Chemical compound CC1(CC1(CN2C=NC3=C2N=C(NC3=O)N)OCP(=O)(OCCC(C)(C)C(=O)O)OCOC(=O)C(C)(C)C)C OAHDFPXZMPHLGP-UHFFFAOYSA-N 0.000 claims description 4
• YMQMBIAIIHITON-UHFFFAOYSA-N [2-[1-[(6-aminopurin-9-yl)methyl]cyclopropyl]propyl-(2,2-dimethylpropanoyloxymethoxy)phosphoryl]oxymethyl 2,2-dimethylpropanoate Chemical compound C1=NC2=C(N)N=CN=C2N1CC1(C(CP(=O)(OCOC(=O)C(C)(C)C)OCOC(=O)C(C)(C)C)C)CC1 YMQMBIAIIHITON-UHFFFAOYSA-N 0.000 claims description 4
• LIABTJQQLNRCSU-UHFFFAOYSA-N [[1-[(2-aminopurin-9-yl)methyl]-2-methylcyclopropyl]peroxy-methylphosphoryl]oxymethyl propan-2-yl carbonate Chemical compound CP(OCOC(=O)OC(C)C)(OOC1(C(C1)C)CN1C2=NC(=NC=C2N=C1)N)=O LIABTJQQLNRCSU-UHFFFAOYSA-N 0.000 claims description 4
• YEWJLUJHAMPZMH-UHFFFAOYSA-N [[1-[(6-aminopurin-9-yl)methyl]-2,2-dimethylcyclopropyl]peroxy-methylphosphoryl]oxymethyl propan-2-yl carbonate Chemical compound CP(OCOC(=O)OC(C)C)(OOC1(C(C1)(C)C)CN1C2=NC=NC(=C2N=C1)N)=O YEWJLUJHAMPZMH-UHFFFAOYSA-N 0.000 claims description 4
• MUNVPQSEWSFCNO-UHFFFAOYSA-N [[1-[(6-aminopurin-9-yl)methyl]cyclopropyl]oxymethyl-(3-methylbutanoyloxymethoxy)phosphoryl]oxymethyl 3-methylbutanoate Chemical compound C1=NC2=C(N)N=CN=C2N1CC1(OCP(=O)(OCOC(=O)CC(C)C)OCOC(=O)CC(C)C)CC1 MUNVPQSEWSFCNO-UHFFFAOYSA-N 0.000 claims description 4
• PSNTZKJYCNHIOZ-UHFFFAOYSA-N [[1-[(6-aminopurin-9-yl)methyl]cyclopropyl]peroxy-methylphosphoryl]oxymethyl propan-2-yl carbonate Chemical compound CP(OCOC(=O)OC(C)C)(OOC1(CC1)CN1C2=NC=NC(=C2N=C1)N)=O PSNTZKJYCNHIOZ-UHFFFAOYSA-N 0.000 claims description 4
• UFYPMIUIQXCMRT-UHFFFAOYSA-N [[[1-[(6-aminopurin-9-yl)methyl]cyclopropyl]-methylamino]oxy-methylphosphoryl]oxymethyl propan-2-yl carbonate Chemical compound CC(C)OC(=O)OCOP(C)(=O)ON(C)C1(CN2C=NC3=C(N)N=CN=C23)CC1 UFYPMIUIQXCMRT-UHFFFAOYSA-N 0.000 claims description 4
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 4
• AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 claims description 3
• IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 claims description 3
• YJLIKUSWRSEPSM-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-amino-8-[(4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1CNC1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O YJLIKUSWRSEPSM-WGQQHEPDSA-N 0.000 claims description 3
• QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 claims description 3
• IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 claims description 3
• OOKAZRDERJMRCJ-KOUAFAAESA-N (3r)-7-[(1s,2s,4ar,6s,8s)-2,6-dimethyl-8-[(2s)-2-methylbutanoyl]oxy-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl]-3-hydroxy-5-oxoheptanoic acid Chemical compound C1=C[C@H](C)[C@H](CCC(=O)C[C@@H](O)CC(O)=O)C2[C@@H](OC(=O)[C@@H](C)CC)C[C@@H](C)C[C@@H]21 OOKAZRDERJMRCJ-KOUAFAAESA-N 0.000 claims description 3
• OIIOPWHTJZYKIL-PMACEKPBSA-N (5S)-5-[[[5-[2-chloro-3-[2-chloro-3-[6-methoxy-5-[[[(2S)-5-oxopyrrolidin-2-yl]methylamino]methyl]pyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methylamino]methyl]pyrrolidin-2-one Chemical compound C1(=C(N=C(C2=C(C(C3=CC=CC(=C3Cl)C3=NC(OC)=C(N=C3)CNC[C@H]3NC(=O)CC3)=CC=C2)Cl)C=N1)OC)CNC[C@H]1NC(=O)CC1 OIIOPWHTJZYKIL-PMACEKPBSA-N 0.000 claims description 3
• DEVSOMFAQLZNKR-RJRFIUFISA-N (z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-n'-pyrazin-2-ylprop-2-enehydrazide Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C2=NN(\C=C/C(=O)NNC=3N=CC=NC=3)C=N2)=C1 DEVSOMFAQLZNKR-RJRFIUFISA-N 0.000 claims description 3
• KKHFRAFPESRGGD-UHFFFAOYSA-N 1,3-dimethyl-7-[3-(n-methylanilino)propyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCCN(C)C1=CC=CC=C1 KKHFRAFPESRGGD-UHFFFAOYSA-N 0.000 claims description 3
• KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 claims description 3
• WGFNXGPBPIJYLI-UHFFFAOYSA-N 2,6-difluoro-3-[(3-fluorophenyl)sulfonylamino]-n-(3-methoxy-1h-pyrazolo[3,4-b]pyridin-5-yl)benzamide Chemical compound C1=C2C(OC)=NNC2=NC=C1NC(=O)C(C=1F)=C(F)C=CC=1NS(=O)(=O)C1=CC=CC(F)=C1 WGFNXGPBPIJYLI-UHFFFAOYSA-N 0.000 claims description 3
• AZEVYGFOCGBUTB-UHFFFAOYSA-N 2-[1-[(2-aminopurin-9-yl)methyl]cyclopropyl]ethylphosphonic acid Chemical compound C12=NC(N)=NC=C2N=CN1CC1(CCP(O)(O)=O)CC1 AZEVYGFOCGBUTB-UHFFFAOYSA-N 0.000 claims description 3
• QIFRUBOFZRICFI-UHFFFAOYSA-N 2-[1-[(6-aminopurin-9-yl)methyl]cyclopropyl]propylphosphonic acid Chemical compound C1=NC2=C(N)N=CN=C2N1CC1(C(CP(O)(O)=O)C)CC1 QIFRUBOFZRICFI-UHFFFAOYSA-N 0.000 claims description 3
• WFOVEDJTASPCIR-UHFFFAOYSA-N 3-[(4-methyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)methylamino]-n-[[2-(trifluoromethyl)phenyl]methyl]benzamide Chemical compound N=1N=C(C=2C=CN=CC=2)N(C)C=1CNC(C=1)=CC=CC=1C(=O)NCC1=CC=CC=C1C(F)(F)F WFOVEDJTASPCIR-UHFFFAOYSA-N 0.000 claims description 3
• MPMKMQHJHDHPBE-RUZDIDTESA-N 4-[[(2r)-1-(1-benzothiophene-3-carbonyl)-2-methylazetidine-2-carbonyl]-[(3-chlorophenyl)methyl]amino]butanoic acid Chemical compound O=C([C@@]1(N(CC1)C(=O)C=1C2=CC=CC=C2SC=1)C)N(CCCC(O)=O)CC1=CC=CC(Cl)=C1 MPMKMQHJHDHPBE-RUZDIDTESA-N 0.000 claims description 3
• IJRKLHTZAIFUTB-UHFFFAOYSA-N 5-nitro-2-(2-phenylethylamino)benzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC=C1NCCC1=CC=CC=C1 IJRKLHTZAIFUTB-UHFFFAOYSA-N 0.000 claims description 3
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 3
• XWHJVRQSJQFWHL-UHFFFAOYSA-N CC1=CC=C(C=C1)SC2=NC(=NC3=C2N=CN3CC4(CC4)OCP(=O)(OCCC(C)(C)C(=O)O)OCOC(=O)C(C)(C)C)N Chemical compound CC1=CC=C(C=C1)SC2=NC(=NC3=C2N=CN3CC4(CC4)OCP(=O)(OCCC(C)(C)C(=O)O)OCOC(=O)C(C)(C)C)N XWHJVRQSJQFWHL-UHFFFAOYSA-N 0.000 claims description 3
• 229940126657 Compound 17 Drugs 0.000 claims description 3
• 239000002841 Lewis acid Substances 0.000 claims description 3
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