JP2010526834A5 - - Google Patents

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Publication number

JP2010526834A5

JP2010526834A5 JP2010507704A JP2010507704A JP2010526834A5 JP 2010526834 A5 JP2010526834 A5 JP 2010526834A5 JP 2010507704 A JP2010507704 A JP 2010507704A JP 2010507704 A JP2010507704 A JP 2010507704A JP 2010526834 A5 JP2010526834 A5 JP 2010526834A5

Authority

JP

Japan

Prior art keywords

optionally substituted

alkyl

fluoro

heteroaryl

cycloalkyl

Prior art date

2008-05-09

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.)

Pending

Links

• Espacenet
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• 125000001153 fluoro group Chemical group F* 0.000 claims 44
• 150000001875 compounds Chemical class 0.000 claims 33
• 229910052739 hydrogen Inorganic materials 0.000 claims 27
• 239000001257 hydrogen Substances 0.000 claims 25
• 125000000623 heterocyclic group Chemical group 0.000 claims 23
• 125000001072 heteroaryl group Chemical group 0.000 claims 21
• 150000002431 hydrogen Chemical group 0.000 claims 20
• 125000000217 alkyl group Chemical group 0.000 claims 19
• 125000000753 cycloalkyl group Chemical group 0.000 claims 17
• 239000008194 pharmaceutical composition Substances 0.000 claims 17
• 125000003107 substituted aryl group Chemical group 0.000 claims 16
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims 12
• 125000004093 cyano group Chemical group *C#N 0.000 claims 11
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims 10
• -1 hydroxy, nitro, amino Chemical group 0.000 claims 10
• 229910052736 halogen Inorganic materials 0.000 claims 9
• 150000002367 halogens Chemical class 0.000 claims 9
• 125000003545 alkoxy group Chemical group 0.000 claims 8
• 125000003282 alkyl amino group Chemical group 0.000 claims 8
• 125000004414 alkyl thio group Chemical group 0.000 claims 8
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 8
• 125000001424 substituent group Chemical group 0.000 claims 8
• 125000003118 aryl group Chemical group 0.000 claims 7
• 125000000547 substituted alkyl group Chemical group 0.000 claims 7
• 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims 6
• 229910052799 carbon Inorganic materials 0.000 claims 6
• 108010047761 Interferon-alpha Proteins 0.000 claims 5
• 102000006992 Interferon-alpha Human genes 0.000 claims 5
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 5
• 125000004008 6 membered carbocyclic group Chemical group 0.000 claims 4
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 4
• 101800001838 Serine protease/helicase NS3 Proteins 0.000 claims 4
• OHDXDNUPVVYWOV-UHFFFAOYSA-N n-methyl-1-(2-naphthalen-1-ylsulfanylphenyl)methanamine Chemical compound CNCC1=CC=CC=C1SC1=CC=CC2=CC=CC=C12 OHDXDNUPVVYWOV-UHFFFAOYSA-N 0.000 claims 4
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 3
• 102100037850 Interferon gamma Human genes 0.000 claims 3
• 108010074328 Interferon-gamma Proteins 0.000 claims 3
• 108091005804 Peptidases Proteins 0.000 claims 3
• 239000004365 Protease Substances 0.000 claims 3
• 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims 3
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims 3
• 125000002837 carbocyclic group Chemical group 0.000 claims 3
• 150000002148 esters Chemical class 0.000 claims 3
• 108010010648 interferon alfacon-1 Proteins 0.000 claims 3
• 239000002777 nucleoside Substances 0.000 claims 3
• 229940002612 prodrug Drugs 0.000 claims 3
• 239000000651 prodrug Substances 0.000 claims 3
• 150000003839 salts Chemical class 0.000 claims 3
• SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims 3
• 229910052717 sulfur Inorganic materials 0.000 claims 3
• 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims 2
• 229940124158 Protease/peptidase inhibitor Drugs 0.000 claims 2
• 125000003710 aryl alkyl group Chemical group 0.000 claims 2
• 125000002619 bicyclic group Chemical group 0.000 claims 2
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 2
• 230000000694 effects Effects 0.000 claims 2
• 208000010710 hepatitis C virus infection Diseases 0.000 claims 2
• 230000002401 inhibitory effect Effects 0.000 claims 2
• 230000003993 interaction Effects 0.000 claims 2
• 125000001624 naphthyl group Chemical group 0.000 claims 2
• 229910052757 nitrogen Inorganic materials 0.000 claims 2
• 150000003833 nucleoside derivatives Chemical class 0.000 claims 2
• 239000000137 peptide hydrolase inhibitor Substances 0.000 claims 2
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims 2
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims 2
• UJQBOUAGWGVOTI-XSSZXYGBSA-N 1-[(2r,4s,5r)-4-azido-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@](O)(N=[N+]=[N-])C1 UJQBOUAGWGVOTI-XSSZXYGBSA-N 0.000 claims 1
• IWUCXVSUMQZMFG-RGDLXGNYSA-N 1-[(2s,3s,4r,5s)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2,4-triazole-3-carboxamide Chemical compound N1=C(C(=O)N)N=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 IWUCXVSUMQZMFG-RGDLXGNYSA-N 0.000 claims 1
• VWFCHDSQECPREK-LURJTMIESA-N Cidofovir Chemical compound NC=1C=CN(C[C@@H](CO)OCP(O)(O)=O)C(=O)N=1 VWFCHDSQECPREK-LURJTMIESA-N 0.000 claims 1
• BXZVVICBKDXVGW-NKWVEPMBSA-N Didanosine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(NC=NC2=O)=C2N=C1 BXZVVICBKDXVGW-NKWVEPMBSA-N 0.000 claims 1
• 208000005176 Hepatitis C Diseases 0.000 claims 1
• 241000713772 Human immunodeficiency virus 1 Species 0.000 claims 1
• 229940121740 Inosine monophosphate dehydrogenase inhibitor Drugs 0.000 claims 1
• 101800001554 RNA-directed RNA polymerase Proteins 0.000 claims 1
• IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims 1
• NCDNCNXCDXHOMX-UHFFFAOYSA-N Ritonavir Natural products C=1C=CC=CC=1CC(NC(=O)OCC=1SC=NC=1)C(O)CC(CC=1C=CC=CC=1)NC(=O)C(C(C)C)NC(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-UHFFFAOYSA-N 0.000 claims 1
• WREGKURFCTUGRC-POYBYMJQSA-N Zalcitabine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)CC1 WREGKURFCTUGRC-POYBYMJQSA-N 0.000 claims 1
• GLWHPRRGGYLLRV-XLPZGREQSA-N [[(2s,3s,5r)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](N=[N+]=[N-])C1 GLWHPRRGGYLLRV-XLPZGREQSA-N 0.000 claims 1
• 229960004748 abacavir Drugs 0.000 claims 1
• MCGSCOLBFJQGHM-SCZZXKLOSA-N abacavir Chemical compound C=12N=CN([C@H]3C=C[C@@H](CO)C3)C2=NC(N)=NC=1NC1CC1 MCGSCOLBFJQGHM-SCZZXKLOSA-N 0.000 claims 1
• 229960001997 adefovir Drugs 0.000 claims 1
• WOZSCQDILHKSGG-UHFFFAOYSA-N adefovir depivoxil Chemical compound N1=CN=C2N(CCOCP(=O)(OCOC(=O)C(C)(C)C)OCOC(=O)C(C)(C)C)C=NC2=C1N WOZSCQDILHKSGG-UHFFFAOYSA-N 0.000 claims 1
• 229960000724 cidofovir Drugs 0.000 claims 1
• 208000019425 cirrhosis of liver Diseases 0.000 claims 1
• 229940014461 combivir Drugs 0.000 claims 1
• 125000004122 cyclic group Chemical group 0.000 claims 1
• 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 claims 1
• 229940079593 drug Drugs 0.000 claims 1
• 239000003814 drug Substances 0.000 claims 1
• 125000002883 imidazolyl group Chemical group 0.000 claims 1
• 238000000338 in vitro Methods 0.000 claims 1
• 239000002348 inosinate dehydrogenase inhibitor Substances 0.000 claims 1
• 229960003130 interferon gamma Drugs 0.000 claims 1
• 230000003908 liver function Effects 0.000 claims 1
• 238000000034 method Methods 0.000 claims 1
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
• 125000004433 nitrogen atom Chemical group N* 0.000 claims 1
• 229910052760 oxygen Inorganic materials 0.000 claims 1
• 239000000546 pharmaceutical excipient Substances 0.000 claims 1
• 229960000329 ribavirin Drugs 0.000 claims 1
• HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 claims 1
• 229960000311 ritonavir Drugs 0.000 claims 1
• NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical group N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 claims 1
• 239000003730 rna directed rna polymerase inhibitor Substances 0.000 claims 1
• 238000006467 substitution reaction Methods 0.000 claims 1
• 230000002459 sustained effect Effects 0.000 claims 1
• 230000003612 virological effect Effects 0.000 claims 1
• 0 CC1C*(C)C(C)C1 Chemical compound CC1C*(C)C(C)C1 0.000 description 2
• KMGVYCLNLPTOSH-RDXZYIDFSA-N CCC(C1)[C@@]1(/C=N\C([C@H](C[C@H](C1)OC(N(Cc2ccc3)Cc2c3Cl)=O)N1C([C@H](C(C)(C)C)Nc1cc(N2CCOCC2)ccc1)=O)=O)C(NS(C1CC1)(=O)=O)=O Chemical compound CCC(C1)[C@@]1(/C=N\C([C@H](C[C@H](C1)OC(N(Cc2ccc3)Cc2c3Cl)=O)N1C([C@H](C(C)(C)C)Nc1cc(N2CCOCC2)ccc1)=O)=O)C(NS(C1CC1)(=O)=O)=O KMGVYCLNLPTOSH-RDXZYIDFSA-N 0.000 description 1
• GDFFZXRRGIUJDR-RLERGYQVSA-N CC[C@H](C1)C1(C(NS(C1(C)CC1)(=O)=[O]1(CC)CC1)=O)NC(C(C[C@H](C1)OC(N(C2)Cc3c2cccc3Cl)=O)N1C([C@H](C(C)(C)C)Nc1cccc(C(F)(F)F)c1)=O)=O Chemical compound CC[C@H](C1)C1(C(NS(C1(C)CC1)(=O)=[O]1(CC)CC1)=O)NC(C(C[C@H](C1)OC(N(C2)Cc3c2cccc3Cl)=O)N1C([C@H](C(C)(C)C)Nc1cccc(C(F)(F)F)c1)=O)=O GDFFZXRRGIUJDR-RLERGYQVSA-N 0.000 description 1
• SALXVJXSTFFYOL-UWWROSJJSA-N CC[C@H](C1)C1(C(NS(C1C2C1C2)(=O)=O)=O)NC([C@H](C[C@H](C1)OC(N(C2)Cc3c2cccc3Cl)=O)N1C([C@H](C(C)(C)C)Nc1cc(S(N2CCOCC2)(=O)=O)ccc1)=O)=O Chemical compound CC[C@H](C1)C1(C(NS(C1C2C1C2)(=O)=O)=O)NC([C@H](C[C@H](C1)OC(N(C2)Cc3c2cccc3Cl)=O)N1C([C@H](C(C)(C)C)Nc1cc(S(N2CCOCC2)(=O)=O)ccc1)=O)=O SALXVJXSTFFYOL-UWWROSJJSA-N 0.000 description 1
• YYTHFNMNYRMEDL-OFWNXAIESA-N CC[C@H](C1)C1(C(NS(C1CC1)(=O)=O)=O)NC([C@H](C[C@H](C1)OC(N(Cc2ccc3)Cc2c3Cl)=O)N1C([C@H](C(C)(C)C)Nc(cc1)cc(F)c1F)=O)=O Chemical compound CC[C@H](C1)C1(C(NS(C1CC1)(=O)=O)=O)NC([C@H](C[C@H](C1)OC(N(Cc2ccc3)Cc2c3Cl)=O)N1C([C@H](C(C)(C)C)Nc(cc1)cc(F)c1F)=O)=O YYTHFNMNYRMEDL-OFWNXAIESA-N 0.000 description 1
• DSRNPGNONJBPER-UHFFFAOYSA-N CN(Cc1c(C2)cccc1)C2I Chemical compound CN(Cc1c(C2)cccc1)C2I DSRNPGNONJBPER-UHFFFAOYSA-N 0.000 description 1