JP2010500414A5 - - Google Patents

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Publication number

JP2010500414A5

JP2010500414A5 JP2009524737A JP2009524737A JP2010500414A5 JP 2010500414 A5 JP2010500414 A5 JP 2010500414A5 JP 2009524737 A JP2009524737 A JP 2009524737A JP 2009524737 A JP2009524737 A JP 2009524737A JP 2010500414 A5 JP2010500414 A5 JP 2010500414A5

Authority

JP

Japan

Prior art keywords

imidazol

pyrrolidinyl

phenyl

oxo

pyrimidinyl

Prior art date

2007-08-09

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.)

Granted

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• GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical group COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 claims 42
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 30
• -1 carboxy, formyl Chemical group 0.000 claims 22
• 150000001875 compounds Chemical class 0.000 claims 21
• 125000000217 alkyl group Chemical group 0.000 claims 18
• 150000003839 salts Chemical class 0.000 claims 17
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 9
• 125000005843 halogen group Chemical group 0.000 claims 9
• 125000000753 cycloalkyl group Chemical group 0.000 claims 8
• 229910052757 nitrogen Inorganic materials 0.000 claims 8
• 108010047761 Interferon-alpha Proteins 0.000 claims 6
• 102000006992 Interferon-alpha Human genes 0.000 claims 6
• 108010050904 Interferons Proteins 0.000 claims 6
• 102000014150 Interferons Human genes 0.000 claims 6
• 125000003545 alkoxy group Chemical group 0.000 claims 6
• 239000003795 chemical substances by application Substances 0.000 claims 6
• 125000001188 haloalkyl group Chemical group 0.000 claims 6
• 229940079322 interferon Drugs 0.000 claims 6
• 239000008194 pharmaceutical composition Substances 0.000 claims 6
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 5
• 229910052739 hydrogen Inorganic materials 0.000 claims 5
• 239000001257 hydrogen Substances 0.000 claims 5
• KPPVNWGJXFMGAM-UUILKARUSA-N (e)-2-methyl-1-(6-methyl-3,4-dihydro-2h-quinolin-1-yl)but-2-en-1-one Chemical compound CC1=CC=C2N(C(=O)C(/C)=C/C)CCCC2=C1 KPPVNWGJXFMGAM-UUILKARUSA-N 0.000 claims 4
• 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 4
• 239000002253 acid Substances 0.000 claims 4
• 125000003342 alkenyl group Chemical group 0.000 claims 4
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 4
• 125000003710 aryl alkyl group Chemical group 0.000 claims 4
• 125000000623 heterocyclic group Chemical group 0.000 claims 4
• 208000015181 infectious disease Diseases 0.000 claims 4
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims 4
• 229960000329 ribavirin Drugs 0.000 claims 4
• 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 4
• 229910052717 sulfur Inorganic materials 0.000 claims 4
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims 3
• 125000003118 aryl group Chemical group 0.000 claims 3
• 230000000694 effects Effects 0.000 claims 3
• 150000002431 hydrogen Chemical class 0.000 claims 3
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims 3
• 108091032973 (ribonucleotides)n+m Proteins 0.000 claims 2
• UBCHPRBFMUDMNC-UHFFFAOYSA-N 1-(1-adamantyl)ethanamine Chemical compound C1C(C2)CC3CC2CC1(C(N)C)C3 UBCHPRBFMUDMNC-UHFFFAOYSA-N 0.000 claims 2
• 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims 2
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 2
• 108020005544 Antisense RNA Proteins 0.000 claims 2
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
• HAEJPQIATWHALX-KQYNXXCUSA-N ITP Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(N=CNC2=O)=C2N=C1 HAEJPQIATWHALX-KQYNXXCUSA-N 0.000 claims 2
• 101710200424 Inosine-5'-monophosphate dehydrogenase Proteins 0.000 claims 2
• 102100040018 Interferon alpha-2 Human genes 0.000 claims 2
• 108010079944 Interferon-alpha2b Proteins 0.000 claims 2
• 102000013462 Interleukin-12 Human genes 0.000 claims 2
• 108010065805 Interleukin-12 Proteins 0.000 claims 2
• 102000000588 Interleukin-2 Human genes 0.000 claims 2
• 108010002350 Interleukin-2 Proteins 0.000 claims 2
• 102000004889 Interleukin-6 Human genes 0.000 claims 2
• 108090001005 Interleukin-6 Proteins 0.000 claims 2
• 102000005741 Metalloproteases Human genes 0.000 claims 2
• 108010006035 Metalloproteases Proteins 0.000 claims 2
• 108060004795 Methyltransferase Proteins 0.000 claims 2
• 101800001019 Non-structural protein 4B Proteins 0.000 claims 2
• 101800001014 Non-structural protein 5A Proteins 0.000 claims 2
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims 2
• 102000012479 Serine Proteases Human genes 0.000 claims 2
• 108010022999 Serine Proteases Proteins 0.000 claims 2
• 230000005867 T cell response Effects 0.000 claims 2
• 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims 2
• 125000005093 alkyl carbonyl alkyl group Chemical group 0.000 claims 2
• DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 claims 2
• 229960003805 amantadine Drugs 0.000 claims 2
• 125000005018 aryl alkenyl group Chemical group 0.000 claims 2
• 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims 2
• 125000002102 aryl alkyloxo group Chemical group 0.000 claims 2
• 125000005160 aryl oxy alkyl group Chemical group 0.000 claims 2
• 239000003184 complementary RNA Substances 0.000 claims 2
• 125000004858 cycloalkoxyalkyl group Chemical group 0.000 claims 2
• 125000001153 fluoro group Chemical group F* 0.000 claims 2
• 210000002443 helper t lymphocyte Anatomy 0.000 claims 2
• 125000001072 heteroaryl group Chemical group 0.000 claims 2
• 125000004449 heterocyclylalkenyl group Chemical group 0.000 claims 2
• 125000004415 heterocyclylalkyl group Chemical group 0.000 claims 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 2
• DOUYETYNHWVLEO-UHFFFAOYSA-N imiquimod Chemical compound C1=CC=CC2=C3N(CC(C)C)C=NC3=C(N)N=C21 DOUYETYNHWVLEO-UHFFFAOYSA-N 0.000 claims 2
• 229960002751 imiquimod Drugs 0.000 claims 2
• 230000002452 interceptive effect Effects 0.000 claims 2
• 229940117681 interleukin-12 Drugs 0.000 claims 2
• 229940100601 interleukin-6 Drugs 0.000 claims 2
• 125000004433 nitrogen atom Chemical group N* 0.000 claims 2
• 229910052760 oxygen Inorganic materials 0.000 claims 2
• 229910052698 phosphorus Inorganic materials 0.000 claims 2
• 239000011574 phosphorus Substances 0.000 claims 2
• 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims 2
• 229960000888 rimantadine Drugs 0.000 claims 2
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
• ZLGUQGPINHQXJL-DLBZAZTESA-N (2R)-2-(diethylamino)-1-[(2S)-2-(1H-imidazol-2-yl)pyrrolidin-1-yl]-2-phenylethanone Chemical compound C(C)N([C@@H](C(=O)N1[C@@H](CCC1)C=1NC=CN=1)C1=CC=CC=C1)CC ZLGUQGPINHQXJL-DLBZAZTESA-N 0.000 claims 1
• WMVKHPHWHCTSQJ-CLLHQPRTSA-N (2r)-2-(dimethylamino)-1-[(2s)-2-[5-[2-[5-[2-[(2s)-1-[(2r)-2-(dimethylamino)-2-phenylacetyl]pyrrolidin-2-yl]-1h-imidazol-5-yl]pyrimidin-2-yl]pyrimidin-5-yl]-1h-imidazol-2-yl]pyrrolidin-1-yl]-2-phenylethanone Chemical compound C1([C@@H](N(C)C)C(=O)N2CCC[C@H]2C2=NC=C(N2)C2=CN=C(N=C2)C2=NC=C(C=N2)C2=CN=C(N2)[C@@H]2CCCN2C(=O)[C@H](N(C)C)C=2C=CC=CC=2)=CC=CC=C1 WMVKHPHWHCTSQJ-CLLHQPRTSA-N 0.000 claims 1
• PWVKLKCCDPYCOM-CDBYGCFJSA-N (2r)-2-(dimethylamino)-1-[(2s)-2-[5-[5-[5-[2-[(2s)-1-[(2r)-2-(dimethylamino)-2-phenylacetyl]pyrrolidin-2-yl]-1h-imidazol-5-yl]pyrazin-2-yl]pyrazin-2-yl]-1h-imidazol-2-yl]pyrrolidin-1-yl]-2-phenylethanone Chemical compound C1([C@@H](N(C)C)C(=O)N2CCC[C@H]2C2=NC=C(N2)C2=NC=C(N=C2)C2=NC=C(N=C2)C2=CN=C(N2)[C@@H]2CCCN2C(=O)[C@H](N(C)C)C=2C=CC=CC=2)=CC=CC=C1 PWVKLKCCDPYCOM-CDBYGCFJSA-N 0.000 claims 1
• QPJOVKKOKPBKGB-CDBYGCFJSA-N (2r)-2-(dimethylamino)-1-[(2s)-2-[5-[6-[6-[2-[(2s)-1-[(2r)-2-(dimethylamino)-2-phenylacetyl]pyrrolidin-2-yl]-1h-imidazol-5-yl]pyridazin-3-yl]pyridazin-3-yl]-1h-imidazol-2-yl]pyrrolidin-1-yl]-2-phenylethanone Chemical compound C1([C@@H](N(C)C)C(=O)N2CCC[C@H]2C2=NC=C(N2)C2=CC=C(N=N2)C2=CC=C(N=N2)C2=CN=C(N2)[C@@H]2CCCN2C(=O)[C@H](N(C)C)C=2C=CC=CC=2)=CC=CC=C1 QPJOVKKOKPBKGB-CDBYGCFJSA-N 0.000 claims 1
• ZFSNKVBEZMCYLQ-IZSXRKQISA-N (2r)-2-methoxy-1-[(2s)-2-[5-[4-[5-[2-[(2s)-1-[(2r)-2-methoxy-2-phenylacetyl]pyrrolidin-2-yl]-1h-imidazol-5-yl]pyridin-2-yl]phenyl]-1h-imidazol-2-yl]pyrrolidin-1-yl]-2-phenylethanone Chemical compound C1([C@@H](OC)C(=O)N2CCC[C@H]2C2=NC=C(N2)C2=CC=C(N=C2)C2=CC=C(C=C2)C2=CN=C(N2)[C@@H]2CCCN2C(=O)[C@H](OC)C=2C=CC=CC=2)=CC=CC=C1 ZFSNKVBEZMCYLQ-IZSXRKQISA-N 0.000 claims 1
• HXKIWLUSLSHHJP-VMPREFPWSA-N (2s)-2-[5-[2-[4-[2-[(2s)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidin-2-yl]-1h-imidazol-5-yl]phenyl]pyrimidin-5-yl]-1-(2-trimethylsilylethoxymethyl)imidazol-2-yl]pyrrolidine-1-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCC[C@H]1C1=NC=C(C=2C=CC(=CC=2)C=2N=CC(=CN=2)C=2N(C([C@H]3N(CCC3)C(O)=O)=NC=2)COCC[Si](C)(C)C)N1 HXKIWLUSLSHHJP-VMPREFPWSA-N 0.000 claims 1
• SOKIWEWZFBQWKH-OALUTQOASA-N 2-[3-fluoro-4-[2-[(2s)-pyrrolidin-2-yl]-1h-imidazol-5-yl]phenyl]-5-[2-[(2s)-pyrrolidin-2-yl]-1h-imidazol-5-yl]pyrimidine Chemical compound FC1=CC(C=2N=CC(=CN=2)C=2NC(=NC=2)[C@H]2NCCC2)=CC=C1C(N1)=CN=C1[C@@H]1CCCN1 SOKIWEWZFBQWKH-OALUTQOASA-N 0.000 claims 1
• SMDBXCNWJLMIOG-OALUTQOASA-N 5-[2-[(2s)-pyrrolidin-2-yl]-1h-imidazol-5-yl]-2-[4-[2-[(2s)-pyrrolidin-2-yl]-1h-imidazol-5-yl]phenyl]pyrimidine Chemical compound C1CCN[C@@H]1C1=NC=C(C=2C=CC(=CC=2)C=2N=CC(=CN=2)C=2NC(=NC=2)[C@H]2NCCC2)N1 SMDBXCNWJLMIOG-OALUTQOASA-N 0.000 claims 1
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims 1
• 101710088194 Dehydrogenase Proteins 0.000 claims 1
• 229940124186 Dehydrogenase inhibitor Drugs 0.000 claims 1
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims 1
• 125000004432 carbon atom Chemical group C* 0.000 claims 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
• 239000003937 drug carrier Substances 0.000 claims 1
• 125000005842 heteroatom Chemical group 0.000 claims 1
• 125000005844 heterocyclyloxy group Chemical group 0.000 claims 1
• 125000000336 imidazol-5-yl group Chemical group [H]N1C([H])=NC([H])=C1[*] 0.000 claims 1
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims 1
• 239000003112 inhibitor Substances 0.000 claims 1
• CJDYTWDZWVAESP-OWPQXHQJSA-N methyl n-[(1r)-2-oxo-1-phenyl-2-[(2s)-2-[5-[4-[5-[2-[(2s)-pyrrolidin-2-yl]-1h-imidazol-5-yl]pyrimidin-2-yl]phenyl]-1h-imidazol-2-yl]pyrrolidin-1-yl]ethyl]carbamate Chemical compound N1C([C@@H]2CCCN2C(=O)[C@H](NC(=O)OC)C=2C=CC=CC=2)=NC=C1C(C=C1)=CC=C1C(N=C1)=NC=C1C(N1)=CN=C1[C@@H]1CCCN1 CJDYTWDZWVAESP-OWPQXHQJSA-N 0.000 claims 1
• 239000006187 pill Substances 0.000 claims 1
• NEOWKUYGCSXQDT-URXFXBBRSA-N tert-butyl (2s)-2-[5-[2-[4-[2-[(2s)-pyrrolidin-2-yl]-1h-imidazol-5-yl]phenyl]pyrimidin-5-yl]-1h-imidazol-2-yl]pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC[C@H]1C1=NC=C(C=2C=NC(=NC=2)C=2C=CC(=CC=2)C=2NC(=NC=2)[C@H]2NCCC2)N1 NEOWKUYGCSXQDT-URXFXBBRSA-N 0.000 claims 1