JP2015520767A5 - - Google Patents

Info

Publication number

JP2015520767A5

JP2015520767A5 JP2015514134A JP2015514134A JP2015520767A5 JP 2015520767 A5 JP2015520767 A5 JP 2015520767A5 JP 2015514134 A JP2015514134 A JP 2015514134A JP 2015514134 A JP2015514134 A JP 2015514134A JP 2015520767 A5 JP2015520767 A5 JP 2015520767A5

Authority

JP

Japan

Prior art keywords

compound

pharmaceutically acceptable

solvate

acceptable salt

inhibitor

Prior art date

2013-05-21

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

Links

• Espacenet
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• 150000001875 compounds Chemical class 0.000 claims description 45
• 150000003839 salts Chemical class 0.000 claims description 13
• 239000012453 solvate Substances 0.000 claims description 13
• 239000000203 mixture Substances 0.000 claims description 9
• 229910052739 hydrogen Inorganic materials 0.000 claims description 5
• 239000001257 hydrogen Substances 0.000 claims description 5
• 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 5
• 229940124158 Protease/peptidase inhibitor Drugs 0.000 claims description 4
• 229910052736 halogen Inorganic materials 0.000 claims description 3
• 150000002367 halogens Chemical class 0.000 claims description 3
• -1 polymerase inhibitor Proteins 0.000 claims description 3
• 229940122806 Cyclophilin inhibitor Drugs 0.000 claims description 2
• 108010050904 Interferons Proteins 0.000 claims description 2
• 102000014150 Interferons Human genes 0.000 claims description 2
• 239000000134 cyclophilin inhibitor Substances 0.000 claims description 2
• 229940079322 interferon Drugs 0.000 claims description 2
• 239000008194 pharmaceutical composition Substances 0.000 claims 8
• 239000003112 inhibitor Substances 0.000 claims 5
• 229940123066 Polymerase inhibitor Drugs 0.000 claims 2
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 2
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 2
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 2
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 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
• JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 claims 1
• PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims 1
• 108010036949 Cyclosporine Proteins 0.000 claims 1
• 241000711549 Hepacivirus C Species 0.000 claims 1
• 101800001020 Non-structural protein 4A Proteins 0.000 claims 1
• 101800001014 Non-structural protein 5A Proteins 0.000 claims 1
• 101800001838 Serine protease/helicase NS3 Proteins 0.000 claims 1
• 239000005557 antagonist Substances 0.000 claims 1
• 239000003443 antiviral agent Substances 0.000 claims 1
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
• 229960001265 ciclosporin Drugs 0.000 claims 1
• 229930182912 cyclosporin Natural products 0.000 claims 1
• 239000003814 drug Substances 0.000 claims 1
• 150000002431 hydrogen Chemical class 0.000 claims 1
• 238000004519 manufacturing process Methods 0.000 claims 1
• 108020004999 messenger RNA Proteins 0.000 claims 1
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
• 108020004707 nucleic acids Proteins 0.000 claims 1
• 150000007523 nucleic acids Chemical class 0.000 claims 1
• 102000039446 nucleic acids Human genes 0.000 claims 1
• 239000002777 nucleoside Substances 0.000 claims 1
• 150000003833 nucleoside derivatives Chemical class 0.000 claims 1
• 125000003729 nucleotide group Chemical group 0.000 claims 1
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
• 238000003419 tautomerization reaction Methods 0.000 claims 1
• 125000000217 alkyl group Chemical group 0.000 description 8
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 7
• 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 description 7
• 150000001540 azides Chemical class 0.000 description 7
• 239000008108 microcrystalline cellulose Substances 0.000 description 7
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 7
• 229940016286 microcrystalline cellulose Drugs 0.000 description 7
• 229960000329 ribavirin Drugs 0.000 description 7
• 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 description 7
• 229910052799 carbon Inorganic materials 0.000 description 6
• 229960000517 boceprevir Drugs 0.000 description 5
• LHHCSNFAOIFYRV-DOVBMPENSA-N boceprevir Chemical compound O=C([C@@H]1[C@@H]2[C@@H](C2(C)C)CN1C(=O)[C@@H](NC(=O)NC(C)(C)C)C(C)(C)C)NC(C(=O)C(N)=O)CC1CCC1 LHHCSNFAOIFYRV-DOVBMPENSA-N 0.000 description 5
• 125000002947 alkylene group Chemical group 0.000 description 4
• 150000001721 carbon Chemical group 0.000 description 4
• 125000000753 cycloalkyl group Chemical group 0.000 description 4
• 229910052760 oxygen Inorganic materials 0.000 description 4
• 125000000547 substituted alkyl group Chemical group 0.000 description 4
• 229910052717 sulfur Inorganic materials 0.000 description 4
• 229960002935 telaprevir Drugs 0.000 description 4
• BBAWEDCPNXPBQM-GDEBMMAJSA-N telaprevir Chemical compound N([C@H](C(=O)N[C@H](C(=O)N1C[C@@H]2CCC[C@@H]2[C@H]1C(=O)N[C@@H](CCC)C(=O)C(=O)NC1CC1)C(C)(C)C)C1CCCCC1)C(=O)C1=CN=CC=N1 BBAWEDCPNXPBQM-GDEBMMAJSA-N 0.000 description 4
• 108010017101 telaprevir Proteins 0.000 description 4
• 125000004011 3 membered carbocyclic group Chemical group 0.000 description 3
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
• 125000003342 alkenyl group Chemical group 0.000 description 3
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
• 125000000623 heterocyclic group Chemical group 0.000 description 3
• 125000004070 6 membered heterocyclic group Chemical group 0.000 description 2
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
• 150000008574 D-amino acids Chemical group 0.000 description 2
• 208000005176 Hepatitis C Diseases 0.000 description 2
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
• 102100040018 Interferon alpha-2 Human genes 0.000 description 2
• 108010079944 Interferon-alpha2b Proteins 0.000 description 2
• 241000700605 Viruses Species 0.000 description 2
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
• 125000003545 alkoxy group Chemical group 0.000 description 2
• 125000003710 aryl alkyl group Chemical group 0.000 description 2
• 125000003118 aryl group Chemical group 0.000 description 2
• 239000011230 binding agent Substances 0.000 description 2
• 239000001768 carboxy methyl cellulose Substances 0.000 description 2
• 125000001309 chloro group Chemical group Cl* 0.000 description 2
• 125000004093 cyano group Chemical group *C#N 0.000 description 2
• ZVTDLPBHTSMEJZ-JSZLBQEHSA-N danoprevir Chemical compound O=C([C@@]12C[C@H]1\C=C/CCCCC[C@@H](C(N1C[C@@H](C[C@H]1C(=O)N2)OC(=O)N1CC2=C(F)C=CC=C2C1)=O)NC(=O)OC(C)(C)C)NS(=O)(=O)C1CC1 ZVTDLPBHTSMEJZ-JSZLBQEHSA-N 0.000 description 2
• 150000002148 esters Chemical group 0.000 description 2
• SWNPNNOMXNOSHW-KQUALDNSSA-N ethyl (3r)-2-chloro-3-[(4r)-2,2-dimethyl-1,3-dioxolan-4-yl]-3-hydroxy-2-methylpropanoate Chemical compound CCOC(=O)C(C)(Cl)[C@H](O)[C@H]1COC(C)(C)O1 SWNPNNOMXNOSHW-KQUALDNSSA-N 0.000 description 2
• 125000001072 heteroaryl group Chemical group 0.000 description 2
• 125000004446 heteroarylalkyl group Chemical group 0.000 description 2
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
• HPAPGONEMPZXMM-CMWVUSIZSA-N vaniprevir Chemical compound O=C([C@H]1C[C@@H]2OC(=O)N3CC=4C=CC=C(C=4C3)CCCCC(C)(C)COC(=O)N[C@@H](C(N1C2)=O)C(C)(C)C)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C HPAPGONEMPZXMM-CMWVUSIZSA-N 0.000 description 2
• 229950000843 vaniprevir Drugs 0.000 description 2
• AQHMBDAHQGYLIU-XNFHFXFQSA-N (3s,6s,9s,12r,15s,18s,21s,24s,27r,30s,33s)-27-[2-(dimethylamino)ethylsulfanyl]-30-ethyl-33-[(e,1r,2r)-1-hydroxy-2-methylhex-4-enyl]-24-(2-hydroxy-2-methylpropyl)-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10, Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)(C)O)N(C)C(=O)[C@@H](SCCN(C)C)N(C)C1=O AQHMBDAHQGYLIU-XNFHFXFQSA-N 0.000 description 1
• OLROWHGDTNFZBH-XEMWPYQTSA-N Alisporivir Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)N(CC)C(=O)[C@@H](C)N(C)C1=O OLROWHGDTNFZBH-XEMWPYQTSA-N 0.000 description 1
• 0 CC(C)OC([C@@](C)NP(OC[C@]([C@@]([C@@]1C)O)O[C@]1N(C=CC(N1)=*)C1=O)(Oc1ccccc1)=O)=O Chemical compound CC(C)OC([C@@](C)NP(OC[C@]([C@@]([C@@]1C)O)O[C@]1N(C=CC(N1)=*)C1=O)(Oc1ccccc1)=O)=O 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 102000001493 Cyclophilins Human genes 0.000 description 1
• 108010068682 Cyclophilins Proteins 0.000 description 1
• CATMPQFFVNKDEY-YPMHNXCESA-N Golotimod Chemical compound C1=CC=C2C(C[C@H](NC(=O)CC[C@@H](N)C(O)=O)C(O)=O)=CNC2=C1 CATMPQFFVNKDEY-YPMHNXCESA-N 0.000 description 1
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• MHFMTUBUVQZIRE-WINRQGAFSA-N Sovaprevir Chemical compound C([C@H](C(=O)N1[C@@H](C[C@H](C1)OC=1C2=CC=C(C=C2N=C(C=1)C=1C=CC=CC=1)OC)C(=O)N[C@]1([C@@H](C1)C=C)C(=O)NS(=O)(=O)C1CC1)C(C)(C)C)C(=O)N1CCCCC1 MHFMTUBUVQZIRE-WINRQGAFSA-N 0.000 description 1
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• XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 1
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• DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 1
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• 229940127073 nucleoside analogue Drugs 0.000 description 1
• UAUIUKWPKRJZJV-MDJGTQRPSA-N paritaprevir Chemical compound C1=NC(C)=CN=C1C(=O)N[C@@H]1C(=O)N2C[C@H](OC=3C4=CC=CC=C4C4=CC=CC=C4N=3)C[C@H]2C(=O)N[C@]2(C(=O)NS(=O)(=O)C3CC3)C[C@@H]2\C=C/CCCCC1 UAUIUKWPKRJZJV-MDJGTQRPSA-N 0.000 description 1
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• NZVYCXVTEHPMHE-ZSUJOUNUSA-N thymalfasin Chemical compound CC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O NZVYCXVTEHPMHE-ZSUJOUNUSA-N 0.000 description 1
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