HU229262B1 - Hepatitis c inhibitor tri-peptides, process for production thereof, pharmaceutical compositions copmprising thereof, intermediates and their use - Google Patents

Info

Publication number

HU229262B1

HU229262B1 HU0105144A HUP0105144A HU229262B1 HU 229262 B1 HU229262 B1 HU 229262B1 HU 0105144 A HU0105144 A HU 0105144A HU P0105144 A HUP0105144 A HU P0105144A HU 229262 B1 HU229262 B1 HU 229262B1

Authority

HU

Hungary

Prior art keywords

alkyl

carbamoyl

optionally

formula

group

Prior art date

1998-08-10

Links

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• Global Dossier
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• 238000000034 method Methods 0.000 title claims description 63
• 239000003112 inhibitor Substances 0.000 title claims description 26
• 239000008194 pharmaceutical composition Substances 0.000 title claims description 17
• 230000008569 process Effects 0.000 title claims description 8
• 238000004519 manufacturing process Methods 0.000 title claims description 6
• 239000000543 intermediate Substances 0.000 title description 7
• 208000006454 hepatitis Diseases 0.000 title 1
• 231100000283 hepatitis Toxicity 0.000 title 1
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 361
• 150000001875 compounds Chemical class 0.000 claims abstract description 197
• 125000003118 aryl group Chemical group 0.000 claims abstract description 98
• 150000002148 esters Chemical class 0.000 claims abstract description 91
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 89
• 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 82
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 77
• 229920006395 saturated elastomer Polymers 0.000 claims abstract description 61
• 150000003839 salts Chemical class 0.000 claims abstract description 60
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 48
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 41
• 125000005843 halogen group Chemical group 0.000 claims abstract description 25
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 24
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 24
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract description 23
• 125000002252 acyl group Chemical group 0.000 claims abstract description 20
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 14
• 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 12
• 125000004966 cyanoalkyl group Chemical group 0.000 claims abstract description 12
• 230000003287 optical effect Effects 0.000 claims abstract description 9
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 7
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims abstract description 7
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 3
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract 3
• -1 Thiocarbamoyl Chemical group 0.000 claims description 163
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 152
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 69
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 65
• 125000003277 amino group Chemical group 0.000 claims description 52
• 241000711549 Hepacivirus C Species 0.000 claims description 51
• 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 46
• 125000004432 carbon atom Chemical group C* 0.000 claims description 42
• 125000003545 alkoxy group Chemical group 0.000 claims description 41
• 150000002367 halogens Chemical class 0.000 claims description 38
• 229910052799 carbon Inorganic materials 0.000 claims description 35
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 32
• 229910052739 hydrogen Inorganic materials 0.000 claims description 32
• 150000001413 amino acids Chemical class 0.000 claims description 31
• 239000001257 hydrogen Substances 0.000 claims description 31
• 125000006239 protecting group Chemical group 0.000 claims description 30
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 26
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 24
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 23
• 238000011282 treatment Methods 0.000 claims description 23
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
• 206010029897 Obsessive thoughts Diseases 0.000 claims description 21
• 239000003795 chemical substances by application Substances 0.000 claims description 21
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 21
• 150000001412 amines Chemical class 0.000 claims description 20
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 18
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 18
• 241000124008 Mammalia Species 0.000 claims description 17
• 125000001424 substituent group Chemical group 0.000 claims description 17
• 229920002554 vinyl polymer Polymers 0.000 claims description 17
• 238000002360 preparation method Methods 0.000 claims description 15
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• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
• 150000001721 carbon Chemical group 0.000 claims description 11
• 229910052757 nitrogen Inorganic materials 0.000 claims description 11
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 8
• 125000000623 heterocyclic group Chemical group 0.000 claims description 8
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
• 125000003396 thiol group Chemical class [H]S* 0.000 claims description 8
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 7
• 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 7
• 239000000460 chlorine Substances 0.000 claims description 7
• 239000003814 drug Substances 0.000 claims description 7
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
• 239000000126 substance Substances 0.000 claims description 7
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 6
• 102000014150 Interferons Human genes 0.000 claims description 6
• 108010050904 Interferons Proteins 0.000 claims description 6
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Chemical compound CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 6
• 150000002431 hydrogen Chemical class 0.000 claims description 6
• 230000002401 inhibitory effect Effects 0.000 claims description 6
• 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 5
• 108060004795 Methyltransferase Proteins 0.000 claims description 5
• 229910052796 boron Inorganic materials 0.000 claims description 5
• 208000010710 hepatitis C virus infection Diseases 0.000 claims description 5
• 229940079322 interferon Drugs 0.000 claims description 5
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
• TXHAHOVNFDVCCC-UHFFFAOYSA-N 2-(tert-butylazaniumyl)acetate Chemical compound CC(C)(C)NCC(O)=O TXHAHOVNFDVCCC-UHFFFAOYSA-N 0.000 claims description 4
• 125000005979 2-naphthyloxy group Chemical group 0.000 claims description 4
• KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical group NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims description 4
• 229910052801 chlorine Inorganic materials 0.000 claims description 4
• 125000000000 cycloalkoxy group Chemical group 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• PAJPWUMXBYXFCZ-UHFFFAOYSA-N 1-aminocyclopropanecarboxylic acid Chemical group OC(=O)C1(N)CC1 PAJPWUMXBYXFCZ-UHFFFAOYSA-N 0.000 claims description 3
• 125000005978 1-naphthyloxy group Chemical group 0.000 claims description 3
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
• 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 description 3
• 125000005907 alkyl ester group Chemical group 0.000 claims description 3
• 125000004414 alkyl thio group Chemical group 0.000 claims description 3
• DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 claims description 3
• 229960003805 amantadine Drugs 0.000 claims description 3
• 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 claims description 3
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
• 230000009467 reduction Effects 0.000 claims description 3
• 229960000329 ribavirin Drugs 0.000 claims description 3
• 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 description 3
• 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 2
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 2
• 102000003996 Interferon-beta Human genes 0.000 claims description 2
• 108090000467 Interferon-beta Proteins 0.000 claims description 2
• 125000001931 aliphatic group Chemical group 0.000 claims description 2
• 125000003342 alkenyl group Chemical group 0.000 claims description 2
• 125000005189 alkyl hydroxy group Chemical group 0.000 claims description 2
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
• 125000005842 heteroatom Chemical group 0.000 claims description 2
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
• 229910052760 oxygen Inorganic materials 0.000 claims description 2
• 239000001301 oxygen Substances 0.000 claims description 2
• 150000003147 proline derivatives Chemical class 0.000 claims description 2
• 230000010076 replication Effects 0.000 claims description 2
• 229910052717 sulfur Inorganic materials 0.000 claims description 2
• 125000004665 trialkylsilyl group Chemical group 0.000 claims description 2
• GBXQPDCOMJJCMJ-UHFFFAOYSA-M trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;bromide Chemical compound [Br-].C[N+](C)(C)CCCCCC[N+](C)(C)C GBXQPDCOMJJCMJ-UHFFFAOYSA-M 0.000 claims 30
• 125000001589 carboacyl group Chemical group 0.000 claims 7
• 125000003282 alkyl amino group Chemical group 0.000 claims 2
• 125000000446 sulfanediyl group Chemical group *S* 0.000 claims 2
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 1
• 125000006546 (C4-C10) cycloalkyl group Chemical group 0.000 claims 1
• MJXWHMDRUYILPC-UHFFFAOYSA-N 2-ethenyl-3-ethyl-1H-indole Chemical compound C1=CC=C2C(CC)=C(C=C)NC2=C1 MJXWHMDRUYILPC-UHFFFAOYSA-N 0.000 claims 1
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims 1
• 125000004647 alkyl sulfenyl group Chemical group 0.000 claims 1
• 125000005418 aryl aryl group Chemical group 0.000 claims 1
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims 1
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims 1
• 125000005112 cycloalkylalkoxy group Chemical group 0.000 claims 1
• 230000003111 delayed effect Effects 0.000 claims 1
• 229960001388 interferon-beta Drugs 0.000 claims 1
• 150000002642 lithium compounds Chemical class 0.000 claims 1
• 125000004434 sulfur atom Chemical group 0.000 claims 1
• 150000001408 amides Chemical class 0.000 abstract description 9
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• 125000004209 (C1-C8) alkyl group Chemical group 0.000 abstract 1
• AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 abstract 1
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