SK288064B6 - Peptide compounds, pharmaceutical compositions comprising them and their use - Google Patents

Info

Publication number

SK288064B6

SK288064B6 SK75-2003A SK752003A SK288064B6 SK 288064 B6 SK288064 B6 SK 288064B6 SK 752003 A SK752003 A SK 752003A SK 288064 B6 SK288064 B6 SK 288064B6

Authority

SK

Slovakia

Prior art keywords

mmol

solution

alkyl

absent

compound

Prior art date

2000-07-21

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• 150000001875 compounds Chemical class 0.000 title claims abstract description 266
• 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 46
• 239000008194 pharmaceutical composition Substances 0.000 title abstract description 15
• 108091005804 Peptidases Proteins 0.000 claims abstract description 20
• 239000004365 Protease Substances 0.000 claims abstract description 20
• 230000002401 inhibitory effect Effects 0.000 claims abstract description 7
• 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims abstract 3
• -1 their enantiomers Chemical class 0.000 claims description 82
• 239000000460 chlorine Substances 0.000 claims description 70
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 35
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 32
• 229910052739 hydrogen Inorganic materials 0.000 claims description 32
• 125000000217 alkyl group Chemical group 0.000 claims description 30
• 229910052757 nitrogen Inorganic materials 0.000 claims description 25
• 125000003118 aryl group Chemical group 0.000 claims description 24
• 229910052799 carbon Inorganic materials 0.000 claims description 22
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 22
• 229910005965 SO 2 Inorganic materials 0.000 claims description 21
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 19
• 125000001072 heteroaryl group Chemical group 0.000 claims description 19
• 229910052760 oxygen Inorganic materials 0.000 claims description 19
• 125000005222 heteroarylaminocarbonyl group Chemical group 0.000 claims description 18
• 229910052717 sulfur Inorganic materials 0.000 claims description 18
• 125000004122 cyclic group Chemical group 0.000 claims description 17
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 17
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 13
• 125000003545 alkoxy group Chemical group 0.000 claims description 11
• 125000002877 alkyl aryl group Chemical group 0.000 claims description 11
• 150000002148 esters Chemical class 0.000 claims description 11
• 125000003342 alkenyl group Chemical group 0.000 claims description 10
• 125000004432 carbon atom Chemical group C* 0.000 claims description 10
• 125000004404 heteroalkyl group Chemical group 0.000 claims description 10
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
• 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 9
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 9
• 125000004104 aryloxy group Chemical group 0.000 claims description 8
• 150000003839 salts Chemical class 0.000 claims description 8
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 7
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
• 229910052736 halogen Inorganic materials 0.000 claims description 7
• 150000002367 halogens Chemical class 0.000 claims description 7
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 6
• 125000004414 alkyl thio group Chemical group 0.000 claims description 6
• 125000000304 alkynyl group Chemical group 0.000 claims description 6
• 125000001769 aryl amino group Chemical group 0.000 claims description 6
• 125000005110 aryl thio group Chemical group 0.000 claims description 6
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 6
• 229910052731 fluorine Inorganic materials 0.000 claims description 6
• 125000000623 heterocyclic group Chemical group 0.000 claims description 6
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 6
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 5
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 5
• 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 5
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
• 150000002576 ketones Chemical class 0.000 claims description 5
• 239000012453 solvate Substances 0.000 claims description 5
• 238000006467 substitution reaction Methods 0.000 claims description 5
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 4
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
• 125000003282 alkyl amino group Chemical group 0.000 claims description 4
• 125000003368 amide group Chemical group 0.000 claims description 4
• 239000004202 carbamide Substances 0.000 claims description 4
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
• 229910052801 chlorine Inorganic materials 0.000 claims description 4
• 125000004475 heteroaralkyl group Chemical group 0.000 claims description 4
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
• 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 4
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 3
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 3
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 3
• 125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 3
• 125000005129 aryl carbonyl group Chemical group 0.000 claims description 3
• 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 3
• 125000002619 bicyclic group Chemical group 0.000 claims description 3
• 229910052794 bromium Inorganic materials 0.000 claims description 3
• 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 3
• 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 3
• 125000005226 heteroaryloxycarbonyl group Chemical group 0.000 claims description 3
• 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 3
• 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims description 3
• 229910052698 phosphorus Inorganic materials 0.000 claims description 3
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 2
• 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 claims description 2
• 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
• 229940100389 Sulfonylurea Drugs 0.000 claims description 2
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
• 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 2
• 125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims description 2
• 125000004947 alkyl aryl amino group Chemical group 0.000 claims description 2
• 125000005248 alkyl aryloxy group Chemical group 0.000 claims description 2
• 125000005422 alkyl sulfonamido group Chemical group 0.000 claims description 2
• 125000005281 alkyl ureido group Chemical group 0.000 claims description 2
• 125000005421 aryl sulfonamido group Chemical group 0.000 claims description 2
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
• UTXKJLXAUOOWAC-UHFFFAOYSA-N azanylidyne-[[cyano(nitrosulfonyl)sulfinamoyl]-nitrosulfonylamino]methane Chemical compound [O-][N+](=O)S(=O)(=O)N(C#N)S(=O)N(C#N)S(=O)(=O)[N+]([O-])=O UTXKJLXAUOOWAC-UHFFFAOYSA-N 0.000 claims description 2
• 125000005518 carboxamido group Chemical group 0.000 claims description 2
• 125000000000 cycloalkoxy group Chemical group 0.000 claims description 2
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 2
• 125000006310 cycloalkyl amino group Chemical group 0.000 claims description 2
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 2
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 2
• 125000005241 heteroarylamino group Chemical group 0.000 claims description 2
• 125000005553 heteroaryloxy group Chemical group 0.000 claims description 2
• 125000005842 heteroatom Chemical group 0.000 claims description 2
• 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 2
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
• 239000001301 oxygen Substances 0.000 claims description 2
• 125000004437 phosphorous atom Chemical group 0.000 claims description 2
• 125000005936 piperidyl group Chemical group 0.000 claims description 2
• 125000004076 pyridyl group Chemical group 0.000 claims description 2
• 150000003457 sulfones Chemical class 0.000 claims description 2
• YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 claims description 2
• 239000011593 sulfur Substances 0.000 claims description 2
• 125000001544 thienyl group Chemical group 0.000 claims description 2
• 125000001424 substituent group Chemical group 0.000 claims 2
• 235000020028 corn beer Nutrition 0.000 claims 1
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 353
• 239000000243 solution Substances 0.000 description 348
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 245
• VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 175
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 141
• 239000011541 reaction mixture Substances 0.000 description 140
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 134
• 235000019439 ethyl acetate Nutrition 0.000 description 132
• 239000000203 mixture Substances 0.000 description 120
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 110
• 230000015572 biosynthetic process Effects 0.000 description 106
• 238000003786 synthesis reaction Methods 0.000 description 104
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 95
• 239000012044 organic layer Substances 0.000 description 93
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 86
• 238000000034 method Methods 0.000 description 85
• 239000000047 product Substances 0.000 description 83
• 229940093499 ethyl acetate Drugs 0.000 description 82
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 80
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 70
• 239000011347 resin Substances 0.000 description 69
• 229920005989 resin Polymers 0.000 description 69
• 239000012267 brine Substances 0.000 description 67
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 57
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 57
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 57
• 0 CCCC(C(C(**C(C(*I)=O)*1=CC(C)C=C1)=O)=O)NC(C(CCC1C)*1C([C@@]1NC(OCC(C)*)=*C1(*)*)=*C)=O Chemical compound CCCC(C(C(**C(C(*I)=O)*1=CC(C)C=C1)=O)=O)NC(C(CCC1C)*1C([C@@]1NC(OCC(C)*)=*C1(*)*)=*C)=O 0.000 description 50
• 241000711549 Hepacivirus C Species 0.000 description 50
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 50
• 238000006243 chemical reaction Methods 0.000 description 50
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 49
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• 239000010410 layer Substances 0.000 description 46
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• 229920006395 saturated elastomer Polymers 0.000 description 42
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 37
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• 238000001819 mass spectrum Methods 0.000 description 32
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• 238000003756 stirring Methods 0.000 description 29
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• KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 14
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