CZ20023963A3 - Nové deriváty (thio)močoviny inhibující faktor VIIa, způsob jejich přípravy a jejich použití - Google Patents

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Publication number

CZ20023963A3

CZ20023963A3 CZ20023963A CZ20023963A CZ20023963A3 CZ 20023963 A3 CZ20023963 A3 CZ 20023963A3 CZ 20023963 A CZ20023963 A CZ 20023963A CZ 20023963 A CZ20023963 A CZ 20023963A CZ 20023963 A3 CZ20023963 A3 CZ 20023963A3

Authority

CZ

Czechia

Prior art keywords

group

carbon atoms

alkyl

aryl

het

Prior art date

2000-06-06

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• 238000000034 method Methods 0.000 title claims abstract description 26
• 238000002360 preparation method Methods 0.000 title claims abstract description 13
• 230000008569 process Effects 0.000 title claims abstract description 7
• 230000002401 inhibitory effect Effects 0.000 title claims description 13
• UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical class NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 title description 4
• 150000001875 compounds Chemical class 0.000 claims abstract description 223
• 230000023555 blood coagulation Effects 0.000 claims abstract description 25
• 125000004432 carbon atom Chemical group C* 0.000 claims description 268
• -1 cyano, hydroxyl Chemical group 0.000 claims description 225
• 125000000217 alkyl group Chemical group 0.000 claims description 177
• 125000003118 aryl group Chemical group 0.000 claims description 145
• 125000003545 alkoxy group Chemical group 0.000 claims description 69
• 125000001424 substituent group Chemical group 0.000 claims description 64
• 150000003839 salts Chemical class 0.000 claims description 53
• 125000000623 heterocyclic group Chemical group 0.000 claims description 38
• 239000000203 mixture Substances 0.000 claims description 33
• 229910052799 carbon Inorganic materials 0.000 claims description 31
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 31
• 229920006395 saturated elastomer Polymers 0.000 claims description 27
• 239000001257 hydrogen Substances 0.000 claims description 26
• 229910052739 hydrogen Inorganic materials 0.000 claims description 26
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 22
• 229910052757 nitrogen Inorganic materials 0.000 claims description 22
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 21
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 21
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 20
• 238000011282 treatment Methods 0.000 claims description 18
• 229910052736 halogen Inorganic materials 0.000 claims description 17
• 150000002367 halogens Chemical class 0.000 claims description 17
• 125000003277 amino group Chemical group 0.000 claims description 16
• 150000001721 carbon Chemical group 0.000 claims description 16
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
• 201000010099 disease Diseases 0.000 claims description 14
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
• 229910052717 sulfur Inorganic materials 0.000 claims description 14
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
• 125000005842 heteroatom Chemical group 0.000 claims description 13
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
• 239000008194 pharmaceutical composition Substances 0.000 claims description 12
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
• 229910052760 oxygen Chemical group 0.000 claims description 11
• 239000001301 oxygen Chemical group 0.000 claims description 11
• 125000002837 carbocyclic group Chemical group 0.000 claims description 10
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 9
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 9
• 239000002243 precursor Substances 0.000 claims description 9
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
• 208000037803 restenosis Diseases 0.000 claims description 8
• 125000006413 ring segment Chemical group 0.000 claims description 8
• 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 8
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
• 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 7
• 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 7
• LCIYFINKFGDAHD-UHFFFAOYSA-N azepane;3-nitrobenzoic acid Chemical compound C1CCCNCC1.OC(=O)C1=CC=CC([N+]([O-])=O)=C1 LCIYFINKFGDAHD-UHFFFAOYSA-N 0.000 claims description 7
• 125000000524 functional group Chemical group 0.000 claims description 7
• ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 7
• 125000002950 monocyclic group Chemical group 0.000 claims description 7
• 239000011593 sulfur Substances 0.000 claims description 7
• 125000004434 sulfur atom Chemical group 0.000 claims description 7
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
• 125000005125 aryl alkyl amino carbonyl group Chemical group 0.000 claims description 6
• 125000002619 bicyclic group Chemical group 0.000 claims description 6
• 125000004043 oxo group Chemical group O=* 0.000 claims description 6
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 6
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 5
• 229940082863 Factor VIIa inhibitor Drugs 0.000 claims description 5
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 5
• 125000003282 alkyl amino group Chemical group 0.000 claims description 5
• 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 5
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
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• 239000003937 drug carrier Substances 0.000 claims description 4
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• 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 3
• 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims description 3
• 125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 3
• 125000005141 aryl amino sulfonyl group Chemical group 0.000 claims description 3
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• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
• 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 2
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• 230000028709 inflammatory response Effects 0.000 claims description 2
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• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
• 108010054265 Factor VIIa Proteins 0.000 abstract description 30
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• 230000002441 reversible effect Effects 0.000 abstract description 2
• 239000000243 solution Substances 0.000 description 58
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• 239000002904 solvent Substances 0.000 description 37
• 238000004949 mass spectrometry Methods 0.000 description 33
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 23
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
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