EA019295B1 - Соединения пуриновых нуклеозидов и способ их получения - Google Patents

Info

Publication number

EA019295B1

EA019295B1 EA201100932A EA201100932A EA019295B1 EA 019295 B1 EA019295 B1 EA 019295B1 EA 201100932 A EA201100932 A EA 201100932A EA 201100932 A EA201100932 A EA 201100932A EA 019295 B1 EA019295 B1 EA 019295B1

Authority

EA

Eurasian Patent Office

Prior art keywords

compound

inhibitor

mmol

mixture

solution

Prior art date

2008-12-23

Links

• Espacenet
• Global Dossier
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• 230000015572 biosynthetic process Effects 0.000 title description 24
• 238000003786 synthesis reaction Methods 0.000 title description 20
• 238000004519 manufacturing process Methods 0.000 title description 2
• 239000002212 purine nucleoside Substances 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 118
• 150000003839 salts Chemical class 0.000 claims abstract description 35
• -1 methoxy, ethoxy, isopropyl Chemical group 0.000 claims description 131
• 125000000217 alkyl group Chemical group 0.000 claims description 71
• 238000000034 method Methods 0.000 claims description 36
• 239000003112 inhibitor Substances 0.000 claims description 22
• 239000003795 chemical substances by application Substances 0.000 claims description 16
• 239000008194 pharmaceutical composition Substances 0.000 claims description 16
• 238000002441 X-ray diffraction Methods 0.000 claims description 13
• 238000011282 treatment Methods 0.000 claims description 11
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
• 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 8
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 5
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
• 239000003937 drug carrier Substances 0.000 claims description 4
• 238000002329 infrared spectrum Methods 0.000 claims description 4
• 208000005176 Hepatitis C Diseases 0.000 claims description 3
• 229940124158 Protease/peptidase inhibitor Drugs 0.000 claims 5
• 208000036142 Viral infection Diseases 0.000 claims 2
• 230000009385 viral infection Effects 0.000 claims 2
• 230000001012 protector Effects 0.000 claims 1
• 230000011514 reflex Effects 0.000 claims 1
• 150000003833 nucleoside derivatives Chemical class 0.000 abstract description 24
• 229910019142 PO4 Inorganic materials 0.000 abstract description 10
• 239000010452 phosphate Substances 0.000 abstract description 9
• 125000004122 cyclic group Chemical group 0.000 abstract description 7
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• 239000002253 acid Substances 0.000 abstract description 6
• 239000012453 solvate Substances 0.000 abstract description 6
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• 150000004677 hydrates Chemical class 0.000 abstract description 2
• 229940002612 prodrug Drugs 0.000 abstract 2
• 239000000651 prodrug Substances 0.000 abstract 2
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• 238000005481 NMR spectroscopy Methods 0.000 description 30
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• 125000004432 carbon atom Chemical group C* 0.000 description 27
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• 239000013078 crystal Substances 0.000 description 15
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• 229910052757 nitrogen Inorganic materials 0.000 description 14
• 235000000346 sugar Nutrition 0.000 description 14
• 239000012223 aqueous fraction Substances 0.000 description 13
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 13
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• 238000000132 electrospray ionisation Methods 0.000 description 13
• 239000011734 sodium Substances 0.000 description 13
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• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 12
• 102100037580 Sesquipedalian-1 Human genes 0.000 description 12
• 101710169844 Sesquipedalian-1 Proteins 0.000 description 12
• 229910052794 bromium Inorganic materials 0.000 description 12
• 229910052799 carbon Inorganic materials 0.000 description 12
• 238000004128 high performance liquid chromatography Methods 0.000 description 12
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 12
• 238000010898 silica gel chromatography Methods 0.000 description 12
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 12
• 241000711549 Hepacivirus C Species 0.000 description 11
• 239000002585 base Substances 0.000 description 11
• 229960004592 isopropanol Drugs 0.000 description 11
• 229910052698 phosphorus Inorganic materials 0.000 description 11
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 11
• 229910052739 hydrogen Inorganic materials 0.000 description 10
• 239000007788 liquid Substances 0.000 description 10
• 238000000746 purification Methods 0.000 description 10
• 239000000523 sample Substances 0.000 description 10
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 9
• 239000004480 active ingredient Substances 0.000 description 9
• 229940024606 amino acid Drugs 0.000 description 9
• 210000004027 cell Anatomy 0.000 description 9
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• 239000007858 starting material Substances 0.000 description 9
• 238000003756 stirring Methods 0.000 description 9
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
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• 241000700605 Viruses Species 0.000 description 8
• 125000003342 alkenyl group Chemical group 0.000 description 8
• 125000000304 alkynyl group Chemical group 0.000 description 8
• 235000001014 amino acid Nutrition 0.000 description 8
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 8
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