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    Macroheterocyclic nucleoside derivatives and their analogues, production and use thereof
    4.
    发明授权
    Macroheterocyclic nucleoside derivatives and their analogues, production and use thereof 有权

    公开(公告)号：US10266558B2

    公开(公告)日：2019-04-23

    申请号：US15287805

    申请日：2016-10-07

    申请人： Alexandre Vasilievich Ivachtchenko ,  Andrey Alexandrovich Ivashchenko ,  Nikolay Filippovich Savchuk ,  ASAVI, LLC ,  Alena Alexandrovna Ivachtchenko ,  Oleg Dmitrievich Mitkin

    发明人： Alexandre Vasilievich Ivachtchenko ,  Oleg Dmitrievich Mitkin ,  Andrey Alexandrovich Ivashchenko ,  Alena Alexandrovna Ivachtchenko ,  Nikolay Filippovich Savchuk

    IPC分类号： A61K31/70 ,  A01N43/04 ,  C07H19/10 ,  A61K31/7072 ,  A61K45/06 ,  A61K31/7068 ,  A61K31/7076 ,  A61K31/708 ,  A61K31/7064 ,  A61K31/7056 ,  A61K31/706 ,  A61K31/7084 ,  A61K31/7052

    摘要： Nucleosides and nucleotides (nucleos(t)ides) have been in clinical use for almost 50 years and have become cornerstones of treatment for patients with viral infections or cancer. The approval of several additional drugs over the past decade demonstrates that this family still possesses strong potential. Therefore nucleos(t)ide are of great interest as promising chemotherapeutic agents, including: 2′-deoxy-L-uridine (CAS 31501-19-6), 2′-deoxy-D-uridine (CAS 951-78-0), telbivudine (CAS 3424-98-4), zidovudine (AZT, CAS 30516-87-1), trifluridine (CAS 70-00-8), clevudine (CAS 163252-36-6), PSI-6206 (CAS 863329-66-2), 2′-(S)-2′-chloro-2′-deoxy-2′-fluorouridine (CAS 1673560-41-2), ND06954 (CAS 114248-23-6), stavudine (CAS 3056-17-5), 5-ethynyltavudine (Festinavir, CAS 634907-30-5), torcitabine (CAS 40093-94-5), (−)-beta-D-(2R,4R)-dioxolane-thymine (DOT, 1-((2R,4R)-2-(hydroxymethyl)-1,3-dioxolan-4-yl)-5-methyl-2,4(1H,3H)-pyrimidinedione, CAS No. 127658-07-5), 2-(6-amino-purin-9-yl)-ethanol (CAS 707-99-3), 2′-C-methylcytidine (CAS 20724-73-6), PSI-6130 (CAS 817204-33-4), gemcitabine (CAS 95058-81-4), 2′-chloro-2′-deoxy-2′-fluorocytidine (CAS 1786426-19-4), 2′,2′-dichloro-2′-deoxycytidine (CAS 1703785-65-2), 2′-C-methylcytidine (CAS 20724-73-6), PSI-6130 (CAS 817204-33-4), lamivudine (3TC, CAS 134678-17-4), emtricitabine (CAS 143491-57-0), 2′-deoxyadenosine (CAS 958-09-8), 2′-deoxy-β-L-adenosine (CAS 14365-45-8), 2′-deoxy-4′-C-ethynyl-2-fluoroadenosine (CAS 865363-93-5), didanosine (CAS 69655-05-6), entecavir (CAS 209216-23-9), FMCA (CAS 1307273-70-6), dioxolane-G (DOG, CAS 145514-01-8), β-D-2′-deoxy-2′-(R)-fluoro-2′-β-C-methylguanosine (CAS No 817204-45-8), abacavir (ABC, CAS 136470-78-5), dioxolane-A (DOA, CAS #145514-02-9), [(2R,4R)-4-(6-cyclopropylamino-purin-9-yl)-[1,3]dioxolan-2-yl]-methanol (CAS 1446751-04-7), amdoxovir (AMDX, CAS 145514-04-1), (R)-1-(6-amino-purin-9-yl)-propan-2-ol (CAS 14047-28-0), and [(2S,5R)-5-(6-amino-purin-9-yl)-4-fluoro-2,5-dihydro-furan-2-yl]-methanol.Macroheterocyclic nucleoside derivative and its analog of the general formula 1 or general formula 2, a stereoisomer, isotope-enriched analog, pharmaceutically acceptable salt, hydrate, solvate, or crystalline or polymorphic form thereof, wherein: Ar is aryl or hetaryl; R1 and R2 are not necessarily the same substituents selected from H, F, Cl, CH3, OH; R3 is H or CH3; X is oxygen or ethanediyl-1,1 (C═CH2); Y is CH(R4)(CH2)k, CH(R4)(CH2)mC(O)O(CH2)n; R4 is H or CH3; k has a value from zero to six; m has a value from zero to two; n has a value of one to four; Q is a radical selected from Q1-Q4; wherein: R5 is the substituent selected from H, F, Cl, CH3, OH; the arrow (→) indicates the location, joined by Q1-Q4.

    Macroheterocyclic nucleoside derivatives and their analogues, production and use thereof
    5.
    发明申请
    Macroheterocyclic nucleoside derivatives and their analogues, production and use thereof 审中-公开

    公开(公告)号：US20180099989A1

    公开(公告)日：2018-04-12

    申请号：US15287805

    申请日：2016-10-07

    申请人： Alexandre Vasilievich Ivachtchenko ,  Andrey Alexandrovich Ivashchenko ,  Nikolay Filippovich Savchuk ,  Alena Alexandrovna Ivachtchenko ,  Oleg Dmitrievich Mitkin ,  ASAVI, LLC

    发明人： Alexandre Vasilievich Ivachtchenko ,  Oleg Dmitrievich Mitkin ,  Andrey Alexandrovich Ivashchenko ,  Alena Alexandrovna Ivachtchenko ,  Nikolay Filippovich Savchuk

    IPC分类号： C07H19/10 ,  A61K45/06 ,  A61K31/7072

    CPC分类号： C07H19/10 ,  A61K31/7068 ,  A61K31/7072 ,  A61K31/7076 ,  A61K31/708 ,  A61K45/06 ,  A61K2300/00

    摘要： Nucleosides and nucleotides (nucleos(t)ides) have been in clinical use for almost 50 years and have become cornerstones of treatment for patients with viral infections or cancer. The approval of several additional drugs over the past decade demonstrates that this family still possesses strong potential. Therefore nucleos(t)ide are of great interest as promising chemotherapeutic agents, including: 2′-deoxy-L-uridine (CAS No 31501-19-6), 2′-deoxy-D-uridine (CAS No 951-78-0), telbivudine (CAS No 3424-98-4), zidovudine (AZT, CAS No 30516-87-1), trifluridine (CAS No 70-00-8), clevudine (CAS No 163252-36-6), PSI-6206 (CAS No 863329-66-2), 2′-(5)-2′-chloro-2′-deoxy-2′-fluorouridine (CAS No 1673560-41-2), ND06954 (CAS No 114248-23-6), stavudine (CAS No 3056-17-5), 5-ethynyltavudine (Festinavir, CAS No 634907-30-5), torcitabine (CAS No 40093-94-5), (−)-beta-D-(2R,4R)-dioxolane-thymine (DOT, 1-((2R,4R)-2-(hydroxymethyl)-1,3-dioxolan-4-yl)-5-methyl-2,4 (1H,3H)-pyrimidinedione, CAS No. 127658-07-5), 2-(6-amino-purin-9-yl)-ethanol (CAS No 707-99-3), 2′-C-methylcytidine (CAS No 20724-73-6), PSI-6130 (CAS No 817204-33-4), gemcitabine (CAS No 95058-81-4), 2′-chloro-2′-deoxy-2′-fluorocytidine (CAS No 1786426-19-4), 2′,2′-dichloro-2′-deoxycytidine (CAS No 1703785-65-2), 2′-C-methylcytidine (CAS No 20724-73-6), PSI-6130 (CAS No 817204-33-4), lamivudine (3TC, CAS No 134678-17-4), emtricitabine (CAS No 143491-57-0), 2′-deoxyadenosine (CAS No 958-09-8), 2′-deoxy-β-L-adenosine (CAS No 14365-45-8), 2′-deoxy-4′-C-ethynyl-2-fluoroadenosine (CAS No 865363-93-5), didanosine (CAS No 69655-05-6), entecavir (CAS No 209216-23-9), FMCA (CAS No 1307273-70-6), dioxolane-G (DOG, CAS No 145514-01-8), β-D-2′-deoxy-2′-(R)-fluoro-2′-β-C-methylguanosine (CAS No 817204-45-8), abacavir (ABC, CAS No 136470-78-5), dioxolane-A (DOA, CAS #145514-02-9), [(2R,4R)-4-(6-cyclopropylamino-purin-9-yl)-[1,3]dioxolan-2-yl]-methanol (CAS No 1446751-04-7), amdoxovir (AMDX, CAS No 145514-04-1), (R)-1-(6-amino-purin-9-yl)-propan-2-ol (CAS No 14047-28-0), and [(2S,5R)-5-(6-amino-purin-9-yl)-4-fluoro-2,5-dihydro-furan-2-yl]-methanol.Macroheterocyclic nucleoside derivative and its analogue of the general formula 1 or general formula 2, a stereoisomer, isotope-enriched analogue, pharmaceutically acceptable salt, hydrate, solvate, or crystalline or polymorphic form thereof, wherein: Ar is aryl or hetaryl; R1 and R2 are not necessarily the same substituents selected from H, F, Cl, CH3, OH; R3 is H or CH3; X is oxygen or ethanediyl-1,1 (C═CH2); Y is CH(R4)(CH2)k, CH(R4)(CH2)mC(O)O(CH2)n; R4 is H or CH3; k has a value from zero to six; m has a value from zero to two; n has a value of one to four; Q is a radical selected from Q1-Q4; wherein: R5 is the substituent selected from H, F, Cl, CH3, OH; the arrow (→) indicates the location, joined by Q1-Q4.