公开(公告)号：US09085539B2

公开(公告)日：2015-07-21

申请号：US13831929

申请日：2013-03-15

申请人： Alexandre Vasilievich Ivachtchenko ,  Oleg Dmitrievich Mitkin

发明人： Alexandre Vasilievich Ivachtchenko ,  Oleg Dmitrievich Mitkin

IPC分类号： A61K31/505 ,  C07D233/86 ,  C07D491/107 ,  C07D471/10

CPC分类号： C07D233/86 ,  C07D471/10 ,  C07D491/107

摘要： The present invention relates to novel cyclic N,N′-diarylurea—androgen receptor antagonist, anti-cancer agent, pharmaceutical composition, medicament, and method for treatment of breast cancer disease.Cyclic N,N′-diarylthioureas or N,N′-diarylureas of the general formula 1, their optical (R)- and (S)-isomers and pharmaceutically acceptable salts thereof exhibiting properties of androgen receptor antagonists have been proposed, wherein: R1 represents C1-C3 alkyl; R4 and R5 represent hydrogen; or R4 represents hydrogen, R5 represents methyl; or R4 represents methyl, R5 represents CH2R6 group in which R6 is C1-C3 alkoxycarbonyl, carboxyl, hydroxyl group optionally substituted with methyl or benzyl; or R4 and R5 together with the carbon atom they are attached to form 5- or 6-membered saturated heterocycle including at least one oxygen atom or nitrogen atom optionally substituted with methyl.

摘要翻译： 本发明涉及新的环状N，N'-二芳基脲 - 雄激素受体拮抗剂，抗癌剂，药物组合物，药物和治疗乳腺癌疾病的方法。 已经提出了通式1的环状N，N'-二芳基硫脲或N，N'-二芳基脲，其表现出雄激素受体拮抗剂性质的光学（R） - 和（S） - 异构体及其药学上可接受的盐，其中：R1 表示C1-C3烷基; R4和R5代表氢; 或R 4表示氢，R 5表示甲基; 或R 4表示甲基，R 5表示CH 2 R 6基，其中R 6为C 1 -C 3烷氧基羰基，羧基，任选被甲基或苄基取代的羟基; 或R 4和R 5与它们连接的碳原子一起形成包含至少一个氧原子或任选被甲基取代的氮原子的5-或6-元饱和杂环。

公开(公告)号：US20180030080A1

公开(公告)日：2018-02-01

申请号：US15221613

申请日：2016-07-28

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： C07H19/16 ,  C07H19/06 ,  C07F9/6558 ,  C07F9/6561

CPC分类号： C07H19/16 ,  A61P31/12 ,  A61P35/00 ,  C07F9/65586 ,  C07F9/65616 ,  C07H19/06 ,  C07H19/10 ,  C07H19/20

摘要： The present invention pertains to chemotherapeutic agents and their use for treating viral and cancerous diseases. These compounds are inhibitors of HCV NS5B polymerase, HBV DNA polymerase and, HIV-1 reverse transcriptase (RT) inhibitor, and for treatment of hepatitis B and C infection in mammals. These compounds are also of interest for the treatment of cancer.The phosphoramidate nucleoside prodrug of the general formula 1, a stereoisomer, isotope-enriched analogue, pharmaceutically acceptable salt, hydrate, solvate, or crystalline or polymorphic form thereof, wherein: Ar is aryl or hetaryl; R1 is H or CH3; R2 is the substituent selected from OCH2CH═CH2, OCH2CH≡CH, OCH2CH2CH2OCH3, R3 is H or CH3; R4 is OH, OR5, NR6R7; R5 is C1-C4-alkyl; R6 and R7 are not necessarily the same substituents selected from H or CH3; Z═O, or NH; an arrow (→) indicates the place of substituent connection; Nuc is R8 and R9 are not necessarily the same substituents selected from H, F, Cl, CH3 or OH provided when continuous line and its accompanying dotted line () together are the single carbon-carbon (C—C) bond or R8 and R9 are hydrogen provided when continuous line and its accompanying dotted line () together are the double carbon-carbon bond (C═C); R10 is the substituent selected from R10.1-R10.5; R11 is the substituent selected from H, F, Cl, CH3, or CF3; R12 is hydrogen, C1-C4-alkyl or C3-C6-cycloalkyl; X is oxygen or ethanediyl-1,1 (C═CH2); Y is O, S, CH2, or HO—CH group provided when continuous line and its accompanying dotted line () together are the single carbon-carbon (C—C) bond or Y is CH group provided when continuous line and its accompanying dotted line () together are the double carbon-carbon bond (C═C), and compound of the general formula 1, stereoisomers, isotope-enriched analogues, pharmaceutically acceptable salts, hydrates, solvates, or crystalline or polymorphic forms thereof, wherein: Ar is aryl or hetaryl; R1 is H or CH3; R is isopropyl; Nuc is

公开(公告)号：US09428491B2

公开(公告)日：2016-08-30

申请号：US13990428

申请日：2011-11-28

申请人： Alexandre Vasilievich Ivachtchenko ,  Vadim Vasilievich Bichko ,  Oleg Dmitrievich Mitkin

发明人： Alexandre Vasilievich Ivachtchenko ,  Vadim Vasilievich Bichko ,  Oleg Dmitrievich Mitkin

IPC分类号： C07D403/14 ,  C07D403/04 ,  C07D409/14 ,  C07D405/14 ,  C07D413/14

CPC分类号： C07D403/14 ,  C07D403/04 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14

摘要： The present invention relates to novel antiviral active 5-{4-[1H-imidazol-5-ylaryl(or hetaryl)]-buta-1,3-diynyl}-1H-imidazoles of the general formula 1 and pharmaceutically acceptable salt thereof, pharmaceutical composition, antiviral medicament, therapeutic kit for prophylaxis and treatment of hepatisis C virus diseases, and method for prophylaxis and treatment of hepatisis C. wherein: R1 and R2—represent optionally identical radicals selected from 2.1 and 2.2, where an asterisk (*) denotes the position of attachment to the imidazole fragment, (S) and (R) are types of chiral centers; R3 is isopropyl or phenyl radicals; Ar an aromatic or heteroaromatic diradical.

摘要翻译： 本发明涉及通式1的新型抗病毒活性5- {4- [1H-咪唑-5-基芳基（或杂芳基）] - 丁-1,3-二炔基} -1H-咪唑及其药学上可接受的盐， 药物组合物，抗病毒药物，用于预防和治疗肝炎C病毒疾病的治疗试剂盒，以及预防和治疗肝炎C.其中：R1和R2代表任选地相同的选自2.1和2.2的基因，其中星号（*） 表示连接到咪唑片段的位置，（S）和（R）是手性中心的类型; R3是异丙基或苯基; Ar是芳族或杂芳族双基。

公开(公告)号：US20130267551A1

公开(公告)日：2013-10-10

申请号：US13993127

申请日：2011-12-13

申请人： Alexandre Vasilievich Ivachtchenko ,  Oleg Dmitrievich Mitkin

发明人： Alexandre Vasilievich Ivachtchenko ,  Oleg Dmitrievich Mitkin

IPC分类号： C07D495/14

CPC分类号： C07D495/14 ,  C07D471/04 ,  C07D495/22

摘要： The present invention relates to novel substituted tetrahydro-4H-thieno-pyrrolo[3,2-c]pyridines of the general formula 1, geometrical isomers, mixtures of geometrical isomers, and pharmaceutically acceptable salts thereof, wherein Th represents annelated thienic cycle; W represents ordinary bond (in this case R3 is bound directly to N-atom of pyrrole cycle), methylene, 1,2-ethylene, 1,2-vinyl, 1,2-ethynylene, 1,3-propanediyl or 1,3-propenylene, optionally substituted with hydroxy group; R1 and R2 represent hydrogen, C1-C4alkyl, halogen or —CH2OH; R3 represents hydrogen, optionally substituted phenyl, optionally substituted azaheteroaryl; R4 represents C1-C4alkyl, CO2C2H5 or CO2C(CH3)3; R5, R6, R7 independently of each other represent hydrogen or C1-C4alkyl, or R5 and R6 form together ethylene bridge, and R7 represents hydrogen, or R5 and R7 form together ethylene bridge, and R6 represents hydrogen. And also to synthesis of novel chemical compounds, novel physiologically active compounds, “molecular tools”, to pharmaceutical composition, methods for preparation thereof and to method of treatment and prophylaxis of various diseases including diseases of central nervous system (CNS).

摘要翻译： 本发明涉及通式1的新型取代的四氢-4H-噻吩并吡咯并[3,2-c]吡啶，几何异构体，几何异构体的混合物及其药学上可接受的盐，其中Th表示环状的环状循环; W代表普通键（在这种情况下，R3直接与吡咯环的N-原子结合），亚甲基，1,2-亚乙基，1,2-乙烯基，1,2-亚乙炔基，1,3-丙二基或1,3 - 亚丙基，任选被羟基取代; R1和R2表示氢，C1-C4烷基，卤素或-CH2OH; R 3表示氢，任选取代的苯基，任选取代的杂芳基; R4表示C1-C4烷基，CO2C2H5或CO2C（CH3）3; R5，R6，R7彼此独立地表示氢或C1-C4烷基，或R5和R6一起形成乙烯桥，R7表示氢，或R5和R7一起形成乙烯桥，R6表示氢。 还涉及新型化学化合物，新型生理活性化合物，“分子工具”，药物组合物，其制备方法以及治疗和预防各种疾病（包括中枢神经系统疾病（CNS））的方法。

公开(公告)号：US20130267536A1

公开(公告)日：2013-10-10

申请号：US13993131

申请日：2011-12-13

申请人： Alexandre Vasilievich Ivachtchenko ,  Oleg Dmitrievich Mitkin ,  Madina Georgievna Kadieva

发明人： Alexandre Vasilievich Ivachtchenko ,  Oleg Dmitrievich Mitkin ,  Madina Georgievna Kadieva

IPC分类号： C07D471/04 ,  C07D215/42 ,  C07D413/14 ,  C07D413/04 ,  C07C317/36 ,  C07D295/135 ,  C07D213/40

CPC分类号： C07D471/04 ,  C07C317/36 ,  C07D213/40 ,  C07D215/42 ,  C07D295/135 ,  C07D413/04 ,  C07D413/14

摘要： The present invention relates to novel substituted methyl-amines, serotonin 5-HT6 receptor antagonists, to active components, pharmaceutical compositions, method for prophylaxis and treatment of CNS diseases and “molecular tools”, in which novel substituted methyl-amines represent compounds of the general formula 1 and their crystalline forms and pharmaceutically acceptable salts, wherein: W represents benzene, naphthalene, indolizine, quinoline or oxazole cycle; R1=H, F, Cl; R2 represents hydrogen, fluoro, methyl, phenyl, thienyl, furan-2-yl, pyridyl, piperazin-1-yl or 4-methylpiperazin-1-yl; R3 represents cyclopropyl or optionally substituted methyl; with the exception of the compounds in which W simultaneously represents oxazole cycle and R2=phenyl or pyridyl.

摘要翻译： 本发明涉及新型取代的甲基胺，5-羟色胺5-HT 6受体拮抗剂，活性组分，药物组合物，预防和治疗CNS疾病的方法和“分子工具”，其中新的取代的甲基胺代表 通式1及其结晶形式和药学上可接受的盐，其中：W代表苯，萘，中氮茚，喹啉或恶唑循环; R1 = H，F，Cl; R 2表示氢，氟，甲基，苯基，噻吩基，呋喃-2-基，吡啶基，哌嗪-1-基或4-甲基哌嗪-1-基; R3表示环丙基或任选取代的甲基; 除了其中W同时表示恶唑循环和R2 =苯基或吡啶基的化合物之外。

公开(公告)号：US20100120792A1

公开(公告)日：2010-05-13

申请号：US12594453

申请日：2008-04-01

申请人： Andrey Alexandrovich Ivashchenko ,  Alexandre Vasilievich Ivachtchenko ,  Sergey Yevgenievich Tkachenko ,  Evgueni Borisovich Frolov ,  Oleg Dmitrievich Mitkin ,  llya Matusovich Okun ,  Nikolay Filippovich Savchuk ,  Yan Lavrovsky

发明人： Andrey Alexandrovich Ivashchenko ,  Alexandre Vasilievich Ivachtchenko ,  Sergey Yevgenievich Tkachenko ,  Evgueni Borisovich Frolov ,  Oleg Dmitrievich Mitkin ,  llya Matusovich Okun ,  Nikolay Filippovich Savchuk ,  Yan Lavrovsky

IPC分类号： A61K31/4427 ,  A61K31/4745 ,  C07D471/04 ,  A61P25/08 ,  A61P25/18 ,  A61P25/28 ,  A61P25/24 ,  A61P25/22 ,  A61P9/10

CPC分类号： A61K31/437 ,  A61K31/444 ,  C07D471/04

摘要： The invention relates to antagonists of serotonin 5-HT6 receptors simultaneously regulating homeostasis of Ca+2 ions in cells, representing substituted 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles of the general formula 1, pharmaceutically acceptable salts and/or hydrate thereof. In the general formula 1: R1 represents amino group substituent selected from optionally substituted C1-C5 alkyl; R2, is one or more substituents selected from hydrogen, halogen, C1-C3 alkyl, CF3, OCF3; Ar is phenyl optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, substituted amino group, or CF3; or optionally substituted aromatic 6-membered heterocycle comprising 1-2 nitrogen atoms in the cycle; W represents ethylene group —CH2—CH2—, ethenyl group —CH═CH—, or ethynyl group —C≡C—. The invention also relates to the novel compounds selected from the compounds of the general formula 1, methods for their preparation, pharmaceutical compositions and methods of their use.

摘要翻译： 本发明涉及同时调节细胞中Ca 2+离子的体内平衡的5-羟色胺5-HT6受体的拮抗剂，代表通式1的取代的2,3,4,5-四氢-1H-吡啶并[4,3-b]吲哚 ，其药学上可接受的盐和/或水合物。 在通式1中：R 1表示选自任选取代的C 1 -C 5烷基的氨基取代基; R2是选自氢，卤素，C1-C3烷基，CF3，OCF3中的一个或多个取代基; Ar是任选被卤素，C 1 -C 6烷基，C 1 -C 6烷氧基，取代的氨基或CF 3取代的苯基; 或在该循环中任选取代的包含1-2个氮原子的芳族6-元杂环; W表示亚乙基-CH 2 -CH 2 - ，乙烯基-CH = CH-或乙炔基-C≡C-。 本发明还涉及选自通式1的化合物，其制备方法，药物组合物及其用途的新化合物。

公开(公告)号：US20130196991A1

公开(公告)日：2013-08-01

申请号：US13811669

申请日：2011-07-19

申请人： Alexandre Vasilievich Ivachtchenko ,  Oleg Dmitrievich Mitkin ,  Vadim Vasilievich Bichko

发明人： Alexandre Vasilievich Ivachtchenko ,  Oleg Dmitrievich Mitkin ,  Vadim Vasilievich Bichko

IPC分类号： C07D487/06 ,  C07D413/14 ,  C07D401/14 ,  C07D401/06

CPC分类号： C07D487/06 ,  A61K9/0019 ,  A61K9/145 ,  A61K9/2059 ,  A61K31/404 ,  A61K31/454 ,  A61K31/496 ,  A61K31/4985 ,  C07D209/82 ,  C07D209/88 ,  C07D401/06 ,  C07D401/14 ,  C07D413/14 ,  C07D487/04

摘要： The invention relates to novel antiviral active components of the general formula 1, pharmaceutical composition, antiviral medicament, method for prophylaxis and treatment of viral diseases, particularly caused by hepatisis C viruses (HCV). In the general formula 1 R1 represents hydrogen, optionally substituted C1-C4 alkyl, C6 cycloalkyl, aryl, ethoxycarbonyl, nitro group; R2 represents hydrogen; R3 represents N-mono- or N,N-disubstituted 1-methylene-piperidine-3-carboxamide of the general formula 1a or N-mono- or N,N-disubstituted 1-methylene-piperidine-4-carboxamide of the general formula 1b; R4 represents hydrogen, optionally substituted C1-C3 alkyl; or R2 and R3 together with the C-atoms they are attached to form substituted 2,3,4,9-tetrahydro-1H-carbazole of the general formula 1.1, or R2, R3, and R4 together with the atoms they are attached to form substituted azaheterocycles of the general formula 1.2; R5 and R6 optionally identical represent hydrogen, optionally substituted C1-C3 alkyl or C3-C6 cycloalkyl, or R5 and R6 together with the N-atom they are attached to form optionally substituted 5- or 6-membered azaheterocyclyl comprising one or two N-atoms and optionally condensed with benzene ring; R7 and R8 represent hydrogen or R7 and R8 together with the C-atom they are attached to form C═0 group; R9 represents azaheterocyclyl comprising at least one N-atom, unsubstituted formamide, or phenyl substituted with ethoxycarbonyl or nitro group; R10 represents hydrogen, optionally substituted C1-C3 alkyl, substituted acetyl; n=1 or 2; solid line accompanied by the dotted line, i.e. (), represents single or double C—C bond.

摘要翻译： 本发明涉及通式1的新型抗病毒活性成分，药物组合物，抗病毒药物，预防和治疗病毒性疾病的方法，尤其是由丙型肝炎病毒（HCV）引起的。 在通式1中，R1表示氢，任选取代的C 1 -C 4烷基，C 6环烷基，芳基，乙氧羰基，硝基; R2表示氢; R 3表示通式1a的N-单 - 或N，N-二取代的1-亚甲基 - 哌啶-3-甲酰胺或通式为N-单 - 或N，N-二取代的1-亚甲基 - 哌啶-4-甲酰胺 1b; R4表示氢，任选取代的C 1 -C 3烷基; 或者R 2和R 3与它们所连接的C原子一起形成通式为1.1的取代的2,3,4,9-四氢-1H-咔唑，或者R2，R3和R4与它们所连接的原子一起 形成通式1.2的取代的氮杂环; R5和R6任选地相同，表示氢，任选取代的C 1 -C 3烷基或C 3 -C 6环烷基，或者R 5和R 6与它们所连接的N-原子一起形成任选取代的含有一个或两个N-烷基的5-或6-元氮杂环基， 原子并任选地与苯环稠合; R 7和R 8表示氢或R 7和R 8与它们连接的C原子一起形成C = O基团; R9表示氮杂环基，其包含至少一个N-原子，未取代的甲酰胺或被乙氧基羰基或硝基取代的苯基; R10表示氢，任选取代的C 1 -C 3烷基，取代的乙酰基; n = 1或2; 伴随着虚线的实线即（）表示单C或C C键。

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.

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.

公开(公告)号：US09073874B2

公开(公告)日：2015-07-07

申请号：US13811282

申请日：2011-07-01

申请人： Alexandre Vasilievich Ivachtchenko ,  Oleg Dmitrievich Mitkin

发明人： Alexandre Vasilievich Ivachtchenko ,  Oleg Dmitrievich Mitkin

IPC分类号： A61K31/505 ,  C07D233/86 ,  C07D233/72 ,  C07D239/10 ,  C07D239/22 ,  C07D249/12 ,  C07D471/10 ,  C07D491/107 ,  A61K9/00 ,  A61K9/20 ,  A61K9/48

CPC分类号： C07D233/86 ,  A61K9/0019 ,  A61K9/2018 ,  A61K9/2059 ,  A61K9/2095 ,  A61K9/4858 ,  C07D233/72 ,  C07D239/10 ,  C07D239/22 ,  C07D249/12 ,  C07D471/10 ,  C07D491/107

摘要： The invention relates to novel N,N′-disubstituted 2-thioxo-7-oxa-1,3-diaza-spiro[4.4]nonan-4-one-androgen receptor (AR) antagonists, an anticancer agent, a pharmaceutical composition, a medicament, and a method for treating prostate cancer.4-[3-(4-Cyano-3-trifluoromethyl-phenyl)-4-oxo-2-thioxo-7-oxa-1,3-diaza-spiro[4.4]non-1-yl]-2-fluoro-benzamide of general formula 1 and enantiomer thereof wherein: R represents C1-C3alkyl.

摘要翻译： 本发明涉及新的N，N'-二取代2-硫代-7-氧杂-1,3-二氮杂 - 螺[4.4]壬-4-酮雄激素受体（AR）拮抗剂，抗癌剂，药物组合物， 药物和治疗前列腺癌的方法。 4- [3-（4-氰基-3-三氟甲基 - 苯基）-4-氧代-2-硫代-7-氧杂-1,3-二氮杂 - 螺[4.4]壬-1-基] -2-氟 - 苯甲酰胺及其对映异构体，其中：R表示C 1 -C 3烷基。