公开(公告)号：US20110046149A1

公开(公告)日：2011-02-24

申请号：US12937718

申请日：2009-04-30

申请人： Andrey Alexandrovich Ivashchenko ,  Volodymyr Mikhailovich Kysil ,  Nikolay Filippovich Savchuk ,  Alexander Vasilievich Ivashchenko

发明人： Andrey Alexandrovich Ivashchenko ,  Volodymyr Mikhailovich Kysil ,  Nikolay Filippovich Savchuk ,  Alexander Vasilievich Ivashchenko

IPC分类号： A61K31/519 ,  C07D471/14 ,  A61P25/00 ,  A61P25/28 ,  A61P25/16 ,  A61P25/18 ,  A61P25/22 ,  A61P3/04 ,  C12N5/02

CPC分类号： C07D471/14 ,  A61K31/519

摘要： The invention relates to serotonin 5-HT6 receptor antagonists—novel 2-amino-3-arylsulfonyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[4,3-e]pyrimidines and substituted 2-amino-3-arylsulfonyl-5,6,7,8-tetrahydropyrazolo[1,5-a]pyrido[4,3-d]pyrimidines, drug substances and pharmaceutical compositions comprising the said drug substances as the said compounds, and also to method of prophylaxis and treatment of various diseases of central nervious system in humans and animals pathogenesis of which is associated with serotonin 5-HT6 receptors including cognitive and neurodegenerative diseases.Substituted 2-amino-3-arylsulfonyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[4,3-e]pyrimidines of the general formula 1 and substituted 2-amino-3-arylsulfonyl-5,6,7,8-tetrahydropyrazolo[1,5-a]pyrido[4,3-d]pyrimidines of the general formula 2 and pharmaceutically acceptable salts and/or hydrates thereof. wherein: Ar is optionally substituted aryl or optionally substituted heteroaryl; R1 is hydrogen, optionally substituted C1-C3 alkyl, C1-C4 alkyloxycarbonyl; R2 is hydrogen, halogen or optionally substituted C1-C3 alkyl; R13 and R23 represent optionally alike: hydrogen, optionally substituted C1-C3 alkyl or R13 and R23 together with the nitrogen atom to which they are attached form an optionally substituted azaheterocycle.

摘要翻译： 本发明涉及5-羟色胺5-HT 6受体拮抗剂 - 新型2-氨基-3-芳基磺酰基-6,7,8,9-四氢吡唑并[1,5-a]吡啶并[4,3-e]嘧啶和取代的2-氨基 -3-芳基磺酰基-5,6,7,8-四氢吡唑并[1,5-a]吡啶并[4,3-d]嘧啶，药物物质和药物组合物，其包含作为所述化合物的所述药物物质， 预防和治疗人类和动物的中枢神经系统的各种疾病，其发病机制与血清素5-HT6受体（包括认知和神经变性疾病）相关。 通式1的取代的2-氨基-3-芳基磺酰基-6,7,8,9-四氢吡唑并[1,5-a]吡啶并[4,3-e]嘧啶和取代的2-氨基-3-芳基磺酰基-5 ，6,7,8-四氢吡唑并[1,5-a]吡啶并[4,3-d]嘧啶，及其药学上可接受的盐和/或水合物。 其中：Ar是任选取代的芳基或任选取代的杂芳基; R 1是氢，任选取代的C 1 -C 3烷基，C 1 -C 4烷氧基羰基; R2是氢，卤素或任选取代的C 1 -C 3烷基; R 13和R 23任选地相似：氢，任选取代的C 1 -C 3烷基或R 13和R 23与它们所连接的氮原子一起形成任选取代的杂环。

公开(公告)号：US20110039870A1

公开(公告)日：2011-02-17

申请号：US12937720

申请日：2009-04-30

申请人： Andrey Alexandrovich Ivashchenko ,  Volodymyr Mikhailovich Kysil ,  Nikolay Filippovich Savchuk ,  Alexander Vasilievich Evashchenko

发明人： Andrey Alexandrovich Ivashchenko ,  Volodymyr Mikhailovich Kysil ,  Nikolay Filippovich Savchuk ,  Alexander Vasilievich Evashchenko

IPC分类号： A61K31/519 ,  C07D471/14 ,  A61P25/00 ,  A61P25/28 ,  A61P25/16 ,  A61P25/18 ,  A61P25/22 ,  A61P3/10 ,  A61P3/04 ,  C12N5/02

CPC分类号： C07D471/14 ,  A61K31/519

摘要： The present invention relates to serotonin 5-HT6 receptor antagonists-novel substituted 3-sulfonyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[4,3-e]pyrimidines and substituted 3-sulfonyl-5,6,7,8-tetrahydropyrazolo[1,5-a]pyrido[4,3-d]pyrimidines, drug substances and pharmaceutical compositions comprising drug substances as the mentioned above compounds and to the method of prophylaxis and treatment of various conditions and diseases of central nervous system in humans and warm-blooded animals pathogenesis of which is associated with serotonin 5-HT6 receptors.In formulas 1 and 2 Ar is optionally substituted aryl or optionally substituted heterocyclyl; R1 is hydrogen, optionally substituted lower C1-C3 alkyl, substituted hydroxyl group, substituted sulfanyl group; R2 is hydrogen or optionally substituted C1-C3 alkyl; R3 is hydrogen, optionally substituted C1-C3 alkyl or tert.-butyloxycarbonyl.

摘要翻译： 本发明涉及5-羟色胺5-HT 6受体拮抗剂 - 新型取代的3-磺酰基-6,7,8,9-四氢吡唑并[1,5-a]吡啶并[4,3-e]嘧啶和取代的3-磺酰基-5 ，6,7,8-四氢吡唑并[1,5-a]吡啶并[4,3-d]嘧啶，包含上述化合物的药物的药物和药物组合物，以及各种条件的预防和治疗方法 人类的中枢神经系统疾病和温血动物，其发病机制与血清素5-HT6受体有关。 在式1和2中Ar是任选取代的芳基或任选取代的杂环基; R1是氢，任选取代的低级C 1 -C 3烷基，取代的羟基，取代的硫烷基; R2是氢或任选取代的C 1 -C 3烷基; R3是氢，任选取代的C 1 -C 3烷基或叔丁氧基羰基。

公开(公告)号：US08829009B2

公开(公告)日：2014-09-09

申请号：US13573818

申请日：2012-10-09

申请人： Alexander Vasillevich Ivashtchenko ,  Andrey Alexandrovich Ivashchenko ,  Nikolay Filippovich Savchuk

发明人： Alexander Vasillevich Ivashtchenko ,  Andrey Alexandrovich Ivashchenko ,  Nikolay Filippovich Savchuk

IPC分类号： A01N43/90 ,  A61K31/519 ,  C07D487/00 ,  C07D487/04

CPC分类号： C07D487/04

摘要： The present invention relates to novel substituted 2-amino-3-(arylsulfonyl)pyrazolo[1,5-a]pyrimidines of general formula 1, to serotonin 5-HT6 receptor antagonists, to novel drug substances and pharmaceutical compositions, to medicaments, methods for preparation thereof, and to methods for prophylaxis and treatment of various CNS diseases, pathogenesis of which is associated with disturbance of monoaminergic signaling pathways, more specifically over- or hypo-activation of serotonin 5-HT6 receptors.In general formula 1 R1 and R3 independently of each other represent C1-C3 alkyl or phenyl; R2 represents hydrogen or C1-C3 alkyl; R41, R42 independently of each other represent hydrogen, optionally substituted C1-C3 alkyl or optionally substituted phenyl, or R41 and R42 together with the nitrogen atom they are attached to form optionally substituted heterocyclyl; Ar is aryl selected from phenyl, optionally substituted with Ri5 that is one or two optionally identical substituents selected from hydrogen, lower alkyl, trifluoromethyl or halogen; or optionally substituted 5-6-membered heteroaryl, containing as the heteroatom nitrogen or sulfur atom.

摘要翻译： 本发明涉及通式1的新的取代的2-氨基-3-（芳基磺酰基）吡唑并[1,5-a]嘧啶，5-羟色胺5-HT 6受体拮抗剂，新药物和药物组合物，药物，方法 以及用于预防和治疗各种CNS疾病的方法，其发病机制与单胺能信号通路的紊乱相关，更具体地说是5-羟色胺5-HT 6受体的过激活或低激活。 在通式1中，R 1和R 3彼此独立地表示C 1 -C 3烷基或苯基; R2代表氢或C1-C3烷基; R 41，R 42彼此独立地表示氢，任选取代的C 1 -C 3烷基或任选取代的苯基，或R 41和R 42与它们连接的氮原子一起形成任选取代的杂环基; Ar是选自苯基的芳基，任选被R 15取代，R 15是选自氢，低级烷基，三氟甲基或卤素的一个或两个任选相同的取代基; 或含有杂原子氮或硫原子的任选取代的5-6元杂芳基。

公开(公告)号：US08618114B2

公开(公告)日：2013-12-31

申请号：US13122152

申请日：2009-10-06

申请人： Andrey Alexandrovich Ivashchenko ,  Nikolay Filippovich Savchuk ,  Alexander Vasilievich Ivashchenko ,  Yan Lavrovsky ,  Oleg Dmitrievich Mitkin ,  Madina Georgievna Kadieva

发明人： Andrey Alexandrovich Ivashchenko ,  Nikolay Filippovich Savchuk ,  Alexander Vasilievich Ivashchenko ,  Yan Lavrovsky ,  Oleg Dmitrievich Mitkin ,  Madina Georgievna Kadieva

IPC分类号： A01N43/90 ,  A61K31/519 ,  C07D487/00

CPC分类号： C07D487/04

摘要： The invention relates to the novel substituted 3-arylsulfonyl-pyrazolo[1,5-a]pyrimidines of the general formula 1, pharmaceutically acceptable salts and/or hydrates thereof, serotonin 5-HT6 receptor antagonists and pharmaceutical compositions, and also to method for prophylaxis and treatment of various diseases of central nervous system at humans and warm-blooded animals pathogenesis of which is associated with serotonin 5-HT6 receptors, in particular, Alzheimer's disease, Parkinson's disease, Huntington's disease, schizophrenia, and other neurodegenerative diseases, cognitive disorders and obesity.In the general formula 1: wherein: X=S, SO or NH; R1 represents hydrogen, optionally substituted C1-C3alkyl, cycloalkyl, adamantyl, aryl or heterocyclyl; R2 represents hydrogen, halogen, optionally substituted C1-C3alkyl, substituted hydroxyl, aryldiazenyl or optionally substituted amino group; R3 represents hydrogen, optionally substituted C1-C3alkyl, substituted hydroxyl, pyridyl or optionally substituted amino group, besides, in cases when X=S or X=NH, at least one of R1, R2 or R3 represent substituted C1-C3alkyl, cycloalkyl, adamantyl, aryl, heterocyclyl, halogen, substituted hydroxyl, optionally substituted amino group, aryldiazenyl, or at least two of R1, R2 or R3 represent hydrogen; R4 represents C1-C3alkyl; R5 represents hydrogen, one or two halogens, C1-C3alkyl or optionally substituted hydroxyl.

摘要翻译： 本发明涉及通式1的新的取代的3-芳基磺酰基 - 吡唑并[1,5-a]嘧啶，其药学上可接受的盐和/或水合物，5-羟色胺5-HT 6受体拮抗剂和药物组合物，还涉及 预防和治疗人类和温血动物的各种中枢神经系统疾病，其发病机制与血清素5-HT6受体，特别是阿尔茨海默病，帕金森病，亨廷顿病，精神分裂症和其他神经变性疾病，认知障碍 和肥胖。 在通式1中：其中：X = S，SO或NH; R 1表示氢，任选取代的C 1 -C 3烷基，环烷基，金刚烷基，芳基或杂环基; R 2表示氢，卤素，任选取代的C 1 -C 3烷基，取代的羟基，芳基二氮烯基或任选取代的氨基; R 3表示氢，任选取代的C 1 -C 3烷基，取代的羟基，吡啶基或任选取代的氨基，此外，在X = S或X = NH的情况下，R 1，R 2或R 3中的至少一个表示取代的C 1 -C 3烷基，环烷基， 金刚烷基，芳基，杂环基，卤素，取代的羟基，任选取代的氨基，芳基二氮烯基或R 1，R 2或R 3中的至少两个表示氢; R4代表C1-C3烷基; R5表示氢，一个或两个卤素，C1-C3烷基或任选取代的羟基。

公开(公告)号：US20120071493A1

公开(公告)日：2012-03-22

申请号：US13320911

申请日：2010-04-30

申请人： Andrey Alexandrovich Ivashchenko ,  Nikolay Filippovich Savchuk ,  Alexander Vasilievich Ivashchenko ,  Oleg Dmitrievich Mitkin ,  Volodymyr Mikhailovich Kysil

发明人： Andrey Alexandrovich Ivashchenko ,  Nikolay Filippovich Savchuk ,  Alexander Vasilievich Ivashchenko ,  Oleg Dmitrievich Mitkin ,  Volodymyr Mikhailovich Kysil

IPC分类号： A61K31/437 ,  A61K31/497 ,  A61P25/24 ,  A61P25/22 ,  A61P25/28 ,  A61P25/18 ,  C07D471/04 ,  A61P25/00

CPC分类号： A61K31/437 ,  A61K9/0019 ,  A61K9/2018 ,  A61K9/2059 ,  A61K9/4858 ,  A61K47/10 ,  C07D471/04

摘要： The invention relates to novel substituted 8-sulfonyl-2,3,4,5-tetrahydro-1H-γ-carbolines of the general formula 1 and their pharmaceutically acceptable salt—ligands exhibiting biological activity simultaneously towards alpha-adrenoceptors, dopamine receptors, histamine receptors, imidazoline receptors, sigma receptors, norepinefrine receptors, serotonin receptors, to active components, pharmaceutical compositions, comprising as an active component novel ligands, to novel medicaments intended for treatment of conditions and diseases of central nervous system. In the general formula 1 R1 represents a substituent selected from hydrogen, optionally substituted C1-C3 alkyl or C1-C4 alkyloxycarbonyl; R2 represents a cyclic system substituent selected from hydrogen, optionally substituted C1-C3 alkyl, optionally substituted C2-C3 alkenyl or substituted sulfonyl; R3 represents optionally substituted aryl or substituted amino group.

摘要翻译： 本发明涉及通式1的新的取代的8-磺酰基-2,3,4,5-四氢-1H-γ-咔啉及其药学上可接受的盐配体，其表现出与α-肾上腺素能受体，多巴胺受体，组胺 受体，咪唑啉受体，西格玛受体，诺诺福瑞汀受体，5-羟色胺受体，活性组分，药物组合物，作为活性成分的新型配体，用于治疗中枢神经系统病症和疾病的新型药物。 在通式1中，R 1表示选自氢，任选取代的C 1 -C 3烷基或C 1 -C 4烷氧基羰基的取代基; R2表示选自氢，任选取代的C 1 -C 3烷基，任选取代的C 2 -C 3烯基或取代的磺酰基的环状体系取代基; R3表示任选取代的芳基或取代的氨基。

公开(公告)号：US20110230524A1

公开(公告)日：2011-09-22

申请号：US13130311

申请日：2009-11-27

申请人： Andrey Alexandrovich Ivashchenko ,  Nikolay Filippovich Savchuk ,  Alexander Vasilievich Ivashchenko ,  Pavel Mikhailovich Yamanushkin ,  Oleg Dmitrievich Mitkin ,  Vladimir Yurievich Vvedensky ,  Vadim Vasilievich Bichko

发明人： Andrey Alexandrovich Ivashchenko ,  Nikolay Filippovich Savchuk ,  Alexander Vasilievich Ivashchenko ,  Pavel Mikhailovich Yamanushkin ,  Oleg Dmitrievich Mitkin ,  Vladimir Yurievich Vvedensky ,  Vadim Vasilievich Bichko

IPC分类号： A61K31/4439 ,  C07D209/18 ,  C07D209/20 ,  C07D209/26 ,  C07D401/12 ,  C07D209/24 ,  C07D401/06 ,  C07D401/10 ,  A61K31/405 ,  A61P31/12 ,  A61P31/16 ,  A61P31/14

CPC分类号： C07F1/005 ,  A61K9/0019 ,  A61K9/2018 ,  A61K9/2059 ,  A61K9/4858 ,  A61K47/10 ,  C07D209/32 ,  C07D209/42 ,  C07D401/04 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/06 ,  C07D409/12

摘要： The present invention relates to novel substituted 2-(5-hydroxy-2-methyl-1H-indol-3-yl)acetic acids, to novel antiviral active ingredients, pharmaceutical compositions, antiviral medicaments, methods for prophylaxis and treatment of viral diseases particularly caused by influenza viruses and infectious hepatisis C (HCV) viruses.Novel substituted 2-(5-hydroxy-2-methyl-1H-indol-3-yl)acetic acids, their esters of the general formula 1 and pharmaceutically acceptable salts and/or hydrates thereof have been disclosed wherein: R1 represents amino group substituent selected from hydrogen, optionally substituted C1-C5 alkyl, acyl or sulfonyl; R2 and R4 independently of each other represent alkyl substituent selected from hydrogen, halogen, optionally substituted C1-C3 alkyl, optionally substituted hydroxyl, optionally substituted amino group, optionally substituted aminomethyl, substituted mercapto group; R3 represents hydrogen, optionally substituted lower C1-C5 alkyl; R5 represents cyclic system substituent selected from hydrogen, fluorine, trifluoromethyl, carboxy group, alkyloxycarbonyl, possibly substituted aryl, heterocyclyl, optionally substituted aminomethyl, cyano group; R6 represents hydroxyl group substituent selected from hydrogen, optionally substituted C1-C5 alkyl, acyl.

摘要翻译： 本发明涉及新的取代的2-（5-羟基-2-甲基-1H-吲哚-3-基）乙酸，新颖的抗病毒活性成分，药物组合物，抗病毒药物，预防和治疗病毒性疾病的方法，特别是 由流感病毒和感染性肝炎C（HCV）病毒引起。 已经公开了新的取代的2-（5-羟基-2-甲基-1H-吲哚-3-基）乙酸，它们的通式1的酯及其药学上可接受的盐和/或水合物，其中：R1代表氨基取代基 选自氢，任选取代的C 1 -C 5烷基，酰基或磺酰基; R 2和R 4彼此独立地表示选自氢，卤素，任选取代的C 1 -C 3烷基，任选取代的羟基，任选取代的氨基，任选取代的氨基甲基，取代的巯基的烷基取代基; R3表示氢，任选取代的低级C 1 -C 5烷基; R5表示选自氢，氟，三氟甲基，羧基，烷氧基羰基，可能取代的芳基，杂环基，任选取代的氨基甲基，氰基的环状体系取代基。 R 6表示选自氢，任选取代的C 1 -C 5烷基，酰基的羟基取代基。

公开(公告)号：US20110178078A1

公开(公告)日：2011-07-21

申请号：US13122152

申请日：2009-10-06

申请人： Andrey Alexandrovich Ivashchenko ,  Nikolay Filippovich Savchuk ,  Alexander Vasilievich Ivashchenko ,  Yan Lavrovsky ,  Oleg Dmitrievich Mitkin ,  Madina Georgievna Kadieva

发明人： Andrey Alexandrovich Ivashchenko ,  Nikolay Filippovich Savchuk ,  Alexander Vasilievich Ivashchenko ,  Yan Lavrovsky ,  Oleg Dmitrievich Mitkin ,  Madina Georgievna Kadieva

IPC分类号： A61K31/5377 ,  A61K31/497 ,  A61K31/519 ,  C07D487/04 ,  A61P3/04 ,  A61P25/28 ,  A61P25/16 ,  A61P25/18 ,  A61P3/10

CPC分类号： C07D487/04

摘要： The invention relates to the novel substituted 3-arylsulfonyl-pyrazolo[1,5-a]pyrimidines of the general formula 1, pharmaceutically acceptable salts and/or hydrates thereof, serotonin 5-HT6 receptor antagonists and pharmaceutical compositions, and also to method for prophylaxis and treatment of various diseases of central nervous system at humans and warm-blooded animals pathogenesis of which is associated with serotonin 5-HT6 receptors, in particular, Alzheimer's disease, Parkinson's disease, Huntington's disease, schizophrenia, and other neurodegenerative diseases, cognitive disorders and obesity.In the general formula 1: wherein: X═S, SO or NH; R1 represents hydrogen, optionally substituted C1-C3alkyl, cycloalkyl, adamantyl, aryl or heterocyclyl; R2 represents hydrogen, halogen, optionally substituted C1-C3alkyl, substituted hydroxyl, aryldiazenyl or optionally substituted amino group; R3 represents hydrogen, optionally substituted C1-C3alkyl, substituted hydroxyl, pyridyl or optionally substituted amino group, besides, in cases when X═S or X═NH, at least one of R1, R2 or R3 represent substituted C1-C3alkyl, cycloalkyl, adamantyl, aryl, heterocyclyl, halogen, substituted hydroxyl, optionally substituted amino group, aryldiazenyl, or at least two of R1, R2 or R3 represent hydrogen; R4 represents C1-C3alkyl; R5 represents hydrogen, one or two halogens, C1-C3alkyl or optionally substituted hydroxyl.

摘要翻译： 本发明涉及通式1的新的取代的3-芳基磺酰基 - 吡唑并[1,5-a]嘧啶，其药学上可接受的盐和/或水合物，5-羟色胺5-HT 6受体拮抗剂和药物组合物，还涉及 预防和治疗人类和温血动物的各种中枢神经系统疾病，其发病机制与血清素5-HT6受体，特别是阿尔茨海默病，帕金森病，亨廷顿病，精神分裂症和其他神经变性疾病，认知障碍 和肥胖。 在通式1中：其中：X = S，SO或NH; R 1表示氢，任选取代的C 1 -C 3烷基，环烷基，金刚烷基，芳基或杂环基; R 2表示氢，卤素，任选取代的C 1 -C 3烷基，取代的羟基，芳基二氮烯基或任选取代的氨基; R 3表示氢，任选取代的C 1 -C 3烷基，取代的羟基，吡啶基或任选取代的氨基，此外，在X = S或X = NH的情况下，R 1，R 2或R 3中的至少一个表示取代的C 1 -C 3烷基，环烷基， 金刚烷基，芳基，杂环基，卤素，取代的羟基，任选取代的氨基，芳基二氮烯基或R 1，R 2或R 3中的至少两个表示氢; R4代表C1-C3烷基; R5表示氢，一个或两个卤素，C1-C3烷基或任选取代的羟基。

公开(公告)号：US20200206248A1

公开(公告)日：2020-07-02

申请号：US16615831

申请日：2018-02-14

申请人： Alena Alexandrovna Ivachtchenko ,  ALLA CHEM, LLC

发明人： Alexandre Vasilievich Ivachtchenko ,  Andrey Alexandrovich Ivashchenko ,  Nikolay Filippovich Savchuk

IPC分类号： A61K31/63 ,  A61K31/513 ,  A61K31/675 ,  A61K9/20 ,  A61P31/18 ,  A61P31/22

摘要： The present invention relates to a novel combination drug in a solid oral dosage form comprising, as one of the three active ingredients, elsulfavirine sodium that may be suitable for medical use when treating viral infections including HIV and HBV.An antiviral combination drug in a solid oral dosage form comprising, as one of the three active ingredients, a therapeutically effective amount of elsulfavirine sodium of formula 1a in a crystalline or polycrystalline form optionally in combination with auxiliary agents: