公开(公告)号：US20110039825A1

公开(公告)日：2011-02-17

申请号：US12810013

申请日：2008-12-19

申请人： Andrey Alexandrovich Ivashchenko ,  Vasilievich Ivashchenko ,  Yan Vadimovich Lavrovsky ,  Oleg Dmitrievich Mitkin ,  Nikolay Filippovich Savchuk ,  Sergey Yevgenievich Tkachenko ,  Ilya Matusovich Okun

发明人： Andrey Alexandrovich Ivashchenko ,  Vasilievich Ivashchenko ,  Yan Vadimovich Lavrovsky ,  Oleg Dmitrievich Mitkin ,  Nikolay Filippovich Savchuk ,  Sergey Yevgenievich Tkachenko ,  Ilya Matusovich Okun

IPC分类号： A61K31/55 ,  C07D471/04 ,  A61K31/437 ,  A61K31/519 ,  C07D519/00 ,  C07D487/04 ,  A61P25/28 ,  A61P25/24

CPC分类号： C07D471/04 ,  A61K9/0019 ,  A61K9/2018 ,  A61K9/2059 ,  A61K9/4858 ,  A61K31/407 ,  A61K31/437 ,  A61K31/55 ,  C07D487/04

摘要： The invention relates to novel ligands the broad spectrum of biological activity of which includes simultaneously α-adrenoceptors, dopamine receptors, histamine receptors, imidazoline receptors and serotonin receptors, among them serotonin 5-HT7 receptors, which are compounds of general formula 1 in the form of free bases, geometrical isomers, racemic mixtures or individual optical isomers, pharmaceutically acceptable salts and/or hydrates, wherein: R1 is a substituent of amino group, selected from hydrogen, optionally substituted C1-C4 alkyl, acyl, heterocyclyl, alkoxycarbonyl, substituted sulfonyl; R2 is a substituent of cyclic system, selected from hydrogen, halogen, optionally substituted C1-C4 alkyl, CF3, CN, alkoxy, alkoxycarbonyl, carboxyl, heterocyclyl or substituted sulfonyl; Ar is optionally substituted aryl not necessarily annalated with heterocyclyl, or optionally substituted aromatic heterocyclyl; W is optionally substituted (CH2)m group, optionally substituted CH═CH group, optionally substituted CH2—CH═CH group, C≡C group, SO2 group; n=1, 2; m=1, 2, 3; solid line accompanied by dotted line, i.e. may represent single or double bond. The invention also relates to active ingredients, pharmaceutical compositions comprising the said ligands as active ingredients; to novel medicaments useful for treatment of diseases and conditions of central nervous system (CNS) of humans and warm-blooded animals.

摘要翻译： 本发明涉及其具有广谱生物活性的新配体，其包括同时α-肾上腺素受体，多巴胺受体，组胺受体，咪唑啉受体和5-羟色胺受体，其中5-羟色胺5-HT 7受体是通式1的化合物，其形式为 游离碱，几何异构体，外消旋混合物或单独的光学异构体，药学上可接受的盐和/或水合物，其中：R1是氨基的取代基，其选自氢，任选取代的C 1 -C 4烷基，酰基，杂环基，烷氧基羰基，取代的 磺酰基 R2是选自氢，卤素，任选取代的C 1 -C 4烷基，CF 3，CN，烷氧基，烷氧基羰基，羧基，杂环基或取代的磺酰基的环状体系的取代基。 Ar是任选取代的芳基，不一定与杂环基或任选取代的芳族杂环基取代; W是任选取代的（CH 2）m基团，任选取代的CH = CH基团，任选取代的CH 2 -CH = CH基团，C≡C基团，SO 2基团; n = 1,2; m = 1,2,3。 伴有虚线的实线即可表示单键或双键。 本发明还涉及活性成分，包含所述配体作为活性成分的药物组合物; 用于治疗人类和温血动物的中枢神经系统（CNS）的疾病和病症的新型药物。

公开(公告)号：US08329689B2

公开(公告)日：2012-12-11

申请号：US12600251

申请日：2007-05-17

申请人： Andrey Alexandrovich Ivashchenko ,  Sergey Yevgenievich Tkachenko ,  Alexander Viktorovich Khvat ,  Oleg Dmitrievich Mitkin ,  Ilya Matusovich Okun ,  Alexandr Sergeevich Kyselvev ,  Volodymyr Mikhailovich Kysil ,  Nikolay Filippovich Savchuk ,  Alexander Vasilievich Ivachtchenko

发明人： Andrey Alexandrovich Ivashchenko ,  Sergey Yevgenievich Tkachenko ,  Alexander Viktorovich Khvat ,  Oleg Dmitrievich Mitkin ,  Ilya Matusovich Okun ,  Alexandr Sergeevich Kyselvev ,  Volodymyr Mikhailovich Kysil ,  Nikolay Filippovich Savchuk ,  Alexander Vasilievich Ivachtchenko

IPC分类号： A61K31/404 ,  A61K31/407 ,  C07D209/12 ,  C07D498/04

CPC分类号： C07D401/14 ,  C07D209/42 ,  C07D401/04 ,  C07D401/06 ,  C07D403/04 ,  C07D403/06 ,  C07D405/04 ,  C07D409/04 ,  C07D413/14 ,  C07D498/04

摘要： The invention relates to novel substituted indoles, to the use thereof in the form of pharmacological composition substances and to use of said composition for producing medicinal preparations used for preventing and treating viral diseases, in particular caused by viruses of infectious hepatitis (HCV, HBV), human immune deficiency (HIV), atypical pneumonia (SARS) and bird flu. The invention proposes novel substituted indoles of general formula (1) or the racemates or the optical isomers or the pharmaceutically acceptable salts and/or hydrates thereof, wherein R1, R14 and R24 independently of each other are an aminogroup substituent selected for hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl or optionally substituted heterocyclyl, or R14 and R24 together with a nitrogen atom, with which they are bound, form through R14 and R24 optionally substituted azaheterocyclyl or guanidyl; R2 is analkyl substituent selected from hydrogen, an optionally substituted mercaptogroup, optionally substituted aminogroup and optionally substituted hydroxyl; R3 is lower alkyl, R5 is an hydrogen atom or R5 together with an oxygen atom with which it is linked or R24 together with a nitrogen atom with which it is linked close, via R5 and R24 an oxazine cycle; R6 is a cyclic system substituent selected for hydrogen, a halogen atom, cyanogroup, optionally substituted aryl or substituted heterocyclyl.

摘要翻译： 本发明涉及以药物组合物物质形式使用的新型取代的吲哚，以及所述组合物用于制备用于预防和治疗病毒性疾病，特别是感染性肝炎（HCV，HBV）病毒引起的药物制剂的用途， ，人类免疫缺陷（HIV），非典型肺炎（SARS）和禽流感。 本发明提出了通式（1）的新型取代吲哚或其外消旋物或光学异构体或其药学上可接受的盐和/或水合物，其中R1，R14和R24彼此独立地是选自氢的氨基取代基， 烷基，任选取代的环烷基，任选取代的芳基或任选取代的杂环基，或R 14和R 24与它们所连接的氮原子一起通过R 14和R 24任选取代的杂环基或胍基形成; R2是选自氢，任选取代的巯基，任选取代的氨基和任选取代的羟基的烷基取代基; R 3是低级烷基，R 5是氢原子或R 5与连接的氧原子连在一起，或者R 24与其连接的氮原子一起通过R5和R24进行恶嗪循环; R6是选择用于氢，卤素原子，氰基，任选取代的芳基或取代的杂环基的环系取代基。

公开(公告)号：US08541437B2

公开(公告)日：2013-09-24

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 ,  Dmitri Vladimirovich Kravchenko ,  Ilya 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 ,  Dmitri Vladimirovich Kravchenko ,  Ilya Matusovich Okun ,  Nikolay Filippovich Savchuk ,  Yan Lavrovsky

IPC分类号： C07D471/04 ,  A61K31/437

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; R2i 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; R2i是一个或多个选自氢，卤素，C1-C3烷基，CF3，OCF3的取代基; 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：US20110160197A1

公开(公告)日：2011-06-30

申请号：US12600251

申请日：2007-05-17

申请人： Andrey Alexandrovich Ivashchenko ,  Sergey Yevgenievich Tkachenko ,  Alexander Viktorovich Khvat ,  Oleg Dmitrievich Mitkin ,  Ilya Matusovich Okun ,  Alexandr Sergeevich Kyselvev ,  Volodymyr Mikhailovich Kysil ,  Nikolay Filippovich Savchuk ,  Alexander Vasilievich Ivachtchenko

发明人： Andrey Alexandrovich Ivashchenko ,  Sergey Yevgenievich Tkachenko ,  Alexander Viktorovich Khvat ,  Oleg Dmitrievich Mitkin ,  Ilya Matusovich Okun ,  Alexandr Sergeevich Kyselvev ,  Volodymyr Mikhailovich Kysil ,  Nikolay Filippovich Savchuk ,  Alexander Vasilievich Ivachtchenko

IPC分类号： A61K31/404 ,  C07D209/42 ,  C07D403/10 ,  C07D401/10 ,  A61K31/4725 ,  A61K31/454 ,  A61K31/496 ,  C07D498/04 ,  A61K31/5365 ,  A61K31/5377 ,  A61P31/16 ,  A61P31/18 ,  A61P31/20 ,  A61P31/14

CPC分类号： C07D401/14 ,  C07D209/42 ,  C07D401/04 ,  C07D401/06 ,  C07D403/04 ,  C07D403/06 ,  C07D405/04 ,  C07D409/04 ,  C07D413/14 ,  C07D498/04

摘要： The invention relates to novel substituted indoles, to the use thereof in the form of pharmacological composition substances and to use of said composition for producing medicinal preparations used for preventing and treating viral diseases, in particular caused by viruses of infectious hepatitis (HCV, HBV), human immune deficiency (HIV), atypical pneumonia (SARS) and bird flu. The invention proposes novel substituted indoles of general formula (1) or the racemates or the optical isomers or the pharmaceutically acceptable salts and/or hydrates thereof, wherein R1, R14 and R24 independently of each other are an aminogroup substituent selected for hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl or optionally substituted heterocyclyl, or R14 and R24 together with a nitrogen atom, with which they are bound, form through R14 and R24 optionally substituted azaheterocyclyl or guanidyl; R2 is analkyl substituent selected from hydrogen, an optionally substituted mercaptogroup, optionally substituted aminogroup and optionally substituted hydroxyl; R3 is lower alkyl, R5 is an hydrogen atom or R5 together with an oxygen atom with which it is linked or R24 together with a nitrogen atom with which it is linked close, via R5 and R24 an oxazine cycle; R6 is a cyclic system substituent selected for hydrogen, a halogen atom, cyanogroup, optionally substituted aryl or substituted heterocyclyl.

摘要翻译： 本发明涉及以药物组合物物质形式使用的新型取代的吲哚，以及所述组合物用于制备用于预防和治疗病毒性疾病的药物制剂的用途，特别是由感染性肝炎（HCV，HBV）病毒引起的病毒性疾病， ，人类免疫缺陷（HIV），非典型肺炎（SARS）和禽流感。 本发明提出了通式（1）的新型取代吲哚或其外消旋体或光学异构体或其药学上可接受的盐和/或水合物，其中R1，R14和R24彼此独立地是选自氢的氨基取代基， 烷基，任选取代的环烷基，任选取代的芳基或任选取代的杂环基，或R 14和R 24与它们所连接的氮原子一起通过R 14和R 24任选取代的杂环基或胍基形成; R2是选自氢，任选取代的巯基，任选取代的氨基和任选取代的羟基的烷基取代基; R 3是低级烷基，R 5是氢原子或R 5与连接的氧原子连在一起，或者R 24与其连接的氮原子一起通过R5和R24进行恶嗪循环; R6是选择用于氢，卤素原子，氰基，任选取代的芳基或取代的杂环基的环系取代基。

公开(公告)号：US20110046368A1

公开(公告)日：2011-02-24

申请号：US12741006

申请日：2007-11-15

申请人： Andrey Alexandrovich Ivashchenko ,  Alexander Vasilievich Ivashchenko ,  Sergey Yevgenievich Tkachenko ,  Ilya Matusovich Okun ,  Nikolay Filippovich Savchuk

发明人： Andrey Alexandrovich Ivashchenko ,  Alexander Vasilievich Ivashchenko ,  Sergey Yevgenievich Tkachenko ,  Ilya Matusovich Okun ,  Nikolay Filippovich Savchuk

IPC分类号： C07D487/04 ,  C07D471/04 ,  C07D473/04

CPC分类号： C07D487/04 ,  C07D471/04 ,  C07D519/00

摘要： The invention relates to novel ligands of 5-HT6 receptor, to a pharmaceutical composition containing said novel ligands of 5-HT6 receptor as active component and to novel medicaments used for humans and warm-blooded animals for treating diseases and conditions of central nervous system, in pathogenesis of which neuromediator systems induced by 5-HT6 receptors are playing an essential role.Azaheterocyclic compounds of the general formula 1 or racemates, or optical or geometrical isomers, or pharmaceutically acceptable salts and/or hydrates thereof are used as 5-HT6 ligands. Wherein R2 and R3 independently of each other represent an amino group substituent selected from hydrogen; substituted carbonyl; substituted aminocarbonyl; substituted aminothiocarbonyl; substituted sulphonyl; C1-C5-alkyl optionally substituted by: C6-C10-arylaminocarbonyl, heterocyclyl, C6-C10-arylaminocarbonyl, C6-C10-arylaminothiocarbonyl, C5-C10-azaheteroaryl, optionally substituted carboxyl, nitryl group, optionally substituted aryl; R1k represents from 1 to 3 substituents of cyclic system, independent of each other and selected from hydrogen, optionally substituted C1-C5-alkyl, C1-C5-alkoxy, C1-C5-alkenyl, C1-C5-alkynyl, halogen, trifluoromethyl, CN-group, carboxyl, optionally substituted aryl, optionally substituted heterocyclyl, substituted sulfonyl, optionally substituted carboxyl; the solid line accompanied by the dotted line represents a single or a double bond; n=1, 2 or 3.

摘要翻译： 本发明涉及含有5-HT 6受体作为活性成分的所述新型配体的药物组合物和用于人和用于治疗中枢神经系统疾病和病症的温血动物的新型药物的5-HT 6受体的新配体， 在5-HT6受体诱导的神经调节因子的发病机理中起着重要的作用。 通式1的氮杂环化合物或其外消旋体或光学或几何异构体或其药学上可接受的盐和/或水合物用作5-HT 6配体。 其中R2和R3彼此独立地表示选自氢的氨基取代基; 取代羰基; 取代的氨基羰基; 取代的氨基硫代羰基; 取代磺酰基; 任选被C 6 -C 10芳基氨基羰基，杂环基，C 6 -C 10 - 芳基氨基羰基，C 6 -C 10 - 芳基氨基硫代羰基，C 5 -C 10 - 氮杂杂芳基，任选取代的羧基，硝基，任选取代的芳基取代的C 1 -C 5 - 任选取代的C 1 -C 5 - 烷基，C 1 -C 5 - 烷氧基，C 1 -C 5 - 烯基，C 1 -C 5 - 炔基，卤素，三氟甲基， CN-基团，羧基，任选取代的芳基，任选取代的杂环基，取代的磺酰基，任选取代的羧基; 伴随虚线的实线表示单键或双键; n = 1,2或3。

公开(公告)号：US20110053915A1

公开(公告)日：2011-03-03

申请号：US12808152

申请日：2008-12-12

申请人： Andrey Alexandrovich Ivaschenko ,  Yan Vadimovich Lavrovsky ,  Sergey Viktorovich Malyarchuk ,  Ilya Matusovich Okun ,  Nikolay Filippovich Savchuk ,  Sergey Yevgenievich Tkachenko ,  Alexander Viktorovich Khvat ,  Alexander Vasilievich Ivaschenko

发明人： Andrey Alexandrovich Ivaschenko ,  Yan Vadimovich Lavrovsky ,  Sergey Viktorovich Malyarchuk ,  Ilya Matusovich Okun ,  Nikolay Filippovich Savchuk ,  Sergey Yevgenievich Tkachenko ,  Alexander Viktorovich Khvat ,  Alexander Vasilievich Ivaschenko

IPC分类号： A61K31/55 ,  A61K31/5025 ,  C07D487/04 ,  A61K31/5377 ,  A61K31/542 ,  C07D513/04 ,  A61P35/00 ,  A61K31/437 ,  C07D471/04 ,  A61K31/519 ,  C07D495/04 ,  A61K31/454 ,  A61K31/496 ,  A61K31/438 ,  A61K31/4545 ,  C07D401/04 ,  C07D215/58 ,  A61K31/47 ,  A61K31/4365

CPC分类号： C07D487/04 ,  A61K9/0019 ,  A61K9/2018 ,  A61K9/205 ,  A61K9/2059 ,  A61K9/4858 ,  C07D215/58 ,  C07D401/04 ,  C07D471/04 ,  C07D495/04 ,  C07D513/04

摘要： The invention relates to novel heterocyclic compounds and to the use thereof, to pharmaceutical compositions containing said chemical compounds as an active ingredient and to the use thereof for producing medicinal preparations for the human being and warm-blood animals for treating diseases caused by the aberrant activity of an Hedgehog (Hh)-signal system, in particular oncological diseases. The invention also relates to the use of the above-mentioned compounds in the form of ‘molecular pharmacological tools’ for examining (in vitro and in vivo) the biochemical features of the Hh-signal system, in particular, the interaction of Hh protein and transmembrane proteins, namely, suppressor Patched (Ptc) and protooncogenic proteins. The eight groups of the claimed compounds comprise the derivatives of 2,6-dihydro-7H-pyrazolo[3,4-d]pyridazine-7-one and 1,4-dihydropyrazolo[3,4-b][1,4]thiazine-5-one; N-acidylated 4-imidazo[1,2-a]pyrimidine-2-il-anilines; ([4H-thino[3,2-b]pyrrol-5-il) carbonyl]piperidine-4-carbonic acid amides; 2-(4carbomoilpyperidine-1-il)-isonicotinic acid amides; N-sylphonyl-1,2,3,4-tetrahydroquinoline-6-carbonic acid amides; and pyridine 2-amino-4,5,6,7-tetrahydrothieno[2,3-c] N-acidylated 3-azole derivatives.

摘要翻译： 本发明涉及新颖的杂环化合物及其用途，含有所述化合物作为活性成分的药物组合物及其用于生产用于治疗由异常活性引起的疾病的人和温血动物的药物制剂的用途 刺猬（Hh） - 信号系统，特别是肿瘤疾病。 本发明还涉及以“分子药理学工具”形式的上述化合物用于检查（体外和体内）Hh信号系统的生物化学特征的用途，特别是Hh蛋白和 跨膜蛋白，即抑制剂Patched（Ptc）和原癌蛋白。 所要求保护的八个化合物组包括2,6-二氢-7H-吡唑并[3,4-d]哒嗪-7-酮和1,4-二氢吡唑并[3,4-b] [1,4] 噻嗪-5-酮; N-酸化的4-咪唑并[1,2-a]嘧啶-2-基]苯胺; （[4H-噻吩并[3,2-b]吡咯-5-基）羰基]哌啶-4-碳酸酰胺; 2-（4-氰基吡啶-1-基） - 异烟酰胺; N-磺酰基-1,2,3,4-四氢喹啉-6-碳酸酰胺; 和吡啶2-氨基-4,5,6,7-四氢噻吩并[2,3-c] N-酸化的3-唑衍生物。