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。

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。