公开(公告)号：US20120184576A1

公开(公告)日：2012-07-19

申请号：US13262040

申请日：2010-03-31

申请人： Santosh Kumar Srivastava ,  Ashok Kumar Agrawal ,  Subhash Chandra Singh ,  Vinay Kumar Khanna ,  Janardan Singh ,  Chandeshwar Nath ,  Madan Mohan Gupta ,  Shikha Gupta ,  Ram Kishor Verma ,  Anirban Pal ,  Duyaneshwar Umrao Bawankule ,  Dharmendra Saikia ,  Anil Kumar Gupta ,  Anupam Maurya ,  Suman Preet Singh Khanuja

发明人： Santosh Kumar Srivastava ,  Ashok Kumar Agrawal ,  Subhash Chandra Singh ,  Vinay Kumar Khanna ,  Janardan Singh ,  Chandeshwar Nath ,  Madan Mohan Gupta ,  Shikha Gupta ,  Ram Kishor Verma ,  Anirban Pal ,  Duyaneshwar Umrao Bawankule ,  Dharmendra Saikia ,  Anil Kumar Gupta ,  Anupam Maurya ,  Suman Preet Singh Khanuja

IPC分类号： A61K31/4375 ,  C07D455/00 ,  A61P25/18 ,  A61K31/475

CPC分类号： A61K36/24

摘要： The present invention relates to bioactive extracts its fractions and isolation of compound from Rauwolfia tetraphylla. The extracts and fractions are useful for the treatment of psychosis based on in-vivo validation on animal model and proportional binding affinities for dopaminergic-D2, Cholinergic (muscarinic) and Serotonergic (5HT2A) receptors for antipsychotic activity. The present invention relates to novel antipsychotic activity in the leaf alkaloids of Formula 1 and 2 named tetrahydroalstonine, 10-methoxytetrahydroalstonine, isoreserpiline, 10-derαethoxyreserpiline, 11-demethoxyreserpiline, reserpiline and α-yohimbine. The present invention also relates to processes for obtaining antipsychotic extracts as well as for the isolation of alkabids of formula 1 and 2 from the leaves of Rauwolfia tetraphylla. The present invention particularly relates to significant antipsychotic activity in the MeOH extract, ethylacetate and chloroform fractions of R. tetraphylla and in the isolated compounds α-yohimbine, reserpiline and in a mixture 10-demethoxyreserpiline and 11-demethoxyreserpiline in 1:1.5 ratios for treating psychosis without any extra pyramidal symptoms (EPS). 1. R1=R2=OMe R3=β-H (Isoreserpiline) 2. R1=R2=OMe R3=β-H (Reserpiline) ″3. R1=OMe R2=HR3=β-H (11-Demethoxy reserpiline) ″4.R1=H R2=OMe R3=β-H (10-Demethoxy reserpiline) ″5. R1=R2=H R3=α-H (Tetrahydroalstonine) *7. R1=OMe R2=H R3=α-H (10-Methoxytetrahudroalstonine).

摘要翻译： 本发明涉及生物活性提取物，其部分和化合物从萝卜（Rauwolfia tetraphylla）分离。 基于动物模型的体内验证和针对抗精神病活性的多巴胺能D2，胆碱能（毒蕈碱）和血清素能（5HT2A）受体的比例结合亲和力，提取物和级分可用于治疗精神病。 本发明涉及式1和2的叶生物碱中的新型抗精神病活性，命名为四氢奥斯汀，10-甲氧基四氢奥斯汀，异丙基苯胺，10-脱乙氧基去甲苯胺，11-去甲氧基甲苯吡胺，储存蛋白和α-育亨宾。 本发明还涉及获得抗精神病药提取物以及分离来自罗非草（Rauwolfia tetraphylla）的叶子的式1和2的烷烃的方法。 本发明特别涉及在四氢叶酸甲酯的MeOH提取物，乙酸乙酯和氯仿级分中以及在分离的化合物α-育亨宾，储存器中和以1:1.5比例混合的10-脱甲氧基对苯二胺和11-脱甲氧基苯甲苯胺中的显着的抗精神病活性，用于治疗 精神病没有任何额外的锥体症状（EPS）。 R1 = R2 = OMe R3 =＆bgr; -H（Isoreserpiline）2.R1 = R2 = OMe R3 =＆bgr; -H（Reserpiline）“3。 R1 = OMe R2 = HR3 =＆bgr; -H（11-甲氧基乙酰胺）“4.R1 = H R2 = OMe R3 =＆bgr; -H（10-甲氧基乙胺） R1 = R2 = H R3 =α-H（四氢奥斯汀）* 7。 R1 = OMe R2 = H R3 =α-H（10-甲氧基四胡司汀）。