公开(公告)号：US09206155B2

公开(公告)日：2015-12-08

申请号：US13995336

申请日：2012-01-12

申请人： Dinesh Kumar Dikshit ,  Madhu Dikshit ,  Tanveer Irshad Siddiqui ,  Anil Kumar ,  Rabi Sankar Bhatta ,  Girish Kumar Jain ,  Manoj Kumar Barthwal ,  Ankita Misra ,  Vivek Khanna ,  Prem Prakash ,  Manish Jain ,  Vishal Singh ,  Varsha Gupta ,  Anil Kumar Dwivedi

发明人： Dinesh Kumar Dikshit ,  Madhu Dikshit ,  Tanveer Irshad Siddiqui ,  Anil Kumar ,  Rabi Sankar Bhatta ,  Girish Kumar Jain ,  Manoj Kumar Barthwal ,  Ankita Misra ,  Vivek Khanna ,  Prem Prakash ,  Manish Jain ,  Vishal Singh ,  Varsha Gupta ,  Anil Kumar Dwivedi

IPC分类号： C07D401/06 ,  C07B53/00

CPC分类号： A61K31/454 ,  C07B53/00 ,  C07D401/06

摘要： Chiral 1-(4-methylphenylmethyl)-5-oxo-{N-[(3-t-butoxycarbonyl-aminomethyl)]-piperidin-1-yl}-pyrrolidine-2-carboxamides as inhibitors of collagen induced platelet activation and adhesion The present invention provides chiral (2S)-1-(4-methyl-phenylmethyl)-5-oxo-(3S)—{N-[(3-t-butoxycarbonyl aminomethyl)]-piperidin-1-yl}-pyrrolidine-2-carboxamide, and (2S)-1-(4-methylphenylmethyl)-5-oxo-(3R)—{N-[(3-t-butoxycarbonyl amino methyl)]-piperidin-1-yl}-pyrrolidine-2-carboxamide of formula 6 and 7 respectively. The present invention also relates to use of these moieties as inhibitors of collagen induced platelet adhesion and aggregation mediated through collagen receptors. The present invention provides a process for preparation of chiral carboxamides of formula 6 and 7 using the process which has advantage to avoid any racemization at the a-carboxylic center, during N-alkylation. The reagent LiHMDS is used at low temperatures to furnish methyl N-(p methylphenylmethyl)lpyroglutamate in good chiral purity.

摘要翻译： 手性1-（4-甲基苯基甲基）-5-氧代 - {N - [（3-叔丁氧基羰基 - 氨基甲基）] - 哌啶-1-基} - 吡咯烷-2-甲酰胺作为胶原诱导的血小板活化和粘附抑制剂 本发明提供手性（2S）-1-（4-甲基 - 苯基甲基）-5-氧代 - （3S） - {N - [（3-叔丁氧基羰基氨基甲基）] - 哌啶-1-基} - 吡咯烷-2-酮 （2S）-1-（4-甲基苯基甲基）-5-氧代 - （3R） - {N - [（3-叔丁氧基羰基氨基甲基）] - 哌啶-1-基} - 吡咯烷-2-酮 分别为式6和7的甲酰胺。 本发明还涉及这些部分作为通过胶原受体介导的胶原诱导的血小板粘附和聚集的抑制剂的用途。 本发明提供了一种制备式6和7的手性羧酰胺的方法，该方法在N-烷基化过程中有利于避免在α-羧酸中心的任何外消旋化。 在低温下使用试剂LiHMDS以提供良好的手性纯度的N-（p甲基苯基甲基）l吡咯烷酸甲酯。

公开(公告)号：US20130338193A1

公开(公告)日：2013-12-19

申请号：US13995336

申请日：2012-01-12

申请人： Dinesh Kumar Dikshit ,  Madhu Dikshit ,  Tanveer Irshad Siddiqui ,  Anil Kumar ,  Rabi Sankar Bhata ,  Girish Kumar Jain ,  Manoj Kumar Barthwal ,  Ankita Misra ,  Vivek Khanna ,  Prem Prakash ,  Manish Jain ,  Vishal Singh ,  Varsha Gupta ,  Anil Kumar Dwivedi

发明人： Dinesh Kumar Dikshit ,  Madhu Dikshit ,  Tanveer Irshad Siddiqui ,  Anil Kumar ,  Rabi Sankar Bhata ,  Girish Kumar Jain ,  Manoj Kumar Barthwal ,  Ankita Misra ,  Vivek Khanna ,  Prem Prakash ,  Manish Jain ,  Vishal Singh ,  Varsha Gupta ,  Anil Kumar Dwivedi

IPC分类号： C07D401/06

CPC分类号： A61K31/454 ,  C07B53/00 ,  C07D401/06

摘要： Chiral 1-(4-methylphenylmethyl)-5-oxo-{N-[(3-t-butoxycarbonyl-aminomethyl)]-piperidin-1-yl}-pyrrolidine-2-carboxamides as inhibitors of collagen induced platelet activation and adhesion The present invention provides chiral (2S)-1-(4-methyl-phenylmethyl)-5-oxo-(3S)-{N-[(3-t butoxycarbonyl aminomethyl)]-piperidin-1-yl}-pyrrolidine-2-carboxamide, and (2S)-1-(4-methylphenylmethyl)-5-oxo-(3R)-{N-[(3-t-butoxycarbonyl amino methyl)]-piperidin-1-yl}-pyrrolidine-2-carboxamide of formula 6 and 7 respectively. The present invention also relates to use of these moieties as inhibitors of collagen induced platelet adhesion and aggregation mediated through collagen receptors. The present invention provides a process for preparation of chiral carboxamides of formula 6 and 7 using the process which has advantage to avoid any racemization at the a-carboxylic center, during N-alkylation. The reagent LiHMDS is used at low temperatures to furnish methyl N-(p methylphenylmethyl)lpyroglutamate in good chiral purity.

摘要翻译： 手性1-（4-甲基苯基甲基）-5-氧代 - {N - [（3-叔丁氧基羰基 - 氨基甲基）] - 哌啶-1-基} - 吡咯烷-2-甲酰胺作为胶原诱导的血小板活化和粘附抑制剂 本发明提供手性（2S）-1-（4-甲基 - 苯基甲基）-5-氧代 - （3S） - {N - [（3-叔丁氧基羰基氨基甲基）] - 哌啶-1-基} - 吡咯烷-2-酮 （2S）-1-（4-甲基苯基甲基）-5-氧代 - （3R） - {N - [（3-叔丁氧基羰基氨基甲基）] - 哌啶-1-基} - 吡咯烷-2-甲酰胺 分别为式6和7。 本发明还涉及这些部分作为通过胶原受体介导的胶原诱导的血小板粘附和聚集的抑制剂的用途。 本发明提供了一种制备式6和7的手性羧酰胺的方法，该方法在N-烷基化过程中有利于避免在α-羧酸中心的任何外消旋化。 在低温下使用试剂LiHMDS以提供良好的手性纯度的N-（p甲基苯基甲基）l吡咯烷酸甲酯。