(2S,3S,11bS)-2-tert-butoxycarbonylamino-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinoline-3-carboxylic acid ethyl ester | 1012065-73-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: (2S,3S,11bS)-2-tert-butoxycarbonylamino-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinoline-3-carboxylic acid ethyl ester
• 英文别名: ethyl (2S,3S,11bS)-9,10-dimethoxy-2-[(2-methylpropan-2-yl)oxycarbonylamino]-2,3,4,6,7,11b-hexahydro-1H-benzo[a]quinolizine-3-carboxylate
• CAS: 1012065-73-4
• 化学式: C₂₃H₃₄N₂O₆
• 分子量: 434.533
• InChiKey: WTWJEJFVUQNVLB-BZSNNMDCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  86.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2S,3S,11bS)-2-tert-butoxycarbonylamino-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinoline-3-carboxylic acid ethyl ester 在 sodium methylate 、 formamide 作用下， 以 四氢呋喃 为溶剂， 以91.3%的产率得到(2S,3S,11bS)-[3-carbamoyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl]carbamic acid tert-butyl ester
  参考文献：
  名称：

  PROCESS FOR THE PREPARATION OF PYRIDO [2,1-a] ISOQUINOLINE DERIVATIVES COMPRISING OPTICAL RESOLUTION OF AN ENAMINE

  摘要：

  本发明涉及一种制备式为pyrido[2,1-a]异喹啉衍生物的方法，其中R1、R2、R3和R4在规范中有定义，包括在具有手性分离剂的存在下，光学分辨式为R1为低级烷基的恩酰胺，形成式为RCO2-的手性(S)-恩酰胺盐。

  公开号：

  US20080071087A1
• 作为产物：
  描述：

  (S)-2-amino-9,10-dimethoxy-1,6,7,11b-tetrahydro-4H-pyrido[2,1-a]isoquinoline-3-carboxylic acid ethyl ester, (S,S)-2,3-bisbenzoyloxysuccinic acid salt 、 二碳酸二叔丁酯 在 三氟乙酸 、 sodium tetrahydroborate 、 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 25.0h， 以64%的产率得到(2S,3S,11bS)-2-tert-butoxycarbonylamino-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinoline-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  PROCESS FOR THE PREPARATION OF PYRIDO [2,1-a] ISOQUINOLINE DERIVATIVES COMPRISING OPTICAL RESOLUTION OF AN ENAMINE

  摘要：

  本发明涉及一种制备式为pyrido[2,1-a]异喹啉衍生物的方法，其中R1、R2、R3和R4在规范中有定义，包括在具有手性分离剂的存在下，光学分辨式为R1为低级烷基的恩酰胺，形成式为RCO2-的手性(S)-恩酰胺盐。

  公开号：

  US20080071087A1

文献信息

• Discovery of carmegliptin: A potent and long-acting dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes
  作者：Patrizio Mattei、Markus Boehringer、Patrick Di Giorgio、Holger Fischer、Michael Hennig、Joerg Huwyler、Buelent Koçer、Bernd Kuhn、Bernd M. Loeffler、Alexander MacDonald、Robert Narquizian、Etienne Rauber、Elena Sebokova、Urs Sprecher

  DOI：10.1016/j.bmcl.2009.12.024

  日期：2010.2

  synthesis, and SAR are described for a class of DPP-IV inhibitors based on aminobenzo[a]quinolizines with non-aromatic substituents in the S1 specificity pocket. One representative thereof, carmegliptin (8p), was chosen for clinical development. Its X-ray structure in complex with the enzyme and early efficacy data in animal models of type 2 diabetes are also presented.

  针对一类基于S1特异性口袋中具有非芳族取代基的氨基苯并[ a ]喹唑啉的DPP-IV抑制剂的设计，合成和SAR进行了描述。选择其代表卡格列汀（8p）进行临床开发。还介绍了其与酶复合的X射线结构以及2型糖尿病动物模型中的早期功效数据。
• Substituted piperidine compounds and methods of their use
  申请人：——

  公开号：US20040254218A1

  公开（公告）日：2004-12-16

  Novel 3,4-disubstituted-4-aryl-piperidine compounds are disclosed. Pharmaceutical compositions containing the 3,4-disubstituted-4-aryl-piperidine compounds and methods of their pharmaceutical uses are also disclosed. The compounds disclosed are useful, inter alia, as antagonists of opioid receptors.

  揭示了小说3,4-二取代-4-芳基哌啶化合物。还揭示了含有3,4-二取代-4-芳基哌啶化合物的药物组合物以及它们的药用方法。所揭示的化合物可用作阿片受体的拮抗剂，等等。
• PROCESS FOR THE PREPARATION OF PYRIDO [ 2-1-A] ISOQUINOLINE DERIVATIVES BY CATALYTIC ASYMMETRIC HYDROGENATION OF AN ENAMINE
  申请人：Abrecht Stefan

  公开号：US20080076925A1

  公开（公告）日：2008-03-27

  The invention relates to a process for the preparation of pyrido[2,1- a ] isoquinoline derivatives of the formula wherein R 2 , R 3 and R 4 are as defined in the specification, comprising the steps of a) catalytic asymmetric hydrogenation of an enamine of the formula wherein R 1 is lower alkyl, in the presence of a transition metal catalyst containing a chiral diphosphane ligand, b) introduction of an amino protecting group Prot and c) amidation of the ester to form an amide of formula wherein R 2 , R 3 , R 4 and Prot are as defined in the specification.

  本发明涉及一种制备式为的吡啶并[2,1-a]异喹啉衍生物的方法，其中R2、R3和R4如规范中所定义，包括以下步骤：a）在手性二膦配体存在下，对式为的烯胺进行催化不对称氢化，其中R1为低碳基；b）引入氨基保护基Prot；c）酰胺化酯，形成式为的酰胺，其中R2、R3、R4和Prot如规范中所定义。
• Pyrido [2,1-a] isoquinoline derivatives
  申请人：——

  公开号：US20040259902A1

  公开（公告）日：2004-12-23

  The present invention relates to compounds of formula (I) 1 wherein R 1 is as defined in the description, and pharmaceutically acceptable salts thereof. The compounds are useful for the treatment and/or prophylaxis of diseases which are associated with DPP-IV, such as diabetes, particularly non-insulin dependent diabetes mellitus, and impaired glucose tolerance.

  本发明涉及式(I)化合物，其中R1如描述中所定义，并且其药学上可接受的盐。该化合物可用于治疗和/或预防与DPP-IV相关的疾病，如糖尿病，特别是非胰岛素依赖性糖尿病和糖耐量受损。
• PROCESS FOR THE PREPARATION OF PYRIDO [2,1-A] ISOQUINOLINE DERIVATIVES COMPRISING OPTICAL RESOLUTION OF AN ENAMINE
  申请人：Abrecht Stefan

  公开号：US20130018191A1

  公开（公告）日：2013-01-17

  This invention relates to a process for the preparation of pyrido[2,1-a] isoquinoline derivatives of the formula wherein R 1 , R 2 , R 3 and R 4 are defined in the specification, comprising the optical resolution of an enamine of the formula wherein R 1 is lower alkyl, in the presence of an optical active resolving agent to form an (S)-enamine salt of the formula wherein RCO 2 − is the conjugate base of the resolving agent.

  本发明涉及一种制备式为pyrido [2,1-a] isoquinoline衍生物的过程，其中R1、R2、R3和R4在说明书中定义，包括在光学活性分离剂的存在下对式为的烯胺进行光学分辨，以形成式为的（S）-烯胺盐，其中RCO2-是分离剂的共轭碱基。