methyl (3S)-3-[(tert-butoxycarbonyl)amino]-4-oxo-4-pyrrolidin-1-ylbutanoate | 869586-96-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl (3S)-3-[(tert-butoxycarbonyl)amino]-4-oxo-4-pyrrolidin-1-ylbutanoate
• 英文别名: methyl (3S)-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxo-4-pyrrolidin-1-ylbutanoate
• CAS: 869586-96-9
• 化学式: C₁₄H₂₄N₂O₅
• 分子量: 300.355
• InChiKey: UVXUOGNFTKXCGR-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  84.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl (3S)-3-[(tert-butoxycarbonyl)amino]-4-oxo-4-pyrrolidin-1-ylbutanoate 在 lithium hydroxide 、 双(三甲基硅烷基)氨基钾 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 生成 (2S,3S)-3-[(tert-butoxycarbonyl)aminol-2-methy]-4-oxo-4-pyrrolidin-1-ylbutanoic acid
  参考文献：
  名称：

  发现有效的，选择性的和口服生物利用的基于恶二唑的二肽基肽酶IV抑制剂。

  摘要：

  一系列新的基于乙二唑的酰胺已被证明是有效的DPP-4抑制剂。优化的化合物43对多种DPP-4同源物显示出极好的选择性。

  DOI：

  10.1016/j.bmcl.2006.07.061
• 作为产物：
  描述：

  四氢吡咯 、 Boc-L-天冬氨酸 4-甲酯 在 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 methyl (3S)-3-[(tert-butoxycarbonyl)amino]-4-oxo-4-pyrrolidin-1-ylbutanoate
  参考文献：
  名称：

  发现有效的，选择性的和口服生物利用的基于恶二唑的二肽基肽酶IV抑制剂。

  摘要：

  一系列新的基于乙二唑的酰胺已被证明是有效的DPP-4抑制剂。优化的化合物43对多种DPP-4同源物显示出极好的选择性。

  DOI：

  10.1016/j.bmcl.2006.07.061

文献信息

• Discovery of an Orally Active Series of Isoxazoline Glycoprotein IIb/IIIa Antagonists
  作者：Chu-Biao Xue、John Wityak、Thais M. Sielecki、Donald J. Pinto、Douglas G. Batt、Gary A. Cain、Michael Sworin、Arlene L. Rockwell、John J. Roderick、Shuaige Wang、Michael J. Orwat、William E. Frietze、Lori L. Bostrom、Jie Liu、C. Anne Higley、F. Wayne Rankin、A. Ewa Tobin、George Emmett、George K. Lalka、Jean Y. Sze、Susan V. Di Meo、Shaker A. Mousa、Martin J. Thoolen、Adrienne L. Racanelli、Elizabeth A. Hausner、Thomas M. Reilly、William F. DeGrado、Ruth R. Wexler、Richard E. Olson

  DOI：10.1021/jm960799i

  日期：1997.6.1

  Using isoxazoline XR299 (1a) as a starting point for the design of highly potent, long-duration GPIIb/IIIa antagonists, the effect of placing lipophilic substituents at positions alpha and beta to the carboxylate moiety was evaluated. Of the compounds studied, it was found that the n-butyl carbamate 24u exhibited superior potency and duration of ex vivo antiplatelet effects in dogs. Replacement of

  使用异恶唑啉XR299（1a）作为设计高效，长效GPIIb / IIIa拮抗剂的起点，评估了将亲脂性取代基置于羧酸酯部分的α和β处的效果。在所研究的化合物中，发现氨基甲酸正丁酯24u在狗中表现出优异的效力和离体抗血小板作用的持续时间。用可替代的碱性基团取代苯并胺丁-4-基部分，消除异恶唑啉立体中心，并改变异恶唑啉环的方向，导致效力和/或作用时间降低。
• [EN] 1,2,4-OXADIAZOLE DERIVATIVES AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES<br/>[FR] DERIVES DE 1,2,4-OXADIAZOLE EN TANT QU'INHIBITEURS DE LA DIPEPTIDYLPEPTIDASE-IV DANS LE TRAITEMENT OU LA PREVENTION DE DIABETES
  申请人：MERCK & CO INC

  公开号：WO2005108382A1

  公开（公告）日：2005-11-17

  The present invention is directed to novel 1,2,4-oxadiazole derivatives which are inhibitors of the dipeptidyl peptidase-IV enzyme ('DP-IV inhibitors') and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.

  本发明涉及一种新颖的1,2,4-噁二唑衍生物，这些衍生物是二肽基肽酶-IV酶（'DP-IV抑制剂'）的抑制剂，并且在治疗或预防涉及二肽基肽酶-IV酶的疾病方面具有用处，例如糖尿病，特别是2型糖尿病。该发明还涉及包含这些化合物的药物组合物，以及这些化合物和组合物在预防或治疗涉及二肽基肽酶-IV酶的疾病方面的用途。
• 1,2,4-Oxadiazole Derivatives as Dipeptidyl Peptidase-IV Inhibitors for the Treatment or Prevention of Diabetes
  申请人：Xu Jinyou

  公开号：US20080021009A1

  公开（公告）日：2008-01-24

  The present invention is directed to novel 1,2,4-oxadiazole derivatives which are inhibitors of the dipeptidyl peptidase-IV enzyme (“DP-IV inhibitors”) and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.

  本发明涉及新型1,2,4-噁二唑衍生物，它们是二肽基肽酶-IV酶（“DP-IV酶”）的抑制剂，可用于治疗或预防涉及DP-IV酶的疾病，如糖尿病，特别是2型糖尿病。该发明还涉及包含这些化合物的制药组合物，以及在涉及DP-IV酶的这些疾病的预防或治疗中使用这些化合物和组合物。
• 1,2,4-Oxadiazole derivatives as dipeptidyl peptidase-IV inhibitors for the treatment or prevention of diabetes
  申请人：Merck Sharp & Dohme Corp.

  公开号：US07687492B2

  公开（公告）日：2010-03-30

  The present invention is directed to novel 1,2,4-oxadiazole derivatives which are inhibitors of the dipeptidyl peptidase-IV enzyme (“DP-IV inhibitors”) and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.

  本发明涉及一种新型1,2,4-噁二唑衍生物，其为二肽基肽酶-IV酶（“DP-IV抑制剂”）的抑制剂，并且对于涉及二肽基肽酶-IV酶的疾病的治疗或预防具有用处，例如糖尿病，特别是2型糖尿病。本发明还涉及包含这些化合物的制药组合物以及在涉及二肽基肽酶-IV酶的这些疾病的预防或治疗中使用这些化合物和组合物。
• Discovery of potent, selective, and orally bioavailable oxadiazole-based dipeptidyl peptidase IV inhibitors
  作者：Jinyou Xu、Lan Wei、Robert J. Mathvink、Scott D. Edmondson、George J. Eiermann、Huaibing He、Joseph F. Leone、Barbara Leiting、Kathryn A. Lyons、Frank Marsilio、Reshma A. Patel、Sangita B. Patel、Aleksandr Petrov、Giovanna Scapin、Joseph K. Wu、Nancy A. Thornberry、Ann E. Weber

  DOI：10.1016/j.bmcl.2006.07.061

  日期：2006.10

  A novel series of oxadiazole based amides have been shown to be potent DPP-4 inhibitors. The optimized compound 43 exhibited excellent selectivity over a variety of DPP-4 homologs.

  一系列新的基于乙二唑的酰胺已被证明是有效的DPP-4抑制剂。优化的化合物43对多种DPP-4同源物显示出极好的选择性。