(1S,2R)-2-Phenylcyclopropanamine, (2S,3S)-2,3-dihydroxybutanedioate | 220241-67-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (1S,2R)-2-Phenylcyclopropanamine, (2S,3S)-2,3-dihydroxybutanedioate
• 英文别名: (2S,3S)-2,3-dihydroxybutanedioic acid;(1S,2R)-2-phenylcyclopropan-1-amine
• CAS: 220241-67-8
• 化学式: C₄H₆O₆*C₉H₁₁N
• 分子量: 283.281
• InChiKey: BMMYXZOHOQZKPZ-DNCFFYMRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.62
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  141
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (1S,2R)-2-Phenylcyclopropanamine, (2S,3S)-2,3-dihydroxybutanedioate 在 sodium hydroxide 作用下， 以 乙醚 、 水 为溶剂， 生成 (1S,2R)-2-苯基环丙胺
  参考文献：
  名称：

  Identification of MK-5710 ((8aS)-8a-methyl-1,3-dioxo-2-[(1S,2R)-2-phenylcyclo- propyl]-N-(1-phenyl-1H-pyrazol-5-yl)hexahydro-imidazo[1,5-a]pyrazine-7(1H)-carboxamide), a potent smoothened antagonist for use in Hedgehog pathway dependent malignancies, Part 2

  摘要：

  The Hedgehog (Hh-) signaling pathway is a key developmental pathway which gets reactivated in many human tumors, and smoothened (Smo) antagonists are emerging as novel agents for the treatment of malignancies dependent on the Hh-pathway, with the most advanced compounds demonstrating encouraging results in initial clinical trials. A novel series of potent bicyclic hydantoin Smo antagonists was reported in the preceding article, these have been resolved, and optimized to identify potent homochiral derivatives with clean off-target profiles and good pharmacokinetic properties in preclinical species. While showing in vivo efficacy in mouse allograft models, unsubstituted bicyclic tetrahydroimidazo[1,5-a]pyrazine-1,3(2H,5H)-diones were shown to epimerize in plasma. Alkylation of the C-8 position blocks this epimerization, resulting in the identification of MK-5710 (47) which was selected for further development. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.06.023
• 作为产物：
  描述：

  L-酒石酸 、 (1R,2S)-2-苯基环丙胺 以 乙醇 为溶剂， 以31%的产率得到(1S,2R)-2-Phenylcyclopropanamine, (2S,3S)-2,3-dihydroxybutanedioate
  参考文献：
  名称：

  Identification of MK-5710 ((8aS)-8a-methyl-1,3-dioxo-2-[(1S,2R)-2-phenylcyclo- propyl]-N-(1-phenyl-1H-pyrazol-5-yl)hexahydro-imidazo[1,5-a]pyrazine-7(1H)-carboxamide), a potent smoothened antagonist for use in Hedgehog pathway dependent malignancies, Part 2

  摘要：

  The Hedgehog (Hh-) signaling pathway is a key developmental pathway which gets reactivated in many human tumors, and smoothened (Smo) antagonists are emerging as novel agents for the treatment of malignancies dependent on the Hh-pathway, with the most advanced compounds demonstrating encouraging results in initial clinical trials. A novel series of potent bicyclic hydantoin Smo antagonists was reported in the preceding article, these have been resolved, and optimized to identify potent homochiral derivatives with clean off-target profiles and good pharmacokinetic properties in preclinical species. While showing in vivo efficacy in mouse allograft models, unsubstituted bicyclic tetrahydroimidazo[1,5-a]pyrazine-1,3(2H,5H)-diones were shown to epimerize in plasma. Alkylation of the C-8 position blocks this epimerization, resulting in the identification of MK-5710 (47) which was selected for further development. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.06.023

文献信息

• TRIAZOLO(4,5-D)PYRIMIDINYL DERIVATIVES AND THEIR USE AS MEDICAMENTS
  申请人：AstraZeneca AB

  公开号：EP0946561B1

  公开（公告）日：2002-02-13
• US6297232B1
  申请人：——

  公开号：US6297232B1

  公开（公告）日：2001-10-02
• Identification of MK-5710 ((8aS)-8a-methyl-1,3-dioxo-2-[(1S,2R)-2-phenylcyclo- propyl]-N-(1-phenyl-1H-pyrazol-5-yl)hexahydro-imidazo[1,5-a]pyrazine-7(1H)-carboxamide), a potent smoothened antagonist for use in Hedgehog pathway dependent malignancies, Part 2
  作者：Olaf Kinzel、Anna Alfieri、Sergio Altamura、Mirko Brunetti、Simone Bufali、Fabrizio Colaceci、Federica Ferrigno、Gessica Filocamo、Massimiliano Fonsi、Paola Gallinari、Savina Malancona、Jose Ignacio Martin Hernando、Edith Monteagudo、Maria Vittoria Orsale、Maria Cecilia Palumbi、Vincenzo Pucci、Michael Rowley、Romina Sasso、Rita Scarpelli、Christian Steinkühler、Philip Jones

  DOI：10.1016/j.bmcl.2011.06.023

  日期：2011.8

  The Hedgehog (Hh-) signaling pathway is a key developmental pathway which gets reactivated in many human tumors, and smoothened (Smo) antagonists are emerging as novel agents for the treatment of malignancies dependent on the Hh-pathway, with the most advanced compounds demonstrating encouraging results in initial clinical trials. A novel series of potent bicyclic hydantoin Smo antagonists was reported in the preceding article, these have been resolved, and optimized to identify potent homochiral derivatives with clean off-target profiles and good pharmacokinetic properties in preclinical species. While showing in vivo efficacy in mouse allograft models, unsubstituted bicyclic tetrahydroimidazo[1,5-a]pyrazine-1,3(2H,5H)-diones were shown to epimerize in plasma. Alkylation of the C-8 position blocks this epimerization, resulting in the identification of MK-5710 (47) which was selected for further development. (C) 2011 Elsevier Ltd. All rights reserved.