(2S,3S)-3-(3-bromophenyl)-4-(4-chlorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol | 1092698-89-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: (2S,3S)-3-(3-bromophenyl)-4-(4-chlorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol
• 英文别名: (2S,3S)-3-(3-bromophenyl)-4-(4-chlorophenyl)-1-(1,2,4-triazol-1-yl)butan-2-ol
• CAS: 1092698-89-9
• 化学式: C₁₈H₁₇BrClN₃O
• 分子量: 406.709
• InChiKey: QDMCOIDNZXEMOL-ZWKOTPCHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  50.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2S,3S)-3-(3-bromophenyl)-4-(4-chlorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol 、 氰化锌 在 四(三苯基膦)钯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.08h， 以47%的产率得到3-[(2S,3S)-1-(4-chlorophenyl)-3-hydroxy-4-(1H-1,2,4-triazol-1-yl)butan-2-yl]benzonitrile
  参考文献：
  名称：

  Design, chemical synthesis, and biological evaluation of novel triazolyl analogues of taranabant (MK-0364), a cannabinoid-1 receptor inverse agonist

  摘要：

  Being obese has various health problems that are related to type 2 diabetes mellitus, cardiovascular disease, hypertension, hyperlipidemia, and fibrinolytic abnormalities. Merck's taranabant (MK-0364), a CB1R inverse agonist, is currently in Phase 3 clinical trials, and is being actively pursued by Merck toward obesity market. Merck intends to file for FDA approval of taranabant in 2008. In order to increase solubility and potency of taranabant, or even possibly improve safety, novel triazole analogues of taranabant have been designed and synthesized. We introduced a pivotal asymmetric center via the Evans chiral auxiliary methodology and set up 1,2,4-triazole via substitution of alpha-bromoketone. Subsequently, diastereoselective reduction was accomplished to install adjacent essential asymmetric center. This method allowed us to prepare readily sub-gram scale of the target compounds in a convenient way. The synthesized analogues were subjected to biological evaluation involving cannabinoid CB1 receptor binding affinity. While the parent taranabant bears highly potent binding affinity to cannabinoid CB1 receptor, neither of the analog structures improved CB1 receptor binding affinities. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2008.09.057
• 作为产物：
  描述：

  (S)-3-(3-bromophenyl)-4-(4-chlorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-one 在 L-Selectride 作用下， 以 四氢呋喃 为溶剂， 以99%的产率得到(2S,3S)-3-(3-bromophenyl)-4-(4-chlorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol
  参考文献：
  名称：

  Design, chemical synthesis, and biological evaluation of novel triazolyl analogues of taranabant (MK-0364), a cannabinoid-1 receptor inverse agonist

  摘要：

  Being obese has various health problems that are related to type 2 diabetes mellitus, cardiovascular disease, hypertension, hyperlipidemia, and fibrinolytic abnormalities. Merck's taranabant (MK-0364), a CB1R inverse agonist, is currently in Phase 3 clinical trials, and is being actively pursued by Merck toward obesity market. Merck intends to file for FDA approval of taranabant in 2008. In order to increase solubility and potency of taranabant, or even possibly improve safety, novel triazole analogues of taranabant have been designed and synthesized. We introduced a pivotal asymmetric center via the Evans chiral auxiliary methodology and set up 1,2,4-triazole via substitution of alpha-bromoketone. Subsequently, diastereoselective reduction was accomplished to install adjacent essential asymmetric center. This method allowed us to prepare readily sub-gram scale of the target compounds in a convenient way. The synthesized analogues were subjected to biological evaluation involving cannabinoid CB1 receptor binding affinity. While the parent taranabant bears highly potent binding affinity to cannabinoid CB1 receptor, neither of the analog structures improved CB1 receptor binding affinities. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2008.09.057