tert-butyl (1R,3R,4S)-3-(phenoxymethyl)-4-(2-(3-(trifluoromethyl)benzamido)acetamido)cyclohexylcarbamate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tert-butyl (1R,3R,4S)-3-(phenoxymethyl)-4-(2-(3-(trifluoromethyl)benzamido)acetamido)cyclohexylcarbamate
• 英文别名: tert-butyl N-[(1R,3R,4S)-3-(phenoxymethyl)-4-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]cyclohexyl]carbamate
• 化学式: C₂₈H₃₄F₃N₃O₅
• 分子量: 549.59
• InChiKey: AEPLOCPCYQFASU-WPYKKVEZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  39
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  106
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl (1R,3R,4S)-3-(phenoxymethyl)-4-(2-(3-(trifluoromethyl)benzamido)acetamido)cyclohexylcarbamate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 N-[2-[[(1S,2R,4R)-4-amino-2-(phenoxymethyl)cyclohexyl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide
  参考文献：
  名称：

  Discovery of a Potent and Orally Bioavailable Dual Antagonist of CC Chemokine Receptors 2 and 5

  摘要：

  We describe the hybridization of our previously reported acyclic and cyclic CC chemokine receptor 2 (CCR2) antagonists to lead to a new series of dual antagonists of CCR2 and CCRS. Installation of a gamma-lactam as the spacer group and a quinazoline as a benzamide mimetic improved oral bioavailability markedly. These efforts led to the identification of 13d, a potent and orally bioavailable dual antagonist suitable for use in both murine and monkey models of inflammation.

  DOI：

  10.1021/ml500505q
• 作为产物：
  描述：

  benzyl (1S,2R,4R)-4-(tert-butoxycarbonylamino)-2-(hydroxymethyl)cyclohexylcarbamate 在 5%-palladium/activated carbon 、 BOP 、 氢气 、 N,N-二异丙基乙胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 tert-butyl (1R,3R,4S)-3-(phenoxymethyl)-4-(2-(3-(trifluoromethyl)benzamido)acetamido)cyclohexylcarbamate
  参考文献：
  名称：

  Discovery of a Potent and Orally Bioavailable Dual Antagonist of CC Chemokine Receptors 2 and 5

  摘要：

  We describe the hybridization of our previously reported acyclic and cyclic CC chemokine receptor 2 (CCR2) antagonists to lead to a new series of dual antagonists of CCR2 and CCRS. Installation of a gamma-lactam as the spacer group and a quinazoline as a benzamide mimetic improved oral bioavailability markedly. These efforts led to the identification of 13d, a potent and orally bioavailable dual antagonist suitable for use in both murine and monkey models of inflammation.

  DOI：

  10.1021/ml500505q

文献信息

• Discovery of a Potent and Orally Bioavailable Dual Antagonist of CC Chemokine Receptors 2 and 5
  作者：Percy H. Carter、Gregory D. Brown、Robert J. Cherney、Douglas G. Batt、Jing Chen、Cheryl M. Clark、Mary Ellen Cvijic、John V. Duncia、Soo S. Ko、Sandhya Mandlekar、Ruowei Mo、David J. Nelson、Jian Pang、Anne V. Rose、Joseph B. Santella、Andrew J. Tebben、Sarah C. Traeger、Songmei Xu、Qihong Zhao、Joel C. Barrish

  DOI：10.1021/ml500505q

  日期：2015.4.9

  We describe the hybridization of our previously reported acyclic and cyclic CC chemokine receptor 2 (CCR2) antagonists to lead to a new series of dual antagonists of CCR2 and CCRS. Installation of a gamma-lactam as the spacer group and a quinazoline as a benzamide mimetic improved oral bioavailability markedly. These efforts led to the identification of 13d, a potent and orally bioavailable dual antagonist suitable for use in both murine and monkey models of inflammation.