tert-butyl (3S,4R)-3-(4-(2-((S)-1-(((S)-tert-butylsulfinyl)amino)-2-methylpropyl)-4-methylphenyl)piperazine-1-carbonyl)-4-(4-chlorophenyl)pyrrolidine-1-carboxylate | 851484-57-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: tert-butyl (3S,4R)-3-(4-(2-((S)-1-(((S)-tert-butylsulfinyl)amino)-2-methylpropyl)-4-methylphenyl)piperazine-1-carbonyl)-4-(4-chlorophenyl)pyrrolidine-1-carboxylate
• CAS: 851484-57-6
• 化学式: C₃₅H₅₁ClN₄O₄S
• 分子量: 659.333
• InChiKey: RAHNKJPRZBCDNC-FOBZEKASSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  45.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  82.19
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (3S,4R)-3-(4-(2-((S)-1-(((S)-tert-butylsulfinyl)amino)-2-methylpropyl)-4-methylphenyl)piperazine-1-carbonyl)-4-(4-chlorophenyl)pyrrolidine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以98%的产率得到(S)-N-((S)-1-(2-(4-((3S,4R)-4-(4-chlorophenyl)pyrrolidine-3-carbonyl)piperazin-1-yl)-5-methylphenyl)-2-methylpropyl)-2-methylpropane-2-sulfinamide
  参考文献：
  名称：

  Synthesis and characterization of pyrrolidine derivatives as potent agonists of the human melanocortin-4 receptor

  摘要：

  A series of trans-4-phenylpyrrolidine-3-carboxamides were synthesized and characterized as potent ligands of the human melanocortin-4 receptor. Interestingly, a pair of diastereoisomers 20f-1 and 20f-2 displayed potent functional agonist and antagonist activity, respectively. Thus, the 3S, 4R-compound 20f-1 possessed a K-i of 11 nM and an EC50 of 24 nM, while its 3R, 4S-isomer 20f-2 exhibited a K-i of 8.6 and an IC50 of 65 nM. Both compounds were highly selective over other melanocortin receptor subtypes. The MC4R agonist 20f-1 also demonstrated efficacy in diet-induced obese rats. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.09.079
• 作为产物：
  描述：

  (S_S)-2-methyl-propane-2-sulfinic acid [(S)-2-methyl-1-(5-methyl-2-piperazin-1-yl-phenyl)-propyl]-amide 、 N-BOC-(3S,4R)-4-(4-氯苯基)吡咯烷-3-羧酸 在 碳酸氢钠 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以88%的产率得到tert-butyl (3S,4R)-3-(4-(2-((S)-1-(((S)-tert-butylsulfinyl)amino)-2-methylpropyl)-4-methylphenyl)piperazine-1-carbonyl)-4-(4-chlorophenyl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  Synthesis and characterization of pyrrolidine derivatives as potent agonists of the human melanocortin-4 receptor

  摘要：

  A series of trans-4-phenylpyrrolidine-3-carboxamides were synthesized and characterized as potent ligands of the human melanocortin-4 receptor. Interestingly, a pair of diastereoisomers 20f-1 and 20f-2 displayed potent functional agonist and antagonist activity, respectively. Thus, the 3S, 4R-compound 20f-1 possessed a K-i of 11 nM and an EC50 of 24 nM, while its 3R, 4S-isomer 20f-2 exhibited a K-i of 8.6 and an IC50 of 65 nM. Both compounds were highly selective over other melanocortin receptor subtypes. The MC4R agonist 20f-1 also demonstrated efficacy in diet-induced obese rats. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.09.079

文献信息

• Pyrrolidines as potent functional agonists of the human melanocortin-4 receptor
  作者：Joe A. Tran、Caroline W. Chen、Wanlong Jiang、Fabio C. Tucci、Beth A. Fleck、Dragan Marinkovic、Melissa Arellano、Chen Chen

  DOI：10.1016/j.bmcl.2007.06.088

  日期：2007.9

  A series of pyrrolidine derivatives were synthesized and characterized as potent agonists of the human melanocortin-4 receptor. For example, 28c had a K-i of 13 nM in binding affinity and EC50 of 6.9 nM in agonist potency with an intrinsic activity of 100% of the endogenous ligand alpha-MSH. (c) 2007 Elsevier Ltd. All rights reserved.
• Synthesis and characterization of pyrrolidine derivatives as potent agonists of the human melanocortin-4 receptor
  作者：Wanlong Jiang、Joe A. Tran、Fabio C. Tucci、Beth A. Fleck、Sam R. Hoare、Stacy Markison、Jenny Wen、Caroline W. Chen、Dragan Marinkovic、Melissa Arellano、Alan C. Foster、Chen Chen

  DOI：10.1016/j.bmcl.2007.09.079

  日期：2007.12

  A series of trans-4-phenylpyrrolidine-3-carboxamides were synthesized and characterized as potent ligands of the human melanocortin-4 receptor. Interestingly, a pair of diastereoisomers 20f-1 and 20f-2 displayed potent functional agonist and antagonist activity, respectively. Thus, the 3S, 4R-compound 20f-1 possessed a K-i of 11 nM and an EC50 of 24 nM, while its 3R, 4S-isomer 20f-2 exhibited a K-i of 8.6 and an IC50 of 65 nM. Both compounds were highly selective over other melanocortin receptor subtypes. The MC4R agonist 20f-1 also demonstrated efficacy in diet-induced obese rats. (c) 2007 Elsevier Ltd. All rights reserved.
• Identification and characterization of pyrrolidine diastereoisomers as potent functional agonists and antagonists of the human melanocortin-4 receptor
  作者：Chen Chen、Wanlong Jiang、Joe A. Tran、Fabio C. Tucci、Beth A. Fleck、Stacy Markison、Jenny Wen、Ajay Madan、Sam R. Hoare、Alan C. Foster、Dragan Marinkovic、Caroline W. Chen、Melissa Arellano、John Saunders

  DOI：10.1016/j.bmcl.2007.10.115

  日期：2008.1

  A series of trans-4-phenylpyrrolidine-3-carboxamides were synthesized and characterized as potent ligands of the human melanocortin-4 receptor. Interestingly, a pair of diastereoisomers 13b displayed potent functional agonist and antagonist activity, respectively. Thus, the 3S,4R-pyrrolidine 13b-1 possessed a K-i of 1.0 nM and an EC50 of 3.8 nM while its 3R,4S-isomer 13b-2 exhibited a K-i of 4.7 and an IC50 of 64 nM. Both compounds were highly selective over other melanocortin receptor subtypes. The MC4R agonist 13b-1 also demonstrated efficacy in a diet-induced obesity model in rats. (C) 2007 Elsevier Ltd. All rights reserved.