tert-butyl (1R)-1-(2-aminopropan-2-yl)-5-chloro-6-methylspiro[1,2-dihydroindene-3,4'-piperidine]-1'-carboxylate | 1007363-00-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: tert-butyl (1R)-1-(2-aminopropan-2-yl)-5-chloro-6-methylspiro[1,2-dihydroindene-3,4'-piperidine]-1'-carboxylate
• CAS: 1007363-00-9
• 化学式: C₂₂H₃₃ClN₂O₂
• 分子量: 392.969
• InChiKey: VPKHSABHUCDSDY-QGZVFWFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl (1R)-1-(2-aminopropan-2-yl)-5-chloro-6-methylspiro[1,2-dihydroindene-3,4'-piperidine]-1'-carboxylate 、 乙酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 (R)-3-(2-乙酰胺基丙-2-基)-6-氯-5-甲基-2,3-二氢螺[叔茚-1,4'-哌啶]-1'-羧酸叔丁酯
  参考文献：
  名称：

  Spiroindane based amides as potent and selective MC4R agonists for the treatment of obesity

  摘要：

  We report a series of potent and selective MC4R agonists based on spiroindane amide privileged structures for potential treatments of obesity. Among the synthetic methods used, Method C allows rapid synthesis of the analogs. The series of compounds can afford high potency on MC4R as well as good rodent pharmacokinetic profiles. Compound 1r (MK-0489) demonstrates MC4R mediated reduction of food intake and body weight in mouse models. Compound 1r is efficacious in 14-day diet-induced obese (DIO) rat models. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.06.062
• 作为产物：
  描述：

  在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 生成 tert-butyl (1R)-1-(2-aminopropan-2-yl)-5-chloro-6-methylspiro[1,2-dihydroindene-3,4'-piperidine]-1'-carboxylate
  参考文献：
  名称：

  Spiroindane based amides as potent and selective MC4R agonists for the treatment of obesity

  摘要：

  We report a series of potent and selective MC4R agonists based on spiroindane amide privileged structures for potential treatments of obesity. Among the synthetic methods used, Method C allows rapid synthesis of the analogs. The series of compounds can afford high potency on MC4R as well as good rodent pharmacokinetic profiles. Compound 1r (MK-0489) demonstrates MC4R mediated reduction of food intake and body weight in mouse models. Compound 1r is efficacious in 14-day diet-induced obese (DIO) rat models. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.06.062

文献信息

• Synthesis of a Tertiary Carbinamide via a Novel Rh-Catalyzed Asymmetric Hydrogenation
  作者：John Limanto、C. Scott Shultz、Benjamin Dorner、Richard A. Desmond、Paul N. Devine、Shane W. Krska

  DOI：10.1021/jo702429u

  日期：2008.2.1

  [GRAPHICS]Asymmetric hydrogenation of allylic dimethylcarbinamide 2 with 1 mol % of cationic Rh(1)-Josiphos complex in THF under 500 psi of H(2) generated the corresponding tertiary carbinamide 1 in 98.5% assay yield and a 94:6 enantiomeric ratio. Upon crystallization, the product was isolated in 91% isolated yield and 95:5 enantiomeric ratio.
• Spiroindane based amides as potent and selective MC4R agonists for the treatment of obesity
  作者：Shuwen He、Zhixiong Ye、Peter H. Dobbelaar、Iyassu K. Sebhat、Liangqin Guo、Jian Liu、Tianying Jian、Yingjie Lai、Christopher L. Franklin、Raman K. Bakshi、James P. Dellureficio、Qingmei Hong、David H. Weinberg、Tanya MacNeil、Rui Tang、Alison M. Strack、Constantin Tamvakopoulos、Qianping Peng、Randy R. Miller、Ralph A. Stearns、Howard Y. Chen、Airu S. Chen、Tung M. Fong、Matthew J. Wyvratt、Ravi P. Nargund

  DOI：10.1016/j.bmcl.2010.06.062

  日期：2010.8

  We report a series of potent and selective MC4R agonists based on spiroindane amide privileged structures for potential treatments of obesity. Among the synthetic methods used, Method C allows rapid synthesis of the analogs. The series of compounds can afford high potency on MC4R as well as good rodent pharmacokinetic profiles. Compound 1r (MK-0489) demonstrates MC4R mediated reduction of food intake and body weight in mouse models. Compound 1r is efficacious in 14-day diet-induced obese (DIO) rat models. (C) 2010 Elsevier Ltd. All rights reserved.