2-[5-Chloro-6-methyl-1'-[(2-methylpropan-2-yl)oxycarbonyl]spiro[1,2-dihydroindene-3,4'-piperidine]-1-yl]-2-methylpropanoic acid | 1243674-87-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 2-[5-Chloro-6-methyl-1'-[(2-methylpropan-2-yl)oxycarbonyl]spiro[1,2-dihydroindene-3,4'-piperidine]-1-yl]-2-methylpropanoic acid
• CAS: 1243674-87-4
• 化学式: C₂₃H₃₂ClNO₄
• 分子量: 421.964
• InChiKey: CFPNXNIOBHEHKX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[5-Chloro-6-methyl-1'-[(2-methylpropan-2-yl)oxycarbonyl]spiro[1,2-dihydroindene-3,4'-piperidine]-1-yl]-2-methylpropanoic acid 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 生成
  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：

  1a(2)-[(1,1-Dimethylethoxy)carbonyl]-2,3-dihydro-I+/-,I+/-,5-trimethylspiro[1H-indene-1,4a(2)-piperidine]-3-acetic acid 在 N-氯代丁二酰亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2-[5-Chloro-6-methyl-1'-[(2-methylpropan-2-yl)oxycarbonyl]spiro[1,2-dihydroindene-3,4'-piperidine]-1-yl]-2-methylpropanoic acid
  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

• WO2007/47496
  申请人：——

  公开号：——

  公开（公告）日：——
• Discovery of highly potent and efficacious MC4R agonists with spiroindane N-Me-1,2,4-triazole privileged structures for the treatment of obesity
  作者：Shuwen He、Zhixiong Ye、Peter H. Dobbelaar、Raman K. Bakshi、Qingmei Hong、James P. Dellureficio、Iyassu K. Sebhat、Liangqin Guo、Jian Liu、Tianying Jian、Yingjie Lai、Christopher L. Franklin、Mikhail Reibarkh、Mark A. Holmes、David H. Weinberg、Tanya MacNeil、Rui Tang、Constantin Tamvakopoulos、Qianping Peng、Randy R. Miller、Ralph A. Stearns、Howard Y. Chen、Airu S. Chen、Alison M. Strack、Tung M. Fong、Matthew J. Wyvratt、Ravi P. Nargund

  DOI：10.1016/j.bmcl.2010.09.049

  日期：2010.11

  We report an SAR study of MC4R analogs containing spiroindane heterocyclic privileged structures. Compound 26 with N-Me-1,2,4-triazole moiety possesses exceptional potency at MC4R and potent anti-obesity efficacy in a mouse model. However, the efficacy is not completely mediated through MC4R. Additional SAR studies led to the discovery of compound 32, which is more potent at MC4R. Compound 32 demonstrates MC4R mediated anti-obesity efficacy in rodent models. (C) 2010 Elsevier Ltd. All rights reserved.
• ACYLATED SPIROPIPERIDINE DERIVATIVES AS MELANOCORTIN-4 RECEPTOR MODULATORS
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP1940401B1

  公开（公告）日：2012-07-11
• US7652024B2
  申请人：——

  公开号：US7652024B2

  公开（公告）日：2010-01-26
• [EN] ACYLATED SPIROPIPERIDINE DERIVATIVES AS MELANOCORTIN-4 RECEPTOR MODULATORS<br/>[FR] DERIVES DE SPIROPIPERIDINE ACYLES UTILISES EN TANT QUE MODULATEURS VIS-A-VIS DU RECEPTEUR DE MELANOCORTINE-4
  申请人：MERCK & CO INC

  公开号：WO2007047496A2

  公开（公告）日：2007-04-26

  [EN] Certain novel N-acylated spiropiperidine derivatives are ligands of the human melanocortin receptor(s) and, in particular, are selective ligands of the human melanocortin-4 receptor (MC-4R). They are therefore useful for the treatment, control, or prevention of diseases and disorders responsive to the modulation of MC-4R, such as obesity, diabetes, nicotine addiction, alcoholism, sexual dysfunction, including erectile dysfunction and female sexual dysfunction.
  [FR] La présente invention concerne certains nouveaux dérivés de spiropipéridine acylés qui sont des ligands du ou des récepteurs de mélanocortine de type humain et, plus particulièrement, des ligands sélectifs du récepteur de mélanocortine-4 de type humain (MC-4R). Ces dérivés sont donc utiles pour le traitement, le contrôle ou la prévention des maladies et des troubles qui peuvent réagir à la modulation du MC-4R, tels que l'obésité, le diabète, l'addiction à la nicotine, l'alcoolisme, le dysfonctionnement sexuel, y compris le dysfonctionnement de l'érection et le dysfonctionnement sexuel chez la femme.