(3R,5S)-1-(4-methoxybenzyl)-3,5-dimethylpiperidin-4-one | 947372-28-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (3R,5S)-1-(4-methoxybenzyl)-3,5-dimethylpiperidin-4-one
• 英文别名: (3R,5S)-1-[(4-methoxyphenyl)methyl]-3,5-dimethylpiperidin-4-one
• CAS: 947372-28-3
• 化学式: C₁₅H₂₁NO₂
• 分子量: 247.337
• InChiKey: HSQBMRZDSKGFNY-TXEJJXNPSA-N

物化性质

• 沸点：
  363.1±27.0 °C(Predicted)
• 密度：
  1.046±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3R,5S)-1-(4-methoxybenzyl)-3,5-dimethylpiperidin-4-one 在 正丁基锂 、 氯化铵 作用下， 以 hexanes 、 甲苯 、 水 为溶剂， 反应 4.37h， 以83%的产率得到(3R,4S,5S)-4-(5-chloropyridin-2-yl)-1-(4-methoxybenzyl)-3,5-dimethylpiperidin-4-ol
  参考文献：
  名称：

  WO2007/96763

  摘要：

  公开号：
• 作为产物：
  描述：

  1-(4-methoxybenzyl)-3,5-dimethyl-4-oxo-piperidine dicarboxylic acid, dimethyl ester 在 盐酸 、 sodium methylate 作用下， 以 水 、 甲醇 为溶剂， 生成 (3R,5S)-1-(4-methoxybenzyl)-3,5-dimethylpiperidin-4-one
  参考文献：
  名称：

  Discovery of a Selective Small-Molecule Melanocortin-4 Receptor Agonist with Efficacy in a Pilot Study of Sexual Dysfunction in Humans

  摘要：

  The relevance of the melanocortin system to sexual activity is well established, and nonselective peptide agonists of the melanocortin receptors have shown evidence of efficacy in human sexual dysfunction. The role of the MC4 receptor subtype has received particular scrutiny, but the sufficiency of its selective activation in potentiating sexual response has remained uncertain owing to conflicting data from studies in preclinical species. We describe here the discovery of a novel series of small-molecule MC4 receptor agonists derived from library hit 2. The addition of methyl substituents at C3 and C5 of the 4-phenylpiperidin-4-ol ring was found to be markedly potency-enhancing, enabling the combination of low nanomolar potencies with full rule-of-five compliance. In general, the series shows only micromolar activity at other melanocortin receptors. Our preferred compound 40a provided significant systemic exposure in humans on both sublingual and oral administration and was safe and well tolerated up to the maximum tested dose. In a pilot clinical study of male erectile dysfunction, the highest dose of 40a tested (200 mg) provided a similar level of efficacy to sildenafil.

  DOI：

  10.1021/jm9017866

文献信息

• Pharmaceutically active compounds
  申请人：Calabrese Antony Andrew

  公开号：US20050176772A1

  公开（公告）日：2005-08-11

  The present invention relates to a class of melanocortin MCR4 agonists of general formula (I) wherein R 1 , R 2 , R 3 , R 4 and R 5 are as defined herein and especially to selective MCR4 agonist compounds, to their use in medicine, to compositions containing them, to processes for their preparation and to intermediates used in such processes.

  本发明涉及一类通式（I）所示的黑素皮质素MCR4激动剂，其中R1、R2、R3、R4和R5如本文所定义，特别涉及选择性MCR4激动剂化合物，它们在医学上的应用，含有它们的组合物，用于它们制备的工艺以及用于这些工艺的中间体。
• Melanocortin Type 4 Receptor Agonist Piperidinoylpyrrolidines
  申请人：Andrews Mark David

  公开号：US20090036459A1

  公开（公告）日：2009-02-05

  The present invention relates to a class of melanocortin MCR4 agonists of general formula (I) wherein the variables and substituents are as defined herein and especially to selective MCR4 agonist compounds, to their use in medicine, particularly in the treatment of sexual dysfunction and obesity, to intermediates useful in their synthesis and to compositions containing them.

  本发明涉及一类黑色素细胞激素MCR4激动剂，其一般式为（I），其中变量和取代基如本文所定义，特别是选择性MCR4激动剂化合物，它们在医学上的用途，特别是在性功能障碍和肥胖症的治疗中，以及在其合成中有用的中间体和含有它们的组合物。
• PIPERIDINYLCARBONYL-PYRROLIDINES AND THEIR USE AS MELANOCORTIN AGONISTS
  申请人：Pfizer Limited

  公开号：EP1716135A1

  公开（公告）日：2006-11-02
• PIPERIDINOYLPYRROLIDINES AS MELANOCORTIN TYPE 4 RECEPTOR AGONISTS
  申请人：Pfizer Limited

  公开号：EP1989196B1

  公开（公告）日：2013-02-13
• US7649002B2
  申请人：——

  公开号：US7649002B2

  公开（公告）日：2010-01-19