4-[(1R,7S,7aR)-7-tert-Butyldimethylsilanoxy-1-methyl-3-oxohexahydropyrrolo[1,2-c]imidazol-2-yl]-2-chloro-3-methylbenzonitrile | 757248-21-8

• 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: 4-[(1R,7S,7aR)-7-tert-Butyldimethylsilanoxy-1-methyl-3-oxohexahydropyrrolo[1,2-c]imidazol-2-yl]-2-chloro-3-methylbenzonitrile
• 英文别名: 4-[(1R,7S,7aR)-7-[tert-butyl(dimethyl)silyl]oxy-1-methyl-3-oxo-5,6,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazol-2-yl]-2-chloro-3-methylbenzonitrile
• CAS: 757248-21-8
• 化学式: C₂₁H₃₀ClN₃O₂Si
• 分子量: 420.027
• InChiKey: YIBPIGDGKIUNBN-DKSSEZFCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.31
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  56.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-[(1R,7S,7aR)-7-tert-Butyldimethylsilanoxy-1-methyl-3-oxohexahydropyrrolo[1,2-c]imidazol-2-yl]-2-chloro-3-methylbenzonitrile 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 2-chloro-4-((1R,7S,7aR)-7-hydroxy-1-methyl-3-oxo-tetrahydro-1H-pyrrolo[1,2-c]imidazol-2(3H)-yl)-3-methylbenzonitrile
  参考文献：
  名称：

  Discovery of Potent and Muscle Selective Androgen Receptor Modulators through Scaffold Modifications

  摘要：

  A novel series of imidazolin-2-ones were designed and synthesized as highly potent, orally active and muscle selective androgen receptor modulators (SARMs), with most of the compounds exhibiting low nM in vitro potency in androgen receptor (AR) binding and functional assays. Once daily oral treatment with the lead compound 11a (AR K-i = 0.9 nM, EC50 = 1.8 nM) for 14 days induced muscle growth with an ED50 of 0.09 mg/kg, providing approximately 50-fold selectivity over prostate growth in an orchidectomized rat model. Pharmacokinetic studies in rats demonstrated that the lead compound 11a had oral bioavailability of 65% and a plasma half-life of 5.5 h. On the basis of their preclinical profiles, the SARMs in this series are expected to provide beneficial anabolic effects on muscle with minimal androgenic effects on prostate tissue.

  DOI：

  10.1021/jm070312d
• 作为产物：
  描述：

  3-氯-2-甲基苯胺 在 tris(dibenzylideneacetone)dipalladium (0) 、 chiral ferrocenyl catalyst 盐酸 、 copper(l) iodide 、 亚硝酸特丁酯 、 乙醇 、 溴 、 caesium carbonate 、 溶剂黄146 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 63.67h， 生成 4-[(1R,7S,7aR)-7-tert-Butyldimethylsilanoxy-1-methyl-3-oxohexahydropyrrolo[1,2-c]imidazol-2-yl]-2-chloro-3-methylbenzonitrile
  参考文献：
  名称：

  Discovery of Potent and Muscle Selective Androgen Receptor Modulators through Scaffold Modifications

  摘要：

  A novel series of imidazolin-2-ones were designed and synthesized as highly potent, orally active and muscle selective androgen receptor modulators (SARMs), with most of the compounds exhibiting low nM in vitro potency in androgen receptor (AR) binding and functional assays. Once daily oral treatment with the lead compound 11a (AR K-i = 0.9 nM, EC50 = 1.8 nM) for 14 days induced muscle growth with an ED50 of 0.09 mg/kg, providing approximately 50-fold selectivity over prostate growth in an orchidectomized rat model. Pharmacokinetic studies in rats demonstrated that the lead compound 11a had oral bioavailability of 65% and a plasma half-life of 5.5 h. On the basis of their preclinical profiles, the SARMs in this series are expected to provide beneficial anabolic effects on muscle with minimal androgenic effects on prostate tissue.

  DOI：

  10.1021/jm070312d

文献信息

• Bicyclic modulators of androgen receptor function
  申请人：——

  公开号：US20040181064A1

  公开（公告）日：2004-09-16

  The invention provides compounds according to formula I 1 wherein the substitutents are as described herein. Further provided are methods of using such compounds for the treatment of nuclear hormone receptor-associated conditions, such as age related diseases, for example sarcopenia. Also provided are pharmaceutical compositions containing such compounds and processes for preparing some of the compounds of the invention.

  本发明提供了式I1的化合物，其中取代基如此处所述。还提供了使用这种化合物治疗核激素受体相关疾病的方法，例如与年龄相关的疾病，例如肌肉萎缩症。还提供了含有这种化合物的制药组合物以及制备本发明部分化合物的方法。
• BICYCLIC MODULATORS OF ANDROGEN RECEPTOR FUNCTION
  申请人：Sun Chong-Qing

  公开号：US20080108649A1

  公开（公告）日：2008-05-08

  There are provided compounds according to formula I wherein the substitutents are as described herein. Further provided are methods of using such compounds for the treatment of nuclear hormone receptor-associated conditions, such as age related diseases, for example sarcopenia. Also provided are pharmaceutical compositions containing such compounds and processes for preparing some of the compounds of the invention. Other embodiments are also disclosed.

  提供了按公式I描述的化合物，其中取代基如此描述。还提供了使用这种化合物治疗核激素受体相关疾病的方法，例如与年龄相关的疾病，例如肌肉萎缩症。还提供了含有这种化合物的药物组合物和制备本发明部分化合物的方法。还揭示了其他实施例。