2-([3-((1,1-dimethyl-2-[4-(methyloxy)phenyl]ethyl)amino)-2-hydroxypropyl]oxy)benzonitrile | 752965-75-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-([3-((1,1-dimethyl-2-[4-(methyloxy)phenyl]ethyl)amino)-2-hydroxypropyl]oxy)benzonitrile
• 英文别名: (+/-)-2-([3-((1,1-Dimethyl-2-[4-(methyloxy)phenyl]ethyl)amino)-2-hydroxypropyl]oxy)benzonitrile；2-[2-hydroxy-3-[[1-(4-methoxyphenyl)-2-methylpropan-2-yl]amino]propoxy]benzonitrile
• CAS: 752965-75-6
• 化学式: C₂₁H₂₆N₂O₃
• 分子量: 354.449
• InChiKey: KCCUCFUQSYGPBH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  74.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  邻羟基苯甲腈 、 (1,1-dimethyl-2-[4-(methyloxy)phenyl]ethyl)(2-oxiranylmethyl)amine 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2-([3-((1,1-dimethyl-2-[4-(methyloxy)phenyl]ethyl)amino)-2-hydroxypropyl]oxy)benzonitrile
  参考文献：
  名称：

  Antagonists of the Calcium Receptor I. Amino Alcohol-Based Parathyroid Hormone Secretagogues

  摘要：

  Functional screening of the former SmithKline Beecham compound collection against the human calcium receptor (CaR) resulted in the identification of the amino alcohol-based hit 2 (IC50 = 11 mu M)Structure-activity Studies of 2 focused on the optimization of the right- and left-hand side aromatic moieties as well as the amino alcohol linker region. Critical to the optimization of this antagonist template was the discovery that the chirality of the C-2 secondary alcohol played a key role in enhancing both CaR potency as well as selectivity over the beta-adrenergic receptor subtypes. These SAR studies ultimately led to the identification of 38 (NPS 2143; SB-262470A), a potent and orally active CaR antagonist. Pharmacokinetic characterization of 38 in the rat revealed that this molecule had a large volume of distribution (11 L/kg), which resulted in a prolonged systemic exposure, protracted increases in the plasma levels of PTH, and an overall lack of net bone formation effect in a rodent model of osteoporosis.

  DOI：

  10.1021/jm900364m

文献信息

• US6022894A
  申请人：——

  公开号：US6022894A

  公开（公告）日：2000-02-08
• US6395919B1
  申请人：——

  公开号：US6395919B1

  公开（公告）日：2002-05-28
• Antagonists of the Calcium Receptor I. Amino Alcohol-Based Parathyroid Hormone Secretagogues
  作者：Robert W. Marquis、Amparo M. Lago、James F. Callahan、Robert E. Lee Trout、Maxine Gowen、Eric G. DelMar、Bradford C. Van Wagenen、Sarah Logan、Scott Shimizu、John Fox、Edward F. Nemeth、Zheng Yang、Theresa Roethke、Brian R. Smith、Keith W. Ward、John Lee、Richard M. Keenan、Pradip Bhatnagar

  DOI：10.1021/jm900364m

  日期：2009.7.9

  Functional screening of the former SmithKline Beecham compound collection against the human calcium receptor (CaR) resulted in the identification of the amino alcohol-based hit 2 (IC50 = 11 mu M)Structure-activity Studies of 2 focused on the optimization of the right- and left-hand side aromatic moieties as well as the amino alcohol linker region. Critical to the optimization of this antagonist template was the discovery that the chirality of the C-2 secondary alcohol played a key role in enhancing both CaR potency as well as selectivity over the beta-adrenergic receptor subtypes. These SAR studies ultimately led to the identification of 38 (NPS 2143; SB-262470A), a potent and orally active CaR antagonist. Pharmacokinetic characterization of 38 in the rat revealed that this molecule had a large volume of distribution (11 L/kg), which resulted in a prolonged systemic exposure, protracted increases in the plasma levels of PTH, and an overall lack of net bone formation effect in a rodent model of osteoporosis.