1-((1,1-dimethyl-3-[4-(methyloxy)phenyl]propyl)amino)-3-(phenyloxy)-2-propanol

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-((1,1-dimethyl-3-[4-(methyloxy)phenyl]propyl)amino)-3-(phenyloxy)-2-propanol
• 英文别名: (+/-)-1-((1,1-Dimethyl-3-[4-(methyloxy)phenyl]propyl)amino)-3-(phenyloxy)-2-propanol；1-[[4-(4-methoxyphenyl)-2-methylbutan-2-yl]amino]-3-phenoxypropan-2-ol
• 化学式: C₂₁H₂₉NO₃
• 分子量: 343.466
• InChiKey: JPEZJLKOTXXNHT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  25
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  50.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1,1-二甲基-3-(4-甲氧基苯基)丙胺 、 苯基缩水甘油醚 以 乙醇 为溶剂， 反应 20.0h， 以58%的产率得到1-((1,1-dimethyl-3-[4-(methyloxy)phenyl]propyl)amino)-3-(phenyloxy)-2-propanol
  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

• CALCILYTIC COMPOUNDS
  申请人：Del Mar Eric G.

  公开号：US20070249702A1

  公开（公告）日：2007-10-25

  The present invention features calcilytic compounds. “Calcilytic compounds” refer to compounds able to inhibit calcium receptor activity. Also described are the use of calcilytic compounds to inhibit calcium receptor activity and/or achieve a beneficial effect in a patient; and techniques which can be used to obtain additional calcilytic compounds.

  本发明涉及钙解离化合物。 “钙解离化合物”是指能够抑制钙受体活性的化合物。同时，本发明还描述了使用钙解离化合物来抑制钙受体活性和/或在患者中获得有益效果的方法；以及可用于获得其他钙解离化合物的技术。
• US7202261B2
  申请人：——

  公开号：US7202261B2

  公开（公告）日：2007-04-10
• 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.