3-(4-methylphenyl)pentan-3-amine hydrochloride | 1268168-26-8

• 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: 3-(4-methylphenyl)pentan-3-amine hydrochloride
• CAS: 1268168-26-8
• 化学式: C₁₂H₁₉N*ClH
• 分子量: 213.75
• InChiKey: SSPALMAZBKTVTR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.39
• 重原子数：
  14.0
• 可旋转键数：
  3.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  26.02
• 氢给体数：
  1.0
• 氢受体数：
  1.0

反应信息

• 作为反应物：
  描述：

  2-ethyl-7,7-dimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acid 、 3-(4-methylphenyl)pentan-3-amine hydrochloride 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2-ethyl-N-[1-ethyl-1-(4-methylphenyl)propyl]-7,7-dimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide
  参考文献：
  名称：

  Novel and potent calcium-sensing receptor antagonists: Discovery of (5R)-N-[1-ethyl-1-(4-ethylphenyl)propyl]-2,7,7-trimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide monotosylate (TAK-075) as an orally active bone anabolic agent

  摘要：

  The calcium-sensing receptor antagonist (CaSR) has been recognized as a promising target of anabolic agents for treating osteoporosis. In the course of developing a new drug candidate for osteoporosis, we found tetrahydropyrazolopyrimidine derivative 1 to be an orally active CaSR antagonist that stimulated transient PTH secretion in rats. However, compound 1 showed poor physical and chemical stability. In order to work out this compound's chemical stability and further understand its in vivo efficacy, we focused on modifying the 2-position of the tetrahydropyrazolopyrimidine. As a result of chemical modification, we discovered (5R)-N-[1-ethyl-1-(4-ethylphenyl)propyl]-2,7,7-trimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide monotosylate 10m (TAK-075), which showed improved solubility, chemical stability, and in vivo efficacy. Furthermore, we describe that evaluating the active metabolite is important during repeated treatment with short-acting CaSR antagonists. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.02.001

文献信息

• Discovery of Novel and Potent Orally Active Calcium-Sensing Receptor Antagonists that Stimulate Pulselike Parathyroid Hormone Secretion: Synthesis and Structure−Activity Relationships of Tetrahydropyrazolopyrimidine Derivatives
  作者：Masato Yoshida、Akira Mori、Etsuo Kotani、Masahiro Oka、Haruhiko Makino、Hisashi Fujita、Junko Ban、Yukihiro Ikeda、Tomohiro Kawamoto、Mika Goto、Hiroyuki Kimura、Atsuo Baba、Tsuneo Yasuma

  DOI：10.1021/jm101452x

  日期：2011.3.10

  bone anabolic agents, we recently reported the discovery of a tetrahydropyrazolopyrimidine derivative featuring adamantyl group 1b with potent CaSR antagonistic activity. To explore the potential of this calcilytic congener, we introduced the gem-dialkyl benzyl group at the 3-position of the tetrahydropyrazolopyrimidine ring, forming a bioisostere of the adamantyl group by mimicking the adamantyl group’s

  作为我们对新型钙敏感受体（CaSR）拮抗剂的研究的一部分，该拮抗剂可作为口服骨合成代谢药物发挥作用，我们最近报道了具有金刚烷基1b的四氢吡唑并嘧啶衍生物的发现，该衍生物具有强大的CaSR拮抗活性。为了探索该煅烧同源物的潜力，我们在四氢吡唑并嘧啶环的3-位引入了宝石-二烷基苄基，通过模仿金刚烷基的亲脂性和蓬松性而形成了金刚烷基的生物等排体。针对溶解度和代谢稳定性改善的优化导致了化合物9e的发现，当向正常大鼠口服时，该化合物可刺激PTH的短暂分泌。此外，复合9e在骨质减少卵巢切除的大鼠模型中被证明是完全有效的。