(2R)-3-naphthalen-1-yl-2-[[4-(2-oxo-3H-benzimidazol-1-yl)piperidine-1-carbonyl]amino]propanoic acid | 262844-87-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2R)-3-naphthalen-1-yl-2-[[4-(2-oxo-3H-benzimidazol-1-yl)piperidine-1-carbonyl]amino]propanoic acid
• CAS: 262844-87-1
• 化学式: C₂₆H₂₆N₄O₄
• 分子量: 458.517
• InChiKey: AOKQUKYHBUOMKQ-JOCHJYFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  102
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-哌啶基哌啶 、 (2R)-3-naphthalen-1-yl-2-[[4-(2-oxo-3H-benzimidazol-1-yl)piperidine-1-carbonyl]amino]propanoic acid 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-[(2R)-3-naphthalen-1-yl-1-oxo-1-(4-piperidin-1-ylpiperidin-1-yl)propan-2-yl]-4-(2-oxo-3H-benzimidazol-1-yl)piperidine-1-carboxamide
  参考文献：
  名称：

  The synthesis and SAR of calcitonin gene-related peptide (CGRP) receptor antagonists derived from tyrosine surrogates. Part 1

  摘要：

  We have systematically studied the effects of varying the central unnatural amino acid moiety on CGRP receptor antagonist potency and CYP inhibition in a series of ureidoamides. In this Letter, we report the discovery of compound 23, a potent CGRP receptor antagonist with only weak CYP3A4 inhibition. Unlike the triptans, compound 23 did not cause active constriction of ex vivo human cerebral arteries. At doses of 0.3-1 mg/kg (sc), 23 showed robust inhibition of CGRP-induced increases in marmoset facial blood flow, a validated migraine model. Ureidoamide 23 derives from a novel amino acid, 1H-indazol-5-yl substituted alanine as a tyrosine surrogate. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.05.074
• 作为产物：
  描述：

  methyl (2R)-3-naphthalen-1-yl-2-[[4-(2-oxo-3H-benzimidazol-1-yl)piperidine-1-carbonyl]amino]propanoate 在 水 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 (2R)-3-naphthalen-1-yl-2-[[4-(2-oxo-3H-benzimidazol-1-yl)piperidine-1-carbonyl]amino]propanoic acid
  参考文献：
  名称：

  The synthesis and SAR of calcitonin gene-related peptide (CGRP) receptor antagonists derived from tyrosine surrogates. Part 1

  摘要：

  We have systematically studied the effects of varying the central unnatural amino acid moiety on CGRP receptor antagonist potency and CYP inhibition in a series of ureidoamides. In this Letter, we report the discovery of compound 23, a potent CGRP receptor antagonist with only weak CYP3A4 inhibition. Unlike the triptans, compound 23 did not cause active constriction of ex vivo human cerebral arteries. At doses of 0.3-1 mg/kg (sc), 23 showed robust inhibition of CGRP-induced increases in marmoset facial blood flow, a validated migraine model. Ureidoamide 23 derives from a novel amino acid, 1H-indazol-5-yl substituted alanine as a tyrosine surrogate. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.05.074