(2-benzhydryl-4-phenyloxazole-5-carbonyl)-L-arginine | 1434873-32-1

• 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-benzhydryl-4-phenyloxazole-5-carbonyl)-L-arginine
• 英文别名: (2S)-2-[(2-benzhydryl-4-phenyl-1,3-oxazole-5-carbonyl)amino]-5-(diaminomethylideneamino)pentanoic acid
• CAS: 1434873-32-1
• 化学式: C₂₉H₂₉N₅O₄
• 分子量: 511.58
• InChiKey: DAFWJIQCPWKKEK-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  38
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  157
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  ethyl 2-chloro-3-oxo-3-phenylpropionate 在 ammonium acetate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 溶剂黄146 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.25h， 生成 (2-benzhydryl-4-phenyloxazole-5-carbonyl)-L-arginine
  参考文献：
  名称：

  Potent Heterocyclic Ligands for Human Complement C3a Receptor

  摘要：

  The G-protein coupled receptor (C3aR) for human inflammatory protein complement C3a is an important component of immune, inflammatory, and metabolic diseases. A flexible compound (N2-[(2,2-diphenylethoxy)acetyl]-l-arginine, 4), known as a weak C3aR antagonist (IC50 mu M), was transformed here into potent agonists (EC50 nM) of human macrophages (Ca2+ release in HMDM) by incorporating aromatic heterocycles. Antagonists were also identified. A linear correlation between binding affinity for C3aR and calculated hydrogen-bond interaction energy of the heteroatom indicated that its hydrogen-bonding capacity influenced ligand affinity and function mediated by C3aR. Hydrogen-bond accepting heterocycles (e.g., imidazole) conferred the highest affinity and agonist potency (e.g., 21, EC50 24 nM, Ca2+, HMDM) with comparable efficacy and immunostimulatory activity as that of C3a in activating human macrophages (Ca2+, IL1 beta, TNF alpha, CCL3). These potent and selective modulators of C3aR, inactivated by a C3aR antagonist, are stable C3a surrogates for interrogating roles for C3aR in physiology and disease.

  DOI：

  10.1021/jm500956p

文献信息

• MODULATORS OF C3A RECEPTORS
  申请人：THE UNIVERSITY OF QUEENSLAND

  公开号：US20140302069A1

  公开（公告）日：2014-10-09

  Heterocyclic compounds that modulate C3a receptors and their use in the treatment or prevention of inflammatory diseases, infectious diseases, cancers, metabolic disorders, obesity, type 2 diabetes, metabolic syndrome and associated cardiovascular diseases are described. The use of the compounds in stimulating or suppressing an immune response is also described together with pharmaceutical compositions comprising the compounds or their pharmaceutically acceptable salts.

  本文描述了调节C3a受体的杂环化合物及其在治疗或预防炎症性疾病、传染性疾病、癌症、代谢性疾病、肥胖症、2型糖尿病、代谢综合征及相关心血管疾病中的应用。本文还描述了利用这些化合物刺激或抑制免疫反应的应用，以及包括这些化合物或其药学上可接受的盐的制药组合物。
• US9586914B2
  申请人：——

  公开号：US9586914B2

  公开（公告）日：2017-03-07
• Potent Heterocyclic Ligands for Human Complement C3a Receptor
  作者：Robert C. Reid、Mei-Kwan Yau、Ranee Singh、Johan K. Hamidon、Junxian Lim、Martin J. Stoermer、David P. Fairlie

  DOI：10.1021/jm500956p

  日期：2014.10.23

  The G-protein coupled receptor (C3aR) for human inflammatory protein complement C3a is an important component of immune, inflammatory, and metabolic diseases. A flexible compound (N2-[(2,2-diphenylethoxy)acetyl]-l-arginine, 4), known as a weak C3aR antagonist (IC50 mu M), was transformed here into potent agonists (EC50 nM) of human macrophages (Ca2+ release in HMDM) by incorporating aromatic heterocycles. Antagonists were also identified. A linear correlation between binding affinity for C3aR and calculated hydrogen-bond interaction energy of the heteroatom indicated that its hydrogen-bonding capacity influenced ligand affinity and function mediated by C3aR. Hydrogen-bond accepting heterocycles (e.g., imidazole) conferred the highest affinity and agonist potency (e.g., 21, EC50 24 nM, Ca2+, HMDM) with comparable efficacy and immunostimulatory activity as that of C3a in activating human macrophages (Ca2+, IL1 beta, TNF alpha, CCL3). These potent and selective modulators of C3aR, inactivated by a C3aR antagonist, are stable C3a surrogates for interrogating roles for C3aR in physiology and disease.