FMOC-2,4-二氯-D-苯丙氨酸 | 352351-61-2

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 苯丙氨酸类衍生物
• 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
• 中文名称: FMOC-2,4-二氯-D-苯丙氨酸
• 英文名称: N-Fmoc-(R)-(2,4-Cl)Phe-OH
• 英文别名: N-Fmoc-D-(2,4-dichlorophenyl)alanine；(R)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)-3-(2,4-dichlorophenyl)propanoic acid；(2R)-3-(2,4-dichlorophenyl)-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoic acid
• CAS: 352351-61-2
• 化学式: C₂₄H₁₉Cl₂NO₄
• 分子量: 456.325
• InChiKey: PGIMVGROPOKRNA-JOCHJYFZSA-N

物化性质

• 沸点：
  659.9±55.0 °C(Predicted)
• 密度：
  1.394±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26,S36
• 危险类别码：
  R36/37/38
• WGK Germany：
  3
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  N-Boc-N-[2-(2-thienyl)ethyl]-2-piperazinebenzylamine 、 FMOC-2,4-二氯-D-苯丙氨酸 在 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 生成 tert-butyl N-[[2-[4-[(2R)-3-(2,4-dichlorophenyl)-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoyl]piperazin-1-yl]phenyl]methyl]-N-(2-thiophen-2-ylethyl)carbamate
  参考文献：
  名称：

  A potent and selective nonpeptide antagonist of the melanocortin-4 receptor induces food intake in satiated mice

  摘要：

  Optimization on a series of piperazinebenzylamines resulted in analogues with low nanomolar binding at the human MC4 receptor but weak affinity (K-i > 500 nM) at the MC3 receptor. Compound 14c was identified to be a potent MC4R antagonist (K-i = 3.2 nM) with a selectivity of 240-fold over MC3R. It proved to be an insurmountable antagonist in a cAMP assay. Compound 14c potently stimulated food intake in satiated mice when given by intracerebroventricular administration. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.03.053

文献信息

• MACROCYCLIC COMPOUNDS FOR INHIBITION OF TUMOR NECROSIS FACTOR ALPHA
  申请人：Lee Jinbo

  公开号：US20100152099A1

  公开（公告）日：2010-06-17

  The invention provides macrocyclic compounds and methods for their synthesis and use. In particular, the invention provides macrocyclic compounds that modulate the activity of tumor necrosis factor alpha and/or are useful in the treatment of medical conditions, such as, rheumatoid arthritis, psoriasis, and asthma.

  该发明提供了大环化合物及其合成和使用方法。具体而言，该发明提供了调节肿瘤坏死因子α活性和/或用于治疗医学状况（如类风湿性关节炎、银屑病和哮喘）的大环化合物。
• 4-{(<i>2R</i>)-[3-Aminopropionylamido]-3-(2,4-dichlorophenyl)propionyl}-1-{2-[(2-thienyl)ethylaminomethyl]phenyl}piperazine as a Potent and Selective Melanocortin-4 Receptor AntagonistDesign, Synthesis, and Characterization
  作者：Chen、Joseph Pontillo、Beth A. Fleck、Yinghong Gao、Jenny Wen、Joe A. Tran、Fabio C. Tucci、Dragan Marinkovic、Alan C. Foster、John Saunders

  DOI：10.1021/jm049278i

  日期：2004.12.1

  Recent studies have demonstrated that melanocortin-4 receptor (MC4R) antagonists can prevent weight loss in tumor-bearing mice, which indicates clinical usage for the treatment of cachexia. In our efforts to develop potent and selective antagonists of the human MC4R, we designed piperazinebenzylamines bearing a 2,4-dichlorophenylalanine, by utilizing information derived from structure-activity relationships of MC4R agonists and mutagenesis results of the MC4R and peptide ligands. On the basis of known MC4R agonists such 6, we successfully synthesized potent MC4R antagonists exemplified by 10, which possesses a K-i value of 1.8 nM in binding affinity. 10 does not stimulate cAMP release in HEK 293 cells expressing the human MC4 receptor at 10 muM concentration. It was demonstrated by Schild analysis that 10 was a competitive functional antagonist with a pA(2) value of 7.9 in the inhibition of alpha-MSH-stimulated cAMP accumulation. 10 also penetrated into the brain when dosed intravenously in rats.
• US8338565B2
  申请人：——

  公开号：US8338565B2

  公开（公告）日：2012-12-25
• [EN] MACROCYCLIC COMPOUNDS FOR INHIBITION OF TUMOR NECROSIS FACTOR ALPHA<br/>[FR] COMPOSÉS DESTINÉS À L'INHIBITION DU FACTEUR DE NÉCROSE TUMORALE ALPHA
  申请人：ENSEMBLE DISCOVERY CORP

  公开号：WO2010022249A2

  公开（公告）日：2010-02-25

  The invention provides macrocyclic compounds and methods for their synthesis and use. In particular, the invention provides macrocyclic compounds that modulate the activity of tumor necrosis factor alpha and/or are useful in the treatment of medical conditions, such as, rheumatoid arthritis, psoriasis, and asthma.