3,4,5-trimethylphenylacetyl chloride | 335293-23-7

• 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: 3,4,5-trimethylphenylacetyl chloride
• 英文别名: 2-(3,4,5-Trimethylphenyl)acetyl chloride
• CAS: 335293-23-7
• 化学式: C₁₁H₁₃ClO
• 分子量: 196.677
• InChiKey: ZKDWZJAXNJGEAA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3,4,5-trimethylphenylacetyl chloride 在 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 、 1,2-二氯乙烷 为溶剂， 生成 7-chloro-4-hydroxy-6-iodo-3-(3,4,5-trimethylphenyl)-1H-quinolin-2-one
  参考文献：
  名称：

  Quinolones as gonadotropin releasing hormone (GnRH) antagonists: simultaneous optimization of the C(3)-aryl and C(6)-substituents

  摘要：

  A series of 3-arylquinolones was prepared and evaluated for their ability to act as gonadotropin releasing hormone (GnRH) antagonists. A variety of substitution patterns of the 3-aryl substituent are described. The 3,4,5-trimethylphenyl substituent (23h) was found to he optimal. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00318-8
• 作为产物：
  描述：

  3,4,5-三甲基苯乙酸 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 生成 3,4,5-trimethylphenylacetyl chloride
  参考文献：
  名称：

  Quinolones as gonadotropin releasing hormone (GnRH) antagonists: simultaneous optimization of the C(3)-aryl and C(6)-substituents

  摘要：

  A series of 3-arylquinolones was prepared and evaluated for their ability to act as gonadotropin releasing hormone (GnRH) antagonists. A variety of substitution patterns of the 3-aryl substituent are described. The 3,4,5-trimethylphenyl substituent (23h) was found to he optimal. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00318-8

文献信息

• Synthesis of two non-peptidyl GnRH receptor antagonists via [14C]carbonylation
  作者：Charles S. Elmore、Dennis C. Dean、Robert J. DeVita、David G. Melillo

  DOI：10.1002/jlcr.733

  日期：2003.9

  In support of a program to develop a new gonadotropin releasing hormone (GnRH) receptor antagonist, two 14C labelled candidate tracers, 14C-1 and 14C-2, were synthesized for utilization in metabolism studies. A slight modification of the Medicinal Chemistry route for the synthesis of the antagonists provided iodide 4. Palladium (0) catalyzed [14C]carbonylation of 4 proceeded in good chemical yield to afford acid 14C-3 which served as a common precursor to 14C-1 and 14C-2. Copyright © 2003 John Wiley & Sons, Ltd.

  为了支持开发新的促性腺激素释放激素（GnRH）受体拮抗剂的计划，我们合成了两种 14C 标记的候选示踪剂 14C-1 和 14C-2，用于代谢研究。对合成拮抗剂的药物化学路线稍作修改，就得到了碘化物 4。在钯（0）催化下，4 的[14C]羰基化反应以良好的化学收率进行，得到了作为 14C-1 和 14C-2 共同前体的酸 14C-3。Copyright © 2003 John Wiley & Sons, Ltd. All Rights Reserved.
• A Potent, Nonpeptidyl 1<i>H</i>-Quinolone Antagonist for the Gonadotropin-Releasing Hormone Receptor
  作者：Robert J. DeVita、Thomas F. Walsh、Jonathan R. Young、Jinlong Jiang、Feroze Ujjainwalla、Richard B. Toupence、Mamta Parikh、Song X. Huang、Jason A. Fair、Mark T. Goulet、Matthew J. Wyvratt、Jane-L. Lo、Ning Ren、Joel B. Yudkovitz、Yi T. Yang、Kang Cheng、Jisong Cui、George Mount、Susan P. Rohrer、James M. Schaeffer、Linda Rhodes、Jennifer E. Drisko、Erin McGowan、D. Euan MacIntyre、Styliani Vincent、Josephine R. Carlin、Judith Cameron、Roy G. Smith

  DOI：10.1021/jm000275p

  日期：2001.3.1

  Extensive development of the structure-activity relationships of a screening lead determined three important pharmacophores for gonadotropin-releasing hormone (GnRH) receptor antagonist activity. Incorporation of the 3,4,5-trimethylphenyl group at the 3-position, 2-(2(S)-azetidinyl)ethoxy group at the 4-position, and N-4-pyrimidinylcarboxamide at the g-position of the quinolone core resulted in the identification of 4-(2-(azetidin-2(S)-yl)ethoxy)-7-chloro-2-oxo-3-(3,4,5-trimethylphenyl)-1,2-dihydroquinoline-6-carboxylic acid pyrimidin-4-ylamide (1) as a potent antagonist of the GnRH receptor. A 104-fold increase in in vitro binding affinity is observed for the GnRH receptor as compared to the initial screening lead. Compound 1 exhibits nanomolar binding activity and functional antagonism at the human receptor and is 7-fold less active at the rhesus receptor. Intravenous administration of compound 1 to rhesus monkeys results in a significant decrease of the serum levels of downstream hormones, luteinizing hormone (79% decrease in area under the curve) and testosterone (92% decrease in area under the curve), at a dose of 3 mg/kg. Quinolone 1 is a potent nonpeptidyl antagonist for the human GnRH receptor that is efficacious for the suppression of luteinizing hormone and testosterone in primates.
• [EN] ANTAGONISTS OF GONADOTROPIN RELEASING HORMONE<br/>[FR] ANTAGONISTES DE L'HORMONE DE LIBERATION DE LA GONADOTROPHINE
  申请人：MERCK & CO INC

  公开号：WO2001070228A1

  公开（公告）日：2001-09-27

  There are disclosed compounds of formula (I) or pharmaceutically acceptable salts thereof which are useful as antagonists of GnRH and as such may be useful for the treatment of a variety of sex-hormone related conditions in both men and women.