2-[[(4-chlorophenyl)carbonyl]amino]-1,3-thiazol-4-yl-acetic acid ethyl ester | 329699-54-9

• 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-[[(4-chlorophenyl)carbonyl]amino]-1,3-thiazol-4-yl-acetic acid ethyl ester
• 英文别名: [2-(4-chloro-benzoylamino)-thiazol-4-yl]-acetic acid ethyl ester；ethyl 2-[2-[(4-chlorobenzoyl)amino]-1,3-thiazol-4-yl]acetate
• CAS: 329699-54-9
• 化学式: C₁₄H₁₃ClN₂O₃S
• mdl: MFCD00249873
• 分子量: 324.788
• InChiKey: GZEBWBPIAMOOLG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  96.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-[[(4-chlorophenyl)carbonyl]amino]-1,3-thiazol-4-yl-acetic acid ethyl ester 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 0.5h， 生成 N-(2-methoxypyridin-5-yl)-2-(4-chlorobenzyl)amidothiazol-4-acetamide
  参考文献：
  名称：

  发现含有2-脲基噻唑支架的新型VEGFR和PI3K激酶双重抑制剂

  摘要：

  设计并合成了一系列具有2-（3-苯基）脲基噻唑-4-甲酰胺衍生物和2-脲基噻唑骨架的化合物。使用索拉非尼作为阳性对照，某些化合物显示出针对MDA-MB-231和HepG2细胞系的细胞增殖抑制作用。化合物6i对VEGFR-2和PI3Kα表现出良好至中度的抑制作用，这已通过进一步的分子对接研究得到证实。这项研究表明化合物6i是VEGFR-2和PI3Kα的潜在双重抑制剂，可用于进一步研究。

  DOI：

  10.1016/j.cclet.2015.09.008
• 作为产物：
  描述：

  2-氨基-4-噻唑乙酸乙酯 、 4-氯苯甲酰氯 在 N-甲基吗啉 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 生成 2-[[(4-chlorophenyl)carbonyl]amino]-1,3-thiazol-4-yl-acetic acid ethyl ester
  参考文献：
  名称：

  发现含有2-脲基噻唑支架的新型VEGFR和PI3K激酶双重抑制剂

  摘要：

  设计并合成了一系列具有2-（3-苯基）脲基噻唑-4-甲酰胺衍生物和2-脲基噻唑骨架的化合物。使用索拉非尼作为阳性对照，某些化合物显示出针对MDA-MB-231和HepG2细胞系的细胞增殖抑制作用。化合物6i对VEGFR-2和PI3Kα表现出良好至中度的抑制作用，这已通过进一步的分子对接研究得到证实。这项研究表明化合物6i是VEGFR-2和PI3Kα的潜在双重抑制剂，可用于进一步研究。

  DOI：

  10.1016/j.cclet.2015.09.008

文献信息

• Heteroarylacetamide inhibitors of factor Xa
  申请人：Boehringer Markus

  公开号：US20060142362A1

  公开（公告）日：2006-06-29

  The invention is concerned with novel heteroarylacetamides of formula (I) R d —C(O)—N(R e )—R c —CH 2 —C(O)—N(R a )(R b )   (I) wherein R a to R e are as defined in the description and in the claims, as well as physiologically acceptable salts thereof. These compounds inhibit the coagulation factor Xa and can be used as medicaments.

  这项发明涉及式(I)的新异杂芳乙酰胺Rd—C(O)—N(Re)—Rc—CH2—C(O)—N(Ra)(Rb)，其中Rato Re的定义如描述和索赔中所述，以及其生理上可接受的盐。这些化合物抑制凝血因子Xa，可用作药物。
• New 2-Amino-thiazole-4-acetamides with Antiplatelet Activity
  作者：Klaus Rehse、Tobias Baselt

  DOI：10.1002/ardp.200700046

  日期：2008.10

  In the Born test, 23 title compounds were synthesized and investigated for their antiplatelet activities against collagen, ADP, adrenaline, and platelet‐activating factor (PAF) as inducers of the aggregation. Using collagen, three compounds with IC50 values below 10 μM were found (3a, 3b, 3c) and 15 compounds with IC50 values between 10 and 100 μM were determined. In general, a cyclohexylamino rest

  在 Born 试验中，合成了 23 种标题化合物，并研究了它们对作为聚集诱导剂的胶原蛋白、ADP、肾上腺素和血小板激活因子 (PAF) 的抗血小板活性。使用胶原蛋白，发现了三种 IC50 值低于 10 μM 的化合物（3a、3b、3c），并确定了 15 种 IC50 值在 10 到 100 μM 之间的化合物。一般来说，环己氨基位于 4-甲酰胺部分是这种药理活性的先决条件。观察到结构元素 Y 中取代基 R1 的明显依赖性。4-甲酰胺取代基中的间隔n也是如此。化合物 3e 显示出强烈的 ADP 拮抗作用（IC50 = 2.2 nM）；3c 拮抗肾上腺素 (IC50 = 2.8 nM)，而 3n 对血小板激活因子非常有效 (IC50 = 0.2 μM)。
• HETEROARYLACETAMIDE INHIBITORS OF FACTOR Xa
  申请人：Boehringer Markus

  公开号：US20080146550A1

  公开（公告）日：2008-06-19

  The invention is concerned with novel heteroarylacetamides of formula (I) R—C(O)—N(R e )—R c —CH 2 —C(O)—N(R a )(R b )   (I) wherein R a to R e are as defined in the description and in the claims, as well as physiologically acceptable salts thereof. These compounds inhibit the coagulation factor Xa and can be used as medicaments.

  这项发明涉及公式(I)的新型杂环基乙酰胺，其中R-C（O）-N（Re）-Rc-CH2-C（O）-N（Ra）（Rb）  （I），其中Ra至Re的定义在说明书和权利要求中，以及其生理上可接受的盐。这些化合物抑制凝血因子Xa，可用作药物。
• Design of novel aminopyrrolidine factor Xa inhibitors from a screening hit
  作者：Katrin Groebke Zbinden、Lilli Anselm、David W. Banner、Jörg Benz、Francesca Blasco、Guillaume Décoret、Jacques Himber、Bernd Kuhn、Narendra Panday、Fabienne Ricklin

  DOI：10.1016/j.ejmech.2008.12.025

  日期：2009.7

  Starting from a hit identified by focused screening, 3-aminopyrrolidine factor Xa inhibitors were designed. The binding mode as determined by X-ray structural analysis as well as the pharmacokinetic behaviour of selected compounds is discussed. (C) 2009 Elsevier Masson SAS. All rights reserved.
• Synthesis and biological evaluation of thiazole derivatives on basic defects underlying cystic fibrosis
  作者：Emanuela Pesce、Nicoletta Pedemonte、Alberto Leoni、Alessandra Locatelli、Rita Morigi

  DOI：10.1016/j.bmcl.2020.127473

  日期：2020.11

  Cystic fibrosis is a genetic disease caused by loss-of-function mutations in the cystic fibrosis transmembrane conductance regulator gene, encoding for CFTR protein. The most frequent mutation is the deletion of phenylalanine at position 508 (F508del), which leads to distinct defects in channel gating and cellular processing. In last years, several thiazole containing small molecules, endowed with dual F508del-CFTR modulator activity, proved to be able to target these defects. In search of new chemical entities able to restore CFTR function, we designed and synthesized a small series of sixteen thiazole derivatives. The designed compounds were studied as correctors and potentiators of F508del-CFTR. Although none of the molecules showed significant corrector activity, compounds 10 and 11 exhibited potentiator effects, thus allowing to determine some basic structural features which enable to obtain F508del-CFTR potentiator activity. In silico ADME studies showed that these derivatives obey Lipinski's rule of five and are expected to be orally bioavailable. Therefore, these molecules may represent a good starting point for the design of analogues endowed with improved CFTR potentiator activity and a good pharmacokinetic profile.