(2-amino-4-(3-chlorophenyl)thiazol-5-yl)(2-chlorophenyl)methanone | 1361413-64-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2-amino-4-(3-chlorophenyl)thiazol-5-yl)(2-chlorophenyl)methanone
• 英文别名: [2-Amino-4-(3-chlorophenyl)-1,3-thiazol-5-yl]-(2-chlorophenyl)methanone；[2-amino-4-(3-chlorophenyl)-1,3-thiazol-5-yl]-(2-chlorophenyl)methanone
• CAS: 1361413-64-0
• 化学式: C₁₆H₁₀Cl₂N₂OS
• 分子量: 349.24
• InChiKey: CYFCXGAUKLSTMF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  84.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2-amino-4-(3-chlorophenyl)thiazol-5-yl)(2-chlorophenyl)methanone 在 2-甲基-2-硝基丙烷 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以59%的产率得到(2-chlorophenyl)(4-(3-chlorophenyl)thiazol-5-yl)methanone
  参考文献：
  名称：

  Identification of potent RORβ modulators: Scaffold variation

  摘要：

  We sought to develop ROR beta-selective probe molecules in order to investigate the function of the receptor in vitro and in vivo and its role in the pathophysiology of disease. To accomplish this, we modified a potent dual ROR beta/ROR gamma inverse agonist from the primary literature with the goal of improving selectivity for ROR beta vs ROR gamma. Truncation of the Western portion of the molecule ablated activity at ROR gamma and led to a potent series of ROR beta modulators. Continued exploration of this series investigated alternate replacement cores for the aminothiazole ring. Numerous suitable replacements were found during the course of our SAR investigations and are reported herein.

  DOI：

  10.1016/j.bmcl.2018.08.017
• 作为产物：
  描述：

  2-溴-2'-氯苯乙酮 在 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 (2-amino-4-(3-chlorophenyl)thiazol-5-yl)(2-chlorophenyl)methanone
  参考文献：
  名称：

  Discovery of novel N-(5-(arylcarbonyl)thiazol-2-yl)amides and N-(5-(arylcarbonyl)thiophen-2-yl)amides as potent RORγt inhibitors

  摘要：

  Novel series of N-(5-(arylcarbonyl) thiazol-2-yl)amides and N-(5-(arylcarbonyl)thiophen-2-yl) amides were discovered as potent retinoic acid receptor-related orphan receptor-gamma-t (ROR gamma t) inhibitors. SAR studies of the ROR gamma t HTS hit 6a led to identification of thiazole ketone amide 8h and thiophene ketone amide 9g with high binding affinity and inhibitory activity of Th17 cell differentiation. Compound 8h showed in vivo efficacy in both mouse experimental autoimmune encephalomyelitis (EAE) and collagen induced arthritis (CIA) models via oral administration. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.12.021

文献信息

• Identification of an aminothiazole series of RORβ modulators
  作者：Rémi Patouret、Christelle Doebelin、Ruben D. Garcia-Ordonez、Mi Ra Chang、Claudia Ruiz、Michael D. Cameron、Patrick R. Griffin、Theodore M. Kamenecka

  DOI：10.1016/j.bmcl.2018.03.001

  日期：2018.4

  Crystallography has identified stearic acid, ALRT 1550 and ATRA as ligands that bind RORβ, however, none of these molecules represent good starting points to develop optimized small molecule modulators. Recently, Compound 1 was identified as a potent dual RORβ and RORγ inverse agonist with no activity towards RORα (Fig. 1). To our knowledge, this is one of only two small molecule RORβ inverse agonists

  晶体学已将硬脂酸、ALRT 1550 和 ATRA 鉴定为结合 RORβ 的配体，但是，这些分子都不是开发优化的小分子调节剂的良好起点。最近，化合物1被鉴定为有效的双重 RORβ 和 RORγ 反向激动剂，对 RORα 没有活性（图 1）。据我们所知，这是主要文献中从易于处理的化学系列中鉴定出的仅有的两种小分子 RORβ 反向激动剂之一，代表了设计 RORβ 选择性调节剂的理想起点。在此，我们描述了我们的 SAR 优化工作，这些工作导致了一系列有效的 RORβ 中性拮抗剂。
• Synthesis and Antioxidant Activity of New Thiazole Analogues Possessing Urea, Thiourea, and Selenourea Functionality
  作者：M. Vijaya Bhaskara Reddy、D. Srinivasulu、K. Peddanna、Ch. Apparao、P. Ramesh

  DOI：10.1080/00397911.2015.1095929

  日期：2015.11.17

  spectroscopic data and screened for their in vitro antioxidant activity using 1,1-diphenylpicrylhydrazyl (DPPH), nitric oxide (NO), and hydrogen peroxide (H2O2) radical scavenging methods. A preliminary study of the structure–activity relationship revealed that the compounds containing selenourea functionality along with halogen group have exhibited potent activity (IC50 ≤ 0.0309 µmol/mL) compared to the standards

  摘要 通过（2-氨基-4-（3-氯苯基）噻唑-5-基）（2-氯苯基）甲酮与各种取代基的亲核加成反应，合成了一系列具有噻唑基团的新型脲、硫脲和硒脲衍生物。异氰酸酯/异硫氰酸酯/异硒炔酸酯在丙酮中具有催化量的氢氧化钠，在室温下具有良好的产率。所有合成的化合物都通过光谱数据进行了充分表征，并使用 1,1-二苯基苦基肼 (DPPH)、一氧化氮 (NO) 和过氧化氢 (H2O2) 自由基清除方法筛选了它们的体外抗氧化活性。构效关系的初步研究表明，含有硒脲官能团和卤素基团的化合物具有很强的活性（IC50 ≤ 0. 0309 µmol/mL) 与标准品 (IC50 ≤ 0.0814 µmol/mL) 相比。因此，标题化合物是一类新的有效抗氧化剂，值得进一步研究。图形概要
• [EN] NOVEL COMPOUNDS<br/>[FR] NOUVEAUX COMPOSÉS
  申请人：GLAXO GROUP LTD

  公开号：WO2012027965A1

  公开（公告）日：2012-03-08

  Disclosed are retinoid-related orphan receptor gamma (RORγ) modulators and their use in the treatment of diseases mediated by RORγ.

  揭示了与视黄醇相关孤儿受体γ（RORγ）调节剂及其在治疗由RORγ介导的疾病中的应用。
• Identification of potent RORβ modulators: Scaffold variation
  作者：Christelle Doebelin、Rémi Patouret、Ruben D. Garcia-Ordonez、Mi Ra Chang、Venkatasubramanian Dharmarajan、Scott Novick、Anthony Ciesla、Sean Campbell、Laura A. Solt、Patrick R. Griffin、Theodore M. Kamenecka

  DOI：10.1016/j.bmcl.2018.08.017

  日期：2018.10

  We sought to develop ROR beta-selective probe molecules in order to investigate the function of the receptor in vitro and in vivo and its role in the pathophysiology of disease. To accomplish this, we modified a potent dual ROR beta/ROR gamma inverse agonist from the primary literature with the goal of improving selectivity for ROR beta vs ROR gamma. Truncation of the Western portion of the molecule ablated activity at ROR gamma and led to a potent series of ROR beta modulators. Continued exploration of this series investigated alternate replacement cores for the aminothiazole ring. Numerous suitable replacements were found during the course of our SAR investigations and are reported herein.
• Discovery of novel N-(5-(arylcarbonyl)thiazol-2-yl)amides and N-(5-(arylcarbonyl)thiophen-2-yl)amides as potent RORγt inhibitors
  作者：Yonghui Wang、Wei Cai、Guifeng Zhang、Ting Yang、Qian Liu、Yaobang Cheng、Ling Zhou、Yingli Ma、Ziqiang Cheng、Sijie Lu、Yong-Gang Zhao、Wei Zhang、Zhijun Xiang、Shuai Wang、Liuqing Yang、Qianqian Wu、Lisa A. Orband-Miller、Yan Xu、Jing Zhang、Ruina Gao、Melanie Huxdorf、Jia-Ning Xiang、Zhong Zhong、John D. Elliott、Stewart Leung、Xichen Lin

  DOI：10.1016/j.bmc.2013.12.021

  日期：2014.1

  Novel series of N-(5-(arylcarbonyl) thiazol-2-yl)amides and N-(5-(arylcarbonyl)thiophen-2-yl) amides were discovered as potent retinoic acid receptor-related orphan receptor-gamma-t (ROR gamma t) inhibitors. SAR studies of the ROR gamma t HTS hit 6a led to identification of thiazole ketone amide 8h and thiophene ketone amide 9g with high binding affinity and inhibitory activity of Th17 cell differentiation. Compound 8h showed in vivo efficacy in both mouse experimental autoimmune encephalomyelitis (EAE) and collagen induced arthritis (CIA) models via oral administration. (C) 2013 Elsevier Ltd. All rights reserved.