N-[4-(1,1-dioxo-thiomorpholin-4-yl)benzyl]-N-isobutyl-1-phenylmethanesulfonamide | 1445901-17-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻嗪类
• 英文名称: N-[4-(1,1-dioxo-thiomorpholin-4-yl)benzyl]-N-isobutyl-1-phenylmethanesulfonamide
• 英文别名: N-[[4-(1,1-dioxo-1,4-thiazinan-4-yl)phenyl]methyl]-N-(2-methylpropyl)-1-phenylmethanesulfonamide
• CAS: 1445901-17-6
• 化学式: C₂₂H₃₀N₂O₄S₂
• 分子量: 450.623
• InChiKey: AYJATBXGTYNDDG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  91.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  硫代吗啉-1,1-二氧化物 、 N-(4-bromobenzyl)-N-isobutyl-1-phenylmethanesulfonamide 生成 N-[4-(1,1-dioxo-thiomorpholin-4-yl)benzyl]-N-isobutyl-1-phenylmethanesulfonamide
  参考文献：
  名称：

  Reduction in lipophilicity improved the solubility, plasma–protein binding, and permeability of tertiary sulfonamide RORc inverse agonists

  摘要：

  Using structure-based drug design principles, we identified opportunities to reduce the lipophilicity of our tertiary sulfonamide RORc inverse agonists. The new analogs possessed improved RORc cellular potencies with >77-fold selectivity for RORc over other nuclear receptors in our cell assay suite. The reduction in lipophilicity also led to an increased plasma-protein unbound fraction and improvements in cellular permeability and aqueous solubility. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.06.048

文献信息

• BENZYL SULFONAMIDE DERIVATIVES AS RORC MODULATORS
  申请人：Genentech, Inc.

  公开号：US20130190288A1

  公开（公告）日：2013-07-25

  Compounds of the formula I: or pharmaceutically acceptable salts thereof, wherein m, n, A, X 1 , X 2 , X 3 , X 4 , R 1 , R 2 , R 3a , R 3b , R 4a and R 4b are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of inflammatory diseases such as arthritis.

  化合物I的公式或其药学上可接受的盐，其中m、n、A、X1、X2、X3、X4、R1、R2、R3a、R3b、R4a和R4b的定义如本文所述。还公开了制备该化合物的方法，并将该化合物用于治疗炎症性疾病，如关节炎。
• US9216988B2
  申请人：——

  公开号：US9216988B2

  公开（公告）日：2015-12-22
• Reduction in lipophilicity improved the solubility, plasma–protein binding, and permeability of tertiary sulfonamide RORc inverse agonists
  作者：Benjamin P. Fauber、Olivier René、Gladys de Leon Boenig、Brenda Burton、Yuzhong Deng、Céline Eidenschenk、Christine Everett、Alberto Gobbi、Sarah G. Hymowitz、Adam R. Johnson、Hank La、Marya Liimatta、Peter Lockey、Maxine Norman、Wenjun Ouyang、Weiru Wang、Harvey Wong

  DOI：10.1016/j.bmcl.2014.06.048

  日期：2014.8

  Using structure-based drug design principles, we identified opportunities to reduce the lipophilicity of our tertiary sulfonamide RORc inverse agonists. The new analogs possessed improved RORc cellular potencies with >77-fold selectivity for RORc over other nuclear receptors in our cell assay suite. The reduction in lipophilicity also led to an increased plasma-protein unbound fraction and improvements in cellular permeability and aqueous solubility. (C) 2014 Elsevier Ltd. All rights reserved.