2(R)-2-biphenyl-4-ylmethyl-1,1-dioxo-λ⁶-isothiazolidine-3-carboxylic acid hydroxyamide

• 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(R)-2-biphenyl-4-ylmethyl-1,1-dioxo-λ⁶-isothiazolidine-3-carboxylic acid hydroxyamide
• 英文别名: (3R)-2-(1,1-biphenyl-4-ylmethyl)-N-hydroxyisothiazolidine-3-carboxamide 1,1-dioxide；(3R)-N-hydroxy-1,1-dioxo-2-[(4-phenylphenyl)methyl]-1,2-thiazolidine-3-carboxamide
• 化学式: C₁₇H₁₈N₂O₄S
• 分子量: 346.407
• InChiKey: CMALBPMZEURNBK-MRXNPFEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  95.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-溴甲基联苯 在 N-甲基吗啉 、 potassium carbonate 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 2.33h， 生成 2(R)-2-biphenyl-4-ylmethyl-1,1-dioxo-λ⁶-isothiazolidine-3-carboxylic acid hydroxyamide
  参考文献：
  名称：

  Sultam Hydroxamates as Novel Matrix Metalloproteinase Inhibitors

  摘要：

  In this communication we describe the design, synthesis, and evaluation of novel sultam hydroxamates 4 as MMP-2, -9, and -13 inhibitors. Compound 26 was found to be an active inhibitor (NIMP-2 IC50 = 1 nM) with 1000-fold selectivity over MMP-1 and good oral bioavailability (F = 43%) in mouse. An X-ray crystal structure of 26 in MMP-13 confirms the key hydrogen bonds and prime side binding in the active site.

  DOI：

  10.1021/jm049833g

文献信息

• Cyclic sulfonyl compounds as inhibitors of metalloproteases
  申请人：——

  公开号：US20020086853A1

  公开（公告）日：2002-07-04

  The present application describes novel cyclic sulfonyl derivatives of formula I: 1 or pharmaceutically acceptable salt forms thereof, wherein ring B is a 5-7 membered cyclic system containing from 0-2 heteroatoms selected from O, N, NR a , and S(O) p , and 0-1 carbonyl groups and the other variables are defined in the present specification, which are useful as metalloprotease inhibitors.

  本申请描述了新颖的公式I的环磺酰衍生物，或其药用盐形式，其中环B是一个含有0-2个来自O、N、NRa和S(O)p的杂原子以及0-1个羰基的5-7元环系统，其他变量在本说明书中定义，这些衍生物可用作金属蛋白酶抑制剂。
• [EN] CYCLIC SULFONYL COMPOUNDS AS INHIBITORS OF METALLOPROTEASES<br/>[FR] COMPOSES SULFONYLE CYCLIQUES INHIBANT LES METALLOPROTEASES
  申请人：DU PONT PHARM CO

  公开号：WO2002028846A1

  公开（公告）日：2002-04-11

  The present application describes novel cyclic sulfonyl derivatives of formula (I) particularly of formulae (II), (III), (IV) and (V) which are useful as metalloprotease inhibitors.

  本申请描述了新型环状磺酰衍生物的公式(I)，特别是公式(II)，(III)，(IV)和(V)，其作为金属蛋白酶抑制剂具有用途。
• CYCLIC SULFONYL COMPOUNDS AS INHIBITORS OF METALLOPROTEASES
  申请人：Bristol-Myers Squibb Pharma Company

  公开号：EP1322627A1

  公开（公告）日：2003-07-02
• US6927216B2
  申请人：——

  公开号：US6927216B2

  公开（公告）日：2005-08-09
• Sultam Hydroxamates as Novel Matrix Metalloproteinase Inhibitors
  作者：Robert J. Cherney、Ruowei Mo、Dayton T. Meyer、Karl D. Hardman、Rui-Qin Liu、Maryanne B. Covington、Mingxin Qian、Zelda R. Wasserman、David D. Christ、James M. Trzaskos、Robert C. Newton、Carl P. Decicco

  DOI：10.1021/jm049833g

  日期：2004.6.1

  In this communication we describe the design, synthesis, and evaluation of novel sultam hydroxamates 4 as MMP-2, -9, and -13 inhibitors. Compound 26 was found to be an active inhibitor (NIMP-2 IC50 = 1 nM) with 1000-fold selectivity over MMP-1 and good oral bioavailability (F = 43%) in mouse. An X-ray crystal structure of 26 in MMP-13 confirms the key hydrogen bonds and prime side binding in the active site.