3-isopropoxyphenylsulfonyl chloride | 69129-61-9

• 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: 3-isopropoxyphenylsulfonyl chloride
• 英文别名: 3-(1-methylethoxy)benzenesulfonyl chloride；3-isopropoxylbenzene-1-sulfonyl chloride；3-Isopropoxybenzene-1-sulfonyl chloride；3-propan-2-yloxybenzenesulfonyl chloride
• CAS: 69129-61-9
• 化学式: C₉H₁₁ClO₃S
• 分子量: 234.704
• InChiKey: HMCKEZVRRQHYFC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  51.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  、 3-isopropoxyphenylsulfonyl chloride 在 吡啶 、 苯胺 作用下， 生成 5-(4-chlorophenyl)-1,2-dimethyl-N-(3-(4-methylpiperazin-1-yl)propyl)-4-(3-(4-(4-(3-isopropoxyphenylsulfonamido)phenyl)piperazin-1-yl)phenyl)-1H-pyrrole-3-carboxamide
  参考文献：
  名称：

  Structure-Based Discovery of BM-957 as a Potent Small-Molecule Inhibitor of Bcl-2 and Bcl-xL Capable of Achieving Complete Tumor Regression

  摘要：

  Bcl-2 and Bcl-xL antiapoptotic proteins are attractive cancer therapeutic targets. We have previously reported the design of 4,5-diphenyl-1H-pyrrole-3-carboxylic acids as a class of potent Bcl-2/Bcl-xL inhibitors. In the present study, we report our structure-based optimization for this class of compounds based upon the crystal structure of Bcl-xL complexed with a potent lead compound. Our efforts accumulated into the design of compound 30 (BM-957), which binds to Bcl-2 and Bcl-xL with K-i < 1 nM and has low nanomolar IC50 values in cell growth inhibition in cancer cell lines. Significantly, compound 30 achieves rapid, complete, and durable tumor regression in the H146 small-cell lung cancer xenograft model at a well-tolerated dose schedule.

  DOI：

  10.1021/jm3010306
• 作为产物：
  描述：

  1-异丙氧基苯 生成 3-isopropoxyphenylsulfonyl chloride
  参考文献：
  名称：

  DE2801478

  摘要：

  公开号：

文献信息

• Design and Synthesis of Pyrrolidine-5,5-<i>trans-</i>lactams (5-Oxohexahydropyrrolo[3,2-<i>b</i>]pyrroles) as Novel Mechanism-Based Inhibitors of Human Cytomegalovirus Protease. 2. Potency and Chirality
  作者：Alan D. Borthwick、Andrew J. Crame、Peter F. Ertl、Anne M. Exall、Terry M. Haley、Graham J. Hart、Andrew M. Mason、Andrew M. K. Pennell、Onkar M. P. Singh、Gordon G. Weingarten、James M. Woolven

  DOI：10.1021/jm0102203

  日期：2002.1.1

  The stereospecific synthesis of a series of alpha-methylpyrrolidine-5,5-trans-lactam inhibitors of human cytomegalovirus (HCMV) protease is described. Examination of the SAR in this series has defined the size and chirality of the alpha-substituent, optimized the acyl substituent on the lactam nitrogen, and defined the steric constraint of this functionality. The SAR of the functionality on the pyrrolidine nitrogen of the trans-lactam has been investigated, and this has led to the discovery of potent serine protease inhibitors that are highly selective for the viral enzyme over the mammalian enzymes elastase, thrombin, and acetylcholine esterase. The mechanism of action of our lead compounds has been established by mass spectrometry, and enzymatic degradation of HCMV deltaAla protease acylated with these inhibitors showed that Ser 132 is the active site nucleophile. The crystal structure of HCMV protease was obtained and used to model the conformationally restricted, chiral (S)-proline-alpha-methyl-5,5-trans-lactams into the active site groove of the enzyme, enabling us to direct and rationalize the SAR in this series. The activity against HCMV deltaAla protease is the greatest with inhibitors based on the dansyl-(S)-proline alpha-methyl-5,5-trans-lactam template, which have low nanomolar activity against the viral enzyme.
• Design and Synthesis of Pyrrolidine-5,5‘-<i>trans-</i>Lactams (5-Oxo-hexahydropyrrolo[3,2-<i>b</i>]pyrroles) as Novel Mechanism-Based Inhibitors of Human Cytomegalovirus Protease. 4. Antiviral Activity and Plasma Stability
  作者：Alan D. Borthwick、Dave E. Davies、Peter F. Ertl、Anne M. Exall、Terry M. Haley、Graham J. Hart、Deborah L. Jackson、Nigel R. Parry、Angela Patikis、Naimisha Trivedi、Gordon G. Weingarten、James M. Woolven

  DOI：10.1021/jm030810w

  日期：2003.10.1

  A series of chiral, (S)-proline-alpha-methylpyrrolidine-5,5-trans-lactam serine protease inhibitors has been developed as antivirals of human cytomegalovirus (HCMV). The SAR of the functionality on the proline nitrogen has shown that derivatives of para-substituted phenyl ureas > para-substituted phenyl sulfonamides > para-substituted phenyl carboxamide for activity against HCMV deltaAla protease, producing para-substituted phenyl ureas with single figure nM potency (K-i) against the viral enzyme. The. SAR of the functionality on the lactam nitrogen has defined the steric and electronic requirements for high human plasma stability while retaining good activity against HCMV protease. The combination of high potency against HCMV deltaAla protease and high human plasma stability has produced compounds with significant in vitro antiviral activity against human cytomegalovirus with the 6-hydroxymethyl benzothiazole derivative 72 being equivalent in potency to ganciclovir. The parent benzothiazole 56 had good pharmacokinetics in dogs with 29% bioavailability and good brain and ocular penetration in guinea pigs.
• Structure-Based Discovery of BM-957 as a Potent Small-Molecule Inhibitor of Bcl-2 and Bcl-xL Capable of Achieving Complete Tumor Regression
  作者：Jianfang Chen、Haibin Zhou、Angelo Aguilar、Liu Liu、Longchuan Bai、Donna McEachern、Chao-Yie Yang、Jennifer L. Meagher、Jeanne A. Stuckey、Shaomeng Wang

  DOI：10.1021/jm3010306

  日期：2012.10.11

  Bcl-2 and Bcl-xL antiapoptotic proteins are attractive cancer therapeutic targets. We have previously reported the design of 4,5-diphenyl-1H-pyrrole-3-carboxylic acids as a class of potent Bcl-2/Bcl-xL inhibitors. In the present study, we report our structure-based optimization for this class of compounds based upon the crystal structure of Bcl-xL complexed with a potent lead compound. Our efforts accumulated into the design of compound 30 (BM-957), which binds to Bcl-2 and Bcl-xL with K-i < 1 nM and has low nanomolar IC50 values in cell growth inhibition in cancer cell lines. Significantly, compound 30 achieves rapid, complete, and durable tumor regression in the H146 small-cell lung cancer xenograft model at a well-tolerated dose schedule.
• DE2801478
  申请人：——

  公开号：——

  公开（公告）日：——