3'-(4-chloro-2,5-dimethyl-benzenesulfonylamino)-3,5-dimethyl-biphenyl-4-carboxylic acid | 1011479-54-1

• 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'-(4-chloro-2,5-dimethyl-benzenesulfonylamino)-3,5-dimethyl-biphenyl-4-carboxylic acid
• 英文别名: 4-[3-[(4-chloro-2,5-dimethylphenyl)sulfonylamino]phenyl]-2,6-dimethylbenzoic acid
• CAS: 1011479-54-1
• 化学式: C₂₃H₂₂ClNO₄S
• 分子量: 443.951
• InChiKey: FDHOCLCGLPIXGX-UHFFFAOYSA-N

物化性质

• 沸点：
  619.5±65.0 °C(Predicted)
• 密度：
  1.331±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  91.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3'-(4-chloro-2,5-dimethyl-benzenesulfonylamino)-3,5-dimethyl-biphenyl-4-carboxylic acid 在 氯化亚砜 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 3'-(4-chloro-2,5-dimethyl-benzenesulfonylamino)-3,5-dimethyl-biphenyl-4-carboxylic acid chloride
  参考文献：
  名称：

  An Oral Sphingosine 1-Phosphate Receptor 1 (S1P₁) Antagonist Prodrug with Efficacy in Vivo: Discovery, Synthesis, and Evaluation

  摘要：

  A prodrug approach to optimize the oral exposure :of a series of sphingosine 1-phosphate receptor 1 (S1P(1)) antagonists for chronic efficacy studies led to the discovery of dimethylphenylsulfonylamino)-3,5-dimethylbiphenyl-4-carbonyl]-methylamino}-4-dimethylaminobutyric acid methyl ester 14. Methyl ester prodrug 14 is hydrolyzed in vivo to the corresponding carboxylic, acid 15, a potent and selective S1P(1) antagonist.: Oral; administration of the prodrug 14 induces sustained peripheral blood lymphocyte reduction.. in rats. In a rat: cardiac transplantation model coadministration of a nonefficacious dose of prodrung 14 with a nonefficacious dose of sotrastaurin (19), a protein kinase C inhibitor, or everolimus mTOR inhibitor, effectively prolonged the survival time of rat cardiac allografts. This demonstrates that clinically useful immunomodulation mediated by the S1P(1) receptor can be achieved with an S1P(1) antagonist generated in vivo after oral administration of its prodrug.

  DOI：

  10.1021/jm3009508
• 作为产物：
  描述：

  3-氨基苯硼酸 在 吡啶 、 四(三苯基膦)钯 、 碳酸氢钠 作用下， 以 乙二醇二甲醚 、 二氯甲烷 、 水 为溶剂， 反应 2.0h， 生成 3'-(4-chloro-2,5-dimethyl-benzenesulfonylamino)-3,5-dimethyl-biphenyl-4-carboxylic acid
  参考文献：
  名称：

  An Oral Sphingosine 1-Phosphate Receptor 1 (S1P₁) Antagonist Prodrug with Efficacy in Vivo: Discovery, Synthesis, and Evaluation

  摘要：

  A prodrug approach to optimize the oral exposure :of a series of sphingosine 1-phosphate receptor 1 (S1P(1)) antagonists for chronic efficacy studies led to the discovery of dimethylphenylsulfonylamino)-3,5-dimethylbiphenyl-4-carbonyl]-methylamino}-4-dimethylaminobutyric acid methyl ester 14. Methyl ester prodrug 14 is hydrolyzed in vivo to the corresponding carboxylic, acid 15, a potent and selective S1P(1) antagonist.: Oral; administration of the prodrug 14 induces sustained peripheral blood lymphocyte reduction.. in rats. In a rat: cardiac transplantation model coadministration of a nonefficacious dose of prodrung 14 with a nonefficacious dose of sotrastaurin (19), a protein kinase C inhibitor, or everolimus mTOR inhibitor, effectively prolonged the survival time of rat cardiac allografts. This demonstrates that clinically useful immunomodulation mediated by the S1P(1) receptor can be achieved with an S1P(1) antagonist generated in vivo after oral administration of its prodrug.

  DOI：

  10.1021/jm3009508

文献信息

• BIARYL SULFONAMIDE DERIVATIVES
  申请人：Berst Frederic

  公开号：US20100029609A1

  公开（公告）日：2010-02-04

  A compound of formula (I) or a pharmaceutically acceptable salt or prodrug ester thereof: wherein the groups R1-R5, R10 and X 1 -X 7 are as defined in the specification.

  化合物的结构式（I）或其药学上可接受的盐或前药酯： 其中，基团R1-R5、R10和X1-X7的定义如规范中所述。
• WO2008/28937
  申请人：——

  公开号：——

  公开（公告）日：——
• N-BIARYL (HETERO) ARYLSULPHONAMIDE DERIVATIVES USEFUL IN THE TREATMENT OF DISEASES MEDIATED BY LYMPHOCYTES INTERACTIONS
  申请人：NOVARTIS AG

  公开号：EP2081888A1

  公开（公告）日：2009-07-29
• [EN] N-BIARYL (HETERO) ARYLSULPHONAMIDE DERIVATIVES USEFUL IN THE TREATMENT OF DISEASES MEDIATED BY LYMPHOCYTES INTERACTIONS<br/>[FR] DÉRIVÉS DU N-BIARYL (HÉTÉRO) ARYLSULPHONAMIDE UTILISABLES POUR TRAITER DES MALADIES INDUITES PAR DES INTERACTIONS AVEC LES LYMPHOCYTES
  申请人：NOVARTIS AG

  公开号：WO2008028937A1

  公开（公告）日：2008-03-13

  [EN] A compound of formula (I) or a pharmaceutically acceptable salt or prodrug ester thereof: Formula (I) wherein the groups R1-R5, R10 and X₁-X₇ are as defined in the specification.
  [FR] La présente invention concerne un composé de formule (I) ou un sel ou un ester promédicament pharmaceutiquement acceptable de celui-ci : Formule (I) dans laquelle les groupes R¹-R⁵, R¹⁰ et X₁-X₇ sont tels que définis dans le mémoire descriptif.
• An Oral Sphingosine 1-Phosphate Receptor 1 (S1P₁) Antagonist Prodrug with Efficacy in Vivo: Discovery, Synthesis, and Evaluation
  作者：Daniela Angst、Philipp Janser、Jean Quancard、Peter Buehlmayer、Frederic Berst、Lukas Oberer、Christian Beerli、Markus Streiff、Charles Pally、Rene Hersperger、Christian Bruns、Frederic Bassilana、Birgit Bollbuck

  DOI：10.1021/jm3009508

  日期：2012.11.26

  A prodrug approach to optimize the oral exposure :of a series of sphingosine 1-phosphate receptor 1 (S1P(1)) antagonists for chronic efficacy studies led to the discovery of dimethylphenylsulfonylamino)-3,5-dimethylbiphenyl-4-carbonyl]-methylamino}-4-dimethylaminobutyric acid methyl ester 14. Methyl ester prodrug 14 is hydrolyzed in vivo to the corresponding carboxylic, acid 15, a potent and selective S1P(1) antagonist.: Oral; administration of the prodrug 14 induces sustained peripheral blood lymphocyte reduction.. in rats. In a rat: cardiac transplantation model coadministration of a nonefficacious dose of prodrung 14 with a nonefficacious dose of sotrastaurin (19), a protein kinase C inhibitor, or everolimus mTOR inhibitor, effectively prolonged the survival time of rat cardiac allografts. This demonstrates that clinically useful immunomodulation mediated by the S1P(1) receptor can be achieved with an S1P(1) antagonist generated in vivo after oral administration of its prodrug.