N-isopropylmesitylenesulfonamide | 161452-11-5

• 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: N-isopropylmesitylenesulfonamide
• 英文别名: 2,4,6-trimethyl-N-propan-2-ylbenzenesulfonamide
• CAS: 161452-11-5
• 化学式: C₁₂H₁₉NO₂S
• mdl: MFCD01115708
• 分子量: 241.354
• InChiKey: LSMIXQRKQYHFDC-UHFFFAOYSA-N

物化性质

• 沸点：
  354.1±52.0 °C(Predicted)
• 密度：
  1.085±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  54.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-isopropylmesitylenesulfonamide 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.58h， 生成 N¹,N¹²-diisopropyl-N¹,N⁴,N⁹,N¹²-tetrakis(mesitylenesulfonyl)spermine
  参考文献：
  名称：

  多胺类似物止泻药：结构活性研究。

  摘要：

  描述了一组精胺多胺类似物的合成及其作为止泻药的评价。在啮齿动物蓖麻油诱发的腹泻模型中评估每种化合物降低粪便量和体重减轻的能力，这些剂量呈剂量依赖性。精胺药效基团被证明是构建止泻药的绝佳平台。化合物的活性非常取决于末端烷基的性质和分隔氮的亚甲基间隔基的几何形状。毒性特征还完全取决于这些相同的结构特征。根据皮下剂量反应数据和毒性概况，将两种化合物N（1），N（12）-二异丙精胺和N（1），N（12）-二乙基精胺进行了更全面的评估。这些测量包括正式的急性和慢性毒性试验，药物和代谢组织分布研究，以及这些类似物对组织多胺库的影响的评估。最后，N，N′-双[3-（乙基氨基）丙基]-反式1，4-环己二胺的显着活性强调需要进一步探索该构架作为构建其他止泻药的药效基团。

  DOI：

  10.1021/jm000277+
• 作为产物：
  描述：

  2,4,6-三甲基苯磺酰氯 、 异丙胺 在 sodium hydroxide 作用下， 以 二氯甲烷 为溶剂， 以83%的产率得到N-isopropylmesitylenesulfonamide
  参考文献：
  名称：

  Antiproliferative Properties of Polyamine Analogs: A Structure-Activity Study

  摘要：

  A basis set of polyamine analogues was designed and synthesized. These compounds were used to initiate a systematic investigation of the role of chain length, terminal nitrogen alkyl group size, and symmetry of the methylene backbone in the antineoplastic properties of polyamine analogues. New synthetic methods predicated on our earlier polyamine fragment synthesis are described for accessing the tetraamines of interest. An unsymmetrically substituted diamine reagent, N-(tert-butoxycarbonyl)-N,N'-bis(mesitylene sulfonyl)-1,4- di-aminobutane, was developed for entry into unsymmetrical tetraamines. All of the tetraamines synthesized were first evaluated in a murine leukemia L1210 cell IC50 assay at 48 and 96 h. In an attempt to correlate this behavior with some aspect of polyamine metabolism, each compound was tested for its ability to compete with spermidine for the polyamine uptake apparatus, its impact on the polyamine biosynthetic enzymes ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC), and its effect on the polyamine-catabolizing enzyme spermidine/spermine N-1-acetyltransferase (SSAT) and on polyamine pools. While there was no obvious correlation between the 48 and 96 h IC50'S and the impact of the analogues on polyamine metabolism, there were other structure-activity relationships. Correlations were observed to exist between chain length and IC50'S and between terminal alkyl substituents and impact on K-i, ODC, and AdoMetDC. Also, preliminary studies suggest a relationship may exist between the 48 and 96 h IC50's activities and the analogue's chronic toxicity in vivo. Finally, when the overall length of the polyamine backbone was held constant, the symmetry of the methylene chains of the polyamine fragments was shown to be unimportant to the compound's activity.

  DOI：

  10.1021/jm00047a004

文献信息

• [EN] PYRROLE AMIDES AS ALPHA V INTEGRIN INHIBITORS<br/>[FR] AMIDES DE PYRROLE EN TANT QU'INHIBITEURS D'INTÉGRINE ALPHA V
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2018089360A1

  公开（公告）日：2018-05-17

  The present invention provides compounds of Formula (I) or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds are inhibitors to αv-containing integrins. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with dysregulation of αv-containing integrins, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.

  本发明提供了具有式（I）的化合物或其立体异构体、互变异构体、或其药用可接受的盐或溶剂，其中所有变量均如本文所定义。这些化合物是αv-含有整合素的抑制剂。本发明还涉及包含这些化合物的药物组合物以及利用这些化合物和药物组合物治疗与αv-含有整合素失调相关的疾病、紊乱或病况的方法，例如病理纤维化、移植排斥、癌症、骨质疏松症和炎症性疾病。
• Indazole derivatives as αv integrin antagonists
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US10745384B2

  公开（公告）日：2020-08-18

  The present invention provides compounds of Formula (Ia) or (Ib): or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds are antagonists to αV-containing integrins. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with dysregulation of αV-containing integrins, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.

  本发明提供了式(Ia)或(Ib)化合物：或其立体异构体、同系物或药学上可接受的盐或溶液，其中所有变量如本文所定义。这些化合物是含αV整合素的拮抗剂。本发明还涉及包含这些化合物的药物组合物，以及通过使用这些化合物和药物组合物治疗与含αV整合素失调有关的疾病、紊乱或病症的方法，如病理性纤维化、移植排斥、癌症、骨质疏松症和炎症性疾病。
• Azole amides and amines as alpha v integrin inhibitors
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US10851098B2

  公开（公告）日：2020-12-01

  The present invention provides compounds of Formula (I): (Formula (I)), or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds are inhibitors to αv-containing integrins. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with dysregulation of αv-containing integrins, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.

  本发明提供了式 (I) 的化合物： 式（I））或其立体异构体、同系物或药学上可接受的盐或溶液，其中所有变量如本文所定义。 这些化合物是含αv整合素的抑制剂。 本发明还涉及包含这些化合物的药物组合物，以及通过使用这些化合物和药物组合物治疗与含αv整合素失调相关的疾病、紊乱或病症的方法，如病理性纤维化、移植排斥、癌症、骨质疏松症和炎症性疾病。
• 3-substituted propionic acids as αV integrin inhibitors
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US10968219B2

  公开（公告）日：2021-04-06

  The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds are antagonists to αv-containing integrins. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with dysregulation of ay-containing integrins, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.

  本发明提供了式（I）化合物：或其立体异构体、同系物或药学上可接受的盐或溶液，其中所有变量如本文所定义。这些化合物是含αv整合素的拮抗剂。本发明还涉及包含这些化合物的药物组合物，以及通过使用这些化合物和药物组合物治疗与含ay整合素失调相关的疾病、紊乱或病症的方法，如病理性纤维化、移植排斥、癌症、骨质疏松症和炎症性疾病。
• Cyclobutane- and azetidine-containing mono and spirocyclic compounds as αV integrin inhibitors
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US11014922B2

  公开（公告）日：2021-05-25

  The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds are antagonists to αv-containing integrins. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with dysregulation of av-containing integrins, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.

  本发明提供了式（I）化合物：或其立体异构体、同系物或药学上可接受的盐或溶液，其中所有变量如本文所定义。这些化合物是含αv整合素的拮抗剂。本发明还涉及包含这些化合物的药物组合物，以及通过使用这些化合物和药物组合物治疗与含av整合素失调相关的疾病、紊乱或病症的方法，如病理性纤维化、移植排斥、癌症、骨质疏松症和炎症性疾病。