N-[4-[2-(4-Methylphenyl)ethynyl]phenylsulfonyl]-D-valine t-butyl ester | 200293-69-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-[4-[2-(4-Methylphenyl)ethynyl]phenylsulfonyl]-D-valine t-butyl ester
• 英文别名: tert-butyl (2R)-3-methyl-2-[[4-[2-(4-methylphenyl)ethynyl]phenyl]sulfonylamino]butanoate
• CAS: 200293-69-2
• 化学式: C₂₄H₂₉NO₄S
• 分子量: 427.565
• InChiKey: OZXVOXJQVNLGCJ-JOCHJYFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  80.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-[4-[2-(4-Methylphenyl)ethynyl]phenylsulfonyl]-D-valine t-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 N-[4-[2-(4-methylphenyl)ethynyl]phenylsulfonyl]-D-valine
  参考文献：
  名称：

  Highly Selective and Orally Active Inhibitors of Type IV Collagenase (MMP-9 and MMP-2):  N-Sulfonylamino Acid Derivatives

  摘要：

  Various N-sulfonylamino acid derivatives were synthesized and evaluated for their in vitro and in vivo activities to inhibit type IV collagenase (MMP-9 and MMP-2). When the amino acid residue and the sulfonamide moiety were modified, their inhibitory activities were greatly affected by the structure of the sulfonamide moiety. A series of aryl sulfonamide derivatives containing biaryl, tetrazole, amide, and triple bond were found to be potent and highly selective inhibitors of MMP-9 and MMP-2 In addition, these compounds were orally active in animal models of tumor growth and metastasis. These results revealed the potential of the N-sulfonylamino acid derivatives as a new type of candidate drug for the treatment of cancer.

  DOI：

  10.1021/jm9707582
• 作为产物：
  描述：

  D-valine t-butyl ester 在 N-甲基吗啉 、 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 N-[4-[2-(4-Methylphenyl)ethynyl]phenylsulfonyl]-D-valine t-butyl ester
  参考文献：
  名称：

  Highly Selective and Orally Active Inhibitors of Type IV Collagenase (MMP-9 and MMP-2):  N-Sulfonylamino Acid Derivatives

  摘要：

  Various N-sulfonylamino acid derivatives were synthesized and evaluated for their in vitro and in vivo activities to inhibit type IV collagenase (MMP-9 and MMP-2). When the amino acid residue and the sulfonamide moiety were modified, their inhibitory activities were greatly affected by the structure of the sulfonamide moiety. A series of aryl sulfonamide derivatives containing biaryl, tetrazole, amide, and triple bond were found to be potent and highly selective inhibitors of MMP-9 and MMP-2 In addition, these compounds were orally active in animal models of tumor growth and metastasis. These results revealed the potential of the N-sulfonylamino acid derivatives as a new type of candidate drug for the treatment of cancer.

  DOI：

  10.1021/jm9707582

文献信息

• PHENYLSULFONAMIDE DERIVATIVES
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP0915086A1

  公开（公告）日：1999-05-12

  A phenylsulfonamide derivative of formula (I) (wherein R1 is H, alkyl; R2 is COOR3, CONHOR4; E is vinylene, ethynylene; A is H, alkyl, a carbocyclic ring, a heterocyclic ring; J is a single bond, aklylene; R9, R10 is H, (substituted) alkyl, COR11, a carbocyclic ring, a heterocyclic ring etc.; R20 is H, (substituted) alkyl etc.) and a non-toxic salt thereof, and a process for the preparation thereof, a matrix metalloproteinase inhibitor containing a compound above, and an agent for prevention and/or treatment of rheumatoid diseases, arthrosteitis, unusual bone resorption, osteoporosis, periodontitis, intestitial nephritis, arteriosclerosis, pulmonary emphysema, cirrhosis, cornea injury, metastasis or invasion of tumor cells, a disease induced by proliferation of tumor cells, an autoimmune disease (Crohn's disease or Sjogren's syndrome), diseases caused by vascular emigration and infiltration of leukocytes, or arterialization.

  式 (I) 的苯磺酰胺衍生物 (其中 R1 是 H、烷基；R2 是 COOR3、CONHOR4；E 是乙烯基、乙炔基；A 是 H、烷基、碳环、杂环；J 是单键、链烯；R9、R10 是 H、(取代)烷基、COR11、碳环、杂环等；R20 是 H、(取代)烷基等。)及其无毒盐，以及其制备方法，一种含有上述化合物的基质金属蛋白酶抑制剂，以及一种预防和/或治疗类风湿病、关节炎、异常骨吸收、骨质疏松症、牙周炎、肠肾炎、动脉硬化、肺动脉粥样硬化、骨质疏松症、牙周炎、肠肾炎的药物、动脉硬化、肺气肿、肝硬化、角膜损伤、肿瘤细胞转移或侵袭、肿瘤细胞增殖诱发的疾病、自身免疫性疾病（克罗恩病或 Sjogren 综合征）、白细胞血管移行和浸润引起的疾病或动脉化。
• Highly Selective and Orally Active Inhibitors of Type IV Collagenase (MMP-9 and MMP-2):  <i>N</i>-Sulfonylamino Acid Derivatives
  作者：Yoshinori Tamura、Fumihiko Watanabe、Takuji Nakatani、Ken Yasui、Masahiro Fuji、Tadafumi Komurasaki、Hiroshige Tsuzuki、Ryuji Maekawa、Takayuki Yoshioka、Kenji Kawada、Kenji Sugita、Mitsuaki Ohtani

  DOI：10.1021/jm9707582

  日期：1998.2.1

  Various N-sulfonylamino acid derivatives were synthesized and evaluated for their in vitro and in vivo activities to inhibit type IV collagenase (MMP-9 and MMP-2). When the amino acid residue and the sulfonamide moiety were modified, their inhibitory activities were greatly affected by the structure of the sulfonamide moiety. A series of aryl sulfonamide derivatives containing biaryl, tetrazole, amide, and triple bond were found to be potent and highly selective inhibitors of MMP-9 and MMP-2 In addition, these compounds were orally active in animal models of tumor growth and metastasis. These results revealed the potential of the N-sulfonylamino acid derivatives as a new type of candidate drug for the treatment of cancer.