N-[(2S)-3-benzoylthio-2-methylpropionyl]-S-(4-dimethylamino)benzyl-L-cysteine | 183121-03-1

• 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-[(2S)-3-benzoylthio-2-methylpropionyl]-S-(4-dimethylamino)benzyl-L-cysteine
• 英文别名: (2R)-2-[[(2S)-3-benzoylsulfanyl-2-methylpropanoyl]amino]-3-[[4-(dimethylamino)phenyl]methylsulfanyl]propanoic acid
• CAS: 183121-03-1
• 化学式: C₂₃H₂₈N₂O₄S₂
• 分子量: 460.618
• InChiKey: UNILKFARWKANJI-UZLBHIALSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  31
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  137
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-[(2S)-3-benzoylthio-2-methylpropionyl]-S-(4-dimethylamino)benzyl-L-cysteine 在 ammonium hydroxide 作用下， 以 水 为溶剂， 反应 1.0h， 以81%的产率得到SA6541
  参考文献：
  名称：

  N-巯基半胱氨酸衍生物作为白三烯A 4水解酶抑制剂的合成及生物学评价

  摘要：

  我们研究了N-巯基酰基氨基酸衍生物的合成修饰，以开发一类新的白三烯A 4（LTA 4）水解酶抑制剂。小号- （4-二甲基氨基）苄基-升-半胱氨酸衍生物2A（SA6541）显示针对LTA抑制活性4水解酶（IC 50，270 nm）的和选择性优于其它金属肽除了血管紧张素转换酶（ACE，IC 50，520 nm）的。化合物2a苯环的对位取代基上的修饰改进了LTA 4水解酶抑制活性以及对ACE的选择性。最后，我们获得了作为有效的和选择性的LTA 4水解酶抑制剂的S-（4-环己基）苯并-1-半胱氨酸衍生物11l和16i。

  DOI：

  10.1016/j.bmcl.2008.11.042
• 作为产物：
  描述：

  (S)-(-)-3-苯甲酰巯基-2-甲基丙酸 在 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 52.0h， 生成 N-[(2S)-3-benzoylthio-2-methylpropionyl]-S-(4-dimethylamino)benzyl-L-cysteine
  参考文献：
  名称：

  Involvement of Leukotriene B4 in Murine Dermatitis Models

  摘要：

  Leukotriene B-4 (LTB4) is a product of the 5-lipoxygenase pathway of arachidonic acid (AA) metabolism. LTB4 is a potent chemotactic factor for neutrophils and has been postulated to play an important role in a variety of pathological conditions including rheumatoid arthritis, psoriasis, and inflammatory bowel disease. To investigate the role of LTB4 in dermatitis, we used S-(4-dimethylaminobenzyl)-N-[(2S) -mercapto-2-methylpropionyl]-L-cysteine (SA6541), a potent leukotriene A(4) (LTA(4)) hydrolase inhibitor. SA6541 inhibited LTB4 production with an IC50 value of 270 nM in vitro. 5-Hydroperoxyeicosatetraenoic acid (5-HPETE) or AA injection induced LTB4 production and neutrophil influx in mouse ear. SA6541 inhibited 5-HPETE- and AA-induced LTB4 production and neutrophil influx in mouse ear when administered orally at a dose of 50 mg/kg. SA6541 also inhibited 5-HPETE induced prostaglandin E-2 (PGE(2)) production, probably by an indirect effect through the inhibition of LTB4 production. These results suggest that LTB4 map be important in the pathogenesis of dermatitides such as psoriasis. (C) 1998 Elsevier Science Inc.

  DOI：

  10.1016/s0006-2952(97)00464-4

文献信息

• NOVEL AMINO ACID DERIVATIVES HAVING N,N-DIALKYLAMINOPHENYL GROUP
  申请人：SANTEN PHARMACEUTICAL CO., LTD.

  公开号：EP0870762A1

  公开（公告）日：1998-10-14

  The present invention relates to novel amino acid derivatives having an N, N-dialkylaminophenyl group represented by the general formula [I]. wherein R1 represents a hydrogen atom, a lower alkyl group, a phenyl-lower alkyl group, a lower alkanoyl group or a benzoyl group, and each phenyl ring in the phenyl-lower alkyl group and the benzoyl group can be substituted by a halogen atom, a lower alkyl group or a lower alkoxy group; R2 represents a carboxyl group which can be converted into an ester, an amide or a hydroxamic acid; R3 represents a lower alkyl group; R4 represents a lower alkyl group; A1 represents a lower alkylene group which can be substituted by a phenyl group, and the phenyl group can be substituted by a halogen atom, a lower alkyl group or a lower alkoxy group; A2 represents a lower alkylene group; A3 represents a lower alkylene group; and "Z" represents a sulfur atom or an oxygen atom. The compounds have inhibitory effects on LTA4 hydrolase and are useful as medicines, in particular, therapeutic agents for inflammatory diseases such as rheumatic diseases, psoriasis, inflammatory intestinal diseases, gout and cystic fibrosis, in which LTB4 is concerned.

  本发明涉及具有通式 [I] 所代表的 N，N-二烷基氨基苯基的新型氨基酸衍生物。 其中 R1 代表氢原子、低级烷基、苯基低级烷基、低级烷酰基或苯甲酰基，苯基低级烷基和苯甲酰基中的每个苯基环可被卤素原子、低级烷基或低级烷氧基取代； R2 代表可转化为酯、酰胺或羟肟酸的羧基； R3 代表低级烷基 R4 代表一个低级烷基； A1 代表可被苯基取代的低级亚烷基，苯基可被卤素原子、低级烷基或低级烷氧基取代； A2 代表一个低级亚烷基 A3 代表一个低级亚烷基；以及 Z "代表硫原子或氧原子。 这些化合物对 LTA4 水解酶有抑制作用，可用作药物，特别是治疗与 LTB4 有关的炎症性疾病，如风湿病、牛皮癣、肠道炎症性疾病、痛风和囊性纤维化。
• Synthesis and biological evaluation of N-mercaptoacylcysteine derivatives as leukotriene A4 hydrolase inhibitors
  作者：Hiroshi Enomoto、Yuko Morikawa、Yurika Miyake、Fumio Tsuji、Maki Mizuchi、Hiroshi Suhara、Ken-ichi Fujimura、Masato Horiuchi、Masakazu Ban

  DOI：10.1016/j.bmcl.2008.11.042

  日期：2009.1

  We studied synthetic modifications of N-mercaptoacylamino acid derivatives to develop a new class of leukotriene A4 (LTA4) hydrolase inhibitors. S-(4-Dimethylamino)benzyl-l-cysteine derivative 2a (SA6541) showed inhibitory activity against LTA4 hydrolase (IC50, 270 nM) and selectivity over other metallopeptidases except angiotensin-converting enzyme (ACE, IC50, 520 nM). Modification at the para-substituent

  我们研究了N-巯基酰基氨基酸衍生物的合成修饰，以开发一类新的白三烯A 4（LTA 4）水解酶抑制剂。小号- （4-二甲基氨基）苄基-升-半胱氨酸衍生物2A（SA6541）显示针对LTA抑制活性4水解酶（IC 50，270 nm）的和选择性优于其它金属肽除了血管紧张素转换酶（ACE，IC 50，520 nm）的。化合物2a苯环的对位取代基上的修饰改进了LTA 4水解酶抑制活性以及对ACE的选择性。最后，我们获得了作为有效的和选择性的LTA 4水解酶抑制剂的S-（4-环己基）苯并-1-半胱氨酸衍生物11l和16i。
• Involvement of Leukotriene B4 in Murine Dermatitis Models
  作者：Fumio Tsuji、Yurika Miyake、Masato Horiuchi、Shiro Mita

  DOI：10.1016/s0006-2952(97)00464-4

  日期：1998.2

  Leukotriene B-4 (LTB4) is a product of the 5-lipoxygenase pathway of arachidonic acid (AA) metabolism. LTB4 is a potent chemotactic factor for neutrophils and has been postulated to play an important role in a variety of pathological conditions including rheumatoid arthritis, psoriasis, and inflammatory bowel disease. To investigate the role of LTB4 in dermatitis, we used S-(4-dimethylaminobenzyl)-N-[(2S) -mercapto-2-methylpropionyl]-L-cysteine (SA6541), a potent leukotriene A(4) (LTA(4)) hydrolase inhibitor. SA6541 inhibited LTB4 production with an IC50 value of 270 nM in vitro. 5-Hydroperoxyeicosatetraenoic acid (5-HPETE) or AA injection induced LTB4 production and neutrophil influx in mouse ear. SA6541 inhibited 5-HPETE- and AA-induced LTB4 production and neutrophil influx in mouse ear when administered orally at a dose of 50 mg/kg. SA6541 also inhibited 5-HPETE induced prostaglandin E-2 (PGE(2)) production, probably by an indirect effect through the inhibition of LTB4 production. These results suggest that LTB4 map be important in the pathogenesis of dermatitides such as psoriasis. (C) 1998 Elsevier Science Inc.