(E)-2(R)-[1(S)-(tert.butoxycarbonyl)-4-phenyl-3-butenyl]-4-methylvaleric acid | 219614-25-2

• 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: (E)-2(R)-[1(S)-(tert.butoxycarbonyl)-4-phenyl-3-butenyl]-4-methylvaleric acid
• 英文别名: (E)-2(R)-[1(S)-(tert-butoxycarbonyl)-4-phenyl-3-butenyl]-4-methylvaleric acid；(E,2R,3S)-3-[(2-methylpropan-2-yl)oxycarbonyl]-2-(2-methylpropyl)-6-phenylhex-5-enoic acid
• CAS: 219614-25-2
• 化学式: C₂₁H₃₀O₄
• 分子量: 346.467
• InChiKey: WNMZLOWDBBFFAU-HZOVXUMNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  25
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-2(R)-[1(S)-(tert.butoxycarbonyl)-4-phenyl-3-butenyl]-4-methylvaleric acid 在 N-乙基吗啉 、 N,N'-二环己基碳二亚胺 作用下， 以 醋酸异丙酯 为溶剂， 反应 28.5h， 生成 (E)-2(R)-[1(S)-(tert-butoxycarbonyl)-4-phenyl-3-butenyl]-2'-isobutyl-4-methylvalerohydrazide
  参考文献：
  名称：

  实际方法对基质金属蛋白酶抑制剂TROCADE ®（罗32-3555）和所述TNF-α转化酶抑制剂Ro 32-7315

  摘要：

  发现立体选择性方法可以有效地制备具有反构型的2-和3-取代的琥珀酸酯。在TROCADE的合成® 1中，hydantoinmethyl残余物通过非螯合钾烯醇化物烷基化引入19与溴甲基乙内酰脲9，得到92:8混合物利于2,3-反可配置琥珀酸盐18。TNF-α转化酶（TACE）抑制剂2的制备是通过使用CF 3 CONH 2对二烷基化的烯醇化物23进行高度立体选择性质子化，从而提供98：2的混合物（有利于2,3-）防琥珀酸24。

  DOI：

  10.1016/s0040-4020(01)00720-7
• 作为产物：
  描述：

  4-tert-butyl (E)-2(R)-isobutyl-3(S)-(3-phenyl-allyl)succinate tert-butylamine salt 在 盐酸 作用下， 以 醋酸异丙酯 为溶剂， 生成 (E)-2(R)-[1(S)-(tert.butoxycarbonyl)-4-phenyl-3-butenyl]-4-methylvaleric acid
  参考文献：
  名称：

  实际方法对基质金属蛋白酶抑制剂TROCADE ®（罗32-3555）和所述TNF-α转化酶抑制剂Ro 32-7315

  摘要：

  发现立体选择性方法可以有效地制备具有反构型的2-和3-取代的琥珀酸酯。在TROCADE的合成® 1中，hydantoinmethyl残余物通过非螯合钾烯醇化物烷基化引入19与溴甲基乙内酰脲9，得到92:8混合物利于2,3-反可配置琥珀酸盐18。TNF-α转化酶（TACE）抑制剂2的制备是通过使用CF 3 CONH 2对二烷基化的烯醇化物23进行高度立体选择性质子化，从而提供98：2的混合物（有利于2,3-）防琥珀酸24。

  DOI：

  10.1016/s0040-4020(01)00720-7

文献信息

• Compounds as inhibitor of tumor necrosis factor alpha release
  申请人：Hoffmann-La Roche Inc.

  公开号：US06239151B1

  公开（公告）日：2001-05-29

  The invention provides hydrazine derivatives of the formula wherein R1 is lower alkyl, lower alkenyl, lower cycloalkyl, lower cycloalkyl-lower alkyl, aryl or aryl-lower alkyl; R2 is an acyl group derived from an &agr;-, &bgr;-, &ggr;- or &dgr;-(amino, hydroxy or thiol)carboxylic acid in which the amino, hydroxy or thiol group is optionally lower alkylated or the amino group is optionally acylated, sulphonylated or amidated and in which any functional group present in a side-chain is optionally protected, or a group of the formula Het(CH2)mCO; R3 is hydrogen, lower alkyl, halo-lower alkyl, cyano-lower alkyl, amino-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, lower alkoxycarbonyl-lower alkyl, lower cycloalkyl-lower alkyl, aryl-lower alkyl, heterocyclyl-lower alkyl, heterocyclylcarbonyl-lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl-lower alkenyl, aryl or heterocyclyl; R4 is lower alkyl, lower alkenyl, lower cycloalkyl, lower cycloalkyl-lower alkyl or a grouping of the formula X-aryl, X-heteroaryl or —(CH2)n—CH═CR5R6; R5 and R6 together are lower alkylene in which one CH2 group is optionally replaced by a hetero atom; Het is heterocyclyl; X is a spacer group; m is 0, 1, 2, 3 or 4; and n is 1 or 2; and their pharmaceutically acceptable salts inhibit the release of tumour necrosis factor alpha (TNF-&agr;) from cells. They can be used as medicaments, especially in the treatment of inflammatory and autoimmune diseases, osteoarthritis, respiratory diseases, tumours, cachexia, cardiovascular diseases, fever, haemorrhage and sepsis.

  该发明提供了以下结构的肼衍生物 其中R1是较低的烷基、较低的烯基、较低的环烷基、较低的环烷基-较低的烷基、芳基或芳基-较低的烷基；R2是从α-、β-、γ-或δ-(氨基、羟基或硫醇)羧酸衍生的酰基，其中氨基、羟基或硫醇基可选择性地被较低的烷基化，或氨基可选择性地被酰化、磺酰化或酰胺化，并且侧链中存在的任何官能团可选择性地被保护，或者是Het(CH2)mCO的结构；R3是氢、较低的烷基、卤代较低的烷基、氰基-较低的烷基、氨基-较低的烷基、羟基-较低的烷基、较低的烷氧基-较低的烷基、较低的烷氧羰基-较低的烷基、较低的环烷基-较低的烷基、芳基-较低的烷基、杂环烷基-较低的烷基、杂环烷基羰基-较低的烷基、较低的烯基、较低的炔基、较低的环烷基、芳基-较低的烯基、芳基或杂环烷基；R4是较低的烷基、较低的烯基、较低的环烷基、较低的环烷基-较低的烷基或X-芳基、X-杂环芳基或—(CH2)n—CH=CR5R6的结构；R5和R6一起是较低的烷基，其中一个CH2基可选择性地被杂原子取代；Het是杂环烷基；X是间隔基；m为0、1、2、3或4；n为1或2；它们的药学上可接受的盐抑制肿瘤坏死因子α(TNF-α)从细胞中释放。它们可用作药物，特别是用于治疗炎症和自身免疫性疾病、骨关节炎、呼吸道疾病、肿瘤、消瘦症、心血管疾病、发热、出血和败血症。
• Hydrazine derivatives
  申请人：Hoffmann-La Roche Inc..

  公开号：US06265446B1

  公开（公告）日：2001-07-24

  Hydrazine derivatives of the formula wherein R1 represents lower alkyl, lower alkenyl, lower cycloalkyl, lower cycloalkyl-lower alkyl, aryl or aryl-lower alkyl, R2 represents heterocyclyl or NR5R6, R3 represents hydrogen, lower alkyl, halo-lower alkyl, cyano-lower alkyl, hydroxy-lower alkyl, amino-lower alkyl, lower alkoxy-lower alkyl, lower alkoxycarbonyl-lower alkyl, lower cycloalkyl-lower alkyl, aryl-lower alkyl, heterocyclyl-lower alkyl, heterocyclylcarbonyl-lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, heteroaryl or aryl-lower alkyl, R4 represents lower alkyl, lower alkenyl, lower cycloalkyl, lower cycloalkyl-lower alkyl or a grouping of the formula -Z-aryl, -Z-heterocyclyl or —(CH2)n—, CH═CR7R8, R5 and R6 each independently represent hydrogen or lower alkyl, R7 and R8 each independently represent hydrogen or lower alkyl or R7 and R8 together represent lower alkylene in which one CH2 group is optionally replaced by a hetero atom, X and Z each represent a spacer group, and n stands for 0, 1 or 2, and their pharmaceutically acceptable salts thereof, inhibit the release of tumor necrosis factor alpha (TNF-&agr;) from cells. They can be used as medicaments, especially in the treatment of inflammatory and autoimmune diseases, osteoarthritis, respiratory diseases, tumors, cachexia, cardiovascular diseases, fever, haemorrhage and sepsis.

  该公式中的肼衍生物，其中R1代表低碳基，低烯基，低环烷基，低环烷基-低碳基，芳基或芳基-低碳基，R2代表杂环基或NR5R6，R3代表氢，低碳基，卤代-低碳基，氰基-低碳基，羟基-低碳基，氨基-低碳基，低烷氧基-低碳基，低烷氧羰基-低碳基，低环烷基-低碳基，芳基-低碳基，杂环基-低碳基，杂环羰基-低碳基，低烯基，低炔基，低环烷基，芳基，杂环基或芳基-低碳基，R4代表低碳基，低烯基，低环烷基，低环烷基-低碳基或公式-Z-芳基，-Z-杂环基或—(CH2)n—，CH═CR7R8的基团，其中R5和R6各自独立地代表氢或低碳基，R7和R8各自独立地代表氢或低碳基或R7和R8一起代表低烷基，其中一个CH2基团可选地被杂原子取代，X和Z各代表一个间隔基团，n代表0、1或2，以及它们的药学上可接受的盐，抑制肿瘤坏死因子α（TNF-&agr;）从细胞中释放。它们可用作药物，特别是在治疗炎症和自身免疫性疾病、骨关节炎、呼吸系统疾病、肿瘤、消瘦、心血管疾病、发热、出血和败血症方面。
• Cyclic hydrazine derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US06281363B1

  公开（公告）日：2001-08-28

  Hydrazine derivatives and their pharmaceutically acceptable salts useful for the treatment of inflammatory and autoimmune diseases, osteoarthritis, respiratory diseases, tumors, cachexia, cardiovascular disease, fever, hemorrhage, and sepsis.

  肼衍生物及其药用可接受盐，用于治疗炎症和自身免疫性疾病、骨关节炎、呼吸系统疾病、肿瘤、消瘦症、心血管疾病、发热、出血和败血症。
• Dioxolane intermediates
  申请人：BRITISH BIOTECH PHARMACEUTICALS LIMITED

  公开号：EP0754688B1

  公开（公告）日：2000-12-27
• HYDRAZINE DERIVATIVES
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0993442A1

  公开（公告）日：2000-04-19