3(S)-tert-butyloxycarbonyl-6-phenyl-2(R)-isobutylhexanoic acid | 219615-70-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 3(S)-tert-butyloxycarbonyl-6-phenyl-2(R)-isobutylhexanoic acid
• 英文别名: 2(R)-[1(S)-(tert-butoxycarbonyl)-4-phenylbutyl]-4-methylvaleric acid；(2R,3S)-3-[(2-methylpropan-2-yl)oxycarbonyl]-2-(2-methylpropyl)-6-phenylhexanoic acid
• CAS: 219615-70-0
• 化学式: C₂₁H₃₂O₄
• 分子量: 348.483
• InChiKey: YBHJBGJZXJBSBO-ZWKOTPCHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  25
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 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：

  3(S)-tert-butyloxycarbonyl-6-phenyl-2(R)-isobutylhexanoic acid 在 硼烷四氢呋喃络合物 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以69%的产率得到tert-butyl 3(R)-hydroxymethyl-5-methyl-2(S)-phenylpropylhexanoate
  参考文献：
  名称：

  Highly water-soluble matrix metalloproteinases inhibitors and their effects in a rat adjuvant-induced arthritis model

  摘要：

  A new series of succinate-based dual inhibitors against matrix metalloproteinases (MMPs) and tumor necrosis factor or. converting enzyme (TACE) possessing highly-water solubility was designed, synthesized, and evaluated for enzyme inhibition. Incorporating of acidic or basic functional groups at the P-2' position afforded sufficient water solubility without significant loss of inhibitory potencies. Compound 18e, which had a guanidino group at the P-2' position as the basic functional group, exhibited broad inhibition against target enzymes for a relatively long period in rat plasma (beta1(1/2): 2.0 h) after sc administration when compared with compounds possessing acidic functional groups (18a and 18b). Consequently, the representative compound 18e together with compound 18b. Marimastat and Trocade were evaluated in the rat adjuvant-induced arthritis model, a model of chronic cartilage destruction. It is concluded that the newly synthesized highly water-soluble compound 18e showed significant activity in suppressing hindpaw swelling and the bone destruction with a minimal administration period (days 3-7). (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00109-8
• 作为产物：
  描述：

  D-亮氨酸 在 palladium on activated charcoal N-乙基吗啉 、 tert-butoxide 、 氢溴酸 、 氢气 、 sodium hydride 、 对甲苯磺酸 、 sodium nitrite 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 44.0h， 生成 3(S)-tert-butyloxycarbonyl-6-phenyl-2(R)-isobutylhexanoic acid
  参考文献：
  名称：

  Highly water-soluble matrix metalloproteinases inhibitors and their effects in a rat adjuvant-induced arthritis model

  摘要：

  A new series of succinate-based dual inhibitors against matrix metalloproteinases (MMPs) and tumor necrosis factor or. converting enzyme (TACE) possessing highly-water solubility was designed, synthesized, and evaluated for enzyme inhibition. Incorporating of acidic or basic functional groups at the P-2' position afforded sufficient water solubility without significant loss of inhibitory potencies. Compound 18e, which had a guanidino group at the P-2' position as the basic functional group, exhibited broad inhibition against target enzymes for a relatively long period in rat plasma (beta1(1/2): 2.0 h) after sc administration when compared with compounds possessing acidic functional groups (18a and 18b). Consequently, the representative compound 18e together with compound 18b. Marimastat and Trocade were evaluated in the rat adjuvant-induced arthritis model, a model of chronic cartilage destruction. It is concluded that the newly synthesized highly water-soluble compound 18e showed significant activity in suppressing hindpaw swelling and the bone destruction with a minimal administration period (days 3-7). (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00109-8

文献信息

• Hydrazine derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US06235787B1

  公开（公告）日：2001-05-22

  Hydrazine derivatives of the formula wherein Y is CO or SO2; R1 is lower alkyl, lower alkenyl, lower cycloalkyl, lower cycloalkyl-lower alkyl, aryl or aryl-lower alkyl; R2 is lower alkyl, halo-lower alkyl, aryl-lower alkyl, aryl-lower alkenyl or aryl when Y is SO2 and is lower alkyl, halo-lower alkyl, lower alkoxy, lower alkoxycarbonyl, acyl, lower cycloalkyl, aryl, aryl-lower alkyl, aryl-lower alkoxy or NR5R6 when Y is CO; and R3 is hydrogen, lower alkyl optionally substituted by cyano, amino, hydroxy, lower alkoxy, lower alkoxycarbonyl, heterocyclyl or heterocyclylcarbonyl, lower alkenyl, lower alkynyl, lower cycloalkyl, lower cycloalkyl-lower alkyl, aryl-lower alkyl, aryl-lower alkenyl, aryl or heterocyclyl; or R2 and R3 together form the residue of a 5-, 6- or 7-membered cyclic amide, cyclic imide, cyclic sulphonamide or cyclic urethane group; R4 is lower alkyl, hydroxy-lower alkyl, lower alkenyl, lower cycloalkyl, lower cycloalkyl-lower alkyl or a group of the formula X-aryl, X-heteroaryl or —(CH2)1-2—CH═CR7R8; X is a spacer group; R5 and R6 each individually are hydrogen, lower alkyl or aryl-lower alkyl; and R7 and R8 together represent a lower alkylene group in which one methylene group is optionally replaced by a hetero atom; and their pharmaceutically acceptable salts inhibit not only the release of tumour necrosis factor (TNF-&agr;) and transforming growth factor (TGF-&agr;) from cells, but also keratinocyte proliferation. They are useful as medicaments, especially for the treatment of inflammation, fever, hemorrhage, sepsis, rheumatoid arthritis, osteoarthritis, multiple sclerosis or psoriasis.

  氢肼衍生物的化学式为其中Y为CO或SO2；R1为较低的烷基、较低的烯基、较低的环烷基、较低的环烷基-烷基、芳基或芳基-烷基；R2为较低的烷基、卤代较低的烷基、芳基-烷基、芳基-烯基或芳基（当Y为SO2时），且为较低的烷基、卤代较低的烷基、较低的烷氧基、较低的烷氧羰基、酰基、较低的环烷基、芳基、芳基-烷基、芳基-烷氧基或NR5R6（当Y为CO时）；R3为氢、较低的烷基（可选择地被氰基、氨基、羟基、较低的烷氧基、较低的烷氧羰基、杂环烷基或杂环烷基羰基取代）、较低的烯基、较低的炔基、较低的环烷基、较低的环烷基-烷基、芳基-烷基、芳基-烯基、芳基或杂环烷基；或者R2和R3一起形成5、6或7成员环酰胺、环亚胺、环磺胺或环脲基团的残基；R4为较低的烷基、羟基-较低的烷基、较低的烯基、较低的环烷基、较低的环烷基-烷基或具有X-芳基、X-杂环芳基或—(CH2)1-2—CH═CR7R8的基团；X为间隔基团；R5和R6各自为氢、较低的烷基或芳基-烷基；R7和R8一起代表较低的烷基烯基，其中一个亚甲基团可选择地被杂原子取代；它们的药学上可接受的盐不仅抑制肿瘤坏死因子（TNF-α）和转化生长因子（TGF-α）从细胞中的释放，还抑制角质细胞增殖。它们可用作药物，特别用于治疗炎症、发热、出血、败血症、类风湿性关节炎、骨关节炎、多发性硬化或牛皮癣。
• 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。
• HYDRAZINE DERIVATIVES
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0993442A1

  公开（公告）日：2000-04-19
• CYCLIC HYDRAZINE DERIVATIVES AS TNF-ALPHA INHIBITORS
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1137640A1

  公开（公告）日：2001-10-04
• US6239151B1
  申请人：——

  公开号：US6239151B1

  公开（公告）日：2001-05-29