dibenzyl 3(RS)-tert-butyloxycarbonyl-3-cinnamyl-2(R)-iso-butylsuccinate | 228261-86-7

• 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: dibenzyl 3(RS)-tert-butyloxycarbonyl-3-cinnamyl-2(R)-iso-butylsuccinate
• CAS: 228261-86-7
• 化学式: C₃₆H₄₂O₆
• 分子量: 570.726
• InChiKey: SLEOLJZYZPTPPE-GPUJMSTISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.57
• 重原子数：
  42.0
• 可旋转键数：
  13.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  78.9
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  dibenzyl 3(RS)-tert-butyloxycarbonyl-3-cinnamyl-2(R)-iso-butylsuccinate 在 palladium on activated charcoal N-乙基吗啉 、 硼烷四氢呋喃络合物 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， 反应 13.0h， 生成 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 tert-butoxide 、 氢溴酸 、 sodium hydride 、 对甲苯磺酸 、 sodium nitrite 作用下， 以 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 35.0h， 生成 dibenzyl 3(RS)-tert-butyloxycarbonyl-3-cinnamyl-2(R)-iso-butylsuccinate
  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

• Amino acid derivatives
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0497192A2

  公开（公告）日：1992-08-05

  The invention provides compounds of the formula wherein A represents the group R1 represents hydrogen, amino, protected amino, acylamino or lower alkyl optionally substituted by aryl, hydroxy, protected hydroxy, amino, protected amino, acylamino, maleimido, succinimido, naphthalimido, 2,3-dihydro-1,3-dioxo-lH-benz[d,e]isoquinol-2-yl, carboxy, protected carboxy, carbamoyl, mono(lower alkyl)-carbamoyl, di(lower alkyl)carbamoyl, di(lower alkyl)amino, carboxy-lower alkanoylamino, pyrrolidino or morpholino; R2 represents hydrogen or lower alkyl optionally substituted by aryl, amino, protected amino, di(lower alkyl)- amino, guanidino, carboxyl, protected carboxyl, carbamoyl, mono(lower alkyl) carbamoyl, di(lower alkyl)-carbamoyl, di(lower alkoxy)phosphinyl, dihydroxyphosphinyl, pyrrolidino, piperidino or morpholino; R3 represents hydrogen or lower alkyl optionally substituted by hydroxy, protected hydroxy, amino or protected amino; R4 represents hydrogen, hydroxy, lower alkoxy or benzyloxy; and R5 represents hydrogen or halogen and their pharmaceutically acceptable salts. These compounds are useful for the control or prevention of degenerative joint diseases or for the treatment of invasive tumours, atherosclerosis or multiple sclerosis. They can be manufactured according to known methods.

  本发明提供了式中化合物 其中 A 代表基团 R1代表氢、氨基、受保护氨基、酰氨基或任选被芳基取代的低级烷基、羟基、受保护羟基、氨基、受保护氨基、酰氨基、马来酰亚胺基、琥珀酰亚胺基、萘酰亚胺基、2、3-二氢-1,3-二氧代-lH-苯并[d,e]异喹啉-2-基、羧基、受保护的羧基、氨基甲酰基、单（低级烷基）氨基甲酰基、二（低级烷基）氨基甲酰基、二（低级烷基）氨基、羧基-低级烷酰氨基、吡咯烷基或吗啉基；R2 代表氢或被芳基、氨基、受保护氨基、二（低级烷基）-氨基、胍基、羧基、受保护羧基、氨基甲酰基、单（低级烷基）氨基甲酰基、二（低级烷基）-氨基甲酰基、二（低级烷氧基）膦酰基、二羟基膦酰基、吡咯烷基、哌啶基或吗啉基任选取代的低级烷基；R3 代表氢或任选被羟基、受保护羟基、氨基或受保护氨基取代的低级烷基；R4 代表氢、羟基、低级烷氧基或苄氧基；R5 代表氢或卤素及其药学上可接受的盐类。这些化合物可用于控制或预防退行性关节疾病，或治疗侵袭性肿瘤、动脉粥样硬化或多发性硬化症。它们可以按照已知的方法制造。
• US5304549A
  申请人：——

  公开号：US5304549A

  公开（公告）日：1994-04-19