(R)-3-((S)-2,2-Dimethyl-1-methylcarbamoyl-propylcarbamoyl)-5-methyl-hexanoic acid tert-butyl ester | 145337-56-0

• 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: (R)-3-((S)-2,2-Dimethyl-1-methylcarbamoyl-propylcarbamoyl)-5-methyl-hexanoic acid tert-butyl ester
• 英文别名: tert-butyl (3R)-3-[[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]carbamoyl]-5-methylhexanoate
• CAS: 145337-56-0
• 化学式: C₁₉H₃₆N₂O₄
• 分子量: 356.506
• InChiKey: BOJBJIBWTGAWOQ-UKRRQHHQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  25
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  84.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-3-((S)-2,2-Dimethyl-1-methylcarbamoyl-propylcarbamoyl)-5-methyl-hexanoic acid tert-butyl ester 在 三氟甲磺酸三甲基硅酯 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 1,4-二氧六环 为溶剂， 生成 (R)-N⁴-Benzyloxy-N¹-((S)-2,2-dimethyl-1-methylcarbamoyl-propyl)-2-isobutyl-succinamide
  参考文献：
  名称：

  Design and synthesis of the cartilage protective agent (CPA, Ro32-3555)

  摘要：

  A novel series of MMP inhibitors has been identified. The compounds are potent selective inhibitors of collagenase with good solubility and oral bioavailability. One compound, designated Ro32-3555, has been selected for development as a cartilage protective agent for use in the treatment of rheumatoid-and osteoarthritis. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00416-2
• 作为产物：
  描述：

  2-(tert-butoxycarbonyl)-(3R)-3-isobutylsuccinic acid 在 N-甲基吗啉 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲苯 为溶剂， 生成 (R)-3-((S)-2,2-Dimethyl-1-methylcarbamoyl-propylcarbamoyl)-5-methyl-hexanoic acid tert-butyl ester
  参考文献：
  名称：

  Design and synthesis of the cartilage protective agent (CPA, Ro32-3555)

  摘要：

  A novel series of MMP inhibitors has been identified. The compounds are potent selective inhibitors of collagenase with good solubility and oral bioavailability. One compound, designated Ro32-3555, has been selected for development as a cartilage protective agent for use in the treatment of rheumatoid-and osteoarthritis. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00416-2

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。
• Design and synthesis of the cartilage protective agent (CPA, Ro32-3555)
  作者：M.J. Broadhurst、P.A. Brown、G. Lawton、N. Ballantyne、N. Borkakoti、K.M.K. Bottomley、M.I. Cooper、A.J. Eatherton、I.R. Kilford、P.J. Malsher、J.S. Nixon、E.J. Lewis、B.M. Sutton、W.H. Johnson

  DOI：10.1016/s0960-894x(97)00416-2

  日期：1997.9

  A novel series of MMP inhibitors has been identified. The compounds are potent selective inhibitors of collagenase with good solubility and oral bioavailability. One compound, designated Ro32-3555, has been selected for development as a cartilage protective agent for use in the treatment of rheumatoid-and osteoarthritis. (C) 1997 Elsevier Science Ltd.