钙蛋白酶抑制剂VI | 190274-53-4

• 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
• 中文名称: 钙蛋白酶抑制剂VI
• 英文名称: N-((4-Fluorophenyl)sulfonyl)-L-valyl-L-leucinal
• 英文别名: SJA 6017；calpain inhibitor VI；(2S)-2-[(4-fluorophenyl)sulfonylamino]-3-methyl-N-[(2S)-4-methyl-1-oxopentan-2-yl]butanamide
• CAS: 190274-53-4
• 化学式: C₁₇H₂₅FN₂O₄S
• 分子量: 372.461
• InChiKey: WSJWUIDLGZAXID-HOCLYGCPSA-N

物化性质

• 密度：
  1.185±0.06 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：5mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  钙蛋白酶抑制剂VI 在 吡啶 、 戴斯-马丁氧化剂 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 36.0h， 生成 (3S)-N-butyl-3-((2S)-2-(((4-fluorophenyl)sulfonyl)amino)-3-methylbutanoylamino)-5-methyl-2-oxohexanamide
  参考文献：
  名称：

  Exploration of cornea permeable calpain inhibitors as anticataract agents

  摘要：

  To explore cornea permeable calpain inhibitors, four compounds displaying different characteristics were designed and synthesized based on the known potent calpain inhibitor, peptidyl aldehyde SJA6017. Two approaches were adopted; an improvement in the physicochemical properties, and conversion of the active aldehyde. The water-soluble peptidyl aldehyde 1 containing a pyridine ring at the P3 site showed a modest inhibition against calpains and an improvement of corneal permeability in comparison with SJA6017. Replacement of the aldehyde of SJA6017 by an alpha-ketoamide provided compound 2 that was approximately equipotent with SJA6017, but it was extremely water-in soluble. However, compound 3, in which the aldehyde was converted into a cyclic hemiacetal, proved to be a less potent calpain inhibitor than SJA6017, but demonstrated excellent transcorneal permeability. Further modification generating the cyclic hermacetal 4 containing a thiourea linker between the P3 and P2 sites exhibited potent inhibitory activities, high cornea permeability and excellent efficacy in the rat lens culture cataract model. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00612-0
• 作为产物：
  描述：

  L-缬氨酸甲酯 在 氢氧化钾 、 二异丁基氢化铝 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 34.0h， 生成 钙蛋白酶抑制剂VI
  参考文献：
  名称：

  基于 α-和 β-氨基酸的肽醛：合成、抑制 m-Calpain 和抗白内障特性

  摘要：

  我们提出了 SJA6017（一种有效的 m-钙蛋白酶抑制剂）的新合成方法及其适应物，以制备其中的组成 Leu 和 Val 残基系统地被其相应的 β-氨基酸和/或 N-末端氟苯磺酰基取代的类似物被水溶性N-吡啶-3-基甲氧羰基取代。所有化合物均已针对 m-calpain 进行了测定，并且最好的抑制剂 SJA6017 已被证明可抑制晶状体培养系统设计中的混浊发展以模拟白内障。

  DOI：

  10.1071/ch04080

文献信息

• [EN] PHARMACEUTICAL COMPOSITIONS WITH IMPROVED DISSOLUTION<br/>[FR] COMPOSITIONS PHARMACEUTIQUES A DISSOLUTION AMELIOREE
  申请人：TRANSFORM PHARMACEUTICALS INC

  公开号：WO2004000284A1

  公开（公告）日：2003-12-31

  The invention relates to methods of screening mixtures containing a pharmaceutical compound an excipient to identify properties of the pharmaceutical compound/excipient combination that retard solid-state nucleation. The invention further relates to increasing the solubility, dissolution and bioavailability of a drug with low solubility in gastric fluids conditions by combining the drug with a recrystallization/precipitation retardant and an optional enhancer.

  本发明涉及筛选包含药物化合物和赋形剂的混合物的方法，以识别延缓固态成核的药物化合物/赋形剂组合的特性。该发明还涉及通过将药物与再结晶/沉淀抑制剂和可选增效剂结合，来增加低溶解度药物在胃液条件下的溶解度、溶出性和生物利用度。
• Pharmaceutical compositions with improved dissolution
  申请人：Tawa Mark

  公开号：US20060134198A1

  公开（公告）日：2006-06-22

  The invention relates to methods of screening mixtures containing a pharmaceutical compound and an excipient to identify properties of the pharmaceutical compound/excipient combination that retard solid-state nucleation. The invention further relates to increasing the solubility, dissolution and bioavailability of a drug with low solubility in gastric fluids conditions by combining the drug with a precipitation retardant and an optional enhancer.

  本发明涉及筛选混合物的方法，该混合物含有药物化合物和赋形剂，以识别药物化合物/赋形剂组合的性质，以延缓固态成核。本发明还涉及通过将药物与沉淀抑制剂和可选增效剂结合，在胃液条件下增加低溶解度药物的溶解度、溶出度和生物利用度的方法。
• Novel alpha-ketomide derivative and use thereof
  申请人：Nakamura Masayuki

  公开号：US20050165113A1

  公开（公告）日：2005-07-28

  The present invention provides a compound represented by the formula (I): wherein R 1 , R 2 and R 3 each represents a lower alkyl group.

  本发明提供了一种由公式（I）表示的化合物：其中R1、R2和R3各代表低碳基团。
• OPHTHALMIC ADHESIVE PREPARATIONS FOR PERCUTANEOUS ABSORPTION
  申请人：Senju Pharmaceutical Co., Ltd.

  公开号：EP1221315A1

  公开（公告）日：2002-07-10

  Ophthalmic transdermal patches are disclosed for treating diseases of the posterior segment of the eye comprising a drug-containing layer uniformly containing in a base matrix a percutaneous absorption enhancer, which is polyoxyethylene oleyl ether and/or isopropyl myristate, and a drug to be delivered to the posterior segment of the eye including the lens, the vitreous body, the uvea and the retina.

  本发明公开了用于治疗眼球后段疾病的眼科透皮贴片，该贴片包括一个含药层，在基质中均匀地含有一种经皮吸收促进剂，该促进剂是聚氧乙烯油基醚和/或肉豆蔻酸异丙酯，以及一种要输送到眼球后段（包括晶状体、玻璃体、葡萄膜和视网膜）的药物。
• AQUEOUS SUSPENSION PREPARATIONS
  申请人：Senju Pharmaceutical Co., Ltd.

  公开号：EP1312356A1

  公开（公告）日：2003-05-21

  Addition of polyvinylpyrrolidone and a water-soluble anionic macromolecular compound to an aqueous suspension of a hardly soluble drug allows to provide an aqueous suspension in which aggregation of drug particles, formation of macro crystals from suspended particles and formation of secondary particles from deposited particles are prevented, and adhesion and adsorption to containers made of plastics, e.g., polypropylene or polyethylene, are avoided. As it has a good redispersibility, the aqueous suspension is useful as eye drops, nasal drops, ear drops, injections, oral preparations, liniments and lotions.

  在难溶性药物的水悬浮液中加入聚乙烯吡咯烷酮和水溶性阴离子大分子化合物，可以提供一种水悬浮液，在这种水悬浮液中，药物颗粒不会聚集，悬浮颗粒不会形成大晶体，沉积颗粒不会形成二次颗粒，也不会粘附和吸附在聚丙烯或聚乙烯等塑料容器上。由于水悬液具有良好的再分散性，因此可用作滴眼剂、滴鼻剂、滴耳剂、注射剂、口服制剂、药剂和洗剂。