(2S,3S)-N-[(2S)-1-hydroxy-3-phenylpropan-2-yl]-3-methyl-2-(naphthalen-1-ylsulfonylamino)pentanamide | 161709-15-5

• 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: (2S,3S)-N-[(2S)-1-hydroxy-3-phenylpropan-2-yl]-3-methyl-2-(naphthalen-1-ylsulfonylamino)pentanamide
• CAS: 161709-15-5
• 化学式: C₂₅H₃₀N₂O₄S
• 分子量: 454.59
• InChiKey: IMETYNGOQPDBHC-XZOYJPPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  32
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S,3S)-N-[(2S)-1-hydroxy-3-phenylpropan-2-yl]-3-methyl-2-(naphthalen-1-ylsulfonylamino)pentanamide 在 pyridine-SO3 complex 、 二甲基亚砜 、 三乙胺 作用下， 反应 0.83h， 以67%的产率得到(2S,3S)-3-methyl-2-(naphthalen-1-ylsulfonylamino)-N-[(2S)-1-oxo-3-phenylpropan-2-yl]pentanamide
  参考文献：
  名称：

  Synthesis of Peptide Aldehyde Derivatives as Selective Inhibitors of Human Cathepsin L and Their Inhibitory Effect on Bone Resorption

  摘要：

  Cathepsin L, a lysosomal cysteine protease, is secreted by osteoclasts and participates in bone collagen degradation. In a search for cathepsin L inhibitors as antiosteoporotic agents, a series of peptide aldehyde derivatives were prepared by two synthetic approaches, DMSO oxidation of the corresponding alcohol derivatives and DIBAL-H reduction of the corresponding N,O-dimethylhydroxylamide derivatives, and evaluated for inhibitory activity against human cathepsin L and for inhibitory effects on bone resorption. Some of the peptide aldehyde derivatives including alpha-acylamino aldehyde derivatives showed potent activities. Among these compounds, N-(1-naphthalenylsulfonyl-L-isoleucyl-L-tryptophanal (12) was selected as a candidate for further investigation. Compound 12, a potent, selective, and reversible inhibitor of human cathepsin L with an IC50 Of 1.9 nM, inhibited the release of Ca2+ and hydroxyproline from bone in in vitro bone culture system and also prevented bone loss in ovariectomized mice at an oral dose of 50 mg/kg.

  DOI：

  10.1021/jm9803065
• 作为产物：
  描述：

  Z-L-苯丙氨醇 在 palladium on activated charcoal 4-二甲氨基吡啶 、 氢气 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 22.0h， 生成 (2S,3S)-N-[(2S)-1-hydroxy-3-phenylpropan-2-yl]-3-methyl-2-(naphthalen-1-ylsulfonylamino)pentanamide
  参考文献：
  名称：

  Synthesis of Peptide Aldehyde Derivatives as Selective Inhibitors of Human Cathepsin L and Their Inhibitory Effect on Bone Resorption

  摘要：

  Cathepsin L, a lysosomal cysteine protease, is secreted by osteoclasts and participates in bone collagen degradation. In a search for cathepsin L inhibitors as antiosteoporotic agents, a series of peptide aldehyde derivatives were prepared by two synthetic approaches, DMSO oxidation of the corresponding alcohol derivatives and DIBAL-H reduction of the corresponding N,O-dimethylhydroxylamide derivatives, and evaluated for inhibitory activity against human cathepsin L and for inhibitory effects on bone resorption. Some of the peptide aldehyde derivatives including alpha-acylamino aldehyde derivatives showed potent activities. Among these compounds, N-(1-naphthalenylsulfonyl-L-isoleucyl-L-tryptophanal (12) was selected as a candidate for further investigation. Compound 12, a potent, selective, and reversible inhibitor of human cathepsin L with an IC50 Of 1.9 nM, inhibited the release of Ca2+ and hydroxyproline from bone in in vitro bone culture system and also prevented bone loss in ovariectomized mice at an oral dose of 50 mg/kg.

  DOI：

  10.1021/jm9803065

文献信息

• ALDEHYDE DERIVATIVES AS UPSTEINE PROTEASE INHIBITORS
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP0783489A1

  公开（公告）日：1997-07-16
• [EN] ALDEHYDE DERIVATIVES AS UPSTEINE PROTEASE INHIBITORS<br/>[FR] DERIVES ALDEHYDES UTILISES COMME INHIBITEURS DE PROTEASE D'UPSTEINE
  申请人：TAKEDA CHEMICAL INDUSTRIES, LTD.

  公开号：WO1996010014A1

  公开（公告）日：1996-04-04

  (EN) The present invention relates to a compound of formula (Ia'), wherein Q' stands for one or two amino acid residual groups which may be substituted; R1 stands for a hydrogen atom or an optinally substituted hydrocarbon or heterocyclic group; R4 stands for an optionally esterified carboxy group or an acyl group; and X stands for an optionally substituted straight-chain or branched divalent hydrocarbon group having a chain length of 1 to 4 atoms as the linear moiety, or a salt thereof, which has strong cysteine protease inhibitory activities and is a useful prophylactic and therapeutic agent of various diseases, including bone diseases, caused by abnormal exasperation of cysteine protease.(FR) Composé de la formule (Ia'). Dans cette formule, Q' représente un ou deux groupes acides aminés résiduels pouvant être substitués; R1 représente un atome d'hydrogène ou un groupe hydrocarbure ou hétérocyclique facultativement substitué; R4 représente un groupe carboxyle ou un groupe acyle facultativement estérifié; et X représente un groupe hydrocarbure divalent ramifié ou à chaîne linéaire facultativement substitués présentant une longueur de chaîne de 1 à 4 atomes comme fraction linéaire, ou un sel de cette substance, exerçant une puissante activité inhibitrice de la protéase de la cystéine et se révélant utile comme agent prophylactique et thérapeutique contre diverses maladies, notamment les maladies osseuses, causées par un déréglement de la protéase de la cystéine.
• Synthesis of Peptide Aldehyde Derivatives as Selective Inhibitors of Human Cathepsin L and Their Inhibitory Effect on Bone Resorption
  作者：Tsuneo Yasuma、Satoru Oi、Nobuo Choh、Toshiyuki Nomura、Naoki Furuyama、Atsushi Nishimura、Yukio Fujisawa、Takashi Sohda

  DOI：10.1021/jm9803065

  日期：1998.10.1

  Cathepsin L, a lysosomal cysteine protease, is secreted by osteoclasts and participates in bone collagen degradation. In a search for cathepsin L inhibitors as antiosteoporotic agents, a series of peptide aldehyde derivatives were prepared by two synthetic approaches, DMSO oxidation of the corresponding alcohol derivatives and DIBAL-H reduction of the corresponding N,O-dimethylhydroxylamide derivatives, and evaluated for inhibitory activity against human cathepsin L and for inhibitory effects on bone resorption. Some of the peptide aldehyde derivatives including alpha-acylamino aldehyde derivatives showed potent activities. Among these compounds, N-(1-naphthalenylsulfonyl-L-isoleucyl-L-tryptophanal (12) was selected as a candidate for further investigation. Compound 12, a potent, selective, and reversible inhibitor of human cathepsin L with an IC50 Of 1.9 nM, inhibited the release of Ca2+ and hydroxyproline from bone in in vitro bone culture system and also prevented bone loss in ovariectomized mice at an oral dose of 50 mg/kg.