(2RS,3S)-2-hydroxy-4-methyl-3-[[(1,1-dimethylethoxy)carbonyl]amino]pentanoic acid

• 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: (2RS,3S)-2-hydroxy-4-methyl-3-[[(1,1-dimethylethoxy)carbonyl]amino]pentanoic acid
• 英文别名: (3S)-2-hydroxy-4-methyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoic acid
• 化学式: C₁₁H₂₁NO₅
• 分子量: 247.291
• InChiKey: COFHICKJCPSJGE-JAMMHHFISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  95.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2RS,3S)-2-hydroxy-4-methyl-3-[[(1,1-dimethylethoxy)carbonyl]amino]pentanoic acid 在 盐酸 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 33.67h， 生成 benzyl 3-(N-tert-butoxycarbonyl-O-benzyl-L-serylamino)-2-hydroxy-4-methylpentanoyl-O-benzyl-Lseryl-O-allyl-L-tyrosyl-N_ε-benzyloxycarbonyl-L-β-lysyl-L-alaninate
  参考文献：
  名称：

  Myxoprincomide 的全合成，一种来自 Myxococcus xanthus 的次级代谢产物

  摘要：

  Myxoprincomide 是粘杆菌 Myxococcus xanthus DK 1622 的次级代谢产物，首次合成。中心的、不寻常的 α-酮酰胺是在合成结束时产生的，以避免在合成这种相当活泼的亚基过程中发生副反应。然而，合成天然产物是作为异构混合物获得的。详细的分析研究表明，在分离的天然产物中发现了相同的异构体混合物。

  DOI：

  10.1039/d2ob02021a
• 作为产物：
  描述：

  N-benzyloxycarbonyl-L-valinal 在 盐酸 、 水 、 sodium hydrogensulfite 、 苯甲醚 、 三乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 61.5h， 生成 (2RS,3S)-2-hydroxy-4-methyl-3-[[(1,1-dimethylethoxy)carbonyl]amino]pentanoic acid
  参考文献：
  名称：

  The Discovery of Potent, Selective, and Reversible Inhibitors of the House Dust Mite Peptidase Allergen Der p 1: An Innovative Approach to the Treatment of Allergic Asthma

  摘要：

  Blocking the bioactivity of allergens is conceptually attractive as a small-molecule therapy for allergic diseases but has not been attempted previously. Group 1 allergens of house dust mites (HDM) are meaningful targets in this quest because they are globally prevalent and clinically important triggers of allergic asthma. Group 1 HDM allergens are cysteine peptidases whose proteolytic activity triggers essential steps in the allergy cascade. Using the HDM allergen Der p 1 as an archetype for structure-based drug discovery, we have identified a series of novel, reversible inhibitors. Potency and selectivity were manipulated by optimizing drug interactions with enzyme binding pockets, while variation of terminal groups conferred the physicochemical and pharmacokinetic attributes required for inhaled delivery. Studies in animals challenged with the gamut of HDM allergens showed an attenuation of allergic responses by targeting just a single component, namely, Der p 1. Our findings suggest that these inhibitors may be used as novel therapies for allergic asthma.

  DOI：

  10.1021/jm501102h

文献信息

• ALPHA-OXOACYL AMINO-CAPROLACTAM DERIVATIVE
  申请人：SEIKAGAKU CORPORATION

  公开号：US20160137691A1

  公开（公告）日：2016-05-19

  The purpose of the present invention is to provide a pharmaceutical composition that is useful for the treatment of diseases that are caused by an increase in bone resorption and that does not cause serious side effects even when used in combination with another drug. The present invention relates to: an α-oxoacyl aminocaprolactam derivative that is represented by formula (I) (in the formula, X is —O— or —N(R 1 )— and R 1 represents an alkoxycarbonyl group having 1-10 carbon atoms); and a bone resorption inhibitor containing the α-oxoacyl aminocaprolactam derivative.

  本发明的目的是提供一种药物组合物，用于治疗由骨吸收增加引起的疾病，并且即使与另一种药物联合使用也不会引起严重副作用。本发明涉及以下内容：一种由式（I）表示的α-氧代酰氨基己内酯衍生物 （在该式中，X为—O—或—N(R 1 )—，R 1 表示具有1-10个碳原子的烷氧羰基基团）；以及含有α-氧代酰氨基己内酯衍生物的骨吸收抑制剂。
• ALPHA-OXOACYL AMINO-CAPROLACTAM BODY
  申请人：SEIKAGAKU CORPORATION

  公开号：US20160130266A1

  公开（公告）日：2016-05-12

  The purpose of the present invention is to provide a pharmaceutical composition that is useful for the treatment of diseases that are caused by an increase in bone resorption and that does not cause serious side effects even when used in combination with another drug. The present invention relates to: an α-oxoacyl amino-caprolactam that is represented by formula (I) (in formula (I), X represents N or CH, Y represents O or CH 2 , and Z represents S or CH 2 ); and a bone resorption inhibitor containing the α-oxoacyl amino-caprolactam.

  本发明的目的是提供一种药物组合物，用于治疗由骨吸收增加引起的疾病，并且即使与另一种药物联合使用也不会引起严重副作用。本发明涉及：由式（I）表示的α-氧代酰氨基己内酯 （在式（I）中，X代表N或CH，Y代表O或CH 2 ，Z代表S或CH 2 ）；以及含有α-氧代酰氨基己内酯的骨吸收抑制剂。
• Pyruvamide Compounds as Inhibitors of Dust Mite Group 1 Peptidase Allergen and Their Use
  申请人：Robinson Clive

  公开号：US20120322722A1

  公开（公告）日：2012-12-20

  The present invention pertains generally to the field of therapeutic compounds and more specifically to certain pyruvamide compounds of the formula (X) (for convenience, collectively referred to herein as “PVA compounds”), which, inter alia, inhibit a dust mite Group 1 peptidase allergen (e.g., Der p 1, Der f 1, Eur m 1). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit a dust mite Group 1 peptidase allergen, and in the treatment of diseases and disorders that are mediated by a dust mite Group 1 peptidase allergen; that are ameliorated by the inhibition of a dust mite Group 1 peptidase allergen; asthma; rhinitis; allergic conjunctivitis; atopic dermatitis; an allergic condition which is triggered by dust mites; an allergic condition which is triggered by a dust mite Group 1 peptidase allergen; and canine atopy.

  本发明一般涉及治疗化合物领域，更具体地涉及某些丙酮酰胺化合物的公式（X）（为方便起见，以下统称为“PVA化合物”），该化合物在某些情况下抑制尘螨1组蛋白酶过敏原（例如Der p 1、Der f 1、Eur m 1）。本发明还涉及包含这种化合物的药物组合物，以及在体外和体内使用这种化合物和组合物来抑制尘螨1组蛋白酶过敏原，并用于治疗由尘螨1组蛋白酶过敏原介导的疾病和疾病，通过抑制尘螨1组蛋白酶过敏原而得到缓解的疾病和疾病；哮喘；鼻炎；过敏性结膜炎；特应性皮炎；由尘螨引发的过敏症状；由尘螨1组蛋白酶过敏原引发的过敏症状；以及犬类特应性。
• ALPHA-OXOACYLAMINOCAPROLACTAM
  申请人：Seikagaku Corporation

  公开号：EP3009425B1

  公开（公告）日：2018-06-06
• US8541363B2
  申请人：——

  公开号：US8541363B2

  公开（公告）日：2013-09-24