[(S)-1-(Cyano-hydroxy-methyl)-pentyl]-carbamic acid tert-butyl ester | 274685-84-6

• 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: [(S)-1-(Cyano-hydroxy-methyl)-pentyl]-carbamic acid tert-butyl ester
• 英文别名: tert-butyl (1S)-1-[cyano(hydroxy)methyl]pentylcarbamate；tert-butyl N-[(2S)-1-cyano-1-hydroxyhexan-2-yl]carbamate
• CAS: 274685-84-6
• 化学式: C₁₂H₂₂N₂O₃
• 分子量: 242.318
• InChiKey: MNNQMHUVVVUWFL-RGURZIINSA-N

物化性质

• 沸点：
  401.8±35.0 °C(Predicted)
• 密度：
  1.050±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  82.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [(S)-1-(Cyano-hydroxy-methyl)-pentyl]-carbamic acid tert-butyl ester 在 盐酸 、 sodium hydroxide 、 二碳酸二叔丁酯 作用下， 以 四氢呋喃 为溶剂， 生成 (2RS,3S)-2-hydroxy-3-[N-(2-methyl-2-propyloxycarbonyl)amino]heptanoic acid
  参考文献：
  名称：

  Design of small molecule ketoamide-based inhibitors of cathepsin K

  摘要：

  A novel series of ketoamide-based inhibitors of cathepsin K has been identified. Modifications to p(2) and p(3) elements were crucial to enhancing inhibitory activity. Although not optimized, a selected inhibitor was effective in attenuating type 1 collagen hydrolysis in a surrogate assay of bone resorption. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.11.029
• 作为产物：
  描述：

  N-Boc-L-正亮氨酸 在 N-甲基吗啉 、 lithium aluminium tetrahydride 、 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 四氢呋喃 、 二氯甲烷 、 氯仿 为溶剂， 反应 34.5h， 生成 [(S)-1-(Cyano-hydroxy-methyl)-pentyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  [EN] CALPAIN MODULATORS AND THERAPEUTIC USES THEREOF
  [FR] MODULATEURS DE CALPAIN ET LEURS UTILISATIONS THÉRAPEUTIQUES

  摘要：

  公开号：

  WO2018064119A8

文献信息

• [EN] ALPHA-KETOAMIDE DERIVATIVES AS CATHEPSIN K INHIBITORS<br/>[FR] DERIVES D'ALPHA-CETOAMIDE UTILISES EN TANT QU'INHIBITEURS DE LA CATHEPSINE K
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2003013518A1

  公开（公告）日：2003-02-20

  Biaryl ketoamide derivatives (I), which are useful as cathepsin K inhibitors are described herein. The described invention also includes methods of making such biaryl ketoamide derivatives as well as methods of using the same in the treatment of disorders, including osteoporosis, associated with enhanced bone turnover which can ultimately lead to fracture.

  本文描述了有用于作为蛋白酶K抑制剂的双芳基酮酰胺衍生物(I)。所述的发明还包括制备这种双芳基酮酰胺衍生物的方法，以及在治疗与增强骨转换相关的疾病，包括骨质疏松症，最终可能导致骨折的方法。
• Derivatives of 1-(oxoaminoacetyl) pentylcarbamate as cathepsin k inhibitors for the treatment of bone loss
  申请人：Barrett Gene David

  公开号：US20050245596A1

  公开（公告）日：2005-11-03

  Heterocycle substituted ketoamide derivatives of Formula (I), wherein the substitutes A, D, A and R are defined as in claim in, which are useful as cathepsin K inhibitors are described herein. The described invention also includes methods of making such heterocycle substituted ketoamide derivatives as well as method of using the same in the manufacture of medicaments for the treatment of disorders, including osteoporosis, associated with an imbalance between bone resorption and formation which can ultimately lead to fracture.

  本文描述了公式(I)的杂环取代酮酰胺衍生物，其中替代基A、D、A和R如权利要求中所定义，这些衍生物可用作卡特普西林K抑制剂。所述发明还包括制备这种杂环取代酮酰胺衍生物的方法，以及使用它们制造治疗与骨吸收和形成失衡有关的疾病（例如骨质疏松症），最终可能导致骨折的药物的方法。
• Cyclic amide derivatives
  申请人：Fujirebio Kabushiki Kaisha

  公开号：US06117870A1

  公开（公告）日：2000-09-12

  A cyclic amide derivative of formula (I): ##STR1## wherein R.sup.1 represents a substituted alkyl group, a substituted alkenyl group, a substituted amino group, a substituted alkoxyl group, a substituted alkylthio group, a substituted carbamoyl group, a substituted sulfonamide group or a substituted amide group; the ring A represents a saturated cyclic alkyl group with 5 to 7 carbon atoms or a hetero-atom-containing saturated heterocyclic group with 3 to 6 carbon atoms; R.sup.2 represents a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted aromatic hydrocarbon group or a substituted or unsubstituted heterocyclic group; R.sup.3 represents a hydrogen atom, a group represented by the general formula R.sup.4 O-- or a group represented by the general formula R.sup.5 (R.sup.6)N-- wherein R.sup.4 represents hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted aromatic hydrocarbon group or a substituted or unsubstituted heterocyclic group; R.sup.5 and R.sup.6 may be the same or different and each represents a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted aromatic hydrocarbon group or a substituted or unsubstituted heterocyclic group. The cyclic amide derivative of formula (I) have a strong and selective inhibitory action of a cathepsin K and a clinical efficacy when administered orally.

  公式（I）的环酰胺衍生物：##STR1## 其中R.sup.1表示取代的烷基，取代的烯基，取代的氨基，取代的烷氧基，取代的烷硫基，取代的氨基甲酰基，取代的磺酰胺基或取代的酰胺基；环A表示具有5到7个碳原子的饱和环烷基或具有3到6个碳原子的含杂原子的饱和杂环基；R.sup.2表示氢原子，取代或未取代的烷基，取代或未取代的芳香族碳氢基或取代或未取代的杂环基；R.sup.3表示氢原子，由一般式R.sup.4 O--表示的基团或由一般式R.sup.5（R.sup.6）N--表示的基团，其中R.sup.4表示氢原子，取代或未取代的烷基，取代或未取代的芳香族碳氢基或取代或未取代的杂环基；R.sup.5和R.sup.6可以相同也可以不同，且每个表示氢原子，取代或未取代的烷基，取代或未取代的芳香族碳氢基或取代或未取代的杂环基。公式（I）的环酰胺衍生物具有强大且选择性的抑制猫hepsin K的作用，且口服时具有临床疗效。
• Derivatives of 1-(oxoaminoacetyl) pentylcarbamate as cathepsin K inhibitors for the treatment of bone loss
  申请人：SmithKline Beecham Corporation

  公开号：US07402606B2

  公开（公告）日：2008-07-22

  Heterocycle substituted ketoamide derivatives of Formula (I), wherein the substitutes A, D, A and R are defined as in claim in, which are useful as cathepsin K inhibitors are described herein. The described invention also includes methods of making such heterocycle substituted ketoamide derivatives as well as method of using the same in the manufacture of medicaments for the treatment of disorders, including osteoporosis, associated with an imbalance between bone resorption and formation which can ultimately lead to fracture.

  本文描述了公式（I）的杂环取代酮酰胺衍生物，其中替代物A、D、A和R如权利要求中所定义，这些衍生物对于作为卡他普星K抑制剂是有用的。所述发明还包括制备这种杂环取代酮酰胺衍生物的方法，以及使用它们制造治疗与骨吸收和形成不平衡相关的疾病，包括骨质疏松症，最终可能导致骨折的药物的方法。
• KETOAMIDE IMMUNOPROTEASOME INHIBITORS
  申请人：HOFFMANN-LA ROCHE INC.

  公开号：US20150274777A1

  公开（公告）日：2015-10-01

  The invention is concerned with the compounds of formula (I): and pharmaceutically acceptable salts thereof, wherein X, R 1 , R 1′ , R 2 , R 2′ , R 3 , R 4 , R 4′ and R 5 are defined in the detailed description and claims. In addition, the present invention relates to methods of manufacturing and using the compounds of formula (I) as well as pharmaceutical compositions containing such compounds. The compounds of formula (I) are LMP7 inhibitors and may be useful in treating associated inflammatory diseases and disorders such as, for example, rheumatoid arthritis, lupus and irritable bowel disease.

  本发明涉及式(I)的化合物及其药学上可接受的盐，其中X、R1、R1'、R2、R2'、R3、R4、R4'和R5在详细说明书和权利要求中有定义。此外，本发明还涉及制造和使用式(I)化合物的方法，以及含有这种化合物的药物组合物。式(I)化合物是LMP7抑制剂，可能有用于治疗相关的炎症性疾病和疾病，例如类风湿性关节炎、狼疮和肠易激综合症。