(S)-2-Amino-N-[(S)-1-(4-chloro-benzyl)-2-ethylcarbamoyl-2-hydroxy-ethyl]-3-methyl-butyramide | 748143-81-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (S)-2-Amino-N-[(S)-1-(4-chloro-benzyl)-2-ethylcarbamoyl-2-hydroxy-ethyl]-3-methyl-butyramide
• 英文别名: H-Val-bAla(2-OH,3S-Bn(4-Cl))-NHEt；(2S)-2-amino-N-[(2S)-1-(4-chlorophenyl)-4-(ethylamino)-3-hydroxy-4-oxobutan-2-yl]-3-methylbutanamide
• CAS: 748143-81-9
• 化学式: C₁₇H₂₆ClN₃O₃
• 分子量: 355.865
• InChiKey: KPRVYHGBOMCBAC-ZYOSVBKOSA-N

物化性质

• 熔点：
  187-190 °C
• 沸点：
  640.6±55.0 °C(Predicted)
• 密度：
  1.196±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  104
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-2-Amino-N-[(S)-1-(4-chloro-benzyl)-2-ethylcarbamoyl-2-hydroxy-ethyl]-3-methyl-butyramide 在 戴斯-马丁氧化剂 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-((S)-1-((S)-1-(4-chlorophenyl)-4-(ethylamino)-3,4-dioxobutan-2-ylamino)-3-methyl-1-oxobutan-2-yl)-5-(1,2-dithiolan-3-yl)pentanamide
  参考文献：
  名称：

  Novel cell-penetrating α-keto-amide calpain inhibitors as potential treatment for muscular dystrophy

  摘要：

  Dipeptide-derived alpha-keto-amide compounds with potent calpain inhibitory activity have been identified. These reversible covalent inhibitors have IC50 values down to 25 nM and exhibit greatly improved activity in muscle cells compared to the reference compound MDL28170. Several novel calpain inhibitors have shown positive effects on histological parameters in an animal model of Duchenne muscular dystrophy demonstrating their potential as a treatment option for this fatal disease. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.08.064
• 作为产物：
  描述：

  tert-butyl N-[(2S)-3-(4-chlorophenyl)-1-[methoxy(methyl)amino]-1-oxopropan-2-yl]carbamate 在 lithium aluminium tetrahydride 、 三乙胺 、 三氟乙酸 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 生成 (S)-2-Amino-N-[(S)-1-(4-chloro-benzyl)-2-ethylcarbamoyl-2-hydroxy-ethyl]-3-methyl-butyramide
  参考文献：
  名称：

  Novel cell-penetrating α-keto-amide calpain inhibitors as potential treatment for muscular dystrophy

  摘要：

  Dipeptide-derived alpha-keto-amide compounds with potent calpain inhibitory activity have been identified. These reversible covalent inhibitors have IC50 values down to 25 nM and exhibit greatly improved activity in muscle cells compared to the reference compound MDL28170. Several novel calpain inhibitors have shown positive effects on histological parameters in an animal model of Duchenne muscular dystrophy demonstrating their potential as a treatment option for this fatal disease. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.08.064

文献信息

• Alpha-Keto carbonyl calpain inhibitors
  申请人：MyoContract Ltd.

  公开号：EP1454627A1

  公开（公告）日：2004-09-08

  The present invention relates to novel α-keto carbonyl calpain inhibitors for the treatment of neurodegenerative diseases and neuromuscular diseases including Duchenne Muscular Dystrophy, Becker Muscular Dystrophy and other muscular dystrophies. Disuse atrophy and general muscle wasting can also be treated. Generally all conditions where elevated levels of calpains are involved can be treated. The compounds of the invention may also inhibit other thiol proteases such as cathepsin B, cathepsin H, cathepsin L, papain or the like. Multicatalytic Protease (MCP) also known as proteasome may also be inhibited. The compounds of the present invention are also inhibitors of cell damage by oxidative stress through free radicals and can be used to treat mitochondrial disorders and neurodegenerative diseases, where elevated levels of oxidative stress are involved.

  本发明涉及用于治疗神经退行性疾病和神经肌肉疾病，包括杜兴氏肌肉萎缩症、贝克氏肌肉萎缩症和其他肌肉萎缩症的新型α-酮羰基卡尔宁抑制剂。也可以治疗运动不足性萎缩和一般肌肉消耗。通常，所有涉及卡尔宁升高水平的情况都可以得到治疗。本发明的化合物还可以抑制其他硫醇蛋白酶，如卡特普辛B、卡特普辛H、卡特普辛L、木瓜蛋白酶等。多催化蛋白酶（MCP），也称为蛋白酶体，也可以被抑制。本发明的化合物还是通过自由基抑制氧化应激引起的细胞损伤的抑制剂，并可用于治疗涉及氧化应激升高水平的线粒体疾病和神经退行性疾病。
• Alpha-Keto Carbonyl Calpain Inhibitors
  申请人：Weyermann Philipp

  公开号：US20070293486A1

  公开（公告）日：2007-12-20

  The present invention relates to novel α-keto carbonyl calpain inhibitors for the treatment of neurodegenerative diseases and neuromuscular diseases including Duchenne Muscular Dystrophy, Becker Muscular Dystrophy and other muscular dystrophies. Disuse atrophy and general muscle wasting can also be treated. Diseases of the eye, in particular cataract, can be treated as well. Generally all condition where elevated levels of calpains are involved can be treated. The compounds of the invention may also inhibit other thiol proteases such as cathepsin B, cathepsin H, cathepsin L, papain or the like. Multicatalytic Protease also known as proteasome may also be inhibited and the compounds can therefore be used to treat cell proliferative diseases such as cancer, psoriasis, and restenosis. The compounds of the present invention are also inhibitors of cell damage by oxidative stress through free radicals can be used to treat mitochondrial disorders and neurodegenerative diseases, where elevated levels of oxidative stress are involved. In addition they introduce the expression of utrophin, which is beneficial for the treatment of Duchenne Muscular Dystrophy and Becker Muscular Dystrophy.
• [EN] ALPHA-KETO CARBONYL CALPAIN INHIBITORS<br/>[FR] INHIBITEURS DE CALPAINE DE TYPE ALPHA-CETO CARBONYLE
  申请人：MYOCONTRACT LTD

  公开号：WO2004078908A2

  公开（公告）日：2004-09-16

  The present invention relates to novel α-keto carbonyl calpain inhibitors for the treatment of neurodegenerative diseases and neuromuscular diseases including Duchenne Muscular Dystrophy, Becker Muscular Dystrophy and other muscular dystrophies. Disuse atrophy and general muscle wasting can also be treated. Diseases of the eye, in particular cataract, can be treated as well. Generally all conditions where elevated levels of calpains are involved can be treated. The compounds of the invention may also inhibit other thiol proteases such as cathepsin B, cathepsin H, cathepsin L, papain or the like. Multicatalytic Protease (MCP) also known as proteasome may also be inhibited and the compounds can therefore be . used to treat cell proliferative diseases such as cancer, psoriasis, and restenosis. The compounds of the present invention are also inhibitors of cell damage by oxidative stress through free radicals and can be used to treat mitochondrial disorders and neurodegenerative diseases, where elevated levels of oxidative stress are involved.
• [EN] ALPHA-KETO CARBONYL CALPAIN INHIBITORS<br/>[FR] INHIBITEURS ALPHA-CÉTOCARBONYLES DE CALPAÏNES
  申请人：SANTHERA PHARMACEUTICALS CH

  公开号：WO2006021413A1

  公开（公告）日：2006-03-02

  The present invention relates to novel α-keto carbonyl calpain inhibitors for the treatment of neurodegenerative diseases and neuromuscular diseases including Duchenne Muscular Dystrophy, Becker Muscular Dystrophy and other muscular dystrophies. Disuse atrophy and general muscle wasting can also be treated. Diseases of the eye, in particular cataract, can be treated as well. Generally all conditions where elevated levels of calpains are involved can be treated. The compounds of the invention may also inhibit other thiol proteases such as cathepsin B, cathepsin H, cathepsin L, papain or the like. Multicatalytic Protease also known as proteasome may also be inhibited and the compounds can therefore be used to treat cell proliferative diseases such as cancer, psoriasis, and restenosis. The compounds of the present invention are also inhibitors of cell damage by oxidative stress through free radicals and can be used to treat mitochondrial disorders and neurodegenerative diseases, where elevated levels of oxidative stress are involved. In addition they induce the expression of utrophin, which is beneficial for the treatment of Duchenne Muscular Dystrophy and Becker Muscular Dystrophy.
• [EN] ALPHA-KETO CARBONYL CALPAIN INHIBITORS<br/>[FR] INHIBITEURS D'ALPHA-CETO CARBONYLE CALPAINE
  申请人：SANTHERA PHARMACEUTICALS CH

  公开号：WO2006021409A1

  公开（公告）日：2006-03-02

  The present invention relates to novel α-keto carbonyl calpain inhibitors for the treatment of neurodegenerative diseases and neuromuscular diseases including Duchenne Muscular Dystrophy, Becker Muscular Dystrophy and other muscular dystrophies. Disuse atrophy and general muscle wasting can also be treated. Diseases of the eye, in particular cataract, can be treated as well. Generally all condition where elevated levels of calpains are involved can be treated. The compounds of the invention may also inhibit other thiol proteases such as cathepsin B, cathepsin H, cathepsin L, papain or the like. Multicatalytic Protease also known as proteasome may also be inhibited and the compounds can therefore be used to treat cell proliferative diseases such as cancer, psoriasis, and restenosis. The compounds of the present invention are also inhibitors of cell damage by oxidative stress through free radicals can be used to treat mitochondrial disorders and neurodegenerative diseases, where elevated levels of oxidative stress are involved. In addition they induce the expression of utrophin, which is beneficial for the treatment of Duchenne Muscular Dystrophy and Becker Muscular Dystrophy.