(2S)-3,3-二甲基-2-甲基氨基-N-[(2S)-4-甲基-2-[[(2S)-2-硫基-4-(3,4,4-三甲基-2,5-二氧代-咪唑烷-1-基)丁酰基]氨基]戊酰]丁酰胺 | 259188-38-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 中文名称: (2S)-3,3-二甲基-2-甲基氨基-N-[(2S)-4-甲基-2-[[(2S)-2-硫基-4-(3,4,4-三甲基-2,5-二氧代-咪唑烷-1-基)丁酰基]氨基]戊酰]丁酰胺
• 英文名称: Rebimastat
• 英文别名: BMS-275291；BMS-27591；2S-[2S-mercapto-4-(3,4, 4-trimethyl-2,5-dioxoimidazolidin-1-yl) butyrylamino]-4-methylpentanoic acid (2,2-dimethyl-1S-methylcarbamoylpropyl) amide；D 2163；(2S)-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-4-methyl-2-[[(2S)-2-sulfanyl-4-(3,4,4-trimethyl-2,5-dioxoimidazolidin-1-yl)butanoyl]amino]pentanamide
• CAS: 259188-38-0
• 化学式: C₂₃H₄₁N₅O₅S
• 分子量: 499.675
• InChiKey: GTXSRFUZSLTDFX-HRCADAONSA-N

物化性质

• 密度：
  1.133±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  34
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  129
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-[2-chloro-4-(1,5,5-trimethylhydantyl)butanoyl]-L-leucyl-L-tert-leucine N-methylamide 在 Amberlite hydrogen sulfide resin 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 10.0h， 以0.055 g的产率得到(2S)-3,3-二甲基-2-甲基氨基-N-[(2S)-4-甲基-2-[[(2S)-2-硫基-4-(3,4,4-三甲基-2,5-二氧代-咪唑烷-1-基)丁酰基]氨基]戊酰]丁酰胺
  参考文献：
  名称：

  Performing the Synthesis of a Complex Molecule on Sequentially Linked Columns:  Toward the Development of a “Synthesis Machine”

  摘要：

  We describe the diastereoselective synthesis of a pharmaceutically active drug candidate via a column-based system. This methodology is complementary to classical solid-phase synthesis; individual columns are packed with resin-bound reagents and then linked in sequence and/or in parallel. In contrast to the traditional solid-phase approach, substrates are introduced in the mobile phase where they build up chemical complexity by percolating through the linked columns, ultimately eluting as the desired product.

  DOI：

  10.1021/ol050980y

文献信息

• Metalloprotein inhibitors containing nitrogen based ligands
  申请人：Cohen Seth M.

  公开号：US20120135959A1

  公开（公告）日：2012-05-31

  Provided herein metalloproteinase inhibitors containing nitrogen or mixed nitrogen/oxygen donating zinc binding groups. Also provided are pharmaceutical compositions containing the compounds and methods of treating preventing or ameliorating the diseases associated with metalloproteinase activity using the compounds and compositions.

  本文提供了含有氮或混合氮/氧供体锌结合基团的金属蛋白酶抑制剂。还提供了含有这些化合物的药物组合物，以及使用这些化合物和组合物治疗、预防或改善与金属蛋白酶活性相关的疾病的方法。
• Compounds and methods for the treatment of pain and other diseases
  申请人：Sucholeiki Irving

  公开号：US20110230452A1

  公开（公告）日：2011-09-22

  The present invention relates generally to pharmaceutical agents, and in particular, to metalloprotease inhibitor compounds. More particularly, the present invention provides a new class of dual acting MMP-2 and MMP-9 inhibiting compounds that exhibit increased potency, metabolic stability and/or reduced toxicity in relation to currently known MMP-2 and MMP-9 inhibitors for the treatment of pain and other diseases. Additionally, the present invention relates to methods for treating pain, addiction and/or withdrawal symptoms in a patient comprising administering to the patient a pain-reducing effective amount of a present compound.

  本发明通常涉及制药剂，特别是金属蛋白酶抑制剂化合物。更具体地，本发明提供了一类新的双重作用MMP-2和MMP-9抑制化合物，这些化合物在与目前已知的MMP-2和MMP-9抑制剂相比具有增强的效力、代谢稳定性和/或降低的毒性，用于治疗疼痛和其他疾病。此外，本发明涉及一种治疗疼痛、成瘾和/或戒断症状的方法，包括向患者施用一定量的具有减轻疼痛作用的本发明化合物。
• [EN] COMPOUNDS AND METHODS FOR THE TREATMENT OF PAIN AND OTHER DISORDERS<br/>[FR] COMPOSÉS ET MÉTHODES DE TRAITEMENT DE LA DOULEUR ET D'AUTRES TROUBLES
  申请人：SUCHOLEIKI IRVING

  公开号：WO2012118498A1

  公开（公告）日：2012-09-07

  The present invention relates generally to pharmaceutical agents, and in particular, to metalloprotease inhibitor compounds. More particularly, the present invention provides a new class of dual acting MMP-2 and MMP-9 inhibiting compounds that exhibit increased potency, metabolic stability and/or reduced toxicity in relation to currently known MMP-2 and MMP-9 inhibitors for the treatment of pain and other diseases. Additionally, the present invention relates to methods for treating pain, addiction and/or withdrawal symptoms in a patient comprising administering to the patient a pain-reducing effective amount of a present compound.

  本发明一般涉及制药剂，特别是金属蛋白酶抑制剂化合物。更具体地说，本发明提供了一类新的双重作用MMP-2和MMP-9抑制化合物，其在与目前已知的MMP-2和MMP-9抑制剂相比，表现出增强的效力、代谢稳定性和/或降低的毒性，用于治疗疼痛和其他疾病。此外，本发明涉及一种治疗疼痛、成瘾和/或戒断症状的方法，包括向患者投予一种疼痛减轻有效量的当前化合物。
• [EN] THIO-SUBSTITUTED PEPTIDES AS INHIBITORS FOR METALLOPROTEINASES AND TNF LIBERATION<br/>[FR] PEPTIDES THIO-SUBSTITUES UTILES COMME INHIBITEURS DE METALLOPROTEASES ET DE LA LIBERATION DU TNF
  申请人：DARWIN DISCOVERY LIMITED

  公开号：WO1997012902A1

  公开（公告）日：1997-04-10

  (EN) Peptide compounds of formula (I). Peptides are inhibitors of (matrix) metalloproteinases like collagenase and stromelysin. Furthermore, they inhibit the liberation of tumor necrosis factor $g(a) (TNF$g(a)).(FR) Cette invention se rapporte à des composés peptidiques de formule (I) qui sont des inhibiteurs des métalloprotéases (matricielles) comme le collagène et la stromélysine. Ils inhibent par ailleurs la libération du facteur de nécrose tumorale $g(a) (TNF$g(a)).

  这是一种公式为(I)的肽化合物。这些肽是(基质)金属蛋白酶如胶原酶和基质金属蛋白酶的抑制剂。此外，它们还抑制肿瘤坏死因子$g(a)(TNF$g(a))的释放。
• [EN] SELECTIVE MMP INHIBITORS HAVING REDUCED SIDE-EFFECTS<br/>[FR] INHIBITEURS SELECTIFS DE LA METALLOPROTEASE MATRICIELLE PRESENTANT DES EFFETS SECONDAIRES REDUITS
  申请人：DARWIN DISCOVERY LIMITED

  公开号：WO1998039024A1

  公开（公告）日：1998-09-11

  (EN) A matrix metalloproteinase (MMP) inhibitor that exhibits an IC50 of below 10-4M against MMP and has substantially no activity against non-MMP metalloproteinase-related events has reduced side-effects, especially with respect to joint pain.(FR) L'invention concerne un inhibiteur de la métalloprotéase matricielle qui présente une concentration inhibitrice 50 de moins de 10-4M contre la métalloprotéase matricielle, et n'exerce sensiblement aucune activité contre les évènements non liés à la métalloprotéase matricielle. Cet inhibiteur présente des effets secondaires réduits, en particulier, dans le domaine des douleurs articulaires.

  一种基质金属蛋白酶（MMP）抑制剂，对MMP的IC50低于10-4M，并且几乎没有对非MMP金属蛋白酶相关事件的活性，具有减少副作用的作用，尤其是对关节疼痛方面的作用。