methyl (R)-4-[2-(tert-butyloxycarbonylamino)propyloxy]-3,5-dimethylbenzoate | 942999-00-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl (R)-4-[2-(tert-butyloxycarbonylamino)propyloxy]-3,5-dimethylbenzoate
• 英文别名: methyl (R)-4-(2-(tert-butoxycarbonylamino)propoxy)-3,5-dimethylbenzoate；methyl 3,5-dimethyl-4-[(2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propoxy]benzoate
• CAS: 942999-00-0
• 化学式: C₁₈H₂₇NO₅
• 分子量: 337.416
• InChiKey: QNZJORDXNYRIRY-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  73.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl (R)-4-[2-(tert-butyloxycarbonylamino)propyloxy]-3,5-dimethylbenzoate 在 盐酸 、 氢氧化钾 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 (R)-N-[3-chloro-2-ethoxy-5-(1-piperidinyl)phenyl] 4-[(2-amino)propyloxy]-3,5-dimethylbenzamide dihydrochloride
  参考文献：
  名称：

  Fragment-Based Discovery of Mexiletine Derivatives as Orally Bioavailable Inhibitors of Urokinase-Type Plasminogen Activator

  摘要：

  Fragment-based lead discovery has been applied to urokinase-type plasminogen activator (uPA). The (R)-enantiomer of the orally active drug mexiletine 5 (a fragment hit from X-ray crystallographic screening) was the chemical starting point. Structure-aided design led to elaborated inhibitors that retained the key interactions of (R)-5 while gaining extra potency by simultaneously occupying neighboring regions of the active site. Subsequent optimization led to 15, a potent, selective, and orally bioavailable inhibitor of uPA.

  DOI：

  10.1021/jm701359z
• 作为产物：
  描述：

  4-羟基-3,5-二甲基苯甲酸 在 盐酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 methyl (R)-4-[2-(tert-butyloxycarbonylamino)propyloxy]-3,5-dimethylbenzoate
  参考文献：
  名称：

  Fragment-Based Discovery of Mexiletine Derivatives as Orally Bioavailable Inhibitors of Urokinase-Type Plasminogen Activator

  摘要：

  Fragment-based lead discovery has been applied to urokinase-type plasminogen activator (uPA). The (R)-enantiomer of the orally active drug mexiletine 5 (a fragment hit from X-ray crystallographic screening) was the chemical starting point. Structure-aided design led to elaborated inhibitors that retained the key interactions of (R)-5 while gaining extra potency by simultaneously occupying neighboring regions of the active site. Subsequent optimization led to 15, a potent, selective, and orally bioavailable inhibitor of uPA.

  DOI：

  10.1021/jm701359z

文献信息

• WO2007/72041
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] THERAPEUTIC COMPOUNDS<br/>[FR] COMPOSES THERAPEUTIQUES
  申请人：ASTEX THERAPEUTICS LTD

  公开号：WO2007072041A1

  公开（公告）日：2007-06-28

  [EN] This invention relates to a novel class of substituted amino-ethoxy benzene derivatives of formula (I) which are inhibitors of serine proteases and to their use in treating aberrant serine protease activity in a mammal, contraception, anti-coagulant methods and methods for treating aberrant cell proliferation, tumours, cancer, angiogenesis, angiogenesis-based retinopathies, autoimmummune disease, inflammation, skin disease, arthritis, rheutmatoid arthritis, asthma, osteoarthritis and multiple sclerosis. (I), Wherein R^m, Rⁿ, R^p, R^q, V, W, X, Y and R⁸ are as defined in the claims.
  [FR] La présente invention concerne une nouvelle classe de dérivés d'amino-éthoxy benzène substitués répondant à la formule (I), qui sont des inhibiteurs des sérine-protéases. Cette invention concerne également leur utilisation dans le traitement de l'activité aberrante de la sérine protéase chez un mammifère, des procédés de contraception, des procédés anti-coagulants et des procédés destinés à traiter la prolifération cellulaire aberrante, les tumeurs, le cancer, l'angiogenèse, les rétinopathies induites par l'angiogenèse, les maladies auto-immunes, l'inflammation, les maladies cutanées, l'arthrite, la polyarthrite rhumatoïde, l'asthme, l'ostéoarthrose et la sclérose en plaques. (I), R^m, Rⁿ, R^p, R^q, V, W, X, Y et R⁸ sont tels que définis dans les revendications.
• Fragment-Based Discovery of Mexiletine Derivatives as Orally Bioavailable Inhibitors of Urokinase-Type Plasminogen Activator
  作者：Martyn Frederickson、Owen Callaghan、Gianni Chessari、Miles Congreve、Suzanna R. Cowan、Julia E. Matthews、Rachel McMenamin、Donna-Michelle Smith、Mladen Vinković、Nicola G. Wallis

  DOI：10.1021/jm701359z

  日期：2008.1.1

  Fragment-based lead discovery has been applied to urokinase-type plasminogen activator (uPA). The (R)-enantiomer of the orally active drug mexiletine 5 (a fragment hit from X-ray crystallographic screening) was the chemical starting point. Structure-aided design led to elaborated inhibitors that retained the key interactions of (R)-5 while gaining extra potency by simultaneously occupying neighboring regions of the active site. Subsequent optimization led to 15, a potent, selective, and orally bioavailable inhibitor of uPA.