(5-hydroxyadamantan-2-ylidene)acetic acid methyl ester | 110511-31-4

• 分子结构分类: 有机化合物
• 英文名称: (5-hydroxyadamantan-2-ylidene)acetic acid methyl ester
• 英文别名: methyl 5-hydroxy-2-adamantylidene acetate
• CAS: 110511-31-4；161786-38-5
• 化学式: C₁₃H₁₈O₃
• 分子量: 222.284
• InChiKey: KYRHZROWMYWDLJ-WCIBSUBMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.66
• 重原子数：
  16.0
• 可旋转键数：
  1.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  46.53
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (5-hydroxyadamantan-2-ylidene)acetic acid methyl ester 在 偶氮二甲酸二异丙酯 、 palladium 10% on activated carbon 、 氢气 、 三苯基膦 作用下， 以 乙酸乙酯 、 苯 为溶剂， 反应 35.0h， 生成 4-(4-methoxycarbonylmethyladamantan-1-yloxy)benzoic acid benzyl ester
  参考文献：
  名称：

  Discovery and optimization of adamantane carboxylic acid derivatives as potent diacylglycerol acyltransferase 1 inhibitors for the potential treatment of obesity and diabetes

  摘要：

  We have developed a series of adamantane carboxylic acid derivatives exhibiting potent diacylglycerol acyltransferase 1 (DGAT1) inhibitory activities. Optimization of the series led to the discovery of E-adamantane carboxylic acid compound 43c, which showed excellent in vitro activity with an IC50 value of 5 nM against human and mouse DGAT1, also good druggability as well as microsomal stability and safety profiles such as hERG, CYP and cytotoxicity. Compound 43c significantly reduced plasma triglyceride levels in vivo (in rodents and zebrafish) and also showed bodyweight gain reduction and glucose area under curve (AUC) lowering efficacy in diet-induced obesity (DIO) mice.[GRAPHICS](C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.06.043
• 作为产物：
  描述：

  5-羟基-2-金刚烷酮 、 三甲基膦酰基乙酸酯 在 sodium hydride 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 反应 6.0h， 以90%的产率得到(5-hydroxyadamantan-2-ylidene)acetic acid methyl ester
  参考文献：
  名称：

  Discovery and optimization of adamantane carboxylic acid derivatives as potent diacylglycerol acyltransferase 1 inhibitors for the potential treatment of obesity and diabetes

  摘要：

  We have developed a series of adamantane carboxylic acid derivatives exhibiting potent diacylglycerol acyltransferase 1 (DGAT1) inhibitory activities. Optimization of the series led to the discovery of E-adamantane carboxylic acid compound 43c, which showed excellent in vitro activity with an IC50 value of 5 nM against human and mouse DGAT1, also good druggability as well as microsomal stability and safety profiles such as hERG, CYP and cytotoxicity. Compound 43c significantly reduced plasma triglyceride levels in vivo (in rodents and zebrafish) and also showed bodyweight gain reduction and glucose area under curve (AUC) lowering efficacy in diet-induced obesity (DIO) mice.[GRAPHICS](C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.06.043

文献信息

• Azepine derivatives and use thereof
  申请人：Asahi Kasei Kogyo Kabushiki Kaisha

  公开号：US05658923A1

  公开（公告）日：1997-08-19

  An azepine compound of the formula ##STR1## wherein R is (a) ##STR2## in which R.sup.1 is hydrogen, lower alkyl, lower alkoxy, hydroxy, halogen, or optionally substituted phenyl, and n is 0 or 1, (b) cycloalkyl of C.sub.5-8 which is optionally substituted by lower alkyl, (c) norbornyl, (d) bicyclo[3.3.1]nonyl, (e) naphthyl, (f) 1,3-benzoxolyl, (g) pyridyl, or (h) thienyl, m is an integer of 0-4, and C* is an asymmetric carbon, and nontoxic salts thereof, processes for producing the same, and therapeutic agents containing the same as the active ingredient for treating diseases related to .sigma.-receptor. The compound (1) and nontoxic salts thereof have a high affinity for .sigma.-receptor but scarcely any affinity for other receptors, thus being utilized for treating diseases related to .sigma.-receptor, such as schizophrenia.

  一种azepine化合物，其化学式为##STR1##其中R为(a) ##STR2##其中R.sup.1为氢、较低烷基、较低烷氧基、羟基、卤素，或者可选择地取代苯基，n为0或1，(b) C.sub.5-8的环烷基，可选择地取代为较低烷基，(c) 诺邦基，(d) 双环[3.3.1]壬基，(e) 萘基，(f) 1,3-苯并噁唑基，(g) 吡啶基，或(h) 噻吩基，m为0-4的整数，C*为不对称碳，以及其无毒盐，制备该化合物的方法，以及包含该化合物作为活性成分的治疗剂，用于治疗与σ-受体相关的疾病。该化合物(1)及其无毒盐对σ-受体具有高亲和力，但几乎不与其他受体结合，因此可用于治疗与σ-受体相关的疾病，如精神分裂症。