methyl 4-(chloroformyl)-2,2-dimethylbutyrate | 98559-84-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: methyl 4-(chloroformyl)-2,2-dimethylbutyrate
• 英文别名: 2,2-Dimethyl-4-chlorformyl-buttersaeure-methylester；2,2-dimethyl-glutaric acid-5-chloride-1-methyl ester；2,2-Dimethyl-glutarsaeure-5-chlorid-1-methylester；4-chlorocarbonyl-2,2-dimethyl-butyric acid methyl ester；5-methoxy-4,4-dimethyl-5-oxopentanoylchloride；Methyl 5-chloro-2,2-dimethyl-5-oxopentanoate
• CAS: 98559-84-3
• 化学式: C₈H₁₃ClO₃
• 分子量: 192.642
• InChiKey: RYVZULLSFMHZHS-UHFFFAOYSA-N

物化性质

• 沸点：
  68-71 °C(Press: 2 Torr)
• 密度：
  1.115±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  12
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 4-(chloroformyl)-2,2-dimethylbutyrate 在 盐酸 作用下， 以 乙醚 为溶剂， 反应 3.0h， 生成 methyl 6-chloro-2,2-dimethyl-5-oxohexanoate
  参考文献：
  名称：

  Substituted thiopyrano[2,3,4-c,d]indoles as potent, selective, and orally active inhibitors of 5-lipoxygenase. Synthesis and biological evaluation of L-691,816

  摘要：

  Thiopyrano[2,3,4-c,d]indoles are a new class of 5-lipoxygenase (5-LO) inhibitors. SAR studies have demonstrated that the thiopyran ring, the 5-phenylpyridine substituent, and an acidic functional group on a four-carbon C-2 side chain are all required for optimal inhibitor potency. In contrast, the indolic nitrogen may be substituted with a variety of lipophilic groups. As a result of the SAR investigation, 44 (L-691,816; 5-[3-[1-(4-chlorobenzyl)-4-methyl-6-[(5-phenylpyridin-2-yl)methoxy]-4,5-dihydro-1H-thiopyrano[2,3,4-c,d]indol-2-yl]-2,2-dimethylpropyl]-1H-tetrazole) has been identified as a potent inhibitor of the 5-LO reaction both in vitro and in a range of in vivo models. Compound 44 inhibits 5-HPETE production by both rat and human 5-LO and LTB4 synthesis in human PMN leukocytes (IC50s 16,75, and 10 nM, respectively). The mechanism of inhibition of 5-LO activity by compound 44 appears to involve the formation of a reversible deadend complex with the enzyme and does not involve reduction of the nonheme iron of 5-LO. Compound 44 is highly selective for 5-LO when compared to the inhibition of human FLAP, porcine 12-LO, and also ram seminal vesicle cyclooxygenase. In addition, 44 is orally active in a rat pleurisy model (inhibition of LTB4, ED50 = 1.9 mg/kg; 8 h pretreatment) as well as in the hyperreactive rat model of antigen-induced dyspnea (ED50 = 0.1 mg/kg;2-h pretreatment). Excellent functional activity was also observed in both the conscious allergic monkey and sheep models of asthma. In the latter case, the functional activity observed correlated with the inhibition of urinary LTE4 excretion.

  DOI：

  10.1021/jm00071a008
• 作为产物：
  描述：

  2,2-二甲基戊二酸二甲酯 在 氯化亚砜 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 64.0h， 生成 methyl 4-(chloroformyl)-2,2-dimethylbutyrate
  参考文献：
  名称：

  Substituted thiopyrano[2,3,4-c,d]indoles as potent, selective, and orally active inhibitors of 5-lipoxygenase. Synthesis and biological evaluation of L-691,816

  摘要：

  Thiopyrano[2,3,4-c,d]indoles are a new class of 5-lipoxygenase (5-LO) inhibitors. SAR studies have demonstrated that the thiopyran ring, the 5-phenylpyridine substituent, and an acidic functional group on a four-carbon C-2 side chain are all required for optimal inhibitor potency. In contrast, the indolic nitrogen may be substituted with a variety of lipophilic groups. As a result of the SAR investigation, 44 (L-691,816; 5-[3-[1-(4-chlorobenzyl)-4-methyl-6-[(5-phenylpyridin-2-yl)methoxy]-4,5-dihydro-1H-thiopyrano[2,3,4-c,d]indol-2-yl]-2,2-dimethylpropyl]-1H-tetrazole) has been identified as a potent inhibitor of the 5-LO reaction both in vitro and in a range of in vivo models. Compound 44 inhibits 5-HPETE production by both rat and human 5-LO and LTB4 synthesis in human PMN leukocytes (IC50s 16,75, and 10 nM, respectively). The mechanism of inhibition of 5-LO activity by compound 44 appears to involve the formation of a reversible deadend complex with the enzyme and does not involve reduction of the nonheme iron of 5-LO. Compound 44 is highly selective for 5-LO when compared to the inhibition of human FLAP, porcine 12-LO, and also ram seminal vesicle cyclooxygenase. In addition, 44 is orally active in a rat pleurisy model (inhibition of LTB4, ED50 = 1.9 mg/kg; 8 h pretreatment) as well as in the hyperreactive rat model of antigen-induced dyspnea (ED50 = 0.1 mg/kg;2-h pretreatment). Excellent functional activity was also observed in both the conscious allergic monkey and sheep models of asthma. In the latter case, the functional activity observed correlated with the inhibition of urinary LTE4 excretion.

  DOI：

  10.1021/jm00071a008

文献信息

• Dioxocyclohexane carboxylic acid phenyl amide derivatives for modulating voltage-gated potassium channels and pharmaceutical compositions containing the same
  申请人：Sarantakis Dimitrios

  公开号：US20060014826A1

  公开（公告）日：2006-01-19

  Dioxocyclohexane carboxylic acid phenyl amide derivatives of Formula (I) or a tautomer or a pharmaceutically acceptable salt thereof or both, and pharmaceutical compositions containing the same are provided: The dioxocyclohexane carboxylic acid phenyl amide derivatives are useful for treating a variety of conditions associated with the abnormal modulation of one or more Kv1.1 voltage-gated potassium channels.

  二氧环己烷羧酸苯胺衍生物，其通式为(I)的化合物或其互变异构体或其药学上可接受的盐，以及含有这些化合物的药物组合物被提供：这些二氧环己烷羧酸苯胺衍生物可用于治疗与一个或多个Kv1.1电压门控钾通道异常调节相关的多种病症。
• Substituted monocyclic CGRP receptor antagonists
  申请人：Wood Michael R.

  公开号：US20070265225A1

  公开（公告）日：2007-11-15

  Compounds of formula I: (wherein variables A 1 , A 2 , A 3 , A 4 , m, n, J, Q, R 4 , E a , E b , E c , R 6 , R 7 , R e , R f , R PG and Y are as described herein) which are antagonists of CGRP receptors and which are useful in the treatment or prevention of diseases in which the CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  式I的化合物：(其中变量A1、A2、A3、A4、m、n、J、Q、R4、Ea、Eb、Ec、R6、R7、Re、Rf、RPG和Y如本文所述)是CGRP受体拮抗剂，可用于治疗或预防涉及CGRP的疾病，如偏头痛。该发明还涉及包含这些化合物的药物组合物以及在预防或治疗涉及CGRP的疾病中使用这些化合物和组合物。
• SUR LA DOUBLE ÉNOLISATION DE LA DIMÉTHYL-3,3 CYCLOHEXANONE
  作者：J. Champagne、H. Favre、D. Vocelle、Mlle I. Zbikowski

  DOI：10.1139/v64-039

  日期：1964.2.1

  not available

  不可用
• Thiopyrano[2,3,4-c,d]indoles as inhibitors of leukotriene biosynthesis
  申请人：Merck Frosst Canada, Inc.

  公开号：US05202321A1

  公开（公告）日：1993-04-13

  Compounds having the formula I: ##STR1## are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating angina, cerebral spasm, glomerular nephritis, hepatitis, endotoxemia, psoriasis, uveitis and allograft rejection and in preventing the formation of atherosclerotic plaques.

  具有公式I的化合物：##STR1## 是白三烯生物合成的抑制剂。这些化合物可用作抗哮喘、抗过敏、抗炎和细胞保护剂。它们还可用于治疗心绞痛、脑血管痉挛、肾小球肾炎、肝炎、内毒素血症、牛皮癣、葡萄膜炎和移植排斥，并预防动脉粥样硬化斑块的形成。
• Biphenylyl compounds
  申请人：Ciba-Geigy Corporation

  公开号：US05369110A1

  公开（公告）日：1994-11-29

  Biphenylyl compounds of formula ##STR1## wherein the variables R.sub.1, R.sub.2, R.sub.3, p, q and X and the rings A and B are as defined in claim 1, in free form or in salt form, can be prepared in a manner known per se and can be used, for example, as active ingredients in medicaments.

  式子为##STR1##的二苯基化合物，其中变量R.sub.1，R.sub.2，R.sub.3，p，q和X以及环A和B如权利要求1所定义，在自由形式或盐形式下，可以按照已知的方法制备，并且可以用作药物的活性成分。