ethyl 2-[4-(bromoacetyl)-3-chlorophenoxy]-2-methylpropionate | 247073-93-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl 2-[4-(bromoacetyl)-3-chlorophenoxy]-2-methylpropionate
• 英文别名: Ethyl 2-[4-(2-bromoacetyl)-3-chlorophenoxy]-2-methyl-propionate；Ethyl 2-[4-(2-bromoacetyl)-3-chlorophenoxy]-2-methylpropionate；ethyl 2-[4-(2-bromoacetyl)-3-chlorophenoxy]-2-methylpropanoate
• CAS: 247073-93-4
• 化学式: C₁₄H₁₆BrClO₄
• 分子量: 363.636
• InChiKey: HHPPJXMLMLHQAX-UHFFFAOYSA-N

物化性质

• 沸点：
  407.4±35.0 °C(Predicted)
• 密度：
  1.419±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 2-[4-(bromoacetyl)-3-chlorophenoxy]-2-methylpropionate 在 三乙基硅烷 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 ethyl 2-[3-chloro-4-[2-[[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino]ethyl]phenoxy]-2-methylpropionate
  参考文献：
  名称：

  β3-Adrenoceptor agonists for the treatment of frequent urination and urinary incontinence: 2-[4-(2-{[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino}ethyl)phenoxy]-2-methylpropionic acid

  摘要：

  In a search for novel analogues of beta (3)-adrenoceptor (AR) agonists relaxing the bladder for treatment of urinary dysfunction, 2-[4-(2-{[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino}ethyl)phenoxy]-2-methylpropionic acids (1a-e), into which a fibrate-like structure ha been incorporated, were synthesised. Compound la was found to be a selective beta (3)-AR agonist in functional assays using the ferret detrusor (VAR), rat uterus (beta (2)-AR), and rat atrium (beta (1)-AR): beta (3): EC50 = 7.8 nM, beta (2): IC50 = 7,300 nM, beta (1): EC20 = 23,000 nM. The introduction of a chlorine atom or methyl substituent at the ortho-position on the phenyl ring of la further improved VAR selectivity. In an in vivo study, la lowered intrabladder pressure (ED50 = 31 mug/kg) in rats, without increasing heart rate, in keeping with the in vitro results. Consequently, it is proposed that la and its analogues (1b e), possess beta (3)-AR agonistic activity in the absence of undesirable beta (1)- or beta (2)-AR mediated actions. and may be useful for clinical treatment and pharmacological studies. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00240-1
• 作为产物：
  描述：

  3-氯苯酚 在 sodium hydroxide 、 三氯化铝 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 12.0h， 生成 ethyl 2-[4-(bromoacetyl)-3-chlorophenoxy]-2-methylpropionate
  参考文献：
  名称：

  β3-Adrenoceptor agonists for the treatment of frequent urination and urinary incontinence: 2-[4-(2-{[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino}ethyl)phenoxy]-2-methylpropionic acid

  摘要：

  In a search for novel analogues of beta (3)-adrenoceptor (AR) agonists relaxing the bladder for treatment of urinary dysfunction, 2-[4-(2-{[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino}ethyl)phenoxy]-2-methylpropionic acids (1a-e), into which a fibrate-like structure ha been incorporated, were synthesised. Compound la was found to be a selective beta (3)-AR agonist in functional assays using the ferret detrusor (VAR), rat uterus (beta (2)-AR), and rat atrium (beta (1)-AR): beta (3): EC50 = 7.8 nM, beta (2): IC50 = 7,300 nM, beta (1): EC20 = 23,000 nM. The introduction of a chlorine atom or methyl substituent at the ortho-position on the phenyl ring of la further improved VAR selectivity. In an in vivo study, la lowered intrabladder pressure (ED50 = 31 mug/kg) in rats, without increasing heart rate, in keeping with the in vitro results. Consequently, it is proposed that la and its analogues (1b e), possess beta (3)-AR agonistic activity in the absence of undesirable beta (1)- or beta (2)-AR mediated actions. and may be useful for clinical treatment and pharmacological studies. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00240-1

文献信息

• 2-methylpropionic acid derivatives and pharmaceutical compositions comprising the same
  申请人：KISSEI PHARMACEUTICAL CO., LTD.

  公开号：US20030166719A1

  公开（公告）日：2003-09-04

  The present invention provides novel 2-methylpropionic acid derivatives represented by the general formula: 1 (wherein R 1 represents a hydroxy group, a lower alkoxy group or an aralkyl group; R 2 represents a hydroxy group, a lower alkyl group or a halogen atom; A represents an oxygen atom or an imino group; the carbon atom marked with (R) represents a carbon atom in R configuration; and the carbon atom marked with (S) represents a carbon atom in S configuration) and pharmaceutically acceptable salts thereof, which have excellent &bgr; 3 -adrenoceptor stimulating effects and are useful as agents for the prevention or treatment of obesity, hyperglycemia, the diseases caused by intestinal hypermotility, pollakiuria, urinary incontinence, depression, or the diseases caused by biliary calculi or hypermotility of biliary tract.

  本发明提供了一种新的2-甲基丙酸衍生物，其通式表示为：1（其中R1代表一个羟基、一个较低的烷氧基或一个芳基烷基；R2代表一个羟基、一个较低的烷基或一个卤原子；A代表一个氧原子或一个亚胺基；标有（R）的碳原子代表R构型中的一个碳原子；标有（S）的碳原子代表S构型中的一个碳原子），以及其药学上可接受的盐，具有优异的β3-肾上腺素受体刺激效应，可用作预防或治疗肥胖、高血糖、由肠道过度运动引起的疾病、尿频、尿失禁、抑郁症或胆结石或胆道过度运动引起的疾病的药剂。
• 2-Methylpropionic acid derivatives and medicinal compositions containing the same
  申请人：Kissei Pharmaceutical Co., Ltd.

  公开号：US06696489B1

  公开（公告）日：2004-02-24

  The present invention provides novel 2-methylpropionic acid derivatives represented by the general formula: (wherein R1 represents a hydrogen atom, a lower alkyl group or an aralkyl group; R2 represents a hydrogen atom a lower alkyl group or a halogen atom; A represents an oxygen atom or an imino group; the carbon atom marked with (R) represents a carbon atom in R configuration; and the carbon atom marked with (S) represents a carbon atom in S configuration) and pharmaceutically acceptable salts thereof, which have excellent &bgr;3-adrenoceptor stimulating effects and are useful as agents for the prevention or treatment of obesity, hyperglycemia, the diseases caused by intestinal hypermotility, pollakiuria, urinary incontinence, depression, or the diseases caused by biliary calculi or hypermotility of the biliary tract.

  本发明提供了一种新型的2-甲基丙酸衍生物，其通式表示为：（其中R1代表氢原子，低碳基或芳基烷基；R2代表氢原子，低碳基或卤原子；A代表氧原子或亚胺基；标有（R）的碳原子代表R构型中的碳原子；标有（S）的碳原子代表S构型中的碳原子），以及其药学上可接受的盐，具有优异的β3-肾上腺素能受体刺激作用，可用作预防或治疗肥胖症、高血糖症、肠道过动症引起的疾病、尿频、尿失禁、抑郁症或胆石或胆道过动症引起的疾病的药剂。
• 2-METHYLPROPIONIC ACID DERIVATIVES AND MEDICINAL COMPOSITIONS CONTAINING THE SAME
  申请人：Kissei Pharmaceutical Co., Ltd.

  公开号：EP1072583B1

  公开（公告）日：2004-09-01
• US6696489B1
  申请人：——

  公开号：US6696489B1

  公开（公告）日：2004-02-24
• US6790865B2
  申请人：——

  公开号：US6790865B2

  公开（公告）日：2004-09-14