2'-chloro-4'-[2-((RS)-tetrahydropyran-2-yloxy)ethyl]-2,2,2-trifluoroacetanilide | 227467-58-5

• 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: 2'-chloro-4'-[2-((RS)-tetrahydropyran-2-yloxy)ethyl]-2,2,2-trifluoroacetanilide
• 英文别名: 2'-chloro-4'-[2-((RS)-tetra-hydropyran-2-yloxy)ethyl]-2,2,2-trifluoroacetanilide；N-[2-chloro-4-[2-(oxan-2-yloxy)ethyl]phenyl]-2,2,2-trifluoroacetamide
• CAS: 227467-58-5
• 化学式: C₁₅H₁₇ClF₃NO₃
• 分子量: 351.753
• InChiKey: VTJCBKFGDOECRT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2'-chloro-4'-[2-((RS)-tetrahydropyran-2-yloxy)ethyl]-2,2,2-trifluoroacetanilide 在 sodium hydride 、 对甲苯磺酸 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.5h， 生成 [[2-Chloro-4-(2-hydroxy-ethyl)-phenyl]-(2,2,2-trifluoro-acetyl)-amino]-acetic acid ethyl ester
  参考文献：
  名称：

  Discovery of Novel N-Phenylglycine Derivatives as Potent and Selective β₃-Adrenoceptor Agonists for the Treatment of Frequent Urination and Urinary Incontinence

  摘要：

  With a novel assay using isolated ferret detrusor to estimate beta (3)-adrenoceptor agonistic activity, we found that a series of glycine derivatives of ritodrine, a beta (2)-adrenoceptor agonist, are potent beta (3)-adrenoceptor agonists, with excellent selectivity versus beta1 and beta (2) subtypes. Substitution of halogens in the phenyl ring increased potency and selectivity for the beta (3)-adrenoceptor, and this was dependent upon the position of the halogens. The chlorine-substituted derivatives 3f-i exhibited potent beta (3)-adrenoceptor-mediated relaxation of ferret detrusor (EC50 = 0.93, 11, 14, and 160 nM) and higher potency at beta (3)-adrenoceptors than at beta (1) or beta (2) The intravenous administration of 3h significantly reduced the urinary bladder pressure in anesthetized male rats (ED50 = 48 mug/kg) without cardiovascular side effects. This article is the first report of structure-activity relationships (SAR) concerning beta (3)-adrenoceptor agonists as agents for the treatment of urinary frequency and incontinence.

  DOI：

  10.1021/jm000455z
• 作为产物：
  描述：

  4-amino-3-chlorophenethyl alcohol 在 4-甲基苯磺酸吡啶 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 1.17h， 生成 2'-chloro-4'-[2-((RS)-tetrahydropyran-2-yloxy)ethyl]-2,2,2-trifluoroacetanilide
  参考文献：
  名称：

  Discovery of Novel N-Phenylglycine Derivatives as Potent and Selective β₃-Adrenoceptor Agonists for the Treatment of Frequent Urination and Urinary Incontinence

  摘要：

  With a novel assay using isolated ferret detrusor to estimate beta (3)-adrenoceptor agonistic activity, we found that a series of glycine derivatives of ritodrine, a beta (2)-adrenoceptor agonist, are potent beta (3)-adrenoceptor agonists, with excellent selectivity versus beta1 and beta (2) subtypes. Substitution of halogens in the phenyl ring increased potency and selectivity for the beta (3)-adrenoceptor, and this was dependent upon the position of the halogens. The chlorine-substituted derivatives 3f-i exhibited potent beta (3)-adrenoceptor-mediated relaxation of ferret detrusor (EC50 = 0.93, 11, 14, and 160 nM) and higher potency at beta (3)-adrenoceptors than at beta (1) or beta (2) The intravenous administration of 3h significantly reduced the urinary bladder pressure in anesthetized male rats (ED50 = 48 mug/kg) without cardiovascular side effects. This article is the first report of structure-activity relationships (SAR) concerning beta (3)-adrenoceptor agonists as agents for the treatment of urinary frequency and incontinence.

  DOI：

  10.1021/jm000455z

文献信息

• Phenylaminoalkylcarboxylic acid derivatives and pharmaceutical compositions comprising the same
  申请人：Kissei Pharmaceutical Co., Ltd.

  公开号：US06353025B1

  公开（公告）日：2002-03-05

  The present invention provides novel phenylaminoalkyl-carboxylic acid derivatives represented by the general formula: (wherein R1 represents a hydroxy group, a lower alkoxy group, an aralkoxy group, an amino group, an alicyclic amino group or a mono or di(lower alkyl)amino group which may have a hydroxy group or a lower alkoxy group as a substituent; R2 represents a hydrogen atom or a lower alkyl group; R3 represents a hydrogen atom or a halogen atom; R4 and R5 are the same or different and each represents a hydrogen atom, a halogen atom or a lower alkyl group; A represents a lower alkylene 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.

  本发明提供了新型的苯基氨基烷基羧酸衍生物，其通式如下：（其中R1代表羟基、较低的烷氧基、芳基烷氧基、氨基、脂环族氨基或单烷基或双（较低的烷基）氨基，可以有羟基或较低的烷氧基作为取代基；R2代表氢原子或较低的烷基；R3代表氢原子或卤素原子；R4和R5相同或不同，每个代表氢原子、卤素原子或较低的烷基；A代表较低的烷基烯基；标记有（R）的碳原子代表（R）构型的碳原子；标记有（S）的碳原子代表（S）构型的碳原子），以及其药学上可接受的盐。这些衍生物具有优异的β3-肾上腺素能受体刺激作用，并可用作预防或治疗肥胖症、高血糖症、肠道过度运动引起的疾病、尿频、尿失禁、抑郁症或胆石或胆道过度运动引起的疾病的药剂。
• PHENYLAMINOALKYLCARBOXYLIC ACID DERIVATIVES AND MEDICINAL COMPOSITIONS CONTAINING THE SAME
  申请人：Kissei Pharmaceutical Co., Ltd.

  公开号：EP1043308A1

  公开（公告）日：2000-10-11

  The present invention provides novel phenylaminoalkylcarboxylic acid derivatives represented by the general formula: wherein R1 represents a hydroxy group, a lower alkoxy group, an aralkoxy group, an amino group, an alicyclic amino group or a mono or di(lower alkyl)amino group which may have a hydroxy group or a lower alkoxy group as a substituent; R2 represents a hydroxy group or a lower alkyl group; R3 represents a hydrogen atom or a halogen atom; R4 and R5 are the same or different and each represents a hydrogen atom, a halogen atom or a lower alkyl group; A represents a lower alkylene 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 β3-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.

  本发明提供由通式表示的新型苯氨基烷基羧酸衍生物： 其中 R1 代表羟基、低级烷氧基、芳烷氧基、氨基、脂环氨基或单或双(低级烷基)氨基，其取代基可以是羟基或低级烷氧基；R2 代表羟基或低级烷基；R3 代表氢原子或卤素原子；R4 和 R5 相同或不同，各自代表氢原子、卤素原子或低级烷基；A 代表低级亚烷基；标有(R)的碳原子代表(R)构型的碳原子；标有(S)的碳原子代表(S)构型的碳原子，以及它们的药学上可接受的盐，它们具有优异的β3-肾上腺素受体刺激作用，可作为预防或治疗肥胖症、高血糖症、肠道过度运动引起的疾病、花粉尿症、尿失禁、抑郁症或胆道结石或胆道过度运动引起的疾病的药物。
• US6353025B1
  申请人：——

  公开号：US6353025B1

  公开（公告）日：2002-03-05