2-(3-Chloro-4-{2-[(1S,2R)-2-hydroxy-2-(4-hydroxy-phenyl)-1-methyl-ethylamino]-ethyl}-phenylamino)-2-methyl-propionic acid ethyl ester | 247073-85-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-(3-Chloro-4-{2-[(1S,2R)-2-hydroxy-2-(4-hydroxy-phenyl)-1-methyl-ethylamino]-ethyl}-phenylamino)-2-methyl-propionic acid ethyl ester
• 英文别名: ethyl 2-[3-chloro-4-[2-[[(1R,2S)-1-hydroxy-1-(4-hydroxyphenyl)propan-2-yl]amino]ethyl]anilino]-2-methylpropanoate
• CAS: 247073-85-4
• 化学式: C₂₃H₃₁ClN₂O₄
• 分子量: 434.963
• InChiKey: ZIZSOZDYLFKBKP-BTYIYWSLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  90.8
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(3-Chloro-4-{2-[(1S,2R)-2-hydroxy-2-(4-hydroxy-phenyl)-1-methyl-ethylamino]-ethyl}-phenylamino)-2-methyl-propionic acid ethyl ester 在 sodium hydroxide 作用下， 反应 1.0h， 生成 2-[[3-Chloro-4-[2-[[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino]ethyl]phenyl]amino]-2-methylpropionic acid
  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：

  3-chloro-4-[2-(methoxymethoxy)ethyl]aniline 在 氢氧化钾 、 氯化亚砜 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 12.0h， 生成 2-(3-Chloro-4-{2-[(1S,2R)-2-hydroxy-2-(4-hydroxy-phenyl)-1-methyl-ethylamino]-ethyl}-phenylamino)-2-methyl-propionic 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

文献信息

• 2-METHYLPROPIONIC ACID DERIVATIVES AND MEDICINAL COMPOSITIONS CONTAINING THE SAME
  申请人：Kissei Pharmaceutical Co., Ltd.

  公开号：EP1072583A1

  公开（公告）日：2001-01-31

  The present invention provides novel 2-methylpropionic acid derivatives represented by the general formula: wherein R1 represents a hydroxy group, a lower alkoxy group or an aralkyl group; R2 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 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 biliary tract.

  本发明提供由通式表示的新型 2-甲基丙酸衍生物： 其中 R1 代表羟基、低级烷氧基或芳烷基；R2 代表羟基、低级烷基或卤原子；A 代表氧原子或亚氨基；标有 (R) 的碳原子代表 R 构型的碳原子；和标有(S)的碳原子代表S构型的碳原子，及其药学上可接受的盐，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、肠道高运动性引起的疾病、花粉尿症、尿失禁、抑郁症或胆道结石或胆道高运动性引起的疾病的药物。
• US6696489B1
  申请人：——

  公开号：US6696489B1

  公开（公告）日：2004-02-24
• Discovery of Novel <i>N</i>-Phenylglycine Derivatives as Potent and Selective β₃-Adrenoceptor Agonists for the Treatment of Frequent Urination and Urinary Incontinence
  作者：Nobuyuki Tanaka、Tetsuro Tamai、Harunobu Mukaiyama、Akihito Hirabayashi、Hideyuki Muranaka、Satoshi Akahane、Hiroshi Miyata、Masuo Akahane

  DOI：10.1021/jm000455z

  日期：2001.4.1

  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.