(S)-4-[2-hydroxy-3-phenoxypropylaminoethoxy]phenoxyacetic acid hydrochloride | 140850-02-8

• 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: (S)-4-[2-hydroxy-3-phenoxypropylaminoethoxy]phenoxyacetic acid hydrochloride
• 英文别名: ICI 215,001；ICI 215001 hydrochloride；2-[4-[2-[[(2S)-2-hydroxy-3-phenoxypropyl]amino]ethoxy]phenoxy]acetic acid;hydrochloride
• CAS: 140850-02-8
• 化学式: C₁₉H₂₃NO₆*ClH
• 分子量: 397.856
• InChiKey: ISFZQNYGEYAUCR-RSAXXLAASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.98
• 重原子数：
  27
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  97.2
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (S)-(-)-methyl <4-<2-<(2-hydroxy-3-phenoxypropyl)amino>ethoxy>phenoxy>acetate hydrochloride 在 盐酸 作用下， 反应 0.5h， 生成 (S)-4-[2-hydroxy-3-phenoxypropylaminoethoxy]phenoxyacetic acid hydrochloride
  参考文献：
  名称：

  Selective .beta.3-adrenergic agonists of brown adipose tissue and thermogenesis. 2. [4-[2-[(2-Hydroxy-3-phenoxypropyl)amino]ethoxy]phenoxy]acetamides

  摘要：

  The ester methyl [4-[2-[(2-hydroxy-3-phenoxypropyl)amino]ethoxy]phenoxy]acetate (1) (R1 = OMe) had previously been identified as the most interesting member of a series of selective beta-3-adrenergic agonists of brown adipose tissue and thermogenesis in the rat. In vivo it acts mainly via the related acid 1 (R1 = OH). Amides have been examined to determine whether they have advantages over the ester. In particular, in the rat and dog the half-lives of amides of appropriate potency were no longer than those of the ester. The amide (S)-4-[2-[(2-hydroxy-3-phenoxypropyl)amino]ethoxy]-N-(2-methoxyethyl)phenoxyacetamide [S-27, ICI D7114] was selected as having properties consistent with a sustained-release formulation should that prove necessary. Unlike the ester it is resistant to hydrolysis in the gut lumen. Further testing of ICI D7114 has shown that in the rat, cat, and dog it stimulates the beta-3-adrenergic receptor in brown adipose tissue at doses lower than those at which it affects beta-1- and beta-2-adrenergic receptors in other tissues. Slimming effects were observed in the dog. ICI D7114 may be a selective thermogenic agent in man and may be useful in the treatment of obesity and diabetes.

  DOI：

  10.1021/jm00088a010

文献信息

• Thiazolidinone, oxazolidinone, and imidazolone derivatives for treating non-inflammatory gastrointestinal tract disorders
  申请人：Fraser Oliver Matthew

  公开号：US20050113421A1

  公开（公告）日：2005-05-26

  A method is provided for using Cav2.2 subunit calcium channel modulators, particularly thiazolidinone, oxazolidinone, and imidazolone derivatives, to treat non-inflammatory gastrointestinal tract disorders.

  提供了一种方法，用于使用Cav2.2亚单位钙通道调节剂，特别是噻唑啉酮、噁唑啉酮和咪唑啉酮衍生物，来治疗非炎症性胃肠道疾病。
• Kinin antagonists for treating bladder dysfunction
  申请人：Jerini AG

  公开号：EP1741444A1

  公开（公告）日：2007-01-10

  The present invention is related to the use of a kinin receptor antagonist for the manufacture of a medicament for the treatment and/or prevention of bladder dysfunction, whereby the kinin receptor is selected from the group comprising B1 and B2 receptors.

  本发明涉及使用激肽受体拮抗剂制造治疗和/或预防膀胱功能障碍的药物，其中激肽受体选自包括 B1 和 B2 受体的组。
• Methods for treating lower urinary tract disorders using smooth muscle modulators and alpha-2-delta subunit calcium channel modulators
  申请人：Dynogen Pharmaceuticals, Inc.

  公开号：EP1721607A1

  公开（公告）日：2006-11-15

  A method is provided for using α2δ subunit calcium channel modulators or other compounds that interact with the α2δ calcium channel subunit in combination with one or more compounds with smooth muscle modulatory effects to treat and/or alleviate the symptoms associated with painful and non-painful lower urinary tract disorders in normal and spinal cord injured patients. According to the present invention, α2δ subunit calcium channel modulators include GABA analogs (e.g. gabapentin and pregabalin), fused bicyclic or tricyclic amino acid analogs of gabapentin, and amino acid compounds. Compounds with smooth muscle modulatory effects include antimuscarinics, β3 adrenergic agonists, spasmolytics, neurokinin receptor antagonists, bradykinin receptor antagonists, and nitric oxide donors.

  本发明提供了一种使用α2δ亚基钙通道调节剂或其他与α2δ钙通道亚基相互作用的化合物与一种或多种具有平滑肌调节作用的化合物联合治疗和/或缓解正常人和脊髓损伤患者疼痛性和非疼痛性下尿路障碍相关症状的方法。根据本发明，α2δ亚基钙通道调节剂包括 GABA 类似物（如加巴喷丁和普瑞巴林）、加巴喷丁的融合双环或三环氨基酸类似物以及氨基酸化合物。具有平滑肌调节作用的化合物包括抗心绞痛药、β3 肾上腺素能激动剂、解痉药、神经激肽受体拮抗剂、缓激肽受体拮抗剂和一氧化氮供体。
• Method of treating lower urinary tract disorders
  申请人：Dynogen Pharmaceuticals, Inc.

  公开号：EP1795196A2

  公开（公告）日：2007-06-13

  The invention relates to the treatment of at least one symptom of a lower urinary tract disorder in a subject in need of treatment wherein the symptom is selected from the group consisting of urinary frequency, urinary urgency, urinary urge incontinence, nocturia and enuresis, and wherein to a subject in need of treatment a therapeutically effective amount of a compound that has 5-HT3 receptor antagonist activity and NorAdrenaline Reuptake Inhibitor (NARI) activity is to be administered. The invention further relates to the treatment of at least one symptom of a lower urinary tract disorder in a subject in need of treatment wherein the symptom is selected from the group consisting of urinary frequency, urinary urgency, urinary urge incontinence, nocturia and enuresis, comprising coadministering to said subject a first amount of a 5HT3 antagonist and a second amount of a NARI, wherein the first and second amounts together comprise a therapeutically effective amount or are each present in a therapeutically effective amount.

  本发明涉及需要治疗的受试者至少一种下尿路疾病症状的治疗，其中该症状选自由尿频、尿急、尿失禁、夜尿和遗尿组成的组，并且对需要治疗的受试者施用治疗有效量的具有5-HT3受体拮抗剂活性和去甲肾上腺素再摄取抑制剂（NARI）活性的化合物。本发明进一步涉及对需要治疗的受试者的至少一种下尿路疾病症状的治疗，其中该症状选自由尿频、尿急、尿失禁、夜尿和遗尿组成的组，包括向所述受试者联合施用第一量的5-HT3受体拮抗剂和第二量的NARI，其中第一量和第二量共同组成治疗有效量或各自以治疗有效量存在。
• Methods of treating gastrointestinal tract disorders using sodium channel modulators
  申请人：Dynogen Pharmaceuticals, Inc.

  公开号：US20040213842A1

  公开（公告）日：2004-10-28

  The invention relates to methods of using sodium channel modulators, particularly TTX-R sodium channel modulators and/or activity dependent sodium channel modulators to treat gastrointestinal tract disorders, particularly inflammatory bowel disorders and irritable bowel syndrome.

  本发明涉及使用钠通道调节剂，特别是 TTX-R 钠通道调节剂和/或活性依赖性钠通道调节剂治疗胃肠道疾病，特别是炎症性肠病和肠易激综合征的方法。