5-(4-benzyloxy-phenyl)-isoxazole-3-carboxylic acid methyl ester | 742058-30-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5-(4-benzyloxy-phenyl)-isoxazole-3-carboxylic acid methyl ester
• 英文别名: 5-(4-benzyloxyphenyl)isoxazole-3-carboxylic acid methyl ester；Methyl 5-[4-(Benzyloxy)phenyl]isoxazole-3-carboxylate；methyl 5-(4-phenylmethoxyphenyl)-1,2-oxazole-3-carboxylate
• CAS: 742058-30-6
• 化学式: C₁₈H₁₅NO₄
• 分子量: 309.321
• InChiKey: OLNOOWNJWWOLPE-UHFFFAOYSA-N

物化性质

• 沸点：
  501.3±50.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  61.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(4-benzyloxy-phenyl)-isoxazole-3-carboxylic acid methyl ester 在 sodium hydroxide 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 4.0h， 以93%的产率得到5-(4-benzyloxy-phenyl)-isoxazole-3-carboxylic acid
  参考文献：
  名称：

  蛋白质酪氨酸磷酸酶抑制剂的固相组装和原位筛选。

  摘要：

  描述了一种高效的固相策略，用于组装针对蛋白质酪氨酸磷酸酶1B（PTP1B）的小分子抑制剂。该方法的简便性和产品纯度突出了该方法。已合成了一个由70个成员组成的已知PTP1B抑制剂类似物组合库，该库在直接原位筛选后显示出一种针对PTP1B的有效抑制剂（Ki = 7.0 microM）。

  DOI：

  10.1021/ol8006875
• 作为产物：
  描述：

  4-(4-(benzyloxy)phenyl)-2,4-dioxo-butyric acid methyl ester 在 盐酸羟胺 、 对甲苯磺酸 作用下， 以 甲醇 为溶剂， 反应 72.0h， 以12.57 g的产率得到5-(4-benzyloxy-phenyl)-isoxazole-3-carboxylic acid methyl ester
  参考文献：
  名称：

  蛋白质酪氨酸磷酸酶抑制剂的固相组装和原位筛选。

  摘要：

  描述了一种高效的固相策略，用于组装针对蛋白质酪氨酸磷酸酶1B（PTP1B）的小分子抑制剂。该方法的简便性和产品纯度突出了该方法。已合成了一个由70个成员组成的已知PTP1B抑制剂类似物组合库，该库在直接原位筛选后显示出一种针对PTP1B的有效抑制剂（Ki = 7.0 microM）。

  DOI：

  10.1021/ol8006875

文献信息

• [EN] BIS(HETERO)ARYL CARBOXAMIDE DERIVATIVES FOR USE AS PGI2 ANTAGONISTS<br/>[FR] DERIVES DE BIS(HETERO)ARYLE CARBOXAMIDE DESTINES A ETRE UTILISES EN TANT QU'ANTAGONISTES DE LA PG12
  申请人：BAYER HEALTHCARE AG

  公开号：WO2004069805A1

  公开（公告）日：2004-08-19

  The present invention relates to aryl or heteroaryl amido alkane derivatives of formula (I) wherein R6 represents carboxy or tetrazolyl, which are useful as an active ingredient of pharmaceutical preparations. The aryl or heteroaryl amido alkanes of the present invention have PGI2 antagonistic activity, and can be used for the prophylaxis and treatment of diseases associated with PGI2 activity.Such diseases include urological diseases or disorder as follows: bladder outlet obstruction, overactive bladder, urinary incontinence, detrusor hyper-reflexia, detrusor instability, reduced bladder capacity, frequency of micturition, urge incontinence, stress incontinence, bladder hyperreactivity, benighn prostatic hypertrophy (BPH), prostatitis, urinary frequency, nocturia, urinary urgency, pelvic hypersensitivity, urethritis, pelvic pain syndrome, prostatodynia, cystitis, or idiophatic bladder hypersensitivity.The compounds of the present invention are also useful for treatment of pain including, but not limited to inflammatory pain, neuropathic pain, acute pain, chronic pain, dental pain, premenstrual pain, visceral pain, headaches, and the like; hypotension;hemophilia and hemorrhage; and inflammation, since the diseases also relate to PGI2.

  本发明涉及式(I)的芳基或杂环芳基酰胺烷基衍生物，其中R6代表羧基或四唑基，其作为药物制剂的活性成分是有用的。本发明的芳基或杂环芳基酰胺烷基具有PGI2拮抗活性，可用于预防和治疗与PGI2活性相关的疾病。这些疾病包括泌尿系统疾病或障碍，如：膀胱出口梗阻、膀胱过度活跃、尿失禁、膀胱逼尿肌过度反射、膀胱逼尿肌不稳定、膀胱容量减少、排尿频率增加、急迫性尿失禁、压力性尿失禁、膀胱高反应性、良性前列腺增生（BPH）、前列腺炎、尿频、夜尿、尿急、盆腔过敏、尿道炎、盆腔疼痛综合征、前列腺疼痛综合征、膀胱炎或特发性膀胱过敏。本发明的化合物还可用于治疗疼痛，包括但不限于炎症性疼痛、神经病性疼痛、急性疼痛、慢性疼痛、牙痛、经前疼痛、内脏疼痛、头痛等；低血压；血友病和出血；以及炎症，因为这些疾病也与PGI2有关。
• Bis (hetero) aryl carboxamide derivatives for use as PG12 antagonists
  申请人：Murata Toshiki

  公开号：US20060247260A1

  公开（公告）日：2006-11-02

  This invention relates to aryl or heteroaryl amido alkane derivatives of formula (I) in which Ar 1 and Ar 2 independently represent phenyl or a 5 or 6-membered heteroaromatic ring, R 6 represents carboxyl or tetrazolyl, and the remaining variables are as defined in the text and claims, which are useful as an active ingredient of pharmaceutical preparations. The aryl or heteroaryl amido alkanes of the present invention have PGI2 antagonistic activity, and can be used for the prophylaxis and treatment of diseases associated with PGI2 activity. Such diseases include urological diseases or disorder as follows: bladder outlet obstruction, overactive bladder, urinary incontinence, detrusor hyper-reflexia, detrusor instability, reduced bladder capacity, frequency of micturition, urge incontinence, stress incontinence, bladder hyperreactivity, benighn prostatic hypertrophy (BPH), prostatitis, urinary frequency, nocturia, urinary urgency, pelvic hypersensitivity, urethritis, pelvic pain syndrome, prostatodynia, cystitis, or idiophatic bladder hypersensitivity. The compounds of the present invention are also useful for treatment of pain including, but not limited to inflammatory pain, neuropathic pain, acute pain, chronic pain, dental pain, premenstrual pain, visceral pain, headaches, and the like; hypotension;hemophilia and hemorrhage; and inflammation, since the diseases also relate to PGI2.

  本发明涉及公式（I）中的芳基或杂环芳基酰胺烷衍生物，其中Ar1和Ar2分别表示苯基或5或6成员杂环芳基环，R6表示羧基或四唑基，其余变量如文本和权利要求所定义，可用作药物制剂的活性成分。本发明的芳基或杂环芳基酰胺烷具有PGI2拮抗活性，可用于预防和治疗与PGI2活性相关的疾病。这些疾病包括以下泌尿系统疾病或障碍：膀胱出口梗阻，过度活动的膀胱，尿失禁，膀胱平滑肌反射亢进，膀胱平滑肌不稳定，膀胱容量减少，排尿频率，急迫性尿失禁，压力性尿失禁，膀胱高反应性，良性前列腺增生（BPH），前列腺炎，尿频，夜尿，尿急，盆腔过敏，尿道炎，盆腔疼痛综合征，前列腺疼痛，膀胱炎或特发性膀胱过敏。本发明化合物还可用于治疗疼痛，包括但不限于炎症性疼痛，神经病理性疼痛，急性疼痛，慢性疼痛，牙痛，经前痛，内脏疼痛，头痛等；低血压；血友病和出血；以及炎症，因为这些疾病也与PGI2有关。
• BIS(HETERO)ARYL CARBOXAMIDE DERIVATIVES FOR USE AS PGI2 ANTAGONISTS
  申请人：Bayer HealthCare AG

  公开号：EP1594846A1

  公开（公告）日：2005-11-16
• Solid-Phase Assembly and In Situ Screening of Protein Tyrosine Phosphatase Inhibitors
  作者：Rajavel Srinivasan、Lay Pheng Tan、Hao Wu、Shao Q. Yao

  DOI：10.1021/ol8006875

  日期：2008.6.5

  highly efficient solid-phase strategy for assembly of small molecule inhibitors against protein tyrosine phosphatase 1B (PTP1B) is described. The method is highlighted by its simplicity and product purity. A 70-member combinatorial library of analogues of a known PTP1B inhibitor has been synthesized, which upon direct in situ screening revealed a potent inhibitor ( Ki = 7.0 microM) against PTP1B.

  描述了一种高效的固相策略，用于组装针对蛋白质酪氨酸磷酸酶1B（PTP1B）的小分子抑制剂。该方法的简便性和产品纯度突出了该方法。已合成了一个由70个成员组成的已知PTP1B抑制剂类似物组合库，该库在直接原位筛选后显示出一种针对PTP1B的有效抑制剂（Ki = 7.0 microM）。