Methyl 3-({4-[4-({[1-(2-chlorophenyl)ethoxy]carbonyl}amino)-3-methyl-5-isoxazolyl]-benzyl}sulfanyl)propanoate

• 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: Methyl 3-({4-[4-({[1-(2-chlorophenyl)ethoxy]carbonyl}amino)-3-methyl-5-isoxazolyl]-benzyl}sulfanyl)propanoate
• 英文别名: methyl 3-([4-[4-([[1-(2-chlorophenyl)ethoxy]carbonyl]amino)-3-methyl-5-isoxazolyl]benzyl]-sulfanyl)propanoate；methyl 3-({4-[4-({[1-(2-chlorophenyl)ethoxy]carbonyl}amino)-3-methyl-5-isoxazolyl] benzyl}sulfanyl)propanoate；methyl 3-({4-[4-({[1-(2-chlorophenyl)ethoxy]carbonyl}amino)-3-methyl-5-isoxazolyl]benzyl}sulfanyl)propanoate；Methyl 3-((4-(4-(((1-(2-chlorophenyl)ethoxy)carbonyl)amino)-3-methylisoxazol-5-yl)benzyl)thio)propanoate；methyl 3-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]methylsulfanyl]propanoate
• 化学式: C₂₄H₂₅ClN₂O₅S
• 分子量: 488.992
• InChiKey: HHVJBROTJWPHHX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  33
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  116
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Methyl 3-({4-[4-({[1-(2-chlorophenyl)ethoxy]carbonyl}amino)-3-methyl-5-isoxazolyl]-benzyl}sulfanyl)propanoate 在 lithium hydroxide monohydrate 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以87%的产率得到Ki 16425; 3-[[[4-[4-[[[1-(2-氯苯基)乙氧基]羰基]氨基]-3-甲基-5-异恶唑基]苯基]甲基]硫基]丙酸
  参考文献：
  名称：

  光学活性Ki16425的合成及生物学评价

  摘要：

  实现了具有选择性LPA拮抗活性的Ki16425的两个对映异构体的对映体选择性合成。异恶唑核心是通过将氧化腈与炔烃进行1,3-偶极环加成并与旋光性α-苯乙醇链段缩合而构建的，旋光性α-苯乙醇链段是通过对映体选择性还原芳基甲基酮而制得的。Ki16425的两个对映异构体的生物学评估表明（R）-异构体对LPA 1和LPA 3受体具有更高的拮抗活性。

  DOI：

  10.1016/j.bmcl.2012.05.012
• 作为产物：
  描述：

  1-(2-氯苯基)乙醇 在 叠氮磷酸二苯酯 、 四丁基碘化铵 、 三乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 2.5h， 生成 Methyl 3-({4-[4-({[1-(2-chlorophenyl)ethoxy]carbonyl}amino)-3-methyl-5-isoxazolyl]-benzyl}sulfanyl)propanoate
  参考文献：
  名称：

  光学活性Ki16425的合成及生物学评价

  摘要：

  实现了具有选择性LPA拮抗活性的Ki16425的两个对映异构体的对映体选择性合成。异恶唑核心是通过将氧化腈与炔烃进行1,3-偶极环加成并与旋光性α-苯乙醇链段缩合而构建的，旋光性α-苯乙醇链段是通过对映体选择性还原芳基甲基酮而制得的。Ki16425的两个对映异构体的生物学评估表明（R）-异构体对LPA 1和LPA 3受体具有更高的拮抗活性。

  DOI：

  10.1016/j.bmcl.2012.05.012

文献信息

• Novel azole compound
  申请人：Yamamoto Takashi

  公开号：US20060194850A1

  公开（公告）日：2006-08-31

  Azole compounds represented by formula I: wherein ring A is isoxazole and the like, R1 is a substituted or unsubstituted aryl group and the like, R2 is a hydrogen atom and the like, and R3 is a substituted or unsubstituted alkyl group and the like, and pharmaceutically acceptable salts thereof inhibit the physiological activity of lysophosphatidic acid (LPA), and are useful as for the prophylaxis or treatment of diseases in which inhibition of the physiological activity of LPA is useful for the prophylaxis or treatment thereof, such as diseases involving the LPA receptor.

  由公式I表示的唑类化合物： 其中环A是异噁唑等，R1是取代的或未取代的芳基团等，R2是氢原子等，R3是取代的或未取代的烷基团等，以及药用可接受的盐，可以抑制溶血磷脂酸（LPA）的生理活性，并且用于预防或治疗抑制LPA生理活性对预防或治疗有用的疾病，如涉及LPA受体的疾病。
• REMEDY FOR CHRONIC DISEASE
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1550461A1

  公开（公告）日：2005-07-06

  A remedy and/or a preventive for a chronic disease which contains an EDG-2 antagonist. Because of binding to a subtype EDG-2 of LPA receptor, an EDG-2 antagonist is useful in treating and/or preventing chronic diseases (for example, diseases caused by the progress of chronic asthma, glomerular nephritis, obesity, arteriosclerosis, rheumatoid and atopic diseases) induced and made chronic by tissue cells whose proliferation is accelerated by LPA mediated by EDG-2.

  一种包含EDG-2拮抗剂的慢性疾病的治疗和/或预防药物。由于结合到LPA受体的亚型EDG-2，EDG-2拮抗剂在治疗和/或预防慢性疾病方面是有用的（例如，由EDG-2介导的LPA加速组织细胞增殖导致并使之慢性化的慢性哮喘、肾小球肾炎、肥胖、动脉硬化、风湿和特应性疾病等疾病）。
• Remedy for chronic disease
  申请人：Nakade Shinji

  公开号：US20060135577A1

  公开（公告）日：2006-06-22

  A remedy and/or a preventive for a chronic disease which contains an EDG-2 antagonist. Because of binding to a subtype EDG-2 of LPA receptor, an EDG-2 antagonist is useful in treating and/or preventing chronic diseases (for example, diseases caused by the progress of chronic asthma, glomerular nephritis, obesity, arteriosclerosis, rheumatoid and atopic diseases) induced and made chronic by tissue cells whose proliferation is accelerated by LPA mediated by EDG-2.

  一种含有EDG-2拮抗剂的慢性疾病的治疗和/或预防方法。由于结合到LPA受体的亚型EDG-2，EDG-2拮抗剂在治疗和/或预防由EDG-2介导的LPA加速组织细胞增殖导致的慢性疾病（例如，由慢性哮喘、肾小球肾炎、肥胖症、动脉硬化、类风湿和过敏性疾病引起的疾病）方面是有用的。
• Novel isoxazole and thiazole compounds and use thereof as drugs
  申请人：——

  公开号：US20030114505A1

  公开（公告）日：2003-06-19

  The present invention relates to novel isoxazole and thiazole compounds having an excellent lysophosphatidic acid (LPA) receptor antagonistic activity represented by general formula [1] or salts thereof: 1 wherein R1 and R2 represents an optionally substituted alkyl group or the like; R3 represents a hydrogen atom or the like; R4 represent a group selected from the group consisting of (I) optionally substituted phenyl, aryl, or heterocycle, (II) substituted or nonsubstituted alkyl, and (III) substituted or nonsubstituted alkenyl, alternatively, R3 and R4 may form a ring structure together with a carbon atom to which they bind; and X represents an oxygen atom or a sulfur atom, provided that, when R3 is a hydrogen atom, R4 represents a group other than methyl, and the use thereof as a medicine.

  本发明涉及一种新型异噁唑和噻唑化合物，其具有优异的溶血磷脂酸（LPA）受体拮抗活性，通式为[1]或其盐：其中，R1和R2代表可选取代的烷基或类似物；R3代表氢原子或类似物；R4代表从（I）可选取代的苯基、芳基或杂环基，（II）取代或未取代的烷基，以及（III）取代或未取代的烯基中选择的基团，或者R3和R4可以与它们所结合的碳原子一起形成环状结构；X代表氧原子或硫原子，前提是当R3是氢原子时，R4代表甲基以外的基团，以及其作为药物的用途。
• Compounds having lysophosphatidic acid receptor antagonism and uses thereof
  申请人：Tanaka Motoyuki

  公开号：US20070149595A1

  公开（公告）日：2007-06-28

  The present invention relates to a compound represented by formula (I): (wherein the symbols in formula were described in the description), a salt thereof, a solvate thereof or a prodrug thereof. Since the compound of the present invention binds to and is antagonistic to an LPA receptor (particularly, EDG-2), it is useful for prevention and/or treatment of urinary system disease (prostatic hypertrophy or neurogenic bladder dysfunction disease, spinal cord neoplasm, nucleous hernia, spinal canal stenosis, diseases caused by diabetes, occlusion disease of lower urinary tract, inflammatory disease of lower urinary tract, and polyuria), carcinoma-associated disease, proliferative disease, inflammation system disease, immune system disease, disease by secretory dysfunction, brain-related disease and/or chronic disease.

  本发明涉及一种由式(I)表示的化合物：（其中式中的符号在说明中被描述），其盐，溶剂化物或前药。由于本发明的化合物与LPA受体（特别是EDG-2）结合并具有拮抗作用，因此它对预防和/或治疗泌尿系统疾病（前列腺增生或神经源性膀胱功能障碍疾病，脊髓肿瘤，核突出，脊柱管狭窄，由糖尿病引起的疾病，下尿路梗阻疾病，下尿路炎症性疾病和多尿症），癌症相关疾病，增殖性疾病，炎症系统疾病，免疫系统疾病，分泌功能障碍疾病，与大脑相关的疾病和/或慢性疾病具有用处。