2-(4-(N-(3,5-dimethoxy-4-methylphenylcarbonyl)-N-(3-phenylpropyl)aminomethyl)phenyloxy)-4-methylbenzoic acid methyl ester

• 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-(4-(N-(3,5-dimethoxy-4-methylphenylcarbonyl)-N-(3-phenylpropyl)aminomethyl)phenyloxy)-4-methylbenzoic acid methyl ester
• 英文别名: Methyl 2-[4-[[(3,5-dimethoxy-4-methylbenzoyl)-(3-phenylpropyl)amino]methyl]phenoxy]-4-methylbenzoate
• 化学式: C₃₅H₃₇NO₆
• 分子量: 567.682
• InChiKey: WCQGNVNLKYSCGF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  42
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  74.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(4-(N-(3,5-dimethoxy-4-methylphenylcarbonyl)-N-(3-phenylpropyl)aminomethyl)phenyloxy)-4-methylbenzoic acid methyl ester 在 水 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 2-(4-{[(3,5-dimethoxy-4-methylbenzoyl)(3-phenylpropyl)amino]methyl}phenoxy)-4-methylbenzoic acid
  参考文献：
  名称：

  从新型的溶血磷脂酸受体1拮抗剂发现ONO-7300243：从命中到领先

  摘要：

  溶血磷脂酸（LPA）通过一系列G蛋白偶联受体LPA 1-6引起各种生理反应。针对LPA 1的高通量筛选得到了化合物7a。随后优化的7a导致了ONO-7300243（17a）作为新型有效的LPA 1拮抗剂，在体内表现出良好的疗效。口服剂量为30 mg / kg的17a导致大鼠尿道内压力降低。值得注意的是，该化合物是在效力的α等于1肾上腺素能受体拮抗剂坦索罗辛，在临床实践中用于治疗伴有前列腺增生（BPH）的排尿困难。与坦洛新相比，化合物17a在该剂量下对平均血压没有影响。这些结果表明，LPA 1拮抗剂可用于治疗BPH而不会影响血压。在此，我们报告了一系列独特的LPA 1拮抗剂的体内领先效果及其体内功效。

  DOI：

  10.1021/acsmedchemlett.6b00225
• 作为产物：
  描述：

  4-甲基水杨酸甲酯 在 三乙酰氧基硼氢化钠 、 potassium carbonate 、 1-羟基苯并三唑 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 17.5h， 生成 2-(4-(N-(3,5-dimethoxy-4-methylphenylcarbonyl)-N-(3-phenylpropyl)aminomethyl)phenyloxy)-4-methylbenzoic acid methyl ester
  参考文献：
  名称：

  从新型的溶血磷脂酸受体1拮抗剂发现ONO-7300243：从命中到领先

  摘要：

  溶血磷脂酸（LPA）通过一系列G蛋白偶联受体LPA 1-6引起各种生理反应。针对LPA 1的高通量筛选得到了化合物7a。随后优化的7a导致了ONO-7300243（17a）作为新型有效的LPA 1拮抗剂，在体内表现出良好的疗效。口服剂量为30 mg / kg的17a导致大鼠尿道内压力降低。值得注意的是，该化合物是在效力的α等于1肾上腺素能受体拮抗剂坦索罗辛，在临床实践中用于治疗伴有前列腺增生（BPH）的排尿困难。与坦洛新相比，化合物17a在该剂量下对平均血压没有影响。这些结果表明，LPA 1拮抗剂可用于治疗BPH而不会影响血压。在此，我们报告了一系列独特的LPA 1拮抗剂的体内领先效果及其体内功效。

  DOI：

  10.1021/acsmedchemlett.6b00225

文献信息

• LPA Receptor Antagonists
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP2565178A1

  公开（公告）日：2013-03-06

  A compound of the general formula (I): (wherein the symbols are as defined in the description), or a non-toxic salt thereof This compound engages in LPA receptor bonding and antagonism and hence is useful in the prevention and/or treatment of urinary system disease (symptom with prostatic hypertrophy or neurogenic bladder dysfunction disease, symptom to be caused by spinal cord neoplasm, nucleous hernia, spinal canal stenosis or diabetes, occlusion disease of lower urinary tract, inflammatory disease of lower urinary tract, polyuria), carcinoma-associated disease (solid tumor, solid tumor metastasis, angiofibroma, myeloma, multiple myeloma, Kaposi's sarcoma, leucemia and carcinomatous infiltration transition), proliferative disease (disorder with aberrant angiogenesis, artery obstruction and pulmonary fibrosis), inflammation / immune system disease (psoriasis, nephropathy, hepatitis and pneumonitis symptom), disease caused by secretory dysfunction (Sjogren syndrome), brain-related disease (brain infarction, cerebral apoplexy and brain or peripheral neuropathy) or chronic disease (chronic asthma, glomerulonephritis, obesity, prostate hyperplasia, diseases caused by arteriosclerosis process, rheumatism or atopic dermatitis).

  通式(I)的化合物： (其中符号如描述中所定义），或其无毒盐 该化合物参与 LPA 受体的结合和拮抗作用，因此可用于预防和/或治疗泌尿系统疾病（症状为前列腺肥大或神经源性膀胱功能障碍疾病、脊髓肿瘤、核疝、椎管狭窄或糖尿病、下尿路闭塞症、下尿路炎症、多尿）、癌症相关疾病（实体瘤、实体瘤转移、血管纤维瘤、骨髓瘤、多发性骨髓瘤卡波西肉瘤、白血病和癌浸润转变）、增殖性疾病（血管异常生成障碍、动脉阻塞和肺纤维化）、炎症/免疫系统疾病（银屑病、肾病、肝炎和肺炎症状）、分泌功能障碍引起的疾病（Sjogren 综合症）、与脑有关的疾病（脑梗塞、脑中风、脑或周围神经病）或慢性疾病（慢性哮喘、肾小球肾炎、肥胖症、前列腺增生、动脉硬化过程引起的疾病、风湿病或特应性皮炎）。
• LPA RECEPTOR ANTAGONISTS
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1553075B1

  公开（公告）日：2013-08-14
• Lpa receptor antagonist
  申请人：Terakado Masahiko

  公开号：US20060148830A1

  公开（公告）日：2006-07-06

  A compound of the general formula (I): (wherein the symbols are as defined in the description), or a non-toxic salt thereof. This compound engages in LPA receptor bonding and antagonism and hence is useful in the prevention and/or treatment of urinary system disease (symptom with prostatic hypertrophy or neurogenic bladder dysfunction disease, symptom to be caused by spinal cord neoplasm, nucleous hernia, spinal canal stenosis or diabetes, occlusion disease of lower urinary tract, inflammatory disease of lower urinary tract, polyuria), carcinoma-associated disease (solid tumor, solid tumor metastasis, angiofibroma, myeloma, multiple myeloma, Kaposi's sarcoma, leucemia and carcinomatous infiltration transition), proliferative disease (disorder with aberrant angiogenesis, artery obstruction and pulmonary fibrosis), inflammation/immune system disease (psoriasis, nephropathy, hepatitis and pneumonitis symptom), disease caused by secretory dysfunction (Sjogren syndrome), brain-related disease (brain infarction, cerebral apoplexy and brain or peripheral neuropathy) or chronic disease (chronic asthma, glomerulonephritis, obesity, prostate hyperplasia, diseases caused by arteriosclerosis process, rheumatism or atopic dermatitis).
• LPA RECEPTOR ANTAGONIST
  申请人：Terakado Masahiko

  公开号：US20080293764A1

  公开（公告）日：2008-11-27

  A compound of the general formula (I): (wherein the symbols are as defined in the description), or a non-toxic salt thereof. This compound engages in LPA receptor bonding and antagonism and hence is useful in the prevention and/or treatment of urinary system disease (symptom with prostatic hypertrophy or neurogenic bladder dysfunction disease, symptom to be caused by spinal cord neoplasm, nucleous hernia, spinal canal stenosis or diabetes, occlusion disease of lower urinary tract, inflammatory disease of lower urinary tract, polyuria), carcinoma-associated disease (solid tumor, solid tumor metastasis, angiofibroma, myeloma, multiple myeloma, Kaposi's sarcoma, leucemia and carcinomatous infiltration transition), proliferative disease (disorder with aberrant angiogenesis, artery obstruction and pulmonary fibrosis), inflammation/immune system disease (psoriasis, nephropathy, hepatitis and pneumonitis symptom), disease caused by secretory dysfunction (Sjogren syndrome), brain-related disease (brain infarction, cerebral apoplexy and brain or peripheral neuropathy) or chronic disease (chronic asthma, glomerulonephritis, obesity, prostate hyperplasia, diseases caused by arteriosclerosis process, rheumatism or atopic dermatitis).
• US7820682B2
  申请人：——

  公开号：US7820682B2

  公开（公告）日：2010-10-26