4-(4-Fluoro-phenyl)-2-methoxy-6-methyl-1,4-dihydro-pyrimidine-5-carboxylic acid methyl ester | 251930-53-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4-(4-Fluoro-phenyl)-2-methoxy-6-methyl-1,4-dihydro-pyrimidine-5-carboxylic acid methyl ester
• 英文别名: Methyl 6-(4-fluorophenyl)-2-methoxy-4-methyl-1,6-dihydro-5-pyrimidinecarboxylate；methyl 4-(4-fluorophenyl)-2-methoxy-6-methyl-1,4-dihydropyrimidine-5-carboxylate
• CAS: 251930-53-7
• 化学式: C₁₄H₁₅FN₂O₃
• 分子量: 278.283
• InChiKey: JZXDEVNMIGVOLE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  59.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(4-Fluoro-phenyl)-2-methoxy-6-methyl-1,4-dihydro-pyrimidine-5-carboxylic acid methyl ester 在 盐酸 、 4-二甲氨基吡啶 、 potassium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 15.0h， 生成 4-(4-Fluoro-phenyl)-3-[3-(4-methoxycarbonyl-4-phenyl-piperidin-1-yl)-propylcarbamoyl]-6-methyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid methyl ester
  参考文献：
  名称：

  Design and Synthesis of Novel α_1a Adrenoceptor-Selective Antagonists. 1. Structure−Activity Relationship in Dihydropyrimidinones

  摘要：

  Dihydropyrimidinones such as compound 12 exhibited high binding affinity and subtype selectivity for the cloned human alpha(1a) receptor. Systematic modifications of 12 led to identification of highly potent and subtype-selective compounds such as (+)-30 and (+)-103, with high binding affinity (K-i = 0.2 nM) for alpha(1a) receptor and greater than 1500-fold selectivity over alpha(1b) and alpha(1d) adrenoceptors. The compounds were found to be functional antagonists in human, rat, and dog prostate tissues. Compound (+)-103 exhibited excellent selectively to inhibit intraurethral pressure (IUP) as compared to lowering diastolic blood pressure (DBP) in mongrel dogs (K-b(DBP)/K-b(IUP) = 40) suggesting uroselectivity for alpha(1a)-selective compounds.

  DOI：

  10.1021/jm990200p
• 作为产物：
  描述：

  对氟苯甲醛 在 哌啶 、 碳酸氢钠 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 24.0h， 生成 4-(4-Fluoro-phenyl)-2-methoxy-6-methyl-1,4-dihydro-pyrimidine-5-carboxylic acid methyl ester
  参考文献：
  名称：

  Design and Synthesis of Novel α_1a Adrenoceptor-Selective Antagonists. 1. Structure−Activity Relationship in Dihydropyrimidinones

  摘要：

  Dihydropyrimidinones such as compound 12 exhibited high binding affinity and subtype selectivity for the cloned human alpha(1a) receptor. Systematic modifications of 12 led to identification of highly potent and subtype-selective compounds such as (+)-30 and (+)-103, with high binding affinity (K-i = 0.2 nM) for alpha(1a) receptor and greater than 1500-fold selectivity over alpha(1b) and alpha(1d) adrenoceptors. The compounds were found to be functional antagonists in human, rat, and dog prostate tissues. Compound (+)-103 exhibited excellent selectively to inhibit intraurethral pressure (IUP) as compared to lowering diastolic blood pressure (DBP) in mongrel dogs (K-b(DBP)/K-b(IUP) = 40) suggesting uroselectivity for alpha(1a)-selective compounds.

  DOI：

  10.1021/jm990200p

文献信息

• [EN] SECONDARY AMINO ANILINIC PIPERIDINES AS MCH1 ANTAGONISTS AND USES THEREOF<br/>[FR] PIPERIDINES AMINOANILINIQUES SECONDAIRES UTILISEES COMME ANTAGONISTES DE LA MCH1 ET UTILISATIONS CORRESPONDANTES
  申请人：SYNAPTIC PHARMACEUTICAL CORPOR

  公开号：WO2004005257A1

  公开（公告）日：2004-01-15

  This invention is directed to compounds which are selective antagonists for melanin concentrating hormone-1 (MCH1) receptors. The invention provides a pharmaceutical composition comprising a therapeutically effective amount of the compound of the invention and a pharmaceutically acceptable carrier. This invention provides a pharmaceutical composition made by combining a therapeutically effective amount of the compound of this invention and a pharmaceutically acceptable carrier. This invention further provides a process for making a pharmaceutical composition comprising combining a therapeutically effective amount of the compounds of the invention and a pharmaceutically acceptable carrier. This invention also provides a method of reducing the body mass of a subject which comprises administering to the subject an amount of a compound of the invention effective to reduce the body mass of the subject. This invention further provides a method of treating a subject suffering from depression and/or anxiety which comprises administering to the subject an amount of a compound of the invention effective to treat the subject=s depression and/or anxiety. This invention further provides a method of treating a subject suffering from a urinary disorder.

  本发明涉及对黑素集中激素-1（MCH1）受体具有选择性的拮抗剂化合物。该发明提供了一种含有治疗有效量的本发明化合物和药用辅料的药物组合物。本发明还提供了一种通过结合治疗有效量的本发明化合物和药用辅料制成的药物组合物。本发明进一步提供了一种制作含有治疗有效量的本发明化合物和药用辅料的药物组合物的方法。本发明还提供了一种减少主体体质量的方法，包括向主体施用有效减少主体体质量的本发明化合物的量。本发明还提供了一种治疗患有抑郁和/或焦虑的主体方法，包括向主体施用有效治疗主体的抑郁和/或焦虑的本发明化合物的量。本发明还提供了一种治疗患有尿路障碍的主体方法。
• Secondary amino anilinic piperidines as mch1 antagonists and uses thereof
  申请人：Marzabadi R. Mohammad

  公开号：US20050245743A1

  公开（公告）日：2005-11-03

  This invention is directed to compounds which are selective antagonists for melanin concentrating hormone-1 (MCH1) receptors. The invention provides a pharmaceutical composition comprising a therapeutically effective amount of the compound of the invention and a pharmaceutically acceptable carrier. This invention provides a pharmaceutical composition made by combining a therapeutically effective amount of the compound of this invention and a pharmaceutically acceptable carrier. This invention further provides a process for making a pharmaceutical composition comprising combining a therapeutically effective amount of the compounds of the invention and a pharmaceutically acceptable carrier. This invention also provides a method of reducing the body mass of a subject which comprises administering to the subject an amount of a compound of the invention effective to reduce the body mass of the subject. This invention further provides a method of treating a subject suffering from depression and/or anxiety which comprises administering to the subject an amount of a compound of the invention effective to treat the subject=s depression and/or anxiety. This invention further provides a method of treating a subject suffering from a urinary disorder.

  本发明涉及一种选择性抗黑色素浓集激素-1（MCH1）受体的化合物。本发明提供一种药物组合物，包括本发明化合物的治疗有效量和药学上可接受的载体。本发明提供一种由本发明化合物的治疗有效量和药学上可接受的载体组成的药物组合物。本发明还提供一种制备药物组合物的方法，包括将本发明化合物的治疗有效量和药学上可接受的载体组合。本发明还提供一种减轻受试者体重的方法，包括向受试者投予本发明化合物的有效量以减轻受试者的体重。本发明还提供一种治疗患有抑郁症和/或焦虑症的受试者的方法，包括向受试者投予本发明化合物的有效量以治疗受试者的抑郁症和/或焦虑症。本发明还提供一种治疗患有泌尿系统疾病的受试者的方法。
• Chemical compounds
  申请人：Drewry David

  公开号：US20070099944A1

  公开（公告）日：2007-05-03

  The present invention relates to indazolo-tetrahydropyrimidine-carboxamide derivatives, compositions and medicaments containing the same, as well as processes for the preparation and use of such compounds, compositions and medicaments. Such indazolo-tetrahydropyrimidine-carboxamide derivatives are useful in the treatment of diseases associated with inappropriate ROCK-1 kinase.

  本发明涉及吲哚唑-四氢嘧啶-羧酰胺衍生物、含有该类化合物的组合物和药物，以及这些化合物、组合物和药物的制备和使用方法。这些吲哚唑-四氢嘧啶-羧酰胺衍生物在治疗与不适当的ROCK-1激酶有关的疾病方面是有用的。
• Indazolo-tetrahydropyrimidine-carboxamide derivative kinase inhibitors
  申请人：SmithKline Beecham Corporation

  公开号：US07560467B2

  公开（公告）日：2009-07-14

  The present invention relates to indazolo-tetrahydropyrimidine-carboxamide derivatives, compositions and medicaments containing the same, as well as processes for the preparation and use of such compounds, compositions and medicaments. Such indazolo-tetrahydropyrimidine-carboxamide derivatives are useful in the treatment of diseases associated with inappropriate ROCK-1 kinase.

  本发明涉及吲唑-四氢嘧啶-羧酰胺衍生物、含有该衍生物的组合物和药物、以及制备和使用这些化合物、组合物和药物的方法。这些吲唑-四氢嘧啶-羧酰胺衍生物在治疗与不适当的ROCK-1激酶有关的疾病方面是有用的。
• Secondary amino anilinic piperidines as MCH1 antagonists and uses thereof
  申请人：H. Lunbeck A/S

  公开号：US07473698B2

  公开（公告）日：2009-01-06

  This invention is directed to compounds which are selective antagonists for melanin concentrating hormone-1 (MCH1) receptors. The invention provides a pharmaceutical composition comprising a therapeutically effective amount of the compound of the invention and a pharmaceutically acceptable carrier. This invention provides a pharmaceutical composition made by combining a therapeutically effective amount of the compound of this invention and a pharmaceutically acceptable carrier. This invention further provides a process for making a pharmaceutical composition comprising combining a therapeutically effective amount of the compounds of the invention and a pharmaceutically acceptable carrier. This invention also provides a method of reducing the body mass of a subject which comprises administering to the subject an amount of a compound of the invention effective to reduce the body mass of the subject. This invention further provides a method of treating a subject suffering from depression and/or anxiety which comprises administering to the subject an amount of a compound of the invention effective to treat the subject=s depression and/or anxiety. This invention further provides a method of treating a subject suffering from a urinary disorder.

  该发明涉及选择性拮抗黑色素浓集激素-1（MCH1）受体的化合物。该发明提供了一种制药组合物，包括本发明化合物的治疗有效量和药学上可接受的载体。该发明提供了一种制药组合物的制备方法，包括将本发明化合物的治疗有效量和药学上可接受的载体结合。该发明还提供了一种减少受试者体重的方法，包括向受试者施用本发明化合物的有效量以减少受试者的体重。该发明还提供了一种治疗患有抑郁症和/或焦虑症的受试者的方法，包括向受试者施用本发明化合物的有效量以治疗受试者的抑郁症和/或焦虑症。该发明还提供了一种治疗患有尿液障碍的受试者的方法。