1,6-dihydro-5-methoxycarbonyl-2-methoxy-1-(4-nitrophenyloxy)carbonyl-6-(3,4,5-trifluorophenyl)-4-methylpyrimidine | 179482-72-5

• 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: 1,6-dihydro-5-methoxycarbonyl-2-methoxy-1-(4-nitrophenyloxy)carbonyl-6-(3,4,5-trifluorophenyl)-4-methylpyrimidine
• 英文别名: 1,6-Dihydro-5-methoxycarbonyl-2-methoxy-4-methyl-1-(4-nitro phenyloxy)carbonyl-6-(3,4,5-trifluorophenyl)-pyrimidine；5-O-methyl 3-O-(4-nitrophenyl) 2-methoxy-6-methyl-4-(3,4,5-trifluorophenyl)-4H-pyrimidine-3,5-dicarboxylate
• CAS: 179482-72-5
• 化学式: C₂₁H₁₆F₃N₃O₇
• 分子量: 479.369
• InChiKey: HRVMTKODCUSKNR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  123
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  3-[4-(pyridin-2-yl)-piperidine-1-yl]propylamine 、 1,6-dihydro-5-methoxycarbonyl-2-methoxy-1-(4-nitrophenyloxy)carbonyl-6-(3,4,5-trifluorophenyl)-4-methylpyrimidine 以57%的产率得到1,6-Dihydro-2-methoxy-5-methoxycarbonyl-4-methyl-1-{N-[4-(2-pyridyl)-piperidin-1-yl]-propyl}carbamoyl-6-(3,4,5-trifluoro-phenyl)-pyrimidine
  参考文献：
  名称：

  5-(heterocyclic alkyl)-6-aryl-dihydropyrimidines

  摘要：

  该发明涉及以下结构的二氢嘧啶化合物，这些化合物是人类α1A受体的选择性拮抗剂。该发明还涉及利用这些化合物降低眼压、抑制胆固醇合成、放松下尿路组织、治疗良性前列腺增生、阳痿、心律失常以及治疗任何需要对α1A受体进行拮抗的疾病。该发明进一步提供了一种包含上述定义化合物的治疗有效量和药用可接受载体的药物组合物。

  公开号：

  US06245773B1
• 作为产物：
  描述：

  Methyl 2-acetyl-3-(3,4,5-trifluoro-phenyl)-acrylate 在 4-二甲氨基吡啶 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 1,6-dihydro-5-methoxycarbonyl-2-methoxy-1-(4-nitrophenyloxy)carbonyl-6-(3,4,5-trifluorophenyl)-4-methylpyrimidine
  参考文献：
  名称：

  5-(heterocyclic alkyl)-6-aryl-dihydropyrimidines

  摘要：

  该发明涉及以下结构的二氢嘧啶化合物，这些化合物是人类α1A受体的选择性拮抗剂。该发明还涉及利用这些化合物降低眼压、抑制胆固醇合成、放松下尿路组织、治疗良性前列腺增生、阳痿、心律失常以及治疗任何需要对α1A受体进行拮抗的疾病。该发明进一步提供了一种包含上述定义化合物的治疗有效量和药用可接受载体的药物组合物。

  公开号：

  US06245773B1

文献信息

• [EN] DIHYDROPYRIMIDINES AND USES THEREOF<br/>[FR] DIHYDROPYRIMIDINES ET LEURS UTILISATIONS
  申请人：SYNAPTIC PHARMACEUTICAL CORPORATION

  公开号：WO1996014846A1

  公开（公告）日：1996-05-23

  (EN) This invention is directed to dihydropyrimidine compounds which are selective antagonists for human $g(a)1C receptors. This invention is also related to uses of these compounds for lowering intraocular pressure, inhibiting cholesterol synthesis, relaxing lower urinary tract tissue, the treatment of benign prostatic hyperplasia, impotence, cardiac arrhythmia and for the treatment of any disease where the antagonism of the $g(a)1C receptor may be useful. The invention further provides a pharmaceutical composition comprising a therapeutically effective amount of the above-defined compounds and a pharmaceutically acceptable carrier.(FR) Cette invention se rapporte à des composés dihydropyrimidine qui sont des antagonistes sélectifs pour les récepteurs $g(a)1C humains, ainsi qu'aux utilisations de ces composés dans la réduction de la pression intraoculaire, l'inhibition de la synthèse du cholestérol, le relâchement des tissus inférieurs des voies urinaires, le traitement de l'hyperplasie prostatique bénigne, l'impuissance, l'arythmie cardiaque et le traitement de toutes maladies pour lesquelles l'antagonisme du récepteur $g(a)1C peut être utile. L'invention se rapporte encore à une composition pharmaceutique comprenant une quantité thérapeutiquement efficace des composés définis ci-dessus et à un excipient pharmaceutiquement acceptable.

  这项发明涉及选择性拮抗人类$g(a)1C受体的二氢嘧啶化合物。该发明还涉及使用这些化合物降低眼内压、抑制胆固醇合成、放松下尿路组织、治疗良性前列腺增生、阳痿、心律失常以及治疗任何需要拮抗$g(a)1C受体的疾病。该发明还提供了一种制药组合物，包括上述定义的化合物的治疗有效量和药用载体。
• [EN] DIDHYDROPYRIMIDINES AND USES THEREOF<br/>[FR] DIHYDROPYRIMIDINES ET LEURS EMPLOIS
  申请人：SYNAPTIC PHARMACEUTICAL CORPORATION

  公开号：WO1997042956A1

  公开（公告）日：1997-11-20

  (EN) This invention is directed to dihydropyrimidine compounds which are selective antagonists for human $g(a)1A receptors. This invention is also related to uses of these compounds for lowering intraocular pressure, inhibiting cholesterol synthesis, relaxing lower urinary tract tissue, the treatment of benign prostatic hyperplasia, impotency, cardiac arrhythmia and for the treatment of any disease where the antagonism of the $g(a)1A receptor may be useful. The invention further provides a pharmaceutical composition comprising a therapeutically effective amount of the above-defined compounds and a pharmaceutically acceptable carrier.(FR) L'invention concerne des composés de dihydropyrimidine qui sont des antagonistes sélectifs de récepteurs humains $g(a)1A. L'invention concerne également les emplois desdits composés pour abaisser la pression intraoculaire, inhiber la synthèse du cholestérol, soulager le tissu du bas appareil urinaire, ainsi que pour traiter l'hyperplasie prostatique bénigne, l'impuissance, l'arythmie cardiaque et toute autre maladie pour laquelle l'antagonisme du récepteur $g(a)1A peut être utile. L'invention décrit en outre une composition pharmaceutique contenant une dose thérapeutiquement efficace des composés susmentionnés et un excipient pharmaceutiquement admissible.

  (中) 本发明涉及二氢嘧啶化合物，其是人类$g(a)1A受体的选择性拮抗剂。本发明还涉及使用这些化合物降低眼压、抑制胆固醇合成、放松下尿路组织、治疗良性前列腺增生、阳痿、心律失常以及治疗任何可能有用的$g(a)1A受体拮抗剂的疾病。本发明还提供了一种药物组合物，包括上述定义化合物的治疗有效量和药用载体。
• Dihydropyrimidines and uses thereof
  申请人：Synaptic Pharmaceutical Corporation

  公开号：US20020010186A1

  公开（公告）日：2002-01-24

  This invention is directed to dihydropyrimidine compounds which are selective antagonists for human &agr; 1A receptors. This invention is also related to uses of these compounds for lowering intraocular pressure, inhibiting cholesterol synthesis, relaxing lower urinary tract tissue, the treatment of benign prostatic hyperplasia, impotency, cardiac arrhythmia and for the treatment of any disease where the antagonism of the &agr; 1A receptor may be useful. The invention further provides a pharmaceutical composition comprising a therapeutically effective amount of the above-defined compounds and a pharmaceutically acceptable carrier.

  这项发明涉及二氢嘧啶化合物，它们是人类α1A受体的选择性拮抗剂。此发明还涉及使用这些化合物降低眼压、抑制胆固醇合成、放松下尿路组织、治疗良性前列腺增生、阳痿、心律失常和治疗任何需要拮抗α1A受体的疾病。该发明还提供一种制药组合物，包括上述定义化合物的治疗有效量和药学可接受的载体。
• Design and Synthesis of Novel α₁_a Adrenoceptor-Selective Antagonists. 3. Approaches To Eliminate Opioid Agonist Metabolites by Using Substituted Phenylpiperazine Side Chains
  作者：Bharat Lagu、Dake Tian、Dhanapalan Nagarathnam、Mohammad R. Marzabadi、Wai C. Wong、Shou W. Miao、Fengqi Zhang、Wanying Sun、George Chiu、James Fang、Carlos Forray、Raymond S. L. Chang、Richard W. Ransom、Tsing B. Chen、Stacey O'Malley、Kanyin Zhang、Kamlesh P. Vyas、Charles Gluchowski

  DOI：10.1021/jm990202+

  日期：1999.11.1

  Dihydropyrimidinones, such as 1, represent a novel class of alpha(1a) adrenoceptor antagonists with potential for the treatment of benign prostatic hyperplasia (BPH) (see part 1 of this series). Analysis of the metabolites of 1 revealed that 4-methoxycarbonyl-4-phenylpiperidine is formed as the major metabolite and is an agonist at the mu-opioid receptor. To circumvent any potential liability resulting from the metabolite, we decided to identify alternate templates devoid of agonist activity at the mu-opioid receptor to replace the 4-methoxycarbonyl-4-phenylpiperidine moiety. The present study describes the synthesis and SAR of dihydropyrimidinones linked to substituted 4-phenylpiperazine containing side chains. Compound (+)-38 was identified as a lead compound with a binding and functional profile comparable to that of 1. The putative metabolite 2-carboxamidophenylpiperazine has negligible affinity for the mu-opioid receptor.
• DIHYDROPYRIMIDINES AND USES THEREOF
  申请人：SYNAPTIC PHARMACEUTICAL CORPORATION

  公开号：EP0790826A1

  公开（公告）日：1997-08-27