3-(N-(4-hydroxyphenyl)-N'methylguanidino)-1-N-(3-(3-isopropylureido)benzyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: 3-(N-(4-hydroxyphenyl)-N'methylguanidino)-1-N-(3-(3-isopropylureido)benzyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one
• 英文别名: 1-[3-[[3-[[N-(4-hydroxyphenyl)-N'-methylcarbamimidoyl]amino]-2-oxo-4,5-dihydro-3H-1-benzazepin-1-yl]methyl]phenyl]-3-propan-2-ylurea
• 化学式: C₂₉H₃₄N₆O₃
• 分子量: 514.627
• InChiKey: BEAHHIZXBVFZJP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  38
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  118
• 氢给体数：
  5
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-叠氮基-2-氧代-2,3,4,5-四氢-1H-苯并b氮杂卓 在 palladium on activated charcoal 氢氧化钾 、 四丁基溴化铵 、 氢气 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 13.33h， 生成 3-(N-(4-hydroxyphenyl)-N'methylguanidino)-1-N-(3-(3-isopropylureido)benzyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one
  参考文献：
  名称：

  1,3-Disubstituted Benzazepines as Novel, Potent, Selective Neuropeptide Y Y1 Receptor Antagonists

  摘要：

  A novel series of potent and selective non-peptide neuropeptide Y (NPY) Y1 receptor antagonists, having benzazepine nuclei, have been designed, synthesized, and evaluated for activity. Chemical modification of the R-1 and R-3 substituents in structure 1 (Chart 1) yields several compounds that show high affinity for the Y1 receptor (K-i values of less than 10 nM). SAR studies revealed that introduction of an isopropylurea group at R-1 and a 3-(benzo-condensed-urea) group, 3-(fluorophenylurea) group, or a 3-(N-(4-hydroxyphenyl)guanidine) group at R-3 in structure 1 afforded potent and subtype-selective NPY Y1 receptor antagonists. 3-(3-(Benzothiazol-6-yl)ureido)-1-N-(3-(N'-(3-isopropylureido))benzyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (21), which was one of the most potent derivatives, competitively inhibited specific [I-125]peptide YY (PW) binding to Y1 receptors in human neuroblastoma SK-N-MC cells (K-i = 5.1 nM). 21 not only inhibited the Y1 receptor-mediated increase in cytosolic free Ca2+ concentration in SK-N-MC cells but also antagonized the Y1 receptor-mediated inhibitory effect of peptide YY on gastrin-induced histamine release in rat enterochromaffin-like cells. 21 showed no significant affinity in 17 receptor binding assays including Y2, Y4, and Y5 receptors.

  DOI：

  10.1021/jm990044m

文献信息

• [EN] SELECTIVE DOPAMIN D3 RECEPTOR AGONISTS FOR THE TREATMENT OF SEXUAL DYSFUNCTION<br/>[FR] AGONISTES SELECTIFS DU RECEPTEUR DE LA DOPAMINE D3 POUR TRAITER LES TROUBLES D'ORDRE SEXUEL
  申请人：PFIZER LTD

  公开号：WO2003051370A1

  公开（公告）日：2003-06-26

  The use of a composition comprising a selective dopamine D3 receptor agonist, wherein said dopamine D3 receptor agonist is at least about 15-times more functionally selective for a dopamine D3 receptor as compared with a dopamine D2 receptor when measured using the same functional assay, in the preparation of a medicament for the treatment and/or prevention of sexual dysfunction.

  使用一种包含选择性多巴胺D3受体激动剂的组合物，其中所述的多巴胺D3受体激动剂在使用相同的功能性测定时，与多巴胺D2受体相比至少具有15倍的功能选择性，用于制备治疗和/或预防性功能障碍的药物。
• 1,3-Disubstituted Benzazepines as Novel, Potent, Selective Neuropeptide Y Y1 Receptor Antagonists
  作者：Yasushi Murakami、Hirokazu Hara、Tetsuo Okada、Hiroshi Hashizume、Makoto Kii、Yasunobu Ishihara、Michio Ishikawa、Mayumi Shimamura、Shin-inchi Mihara、Goro Kato、Kohji Hanasaki、Sanji Hagishita、Masafumi Fujimoto

  DOI：10.1021/jm990044m

  日期：1999.7.1

  A novel series of potent and selective non-peptide neuropeptide Y (NPY) Y1 receptor antagonists, having benzazepine nuclei, have been designed, synthesized, and evaluated for activity. Chemical modification of the R-1 and R-3 substituents in structure 1 (Chart 1) yields several compounds that show high affinity for the Y1 receptor (K-i values of less than 10 nM). SAR studies revealed that introduction of an isopropylurea group at R-1 and a 3-(benzo-condensed-urea) group, 3-(fluorophenylurea) group, or a 3-(N-(4-hydroxyphenyl)guanidine) group at R-3 in structure 1 afforded potent and subtype-selective NPY Y1 receptor antagonists. 3-(3-(Benzothiazol-6-yl)ureido)-1-N-(3-(N'-(3-isopropylureido))benzyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (21), which was one of the most potent derivatives, competitively inhibited specific [I-125]peptide YY (PW) binding to Y1 receptors in human neuroblastoma SK-N-MC cells (K-i = 5.1 nM). 21 not only inhibited the Y1 receptor-mediated increase in cytosolic free Ca2+ concentration in SK-N-MC cells but also antagonized the Y1 receptor-mediated inhibitory effect of peptide YY on gastrin-induced histamine release in rat enterochromaffin-like cells. 21 showed no significant affinity in 17 receptor binding assays including Y2, Y4, and Y5 receptors.