avanafil

• 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: avanafil
• 英文别名: R-Avanafil；4-[(3-chloro-4-methoxyphenyl)methylamino]-2-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]-N-(pyrimidin-2-ylmethyl)pyrimidine-5-carboxamide
• 化学式: C₂₃H₂₆ClN₇O₃
• 分子量: 483.958
• InChiKey: WEAJZXNPAWBCOA-MRXNPFEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  125
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  avanafil 在 双氧水 作用下， 以 二甲基亚砜 、 乙腈 为溶剂， 反应 24.0h， 生成
  参考文献：
  名称：

  开发用于测定药物制剂中阿伐那非的经验证和稳定性指示的 LC-DAD 和 LC-MS/MS 方法以及通过 LCMS-IT-TOF 鉴定新型降解产物

  摘要：

  Avanafil (AVA) 是治疗勃起功能障碍的最有效药物之一，是一种嘧啶衍生物 PDE5 抑制剂。在目前的工作中，开发并验证了新的液相色谱方法，用于阿伐那非的定量测定及其降解产物的定性测定。阿伐那非的定量测定采用液相色谱-光电二极管阵列检测 (LC-DAD) 和液相色谱-串联质谱 LC-MS/MS 方法，并根据 ICH Q2 (R1) 指南进行充分验证，同时定性测定使用液相色谱质谱 - 离子阱 - 飞行时间（LCMS-IT-TOF）仪器进行。使用相同的反相色谱条件分离阿伐那非及其降解产物，其中使用第二代 C18 键合硅胶整体柱（Chromolith® High Resolution RP-18e，100 × 4.6 mm，Merck KGaA）作为固定相。简而言之，这些方法能够以高精度（回收率 > 95%）和精密度（RSD% < 2.0）对阿伐那非进行定量，LC-DAD 的范围为 0.5–20

  DOI：

  10.3390/molecules23071771
• 作为产物：
  描述：

  3-氯-4-甲氧基苄胺 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 间氯过氧苯甲酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 氯仿 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 avanafil
  参考文献：
  名称：

  The discovery of avanafil for the treatment of erectile dysfunction: A novel pyrimidine-5-carboxamide derivative as a potent and highly selective phosphodiesterase 5 inhibitor

  摘要：

  Novel pyrimidine-5-carboxamide derivatives bearing a 3-chloro-4-methoxybenzylamino group at the 4-position were identified as potent and highly selective phosphodiesterase 5 inhibitors. Among them, we successfully found 10j (avanafil) which exhibited a potent relaxant effect on isolated rabbit cavernosum (EC30 = 2.1 nM) and a high isozyme selectivity. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.10.008

文献信息

• [EN] A PROCESS FOR THE PREPARATION OF AVANAFIL AND ITS NOVEL INTERMEDIATES<br/>[FR] PROCÉDÉ DE PRÉPARATION D'AVANAFIL ET DE SES NOUVEAUX INTERMÉDIAIRES
  申请人：WANBURY LTD

  公开号：WO2015177807A1

  公开（公告）日：2015-11-26

  The present invention relates to a novel compound of Formula (II), and its use in preparation of Avanafil, [Formula should be inserted here] wherein R is -OH, -CI or -OR1 and R1 is C1 to C3 alkyl group.

  本发明涉及一种新型的化合物（II）及其在阿伐那非制备中的应用，[应在此处插入公式]其中R为-OH，-CI或-OR1，R1为C1到C3烷基。
• [EN] PROCESS FOR THE PREPARATION OF (S)-4-[(3-CHLORO-4-METHOXYBENZYL)AMINO]-2-[2- (HYDROXYMETHYL)-1-PYRROLIDINYL]-N-(2-PYRIMIDINYL METHYL-5-PYRIMIDINE CARBOXAMIDE<br/>[FR] PROCÉDÉ POUR LA PRÉPARATION DE (S)-4-[(3-CHLORO -4-MÉTHOXYBENZYL)AMINO]-2-[2- (HYDROXYMÉTHYL)-1-PYRROLIDINYL-N-(2-PYRIMIDINYL MÉTHYL-5-PYRIMIDINE CARBOXAMIDE
  申请人：MSN LAB PRIVATE LTD

  公开号：WO2015001567A1

  公开（公告）日：2015-01-08

  The present invention relates to an improved process for the preparation of (S)-4-[(3- chloro-4-methoxybenzyl)amino]-2-[2-(hydroxymethyl)-1-pyrrolidinyl]-N-(2-pyrimidinyl ethyl)- 5-pyrimidine carboxamide compound of formula-1 represented by the following structural formula.

  本发明涉及一种改进的制备(S)-4-[(3-氯-4-甲氧基苯基)氨基]-2-[2-(羟甲基)-1-吡咯烷基]-N-(2-嘧啶基乙基)-5-嘧啶羧酰胺化合物的方法，该化合物的化学式为1，其结构式如下：
• Orally disintegrating dosage form for administration of avanafil, and associated methods of manufacture and use
  申请人：Vivus, Inc.

  公开号：US10028916B2

  公开（公告）日：2018-07-24

  Formulations are provided for the oral administration of avanafil, a Type V phosphodiesterase inhibitor (“PDE V inhibitor”), and analogs thereof. The formulations are orally disintegrating tablets (ODTs) that rapidly dissolve or disintegrate in the oral cavity. The tablets contain an absorption enhancing composition that increases the duodenal absorption of the active agent, following transfer from the low pH environment of the stomach to the more basic pH of the duodenum. Methods for administering the active agent using the dosage forms are provided. The invention also encompasses a method of selecting components and compositions to incorporate in the formulations which will facilitate increased absorption of the active agent in the duodenum and thus serve as “absorption enhancing compositions” herein. Also provided are methods for manufacturing orally disintegrating tablets to optimize the physical properties of the dosage forms, particularly hardness and disintegration time.

  本研究提供了口服阿伐那非（一种 V 型磷酸二酯酶抑制剂（"PDE V 抑制剂"））及其类似物的制剂。这些制剂为口腔崩解片（ODT），可在口腔中快速溶解或崩解。片剂中含有一种促进吸收的成分，可在活性剂从胃的低 pH 值环境转移到十二指肠的较碱性 pH 值环境后，增加十二指肠对活性剂的吸收。本发明提供了使用该剂型给药活性剂的方法。本发明还包括一种选择成分和组合物的方法，在制剂中加入这些成分和组合物将有助于增加活性剂在十二指肠中的吸收，因此可作为本发明中的 "增强吸收组合物"。本发明还提供了制造口腔崩解片的方法，以优化剂型的物理性质，特别是硬度和崩解时间。
• ORALLY DISINTEGRATING DOSAGE FORM FOR ADMINISTRATION OF AVANAFIL, AND ASSOCIATED METHODS OF MANUFACTURE AND USE
  申请人：Vivus, Inc.

  公开号：US20160331687A1

  公开（公告）日：2016-11-17

  Formulations are provided for the oral administration of avanafil, a Type V phosphodiesterase inhibitor (“PDE V inhibitor”), and analogs thereof. The formulations are orally disintegrating tablets (ODTs) that rapidly dissolve or disintegrate in the oral cavity. The tablets contain an absorption enhancing composition that increases the duodenal absorption of the active agent, following transfer from the low pH environment of the stomach to the more basic pH of the duodenum. Methods for administering the active agent using the dosage forms are provided. The invention also encompasses a method of selecting components and compositions to incorporate in the formulations which will facilitate increased absorption of the active agent in the duodenum and thus serve as “absorption enhancing compositions” herein. Also provided are methods for manufacturing orally disintegrating tablets to optimize the physical properties of the dosage forms, particularly hardness and disintegration time.