2-[[2-[Bis(2-hydroxyethyl)amino]-4,8-di(piperidin-1-yl)pyrimido[5,4-d]pyrimidin-6-yl]-(2-hydroxyethyl)amino]ethanol;hydrochloride | 35763-39-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-[[2-[Bis(2-hydroxyethyl)amino]-4,8-di(piperidin-1-yl)pyrimido[5,4-d]pyrimidin-6-yl]-(2-hydroxyethyl)amino]ethanol;hydrochloride
• CAS: 35763-39-4
• 化学式: C₂₄H₄₀N₈O₄*ClH
• 分子量: 541.094
• InChiKey: AMZYKVBMOGPVGN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  37
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  145
• 氢给体数：
  5
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  双嘧达莫 在 盐酸 作用下， 以 异丙醇 为溶剂， 以62.7%的产率得到2-[[2-[Bis(2-hydroxyethyl)amino]-4,8-di(piperidin-1-yl)pyrimido[5,4-d]pyrimidin-6-yl]-(2-hydroxyethyl)amino]ethanol;hydrochloride
  参考文献：
  名称：

  New Dipyridamole Salt with Improved Dissolution and Oral Bioavailability under Hypochlorhydric Conditions

  摘要：

  The aim of this study was to develop new dipyridamole (DP) salts with pH-independent solubility for improving oral bioavailability under hypochlorhydria. Salt screening was carried out using nine counterions by the temperature gradient method. Six DP salts were obtained, and there was marked improvement in dissolution behavior for all DP salts in a neutral medium. Most DP salts were stable under accelerated conditions. On the basis of the dissolution and stability data, DP tosylate (DP/TS) was selected as a promising DP salt. The pharmacokinetics of DP and the promising DP salt were assessed in normal rats and omeprazole-treated rats as a hypochlorhydric model. After oral administration of DP/TS (10 mg-DP/kg) in normal rats, enhanced DP exposures with increased C-max and AUC(0-3) were observed compared with those with DP by ca. 2.8- and 1.7-fold, respectively. There was ca. 1 h delay of T-max and ca. 62% reduction of AUC(0-3) for DP in omeprazole-treated rats compared with those for DP in normal rats; however, oral absorption for DP/TS under hypochlorhydria was almost identical to that in normal rats. The newly developed DP/TS might provide better therapeutic efficacy in clinical use for hypochlorhydric patients.

  DOI：

  10.2133/dmpk.dmpk-12-rg-139

文献信息

• Inclusion complexes of dipyridamole with cyclodextrins
  申请人：EDMOND PHARMA S.R.L.

  公开号：EP0295476B1

  公开（公告）日：1992-01-15
• New Dipyridamole Salt with Improved Dissolution and Oral Bioavailability under Hypochlorhydric Conditions
  作者：Chika Taniguchi、Ryo Inoue、Masashi Kato、Kazuhiro Yamashita、Yohei Kawabata、Koichi Wada、Shizuo Yamada、Satomi Onoue

  DOI：10.2133/dmpk.dmpk-12-rg-139

  日期：——

  The aim of this study was to develop new dipyridamole (DP) salts with pH-independent solubility for improving oral bioavailability under hypochlorhydria. Salt screening was carried out using nine counterions by the temperature gradient method. Six DP salts were obtained, and there was marked improvement in dissolution behavior for all DP salts in a neutral medium. Most DP salts were stable under accelerated conditions. On the basis of the dissolution and stability data, DP tosylate (DP/TS) was selected as a promising DP salt. The pharmacokinetics of DP and the promising DP salt were assessed in normal rats and omeprazole-treated rats as a hypochlorhydric model. After oral administration of DP/TS (10 mg-DP/kg) in normal rats, enhanced DP exposures with increased C-max and AUC(0-3) were observed compared with those with DP by ca. 2.8- and 1.7-fold, respectively. There was ca. 1 h delay of T-max and ca. 62% reduction of AUC(0-3) for DP in omeprazole-treated rats compared with those for DP in normal rats; however, oral absorption for DP/TS under hypochlorhydria was almost identical to that in normal rats. The newly developed DP/TS might provide better therapeutic efficacy in clinical use for hypochlorhydric patients.