Design, synthesis, and in vivo evaluation of oxamniquine methacrylate and acrylamide prodrugs
- 作者：Roberto Parise Filho ; Carla Maria de Souza Menezes ; Pedro Luiz Silva Pinto ; Gilberto Alvarenga Paula ; Carlos Alberto Br ; t ; Maria Amé ; lia Barata da Silveira
- 关键词：Oxamniquine ; Schistosomicide ; Polymeric prodrug ; Molecular modeling
- 刊名：Bioorganic and Medicinal Chemistry
- 出版年：2007
- 期刊代码：9_09680896
- 类别：ch
- 出版时间：1 February 2007
- 卷：15
- 期：3
- 页码：1229-1236
- 文件大小：1233 K
摘要
Oxamniquine is an antiparasitic agent commonly used in therapeutics against Schistosoma mansoni. Although it is well tolerated, some adverse effects justify the search for new compounds with prolonged biological action, so that monomeric and polymeric oxamniquine prodrugs were designed. Synthetic results assisted by molecular modeling study showed the possibility to obtain the corresponding monomeric forms of the oxamniquine methacrylate (1) and oxamniquine acrylamide (2). Successful copolymerization procedure only occurred on the methacrylic compound, generating the oxamniquine methacrylate copolymer (3). Submitted to a preliminary in vivo biological evaluation, a similar oxamniquine profile was observed to the monomeric forms although an inadequate drug release may be responsible for the methacrylic copolymer failure.