Barreca Maria Letizia, Gitto Rosaria, Quartarone Silvana, De Luca Laura, De Sarro Giovambattista, Chimirri Alba
Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy.
J Chem Inf Comput Sci. 2003 Mar-Apr;43(2):651-5. doi: 10.1021/ci025625q.
A three-dimensional pharmacophore model for the binding of noncompetitive AMPA receptor antagonists was developed in order to map common structural features of highly active compounds. This hypothesis, which consists of two hydrophobic regions, one hydrogen bond acceptor and one aromatic region, was successfully used as framework for the design of a new class of allosteric modulators containing a tetrahydroisoquinoline skeleton and for in silico screening. The promising biological results suggested that the identified molecules might be useful "lead compounds" for future drug development.
为了描绘高活性化合物的共同结构特征，开发了一种用于非竞争性AMPA受体拮抗剂结合的三维药效团模型。该假说由两个疏水区域、一个氢键受体和一个芳香区域组成，已成功用作设计一类含有四氢异喹啉骨架的新型变构调节剂以及计算机筛选的框架。有前景的生物学结果表明，所鉴定的分子可能是未来药物开发中有用的“先导化合物”。
