Sharma B K, Singh P
Department of Chemistry, S. K. Government College, Sikar 332 001, India.
J Enzyme Inhib Med Chem. 2007 Apr;22(2):165-9. doi: 10.1080/14756360601051290.
A quantitative structure-activity relationship (QSAR) study was conducted on the antagonistic activities of derivatives of 2-aryl-1,2,4-triazolo[4,3-alpha]quinoxaline at the human A3 adenosine receptor. As per the structural framework, the title analogues were subdivided into two congeneric series, namely the 1,4-dione and the 4-amino-1-one series. A majority of substituents occurred at the R- and a limited number at the X-positions in both of these series. In the case of the 1,4-dione series, the derived significant QSAR equation revealed that those substituents exhibiting a larger field effect at R renders the molecule to more efficiently bind at the receptor site. The study also extrapolated the requirement of electron-donor substituents at the X-position which, at present, is regarded as insensitive to any interaction due to limited substitution. However, the X-position may be explored in a further synthetic study. From the derived correlation equation for the 4-amino-1-one series, it appeared that a strong electron-withdrawing substituent at R will enhance the pK(i) value of a compound while a strong electron-donor at this position will have a detrimental effect on it. Based on correlation equations, derived using different electronic parameters, it may be interpreted that the two series of compounds attain different orientation inside the recognition site of the receptor.
对2-芳基-1,2,4-三唑并[4,3-α]喹喔啉衍生物在人A3腺苷受体上的拮抗活性进行了定量构效关系（QSAR）研究。根据结构框架，标题类似物被细分为两个同系物系列，即1,4-二酮系列和4-氨基-1-酮系列。在这两个系列中，大多数取代基出现在R位，少数出现在X位。对于1,4-二酮系列，推导得到的显著QSAR方程表明，在R位表现出较大场效应的取代基使分子更有效地结合在受体位点。该研究还推断了X位对供电子取代基的需求，目前由于取代有限，该位置被认为对任何相互作用不敏感。然而，在进一步的合成研究中可以探索X位。从4-氨基-1-酮系列推导得到的相关方程来看，R位上强吸电子取代基会提高化合物的pK(i)值，而该位置上的强供电子取代基则会对其产生不利影响。基于使用不同电子参数推导得到的相关方程，可以解释这两个系列的化合物在受体识别位点内具有不同的取向。
