81995-83-7Relevant academic research and scientific papers
Synthesis, 5-HT1A and 5-HT2A receptor affinity and QSAR study of 1-benzhydryl-piperazine derivatives with xanthine moiety at N4
Valkova, Iva,Zlatkov, Alexander,N?dza, Krystyna,Doytchinova, Irini
experimental part, p. 477 - 486 (2012/10/07)
Three novel 1-benzhydryl-piperazines with xanthine moiety at N4 were synthesized and tested for 5-HT1A and 5-HT2A receptor affinity. One of the compounds showed the highest affinity (58.6 nM) and selectivity (34 times) to 5-HT2A receptor known for this class of compounds. A set of the three new and 31 previously synthesized 1-arylpiperazines with xanthine moiety at N4 was compiled and a QSAR study was performed in order to rationalize the further synthesis. It was found that the 5-HT1A affinity depends on the shape of the molecules (ovality and number of circuits), the distribution of the electron density in the structures (partial charges at piperazine N1 and xanthine N1) and their charge transfer ability (HOMO energy). The 5-HT2A affinity depends on the lipophilicity of the ligands and the distribution of the electron density in the structures (partial charges at piperazine N4 and xanthine O6). The QSAR results are in a good agreement with known pharmacophore models. Springer Science+Business Media, LLC 2011.
