Author/Authors :
Ashraf A. Rahman، نويسنده , , Maha Khalifa Daoud، نويسنده , , Ma gorzata Dukat، نويسنده , , Katharine Herrick-Davis، نويسنده , , Anil Purohit، نويسنده , , Milt Teitler، نويسنده , , Antonia Taveres do Amaral، نويسنده , , Alberto Malvezzi، نويسنده , , Richard A. Glennon، نويسنده ,
Abstract :
The present investigation examined two features of arylbiguanide and arylguanidine 5-HT3 ligands: conformation and partition coefficients. Several conformationally-constrained analogues of mCPBG (2) and mCPG (11; Ki=32 nM) were prepared and of these only 2-amino-5-chloro-3,4-dihydroquinazoline (14; Ki=34 nM) retained high affinity. The partition coefficient of compound 11 (LogPapp=−0.64) was less than that of its corresponding arylbiguanide 2 (LogPapp=−0.38). The quinazoline structure may represent a pharmacologically-active conformation of these agents, and the arylbiguanides were found more lipid soluble than their arylguanidine counterparts at physiological pH.
