ABSTRACT
The GEometry, Topology and Atom-Weights AssemblY approach has been applied to the study of the A(2A) adenosine receptors agonist effect of 29 adenosine analogues: N(6)-arylcarbamoyl, 2-arylalkynyl-N(6)-arylcarbamoyl, and N(6)-carboxamido derivatives. A model able to describe more than 77% of the variance in the experimental activity was developed with the use of the mentioned approach. In contrast, no one of four different approaches, including the use of Topological, Galvez Topological Charges indexes, Geometrical and WHIM descriptors were able to explain more than 70% of the variance in the mentioned property with the same number of variables in the equation.
Subject(s)
Adenosine A2 Receptor Agonists , Models, Theoretical , Adenosine/analogs & derivatives , Animals , Computer Simulation , Models, Molecular , Quantitative Structure-Activity Relationship , RatsABSTRACT
A new class of 1,2-disubstituted carbocyclic nucleosides of MECA and NECA analogues was synthesized in good yield starting from (+/-) 6-azabicyclo[3.2.0]heptan-7-one.
Subject(s)
Adenosine-5'-(N-ethylcarboxamide)/analogs & derivatives , Adenosine-5'-(N-ethylcarboxamide)/chemical synthesis , Adenosine/analogs & derivatives , Adenosine/chemical synthesis , Purinergic P1 Receptor Agonists , Adenosine/chemistry , Indicators and Reagents , Models, Molecular , Molecular Conformation , Purines/chemical synthesisABSTRACT
A series of 1,2-disubstituted carbonucleoside analogues of pyrimidine and 5-halopyrimidines with the unsaturated carbocycle cyclopentene was synthesized. AIM theory was applied to analyse the conformational and electronic effects of 5-halogenation.
