Prediction of properties of chiral compounds by molecular topology.
A common assumption in chemistry is that chiral behavior is associated with 3-D geometry. However, chiral information is related to symmetry, which allows the topological handling of chiral atoms by weighted graphs and the calculation of new descriptors that give a weight to the corresponding entry in the main diagonal of the topological matrix. In this study, it is demonstrated that, operating in this way, chiral topological indices are obtained that can differentiate the pharmacological activity between pairs of enantiomers. The 50% inhibitory concentration (IC50) values of the D2 dopamine receptor and the sigma receptor for a group of 3-hydroxy phenyl piperidines are specifically predicted. Moreover, the sedative character of a group of chiral barbiturates can be identified.
Departamento de Química Física, Facultad de Farmacia, Universitat de València, Spain.
J V
JV
de Julián-Ortiz
C
C
de Gregorio Alapont
I
I
Ríos-Santamarina
R
R
García-Doménech
J
J
Gálvez
D000818:Animals; D000697:Central Nervous System Stimulants / Q000737:chemistry / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D015195:Drug Design; D006993:Hypnotics and Sedatives / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D008956:Models, Chemical; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology; D017480:Receptors, sigma / Q000037:antagonists & inhibitors; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000697:Central Nervous System Stimulants; D065127:Dopamine D2 Receptor Antagonists; D006993:Hypnotics and Sedatives; D010880:Piperidines; D017480:Receptors, sigma