title: Chromatographic retention parameters in correlation analysis with in silico biological descriptors of a novel series of N-phenyl-3-methyl succinimide derivatives.
abstract: Reversed-phase thin-layer chromatographic (RP TLC) retention coefficients for a newly designed series of N-phenyl-3-methyl succinimide derivatives, of a rationally expected anticonvusant activity, were determined as parameters of their lipophilicity. Basic pharmacokinetic descriptors of the agents were calculated in silico with the use of the established medicinal chemistry/drug design software. Highly significant, predictive relationships were found between the chromatographic retention constants and the bioactivity descriptors, which are assumed to account for drug absorption, distribution, elimination and toxicity (ADMETox) in humans. Among the agents investigated, the compounds with halogen substituent (Compounds nos. 9-13 in Fig. 1), were identified as the best drug candidates, because of their predicted proper pharmacokinetics, and have been selected for further research and development studies on new antiepileptic drugs. At the same time, among the congeners studied these can be indicated, which should not be rationally subjected to bioactivity tests.
authors.affiliation: Academy of Sciences and Arts of Vojvodina, Univesity of Novi Sad, Vojvode Putnika 1, 21000 Novi Sad, Serbia. nadap@uns.ac.rs
authors.forename: Nada
authors.initials: N
authors.lastname: Perisic-Janjic
authors.forename: Roman
authors.initials: R
authors.lastname: Kaliszan
authors.forename: Natasa
authors.initials: N
authors.lastname: Milosevic
authors.forename: Gordana
authors.initials: G
authors.lastname: Uscumlic
authors.forename: Nebojsa
authors.initials: N
authors.lastname: Banjac
mesh_terms: D000042:Absorption; D000927:Anticonvulsants / Q000737:chemistry; D056148:Chromatography, Reverse-Phase / Q000379:methods*; D002855:Chromatography, Thin Layer / Q000379:methods*; D003198:Computer Simulation; D015195:Drug Design; D006219:Halogens / Q000737:chemistry; D006801:Humans; D021281:Quantitative Structure-Activity Relationship; D012984:Software; D013388:Succinimides / Q000737:chemistry*
chemical_list: D000927:Anticonvulsants; D006219:Halogens; D013388:Succinimides; C032620:succinimide