Predictive comparative QSAR modelling of (phenylpiperazinyl-alkyl) oxindoles as selective 5-HT1A antagonists by stepwise regression, PCRA, FA-MLR and PLS techniques.
5-Hydroxytryptamine, a neurotransmitter released by 5-HT neurons in raphe nuclei and 5-HT(1A) receptors are involved in the pain mechanism of migraine, prevention of postpartum haemorrhage, CNS effects like sleep, anxiety and thermoregulation. Comparative QSAR study was done on thirtytwo (phenylpiperazinyl-alkyl) oxindoles using stepwise regression, PCRA, FA-MLR and PLS techniques to find structurally significant models. ETSA indices at atom numbers 19, 20 and 22, RTSA indices at atom numbers 6, 10 and 20, charge at atom number 19 and presence of chlorine at the atom number 6 may be conducive for the receptor inhibition. Electrophilic attack at atom number 21 may be unfavourable but nucleophilic attack at atom numbers 8 and 14 may be beneficial for % 5-HT(1A) inhibition.
Adhikari
Nilanjan
N
Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, P.O. Box 17020, Jadavpur University, Kolkata 700032, India.
Maiti
Milan K
MK
Jha
Tarun
T
D003198:Computer Simulation; D007211:Indoles / Q000737:chemistry*; D016014:Linear Models; D008958:Models, Molecular; D015233:Models, Statistical; D015394:Molecular Structure; D000078183:Oxindoles; D021281:Quantitative Structure-Activity Relationship; D058829:Serotonin 5-HT1 Receptor Antagonists
D007211:Indoles; D000078183:Oxindoles; D058829:Serotonin 5-HT1 Receptor Antagonists; C022960:2-oxindole