QSAR studies in substituted 1,2,3,4,6,7,12,12a-octa-hydropyrazino[2',1':6,1]pyrido[3,4-b]indoles--a potent class of neuroleptics

Bioorg Med Chem. 2003 May 1;11(9):2085-90. doi: 10.1016/s0968-0896(02)00652-1.

Abstract

A series of nineteen substituted 1,2,3,4,6,7,12,12a-octahydropyrazino[2',1':6,1]pyrido[3, 4-b]indoles analogues of neuroleptic drug, Centbutindole have been studied using quantitative structure-activity relationship analysis. The derived models display good fits to the experimental data (r>or=0.75) having good predictive power (r(cv)>or=0.688). The best model describes a high correlation between predicted and experimental activity data (r=0.967). Statistical analysis of the equation populations indicates that hydrophobicity (as measured by pi(R), logP(o/w) and SlogP_VSA8), dipole y and structural parameters in terms of indicator variable, (In(1)) and globularity are important variables in describing the variation in the neuroleptic activity in the series.

MeSH terms

  • Animals
  • Antipsychotic Agents / chemistry*
  • Antipsychotic Agents / pharmacology
  • Avoidance Learning / drug effects
  • Avoidance Learning / physiology
  • Indoles / chemistry*
  • Indoles / pharmacology
  • Pyrazines / chemistry*
  • Pyrazines / pharmacology
  • Quantitative Structure-Activity Relationship*
  • Rats

Substances

  • Antipsychotic Agents
  • Indoles
  • Pyrazines
  • centbutindole