Ionic interactions for substituted MCH1R inhibitors studied by pK(a) values

Bioorg Med Chem Lett. 2009 Aug 1;19(15):4376-9. doi: 10.1016/j.bmcl.2009.05.075. Epub 2009 May 27.

Abstract

MCH1R inhibitors with the quinoline moiety having the aromatic amine and aliphatic amine chain were selected, and then the effect of substituents of the quinoline ring on the ionic interaction were studied by calculating pK(a) values for these amines at the B3LYP/6-311++G(d,p)//B3LYP/6-31+G(d) level in the gas phase and in water. For substituent with C, N, O, and S atoms next to the quinoline ring, respectively, the pK(a) values of aromatic amines are estimated to be 8.98, 12.19, 4.64, and 4.33 and those of the aliphatic amines are 12.65, 10.82, 9.94, and 11.55, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines
  • Chemistry, Pharmaceutical / methods
  • Drug Design
  • Humans
  • Hydrogen-Ion Concentration
  • Ions
  • Ligands
  • Models, Chemical
  • Molecular Conformation
  • Molecular Structure
  • Protein Binding
  • Quinolines / chemistry
  • Receptors, Somatostatin / antagonists & inhibitors*
  • Receptors, Somatostatin / chemistry*
  • Static Electricity
  • Thermodynamics

Substances

  • Amines
  • Ions
  • Ligands
  • MCHR1 protein, human
  • Quinolines
  • Receptors, Somatostatin