Ionic interactions for substituted MCH1R inhibitors studied by pK(a) values.
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.
Lee
Joo Yun
JY
Bio-Organic Science Division, Korea Research Institute of Chemical Technology, Daejon 305-600, Republic of Korea.
Lee
Hyuk
H
Lim
Jung Yun
JY
Yoo
Seung-Eun
SE
Kang
Nam Sook
NS
D000588:Amines; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007477:Ions; D008024:Ligands; D008956:Models, Chemical; D008968:Molecular Conformation; D015394:Molecular Structure; D011485:Protein Binding; D011804:Quinolines / Q000737:chemistry; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D055672:Static Electricity; D013816:Thermodynamics
D000588:Amines; D007477:Ions; D008024:Ligands; C103263:MCHR1 protein, human; D011804:Quinolines; D017481:Receptors, Somatostatin