Molecular geometry and physiochemical characteristics of selected anilinoquinolines, indolo[3,2-c]quinolines and tetrahydroindolo[3,2-d]benzazepines

Abstract

The molecular geometry, acid dissociation constants and partition coefficients of the anilinoquinoline (I), indolo[3,2-c]quinoline (II) and tetrahydroindolo[3,2-d] [1]benzazepine (III) ring systems have been determined using representative compounds: 7-chloro-4-(p-anisidino)quinoline (Ia), 3-chloro-8-methoxy-11H-indolo[3,2-c]-quinoline (IIa) and 3-chloro-9-methoxy-5,6,7,12-tetrahydroindolo[3,2-d] [1]benzazepine (IIIa). Ring systems II and III are cyclic analogues of I. The minimum energy conformation was determined by molecular mechanics. Compound IIa is the most planar and conformationally restricted, followed by IIIa and Ia. The acid dissociation constants (pKa) were determined by the solubility method. The ring nitrogen of Ia is most basic, followed by that of IIa and IIIa. The partition coefficient (log P) was determined between octanol and appropriate aqueous buffers by the shaken flask method. Hydrophobicity decreases in the order of Ia > IIa > IIIa. Factors contributing to the different molecular geometry, pKa and hydrophobicity of these related compounds are discussed. The present study may contribute to the design of better drugs with ring system I, II or III.