MOLECULAR-GEOMETRY AND PHYSICOCHEMICAL CHARACTERISTICS OF SELECTED ANILINOQUINOLINES, INDOLO[3,2-C]QUINOLINES AND TETRAHYDROINDOLO[3,2-D]BENZAZEPINES

The molecular geometry, acid dissociation constants and partition coef ficients of the anilinoquinoline (I), indole[3,2-c]quinoline (II) and tetrahydroindolo[3,2-d] [1]benzazepine (III) ring systems have been de termined using representative compounds: 7-chloro-4-(p-anisidino)quino line (Ia), 3-chloro-8-methoxy-11H-indolo[3,2-c]quinoline (IIa) and 3-c hloro-9-methoxy-5,6,7,12-tetrahydroidolo[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 t he most planar and conformationally restricted, followed by IIIa and I a. The acid dissociation constants (pK(a)) were determined by the solu bility method. The ring nitrogen of Ia is most basic, followed by that of IIa and IIIa. The partition coefficient (log P) was determined bet ween octanol and appropriate aqueous buffers by the shaken Bask method . Hydrophobicity decreases in the order of Ia > IIa > IIIa. Factors co ntributing to the different molecular geometry, pK(a) and hydrophobici ty of these related compounds are discussed. The present study may con tribute to the design of better drugs with ring system I, II or III.