Hl. Koh et al., MOLECULAR-GEOMETRY AND PHYSICOCHEMICAL CHARACTERISTICS OF SELECTED ANILINOQUINOLINES, INDOLO[3,2-C]QUINOLINES AND TETRAHYDROINDOLO[3,2-D]BENZAZEPINES, Chemical and Pharmaceutical Bulletin, 42(5), 1994, pp. 1084-1087
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.