Study of the relationship between nitrogen basicity and receptor affinity in a substituted quinoline series.
In buffered water:methanol media, the pKa values of acid-base equilibria involved in the protonation of substituted quinolines are determined by UV-visible absorption spectrometry. The observed behavior depends on the nature of R2: the N-CH3 derivatives exist as quinoline, the N-H derivatives as 4-iminoquinoline tautomers. The iminoquinoline zwitterionic species present at physiological pH may have high receptor affinity. A linear relationship between pKa of the endocyclic nitrogen and log IC50 is discussed.
Fleury
M B
MB
Laboratoire de Chimie Analytique, U.R.A. C.N.R.S. 1310, Faculté de Pharmacie, Paris, France.
Largeron
M
M
Fleury
D
D
Vernieres
J C
JC
D006868:Hydrolysis; D009584:Nitrogen; D011804:Quinolines / Q000737:chemistry / Q000378:metabolism*; D011955:Receptors, Drug / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
D011804:Quinolines; D011955:Receptors, Drug; D009584:Nitrogen