Quantitative structure-activity relationships of inhibitors of immune complex-induced inflammation: 1-phenyl-3-aminopyrazoline derivatives.
Quantitative structure-activity relationships (QSAR) of the 1-phenyl-3-aminopyrazoline analogues as inhibitors of immune complex-induced inflammation have been studied. The correlation suggests that the overall size of the phenyl substituents are of importance, and bulky groups have negative effects on potency. The negative steric effects are gradually increased from ortho to meta to para positions. The negative steric effects were sometimes altered by the electronic effects of the substituents. Electron-releasing groups on the phenyl ring increased potency, while electron-withdrawing groups decreased it. Ortho substituents, however, have unaccounted for additional deleterious effects described here with an indicator variable. The octanol-water partition coefficient (log P) and dissociation constants (pKa) of the 1-(m-trifluoromethylphenyl)-3-aminopyrazoline analogue have been experimentally determined.
Kim
K H
KH
Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064.
Martin
Y C
YC
Norris
B
B
Young
P R
PR
Carter
G W
GW
Haviv
F
F
Walters
R L
RL
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001183:Arthus Reaction / Q000276:immunology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D007105:Immune Complex Diseases / Q000150:complications*; D007958:Leukocyte Count; D011720:Pyrazoles / Q000494:pharmacology*; D012995:Solubility; D013329:Structure-Activity Relationship
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011720:Pyrazoles