Predictive structure-activity relationships in a series of pyranoquinoline derivatives. A new primate model for the identification of antiallergic activity.
A new primate model has been developed for the evaluation of antiallergic agents. Compounds are tested for their ability to inhibit anti-IgE induced histamine release from the bronchoalveolar mast cells lavaged from the lungs of Macaca arctoides infected with the parasite Ascaris suum. A number of 6-substituted pyranoquinoline derivatives have been evaluated and the activities were subjected to Hansch analysis. A highly significant correlation with lipophilicity (pi) and Hammett sigma p values was obtained. The relationship was used to predict further compounds for synthesis giving rise to new, potent analogues. Some apparently anomalous results could be explained by differences in the ionization of, or tautomerism in, the quinoline ring.
Gould
K J
KJ
Fisions plc-Pharmaceutical Division, Research and Development Laboratories, Loughborough, Leicestershire, U.K.
Manners
C N
CN
Payling
D W
DW
Suschitzky
J L
JL
Wells
E
E
D000818:Animals; D001196:Ascariasis / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D055598:Chemical Phenomena; D002621:Chemistry; D004205:Cromolyn Sodium / Q000627:therapeutic use; D004195:Disease Models, Animal; D006636:Histamine Release / Q000187:drug effects; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology; D008251:Macaca; D008407:Mast Cells / Q000502:physiology; D011714:Pyrans / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D011804:Quinolines / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
D011714:Pyrans; D011804:Quinolines; D007073:Immunoglobulin E; D004205:Cromolyn Sodium