Synthesis and quantitative structure-activity relationships of antiallergic 2-hydroxy-N-1H-tetrazol-5-ylbenzamides and N-(2-hydroxyphenyl)-1H-tetrazole-5-carboxamides.
The synthesis and antiallergic activity of a series of 2-hydroxy-N-1H-tetrazol-5-ylbenzamides and isomeric N-(2-hydroxyphenyl)-1H-tetrazole-5-carboxamides is described. A relationship between structure and intravenous antiallergic activity in the rat passive cutaneous anaphylaxis (PCA) test has been established using a Hansch/Free-Wilson model and used to direct studies toward potent derivatives. The contribution of physicochemical properties to activity is discussed. One member of this series, N-(3-acetyl-5-fluoro-2-hydroxyphenyl)-1H-tetrazole-5-carboxamide (3f), which was selected for further evaluation, has an ID50 value of 0.16 mg/kg po and is 130 times more potent than disodium cromoglycate (DSCG) on intravenous administration.
Ford
R E
RE
Knowles
P
P
Lunt
E
E
Marshall
S M
SM
Penrose
A J
AJ
Ramsden
C A
CA
Summers
A J
AJ
Walker
J L
JL
Wright
D E
DE
D000818:Animals; D001393:Azoles / Q000138:chemical synthesis*; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D006860:Hydrogen Bonding; D006967:Hypersensitivity / Q000188:drug therapy*; D008297:Male; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D010636:Phenols / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D001393:Azoles; D006634:Histamine H1 Antagonists; D010636:Phenols; D013777:Tetrazoles