Novel indolecarboxamidotetrazoles as potential antiallergy agents.
The synthesis and antiallergic potential of a series of novel indolecarboxamidotetrazoles are described. A number of compounds inhibit the release of histamine from anti-IgE-stimulated basophilic leukocytes obtained from allergic donors. Optimal inhibition is exhibited by compounds with 3-alkoxy, 5-methoxy, and 1-phenyl substituents on the indole core structure. Compound 8d (5-methoxy-3-(1-methylethoxy)-1-phenyl-N-1H-tetrazol-5-yl-1H -indole-2-carboxamide; designated CI-949) is a potent inhibitor of histamine release from human basophils and from guinea pig and human chopped lung.
Unangst
P C
PC
Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105.
Connor
D T
DT
Stabler
S R
SR
Weikert
R J
RJ
Carethers
M E
ME
Kennedy
J A
JA
Thueson
D O
DO
Chestnut
J C
JC
Adolphson
R L
RL
Conroy
M C
MC
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001393:Azoles / Q000494:pharmacology*; D001491:Basophils / Q000276:immunology / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D006168:Guinea Pigs; D006633:Histamine Antagonists / Q000138:chemical synthesis / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy; D007073:Immunoglobulin E / Q000276:immunology; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology*; D008168:Lung / Q000166:cytology; D008407:Mast Cells / Q000378:metabolism; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000138:chemical synthesis / Q000494:pharmacology*
D000888:Antibodies, Anti-Idiotypic; D001393:Azoles; D006633:Histamine Antagonists; D007211:Indoles; D013777:Tetrazoles; D007073:Immunoglobulin E