Development of a series of phenyltetrazole leukotriene D4 (LTD4) receptor antagonists.
A hypothetical model for receptor binding of leukotriene D4 (LTD4) was deduced from conformational analysis of LTD4 and from the structure-activity relationships (SAR) of known LTD4 receptor antagonists. A new structural series of LTD4 receptor antagonists exemplified by 5-[4-(4-phenylbutoxy)phenyl]-2-[4-(tetrazol-5-yl)butyl]-2H-t etrazole was designed in which a phenyltetrazole moiety was incorporated as a receptor binding equivalent of the triene unit of LTD4. A number of these phenyltetrazoles were prepared and found to possess LTD4 receptor antagonist activity. The structure-activity relationship (SAR) of this series is described.
Harper
R W
RW
Eli Lilly and Company, Indianapolis, Indiana 46285.
Herron
D K
DK
Bollinger
N G
NG
Sawyer
J S
JS
Baldwin
R F
RF
Roman
C R
CR
Rinkema
L E
LE
Fleisch
J H
JH
D000818:Animals; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D011487:Protein Conformation; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D018077:Receptors, Leukotriene; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D011971:Receptors, Immunologic; D018077:Receptors, Leukotriene; D013777:Tetrazoles