Synthesis and SAR of a novel, potent and structurally simple LTD4 antagonist of the quinoline class.
The two geminal ethyl groups in the succinic acid moiety of CGP57698 (4-[3-(7-fluoro-2-quinolinyl-methoxy)phenyl-amino]-2,2-diethyl-4-oxo- butanoic acid) are responsible for the high in vitro and in vivo potency of this peptidoleukotriene antagonist of the quinoline type. The synthesis and structure activity relationships of CGP57698 and its analogs are described.
von Sprecher
A
A
Research Department, Novartis Pharma AG, Basel, Switzerland. andreas.von_sprecher@pharma.novartis.com
Gerspacher
M
M
Beck
A
A
Kimmel
S
S
Wiestner
H
H
Anderson
G P
GP
Niederhauser
U
U
Subramanian
N
N
Bray
M A
MA
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001682:Biological Availability; D016084:Bronchoconstriction / Q000187:drug effects; D002144:Callithrix; D006168:Guinea Pigs; D007202:Indicators and Reagents; D020024:Leukotriene Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017998:Leukotriene D4 / Q000037:antagonists & inhibitors*; D017999:Leukotriene E4 / Q000037:antagonists & inhibitors; D008968:Molecular Conformation; D015394:Molecular Structure; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
D018927:Anti-Asthmatic Agents; C112382:CGP 57698; D007202:Indicators and Reagents; D020024:Leukotriene Antagonists; D011804:Quinolines; D017998:Leukotriene D4; D017999:Leukotriene E4