N-terminal anthranoyl-phenylalanine derivatives as CCK1 receptor antagonists: the final approach.
Starting from our lead compound, VL-0395, an anthranilic acid based CCK1 receptor antagonist, and following the well established "step by step" lead investigation strategy, we describe the final step of the anthranilic acid N-terminal optimization. Improvements for both affinity and selectivity towards CCK1 receptors have been accomplished through introduction of the fluoro substituent at C-5 and C-7 position of the indole ring together with the appropriate configuration of the aminoacidic chiral center.
Varnavas
A
A
Department of Pharmaceutical Sciences, University of Trieste, P.le Europa 1, 34127 Trieste, Italy. varnavas@units.it
Lassiani
L
L
Valenta
V
V
Ciogli
A
A
Gasparrini
F
F
Mennuni
L
L
Makovec
F
F
D000818:Animals; D001665:Binding Sites; D006168:Guinea Pigs; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D015394:Molecular Structure; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043886:Receptor, Cholecystokinin A / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013997:Time Factors; D062367:ortho-Aminobenzoates / Q000737:chemistry*
D007211:Indoles; D043886:Receptor, Cholecystokinin A; C492564:VL-0395; D062367:ortho-Aminobenzoates; D010649:Phenylalanine