Non-peptide alphavbeta3 antagonists. Part 6: design and synthesis of alphavbeta3 antagonists containing a pyridone or pyrazinone central scaffold.
Two novel series of small-molecule RGD mimetics containing either a substituted pyridone or pyrazinone central constraint were prepared. Modification of the beta-alanine 3-substituent produced compounds that are potent and selective alpha(v)beta(3) antagonists and exhibit a range of physicochemical properties.
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 4, West Point, PA 19486, USA. john_hutchinson@merck.com
Michael J
MJ
Breslin
Mark E
ME
Duggan
Wasyl
W
Halczenko
Carmen
C
Fernandez-Metzler
Cecilia A
CA
Hunt
Chih-Tai
CT
Leu
Kara M
KM
Merkle
Adel M
AM
Naylor-Olsen
Thomayant
T
Prueksaritanont
Gary
G
Stump
Audrey
A
Wallace
Sevgi B
SB
Rodan
John H
JH
Hutchinson
D000409:Alanine / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors*; D018716:Molecular Mimicry; D009842:Oligopeptides; D011485:Protein Binding; D011719:Pyrazines / Q000737:chemistry* / Q000493:pharmacokinetics; D011728:Pyridones / Q000737:chemistry* / Q000493:pharmacokinetics; D011863:Radioimmunoassay; D013329:Structure-Activity Relationship
D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D011719:Pyrazines; D011728:Pyridones; C047981:arginyl-glycyl-aspartic acid; D000409:Alanine