alpha(v)beta(3) Antagonists based on a central thiophene scaffold.
A series of novel, highly potent alpha(v)beta(3) antagonists based on a thiophene scaffold and containing an acylguanidine as an Arg-mimetic is described. A number of structural features, such as cyclic versus open guanidine and a variety of lipophilic side chains, carbamates, sulfonamides and beta-amino acids were explored with respect to inhibition of alpha(v)beta(3) mediated cell adhesion and selectivity versus alpha(IIb)beta(3) binding. In addition, compound 19 was found to be active in the TPTX model of osteoporosis.
Peyman
A
A
Aventis Pharma Deutschland GmbH, D-65926, Frankfurt, Germany. anusch.peyman@aventis.com
Scheunemann
K
K
Will
D W
DW
Knolle
J
J
Wehner
V
V
Breipohl
G
G
Stilz
H U
HU
Carniato
D
D
Ruxer
J
J
Gourvest
J
J
Auberval
M
M
Doucet
B
B
Baron
R
R
Gaillard
M
M
Gadek
T R
TR
Bodary
S
S
D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D002219:Carbamates / Q000737:chemistry; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019791:Guanidine / Q000737:chemistry; D010024:Osteoporosis / Q000517:prevention & control*; D016105:Parathyroidectomy; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012680:Sensitivity and Specificity; D013449:Sulfonamides / Q000737:chemistry; D013876:Thiophenes / Q000138:chemical synthesis / Q000494:pharmacology; D013965:Thyroidectomy
D002219:Carbamates; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019030:Receptors, Vitronectin; D013449:Sulfonamides; D013876:Thiophenes; D019791:Guanidine