1,2,3,4-Tetrahydroquinoline-containing alphaVbeta3 integrin antagonists with enhanced oral bioavailability.
Reduction of the quinoline ring in an alpha(v)beta(3) antagonist yielded a 1,2,3,4-tetrahydro derivative as two diastereomers, the four isomers of which were separated by sequential chiral HPLC. Two isomers had significant alpha(V)beta(3) antagonist activity with improved oral bioavailability, relative to the corresponding quinoline derivative.
Ghosh
Shyamali
S
Drug Discovery, Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Welsh & McKean Roads, Spring House, PA 19477-0776, USA.
Santulli
Rosemary J
RJ
Kinney
William A
WA
Decorte
Bart L
BL
Liu
Li
L
Lewis
Joan M
JM
Proost
Jef C
JC
Leo
Gregory C
GC
Masucci
John
J
Hageman
William E
WE
Thompson
Andrew S
AS
Chen
Ian
I
Kawahama
Reiko
R
Tuman
Robert W
RW
Galemmo
Robert A
RA
Johnson
Dana L
DL
Damiano
Bruce P
BP
Maryanoff
Bruce E
BE
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D011804:Quinolines / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism*; D051381:Rats
D039302:Integrin alphaVbeta3; D011804:Quinolines