Reversal of P-glycoprotein mediated multidrug resistance by novel anthranilamide derivatives.
We have synthesised and evaluated a series of anthranilamide based modulators of P-glycoprotein. These studies have identified XR9576(2), a potent inhibitor of P-glycoprotein in vitro and in vivo. The general synthesis and the SAR of these compounds are described.
Roe
M
M
Xenova Ltd., Slough, England.
Folkes
A
A
Ashworth
P
P
Brumwell
J
J
Chima
L
L
Hunjan
S
S
Pretswell
I
I
Dangerfield
W
W
Ryder
H
H
Charlton
P
P
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D004357:Drug Synergism; D006801:Humans; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D062367:ortho-Aminobenzoates / Q000737:chemistry / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D062367:ortho-Aminobenzoates; D004317:Doxorubicin; C000219:anthranilamide