Reversible and competitive cinnamoyl triazole inhibitors of tissue transglutaminase.
A series of 15 cinnamoyl triazole derivatives was prepared by Cu(I)-catalyzed azide/alkyne [3+2]-cycloaddition reactions and examined as inhibitors of guinea-pig liver transglutaminase. Several compounds exhibited activity as reversible inhibitors that were competitive with acyl donor transglutaminase substrates. For example, triazole 4d has a K(i) value of 174 nM and represents one of the most potent reversible transglutaminase inhibitors reported to date.
Pardin
Christophe
C
Département de chimie, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, QC H3C 3J7, Canada.
Roy
Isabelle
I
Lubell
William D
WD
Keillor
Jeffrey W
JW
D000480:Alkynes / Q000737:chemistry; D000818:Animals; D001386:Azides / Q000737:chemistry; D002384:Catalysis; D002934:Cinnamates / Q000737:chemistry* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006168:Guinea Pigs; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000480:Alkynes; D001386:Azides; D002934:Cinnamates; D004791:Enzyme Inhibitors; D014230:Triazoles; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins