Synthesis and structure-activity relationship of N-alkyl Gly-boro-Pro inhibitors of DPP4, FAP, and DPP7.
The structure-activity relationship of various N-alkyl Gly-boro-Pro derivatives against three dipeptidyl peptidases (DPPs) was studied. In a series of N-cycloalkyl analogs, DPP4 and fibroblast activation protein-alpha (FAP) optimally preferred N-cycloheptyl whereas DPP7 tolerated even larger cycloalkyl rings. Gly alpha-carbon derivatization of N-cyclohexyl or N-(2-adamantyl) Gly-boro-Pro resulted in a significant decrease in potency against all the three DPPs.
Hu
Yi
Y
ActivX Biosciences, Inc., 11025 N. Torrey Pines Road, La Jolla, CA 92037, USA.
Ma
Lifu
L
Wu
Min
M
Wong
Melissa S
MS
Li
Bei
B
Corral
Sergio
S
Yu
Zhizhou
Z
Nomanbhoy
Tyzoon
T
Alemayehu
Senaiet
S
Fuller
Stacy R
SR
Rosenblum
Jonathan S
JS
Rozenkrants
Natasha
N
Minimo
Lauro C
LC
Ripka
William C
WC
Szardenings
Anna K
AK
Kozarich
John W
JW
Shreder
Kevin R
KR
D058892:Adenosine Deaminase Inhibitors; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors; D001897:Boronic Acids; D004151:Dipeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D018819:Dipeptidyl Peptidase 4; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors*; D010450:Endopeptidases; D018093:Gelatinases; D006023:Glycoproteins / Q000037:antagonists & inhibitors; D006801:Humans; D007155:Immunologic Factors / Q000138:chemical synthesis / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D013329:Structure-Activity Relationship; D000099167:Fibroblast Activation Protein Alpha
D058892:Adenosine Deaminase Inhibitors; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D001897:Boronic Acids; D004151:Dipeptides; D018819:Dipeptidyl Peptidase 4; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D010450:Endopeptidases; D018093:Gelatinases; D006023:Glycoproteins; D007155:Immunologic Factors; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha; C100151:dipeptidyl peptidase II; C042807:DPP4 protein, human