(3R,4S)-4-(2,4,5-Trifluorophenyl)-pyrrolidin-3-ylamine inhibitors of dipeptidyl peptidase IV: synthesis, in vitro, in vivo, and X-ray crystallographic characterization.
A series of pyrrolidine based inhibitors of dipeptidyl peptidase IV were developed from a high throughput screening hit for the treatment of type 2 diabetes. Potency, selectivity, and pharmacokinetic properties were optimized resulting in the identification of a pre-clinical candidate for further profiling.
Wright
Stephen W
SW
Pfizer Global Research and Development, Cardiovascular and Metabolic Diseases, MS 8220-3141, Eastern Point Road, Groton, CT 06340, USA.
Ammirati
Mark J
MJ
Andrews
Kim M
KM
Brodeur
Anne M
AM
Danley
Dennis E
DE
Doran
Shawn D
SD
Lillquist
Jay S
JS
Liu
Shenping
S
McClure
Lester D
LD
McPherson
R Kirk
RK
Olson
Thanh V
TV
Orena
Stephen J
SJ
Parker
Janice C
JC
Rocke
Benjamin N
BN
Soeller
Walter C
WC
Soglia
Carolyn B
CB
Treadway
Judith L
JL
Vanvolkenburg
Maria A
MA
Zhao
Zhengrong
Z
Cox
Eric D
ED
D000818:Animals; D018360:Crystallography, X-Ray; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004285:Dogs; D005461:Fluorine / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D013237:Stereoisomerism