Fluoropyrrolidine amides as dipeptidyl peptidase IV inhibitors.
Amides derived from fluorinated pyrrolidines and 4-substituted cyclohexylglycine analogues have been prepared and evaluated as inhibitors of dipeptidyl dipeptidase IV (DP-IV). Analogues which incorporated (S)-3-fluoropyrrolidine showed good selectivity for DP-IV over quiescent cell proline dipeptidase (QPP). Compound 48 had good pharmacokinetic properties and was orally active in an oral glucose tolerance test in lean mice.
Caldwell
Charles G
CG
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. chuck_caldwell@merck.com
Chen
Ping
P
He
Jiafang
J
Parmee
Emma R
ER
Leiting
Barbara
B
Marsilio
Frank
F
Patel
Reshma A
RA
Wu
Joseph K
JK
Eiermann
George J
GJ
Petrov
Aleksandr
A
He
Huaibing
H
Lyons
Kathryn A
KA
Thornberry
Nancy A
NA
Weber
Ann E
AE
D000243:Adenosine Deaminase / Q000378:metabolism; D058892:Adenosine Deaminase Inhibitors; D000577:Amides / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D005461:Fluorine / Q000737:chemistry / Q000494:pharmacology; D006023:Glycoproteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D011759:Pyrrolidines / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats
D058892:Adenosine Deaminase Inhibitors; D000577:Amides; D006023:Glycoproteins; D007527:Isoenzymes; D011480:Protease Inhibitors; D011759:Pyrrolidines; D005461:Fluorine; D000243:Adenosine Deaminase