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.
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. chuck_caldwell@merck.com
Charles G
CG
Caldwell
Ping
P
Chen
Jiafang
J
He
Emma R
ER
Parmee
Barbara
B
Leiting
Frank
F
Marsilio
Reshma A
RA
Patel
Joseph K
JK
Wu
George J
GJ
Eiermann
Aleksandr
A
Petrov
Huaibing
H
He
Kathryn A
KA
Lyons
Nancy A
NA
Thornberry
Ann E
AE
Weber
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