Potent and selective proline derived dipeptidyl peptidase IV inhibitors.
In-house screening of the Merck sample collection identified proline derived homophenylalanine 3 as a DPP-IV inhibitor with modest potency (DPP-IV IC50=1.9 microM). Optimization of 3 led to compound 37, which is among the most potent and selective DPP-IV inhibitors discovered to date.
Edmondson
Scott D
SD
Department of Medicinal Chemistry, Merck & Co. Inc., PO Box 2000, Rahway, NJ 07065, USA. scott_edmondson@merck.com
Mastracchio
Anthony
A
Beconi
Maria
M
Colwell
Lawrence F
LF
Habulihaz
Bahanu
B
He
Huaibing
H
Kumar
Sanjeev
S
Leiting
Barbara
B
Lyons
Kathryn A
KA
Mao
Ann
A
Marsilio
Frank
F
Patel
Reshma A
RA
Wu
Joseph K
JK
Zhu
Lan
L
Thornberry
Nancy A
NA
Weber
Ann E
AE
Parmee
Emma R
ER
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
D011480:Protease Inhibitors; D011392:Proline; D018819:Dipeptidyl Peptidase 4