Discovery, SAR, and X-ray structure of novel biaryl-based dipeptidyl peptidase IV inhibitors.
The discovery, SAR, and X-ray crystal structure of novel biarylaminoacyl-(S)-2-cyano-pyrrolidines and biarylaminoacylthiazolidines as potent inhibitors of dipeptidyl peptidase IV (DPP IV) are reported.
Qiao
Lei
L
Johnson and Johnson Pharmaceutical Research and Development, 665 Stockton Drive, Exton, PA 19341, USA.
Baumann
Christian A
CA
Crysler
Carl S
CS
Ninan
Nisha S
NS
Abad
Marta C
MC
Spurlino
John C
JC
Desjarlais
Renee L
RL
Kervinen
Jukka
J
Neeper
Mike P
MP
Bayoumy
Shariff S
SS
Williams
Robyn
R
Deckman
Ingrid C
IC
Dasgupta
Malini
M
Reed
Rolanda L
RL
Huebert
Norman D
ND
Tomczuk
Bruce E
BE
Moriarty
Kevin J
KJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001665:Binding Sites; D001786:Blood Glucose / Q000378:metabolism; D018938:Caco-2 Cells; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D018360:Crystallography, X-Ray / Q000379:methods*; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry* / Q000378:metabolism; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D051379:Mice; D008956:Models, Chemical; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D011480:Protease Inhibitors; D018819:Dipeptidyl Peptidase 4