Discovery and optimization of a novel series of GPR142 agonists for the treatment of type 2 diabetes mellitus

Bioorganic and Medicinal Chemistry Letters

Volumn 22, Issue 18, 2012, Pages 5942-5947

  Lizarzaburu, Mike ^a   Turcotte, Simon ^a   Du, Xiaohui ^a   Duquette, Jason ^a   Fu, Angela ^a   Houze, Jonathan ^a   Li, Leping ^a   Liu, Jinqian ^a   Murakoshi, Michiko ^b   Oda, Kozo ^b   Okuyama, Ryo ^b   Nara, Futoshi ^b   Reagan, Jeff ^a   Yu, Ming ^a   Medina, Julio C ^a  

^a AMGEN INC   (United States)

^b DAIICHI SANKYO CO   (Japan)

Author keywords

CYP inhibition reduction; GPR142 agonist; Insulin secretagogue; Type 2 diabetes mellitus

Indexed keywords

ANTIDIABETIC AGENT; CARBOXYLIC ACID DERIVATIVE; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; GPR142 AGONIST; INOSITOL PHOSPHATE; PHENYLALANINE; PYRIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG POTENCY; DRUG SYNTHESIS; ENZYME INHIBITION; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN CELL; IN VITRO STUDY; LIVER MICROSOME; MEAN RESIDENCE TIME; MOUSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION;

ANIMALS; DIABETES MELLITUS, TYPE 2; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DISCOVERY; HUMANS; HYPOGLYCEMIC AGENTS; MICROSOMES, LIVER; MOLECULAR STRUCTURE; PHENYLALANINE; RATS; RECEPTORS, G-PROTEIN-COUPLED; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84865522942     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2012.07.063     Document Type: Article

References (8)

1. R.J. Koopman, A.G. Mainous III, V.A. Diaz, and M.E. Geeseey Ann. Fam. Med. 3 2005 60 63
2. A.S. Gangji, C.H. Goldsmith, T. Cukierman, C.M. Clase, and H.C. Gerstein Diabetes Care 2 2007 389
3. Xiong, Y.; Motani, A.; Reagan, J.; Gao, X.; Yang, H.; Ma, J.; Schwandner, R.; Zhang, Y.; Liu, Q.; Miao, L.; Luo, J.; Tian, H.; Chen, J-L.; Murakoshi, M.; Nara, F.; Yeh, W.-C.; Cao, Z. manuscript is in preparation.
4. S.-H. Xiao, J.D. Reagan, P.H. Lee, A. Fu, R. Schwandner, X. Zhao, J. Knop, H. Beckmann, and S.W. Young Comb. Chem. High Throughput Screening 11 3 2008 195 215
5. Mouse islets were run with 16.7 mM Glucose, 0.625% HAS and 1% DMSO. For details of assay conditions and mouse islet isolation see DC -H Lin, R. Zhang, F. Li, K. Nguyen, M. Chen, T. Tran, E. Lopez, J.Y.L. Lu, X.N. Li, L. Tang, G.R. Tonn, G. Swaminath, J.D. Reagan, H. Tian, Y.-J. Lin, J.B. Houze, and J Luo PLoS ONE 6 2011 e27270 10.1371/journal.pone.0027270
6. S.D. Knight, N.D. Adams, J.L. Burgess, A.M. Chaudhari, G.M. Darcy, A.C. Donatelli, J.I. Luengo, K.A. Newlander, C.A. Parrish, L.H. Ridgers, M.A. Sarpong, S.J. Schmidt, G.S. Van Aller, J.D. Carson, M.A. Diamond, P.A. Elkins, C-M. Gardiner, E. Garver, S.A. Gilbert, R.R. Gontarek, J.R. Jackson, K.L. Kershner, L. Luo, K. Raha, C.S. Sherk, C.M. Sung, D. Sutton, P.J. Tummino, R.J. Wegrzyn, K.R. Auger, and D. Dhanak ACS Med. Chem. Lett. 1 2010 39 43
7. Du, X.; Kim, Y-J; Lai, S-J.; Chen, X.; Lizarzaburu, M.; Turcotte, S.; Fu, Z.; Liu, Q.; Zhang, Y.; Motani, A.; Oda, K.; Okuyama, R.; Nara, F.; Murakoshi, M.; Fu, A.; Reagan, J.D.; Fan, P.; Xiong, Y.; Shen, W.; Li, L.; Houze, J.; Medina, J.C. Bioorg. Med. Chem. Lett. accepted for publication
8. Yu, M.; Lizarzaburu, M.; Motani, A.; Fu, Z.; Du, X.; Liu, J.; Jiao, X.; Lai, S-J.; Fu, A.; Lin, D.; Liu, Q.; Murakoshi, M.; Nara, F.; Oda, K.; Okuyama, R.; Reagan, J.; Turcotte, S.; Zhang, Y.; Houze, J.; Medina, J.C.; Li, L. manuscript in preparation to ACS Med. Chem. Lett.