Dipeptidyl Peptidase IV Inhibitors for the Treatment of Type 2 Diabetes

Ann E. Weber, Nancy Thornberry, Chapter 7 Case History: JANUVIA™ (Sitagliptin), a Selective Dipeptidyl Peptidase IV Inhibitor for the Treatment of Type 2 Diabetes Annual Reports in Medicinal Chemistry Volume 42. ,vol. 42, pp. 95- 109 ,(2007) , 10.1016/S0065-7743(07)42007-3

Edwin B. Villhauer, John A. Brinkman, Goli B. Naderi, Beth E. Dunning, Bonnie L. Mangold, Manisha D. Mone, Mary E. Russell, Stephen C. Weldon, Thomas E. Hughes, 1-[2-[(5-Cyanopyridin-2-yl)amino]ethylamino]acetyl-2-(S)-pyrrolidinecarbonitrile: a potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitor with antihyperglycemic properties. Journal of Medicinal Chemistry. ,vol. 45, pp. 2362- 2365 ,(2002) , 10.1021/JM025522Z

Zhonghua Pei, Xiaofeng Li, Thomas W. von Geldern, David J. Madar, Kenton Longenecker, Hong Yong, Thomas H. Lubben, Kent D. Stewart, Bradley A. Zinker, Bradley J. Backes, Andrew S. Judd, Mathew Mulhern, Stephen J. Ballaron, Michael A. Stashko, Amanda K. Mika, David W. A. Beno, Glenn A. Reinhart, Ryan M. Fryer, Lee C. Preusser, Anita J. Kempf-Grote, Hing L. Sham, James M. Trevillyan, Discovery of ((4R,5S)-5-Amino-4-(2,4,5- trifluorophenyl)cyclohex-1-enyl)-(3- (trifluoromethyl)-5,6-dihydro- [1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methanone (ABT-341), a Highly Potent, Selective, Orally Efficacious, and Safe Dipeptidyl Peptidase IV Inhibitor for the Treatment of Type 2 Diabetes Journal of Medicinal Chemistry. ,vol. 49, pp. 6439- 6442 ,(2006) , 10.1021/JM060955D

Nancy A. Thornberry, Ann E. Weber, Emma R. Parmee, Linda L. Brockunier, Jiafang He, Lawrence F. Colwell, Bahanu Habulihaz, Huaibing He, Barbara Leiting, Kathryn A. Lyons, Frank Marsilio, Reshma A. Patel, Yohannes Teffera, Joseph K. Wu, Substituted piperazines as novel dipeptidyl peptidase IV inhibitors Bioorganic & Medicinal Chemistry Letters. ,vol. 14, pp. 4763- 4766 ,(2004) , 10.1016/J.BMCL.2004.06.065

J. Heins, P. Welker, Chr. Schönlein, I. Born, B. Hartrodt, K. Neubert, D. Tsuru, A. Barth, Mechanism of proline-specific proteinases: (I) Substrate specificity of dipeptidyl peptidase IV from pig kidney and proline-specific endopeptidase from Flavobacterium meningosepticum. Biochimica et Biophysica Acta. ,vol. 954, pp. 161- 169 ,(1988) , 10.1016/0167-4838(88)90067-2

Zhongbo Fei, Quanbing Wu, Fei Zhang, Yudong Cao, Chuanqin Liu, Wen-Chung Shieh, Song Xue, Joe McKenna, Kapa Prasad, Mahavir Prashad, Daniel Baeschlin, Kenji Namoto, A Scalable Synthesis of an Azabicyclooctanyl Derivative, a Novel DPP-4 Inhibitor Journal of Organic Chemistry. ,vol. 73, pp. 9016- 9021 ,(2008) , 10.1021/JO801830X

Yoshiaki Tanaka, Seiichi Niwa, Hiroyasu Nishioka, Takeshi Yamanaka, Motoki Torizuka, Koji Yoshinaga, Naomi Kobayashi, Yugo Ikeda, Heihachiro Arai, New potent prolyl endopeptidase inhibitors: synthesis and structure-activity relationships of indan and tetralin derivatives and their analogues. Journal of Medicinal Chemistry. ,vol. 37, pp. 2071- 2078 ,(1994) , 10.1021/JM00039A019

A. Marie O'Farrell, Andre van Vliet, Khalid Abou Farha, Julie M. Cherrington, David A. Campbell, Xinqiang Li, Denise Hanway, Jianke Li, Hans-Peter Guler, Pharmacokinetic and pharmacodynamic assessments of the dipeptidyl peptidase-4 inhibitor PHX1149: double-blind, placebo-controlled, single- and multiple-dose studies in healthy subjects. Clinical Therapeutics. ,vol. 29, pp. 1692- 1705 ,(2007) , 10.1016/J.CLINTHERA.2007.08.005

David J. Madar, Hana Kopecka, Daisy Pireh, Hong Yong, Zhonghua Pei, Xiaofeng Li, Paul E. Wiedeman, Stevan W. Djuric, Thomas W. Von Geldern, Michael G. Fickes, Lakshmi Bhagavatula, Todd McDermott, Steven Wittenberger, Steven J. Richards, Kenton L. Longenecker, Kent D. Stewart, Thomas H. Lubben, Stephen J. Ballaron, Michael A. Stashko, Michelle A. Long, Heidi Wells, Bradley A. Zinker, Amanda K. Mika, David W. A. Beno, Anita J. Kempf-Grote, James Polakowski, Jason Segreti, Glenn A. Reinhart, Ryan M. Fryer, Hing L. Sham, James M. Trevillyan, Discovery of 2-[4-{{2-(2S,5R)-2-Cyano-5-ethynyl-1-pyrrolidinyl]-2-oxoethyl]amino]- 4-methyl-1-piperidinyl]-4-pyridinecarboxylic Acid (ABT-279): A Very Potent, Selective, Effective, and Well-Tolerated Inhibitor of Dipeptidyl Peptidase-IV, Useful for the Treatment of Diabetes Journal of Medicinal Chemistry. ,vol. 49, pp. 6416- 6420 ,(2006) , 10.1021/JM060777O

B. Ahren, R. Gomis, E. Standl, D. Mills, A. Schweizer, Twelve- and 52-Week Efficacy of the Dipeptidyl Peptidase IV Inhibitor LAF237 in Metformin-Treated Patients With Type 2 Diabetes. Diabetes Care. ,vol. 27, pp. 2874- 2880 ,(2004) , 10.2337/DIACARE.27.12.2874