Improving the pharmacokinetics of GPR40/FFA1 full agonists

ACS Medicinal Chemistry Letters

Volumn 5, Issue 4, 2014, Pages 384-389

  Du, Xiaohui ^a   Dransfield, Paul J ^a   Lin, Daniel C H ^a   Wong, Simon ^a   Wang, Yingcai ^a   Wang, Zhongyu ^a   Kohn, Todd ^a   Yu, Ming ^a   Brown, Sean P ^a   Vimolratana, Marc ^a   Zhu, Liusheng ^a   Li, An Rong ^a   Su, Yongli ^a   Jiao, Xianyun ^a   Liu, Jiwen ^a   Swaminath, Gayathri ^a   Tran, Thanhvien ^a   Luo, Jian ^a   Zhuang, Run ^a   Zhang, Jane ^a   Guo, Qi ^a   Li, Frank ^a   Connors, Richard ^a   Medina, Julio C ^a   Houze, Jonathan B ^a   more..

^a AMGEN INC   (United States)

Author keywords

FFA1; full agonist; GPR40; insulin secretagoue; type 2 diabetes

Indexed keywords

AGENTS INTERACTING WITH TRANSMITTER, HORMONE OR DRUG RECEPTORS; AM 1638; BENZENE DERIVATIVE; FLUORINE; FUNCTIONAL GROUP; G PROTEIN COUPLED RECEPTOR 40; PYRIDINE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG EFFICACY; DRUG HALF LIFE; DRUG METABOLISM; DRUG SCREENING; DRUG STABILITY; IN VIVO STUDY; MOUSE; NONHUMAN; ORAL GLUCOSE TOLERANCE TEST; PRIORITY JOURNAL; STRUCTURE ACTIVITY RELATION;

EID: 84898020651     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml4005123     Document Type: Article

References (16)

1. Defronzo, R. A. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes Diabetes 2009, 58, 773-795
2. Nazimek-Siewniak, B.; Moczulski, D.; Grzeszczak, W. Risk of macrovascular and microvascular complications in Type 2 diabetes: results of longitudinal study design J. Diabetes Complications 2002, 16, 271-276
3. Kles, K. A.; Vinik, A. I. Pathophysiology and treatment of diabetic peripheral neuropathy: the case for diabetic neurovascular function as an essential component Curr. Diabetes Rev. 2006, 2, 131-145
4. Rahman, S.; Rahman, T.; Ismail, A. A.; Rashid, A. R. Diabetes-associated macrovasculopathy: pathophysiology and pathogenesis Diabetes Obes. Metab. 2007, 9, 767-780
5. Edfalk, S.; Steneberg, P.; Edlund, H. GPR40 is expressed in enteroendocrine cells and mediates free fatty acid stimulation of incretin secretion Diabetes 2008, 57, 2280-2287
6. Houze, J. B. Long-Chain Free Fatty Acid Receptor Agonists. In New Therapeutic Strategies for Type 2 Diabetes: Small Molecule Approaches; Royal Society of Chemistry: London, U.K., 2012; pp 403-422.
7. Bharate, S. B.; Nemmani, K. S.; Vishwakarma, R. A. Progress in the discovery and development of small-molecule modulators of G-protein-coupled receptor 40 (GPR40/FFA1/FFAR1): An emerging target for type 2 diabetes Expert Opin. Ther. Pat. 2009, 19, 237-264
8. Medina, J. C.; Houze, J. B. GPR40 (FFAR1) modulators Annu. Rep. Med. Chem. 2008, 43, 75-85
9. Negoro, N.; Sasaki, S.; Mikami, S.; Ito, M.; Suzuki, M.; Tsujihata, Y.; Ito, R.; Harada, A.; Takeuchi, K.; Suzuki, N.; Miyazaki, J.; Santou, T.; Odani, T.; Kanzaki, N.; Funami, M.; Tanaka, T.; Kogame, A.; Matsunaga, S.; Yasuma, T.; Momose, Y. Discovery of TAK-875: A potent, selective, and orally bioavailable GPR40 agonist ACS Med. Chem. Lett. 2010, 1, 290-294
10. Christiansen, E.; Due-Hansen, M. E.; Urban, C.; Merten, N.; Pfleiderer, M.; Karlsen, K. K.; Rasmussen, S. S.; Steensgaard, M.; Hamacher, A.; Schmidt, J.; Drewke, C.; Petersen, R. K.; Kristiansen, K.; Ullrich, S.; Kostenis, E.; Kassack, M. U.; Ulven, T. Structure-activity study of dihydrocinnamic acids and discovery of the potent FFA1 (GPR40) agonist TUG-469 ACS Med. Chem. Lett. 2010, 1, 345-349
11. Sasaki, S.; Kitamura, S.; Negoro, N.; Suzuki, M.; Tsujihata, Y.; Suzuki, N.; Santou, T.; Kanzaki, N.; Harada, M.; Tanaka, Y.; Kobayashi, M.; Tada, N.; Funami, M.; Tanaka, T.; Yamamoto, Y.; Fukatsu, K.; Yasuma, T.; Momose, Y. Design, synthesis, and biological activity of potent and orally available G protein-coupled receptor 40 agonists J. Med. Chem. 2011, 54, 1365-1378
12. Brown, S. P.; Dransfield, P. J.; Vimolratana, M.; Jiao, X.; Zhu, L.; Pattaropong, V.; Sun, Y.; Liu, J.; Luo, J.; Zhang, J.; Wong, S.; Zhuang, R.; Guo, Q.; Li, F.; Medina, J. C.; Swaminath, G.; Lin, D. C.-H.; Houze, J. B. Discovery of AM-1638: A potent and orally bioavailable GPR40/FFA1 full agonist ACS Med. Chem. Lett. 2012, 3, 726-730
13. Luo, J.; Swaminath, G.; Brown, S. P.; Zhang, J.; Guo, Q.; Chen, M.; Nguyen, K.; Tran, T.; Miao, L.; Dransfield, P. J.; Vimolratana, M.; Houze, J. B.; Wong, S.; Toteva, M.; Shan, B.; Li, F.; Zhuang, R.; Lin, D. C.-H. A potent class of GPR40 full agonists engages the enteroinsular axis to promote glucose control in rodents PLoS One 2012, 7, e46300
14. Wang, Y.; Liu, J.; Dransfield, P. J.; Zhu, L.; Wang, Z.; Du, X.; Jiao, X.; Su, Y.; Li, A.; Brown, S. P.; Kasparian, A.; Vimolratana, M.; Yu, M.; Pattaropong, V.; Houze, J. B.; Swaminath, G.; Tran, T.; Nguyen, K.; Guo, Q.; Zhang, J.; Zhuang, R.; Li, F.; Miao, L.; Bartberger, M. D.; Correll, T. L.; Chow, D.; Wong, S.; Luo, J.; Lin, D. C.-H; Medina, J. C. Discovery and optimization of potent GPR40 full agonists containing tricyclic spirocycles ACS Med. Chem. Lett. 2013, 4, 551-555
15. Christiansen, E.; Urban, C.; Grundmann, M.; Due-Hansen, M. E.; Hagesaether, E.; Schmidt, J.; Pardo, L.; Ullrich, S.; Kostenis, E.; Kassack, M.; Ulven, T. Identification of a potent and selective free fatty acid receptor 1 (FFA1/GPR40) agonist with favorable physicochemical and in vitro ADME properties J. Med. Chem. 2011, 54, 6691-6703
16. Karasawa, H.; Nagata-Goto, S.; Takaishi, K.; Kumagae, Y. A novel model of type 2 diabetes mellitus based on obesity induced by high-fat diet in BDF1 mice Metabolism 2009, 58, 296-303