Discovery of piragliatin-first glucokinase activator studied in type 2 diabetic patients

Journal of Medicinal Chemistry

Volumn 55, Issue 16, 2012, Pages 7021-7036

  Sarabu, Ramakanth ^a   Bizzarro, Fred T ^a   Corbett, Wendy L ^a   Dvorozniak, Mark T ^a   Geng, Wanping ^a   Grippo, Joseph F ^a   Haynes, Nancy Ellen ^a   Hutchings, Stanley ^a   Garofalo, Lisa ^a   Guertin, Kevin R ^a   Hilliard, Darryl W ^a   Kabat, Marek ^a   Kester, Robert F ^a   Ka, Wang ^a   Liang, Zhenmin ^a   Mahaney, Paige E ^a   Marcus, Linda ^a   Matschinsky, Franz M ^b   Moore, David ^a   Racha, Jagdish ^a   Radinov, Roumen ^a   Ren, Yi ^a   Qi, Lida ^a   Pignatello, Michael ^a   Spence, Cheryl L ^a   Steele, Thomas ^a   Tengi, John ^a   Grimsby, Joseph ^a   more..

^a HOFFMANN LA ROCHE INC   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DRUG METABOLITE; GLUCOKINASE; GLUCOSE; HYDROXYL GROUP; INSULIN; KETONE DERIVATIVE; PIRAGLIATIN; PYRAZINE DERIVATIVE; THIAZOLE; THIOUREA DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DIABETIC PATIENT; DISTRIBUTION VOLUME; DOSE RESPONSE; DRUG ABSORPTION; DRUG CLEARANCE; DRUG DOSE COMPARISON; DRUG ELIMINATION; DRUG METABOLISM; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG SAFETY; DRUG SYNTHESIS; ENZYME ACTIVATION; GLUCOSE BLOOD LEVEL; HUMAN; IN VIVO STUDY; INSULIN RELEASE; LIPIDOSIS; MALE; MOUSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; ORAL GLUCOSE TOLERANCE TEST; PANCREAS ISLET BETA CELL; POSTPRANDIAL STATE; STRUCTURE ACTIVITY RELATION;

ANIMALS; BENZENEACETAMIDES; DIABETES MELLITUS, TYPE 2; DOGS; ENZYME ACTIVATORS; FEMALE; GLUCOKINASE; GLUCOSE; HUMANS; HYPOGLYCEMIC AGENTS; LIPIDOSES; LIVER; MACACA FASCICULARIS; MALE; MICE; MICE, INBRED C57BL; POSTPRANDIAL PERIOD; RABBITS; RATS; RATS, WISTAR; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84866927400     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm3008689     Document Type: Article

References (22)

1. Matschinsky, F. M. Assessing the potential of glucokinase activators in diabetes therapy. Nat. Rev. Drug Discovery 2009, 8, 399-416.
2. Matschinsky, F. M.; Ellerman, J. E. Metabolism of glucose in islets of Langerhans. J. Biol. Chem. 1968, 243, 2730-2736.
3. Sharma, C.; Manjeshwar, R.; Weinhouse, S. Hormonal and dietary regulation of hepatic glucokinase. Adv. Enzyme Regul. 1964, 2, 189-200.
4. Van Schaftingen, E. A protein from rat liver confers to glucokinase the property of being antagonistically regulated by fructose 6-phosphate and fructose 1-phosphate. Eur. J. Biochem. 1989, 179, 179-184.
5. Matschinsky, F. M.; Magnuson, M. A.; Zelent, D.; Jetton, T. L.; Doliba, N.; Han, Y.; Taub, R.; Grimsby, J. The network of glucokinase-expressing cells in glucose homeostasis and the potential of glucokinase activators for diabetes therapy. Diabetes 2006, 55, 1-12.
6. Edghill, E. L.; Hattersley, A. T. Genetic disorders of the pancreatic beta cell and diabetes (Permanent neonatal diabetes and maturity onset diabetes of the young). In Pancreatic Beta Cell in Health and Disease; Seino, S., Bell, G. I., Eds.; Springer: Tokyo, 2008; pp 399-430.
7. Glaser, B.; Kesavan, P.; Heyman, M.; Davis, E.; Cuesta, A.; Buchs, A.; Stanley, C. A.; Thornton, P. S.; Permutt, M. A.; Matschinsky, F. M.; Herold, K. C. Familial hyperinsulinism caused by an activating glucokinase mutation. N. Engl. J. Med. 1998, 338, 226-230.
8. Grimsby, J.; Sarabu, R.; Corbett, W. L.; Haynes, N. E.; Bizzarro, F. T.; Coffey, J. W.; Guertin, K. R.; Hilliard, D. H.; Kester, R. F.; Mahaney, P. E.; Marcus, L.; Qi, L.; Spence, C. L.; Tengi, J.; Magnuson, M. A.; Chu, C. A.; Dvorozniak, M. T.; Matschinsky, F. M.; Grippo, J. F. Allosteric activators of glucokinase: Potential role in diabetes therapy. Science 2003, 301, 370-373.
9. Grimsby, J.; Zhi, J.; Mulligan, M. E.; Arbet-Engels, C.; Taub, R.; Balena, R. Presented at the Keystone Symposia: Diabetes Mellitus, Insulin Action and Resistance, January 2008, Breckenridge, CO, United States, poster 151.
10. Haynes, N. E.; Corbett, W. L.; Bizzarro, F. T.; Guertin, K. G.; Hilliard, D. W.; Holland, G. W.; Kester, R. F. K.; Mahaney, P. E.; Qi, L.; Spence, C. L.; Tengi, J.; Dvorozniak, M. T.; Railkar, A.; Matschinsky, F. M.; Grippo, J. F.; Grimsby, J. G.; Sarabu, R. Discovery, structure-activity relationships, pharmacokinetics, and efficacy of glucokinase activator (2R)-3-cyclopentyl-2-(4- methanesul-fonylphenyl)-N-thiazol-2-yl-propianamide. J. Med. Chem. 2010, 53, 3618-3625.
11. Kester, R. F.; Corbett, W. L.; Sarabu, R.; Mahaney, P. E.; Haynes, N.-E.; Guertin, K. R.; Bizzarro, F. T.; Hilliard, D. W.; Qi, L.; Tengi, J.; Grippo, J. F.; Grimsby, J.; Marcus, L.; Dvorozniak, M.; Racha, J.; Wang, K. Discovery of piragliatin, a small molecule activator of GK (MEDI-005). 238th ACS National Meeting, Washington DC, August 16-20, 2009.
12. Sarabu, R.; Tilley, J. W.; Grimsby, J. The discovery of piragliatin, a glucokinase activator. RSC Drug Discovery Ser. 2011, 4, 51-70.
13. Myers, A. G.; Yang, H. B.; Chen, H.; Gleason, J. L. Use of pseudoephedrine as a practical chiral auxiliary for symmetric synthesis. J. Am. Chem. Soc. 1994, 116, 9361-9362.
14. Miller, R. D.; McKean, D. R. Ring opening of cyclopropyl ketones by trimethylsilyl iodide. J. Org. Chem. 1981, 46, 2412-2414.
15. Mash, E. A; Torok, D. S. Homochiral ketals in organic Synthesis. Diastereoselective cyclopropanation of α, β-unsaturated ketals derived from (S, S)-(-)-hydrobenzoin. J. Org. Chem. 1989, 54, 250-253.
16. Dieter, R. K.; Pounds, S. Ring-opening reactions of electrophilic cyclopropanes. J. Org. Chem. 1982, 47, 3174-3177.
17. O'Doherty, R. M.; Lehman, D. L.; Telemaque-Potts, S.; Newgard, C. B. Metabolic impact of glucokinase overexpression in liver: Lowering of blood glucose in fed rats is accompanied by hyperlipidemia. Diabetes 1999, 48, 2022-2027.
18. Mizutani, T.; Yoshida, K.; Kawazoe, S. Formation of toxic metabolites from thiabendazole and other thiazoles in mice. Drug Metab. Dispos. 1994, 22, 750-755.
19. Stevens, G. J.; Hitchcock, K.; Wang, Y. K.; Coppola, G. M.; Versace, R. W.; Chin, J. A.; Shapiro, M.; Suwanrumpha, S.; Mangold, L. K. In vitro metabolism of N-(5-chloro-2-methylphenyl)-N-(2-methylproyl)thiourea: Species comparison and identification of a novel thiocarbamide-glutathione adduct. Chem. Res. Toxicol. 1997, 10, 733-741.
20. Bonadonna, R. C.; Heise, T.; Arbet-Engels, C.; Kapitza, C; Avogaro, A.; Grimsby, J.; Zhi, J.; Grippo, J. F.; Balena, R. Piragliatin (RO4389620), a novel glucokinase activator, lowers plasma glucose both in the postabsorptive state and after a glucose challenge in patients with type 2 diabetes mellitus: A mechanistic study. J. Clin. Endocrinol. Metab. 2010, 95, 5028-5036.
21. http://www.scripintelligence.com/home/Roche-licenses-GKA-diabetes- candidates-to-Chinas-Hua-Medicine-325220.
22. Wang, Z. M.; Sharpless, K. B. A Solid-to-solid asymmetric dihydroxylation procedure for kilogram-scale preparation of enantio-pure hydrobenzoin. J. Org. Chem. 1994, 59, 8302-8303.