Optimization of orally bioavailable alkyl amine renin inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 2, 2010, Pages 694-699

  Xu, Zhenrong ^a   Cacatian, Salvacion ^a   Yuan, Jing ^a   Simpson, Robert D ^a   Jia, Lanqi ^a   Zhao, Wei ^a   Tice, Colin M ^a   Flaherty, Patrick T ^a   Guo, Joan ^a   Ishchenko, Alexey ^a   Singh, Suresh B ^a   Wu, Zhongren ^a   McKeever, Brian M ^a   Scott, Boyd B ^a   Bukhtiyarov, Yuri ^a   Berbaum, Jennifer ^a   Mason, Jennifer ^a   Panemangalore, Reshma ^a   Cappiello, Maria Grazia ^a   Bentley, Ross ^b   Doe, Christopher P ^b   Harrison, Richard K ^a   McGeehan, Gerard M ^a   Dillard, Lawrence W ^a   Baldwin, John J ^a   Claremon, David A ^a   more..

^a Vitae Pharmaceuticals   (United States)

^b GLAXOSMITHKLINE   (United States)

Author keywords

Aspartyl protease; Hypertension; Renin; Structure based drug design; X ray crystallography

Indexed keywords

ALIPHATIC AMINE; ALISKIREN; ANTIHYPERTENSIVE AGENT; RENIN; RENIN INHIBITOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIHYPERTENSIVE THERAPY; AREA UNDER THE CURVE; ARTICLE; BLOOD PRESSURE REGULATION; CONTROLLED STUDY; DISEASE MODEL; DRUG DESIGN; DRUG HALF LIFE; DRUG SELECTIVITY; DRUG STRUCTURE; ENZYME INHIBITION; HYPERTENSION; IC 50; IN VITRO STUDY; IN VIVO STUDY; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; RAT; TIME TO MAXIMUM PLASMA CONCENTRATION;

ADMINISTRATION, ORAL; AMINES; ANIMALS; BINDING SITES; BLOOD PRESSURE; CARBAMATES; CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; ENZYME INHIBITORS; HAPLORHINI; HUMANS; PIPERIDINES; RATS; RATS, TRANSGENIC; RENIN; STRUCTURE-ACTIVITY RELATIONSHIP;

RATTUS;

EID: 72249105528     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.11.066     Document Type: Article

References (20)

1. Zaman M.A., Oparil S., and Calhoun D.A. Nat. Rev. Drug Disc. 1 (2002) 621
2. Greenlee W.J. Med. Res. Rev. 10 (1990) 173
3. Rosenburg S.H. Prog. Med. Chem. 32 (1995) 37
4. Rosenburg, S. H.; Boyd, S. A. Antihypertensive Drugs; Van Zweiten, P. A.; Greenlee, W. J., Ed.; Harwood: Amsterdam, The Netherlands, 1997; pp 77-111.
5. Stanton A. J. Renin Angiotensin Aldosterone Syst. 4 (2003) 6-10
6. Fisher N.D.L., and Hollenburg N.K. J. Am. Soc. Nephrol. 16 (2005) 592
7. Scott B.B., McGeehan G., and Harrison R.K. Curr. Protein Pept. Sci. 7 (2006) 241-254
8. Tice C.M. Ann. Rep. Med. Chem. (2006) 155
9. Maibaum J., Stutz S., Goeschke R., Rigollier P., Yamaguchi Y., Cumin F., Rahuel J., Baum H.-P., Cohen N.-C., Schnell C.R., Fuhrer W., Gruetter M.G., Schilling W., and Wood J.M. J. Med. Chem. 50 (2007) 4832
10. Jensen C., Herold P., and Brunner H.R. Nat. Rev. Drug Disc. 7 (2008) 399
11. Tice C.M., Xu Z., Yuan J., Simpson R.D., Cacatian S., Flaherty P.T., Zhao W., Guo J., Ishchenko A., Singh S., Wu Z., Scott B.B., Bukhtiyarov Y., Berbaum J., Mason J., Panemangalore R., Cappiello M.G., Harrison R.K., McGeehan G., Dillard L.W., Baldwin J.J., and Claremon D.A. Bioorg. Med. Chem. Lett. 19 (2009) 3541-3545
12. Kerns E.H., and Di L. Drug-like Properties: Concepts, Structure Design and Methods (2008), Academic Press pp 193-194
13. Gleeson M.P. J. Med. Chem. 51 (2008) 817
14. Leach A.G., Jones H.D., Cosgrove D.A., Kenny P.W., Ruston L., MacFaul P., Wood J.M., Colclough N., and Law B. J. Med. Chem. 49 (2006) 6672
15. Märki H.P., Binggeli A., Bittner B., Bohner-Lang V., Breu V., Bur D., Coassolo P., Clozel J.P., D'Arcy A., Doebeli H., Fischli W., Funk C., Foricher J., Giller T., Gruninger F., Guenzi A., Guller T., Hartung R., Hirth G., Jenny C., Kansy M., Klinkhammer U., Lave T., Lohri B., Luft F.C., Mervaala E.M., Muller D.N., Muller M., Montavon F., Oefner C., Qiu C., Reichel A., Sanwald-Ducray P., Scalone M., Schleimer M., Schmid R., Stadler H., Treiber A., Valdenaire O., Vieira E., Waldmeier P., Wiegand-Chou R., Wilhelm M., Wostl W., Zell M., and Zell R. Il Farmaco 56 (2001) 21
16. Rosowsky A., and Wright J.E. J. Org. Chem. 48 (1983) 1539
17. Corey E.J., Bakshi R.K., Shibata S., Chen C.P., and Singh V.K. J. Am. Chem. Soc. 109 (1987) 7925
18. 50 is defined as the concentration of a particular inhibitor that reduces the formation of product by 50% relative to a control sample containing no inhibitor. (Wang, G. T. et al. Anal. Biochem. 1993, 210, 351; Nakamura, N. et al. J. Biochem. (Tokyo) 1991, 109, 741; Murakami, K. et al. Anal Biochem. 1981, 110, 232).
19. 50 is defined as the concentration of a particular inhibitor that reduces the formation of product by 50% relative to a control sample containing no inhibitor.
20. Ganten D., Wagner J., Zeb K., Bader M., Michel J.B., Paul M., Zimmermann F., Ruf P., Hilgenfeldt U., Ganten U., Kaling M., Bachmann S., Fukamizu A., Mullins J.J., and Murakami K. Proc. Natl. Acad. Sci. U.S.A. 89 (1992) 7806