Structure-based design of cycloamide-urethane-derived novel inhibitors of human brain memapsin 2 (beta-secretase) - PubMed (original) (raw)
Structure-based design of cycloamide-urethane-derived novel inhibitors of human brain memapsin 2 (beta-secretase)
Arun K Ghosh et al. Bioorg Med Chem Lett. 2005.
Abstract
A series of novel macrocyclic amide-urethanes was designed and synthesized based upon the X-ray crystal structure of our lead inhibitor (1, OM99-2 with eight residues) bound to memapsin 2. Ring size and substituent effects have been investigated. Cycloamide-urethanes containing 14- to 16-membered rings exhibited low nanomolar inhibitory potencies against human brain memapsin 2 (beta-secretase).
Similar articles
- Design, synthesis, and X-ray structure of potent memapsin 2 (beta-secretase) inhibitors with isophthalamide derivatives as the P2-P3-ligands.
Ghosh AK, Kumaragurubaran N, Hong L, Kulkarni SS, Xu X, Chang W, Weerasena V, Turner R, Koelsch G, Bilcer G, Tang J. Ghosh AK, et al. J Med Chem. 2007 May 17;50(10):2399-407. doi: 10.1021/jm061338s. Epub 2007 Apr 14. J Med Chem. 2007. PMID: 17432843 - Structure-based design: potent inhibitors of human brain memapsin 2 (beta-secretase).
Ghosh AK, Bilcer G, Harwood C, Kawahama R, Shin D, Hussain KA, Hong L, Loy JA, Nguyen C, Koelsch G, Ermolieff J, Tang J. Ghosh AK, et al. J Med Chem. 2001 Aug 30;44(18):2865-8. doi: 10.1021/jm0101803. J Med Chem. 2001. PMID: 11520194 - Fragment-based discovery of BACE1 inhibitors using functional assays.
Godemann R, Madden J, Krämer J, Smith M, Fritz U, Hesterkamp T, Barker J, Höppner S, Hallett D, Cesura A, Ebneth A, Kemp J. Godemann R, et al. Biochemistry. 2009 Nov 17;48(45):10743-51. doi: 10.1021/bi901061a. Biochemistry. 2009. PMID: 19799414 - Human beta-secretase (BACE) and BACE inhibitors.
John V, Beck JP, Bienkowski MJ, Sinha S, Heinrikson RL. John V, et al. J Med Chem. 2003 Oct 23;46(22):4625-30. doi: 10.1021/jm030247h. J Med Chem. 2003. PMID: 14561080 Review. No abstract available. - Memapsin 2 (beta-secretase) as a therapeutic target.
Hong L, Turner RT 3rd, Koelsch G, Ghosh AK, Tang J. Hong L, et al. Biochem Soc Trans. 2002 Aug;30(4):530-4. doi: 10.1042/bst0300530. Biochem Soc Trans. 2002. PMID: 12196130 Review.
Cited by
- Drug Repurposing and Polypharmacology to Fight SARS-CoV-2 Through Inhibition of the Main Protease.
Pinzi L, Tinivella A, Caporuscio F, Rastelli G. Pinzi L, et al. Front Pharmacol. 2021 Feb 22;12:636989. doi: 10.3389/fphar.2021.636989. eCollection 2021. Front Pharmacol. 2021. PMID: 33692695 Free PMC article. - Structure of the complex of porcine pancreatic elastase with a trimacrocyclic peptide inhibitor FR901451.
Kinoshita T, Kitatani T, Warizaya M, Tada T. Kinoshita T, et al. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005 Sep 1;61(Pt 9):808-11. doi: 10.1107/S1744309105026047. Epub 2005 Aug 31. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005. PMID: 16511165 Free PMC article. - A Structure-Based Discovery Platform for BACE2 and the Development of Selective BACE Inhibitors.
Yen YC, Kammeyer AM, Tirlangi J, Ghosh AK, Mesecar AD. Yen YC, et al. ACS Chem Neurosci. 2021 Feb 17;12(4):581-588. doi: 10.1021/acschemneuro.0c00629. Epub 2021 Feb 5. ACS Chem Neurosci. 2021. PMID: 33544569 Free PMC article. - Protein flexibility in virtual screening: the BACE-1 case study.
Cosconati S, Marinelli L, Di Leva FS, La Pietra V, De Simone A, Mancini F, Andrisano V, Novellino E, Goodsell DS, Olson AJ. Cosconati S, et al. J Chem Inf Model. 2012 Oct 22;52(10):2697-704. doi: 10.1021/ci300390h. Epub 2012 Oct 8. J Chem Inf Model. 2012. PMID: 23005250 Free PMC article. - Exploring the binding of BACE-1 inhibitors using comparative binding energy analysis (COMBINE).
Liu S, Fu R, Cheng X, Chen SP, Zhou LH. Liu S, et al. BMC Struct Biol. 2012 Aug 27;12:21. doi: 10.1186/1472-6807-12-21. BMC Struct Biol. 2012. PMID: 22925713 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Chemical Information