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Review

Cathepsin B and L inhibitors: a patent review (2010 - present)

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Pages 643-656 | Received 18 May 2016, Accepted 06 Dec 2016, Published online: 23 Dec 2016

References

  • Kim W, Kang K. Recent developments of cathepsin inhibitors and their selectivity. Expert Opin Ther Pat. 2002;12:419–432.
  • Grabowska UB, Chambers TJ, Shiroo M. Recent developments in cathepsin K inhibitor design. Curr Opin Drug Disc. 2005;8:619–630.
  • Thurmond RL, Sun S, Karlsson L, et al. Cathepsin S inhibitors as novel immunomodulators. Curr Opin Invest Dr. 2005;6:473–482.
  • Frizler M, Stirnberg M, Sisay MT, et al. Development of nitrile-based peptidic inhibitors of cysteine cathepsins. Curr Top Med Chem. 2010;10:294–322.
  • Lee-Dutra A, Wiener DK, Sun S. Cathepsin S inhibitors: 2004-2010. Expert Opin Ther Pat. 2011;2:311–337.
  • Hernandez AA, Roush WR. Recent advances in the synthesis, design and selection of cysteine protease inhibitors. Curr Opin Chem Biol. 2002;6:459–465.
  • Biniossek ML, Nägler DK, Becker-Pauly C, et al. Proteomic identification of protease cleavage sites characterizes prime and non-prime specificity of cysteine cathepsins B, L, and S. J Proteome Res. 2011;10:5363–5373.
  • Illy C, Quraishi O, Wang J, et al. Role of the occluding loop in cathepsin B activity. J Biol Chem. 1997;272:1197–1202.
  • Musil D, Zucic D, Turk D, et al. The refined 2.15-A X-ray crystal structure of human liver cathepsin B: the structural basis for its specificity. Embo J. 1991;10:2321−30.
  • Almeida PC, Nantes IL, Chagas JR, et al. Cathepsin B activity regulation-heparin-like glycosaminoglycans protect human cathepsin B from alkaline pH-induced inactivation. J Biol Chem. 2001;276:944–951.
  • Cotrin SS, Puzer L, Judice WAD, et al. Positional-scanning combinatorial libraries of fluorescence resonance energy transfer peptides to define substrate specificity of carboxydipeptidases: assays with human cathepsin B. Anal Biochem. 2004;335:244–252.
  • Schenker P, Alfarano P, Kolb P, et al. A double headed cathepsin B inhibitor devoid of warhead. Protein Sci. 2008;17:2145–2155.
  • Schmitz J, Li T, Bartz U, et al. Cathepsin B inhibitors: combining dipeptide nitriles with an occluding loop recognition element by click chemistry. ACS Med Chem Lett. 2016;7:211–216.
  • Shah PP, Wang T, Kaletsky RL, et al. A small-molecule oxocarbazate inhibitor of human cathepsin L blocks severe acute respiratory syndrome and ebola pseudotype virus infection into human embryonic kidney 293T cells. Mol Pharmacol. 2010;78:319–324.
  • Turk V, Stoka V, Vasiljeva O, et al. Cysteine cathepsins: from structure, function and regulation to new frontiers. BBA-Proteins Proteom. 2012;1824:68–88.
  • Kaletsky RL, Simmons G, Bates P. Proteolysis of the ebola virus glycoproteins enhances virus binding and infectivity. J Virol. 2007;81:13378–13384.
  • Pager CT, Craft WW, Patch J, et al. A mature and fasogenic form of the nipah requires proteolytic processing by virus fusion protein cathepsin L. J Virol. 2006;346:251–257.
  • University of Illinois. Methods for inhibiting viruses by targeting cathepsin-L cleavage sites in the viruses glycoproteins. WO 2013152223A2 (2013); also published as US 20150150878A1 (2015).
  • Shulla A, Heald-Sargent T, Subramanya G, et al. A transmembrane serine protease is linked to the severe acute respiratory syndrome coronavirus receptor and activates virus entry. J Virol. 2011;85:873–882.
  • Matsuyama S, Nagata N, Shirato K, et al. Efficient activation of the severe acute respiratory syndrome coronavirus spike protein by the transmembrane protease TMPRSS2. J Virol. 2010;84:12658–12664.
  • Gong YS, Chang L, Viola KL, et al. Alzheimer’s disease-affected brain: presence of oligomeric A beta ligands (ADDLs) suggests a molecular basis for reversible memory loss. P Natl Acad Sci USA. 2003;100:10417–10422.
  • Hook V, Toneff T, Bogyo M, et al. Inhibition of cathepsin B reduces beta-amyloid production in regulated secretory vesicles of neuronal chromaffin cells: evidence for cathepsin B as a candidate beta-secretase of Alzheimer’s disease. Biol Chem. 2005;386:931–940.
  • Merck Frosst Canada, Ltd. Preparation of diarylalkynyltrifluoroethyl sulfonylalaninamides as cathepsin B inhibitors. US 2010004871A1 (2010); also published as WO 2008037072A1 (2008), EP 2076490A1 (2009).
  • Merck Frosst Canada, Ltd. preparation of phenylalanine cyanomethylamides as cathepsin B inhibitors. WO 2010069069A1 (2010).
  • Virobay Inc. Preparation of fluoroalkyl amino acid amides as inhibitors of cathepsin B, K, L, F, or S. WO 2010056877A2 (2010); also published as WO 2010056877A3 (2010), CA 2743749A1 (2010), EP 2361243A2 (2011), EP 2361243 (2013), CN 102264695A (2011), CN 102264695B (2014), JP 2012508758T (2012), JP 5540004B2 (2014), IN 2011KN02004A (2011).
  • Hoffman La Roche Inc. Preparation of proline dipetidyl nitrile derivatives as cathepsin particularly cathepsin S and L inhibitor. US 8163793B2 (2010); also published as US 20100267722A1 (2010), CA 2758210A1 (2010), WO 2010121918A1 (2010), AU 2010241084A1 (2011), AU 2010241084B2 (2014), KR 2011140136A (2011), KR 1320790B1 (2013), EP 2421826A1 (2012), EP 2421826B1 (2013), CN 102405211A (2012), CN 102405211B (2015), JP 2012524116T (2012), JP 5518997B2 (2014), NZ 595073A (2012), IL 215065A (2013), ES 2436550T3 (2014), PT 2421826E (2014), RU 2535479C2 (2014).
  • Hoffman La Roche Inc. Novel pyridine derivatives as cathepsin inhibitors and their preparation. US 20150307472A1 (2015); also published as WO 2014029722A1 (2014), CA 2879796A1 (2014), AU 2013305102A1 (2015), IL 237128A (2015), KR 2015044947A (2015), CN 104583198A (2015), EP 2888244A1 (2015), JP 201553099T (2015), AR 92172A1 (2015), IN 2015DN00962A (2015), CR 20150073A (2015), MX 2015002026A (2015).
  • Hoffman La Roche Inc. Novel cyclopentane derivatives as cysteine protease cathepsin inhibitors and their preparation use in the treatment of diseases. US 7893099B2 (2011); also published as WO 2010142650A1 (2010), US 20100317647A1 (2010), CA 2762619A1 (2010), AU 2010257586A1 (2011), AU 2010257586B2 (2015), KR 2012034727A (2012), EP 2440521A1 (2012).
  • Loeser R, Frizler M, Schilling K, et al. Azadipeptide nitriles: highly potent and proteolytically stable inhibitors of papain-like cysteine proteases. Angew Chem Int Edit. 2008;47:4331–4334.
  • Jilin University. Preparation of hydrazine nitrile compounds as cathepsin inhibitors. CN 102731344A (2012). also published as CN 102731344B (2014).
  • Frizler M, Lohr F, Furtmann N, et al. Structural optimization of azadipeptide nitriles strongly increases association rates and allows the development of selective cathepsin inhibitors. J Med Chem. 2011;54:396–400.
  • Jilin University. Hydrazine nitriles as cathepsin K inhibitor and their preparation use in the treatment of osteoporosis. CN 103086923B (2013).
  • Viro Bay Inc. Preparation of substituted 2-(1-phenylethylamino)-3-phenylpropanamide derivatives as cathepsin inhibitors. US 20140256698A1 (2014); also published as WO 2014164844A1 (2014), US 20150191459A1 (2015).
  • Viro Bay Inc. Cathepsin inhibitors for the treatment of bone cancer and bone cancer pain. US 8680152B2 (2014); also published as WO 2012151319A1 (2012), US 20120282267A1 (2012).
  • Viro Bay Inc. Preparation of prolyl peptides as HCV inhibitors. US 20070054864A1 (2007); also published as US 7608592B2 (2009), AU 2006265632A1 (2007), AU 2006265632B2 (2012), CA 2613112A1 (2007), WO 2007005838A2 (2007), WO 2007005838A3 (2008), KR 2008027803A (2008), KR 1369872B1 (2014), EP 1906945A2 (2008), EP 1906945B1 (2015), CN 101242816A (2008), CN 101242816B (2012), JP 2009500353T (2009), JP 5368089B2 (2013), ZA 2007011069 (2009), EA 15415B1 (2011), NZ 564257A (2012), EP 2431379A2 (2012).
  • Viro Bay Inc. Preparation of peptides as inhibitors of cathepsin B. US 8211897B2 (2012); also published as WO 2009100225A1 (2009), CA 2713108A1 (2009), US 20090203629A1 (2009), EP 2237793A1 (2010), CN 101969973A (2011), CN 101969973B (2015), JP 2011511089T (2011), JP 5718647B2 (2015), JP 2015051985A (2015), BR 200900772A2 (2015), MX 2010008371A (2010).
  • Amura Therapeutics Ltd. Preparation of furopyrrolyl amino acid amides as dual cathepsin S and K inhibitors. WO 2009112839A1 (2009).
  • Gruenental GMB. 3-Oxo-tetrahydro-furo[3,2-b]pyrrol-4(5H)-yl derivatives I as cathepsin inhibitors and their preparation. WO 2015161928A1 (2015); also published as US 20150307507A1 (2015).
  • Xu M, Yang L, Rong JG, et al. Inhibition of cysteine cathepsin B and L activation in astrocytes contributes to neuroprotection against cerebral ischemia via blocking the tBid-mitochondrial apoptotic signaling pathway. Glia. 2014;62:855–880.
  • Soochow University. 2-(3,5-dimethoxybenzylidene) cyclopentanone, A novel synthetic small-molecule compound, provides effectes against ischemic stroke. CN 103330708A (2013).
  • The University of Pennsylvania. Inhibitors of human cathepsin L, cathepsin B and cathepsin S and therapeutic uses thereof. US 20110207726A1 (2011); as WO 2009136997A2 (2009), WO 2009136997A3 (2009).
  • Katunuma N, Murata E, Kakegawa H, et al. Structure based development of novel specific inhibitors for cathepsin L and cathepsin S in vitro and in vivo. Febs Lett. 1999;458:6–10.
  • Research Foundation of the city, University of New York. Vinyl sulfonate ester inhibitors of cathepsin L inhibitors and their analytical uses. US 2015337286A1 (2015).
  • Rosser CJ, Gaar M, Porvasnik S. Molecular fingerprinting of radiation resistant tumors: can we apprehend and rehabilitate the suspects?. BMC Cancer. 2009;9:225.
  • Xiang B, Fei X, Zhuang W, et al. Cathepsin L is involved in 6-hydroxydopamine induced apoptosis of SH-SY5Y neuroblastoma cells. Brain Res. 2011;1387:29–38.
  • Soochow University. Application of cathepsin L inhibitor in preparing radiotherapy sensitizing agents. CN 102423489A (2012).
  • University of Ljubljana. 8-hydroxyquinolines as inhibitors of cathepsin B. EP 2353599A1 (2010); also published as WO 2011091973A1 (2011).
  • Sosic I, Mirkovic B, Arenz K, et al. Development of new cathepsin B inhibitors: combining bioisosteric replacements and structure-based design to explore the structure-activity relationships of nitroxoline derivatives. J Med Chem. 2013;56:521−33.
  • Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences. Cathepsin B inhibitors. CN 103006621A (2012).
  • Zhou YJ, Gao W, Rong Q, et al. Modular pathway engineering of diterpenoid synthases and the mevalonic acid pathway for miltiradiene production. J Am Chem Soc. 2012;134:3234–3241.
  • Kunming University of Science and Technology. Black orbit toad bladder inhibition and their gene. CN 103172730B (2014).

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