Therapeutic Potential of Boron-Containing Compounds

• Julian A dams. Protein homeostasis in cancer. Presented at: ACS ProSpectives: the discovery and selection of successful drug candidates. Boston, MA, USA, 29 April–2 May 2007.
   Google Scholar
• Rainey CJ , NyquistLA, ChristensenRE, StrongPL, CulverBD, CoughlinJR. Daily boron intake from the American diet.J. Am. Diet Assoc.99(3), 335–340 (1999).
   PubMed Web of Science ®Google Scholar
• Pekol T , DanielsJS, LabuttiJet al. Human metabolism of the proteasome inhibitor bortezomib: identification of circulating metabolites. Drug Met. Disp. 33(6), 771–777 (2005).
   PubMed Web of Science ®Google Scholar
• Taniyama K , FujiwaraH, KunoTet al. Acute and subacute toxicity of 10B-paraboronophenylalanine. Pigment Cell Res. 2, 291–296 (1989).
   PubMedGoogle Scholar
• Henriksson R , CapalaJ, MichanekAet al. Boron neutron capture therapy (BNCT) for glioblastoma multiforme: a Phase II study evaluating a prolonged high-dose of boronophenylalanine (BPA). Radiother. Oncol. 88, 183–191 (2008).
   PubMed Web of Science ®Google Scholar
• Hideghety K , SauerweinW, WittigAet al. Tissue uptake of BSH in patients with glioblastoma in the EORTC 11961 Phase I BNCT trial. J. Neuro. Oncol. 62, 145–156 (2003).
   PubMed Web of Science ®Google Scholar
• Hall DG . Boronic acids. Preparation, Applications in Organic Synthesis and Medicine. Wiley-VCH Verlag GmbH & Co., Weinheim, Germany (2005).
   Google Scholar
• Yang W , GaoX, WangB. Boronic acid compounds as potential pharmaceutical agents.Med. Res. Rev.23(3), 346–368 (2003).
   PubMed Web of Science ®Google Scholar
• Groziak MP . Boron therapeutics on the horizon.Am. J. Ther.8, 321–328 (2001).
   PubMedGoogle Scholar
• Barth RF , CoderreJA, VicenteMG, BlueTE. Boron neutron capture therapy of cancer: current status and future prospects.Clin. Cancer Res.11(11), 3987–4002 (2005).
   PubMed Web of Science ®Google Scholar
• Dewar MJS . Progress in Boron Chemistry (Volume 1). Steinberg H, McCloskey AL (Eds). Macmillan, NY, USA (1964).
   Google Scholar
• Gronowitz S , DahlgrenT, NamtvedtJet al. Antibacterial borazaro derivatives. I. 5-arylsulfonyl-4-hydroxy-4,5-borazarothieno[2,3-c]pyridines and 6-arylsulfonyl-7-hydroxy-7,6-borazarothieno[3,2-c]pyridines. Acta Pharmaceutica Suecica 8(4), 377–390 (1971).
   PubMedGoogle Scholar
• Gronowitz S , DahlgrenT, NamtvedtJet al. Antibacterial borazaro derivatives. II. Effect of substituents on the antibacterial activity of 5-arylsulfonyl-4-hydroxy-4,5-borazarothieno[2,3-c]pyridines and 6-arylsulfonyl-7-hydroxy-7,6-borazarothieno[3,2-c]pyridines. Acta Pharmaceutica Suecica 8(6), 623–638 (1971).
   PubMedGoogle Scholar
• Grassberger MA , TurnowskyF, HildebrandtJ. Preparation and antibacterial activities of new 1,2,3-diazaborine derivatives and analogues.J. Med. Chem.27, 947–953 (1984).
   PubMed Web of Science ®Google Scholar
• Högenauer G , WoisetschlaegerM. A diazaborine derivative inhibits lipopolysaccharide biosynthesis.Nature293, 662–664 (1981).
   PubMed Web of Science ®Google Scholar
• Baldock C , RaffertyJB, SedelnikovaSEet al. A mechanism of drug action revealed by structural studies of enoyl reductase. Science 274, 2107–2110 (1996).
   PubMed Web of Science ®Google Scholar
• Baldock C , RaffertyJB, SedelnikovaSEet al. Crystallization of Escherichia coli enoyl reductase and its complex with diazaborine. Acta Crystallogr D52, 1181–1184 (1996).
   Google Scholar
• Forbes D , DaviesG. Antibacterial activity of ICI 78,911 and a metabolite, ICI 79,489.Curr. Chemother. Proc. Int. Congr. Chemother.10(1), 572–574 (1978).
   Google Scholar
• Baldock C , de BoerGJ, RaffertyJBet al. Mechanism of action of diazaborines. Biochem. Pharmacol.55, 1541–1549 (1998).
   PubMed Web of Science ®Google Scholar
• Groziak MP , GangulyAD, RobinsonPD. Boron heterocycles bearing a peripheral resemblance to naturally occurring purines: design, syntheses, structures, and properties.J. Am. Chem. Soc.116, 7597–7605 (1994).
   Web of Science ®Google Scholar
• Groziak MP , ChenL, YiLet al. Planar boron heterocycles with nucleic acid-like hydrogen-bonding motifs. J. Am. Chem. Soc. 119, 7817–7826 (1997).
   Web of Science ®Google Scholar
• Robinson PD , GroziakMP, ChenL. A 2-alkyl substituted 2,3,1-benzodiazaborine.Acta Crystallogr.C54, 71–73 (1998).
   Google Scholar
• Robinson PD , GroziakMP. A boron-containing estrogen mimic.Acta Crystallogr.C55, 1701–1704 (1999).
   Google Scholar
• Davis MC , FranzblauSG, MartinAR. Syntheses and evaluation of benzodiazaborine compounds against M.tuberculosis H37RV in vitro. Bioorg. Med. Chem. Lett.8, 843–846 (1998).
   PubMed Web of Science ®Google Scholar
• Levy CW , BaldockC, WallaceAJet al. A study of the structure–activity relationship for diazaborin inhibition of Escherichia coli enoyl-ACP reductase. J. Mol. Biol. 309, 171–180 (2001).
   PubMed Web of Science ®Google Scholar
• Choo QL , KuoG, WeinerAJ. Isolation of a cDNA derived from a blood-borne non-A non-B viral hepatitis genome.Science244, 359–362 (1989).
   PubMed Web of Science ®Google Scholar
• Llinàs-Brunet M , BaileyMD, BolgerGet al. Structure–activity study on a novel series of macrocyclic inhibitors of the hepatitis C virus NS3 protease leading to the discovery of BILN 2061. J. Med. Chem. 47(7), 1605–1608 (2004).
   PubMed Web of Science ®Google Scholar
• Priestley ES , LuccaID, GhavimiB, Erickson-ViitanenS, DeciccoCP. P1 phenethyl peptide boronic acid inhibitors of HCV NS3 protease.Bioorg. Med. Chem. Let.12(21), 3199–3202 (2002).
   PubMed Web of Science ®Google Scholar
• Venkatraman S , WuW, ProngayA, GirijavallabhanV, NjorogeFG. Potent inhibitors of HCV-NS3 protease derived from boronic acids.Bioorg. Med. Chem. Lett.19(1), 180–183 (2009).
   PubMed Web of Science ®Google Scholar
• Goffin C , GhuysenJM. Multimodular penicillin-binding proteins: an enigmatic family of orthologs and paralogs.Microbiol. Mol. Bio. Rev.62, 1079–1093 (1998).
   PubMed Web of Science ®Google Scholar
• Bassetti M , RighiE, ViscoliC. Novel β-lactam antibiotics and inhibitor combinations.Expert Opin. Investig. Drugs17(3), 285–296 (2008).
   PubMed Web of Science ®Google Scholar
• Neu HC . The crisis in antibiotic resistance.Science257, 1064–1073 (1992).
   PubMed Web of Science ®Google Scholar
• Livermore DM . β-Lactamase-mediated resistance and opportunities for its control.J. Antimicrob. Chemother.41, 25–41 (1998).
   PubMed Web of Science ®Google Scholar
• Bush K , JacobyGA, MedeirosAA. A functional classification scheme for β-lactamse and its correlation with molecular structure.Antimicrob. Agents Chemother.39, 1211–1233 (1995).
   PubMed Web of Science ®Google Scholar
• Miller LA , RatnamK, PayneDJ. β-lactamase – inhibitor combinations in the 21st Century: current agents and new developments.Curr. Opin. Pharmacol.1, 451–458 (2001).
   PubMedGoogle Scholar
• Mansour TS , BradfordPA, VenkatesanAM. Recent developments in β-lactamases and inhibitors.Ann. Rep. Med. Chem.43, 247–267 (2008).
   Web of Science ®Google Scholar
• Morandi S , MorandiF, CaselliE, ShoichetB, PratiF. Structure-based optimization of cephalothin-analogue boronic acids as β-lactamase inhibitors.Bioorg. Med. Chem.16, 1195–1205 (2008).
   PubMed Web of Science ®Google Scholar
• Chen Y , ShoichetB, BonnetR. Structure, function, and inhibition along the reaction corordinate of CTX-M β-lactamase.J. Am. Chem. Soc.127, 5423–5434 (2005).
   PubMed Web of Science ®Google Scholar
• Baker SJ , Zhang Y-K, Akama T et al. Discovery of a new boron-containing anti-fungal agent, 5-fluoro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole (AN2690), for the potential treatment of onychomycosis. J. Med. Chem.49(15), 4447–4450 (2006).
   PubMed Web of Science ®Google Scholar
• Hui X , BakerSJ, WesterRCet al. In vitro penetration of a novel oxaborole antifungal (AN2690) into the human nail plate. J. Pharm. Sci.96(10), 2622–2631 (2007).
   PubMed Web of Science ®Google Scholar
• Rock FL , MaoW, YaremchukAet al. An antifungal agent inhibits an aminoacyl-tRNA synthetase by trapping tRNA in the editing site. Science 316, 1759–1761 (2007).
   PubMed Web of Science ®Google Scholar
• Lazarova TI , JinL, RynKiewicsMet al. Synthesis and in vitro biological evaluation of aryl boronic acids as potential inhibitors of factor Xia. Bioorg. Med. Chem. Lett. 16, 5022–5027 (2006).
   PubMed Web of Science ®Google Scholar
• Heins J , WelkerP, SchönleinCet al. Mechanism of proline-specific proteinases: 1 substrate specificity of dipeptidyl peptidase IV from pig Kidney and proline-endopeptidase from Flavobacterium meningosepticum. Biochim. Biophys. Acta 954(2), 161–169 (1988).
   PubMedGoogle Scholar
• Gossrau R . Cytochemistry of membrane proteases.Histochem. J.17(7), 737–771 (1985).
   PubMedGoogle Scholar
• Kieffer TJ , McintoshCHS, PedersonRA. Degradation of glucose-dependent insulinotoropic polypeptide and truncated glucagons-like peptidase 1 in vitroand in vivo by dipeptidyl peptidase IV. Endocrinology136(8), 3585–3596 (1995).
   PubMed Web of Science ®Google Scholar
• Pauly RP , RoscheF, WermannMet al. Investigation of glucose-dependent insulinotropic polypeptide-(1–42) and glucagons-like peptide-1-(7–36) degradation in vitro by dipeptidyl peptidase IV using matrix-assisted laser desorption/ionization–time of flight mass spectrometry. J. Biol. Chem. 271(38), 23222–23229 (1996).
   PubMed Web of Science ®Google Scholar
• Holst JJ . Enteroglucagon.Ann. Rev. Physiol.59, 257–271 (1997).
   PubMed Web of Science ®Google Scholar
• Deacon CF , HughesTE, HoistJH. Dipeptidyl peptidase IV inhibition potentiates the insulinotropic effect of glucagons-like peptide 1 in the anesthetized pig.Diabetes47, 764–769 (1998).
   PubMed Web of Science ®Google Scholar
• Gellwitz B . Sitagliptin: profile of a novel DPP-4 inhibitor for the treatment of Type 2 diabetes (update).Drugs Today43(11), 801–814 (2007).
   PubMed Web of Science ®Google Scholar
• Bachovchin WW , PlautAG, FlentkeGRet al. Inhibition of IgA1 proteinases from Neisseria gonorrhoeae and Hemophilus influenzae by peptide prolyl boronic acids. J. Biol. Chem. 265(7), 3738–3743 (1990).
   PubMed Web of Science ®Google Scholar
• Flentke GR , MunozE, HuberBTet al. Inhibition of dipeptidyl aminopeptidase IV (DP-IV) by Xaa-boroPro dipeptides and use of these inhibitors to examine the role of DP-IV in T-cell function. Proc. Natl Acad. Sci. USA 88, 1556–1559 (1991).
   PubMed Web of Science ®Google Scholar
• Coutts SJ , KellyTA, SnowRJet al. Structure–activity relationships of boronic acid inhibitors of dipeptidyl peptidase IV. 1. Variation of the P2 position of Xaa-boroPro dipeptides. J. Med. Chem. 39, 2087–2094 (1996).
   PubMed Web of Science ®Google Scholar
• Connolly BA , SanfordDG, ChiluwalAKet al. Dipeptidyl boronic acid inhibitors of dipeptidyl peptidase IV: determination of potency and in vivo efficacy and safety . J. Med. Chem. 51, 6005–6013 (2008).
   PubMed Web of Science ®Google Scholar
• Narra K , MullinsSR, Lee H-O et al. Phase II trial of single agent Val-boroPro (talabostat) inhibiting fibroblast activation protein in patients with metastatic colorectal cancer. Cancer Biol. Ther.6(11), 1691–1699 (2007).
   PubMed Web of Science ®Google Scholar
• Garcia-Soria G , Gonzalez-GalvezG, ArgoudGMet al. The dipeptidyl peptidase-4 inhibitor PHX1149 improves blood glucose control in patients with Type 2 diabetes mellitus. Diabetes Obes. Metab. 10(4), 293–300 (2008).
   PubMed Web of Science ®Google Scholar
• Gupta R , WalunjS, TokalaRKet al. Emerging drug candidates of dipeptidyl peptidase IV (DPP IV) inhibitor class for the treatment of Type 2 diabetes. Curr. Drug Targets 10(1), 71–87 (2009).
   PubMed Web of Science ®Google Scholar
• O‘Farrell AM , VanVA, FarhaKAet al. PharmacoKinetic and pharmacodynamic assessments of the dipeptidyl peptidase-4 inhibitor PHX1149 : double-blind, placebo-controlled, single- and multiple-dose studies in healthy subjects. Clin. Ther. 29(8), 1692–1705 (2007).
   PubMed Web of Science ®Google Scholar
• Antoni FA . Molecular diversity of cyclic AMP signaling.Front. Neuroendocrinol.21(2), 103–132 (2000).
   PubMed Web of Science ®Google Scholar
• Beavo JA . Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms.Physiol. Rev.75(4), 725–748 (1995).
   PubMed Web of Science ®Google Scholar
• Bender AT , BeavoJA. Cyclic nucleotide phosphodiesterases: molecular recognition to clinical use.Pharmacol. Rev.58, 488–520 (2006).
   PubMed Web of Science ®Google Scholar
• Torphy TJ , UndemBJ. Phosphodiesterase inhibitors: new opportunities for the treatment of asthma.Thorax46(7), 512–523 (1991).
   PubMed Web of Science ®Google Scholar
• Fleming YM , FrameMC, HouslayMD. PDE4-regulated cAMP degradation controls the assembly of integrin-dependent action adhesion structures and REF52 cell migration.J. Cell Sci.117(11), 2377–2388 (2004).
   PubMed Web of Science ®Google Scholar
• Dastidar SG , RajagopalD, RayA. Therapeutic benefit of PDE4 inhibitors in inflammatory diseases. Curr. Opin. Invest. Drugs8(5), 364–372 (2007).
   PubMed Web of Science ®Google Scholar
• Akama T , BakerSJ, Zhang Y-K et al. Discovery and structure–activity study of a novel benzoxaborole anti-inflammatory agent (AN2728) for the topical treatment of psoriasis and atopic dermatitis. Bioorg. Med. Chem. Lett.19, 2129–2132 (2009).
   PubMed Web of Science ®Google Scholar
• Baker SJ , AkamaT, Zhang Y-K et al. Identification of a novel boron-containing antibacterial agent (AN0128) with anti-inflammatory activity, for the potential treatment of cutaneous diseases. Bioorg. Med. Chem. Lett.16, 5963–5967 (2006).
   PubMed Web of Science ®Google Scholar

Websites

• Material Safety Data Sheets available from Sigma-Aldrich www.sial.com
   Google Scholar
• Combe S, Allen G, Kennedy A. A Phase I double-blind, ascending dose study of an oral synthetic direct thrombin inhibitor, TGN167. Blood 106, 1863 (2005) http://abstracts.hematologylibrary.org/cgi/content/abstract/106/11/1863
   Google Scholar
• Trigen opens IND for the initiation of a Phase III programme for flovagatran (formerly TGN 255), its novel intravenous direct thrombin inhibitor (DTI). BNET Business Publications, February 2007 http://findarticles.com/p/articles/mi_pwwi/is_200702/ai_n17169523
   Google Scholar
• Phenomix announces PHX1149 Phase 2b clinical trial results for Type 2 Diabetes. Medical News Today, May 2008 www.medicalnewstoday.com/articles/107950.php
   Google Scholar
• Anacor announces positive results from Phase 2 psoriasis trial. Anacor Press Release, February 2009 www.anacor.com/press_release_2009–2002–2019.php
   Google Scholar
• Drug details on Velcade from Drugs@FDA www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=search.DrugDetails
   Google Scholar
• Phenomix announces Phx1149 Phase 2b Clinical trial results for Type 2 Diabetes. Phenomix press release, May 2008 www.phenomix.com/news-08-05-16.asp
   Google Scholar
• Update on Point Therapeutics Merger with DARA BioSciences. DARA Press release February 2008 http://phx.corporate-ir.net/phoenix.zhtml?c=219408&p=irol-newsArticle&ID=1106638&highlight=Talabostat
   Google Scholar

Patents

• F Hoffmann-La Roche AG: WO98022496 (1998).
   Google Scholar
• Du Pont Pharmaceuticals Company: WO2001002424 (2001).
   Google Scholar
• Bristol-Myers Squibb Pharma Company: WO2001007407 (2001).
   Google Scholar
• Bristol-Myers Squibb Pharma Company: WO2001064678 (2001).
   Google Scholar
• Phenomix Corporation: WO2007016476 (2007).
   Google Scholar
• Phenomix Corporation: WO2007089618 (2007).
   Google Scholar
• Phenomix Corporation: WO2008070733 (2008).
   Google Scholar
• Anacor Pharmaceuticals, Inc.: WO2007078340 (2007).
   Google Scholar
• Trigen Limited: US20080234228 (2008).
   Google Scholar
• Trigen Limited: US20080287370 (2008).
   Google Scholar