198
Views
5
CrossRef citations to date
0
Altmetric
Review

Monocyclic beta–lactams for therapeutic uses: a patent overview (2010–2020)

, &
Pages 247-266 | Received 28 Aug 2020, Accepted 15 Dec 2020, Published online: 07 Jan 2021

References

  • Sykes RB, Bonner DP. Aztreonam: the first monobactam. Am J Med. 1985;78(2):2–10.
  • Mehta PD, Sengar NPS, Pathak AK. 2-Azetidinone – A new profile of various pharmacological activities. Eur J Med Chem. 2010;45(12):5541–5560.
  • Galletti P, Giacomini D. Monocyclic β-Lactams: new structures for new biological activities. Curr Med Chem. 2011;18(28):4265–4283.
  • Decuyper L, Jukič M, Sosič I. Antibacterial and β-lactamase inhibitory activity of monocyclic β-lactams. Med Res Rev. 2018;38(2):426–503. .
  • Dražić T, Kopf S, Corridan J. Peptide-β-lactam inhibitors of dengue and west nile virus NS2B-NS3 protease display two distinct binding modes. J Med Chem. 2020;63(1):140–156.
  • Singh GS. Recent progress in the synthesis and chemistry of azetidinones. Tetrahedron. 2003;59(39):7631–7649.
  • Kamath A, Ojima I. Advances in the chemistry of β-lactam and its medicinal applications. Tetrahedron. 2012;68(52):10640–10664.
  • Ojima I. Recent advances in the beta-lactam synthon method. Acc Chem Res. 1995;28(9):383–389.
  • Shattat GF. A Review article on hyperlipidemia: types, treatments and new drug targets. Biomed Pharmacol J. 2014;7(2):399–409.
  • Hawwari A, Qarni AA, Iqbal J. Regulation of intestinal cholesterol absorption: A disease perspective. Adv Biol Chem. 2017;7:720–726.
  • Wang L-J, Song B-L. Niemann–pick C1-like 1 and cholesterol uptake. Biochim Biophys Acta BBA - Mol Cell Biol Lipids. 2012;1821:964–972.
  • van Heek M, Farley C, Compton DS. Ezetimibe selectively inhibits intestinal cholesterol absorption in rodents in the presence and absence of exocrine pancreatic function. Br J Pharmacol. 2001;134(2):409–417.
  • Brown WV. Cholesterol absorption inhibitors: defining new options in lipid management. Clin Cardiol. 2006;26(6):259–264.
  • Huang C-S, Yu X, Fordstrom P. Cryo-EM structures of NPC1L1 reveal mechanisms of cholesterol transport and ezetimibe inhibition. Sci Adv. 2020;6(25):eabb1989.
  • Davidson MH. Novel nonstatin strategies to lower low-density lipoprotein cholesterol. Curr Atheroscler Rep. 2009;11(1):67–70.
  • AstraZeneca. 2-azetidinone derivatives as cholesterol absorption inhibitors for the treatment of hyperlipidaemic conditions. 2011. US7906502.
  • Jonas A. Lecithin cholesterol acyltransferase. Biochim Biophys Acta. 2000;1529(1–3):245–256.
  • Rousset X, Vaisman B, Amar M. Lecithin: cholesterol acyltransferase – from biochemistry to role in cardiovascular disease. Curr Opin Endocrinol Diabetes Obes. 2009;16(2):163–171.
  • Norum KR, Remaley AT, Miettinen HE. Lecithin:cholesterol acyltransferase: symposium on 50 years of biomedical research from its discovery to latest findings. J Lipid Res. 2020;61(8):1142–1149. .
  • Gunawardane RN, Fordstrom P, Piper DE. Agonistic human antibodies binding to lecithin-cholesterol acyltransferase modulate high density lipoprotein metabolism. J Biol Chem. 2016;291(6):2799–2811.
  • Manthei KA, Yang S-M, Baljinnyam B. Molecular basis for activation of lecithin:cholesterol acyltransferase by a compound that increases HDL. Cholesterol eLife. 2018;7:e41604.
  • The United States of America, as represented by the Secretary, Department of health and human service, American university. Small molecule activators and inhibitors of Lecithin: Cholesterol acyltransferase. WO2015179293. 2015.
  • Freeman LA, Demosky SJ, Konaklieva M. Lecithin:cholesterol acyltransferase activation by sulfhydryl-reactive small molecules: role of cysteine-31. J Pharmacol Exp Ther. 2017;362(2):306–318.
  • Manthei KA, Patra D, Wilson CJ. Structural analysis of lecithin:cholesterol acyltransferase bound to high density lipoprotein particles. Commun Biol. 2020;3(1):28.
  • Jetten AM. Retinoid-related orphan receptors (RORs): critical roles in development, immunity, circadian rhythm, and cellular metabolism. Nucl Recept Signal. 2009;7(1):e003.
  • Fauber BP, Magnuson S. Modulators of the nuclear receptor retinoic acid receptor-related orphan receptor-γ (RORγ or RORc). J Med Chem. 2014;57(14):5871–5892.
  • Ivanov II, McKenzie BS, Zhou L. The orphan nuclear receptor RORγt directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell. 2006;126(6):1121–1133.
  • Zhang Y, Luo X, Wu D. ROR nuclear receptors: structures, related diseases, and drug discovery. Acta Pharmacol Sin. 2015;36(1):71–87.
  • Sun N, Guo H, Wang Y. Retinoic acid receptor-related orphan receptor gamma-t (RORγt) inhibitors in clinical development for the treatment of autoimmune diseases: a patent review (2016-present). Expert Opin Ther Pat. 2019;29(9):663–674. .
  • Bronner SM, Zbieg JR, Crawford JJ. RORγ antagonists and inverse agonists: a patent review. Expert Opin Ther Pat. 2017;27(1):101–112.
  • Pandya VB, Kumar S, Sachchidanand. Combating autoimmune diseases with retinoic acid receptor-related orphan receptor-γ (RORγ or RORc) inhibitors: hits and misses. J Med Chem. 2018;61(24):10976–10995. .
  • Huh JR, Leung MWL, Huang P. Digoxin and its derivatives suppress Th17 cell differentiation by antagonizing RORγt activity. Nature. 2011;472(7344):486–490.
  • Karaś K, Sałkowska A, Sobalska-Kwapis M. Digoxin, an overlooked agonist of RORγ/RORγT. Front Pharmacol. 2019;9:1460.
  • Glenmark Pharmaceuticals. Substituted Oxoazetidine Analogues as Ror Gamma Modulators. 2018. WO2018185675.
  • McEntee WJ, Crook TH. Glutamate: its role in learning, memory, and the aging brain. Psychopharmacology (Berl). 1993;111(4):391–401.
  • Fontana A. Drugs to alter extracellular concentration of glutamate: modulators of glutamate uptake systems. Neuromethods. 2018;130:169–225.
  • Kanai Y, Hediger MA. The glutamate and neutral amino acid transporter family: physiological and pharmacological implications. Eur J Pharmacol. 2003;479(1–3):237–247.
  • Zhou Y, Danbolt NC. Glutamate as a neurotransmitter in the healthy brain. J Neural Transm. 2014;121:799–817.
  • Beart PM, O’Shea RD. Transporters for L-glutamate: an update on their molecular pharmacology and pathological involvement: roles and regulation of EAATs. Br J Pharmacol. 2009;150:5–17.
  • Fontana ACK. Current approaches to enhance glutamate transporter function and expression. J Neurochem. 2015;134:982–1007.
  • Scofield MD, Kalivas PW. Astrocytic dysfunction and addiction: consequences of impaired glutamate homeostasis. Neuroscientist. 2014;20(6):610–622.
  • Rothstein JD, Patel S, Regan MR. b-Lactam antibiotics offer neuroprotection by increasing glutamate transporter expression. Nature. 2005;433(7021):73–77. .
  • Lee SG, Su ZZ, Emdad L. Mechanism of ceftriaxone induction of excitatory amino acid transporter-2 expression and glutamate uptake in primary human astrocytes. J Biol Chem. 2008;283(19):13116–13123.
  • Cui X, Li L, Hu -Y-Y. Sulbactam plays neuronal protective effect against brain ischemia via upregulating GLT1 in rats. Mol Neurobiol. 2015;51(3):1322–1333.
  • Cudkowicz ME, Titus S, Kearney M. Efficacy and safety of ceftriaxone for amyotrophic lateral sclerosis: results of a multi-stage, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Neurol. 2014;13(11):1083–1091.
  • Xing X, Chang L-C, Kong Q. Structure–activity relationship study of pyridazine derivatives as glutamate transporter EAAT2 activators. Bioorg Med Chem Lett. 2011;21(19):5774–5777.
  • Kong Q, Chang L-C, Takahashi K. Small-molecule activator of glutamate transporter EAAT2 translation provides neuroprotection. J Clin Invest. 2014;124(3):1255–1267.
  • Temple University from Philadelphia. Novel Beta Lactams as Modulators of Glutamate Uptake and Methods for Use Thereof. 2014. WO2014197536.
  • Temple University from Philadelphia. Novel Beta Lactams as Modulators of Glutamate Uptake and Methods for Use Thereof. 2017. WO2017189831.
  • Caldwell HK, Young WS. Oxytocin and Vasopressin: genetics and Behavioral Implications. Handbook of Neurochemistry and Molecular Neurobiology. Boston, MA: Springer; 2006.
  • Favory R, Salgado DR, Vincent J-L. Investigational vasopressin receptor modulators in the pipeline. Expert Opin Investig Drugs. 2009;18(8):1119–1131.
  • Trybulski EJ. Chapter 16. Vasopressin receptor modulators: From non-peptide antagonists to agonists. Annual Reports in Medicinal Chemistry. Elsevier, 2001.
  • Simon NG, Guillon C, Fabio K. Vasopressin antagonists as anxiolytics and antidepressants: recent developments. Recent Pat CNS Drug Discov. 2008;3(2):77–93.
  • Guillon CD, Koppel GA, Brownstein MJ. Azetidinones as vasopressin V1a antagonists. Bioorg Med Chem. 2007;15(5):2054–2080. .
  • Fabio KM, Guillon CD, Lu S-F. Pharmacokinetics and metabolism of SRX246: A potent and selective vasopressin 1a antagonist. J Pharm Sci. 2013;102(6):2033–2043.
  • Azevan Pharmaceuticals. Compositions and methods for treating neurodegenerative diseases. 2015. WO2015148962A1.
  • Fischer PM. Design of small-molecule active-site inhibitors of the S1A family proteases as procoagulant and anticoagulant drugs. J Med Chem. 2018;61(9):3799–3822.
  • Gailani D, Gruber A. Factor XI as a therapeutic target. Arterioscler Thromb Vasc Biol. 2016;36(7):1316–1322.
  • Quan ML, Pinto DJP, Smallheer JM. Factor XIa inhibitors as new anticoagulants. J Med Chem. 2018;61(17):7425–7447.
  • Al-Horani RA. Factor XI(a) inhibitors for thrombosis: an updated patent review (2016-present). Expert Opin Ther Pat. 2020;30(1):39–55.
  • Xie Z, Li Z, Shao Y. Discovery and development of plasma kallikrein inhibitors for multiple diseases. Eur J Med Chem. 2020;190:112–137. .
  • Prassas I, Eissa A, Poda G. Unleashing the therapeutic potential of human kallikrein-related serine proteases. Nat Rev Drug Discov. 2015;14:183–202.
  • eXIthera Pharmaceuticals. Therapeutic compounds and compositions. WO2015120062. 2015.
  • Wong PC, Crain EJ, Watson CA. A small-molecule factor XIa inhibitor produces antithrombotic efficacy with minimal bleeding time prolongation in rabbits. J Thromb Thrombolysis. 2011;32(2):129–137.
  • eXIthera Pharmaceuticals. Therapeutic compounds and compositions. 2018. WO2018118705.
  • eXIthera Pharmaceuticals. Therapeutic compounds and compositions. WO2020092592. 2020.
  • eXIthera Pharmaceuticals. Therapeutic compounds and compositions. 2020. WO2020092594.
  • Decuyper L, Magdalenić K, Verstraete M. α‐Unsaturated 3‐Amino‐1‐carboxymethyl‐β‐lactams as bacterial PBP inhibitors: synthesis and biochemical assessment. Chem – Eur J. 2019;25(70):16128–16140.
  • Butler MS, Paterson DL. Antibiotics in the clinical pipeline in October 2019. J Antibiot (Tokyo). 2020;73:329–364.
  • Kou Q, Wang T, Zou F. Design, synthesis and biological evaluation of C(4) substituted monobactams as antibacterial agents against multidrug-resistant gram-negative bacteria. Eur J Med Chem. 2018;151:98–109.
  • Macheboeuf P, Contreras-Martel C, Job V. Penicillin binding proteins: key players in bacterial cell cycle and drug resistance processes. FEMS Microbiol Rev. 2006;30(5):673–691.
  • Page MGP. The role of iron and siderophores in infection, and the development of siderophore antibiotics. Clin Infect Dis. 2019;69(Supplement_7): 529–537. .
  • Lakemeyer M, Zhao W, Mandl FA. Thinking outside the box—novel antibacterials to tackle the resistance crisis. Angew Chem Int Ed. 2018;57:14440–14475.
  • 2019 Antibacterial agents in clinical development: an analysis of the antibacterial clinical development pipeline. Geneva: world Health Organization, 2019. Available at: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&cad=rja&uact=8&ved=2ahUKEwjwy7_Fx4PrAhWR26QKHeTCCnUQFjACegQIARAB&url=https%3A%2F%2Fapps.who.int%2Firis%2Frest%2Fbitstreams%2F1265033%2Fretrieve&usg=AOvVaw2ss-f9BH0IqrbN4saxaD7Z. [ Last accessed 2020 Aug 3].
  • Pfizer Inc. Monobactams. 2012. WO2012073138.
  • Brown MF, Mitton-Fry MJ, Arcari JT. Pyridone-conjugated monobactam antibiotics with gram-negative activity. J Med Chem. 2013;56(13):5541–5552.
  • Tao Y, Lall MS, Boyles DC. Enabled process to synthesize monobactam 1 for early development. Org Process Res Dev. 2019;23(11):2499–2509.
  • GmbH A, Co. KG. 2013. Amidine substituted beta - lactam compounds, their preparation and use as antibacterial agents. WO2013110643.
  • Pharmacodynamics of aztreonam against E.coli studied in an in vitro model of infection. Available at: https://www.nbt.nhs.uk/sites/default/files/Pharmacodynamics%20of%20aztreonam%20against%20E.coli%20studied%20in%20an%20in%20vitro%20model%20of%20infection.pdf. [ Last accessed 2020 Aug 18].
  • GmbH A, Co. KG. 2002. 3-(heteroaryl acetamido)-2-oxo-azetidine-1-sulfonic acids derivatives as antibacterial agents. WO2002022613.
  • GmbH A, Co. KG. 2019. Crystalline form of (2s)-2-[[(z)-[−1-(2-amino-4-thiazolyl)-2-[[(3s)-2,2-dimethyl-4-oxo-1-(sulfooxy)-3-azetidinyl]amino]-2-oxoethylidene]amino]oxy]-3-[4-[imino[(3r)-3- piperidinylamino]methyl]phenoxy]-propanoic acid. WO2019020810.
  • GmbH A, Co. KG. 2018. Novel formulations of amidine substituted beta-lactam compounds on the basis of modified cyclodextrins and acidifying agents, their preparation and use as antimicrobial pharmaceutical compositions. WO2018091668.
  • AiCuris Initiates Clinical Development of AIC499, a Novel Resistance-Breaking Antibiotic against a Broad Range of MDR Gram-Negative Bacteria. Available at: https://www.aicuris.com/74n93AiCuris-Initiates-Clinical-Development-of-AIC499,-a-Novel-Resistance-Breaking-Antibiotic-against-a-Broad-Range-of-MDR-Gram-Negative-Bacteria.htm. [ Last accessed 2020 Aug 25].
  • Rempex Pharmaceuticals, Inc. Oxamazin antibiotics. 2014. WO2014164526.
  • Novartis AG. 2015. Monobactam organic compounds for the treatment of bacterial infections. US20150266867.
  • Novartis AG. 2019. Chemical process for manufacturing monobactam antibiotic and intermediates thereof. WO2019026004.
  • Novartis AG. 2017. Salts and solid forms of monobactam antibiotic. WO2017050218.
  • Novartis AG. 2019. Administration of monobactam in combination with antibiotic agent for the treatment of complicated intra-abdominal infection. WO2019058346.
  • Novartis AG. 2019. Administration of monobactam for the treatment of urinary tract infection. WO2019092180.
  • Reck F, Bermingham A, Blais J. Optimization of novel monobactams with activity against carbapenem-resistant enterobacteriaceae – identification of LYS228. Bioorg Med Chem Lett. 2018;28(4):748–755.
  • Osborn M, Stachulski N, Sun H. A First-in-human study to assess the safety and pharmacokinetics of LYS228, a novel intravenous monobactam antibiotic in healthy volunteers. Antimicrob Agents Chemother. 2019;63(7):e02592.
  • Fei Z, Wu Q, Li L. New synthesis for the monobactam antibiotic—LYS228. J Org Chem. 2020;85(11):6854–6861.
  • Fei Z, Wu Q, Gong W. Process development for the synthesis of a monobactam antibiotic—LYS228. Org Process Res Dev. 2020;24(3):363–370.
  • President and fellows of Harvard College. Monobactams and methods of their synthesis and use. 2015. WO2015103583.
  • University of Notre Dame du Lac. Antibacterial monobactams. 2019. WO2019070672.
  • Carosso S, Liu R, Miller PA. Methodology for monobactam diversification: syntheses and studies of 4-Thiomethyl substituted β-lactams with activity against gram-negative bacteria, including carbapenemase producing acinetobacter baumannii. J Med Chem. 2017;60(21):8933–8944.
  • University of Notre Dame du Lac. Peripherally substituted monocyclic beta-lactams. 2017. US20170355671.
  • Carosso S, Miller MJ. Syntheses and studies of new forms of N-sulfonyloxy β-lactams as potential antibacterial agents and β-lactamase inhibitors. Bioorg Med Chem. 2015;23(18):6138–6147.
  • Merck Sharp and Dome Corporation. Bicyclic aryl monobactam compounds and methods of use thereof for the treatment of bacterial infections. 2017. WO2017155765A1.
  • Merck Sharp and Dome Corporation. Chromane monobactam compounds for the treatment of bacterial infections. 2019. WO2019070492A1.
  • Jordan A, Hadfield JA, Lawrence NJ. Tubulin as a target for anticancer drugs: agents which interact with the mitotic spindle. Med Res Rev. 1998;18(4):259–296.
  • Kaur R, Kaur G, Gill RK. Recent developments in tubulin polymerization inhibitors: an overview. Eur J Med Chem. 2014;87:89–124.
  • Pettit GR, Singh SB, Niven ML. Isolation, structure, and synthesis of combretastatins A-1 and B-1, potent new inhibitors of microtubule assembly, derived from combretum caffrum. J Nat Prod. 1987;50(1):119–131.
  • Mikstacka R, Stefański T, Różański J. Tubulin-interactive stilbene derivatives as anticancer agents. Cell Mol Biol Lett. 2013;18(3):368–397.
  • Malebari AM, Fayne D, Nathwani SM. β-Lactams with antiproliferative and antiapoptotic activity in breast and chemoresistant colon cancer cells. Eur J Med Chem. 2020;189:112050.
  • Malebari AM, Greene LM, Nathwani SM. β-Lactam analogues of combretastatin A-4 prevent metabolic inactivation by glucuronidation in chemoresistant HT-29 colon cancer cells. Eur J Med Chem. 2017;130:261–285.
  • Trinity College, University of Dublin. Combretastatin Derivatives and Uses Therefor. 2011. WO201107321.
  • Joyce JA, Hanahan D. Multiple roles for cysteine cathepsins in cancer. Cell Cycle. 2004;3(12):1516–1619.
  • Piomelli D, Scalvini L, Fotio Y. N-Acylethanolamine Acid Amidase (NAAA): structure, function, and inhibition. J Med Chem. 2020;63(14):7475–7490.
  • Bottemanne P, Muccioli GG, Alhouayek M. N-acylethanolamine hydrolyzing acid amidase inhibition: tools and potential therapeutic opportunities. Drug Discov Today. 2018;23(8):1520–1529.
  • Gorelik A, Gebai A, Illes K. Molecular mechanism of activation of the immunoregulatory amidase NAAA. Proc Natl Acad Sci. 2018;115(43):E10032–E10040.
  • Tai T, Tsuboi K, Uyama T. Endogenous molecules stimulating N-Acylethanolamine-Hydrolyzing Acid Amidase (NAAA). ACS Chem Neurosci. 2012;3(5):379–385.
  • Wei T, Leleu-Chavain N, Spencer J. Therapeutic potential of fatty acid amide hydrolase, monoacylglycerol lipase, and N-Acylethanolamine acid amidase inhibitors. J Med Chem. 2017;60:4–46.
  • The regents of the University of California. Amide derivatives of lactam based N-acylethanolamine acid amidase (NAAA) inhibitors. 2014. WO2014144547A2.
  • The regents of the University of California. Carbamate derivatives of lactam based N-acylethanolamine acid amidase (NAAA) inhibitors. 2014. WO2014144836A2.
  • Ribeiro A, Pontis S, Mengatto L. A Potent systemically active N-Acylethanolamine Acid amidase inhibitor that suppresses inflammation and human macrophage activation. ACS Chem Biol. 2015;10(8):1838–1846.
  • Fiasella A, Nuzzi A, Summa M. 3-Aminoazetidin-2-one derivatives as N-Acylethanolamine Acid Amidase (NAAA) inhibitors suitable for systemic administration. ChemMedChem. 2014;9(7):1602–1614.
  • Nuzzi A, Fiasella A, Ortega JA. Potent α-amino-β-lactam carbamic acid ester as NAAA inhibitors. Synthesis and structure–activity relationship (SAR) studies. Eur J Med Chem. 2016;111:138–159.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.