P2X receptor antagonists and their potential as therapeutics: a patent review (2010–2021)

References

• Burnstock G. Purine and purinergic receptors. Brain Neurosci Adv. 2018;2:2398212818817494.
   Google Scholar
• Burnstock G. Purinergic Signalling: therapeutic developments [review]. Front Pharmacol. 2017;8:661.
   PubMed Web of Science ®Google Scholar
• Verkhratsky A, Burnstock G. Biology of purinergic signalling: its ancient evolutionary roots, its omnipresence and its multiple functional significance. BioEssays. 2014;36(7):697–705.
   PubMedGoogle Scholar
• Burnstock G.Physiology and pathophysiology of purinergic neurotransmission.Physiological Review.2007:87.659–797.
   PubMedGoogle Scholar
• Burnstock G. Pathophysiology and therapeutic potential of purinergic signaling. Pharmacol Rev. 2006;58(1):58–86.
   PubMedGoogle Scholar
• Habermacher C, Dunning K, Chataigneau T, et al. Molecular structure and function of P2X receptors. Neuropharmacology. 2016;104:18–30.
   PubMed Web of Science ®Google Scholar
• Costa-Junior HM, Sarmento Vieira F, Coutinho-Silva R. C terminus of the P2X7 receptor: treasure hunting. Purinergic Signal. 2011;7(1):7–19.
   PubMed Web of Science ®Google Scholar
• Zarrinmayeh H, Territo PR. Purinergic Receptors of the Central Nervous System: biology, PET Ligands, and Their Applications. Mol Imaging. 2020;19:1536012120927609.
   Google Scholar
• Browne LE, Jiang LH, North RA. New structure enlivens interest in P2X receptors. Trends Pharmacol Sci. 2010;31(5):229–237.
   PubMedGoogle Scholar
• N-i-h S, Kennedy C. Pharmacology of P2X receptors [10.1002/wmts.1]. Wiley interdisciplinary reviews. Membrane Transport and Signaling. 2012;1(1):16–30.
   Google Scholar
• Müller CE, Namasivayam V. Recommended tool compounds and drugs for blocking P2X and P2Y receptors. Purinergic Signal. 2021;17:633–648.
   PubMedGoogle Scholar
• Stokes L, Bidula S, Bibič L, et al. To Inhibit or Enhance? Is There a Benefit to Positive Allosteric Modulation of P2X Receptors? Front Pharmacol. 2020;11:626–627.
   PubMedGoogle Scholar
• Mulryan K, Gitterman DP, Lewis CJ, et al. Reduced vas deferens contraction and male infertility in mice lacking P2X1 receptors. Nature. 2000;403(6765):86–89.
   PubMed Web of Science ®Google Scholar
• Soare AY, Malik HS, Durham ND, et al. P2X1 selective antagonists block hiv-1 infection through inhibition of envelope conformation-dependent fusion. J Virol. 2020;94(6):e01622–19.
   PubMedGoogle Scholar
• Kozian D, Rmann M, Deleuze J-F, et al., inventors; Aventis Pharma Deutschland GMBH, assignee. Method of diagnosis of a predisposition to develop thrombotic disease and its uses . World Intellectual Property Organisation patent WO2005095642. 2005.
   Google Scholar
• Kassack MU, Braun K, Ganso M, et al. Structure–activity relationships of analogues of NF449 confirm NF449 as the most potent and selective known P2X1 receptor antagonist. Eur J Med Chem. 2004;39(4):345–357.
   PubMed Web of Science ®Google Scholar
• Hülsmann M, Nickel P, Kassack M, et al. NF449, a novel picomolar potency antagonist at human P2X1 receptors. Eur J Pharmacol. 2003;470(1):1–7.
   PubMedGoogle Scholar
• Rettinger J, Braun K, Hochmann H, et al. Profiling at recombinant homomeric and heteromeric rat P2X receptors identifies the suramin analogue NF449 as a highly potent P2X1 receptor antagonist. Neuropharmacology. 2005;48(3):461–468.
   PubMed Web of Science ®Google Scholar
• Jacobson KA, Müller CE. Medicinal chemistry of adenosine, P2Y and P2X receptors. Neuropharmacology. 2016;104:31–49.
   PubMed Web of Science ®Google Scholar
• Jaime-Figueroa S, Greenhouse R, Padilla F, et al. Discovery and synthesis of a novel and selective drug-like P2X1 antagonist. Bioorg Med Chem Lett. 2005;15(13):3292–3295.
   PubMed Web of Science ®Google Scholar
• Branca Q, Neidhart W, Ramuz H, et al., inventors; Hoffmann La Roche Inc., assignee. Amino acid derivatives having renin inhibiting activity . United States patent US005688946. 1997.
   Google Scholar
• Soto F, Lambrecht G, Nickel P, et al. Antagonistic properties of the suramin analogue NF023 at heterologously expressed P2X receptors. Neuropharmacology. 1999;38(1):141–149.
   PubMed Web of Science ®Google Scholar
• Brown SG, Kim Y-C, Kim S-A, et al. Actions of a Series of PPADS Analogs at P2X(1) and P2X(3) Receptors. Drug Dev Res. 2001;53(4):281–291.
   PubMed Web of Science ®Google Scholar
• Eugenin E, Berman JW, inventors; Albert Einstein College of Medicine of Yeshiva University, assignee. Screening methods for identifying purinergic receptor antagonists and Panx-1 hemi-channel blockers and uses thereof for treating HIV infection . World Intellectual Property Organisation patent WO2013134030. 2013.
   Google Scholar
• Pinsky D, Visovatti SH, inventors; The Regents of the University of Michigan, assignee. Compositions and methods comprising adenosine receptor agonist for the treatment of pulmonary arterial hypertension . World Intellectual Property Organisation patent WO2017192553. 2017
   Google Scholar
• Kim Y-C, Jung Y-H, inventors; Gwangju Institute of Science and Technology, assignee. Novel 5-hydroxy pyridine based compound for the use as P2X1 and P2X3 receptor antagonist and pharmaceutical composition comprising same. World Intellectual Property Organisation patent WO2018169286. 2018.
   Google Scholar
• Kim Y-C, Jung K-Y, Cho JH, inventors; Gwangju Institute of Science and Technology, assignee. Novel Pyridine Carboxylic Acid Based Compound Used as a P2X1 and P2X3 Receptor Antagonist, A Production Method For The Same and a Composition Comprising The Same . World Intellectual Property Organisation patent WO2011136459. 2011.
   Google Scholar
• Mancini JE, Ortiz G, Potilinstki C, et al. Possible neuroprotective role of P2X2 in the retina of diabetic rats. Diabetol Metab Syndr. 2018;10(1):31.
   PubMedGoogle Scholar
• Baqi Y, Hausmann R, Rosefort C, et al. Discovery of potent competitive antagonists and positive modulators of the P2X2 receptor. J Med Chem. 2011;54(3):817–830.
   PubMed Web of Science ®Google Scholar
• North RA, Jarvis MF. P2X receptors as drug targets. Mol Pharmacol. 2013;83(4):759–769.
   PubMed Web of Science ®Google Scholar
• Wolf C, Rosefort C, Fallah G, et al. Molecular Determinants of Potent P2X2 Antagonism Identified by Functional Analysis, Mutagenesis, and Homology Docking. Mol Pharmacol. 2011;79(4):649.
   PubMedGoogle Scholar
• Spinaci A, Buccioni M, Dal Ben D, et al. P2X3 Receptor Ligands: structural Features and Potential Therapeutic Applications [Opinion]. Front Pharmacol. 2021;12(525):653561.
   PubMedGoogle Scholar
• Jarvis MF. Contributions of P2X3 homomeric and heteromeric channels to acute and chronic pain. Expert Opin Ther Targets. 2003;7(4):513–522.
   PubMed Web of Science ®Google Scholar
• Ford AP. In pursuit of P2X3 antagonists: novel therapeutics for chronic pain and afferent sensitization. Purinergic Signal. 2012;8(Suppl 1):3–26.
   PubMedGoogle Scholar
• Marucci G, Dal Ben D, Buccioni M, et al. Update on novel purinergic P2X3 and P2X2/3 receptor antagonists and their potential therapeutic applications. Expert Opin Ther Pat. 2019;29(12):943–963.
   PubMed Web of Science ®Google Scholar
• Inserro A Companies Provide Trial Updates on P2X3 Blockers for Chronic Cough. American Cough Conference. 2021.
   Google Scholar
• Smith JA, Kitt MM, Morice AH, et al. Gefapixant, a P2X3 receptor antagonist, for the treatment of refractory or unexplained chronic cough: a randomised, double-blind, controlled, parallel-group, phase 2b trial. Lancet Respir Med. 2020;8(8):775–785.
   PubMed Web of Science ®Google Scholar
• Friedrich C, Francke K, Birring SS, et al. Safety and efficacy of P2X3 antagonist BAY 1902607 in refractory chronic cough. Eur Respir J. 2020;56(suppl 64):4566.
   Google Scholar
• Chen L, Dillon MP, Feng L, et al., inventors; Roche Palo Alto LLC, assignee. Pyrazole-substituted arylamides as P2X3 and P2X2/3 antagonists . United States patent US9896439. 2018.
   Google Scholar
• Chen L, Michael PD, Feng L, et al., inventors; Roche Palo Alto LLC., assignee. Triazole-substituted arylamides as P2X3 and P2X2/3 antagonists . United States patent US8440708. 2013.
   Google Scholar
• Dillon MP, Hawley RC, Chen L, et al., inventors; Roche Palo Alto LLC., assignee. Tetrazole-substituted arylamides as PX2 and PX2/3 antagonists . United States patent US10201525. 2019.
   Google Scholar
• Chen L, Dillon MP, Feng L, et al., inventors; Roche Palo Alto LLC, assignee. Triazole-substituted arylamides as P2X3 and P2X2/3 modulators . United States patent US20150065521. 2015.
   Google Scholar
• Chen L, Dillon MP, Feng L, et al., inventors; Roche Palo Alto LLC, assignee. Triazole-substituted arylamides as P2X3 and P2X2/3 antagonists . United States patent US20110245271. 2011.
   Google Scholar
• Chen L, Dillon MP, Feng L, et al., inventors; Roche Palo Alto LLC, assignee. Pyrazole-substituted arylamides as P2X3 and P2X2/3 antagonists . United States patent US20130289025. 2013.
   Google Scholar
• Dillon MP, Hawley RC, Chen L, et al., inventors; Roche Palo Alto LLC, assignee. Tetrazole-substituted arylamides as P2X3 and P2X2/3 antagonists . United States patent US20120214789. 2012.
   Google Scholar
• Chen L, Dillon MP, Feng L, et al., inventors; Roche Palo Alto LLC, assignee. Tetrazole-substituted arylamides as P2X3 and P2X2/3 . United States patent US20120015944. 2012.
   Google Scholar
• Chen L, Dillon MP, Feng L, et al., inventors; Roche Palo Alto LLC, assignee. Tetrazole-substituted arylamides as P2X3 and P2X2/3 antagonists . United States patent US20150065506. 2015.
   Google Scholar
• Chen L, Dillon MP, Feng L, et al., inventors; Roche Palo Alto LLC, assignee. Thiazole and oxazole-substituted arylamides as P2X3 and P2X2/3 antagonists . United States patent US20120022067. 2012.
   Google Scholar
• Chen L, Dillon MP, Feng L, et al., inventors; Roche Palo Alto LLC, assignee. Thiazole and oxazole-substituted arylamides as P2X3 and P2X2/3 antagonists . United States patent US20170182057. 2017.
   Google Scholar
• Chen L, Feng L, Yang M, et al., inventors; Roche Palo Alto LLC, assignee. Thiadiazole-substituted arylamides as P2X3 and P2X2/3 antagonists . United States patent US20120122886. 2012.
   Google Scholar
• Chen L, Dillon MP, Feng L, et al., inventors; Roche Palo Alto LLC, assignee. Pyrazole-substituted arylamides as P2X3 and P2X2/3 antagonists . United States patent US20170096416. 2017.
   Google Scholar
• Dillon MP, Krauss NE, inventors; Roche Palo Alto LLC, assignee. Indole, indazole and benzamidazole arylamides as P2X3 and P2X2/3 antagonists . United States patent US9440956. 2016.
   Google Scholar
• Dillon MP, Krauss NE, inventors; Roche Palo Alto LLC, assignee. Indole, indazole and benzimidazole arylamides as P2X3 and P2X2/3 antagonists . United States patent US20100324070. 2010.
   Google Scholar
• Dillon MP, Krauss NE, inventors; Roche Palo Alto LLC, assignee. Indole, indazole and benzimidazole arylamides as P2X3 and P2X2/3 antagonists. United States patent US20130267529. 2013.
   Google Scholar
• Broka CA, Hawley RC, inventors; F. Hoffmann-La Roche AG, assignee. Novel biphenyl and phenyl-pyridine amides patent . World Intellectual Property Organisation WO2010149578. 2010.
   Google Scholar
• Chen L, Dillon MP, Feng L, et al., inventors; Roche Palo Alto LLC, assignee. Substituted pyridines as P2X3 and P2X2/3 antagonists patent . United States US20170056398. 2017.
   Google Scholar
• Chen L, Dillon MP, Feng L, et al., inventors; Roche Palo Alto LLC, assignee. Oxazolone and pyrrolidnone-substituted biphenyls as P2X3 and P2X2/3 antagonists . United States patent US20120083500. 2012.
   Google Scholar
• Chen L, Dillon MP, Feng L, et al., inventors; Roche Palo Alto LLC, assignee. Oxazolone and pyrrolidnone-substituted pyridine amides as P2X3 and P2X2/3 antagonists . United States patent US20100324069. 2010.
   Google Scholar
• Davenport AJ, Brauer N, Fischer OM, et al., inventors; Bayer Aktiengeselschaft, assignee. 1,3-Thiazol-2-yl substituted benzamides . United States patent US20200131169. 2020.
   Google Scholar
• Hofmeister LH, Fischer OM, inventors; Bayer Aktiengesellschaft, assignee. 1,3-Thiazol-2-yl substituted benzamides for treatment of diseases associated with nerve fiber sensitization . World Intellectual Property Organisation patent WO2019219672. 2019.
   Google Scholar
• Merck Provides U.S. and Japan Regulatory Update for Gefapixant. [Internet]. 2022; 2022 january 24. Available from: https://www.businesswire.com/news/home/20220124005238/en/
   Google Scholar
• Wang J, Wang Y, Cui -W-W, et al. Druggable negative allosteric site of P2X3 receptors. Proc Natl Acad Sci U S A. 2018;115(19):4939–4944.
   PubMedGoogle Scholar
• Ford AP, Glaub KS, Kitt MM, et al., inventors; Afferent Pharmaceuticals, Inc., assignee. Diaminopyrimidine P2X3 and P2X2/3 receptor modulators for use in the treatment of cough. World Intellectual Property Organisation patent WO2017058645. 2017.
   Google Scholar
• Ford AP, McCarthy BG, inventors; Afferent Pharmaceuticals, assignee. Diaminopyrimidine P2X3 and P2X2/3 receptor modulators for treatment of acute, sub-acute or chronic cough . World Intellectual Property Organisation patent WO2015027212. 2015.
   Google Scholar
• Hawley RC, Ibrahim P, Ford AP, et al., inventors; Afferent Pharmaceuticals, Inc., assignee. Pyrimidines and variants thereof, and uses therefore. World Intellectual Property Organisation patent WO2017160569. 2017.
   Google Scholar
• Hawley RC, Ibrahim P, Ford AP, et al., inventors; Afferent Pharmaceuticals, Inc., assignee. Substituted pyrazole-pyrimidines, variants thereof, and uses therefore . World Intellectual Property Organisation patent WO2018111738. 2018.
   Google Scholar
• Zhao Y, Wang H, Li G, et al., inventors; NTD Univation Intellectual Property Agency Ltd., assignee. P2X3 and/or P2X2/3 receptor antagonist, pharmaceutical composition comprising same, and use thereof . World Intellectual Property Organisation patent WO2019085916. 2019.
   Google Scholar
• Gerhart W, Soni P, Tutuncu A, et al. Combination therapies for the treatment of lung diseases. World Intellectual Property Organisation patent WO2017011729. 2017.
   Google Scholar
• Burgey C, Deng Z, Nguyen D, et al., inventors; Merck Sharp & Dohme, assignee. P2X3 receptor antagonists for treatment of pain. European patent EP2860178A2. 2015.
   Google Scholar
• Broka CA, Hawley RC, inventors RPALLC, assignee. Pyridinyl amides as P2X3 and P2X2/3 inhibitors patent . United States US8895589. 2014.
   Google Scholar
• Burgey C, Nguyen D, Paone D, et al., inventors; Merck Sharp & Dohme Corp, assignee. P2X3 receptor antagonists for treatment of pain. United States patent US20110003822. 2011.
   Google Scholar
• Kim Y-C, Jung K-Y, Cho JH, inventors; Gwangju Institute of Science and Technology, assignee. Pyridine carboxylic acid based compound used as a P2X1 and P2X3 receptor antagonist, a production method for the same and a composition comprising the same . World Intellectual Property Organisation patent WO2011136459. 2011.
   Google Scholar
• Jung Y-H, Kim YO, Lin H, et al. Discovery of potent antiallodynic agents for neuropathic pain targeting P2X3 receptors. ACS Chem Neurosci. 2017;8(7):1465–1478.
   PubMedGoogle Scholar
• Burgey C, Deng Z, Nguyen D, et al., inventors; Merck Sharp & Dohme Corp., assignee. P2X3, Receptor Anatagonists for Treatment of Pain . World Intellectual Property Organisation patent WO2010051188. 2010.
   Google Scholar
• Dillon MP, Du Bois DJ, Hawley RC, et al., inventors; F. Hoffmann-La Roche AG, assignee. Novel Azaindoles . World Intellectual Property Organisation patent WO2010066629. 2010.
   Google Scholar
• Burgey C, Deng Z, Nguyen D, et al., inventors; Merck Sharp & Dohme Corp., assignee. P2X3 receptor antagonists for treatment of pain . World Intellectual Property Organisation patent WO2010111058. 2010.
   Google Scholar
• Thompson SK, Priestley T, Kundu M, et al., inventors; Asana Biosciences, LLC, assignee. P2X3 and/or P2X2/3 compounds and methods . World Intellectual Property Organisation patent WO2018064135. 2018.
   Google Scholar
• Garceau D, Matzouranis A, Bellini R, et al., inventors; Bellus Health Cough Inc, assignee. Selective P2X3 Modulators. World Intellectual Property Organisation patent WO2019064079. 2019.
   Google Scholar
• Thompson SK, Priestley T, Kundu M, et al., inventors; Asana BioSciences, LLC., assignee. P2X3 and/or P2X2/3 compounds and methods . United States patent US20200190096. 2020.
   Google Scholar
• Thompson SK, Venkatesan A, Priestley T, et al., inventors; Asana Biosciences, LLC, assignee. P2X3 and/or P2X2/3 compounds and methods . World Intellectual Property Organisation patent WO2015095128. 2015.
   Google Scholar
• Graziani D, Menegon S, Angelico P, et al., inventors; Recordati Industria Chimica E Farmaceutica SPA, assignee. P2X3 Receptor Antagonists. World Intellectual Property Organisation patent WO2020011921. 2020.
   Google Scholar
• Kai H, Kameyama T, Hasegawa T, et al., inventors; Shionogi & Co., Ltd, assignee. Novel triazine derivative and pharmaceutical composition containing same . World Intellectual Property Organisation patent WO2010092966. 2010.
   Google Scholar
• Kai H, inventor; Shionogi & Co., Ltd., assignee. Amino-triazine derivatives and pharmaceutical composition containing said derivatives . World Intellectual Property Organisation patent WO2014200078. 2014.
   Google Scholar
• Kai H, Tanaka S, Hiramatsu Y, et al., inventors; Shionogi & Co., Ltd., assignee. Heterocyclic ring and carbocyclic derivative. World Intellectual Property Organisation patent WO2013118855. 2013.
   Google Scholar
• Kai H, Endoh T, Jolohara S, et al.,inventors; Shionogi & Co., Ltd., assignee.Novel heterocyclic derivatives and pharmaceutical composition containing same.World Intellectual Property Organisation patent WO2012020742.2012.
   Google Scholar
• Pelleg A, Mahadevan A, Li J, et al., inventors; Danmir Therapeutics, LLC., assignee. 3”,5”-dialkoxybenzoyl-3’-amino-3’-deoxyadenosine-5’-triphosphates and pharmaceutical uses thereof . World Intellectual Property Organisation patent WO2019178331. 2019.
   Google Scholar
• Kuan Y, Shyu B. Nociceptive transmission and modulation via P2X receptors in central pain syndrome. Mol Brain. 2016;9:58.
   PubMedGoogle Scholar
• Tsuda M, Kuboyama K, Inoue T, et al. Behavioral phenotypes of mice lacking purinergic P2X4 receptors in acute and chronic pain assays. Mol Pain. 2009;5:28.
   PubMed Web of Science ®Google Scholar
• Ulmann L, Hirbec H, Rassendren F. P2X4 receptors mediate PGE2 release by tissue-resident macrophages and initiate inflammatory pain. Embo J. 2010 Jul 21; 29(14):2290–2300.
   PubMedGoogle Scholar
• Imai T, inventor; Nippon Chemiphar Co., Ltd., assignee. Medicine for diabetic peripheral neuropathy . World Intellectual Property Organisation patent WO2020050253. 2020.
   Google Scholar
• Sakuma S, Endo T, Kanakubo N, et al., inventors; Nippon Chemiphar Co., Ltd., assignee. P2X4 Receptor Antagonist. United States patent US20110092703. 2011.
   Google Scholar
• Ase AR, Honson NS, Zaghdane H, et al. Identification and characterization of a selective allosteric antagonist of human p2x4 receptor channels. Mol Pharmacol. 2015;87(4):606.
   PubMed Web of Science ®Google Scholar
• Hernandez-Olmos V, Abdelrahman A, El-Tayeb A, et al. N-substituted phenoxazine and acridone derivatives: structure-activity relationships of potent P2X4 receptor antagonists. J Med Chem. 2012;55(22):9576–9588.
   PubMed Web of Science ®Google Scholar
• Ushioda M, Sakuma S, Imai T, et al., inventors; Nippon Chemiphar Co., Ltd., assignee. P2X4 Receptor Antagonist. World Intellectual Property Organisation patent WO2012017876. 2012.
   Google Scholar
• Ushioda M, Sakuma S, Tendo A, et al., inventors; Nippon Chemiphar Co., Ltd., assignee. P2X4 Receptor Antagonist. World Intellectual Property Organisation patent WO2012014910. 2012.
   Google Scholar
• Newcom J, Spear K, inventors; Sunovion Pharmaceuticals Inc., assignee. P2X4 receptor modulating compounds . World Intellectual Property Organisation patent WO2015088564. 2015.
   Google Scholar
• Balázs B, Dankó T, Kovács G, et al. Investigation of the inhibitory effects of the benzodiazepine derivative, 5-BDBD on P2X4 purinergic receptors by two complementary methods. Cell Physiol Biochem. 2013;32(1):11–24.
   PubMedGoogle Scholar
• Abdelrahman A, Namasivayam V, Hinz S, et al. Characterization of P2X4 receptor agonists and antagonists by calcium influx and radioligand binding studies. Biochem Pharmacol. 2017;125:41–54.
   PubMed Web of Science ®Google Scholar
• Newcom J, Spear K, inventors; Sunovion Pharmaceuticals Inc., assignee. P2X4 receptor modulating compounds and methods of use thereof . World Intellectual Property Organisation patent WO2015088565. 2015.
   Google Scholar
• Coddou C, Sandoval R, Hevia MJ, et al. Characterization of the antagonist actions of 5-BDBD at the rat P2X4 receptor. Neurosci Lett. 2019;690:219–224.
   PubMedGoogle Scholar
• Imai T, Kamei J, inventors; Nippon Chemiphar Co., Ltd., Hoshi University, assignee. Drug for preventing and treating cough containing P2X4 receptor antagonist. World Intellectual Property Organisation patent WO2019177117. 2019.
   Google Scholar
• Sakuma S, Kobayashi K, Ushioda M, et al., inventors; Kyushu University, Nippon Chemiphar Co., Ltd, assignee. P2X4 receptor antagonist. World Intellectual Property Organisation patent WO2015005467. 2015.
   Google Scholar
• Sakuma S, Endo T, Takahashi T, et al., inventors; Nippon Chemiphar Co., Ltd., assignee. Diazepinedione Derivatives. World Intellectual Property Organisation patent WO2010090300. 2010.
   Google Scholar
• Sakuma S, Takahashi T, Ushioda M, et al., inventors; Nippon Chemiphar Co., Ltd., assignee. Preparation of 1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione derivatives as P2X4 receptor antagonists . World Intellectual Property Organisation patent WO2010093061. 2010.
   Google Scholar
• Sakuma S, Arai M, Kobayashi K, et al., inventors; Nippon Chemiphar Co., Ltd., assignee. P2X4 Receptor Antagonist. World Intellectual Property Organisation patent WO2012008478. 2012.
   Google Scholar
• Sakuma S, Arai M, Kobayashi K, et al., inventors; Nippon Chemiphar Co., Ltd., assignee. P2X4 Receptor Antagonist. World Intellectual Property Organisation patent WO2012011549. 2012.
   Google Scholar
• Ushioda M, Kobayashi K, Saito D, et al., inventors; Nippon Chemiphar Co., Ltd., assignee. P2X4 Receptor Antagonist. World Intellectual Property Organisation patent WO2013105608. 2013.
   Google Scholar
• Sakuma S, Kobayashi K, Ushioda M, et al., inventors; Nippon Chemiphar Co., Ltd., assignee. P2X4 Receptor Antagonist. World Intellectual Property Organisation patent WO2015005468. 2015.
   Google Scholar
• Imai T, Kawasaki T, Ogawa T, et al.,inventors; Nippon Chemiphar Co., Ltd., Kyushu University, National University Corporation, assignee.Pharmaceutical composition containing compound having an antagonistic activity on P2X4 receptors for treating multiple sclerosis.World intellectual property organisation patent WO2017188365.2017.
   Google Scholar
• Matsumura Y, Yamashita T, Sasaki A, et al. A novel P2X4 receptor-selective antagonist produces anti-allodynic effect in a mouse model of herpetic pain. Sci Rep. 2016;6:32461.
   PubMedGoogle Scholar
• Jacobson K, Giancotti L, Lauro F, et al. Treatment of chronic neuropathic pain: purine receptor modulation. Pain. 2020 Jul;161(7):1425-1441.
   Google Scholar
• Werner S, Mesch S, Braeuer N, et al., inventors; Bayer Pharma Aktiengesellschaft, assignee. Preparation of aromatic sulfonamide derivatives as P2X4 antagonists or negative allosteric modulators useful for treating and preventing diseases . World Intellectual Property Organisation patent WO2016198374. 2016.
   Google Scholar
• Werner S, Mesch S, Cleve A, et al., inventors; Bayer Pharma Aktiengesellschaft, assignee. Preparation of aromatic sulfonamide derivatives as inhibitors of P2X4 . World Intellectual Property Organisation patent WO2017191000. 2017.
   Google Scholar
• Werner S, Mesch S, Osmers M, et al., inventors; Bayer Pharma Aktiengesellschaft, assignee. Preparation of sulfamoylbenzamides as P2X4 antagonists or negative allosteric modulators useful for treating and preventing diseases . World Intellectual Property Organisation patent WO2018104305. 2018.
   Google Scholar
• Werner S, Mesch S, Braeuer N, inventors; Bayer Pharma Aktiengesellschaft, assignee. Aromatic sulfonamide derivatives and their use as antaongists or negative allosteric modulators of P2X4 . World Intellectual Property Organisation patent WO2018104307. 2018.
   Google Scholar
• Werner S, Cleve A, inventors; Bayer Pharma Aktiengesellschaft, assignee. Preparation of aromatic sulfonamide derivatives as antagonists or negative allosteric modulators of P2X4 receptor . World Intellectual Property Organisation patent WO2018210729. 2018.
   Google Scholar
• Werner S, Mesch S, Braeuer N, inventors; Bayer Pharma Aktiengesellschaft, assignee. Preparation of aromatic sulfonamide derivatives as P2X4 antagonists or negative allosteric modulators useful for treating and preventing diseases . World Intellectual Property Organisation patent WO2018104307. 2018.
   Google Scholar
• Werner S, Mesch S, Hillig RC, et al. Discovery and Characterization of the Potent and Selective P2X4 Inhibitor N-[4-(3-Chlorophenoxy)-3-sulfamoylphenyl]-2-phenylacetamide (BAY-1797) and Structure-Guided Amelioration of Its CYP3A4 Induction Profile. J Med Chem. 2019;62(24):11194–11217.
   PubMed Web of Science ®Google Scholar
• Lou J, Chen Y, Zhang Y, et al., inventors; Wuhan LL Science and Technology Development Co., Ltd., assignee. Fused ring compound and application thereof . World Intellectual Property Organisation patent WO2021136238. 2021.
   Google Scholar
• Kotnis S, Bingham B, Vasilyev DV, et al. Genetic and functional analysis of human p2x5 reveals a distinct pattern of exon 10 polymorphism with predominant expression of the nonfunctional receptor Isoform. Mol Pharmacol. 2010;77(6):953.
   PubMedGoogle Scholar
• Samways D, Li Z, Egan T. Principles and properties of ion flow in P2X receptors[Review]. Frontiers in Cellular Neuroscience. 2014;8:6.
   PubMedGoogle Scholar
• Jeong YH, Walsh MC, Yu J, et al., mice lacking the purinergic receptor p2x5 exhibit defective inflammasome activation and early Susceptibility to Listeria monocytogenes. J Immunol. 205(3): 760–766. 2020.
   PubMedGoogle Scholar
• Kim H, Kajikawa T, Walsh MC, et al. The purinergic receptor P2X5 contributes to bone loss in experimental periodontitis. BMB Rep. 2018;51(9):468–473.
   PubMedGoogle Scholar
• Kim H, Walsh MC, Takegahara N, et al. The purinergic receptor P2X5 regulates inflammasome activity and hyper-multinucleation of murine osteoclasts. Sci Rep. 2017;7(1):196.
   PubMedGoogle Scholar
• Andrejew R, Oliveira-Giacomelli Á, Ribeiro DE, et al. The P2X7 receptor: central hub of brain diseases [review]. Front Mol Neurosci. 2020;13:124.
   PubMedGoogle Scholar
• McClure M, Dodson G, inventors; Second Genome, Inc., assignee. Use of P2X7 receptor antagonist to treat an inflammatory disease or disorder . World Intellectual Property Organisation patent WO2019099509. 2019.
   Google Scholar
• McNulty S, Lara R, Oliphant C, et al., inventors; Biosceptre (UK) Limited, assignee. P2X7 Receptor Targeted Therapy . World Intellectual Property Organisation patent WO2021019222. 2021.
   Google Scholar
• Bryson N, inventor; University Hospitals Cleveland Medical Center, assignee. Activation of P2X7 Receptors with Non-BZBZ Adenosine Triphosphate Derivatives . World Intellectual Property Organisation patent WO2018187374. 2018
   Google Scholar
• Park JH, Kim YC. P2X7 receptor antagonists: a patent review (2010-2015). Expert Opin Ther Pat. 2017;27(3):257–267.
   PubMed Web of Science ®Google Scholar
• Karasawa A, Kawate T. Structural basis for subtype-specific inhibition of the P2X7 receptor. Elife. 2016;5:e22153.
   PubMedGoogle Scholar
• Allsopp RC, Dayl S, Schmid R, et al. Unique residues in the ATP gated human P2X7 receptor define a novel allosteric binding pocket for the selective antagonist AZ10606120. Sci Rep. 2017;7(1):725.
   PubMedGoogle Scholar
• Kilburn J, Rasmussen L, Jessing M, et al., inventors; Mindimmune Therapeutics, Inc., assignee. Cyclic Amines. United States patent US20190307766. 2019.
   Google Scholar
• Kilburn J, Rasmussen L, Jessing M, et al., inventors; H. Lundbeck A/S, assignee. Cyclic Amines. United States patent US20170128460. 2017.
   Google Scholar
• Kilburn J, Rasmussen L, Jessing M, et al., inventors; H. Lundbeck A/S, assignee. Benzamide-containing compounds and their use in the treatment of pain. United States patent US20150283134. 2015.
   Google Scholar
• Kassiou M, Figtree G, O’Brien-Brown J, et al.,inventors; The University of Sydney, assignee. Adamantanyl-substituted benzamide compound and their use as P2X7 receptor antagonists .World intellectual property organisation patent WO2020037350.2020.
   Google Scholar
• Tanaka S, Ogawa T, Kai H, et al., inventors; Shionogi & Co., Ltd., assignee. 6-membered heterocyclic derivative and pharmaceutical composition comprising same . World Intellectual Property Organisation patent WO2016171249. 2016.
   Google Scholar
• Masuda K, Sugiyama S, Yamada T, et al., inventors; Shionogi & Co., Ltd., assignee. Bicyclic nitrogenated heterocyclic derivative and pharmaceutical composition containing same. World Intellectual Property Organisation patent WO2018074390. 2018.
   Google Scholar
• Kilburn J, Hopper A, Juhl M, inventors; H. Lundbeck A/S, assignee. Inhibitor of the P2X7 receptor . World Intellectual Property Organisation patent WO2017076825 2017.
   Google Scholar
• Pevarello P, Lohmer S, Liberati C, et al., inventors; Axxam S.P.A, assignee. Substituted thiazole or oxazole P2X7 receptor antagonists . United States patent US20170283409. 2017
   Google Scholar
• Pevarello P, Lohmer S, Liberati C, et al., inventors; Axxam S.P.A, assignee. Substituted thiazole or oxazole P2X7 receptor antagonists . World Intellectual Property Organisation patent WO2015118019. 2015.
   Google Scholar
• Pevarello P, Prandi A, inventors A, et al. Substituted N-[2-(4-phenoxypiperidin-1-yl)-2-(1,3-thiazol-5-yl)ethyl]benzamide and N-[2-(4-benzyloxypiperidin-1-yl)-2-(1,3-thiazol-5-yl)ethyl]benzamide derivatives P2X7 receptor antagonists . World Intellectual Property Organisation patent WO2018041563. 2018.
   Google Scholar
• Pevarello P, Severi E, Sodano M, et al., inventors; Axxam S.P.A., assignee. 2-chloro-N-[2-(1,3-thiazol-5-yl)ethyl]-5-(5-fluoropyrimidin-2-yl)-benzamides and their use as P2X7 receptor antagonists . European patent EP3290417. 2018.
   Google Scholar
• Pevarello P, Sodano M, Severi E, et al., inventors; Axxam S.P.A., assignee. Heterocyclic P2X7 antagonists . World Intellectual Property Organisation patent WO2018202694. 2018.
   Google Scholar
• Karra S, Xiao Y, Seenisamy J, et al., inventors; Merck Patent GmbH, assignee. Quinoline derivatives and their use in neurodegenerative diseases. United States patent US20150353497. 2015.
   Google Scholar
• Karra S, Xiao Y, Seenisamy J, et al., inventors; Merck Patent GmbH, assignee. Novel quinoline derivatives and their use in neurodegenerative diseases. United States patent US20160296509. 2016.
   Google Scholar
• Hilpert K, Hubler F, Kimmerlin T, et al., inventors; Acetelion Pharmaceuticals LTD Idorsia Pharmaceuticals LTD, assignee. Indole carboxamide derivatives as P2X7 receptor antagonist . United States patent US20150322008. 2015.
   Google Scholar
• Hilpert K, Hubler F, Renneberg D, et al., inventors; Actelion Pharmaceuticals LTD, assignee. Indole carboxamide derivatives as P2X7 receptor antagonists . United States patent US20150344425. 2015.
   Google Scholar
• Karra S, inventor; Merck Patent GmbH, assignee. Indole derivatives and their use in neurodegenerative diseases . United States patent US20160168090. 2016.
   Google Scholar
• Karra S, inventor; Merck Patent GmbH, assignee. Indole derivatives and their use in neurodegenerative diseases . United States patent US20190161447. 2019.
   Google Scholar
• Karra S, Goutopoulos A, inventors; Merck Patent GMBH, assignee. Indolizine derivatives which are applicable to neurodegenerative diseases . World Intellectual Property Organisation patent WO2016019228. 2016.
   Google Scholar
• Karra S, Goutopoulos A, inventors; Merck Patent GmbH, assignee. Indolizine derivatives and their use in neurodegenerative diseases . United States patent US20170079965. 2017.
   Google Scholar
• Andres Gil J, Letavic M, Rech J, et al., inventors; Janssen Pharmaceutica NV, assignee. P2X7 modulating N-acyl-triazolopyrazines. World Intellectual Property Organisation patent WO2016039983. 2016.
   Google Scholar
• Ameriks M, Rech J, Savail B, inventors; Janssen Pharmaceutica NV, assignee. Substituted [1,2,4]triazolo[4,3-a]pyrazines as P2X7 modulators . United States patent US20150290190. 2015.
   Google Scholar
• Noguchi H, Arano Y, Ando K, et al., inventors; Raqualia Pharma Inc.,Asahi Kasei Pharma Corporation, assignee. Tetrahydroquinoline derivatives as P2X7 receptor antagonists. World Intellectual Property Organisation patent WO2018168818. 2018.
   Google Scholar
• Vaca M, Gil J, Chrovian C, et al., inventors; Janssen Pharmaceutica NV, assignee. P2X7 Modulators. United States patent US20200325138. 2020.
   Google Scholar
• Hilpert K, Hubler F, Renneberg D, et al., inventors; Actelion Pharmaceuticals Ltd., assignee. Heterocyclic amide derivatives as P2X7 receptor antagonists. United States patent US20150361096. 2015.
   Google Scholar
• Hilpert K, Hubler F, Kimmerlin T, et al., inventors; Actelion Pharmaceuticals Ltd., assignee. Heterocyclic amide derivatives as P2X7 receptor antagonists. United States patent US20150025075. 2015.
   Google Scholar
• Gargett CE, Wiley JS. The isoquinoline derivative KN-62 a potent antagonist of the P2Z-receptor of human lymphocytes. Br J Pharmacol. 1997;120(8):760–766.
   Google Scholar
• Park J-H, Lee G-E, Lee S-D, et al. Discovery of novel 2,5-dioxoimidazolidine-based P2X7 receptor antagonists as constrained analogues of KN62. J Med Chem. 2015;58(5):2114–2134.
   PubMed Web of Science ®Google Scholar
• Yong-cheol K, Jin-hee P, Williams D, inventors; Gwangju Institute of Science and Technology, assignee. Novel P2X7 receptor antagonists based on 1-piperidinyl imidazole and compositions for inhibiting cancer call migration and invasion. Korean patent KR101787709B1. 2017.
   Google Scholar
• Mansoor SE, Lü W, Oosterheert W, et al. X-ray structures define human P2X(3) receptor gating cycle and antagonist action. Nature. 2016;538(7623):66–71.
   PubMedGoogle Scholar
• Sheng D, Hattori M Recent progress in the structural biology of P2X receptors. Proteins: structure, Function, and Bioinformatics. 2022.
   Google Scholar
• Müller CE. Medicinal chemistry of P2X receptors: allosteric modulators. Curr Med Chem. 2015;22(7):929–941.
   PubMed Web of Science ®Google Scholar