Transient receptor potential ankyrin 1 (TRPA1) antagonists: a patent review (2015–2019)

References

• Venkatachalam K, Montell C. TRP channels. Annu Rev Biochem. 2007;76:387–417.
   PubMed Web of Science ®Google Scholar
• Samanta A, Hughes TET. Moiseenkova-Bell, V. Y. Transient receptor potential (TRP) channels. Subcell Biochem. 2018;87:141–165.
   Google Scholar
• Nilius B, Szallasi A. Transient receptor potential channels as drug targets: from the science of basic research to the art of medicine. Pharmacol Rev. 2014;66:676–814.
   PubMed Web of Science ®Google Scholar
• Moran MM. TRP channels as potential drug targets. Annu Rev Pharmacol Toxicol. 2018;58:309–330.
   PubMed Web of Science ®Google Scholar
• Jaquemar D, Schenker T, Trueb B. An ankyrin-like protein with transmembrane domains is specifically lost after oncogenic transformation of human fibroblasts. J Biol Chem. 1999;274:7325–7333.
   PubMed Web of Science ®Google Scholar
• Story GM, Peier AM, Reeve AJ, et al. ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell. 2003;112:819–829.
   PubMed Web of Science ®Google Scholar
• Chen J, Hackos DH. TRPA1 as a drug target—promise and challenges. Naunyn-Schmiedeberg’s Arch Pharmacol. 2015;388:451–463.
   Google Scholar
• Meents JE, Ciotu CI, Fischer MJM. TRPA1: a molecular view. J Neurophysiol. 2019;121:427–443.
   PubMed Web of Science ®Google Scholar
• Logashina YA, Korolkova YV, Kozlov SA, et al. TRPA1 channel as a regulator of neurogenic inflammation and pain: structure, function, role in pathophysiology, and therapeutic potential of ligands. Biochemistry (Mosc). 2019;84:101–118.
   PubMed Web of Science ®Google Scholar
• Talavera K, Startek JB, Alvarez-Collazo J, et al. Mammalian Transient receptor potential TRPA1 channels: from structure to disease. Physiol Rev. 2020;100:725–803.
   PubMed Web of Science ®Google Scholar
• Nagata K, Duggan A, Kumar G, et al. Nociceptor and hair cell transducer properties of TRPA1, a channel for pain and hearing. J Neurosci. 2005;25:4052–4061.
   PubMed Web of Science ®Google Scholar
• Bautista DM, Movahed P, Hinman A, et al. Pungent products from garlic activate the sensory ion channel TRPA1. Proc Natl Acad Sci. 2005;102:12248–12252.
   PubMed Web of Science ®Google Scholar
• Bautista DM, Jordt SE, Nikai T, et al. TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell. 2006;124:1269–1282.
   PubMed Web of Science ®Google Scholar
• Kwan KY, Allchorne AJ, Vollrath MA, et al. TRPA1 contributes to cold, mechanical, and chemical nociception but is not essential for hair-cell transduction. Neuron. 2006;50:277–289.
   PubMed Web of Science ®Google Scholar
• Jordt S-E, Bautista DM, Chuang H, et al. Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature. 2004;427:260–265.
   PubMed Web of Science ®Google Scholar
• Hinman A, Chuang H, Bautista DM, et al. TRP channel activation by reversible covalent modification. Proc Natl Acad Sci. 2006;103:19564–19568.
   PubMed Web of Science ®Google Scholar
• Mukhopadhyay I, Gomes P, Aranake S, et al. Expression of functional TRPA1 receptor on human lung fibroblast and epithelial cells. J Recept Signal Transduct. 2011;31:350–358.
   PubMed Web of Science ®Google Scholar
• Nassini R, Pedretti P, Moretto N, et al. Transient receptor potential ankyrin 1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation. PLoS One. 2012;7:e42454.
   PubMed Web of Science ®Google Scholar
• Nassenstein C, Kwong K, Taylor-Clark T, et al. Expression and function of the ion channel TRPA1 in vagal afferent nerves innervating mouse lungs. J Physiol. 2008;586:1595–1604.
   PubMed Web of Science ®Google Scholar
• Bessac BF, Sivula M, von Hehn CA, et al. TRPA1 is a major oxidant sensor in murine airway sensory neurons. J Clin Invest. 2008;118:1899–1910.
   PubMed Web of Science ®Google Scholar
• Caceres AI, Brackmann M, Elia MD, et al. A sensory neuronal ion channel essential for airway inflammation and hyperreactivity in asthma. Proc Natl Acad Sci U S A. 2009;106:9099–9104.
   PubMed Web of Science ®Google Scholar
• Raemdonck K, de Alba J, Birrell MA, et al. A role for sensory nerves in the late asthmatic response. Thorax. 2012;67:19–25.
   PubMed Web of Science ®Google Scholar
• Jardín I, López JJ, Diez R, et al. TRPs in Pain Sensation. Front Physiol. 2017;8:392.
   PubMed Web of Science ®Google Scholar
• Kremeyer B, Lopera F, Cox JJ, et al. A gain-of-function mutation in TRPA1 causes familial episodic pain syndrome. Neuron. 2010;66:671–680.
   PubMed Web of Science ®Google Scholar
• McNamara CR, Mandel-Brehm J, Bautista DM, et al. TRPA1 mediates formalin-induced pain. Proc Natl Acad Sci U S A. 2007;104:13525–13530.
   PubMed Web of Science ®Google Scholar
• Trevisani M, Siemens J, Materazzi S, et al. 4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1. Proc Natl Acad Sci U S A. 2007;104:13519–13524.
   PubMed Web of Science ®Google Scholar
• Kwan KY, Glazer JM, Corey DP, et al. TRPA1 modulates mechanotransduction in cutaneous sensory neurons. J Neurosci. 2009;29:4808–4819.
   PubMed Web of Science ®Google Scholar
• Petrus M, Peier AM, Bandell M, et al. A role of TRPA1 in mechanical hyperalgesia is revealed by pharmacological inhibition. Mol Pain. 2007;3:40.
   PubMed Web of Science ®Google Scholar
• Eid SR, Crown ED, Moore EL, et al. HC-030031, a TRPA1 selective antagonist, attenuates inflammatory- and neuropathy-induced mechanical hypersensitivity. Mol Pain. 2008;4:48.
   PubMed Web of Science ®Google Scholar
• Chen J, Joshi SK, DiDomenico S, et al. Selective blockade of TRPA1 channel attenuates pathological pain without altering noxious cold sensation or body temperature regulation. Pain. 2011;152:1165–1172.
   PubMed Web of Science ®Google Scholar
• Nyman E, Franzén B, Nolting A, et al. In vitro pharmacological characterization of a novel TRPA1 antagonist and proof of mechanism in a human dental pulp model. J Pain Res. 2013;6:59–70.
   PubMed Web of Science ®Google Scholar
• Copeland KW, Boezio AA, Cheung E, et al. Development of novel azabenzofuran TRPA1 antagonists as in vivo tools. Bioorg Med Chem Lett. 2014;24:3464–3468.
   PubMed Web of Science ®Google Scholar
• Rooney L, Vidal A, D’Souza AM, et al. Discovery, optimization, and biological evaluation of 5-(2-(trifluoromethyl)phenyl)indazoles as a novel class of transient receptor potential A1 (TRPA1) antagonists. J Med Chem. 2014;57:5129–5140.
   PubMed Web of Science ®Google Scholar
• Schenkel LB, Oliveri PR, Boezio AA, et al. Optimization of a novel quinazolinone-based series of transient receptor potential A1 (TRPA1) antagonists demonstrating potent in vivo activity. J Med Chem. 2016;59:2794–2809.
   PubMed Web of Science ®Google Scholar
• Pryde DC, Marron BE, West CW, et al. Discovery of a series of Indazole TRPA1 antagonists. ACS Med Chem Lett. 2017;8:666–671.
   PubMed Web of Science ®Google Scholar
• Tseng WC, Pryde DC, Yoger KE, et al. TRPA1 ankyrin repeat six interacts with a small molecule inhibitor chemotype. Proc Natl Acad Sci U S A. 2018;115:12301–12306.
   PubMed Web of Science ®Google Scholar
• Chen H, Volgraf M, Do S, et al. Discovery of a potent (4R,5S)-4-Fluoro-5-methylproline Sulfonamide transient receptor potential Ankyrin 1 Antagonist and its Methylene Phosphate prodrug guided by molecular modeling. J Med Chem. 2018;61:3641–3659.
   PubMed Web of Science ®Google Scholar
• Heber S, Gold-Binder M, Ciotu CI, et al. A human TRPA1-specific pain model. J Neurosci. 2019;39:3845–3855.
   PubMed Web of Science ®Google Scholar
• Mukhopadhyay I, Kulkarni A, Khairatkar-Joshi N. Blocking TRPA1 in respiratory disorders: does it hold a promise? Pharmaceuticals. 2016;9:70–80.
   Web of Science ®Google Scholar
• Birrell MA, Belvisi MG, Grace M, et al. TRPA1 agonists evoke coughing in guinea pig and human volunteers. Am J Respir Crit Care Med. 2009;180:1042–1047.
   PubMed Web of Science ®Google Scholar
• Andrè E, Gatti R, Trevisani M, et al. Transient receptor potential ankyrin receptor 1 is a novel target for pro-tussive agents. Br J Pharmacol. 2009;158:1621–1628.
   PubMed Web of Science ®Google Scholar
• Mukhopadhyay I, Kulkarni A, Aranake S, et al. Transient receptor potential Ankyrin 1 receptor activation in vitro and in vivo by pro-tussive Agents: GRC 17536 as a promising anti-tussive therapeutic. PLoS ONE. 2014;9:e97005.
   PubMed Web of Science ®Google Scholar
• Reese RM, Dourado M, Anderson K, et al. Behavioral characterization of a CRISPR-generated TRPA1 knockout rat in models of pain, itch, and asthma. Sci Rep. 2020;10:1–11.
   PubMed Web of Science ®Google Scholar
• Paulsen CE, Armache JP, Gao Y, et al. Structure of the TRPA1 ion channel suggests regulatory mechanisms. Nature. 2015;525:511–517.
   PubMed Web of Science ®Google Scholar
• Chernov-Rogan T, Gianti E, Liu C, et al. TRPA1 modulation by piperidine carboxamides suggests an evolutionarily conserved binding site and gating mechanism. Proc Natl Acad Sci U S A. 2019;116:26008–26019.
   PubMed Web of Science ®Google Scholar
• Chandrabalan A, McPhillie MJ, Morice AH, et al. N-Cinnamoylanthranilates as human TRPA1 modulators: structure-activity relationships and channel binding sites. Eur J Med Chem. 2019;170:141–156.
   PubMed Web of Science ®Google Scholar
• Suo Y, Wang Z, Zubcevic L, et al. Structural Insights into Electrophile Irritant Sensing by the Human TRPA1 Channel. Neuron. 2020;105:882–894.
   PubMed Web of Science ®Google Scholar
• Wrona IE, Lucas MC. Recent advances in the discovery and development of transient receptor potential Ankyrin 1 (TRPA1) antagonists. Med Chem Rev. 2016;51:117–133.
   Google Scholar
• Skerratt S. Recent progress in the discovery and development of TRPA1 modulators. Prog Med Chem. 2017;56:81–115.
   PubMedGoogle Scholar
• Heber S, Fischer MJM. Non-Analgesic symptomatic or disease-modifying potential of TRPA1. Med Sci. 2019;7:99–110.
   Google Scholar
• Preti D, Szallasi A, Patacchini R. TRP channels as therapeutic targets in airway disorders: a patent review. Expert Opin Ther Pat. 2012;22:663–695. .
   PubMed Web of Science ®Google Scholar
• Preti D, Saponaro G, Szallasi A. Transient receptor potential ankyrin 1 (TRPA1) antagonists. Pharm Pat Anal. 2015;4:75–94. .
   PubMed Web of Science ®Google Scholar
• Algomedix, Inc. TRPA1 modulators. WO2015103060. 2015.
   Google Scholar
• Kim SH, Chung JM. An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the Rat. Pain. 1992;50:355–363.
   PubMed Web of Science ®Google Scholar
• Chaplan SR, Bach FW, Pogrel JW, et al. Quantitative assessment of tactile Allodynia in the Rat paw. J Neurosci Methods. 1994;53:55–63.
   PubMed Web of Science ®Google Scholar
• Almirall SA; New TRPA1 antagonists. WO2015155306. 2015.
   Google Scholar
• Almirall SA New TRPA1 antagonists. WO2017060488. 2017.
   Google Scholar
• Almirall SA. New TRPA1 antagonists. WO2017064068. 2017.
   Google Scholar
• Duke University, The Regents of the University of California. TRPA1 and TRPV4 inhibitors and methods of using the same for organ-specific inflammation and itch. WO2016028325. 2016.
   Google Scholar
• Phan MN, Leddy HA, Votta BJ, et al. Functional characterization of TRPV4 as an osmotically sensitive ion channel in porcine articular chondrocytes. Arthritis Rheum. 2009;60:3028–3037.
   PubMed Web of Science ®Google Scholar
• Duke University. Small molecule dual-inhibitors of TRPV4 and TRPA1 for sanitizing and anesthetizing. WO2017177200. 2017.
   Google Scholar
• Kanju P, Chen Y, Lee W, et al. Small molecule dual-inhibitors of TRPV4 and TRPA1 for attenuation of inflammation and pain. Sci Rep. 2016;6:26894–26905.
   PubMed Web of Science ®Google Scholar
• Ajinomoto Co., Inc. Heterocyclic sulfonamide derivative and medicine comprising same. WO2015115507. 2015.
   Google Scholar
• EA Pharma Co., Ltd. Cyclopropane derivative and drug containing same. WO2017018495. 2017.
   Google Scholar
• EA Pharma Co., Ltd. Heterocyclic sulfonamide derivative and medicine containing same. WO2017135462. 2017.
   Google Scholar
• Eli Lilly and Company. Inhibiting the transient receptor potential A1 ion channel. WO2019152465. 2019.
   Google Scholar
• Del Camino D, Murphy S, Heiry M, et al. TRPA1 contributes to cold hypersensitivity. J Neurosci. 2010;30:15165–15174.
   PubMed Web of Science ®Google Scholar
• Galderma Research & Development. TRPA1 antagonists for use in the treatment of atopic dermatitis. WO2018109155. 2018.
   Google Scholar
• A study of the safety, tolerability, pharmacokinetics and pharmacodynamic effects of single and multiple ascending doses of GDC-0334 and the effect of food on the pharmacokinetics of GDC-0334 in healthy adult participants – ClinicalTrials.gov. [cited 20202 Mar 8]. Available from: https://clinicaltrials.gov/ct2/show/NCT03381144
   Google Scholar
• F. Hoffmann-La Roche AG/Genentech, Inc. Substituted sulfonamide compounds. WO2014049047. 2014.
   Google Scholar
• F. Hoffmann-La Roche AG/Genentech, Inc. Substituted heterocyclic sulfonamide compounds useful as TRPA1 modulators. WO2015052264. 2015.
   Google Scholar
• F. Hoffmann-La Roche AG/Genentech, Inc. 1-(het)arylsulfonyl-(pyrrolidine or piperidine)-2-carboxamide derivatives and their use as TRPA1 antagonists. WO2016128529. 2016.
   Google Scholar
• F. Hoffmann-La Roche AG/Genentech, Inc. Bicyclic proline compounds. WO2018015410. 2018.
   Google Scholar
• F. Hoffmann-La Roche AG/Genentech, Inc. Sulfonylcycloalkyl carboxamide compounds as TRPA1 modulators. WO2018015411. 2018.
   Google Scholar
• F. Hoffmann-La Roche AG/Genentech, Inc. Sulfonyl pyridyl TRP inhibitors. WO2018029288. 2018.
   Google Scholar
• F. Hoffmann-La Roche AG/Genentech, Inc. Oxadiazolones as transient receptor potential channel inhibitors. WO2018096159. 2018.
   Google Scholar
• F. Hoffmann-La Roche AG/Genentech, Inc. Oxadiazole transient receptor potential channel inhibitors. WO2018162607. 2018.
   Google Scholar
• F. Hoffmann-La Roche AG/Genentech, Inc. Oxadiazole transient receptor potential channel inhibitors. WO2019182925. 2019.
   Google Scholar
• A clinical trial to study the effects GRC 17536 in patients with painful diabetic peripheral neuropathy (painful extremities due to peripheral nerve damage in diabetic patients) – ClinicalTrials.gov.  Available from: https://clinicaltrials.gov/ct2/show/NCT01726413 [Last accessed 13 March 2020]
   Google Scholar
• Glenmark Pharmaceuticals S.A. Pharmaceutical composition comprising a TRPA1 antagonist and an analgesic agent. WO2015056094. 2015.
   Google Scholar
• Glenmark Pharmaceuticals S.A. TRPA1 antagonist for the treatment of pain associated to diabetic neuropathic pain. WO2016042501. 2016
   Google Scholar
• Hydra Biosciences. Inhibiting the transient receptor potential A1 ion channel. WO2015164643. 2015.
   Google Scholar
• Hydra Biosciences. Inhibiting the transient receptor potential A1 ion channel. WO2016044792. 2016.
   Google Scholar
• Dubuisson D, Dennis SG. The formalin test: a quantitative study of the analgesic effects of morphine, meperidine, and brain stem stimulation in rats and cats. Pain. 1977;4:161–174.
   PubMed Web of Science ®Google Scholar
• Kao Corporation. Irritation relieving agent. WO2015002095. 2015.
   Google Scholar
• Mandom Corporation. TRPA1 activity inhibitor. WO2018180460. 2018.
   Google Scholar
• Karashima Y, Damann N, Prenen J, et al. Bimodal action of Menthol on the transient receptor potential channel TRPA1. J Neurosci. 2007;27:9874–9884.
   PubMed Web of Science ®Google Scholar
• Xiao B, Dubin AE, Bursulaya B, et al. Identification of transmembrane domain 5 as a critical molecular determinant of Menthol sensitivity in mammalian TRPA1 channels. J Neurosci. 2008;28:9640–9651.
   PubMed Web of Science ®Google Scholar
• Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Effects of ODM-108: in healthy Male volunteers – ClinicalTrials.gov. Available from: https://clinicaltrials.gov/ct2/show/NCT02432664 [Last accessed 13 March 2020]
   Google Scholar
• Orion Corporation. N-prop-2-ynyl carboxamide derivatives and their use as TRPA1 antagonists. WO2014053694. 2014.
   Google Scholar
• Orion Corporation. TRPA1 modulators. WO2015144976. 2015.
   Google Scholar
• Orion Corporation. TRPA1 modulators. WO2015144977. 2015.
   Google Scholar
• Wei H, Hämäläinen MM, Saarnilehto M, et al. Attenuation of mechanical hypersensitivity by an antagonist of the TRPA1 ion channel in diabetic animals. Anesthesiology. 2009;111:147–154.
   PubMed Web of Science ®Google Scholar
• Ryckmans T, Aubdool AA, Bodkin JV, et al. Design and pharmacological evaluation of PF-4840154, a non-electrophilic reference agonist of the TrpA1 channel. Bioorg Med Chem Lett. 2011;21:4857–4859.
   PubMed Web of Science ®Google Scholar
• Pfizer Inc. N-(2-alkyleneimino-3-phenylpropyl)acetamide compounds and their use against pain and pruritus via inhibition of TRPA1 channels. WO2016067143. 2016.
   Google Scholar
• Chen J, Kym PR. TRPA1: the species difference. J Gen Physiol. 2009;133:623–625.
   PubMed Web of Science ®Google Scholar
• Bianchi BR, Zhang X-F, Reillyet RM, et al. Species comparison and pharmacological characterization of human, Monkey, Rat, and Mouse TRPA1 channels. J Pharmacol Exp Ther. 2012;341:360–368.
   PubMed Web of Science ®Google Scholar