HC-030031

Last updated
HC-030031
HC-030031.svg
Identifiers
  • 2-(1,3-dimethyl-2,6-dioxopurin-7-yl)-N-(4-propan-2-ylphenyl)acetamide
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.159.785 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C18H21N5O3
Molar mass 355.398 g·mol−1
3D model (JSmol)
  • CC(C)C1=CC=C(C=C1)NC(=O)CN2C=NC3=C2C(=O)N(C(=O)N3C)C
  • InChI=1S/C18H21N5O3/c1-11(2)12-5-7-13(8-6-12)20-14(24)9-23-10-19-16-15(23)17(25)22(4)18(26)21(16)3/h5-8,10-11H,9H2,1-4H3,(H,20,24)
  • Key:HEQDZPHDVAOBLN-UHFFFAOYSA-N

HC-030031 is a drug which acts as a potent and selective antagonist for the TRPA1 receptor, and has analgesic and antiinflammatory effects. [1] [2] [3] [4]

Related Research Articles

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Hyperalgesia is an abnormally increased sensitivity to pain, which may be caused by damage to nociceptors or peripheral nerves and can cause hypersensitivity to stimulus. Prostaglandins E and F are largely responsible for sensitizing the nociceptors. Temporary increased sensitivity to pain also occurs as part of sickness behavior, the evolved response to infection.

Neurogenic inflammation is inflammation arising from the local release by afferent neurons of inflammatory mediators such as Substance P, Calcitonin Gene-Related Peptide (CGRP), neurokinin A (NKA), and endothelin-3 (ET-3). In such neurons, release of these pro-inflammatory mediators is thought to be triggered by the activation of ion channels that are the principal detectors of noxious environmental stimuli. In particular, the heat/capsaicin receptor TRPV1 and the irritant/wasabi receptor TRPA1. TRPA1 channels stimulated by lipopolysaccharide (LPS) may also cause acute neurogenic inflammation. Once released, these neuropeptides induce the release of histamine from adjacent mast cells. In turn, histamine evokes the release of substance P and calcitonin gene-related peptide; thus, a bidirectional link between histamine and neuropeptides in neurogenic inflammation is established.

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<span class="mw-page-title-main">TRPV1</span> Human protein for regulating body temperature

The transient receptor potential cation channel subfamily V member 1 (TRPV1), also known as the capsaicin receptor and the vanilloid receptor 1, is a protein that, in humans, is encoded by the TRPV1 gene. It was the first isolated member of the transient receptor potential vanilloid receptor proteins that in turn are a sub-family of the transient receptor potential protein group. This protein is a member of the TRPV group of transient receptor potential family of ion channels. Fatty acid metabolites with affinity for this receptor are produced by cyanobacteria, which diverged from eukaryotes at least 2000 million years ago (MYA). The function of TRPV1 is detection and regulation of body temperature. In addition, TRPV1 provides a sensation of scalding heat and pain (nociception). In primary afferent sensory neurons, it cooperates with TRPA1 to mediate the detection of noxious environmental stimuli.

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Transient receptor potential cation channel, subfamily A, member 1, also known as transient receptor potential ankyrin 1, TRPA1, or The Wasabi Receptor, is a protein that in humans is encoded by the TRPA1 gene.

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<span class="mw-page-title-main">PF-4840154</span> Pyrimidine derivative chemical

PF-4840154 is a pyrimidine derivative discovered by Pfizer at its Sandwich, Kent research center. The compound is a potent, selective activator of both the human (EC50 = 23 nM) and rat (EC50 = 97 nM) TRPA1 channels. This compound elicits nociception in a mouse model through TRPA1 activation. PF-4840154 is used as a reference agonist of the TRPA1 channel for in-vitro high-throughput screening purposes, and is superior to allyl isothiocyanate for this use. The TRPA1 channel is considered an attractive pain target based on the fact that TRPA1 knockout mice showed near complete attenuation of pain behaviors in some pre-clinical development models.

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<span class="mw-page-title-main">A-967079</span> Chemical compound

A-967079 is a drug which acts as a potent and selective antagonist for the TRPA1 receptor. It has analgesic and antiinflammatory effects and is used in scientific research, but has not been developed for medical use.

<span class="mw-page-title-main">AMG-9810</span> Chemical compound

AMG-9810 is a drug which acts as a potent and selective antagonist for the TRPV1 receptor. It has analgesic and antiinflammatory effects and is used in scientific research, but has not been developed for medical use. It has high antagonist potency and good bioavailability and pharmacokinetics, and so has been used to study the role of TRPV1 in areas other than pain perception, such as its roles in the brain.

<span class="mw-page-title-main">HC-067047</span> Chemical compound

HC-067047 is a drug which acts as a potent and selective antagonist for the TRPV4 receptor. It has been used to investigate the role of TRPV4 receptors in a number of areas, such as regulation of blood pressure, bladder function and some forms of pain, as well as neurological functions.

<span class="mw-page-title-main">AMG-517</span> Chemical compound

AMG-517 is a drug which acts as a potent and selective blocker of the TRPV1 ion channel. It was developed as a potential treatment for chronic pain, but while it was an effective analgesic in animal studies it was dropped from human clinical trials at Phase I due to producing hyperthermia as a side effect, as well as poor water solubility. It is still used in scientific research into the function of the TRPV1 channel and its role in pain and inflammation, and has been used as a template for the design of several newer analogues which have improved properties.

References

  1. ↑ Eid SR, Crown ED, Moore EL, Liang HA, Choong KC, Dima S, et al. (October 2008). "HC-030031, a TRPA1 selective antagonist, attenuates inflammatory- and neuropathy-induced mechanical hypersensitivity". Molecular Pain. 4: 1744-8069–4-48. doi: 10.1186/1744-8069-4-48 . PMC   2584039 . PMID   18954467.
  2. ↑ Pereira LM, Lima-Júnior RC, Bem AX, Teixeira CG, Grassi LS, Medeiros RP, et al. (February 2013). "Blockade of TRPA1 with HC-030031 attenuates visceral nociception by a mechanism independent of inflammatory resident cells, nitric oxide and the opioid system". European Journal of Pain. 17 (2): 223–33. doi:10.1002/j.1532-2149.2012.00177.x. PMID   22689151. S2CID   9421113.
  3. ↑ Koivisto A, Chapman H, Jalava N, Korjamo T, Saarnilehto M, Lindstedt K, Pertovaara A (January 2014). "TRPA1: a transducer and amplifier of pain and inflammation". Basic & Clinical Pharmacology & Toxicology. 114 (1): 50–5. doi: 10.1111/bcpt.12138 . PMID   24102997.
  4. ↑ Achanta S, Chintagari NR, Brackmann M, Balakrishna S, Jordt SE (September 2018). "TRPA1 and CGRP antagonists counteract vesicant-induced skin injury and inflammation". Toxicology Letters. 293: 140–148. doi:10.1016/j.toxlet.2018.03.007. PMC   5975083 . PMID   29535050.


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