AM-0902

Last updated
AM-0902
AM-0902 Structure.svg
Identifiers
  • 1-({3-[2-(4-chlorophenyl)ethyl]-1,2,4-oxadiazol-5-yl}methyl)-7-methylpurin-6-one
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
Chemical and physical data
Formula C17H15ClN6O2
Molar mass 370.80 g·mol−1
3D model (JSmol)
  • CN1C=NC2=C1C(=O)N(C=N2)CC3=NC(=NO3)CCC4=CC=C(C=C4)Cl
  • InChI=1S/C17H15ClN6O2/c1-23-9-19-16-15(23)17(25)24(10-20-16)8-14-21-13(22-26-14)7-4-11-2-5-12(18)6-3-11/h2-3,5-6,9-10H,4,7-8H2,1H3
  • Key:AWJBWNUUODWOKQ-UHFFFAOYSA-N

AM-0902 is a drug which acts as a potent and selective antagonist for the TRPA1 receptor, and has analgesic and antiinflammatory effects. [1] [2]

Related Research Articles

Transient receptor potential channels are a group of ion channels located mostly on the plasma membrane of numerous animal cell types. Most of these are grouped into two broad groups: Group 1 includes TRPC, TRPV, TRPVL, TRPM, TRPS, TRPN, and TRPA. Group 2 consists of TRPP and TRPML. Other less-well categorized TRP channels exist, including yeast channels and a number of Group 1 and Group 2 channels present in non-animals. Many of these channels mediate a variety of sensations such as pain, temperature, different kinds of taste, pressure, and vision. In the body, some TRP channels are thought to behave like microscopic thermometers and used in animals to sense hot or cold. Some TRP channels are activated by molecules found in spices like garlic (allicin), chili pepper (capsaicin), wasabi ; others are activated by menthol, camphor, peppermint, and cooling agents; yet others are activated by molecules found in cannabis or stevia. Some act as sensors of osmotic pressure, volume, stretch, and vibration. Most of the channels are activated or inhibited by signaling lipids and contribute to a family of lipid-gated ion channels.

<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.

<span class="mw-page-title-main">TRPV</span> Subgroup of TRP cation channels named after the vanilloid receptor

TRPV is a family of transient receptor potential cation channels in animals. All TRPVs are highly calcium selective.

<span class="mw-page-title-main">Cannabigerol</span> Minor cannabinoid

Cannabigerol (CBG) is a non-psychoactive cannabinoid and minor constituent of cannabis. It is one of more than 120 identified cannabinoids found in the plant genus Cannabis. The compound is the decarboxylated form of cannabigerolic acid (CBGA), the parent molecule from which other cannabinoids are biosynthesized.

<span class="mw-page-title-main">TRPA (ion channel)</span> Family of transport proteins

TRPA is a family of transient receptor potential ion channels. The TRPA family is made up of 7 subfamilies: TRPA1, TRPA- or TRPA1-like, TRPA5, painless, pyrexia, waterwitch, and HsTRPA. TRPA1 is the only subfamily widely expressed across animals, while the other subfamilies are largely absent in deuterostomes.

<span class="mw-page-title-main">TRPA1</span> Protein and coding gene in humans

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.

<span class="mw-page-title-main">TRPV4</span> Protein-coding gene in humans

Transient receptor potential cation channel subfamily V member 4 is an ion channel protein that in humans is encoded by the TRPV4 gene.

<span class="mw-page-title-main">5'-Guanidinonaltrindole</span> Chemical compound

5'-Guanidinonaltrindole (5'-GNTI) is an opioid antagonist used in scientific research which is highly selective for the κ opioid receptor. It is 5x more potent and 500 times more selective than the commonly used κ-opioid antagonist norbinaltorphimine. It has a slow onset and long duration of action, and produces antidepressant effects in animal studies. It also increases allodynia by interfering with the action of the κ-opioid peptide dynorphin.

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

Midafotel is a potent, competitive antagonist at the NMDA receptor. It was originally designed as a potential therapy for excitotoxicity, epilepsy or neuropathic pain. It looked very promising in in vitro trials proving to be a potent competitive antagonist at the NMDA without affecting other receptors. Research continued through to in vivo cat studies where it proved to limit damage after occluding the middle cerebral artery, leading to ischaemia. It also blocked photosensitive epilepsies in baboons.

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

Metribolone is a synthetic and orally active anabolic–androgenic steroid (AAS) and a 17α-alkylated nandrolone (19-nortestosterone) derivative which was never marketed for medical use but has been widely used in scientific research as a hot ligand in androgen receptor (AR) ligand binding assays (LBAs) and as a photoaffinity label for the AR. More precisely, metribolone is the 17α-methylated derivative of trenbolone. It was investigated briefly for the treatment of advanced breast cancer in women in the late 1960s and early 1970s, but was found to produce signs of severe hepatotoxicity at very low dosages, and its development was subsequently discontinued.

Relief from chronic pain remains a recognized unmet medical need. Consequently, the search for new analgesic agents is being intensively studied by the pharmaceutical industry. The TRPV1 receptor is a ligand gated ion channel that has been implicated in mediation of many types of pain and therefore studied most extensively. The first competitive antagonist, capsazepine, was first described in 1990; since then, several TRPV1 antagonists have entered clinical trials as analgesic agents. Should these new chemical entities relieve symptoms of chronic pain, then this class of compounds may offer one of the first novel mechanisms for the treatment of pain in many years.

Susan Diana Brain is a professor of pharmacology at the School of Cardiovascular Medicine and Sciences at King's College London where she has worked since 1989.

<span class="mw-page-title-main">GRC-6211</span> Chemical compound

GRC-6211 is a drug developed by Glenmark Pharmaceuticals which acts as a potent and selective antagonist for the TRPV1 receptor. It has analgesic and antiinflammatory effects and reached Phase IIb human trials, but was ultimately discontinued from development as a medicine, though it continues to have applications in scientific research.

<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">ASP-7663</span> Chemical compound

ASP-7663 is a chemical compound which acts as a potent, selective activator of the TRPA1 channel. It has protective effects on cardiac tissue, and is used for research into the function of the TRPA1 receptor.

<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">JT-010</span> Chemical compound

JT-010 is a chemical compound which acts as a potent, selective activator of the TRPA1 channel, and has been used to study the role of this receptor in the perception of pain, as well as other actions such as promoting repair of dental tissue after damage.

<span class="mw-page-title-main">HC-030031</span> Chemical compound

HC-030031 is a drug which acts as a potent and selective antagonist for the TRPA1 receptor, and has analgesic and antiinflammatory effects.

<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. Schenkel LB, Olivieri PR, Boezio AA, Deak HL, Emkey R, Graceffa RF, et al. (March 2016). "Optimization of a Novel Quinazolinone-Based Series of Transient Receptor Potential A1 (TRPA1) Antagonists Demonstrating Potent in Vivo Activity". Journal of Medicinal Chemistry. 59 (6): 2794–809. doi:10.1021/acs.jmedchem.6b00039. PMID   26942860.
  2. Huang Y, Chen SR, Chen H, Pan HL (May 2019). "Endogenous transient receptor potential ankyrin 1 and vanilloid 1 activity potentiates glutamatergic input to spinal lamina I neurons in inflammatory pain". Journal of Neurochemistry. 149 (3): 381–398. doi:10.1111/jnc.14677. PMC   6483867 . PMID   30716174.