AMG-9810

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H23NO3
Molecular Weight	337.4122
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)(C)C1=CC=C(C=C1)\C=C\C(=O)NC2=CC=C3OCCOC3=C2

InChI

InChIKey=GZTFUVZVLYUPRG-IZZDOVSWSA-N

InChI=1S/C21H23NO3/c1-21(2,3)16-7-4-15(5-8-16)6-11-20(23)22-17-9-10-18-19(14-17)25-13-12-24-18/h4-11,14H,12-13H2,1-3H3,(H,22,23)/b11-6+

HIDE SMILES / InChI

Molecular Formula	C21H23NO3
Molecular Weight	337.4122
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15615864 | http://digitalcommons.library.tmc.edu/cgi/viewcontent.cgi?article=1390&context=utgsbs_dissertations

AMG-9810, is a TRPV1 (vanilloid receptor 1) antagonist which blocks all known modes of TRPV1 activation, including heat, proton, and endogenous ligand activation. TRPV1 is a membrane-bound cation channel in peripheral sensory neurons. Inhibition of this receptor has been noted to cause anti-inflammatory effects. In murine dorsal root ganglion primary neuron studies, this compound has been shown to block capsaicin-evoked depolarization and calcitonin gene-related peptide release. Screening of AMG 9810 against a panel of G protein-coupled receptors and ion channels indicated selectivity toward TRPV1. In vivo, AMG-9810 is effective at preventing capsaicin-induced eye wiping in a dose-dependent manner, and it reverses thermal and mechanical hyperalgesia in a model of inflammatory pain induced by intraplantar injection of complete Freund's adjuvant. AMG-9810 is the first cinnamide TRPV1 antagonist reported to block capsaicin-induced eye wiping behavior and reverse hyperalgesia in an animal model of inflammatory pain.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Vanilloid receptor 53 Target ID: CHEMBL4794 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17585749 \| https://www.ncbi.nlm.nih.gov/pubmed/15615864	Antagonist 2778		24.5 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 614 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15615864 http://adisinsight.springer.com/drugs/800020509 https://www.ncbi.nlm.nih.gov/pubmed/17603899	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
AMG 9810 [(E)-3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo[b][1,4] dioxin-6-yl)acrylamide], a novel vanilloid receptor 1 (TRPV1) antagonist with antihyperalgesic properties.	2005 Apr	15615864
Thermal sensitivity of isolated vagal pulmonary sensory neurons: role of transient receptor potential vanilloid receptors.	2006 Sep	16513770
Novel vanilloid receptor-1 antagonists: 1. Conformationally restricted analogues of trans-cinnamides.	2007 Jul 26	17585749
TRPV1-antagonist AMG9810 promotes mouse skin tumorigenesis through EGFR/Akt signaling.	2011 May	21349818

Patents

Sample Use Guides

In Vivo Use Guide

Rats: a dose-dependent decrease of capsaicin-induced eye wipes was observed at 15 min with all AMG-9810 doses tested (3, 10, and 30 mg/kg intraperitoneal). In animals treated with AMG 9810, 30 min before capsaicin treatment, statistically significant reductions of the number of eye wipes were observed with 10 and 30 mg/kg AMG-9810.

Route of Administration: Intraperitoneal

In Vitro Use Guide

AMG-9810 potently and concentration-dependently inhibited capsaicin- and proton-induced 45Ca2+ uptake into CHO cells expressing r/h chimera with IC50 values of 19.1 +/- 7.9 and 90.3 +/- 53.1 nM, respectively. IC50 values for blocking capsaicin activation of at rat and human TRPV1 were 85.6 +/-39.4 and 24.5 +/- 15.7 nM, respectively. IC50 values for blocking proton activation of rat and human TRPV1 were 294 +/- 192 and 92.7 +/- 72.8 nM, respectively.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 08:36:55 GMT 2023` Edited by `admin` on `Sat Dec 16 08:36:55 GMT 2023`
Record UNII	182HIJ2D7F
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AMG-9810

Common Name

English

2-PROPENAMIDE, N-(2,3-DIHYDRO-1,4-BENZODIOXIN-6-YL)-3-(4-(1,1-DIMETHYLETHYL)PHENYL)-, (2E)-

Systematic Name

English

(2E)-N-(2H,3H-BENZO(3,4-E)-1,4-DIOXAN-6-YL)-3-(4-(TERT-BUTYL)PHENYL)PROP-2-ENAMIDE

Systematic Name

English

Code System Code Type Description

EPA CompTox

DTXSID40202960