ADX-71441
ADX71441
Names
IUPAC name
N -[5-[4-[(4-chloro-3-fluorophenyl)methyl]-6-methoxy-3,5-dioxo-1,2,4-triazin-2-yl]-2-fluorophenyl]acetamide
Identifiers
Key: BQDMEJYNGXEHSW-UHFFFAOYSA-N
InChI=1S/C19H15ClF2N4O4/c1-10(27)23-16-8-12(4-6-14(16)21)26-19(29)25(18(28)17(24-26)30-2)9-11-3-5-13(20)15(22)7-11/h3-8H,9H2,1-2H3,(H,23,27)
CC(=O)NC1=C(C=CC(=C1)N2C(=O)N(C(=O)C(=N2)OC)CC3=CC(=C(C=C3)Cl)F)F
Properties
C 19 H 15 Cl F 2 N 4 O 4
Molar mass
436.80 g·mol−1
Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
Chemical compound
ADX-71441 is a GABAB receptor positive allosteric modulator currently being investigated as a potential treatment for anxiety, epilepsy, pain and other conditions.
Therapeutic potential
Addiction
ADX-71441 has been shown to reduce alcohol consumption .[ 1] This result was observed in both alcohol dependent and non-dependent animals.[ 2] [ 3]
There were also trials about nicotine addiction , which showed positive results: ADX-71441 was able to decrease some withdrawal symptoms of nicotine withdrawal .[ 4]
Anxiety
This compound has also been shown to reduce anxiety in people with PTSD .[ 5]
Pain
Experiments have shown that this compound was able to decrease hypersensitivity to pain in mice, Guinea pigs and rats.[ 5]
Tolerance
ADX-71441 has been shown to have less tolerance and side effects than direct GABAB agonists, such as baclofen .[ 2]
References
^ "Addex Reports ADX71441 Reduces Alcohol Intake in a Preclinical Model of Chronic Alcohol Dependence" . Addex therapeutics . Retrieved 2024-02-03 .
^ a b Augier E, Dulman RS, Damadzic R, Pilling A, Hamilton JP, Heilig M (August 2017). "The GABAB Positive Allosteric Modulator ADX71441 Attenuates Alcohol Self-Administration and Relapse to Alcohol Seeking in Rats" . Neuropsychopharmacology . 42 (9): 1789–1799. doi :10.1038/npp.2017.53 . PMC 5520784 . PMID 28294133 .
^ Colombo G (March 2024). "Positive allosteric modulators of the GABAB receptor: a new class of ligands with therapeutic potential for alcohol use disorder". Alcohol and Alcoholism . 59 (3). Oxford, Oxfordshire. doi :10.1093/alcalc/agae018 . PMID 38566580 .
^ "Addex ADX71441 Positive Results in Preclinical Model of Nicotine Addiction" . Addex therapeutics . Retrieved 2024-02-03 .
^ a b Kalinichev M, Girard F, Haddouk H, Rouillier M, Riguet E, Royer-Urios I, et al. (March 2017). "The drug candidate, ADX71441, is a novel, potent and selective positive allosteric modulator of the GABAB receptor with a potential for treatment of anxiety, pain and spasticity". Neuropharmacology . 114 : 34–47. doi :10.1016/j.neuropharm.2016.11.016 . PMID 27889489 . S2CID 36606154 .
Ionotropic
GABAA Tooltip γ-Aminobutyric acid A receptor
Positive modulators (abridged; see here for a full list): α-EMTBL
Alcohols (e.g., drinking alcohol , 2M2B )
Anabolic steroids
Avermectins (e.g., ivermectin )
Barbiturates (e.g., phenobarbital )
Benzodiazepines (e.g., diazepam )
Bromide compounds (e.g., potassium bromide )
Carbamates (e.g., meprobamate )
Carbamazepine
Chloralose
Chlormezanone
Clomethiazole
Dihydroergolines (e.g., ergoloid (dihydroergotoxine) )
Etazepine
Etifoxine
Fenamates (e.g., mefenamic acid )
Flavonoids (e.g., apigenin , hispidulin )
Fluoxetine
Flupirtine
Imidazoles (e.g., etomidate )
Kava constituents (e.g., kavain )
Lanthanum
Loreclezole
Monastrol
Neuroactive steroids (e.g., allopregnanolone , cholesterol , THDOC )
Niacin
Niacinamide
Nonbenzodiazepines (e.g., β-carbolines (e.g., abecarnil ), cyclopyrrolones (e.g., zopiclone ), imidazopyridines (e.g., zolpidem ), pyrazolopyrimidines (e.g., zaleplon ))
Norfluoxetine
Petrichloral
Phenols (e.g., propofol )
Phenytoin
Piperidinediones (e.g., glutethimide )
Propanidid
Pyrazolopyridines (e.g., etazolate )
Quinazolinones (e.g., methaqualone )
Retigabine (ezogabine)
ROD-188
Skullcap constituents (e.g., baicalin )
Stiripentol
Sulfonylalkanes (e.g., sulfonmethane (sulfonal) )
Topiramate
Valerian constituents (e.g., valerenic acid )
Volatiles /gases (e.g., chloral hydrate , chloroform , diethyl ether , paraldehyde , sevoflurane )
Negative modulators: 1,3M1B
3M2B
11-Ketoprogesterone
17-Phenylandrostenol
α3IA
α5IA (LS-193,268)
β-CCB
β-CCE
β-CCM
β-CCP
β-EMGBL
Anabolic steroids
Amiloride
Anisatin
β-Lactams (e.g., penicillins , cephalosporins , carbapenems )
Basmisanil
Bemegride
Bicyclic phosphates (TBPS , TBPO , IPTBO )
BIDN
Bilobalide
Bupropion
CHEB
Chlorophenylsilatrane
Cicutoxin
Cloflubicyne
Cyclothiazide
DHEA
DHEA-S
Dieldrin
(+)-DMBB
DMCM
DMPC
EBOB
Etbicyphat
FG-7142 (ZK-31906)
Fiproles (e.g., fipronil )
Flavonoids (e.g., amentoflavone , oroxylin A )
Flumazenil
Fluoroquinolones (e.g., ciprofloxacin )
Flurothyl
Furosemide
Golexanolone
Iomazenil (123 I)
IPTBO
Isopregnanolone (sepranolone)
L-655,708
Laudanosine
Lindane
MaxiPost
Morphine
Morphine-3-glucuronide
MRK-016
Naloxone
Naltrexone
Nicardipine
Nonsteroidal antiandrogens (e.g., apalutamide , bicalutamide , enzalutamide , flutamide , nilutamide )
Oenanthotoxin
Pentylenetetrazol (pentetrazol)
Phenylsilatrane
Picrotoxin (i.e., picrotin , picrotoxinin and dihydropicrotoxinin )
Pregnenolone sulfate
Propybicyphat
PWZ-029
Radequinil
Ro 15-4513
Ro 19-4603
RO4882224
RO4938581
Sarmazenil
SCS
Suritozole
TB-21007
TBOB
TBPS
TCS-1105
Terbequinil
TETS
Thujone
U-93631
Zinc
ZK-93426
GABAA -ρ Tooltip γ-Aminobutyric acid A-rho receptor
Metabotropic
GABAB Tooltip γ-Aminobutyric acid B receptor