From Wikipedia, the free encyclopedia
VU-0238429
1-(4-methoxybenzyl)-5-(trifluoromethoxy)indole-2,3-dione
CAS Number PubChem CID ChemSpider UNII ChEMBL CompTox Dashboard (EPA ) Formula C 17 H 12 F 3 N O 4 Molar mass 351.281 g·mol−1 3D model (JSmol )
c2cc(OC)ccc2CN(C(=O)C1=O)c3ccc(cc13)OC(F)(F)F
COc1ccc(cc1)CN2c3ccc(cc3C(=O)C2=O)OC(F)(F)F
InChI=1S/C17H12F3NO4/c1-24-11-4-2-10(3-5-11)9-21-14-7-6-12(25-17(18,19)20)8-13(14)15(22)16(21)23/h2-8H,9H2,1H3
Y Key:CKLGZXFOLMHCMC-UHFFFAOYSA-N
Y
VU-0238429 is a drug which acts as a selective positive allosteric modulator for the muscarinic acetylcholine receptor M5 . It was the first selective ligand developed for the M5 subtype,[1] and is structurally derived from older M1 -selective positive allosteric modulators such as .[2] [3] Replacing the O -methyl- by a phenyl group further improves the receptor subtype selectivity.[4]
References [ ]
^ Bridges TM, Marlo JE, Niswender CM, et al. (June 2009). "Discovery of the first highly M5-preferring muscarinic acetylcholine receptor ligand, an M5 positive allosteric modulator derived from a series of 5-trifluoromethoxy N-benzyl isatins" . Journal of Medicinal Chemistry . 52 (11): 3445–8. doi :10.1021/jm900286j . PMC 3875304 . PMID 19438238 .
^ Conn PJ, Jones CK, Lindsley CW (March 2009). "Subtype-selective allosteric modulators of muscarinic receptors for the treatment of CNS disorders" . Trends in Pharmacological Sciences . 30 (3): 148–55. doi :10.1016/j.tips.2008.12.002 . PMC 2907736 . PMID 19201489 .
^ Bridges, T. M.; Kennedy, J. P.; Hopkins, C. R.; Conn, P. J.; Lindsley, C. W. (2010). "Heterobiaryl and heterobiaryl ether derived M5 positive allosteric modulators" . Bioorganic & Medicinal Chemistry Letters . 20 (19): 5617–22. doi :10.1016/j.bmcl.2010.08.042 . PMC 3179183 . PMID 20801651 .
^ Bridges, Thomas M.; Kennedy, J. Phillip; Noetzel, Meredith J.; Breininger, Micah L.; Gentry, Patrick R.; Conn, P. Jeffrey; Lindsley, Craig W. (15 March 2010). "Chemical Lead Optimization of a pan Gq mAChR M1, M3, M5 Positive Allosteric Modulator (PAM) Lead. Part II. Development of potent and highly selective M1 PAM" . Bioorganic & Medicinal Chemistry Letters . 20 (6): 1972–1975. doi :10.1016/j.bmcl.2010.01.109 . PMC 2834874 . PMID 20156687 .
mAChRs
Agonists Antagonists
3-Quinuclidinyl benzilate
4-DAMP
Aclidinium bromide (+formoterol )
Abediterol
AF-DX 384
Ambutonium bromide
Anisodamine
Anisodine
Antihistamines (first-generation) (e.g., brompheniramine , buclizine , captodiame , chlorphenamine (chlorpheniramine) , cinnarizine , clemastine , cyproheptadine , dimenhydrinate , dimetindene , diphenhydramine , doxylamine , meclizine , mequitazine , perlapine , phenindamine , pheniramine , phenyltoloxamine , promethazine , propiomazine , triprolidine )
Atropine
Atropine methonitrate
Atypical antipsychotics (e.g., clozapine , fluperlapine , olanzapine (+fluoxetine ), , quetiapine , tenilapine , zotepine )
Benactyzine
Benzatropine (benztropine)
Benzilone
Benzilylcholine mustard
Benzydamine
Biperiden
Bornaprine
Camylofin
CAR-226,086
CAR-301,060
CAR-302,196
CAR-302,282
CAR-302,668
Caramiphen
Cimetropium bromide
Clidinium bromide
Cloperastine
CS-27349
Cyclobenzaprine
Cyclopentolate
Darifenacin
Desfesoterodine
Dexetimide
Dicycloverine (dicyclomine)
Dihexyverine
Difemerine
Diphemanil metilsulfate
Ditran
Drofenine
EA-3167
EA-3443
EA-3580
EA-3834
Emepronium bromide
Etanautine
Etybenzatropine (ethybenztropine)
Fenpiverinium
Fentonium bromide
Fesoterodine
Flavoxate
Glycopyrronium bromide (+beclometasone/formoterol , +indacaterol )
Hexocyclium
Himbacine
Homatropine
Imidafenacin
Ipratropium bromide (+salbutamol )
Isopropamide
Hyoscyamine
Mamba toxin 3
Mamba toxin 7
Mazaticol
Mebeverine
Meladrazine
Mepenzolate
Methantheline
Methoctramine
Methylatropine
Methylhomatropine
Methylscopolamine
Metixene
Muscarinic toxin 7
N-Ethyl-3-piperidyl benzilate
N-Methyl-3-piperidyl benzilate
Nefopam
Octatropine methylbromide (anisotropine methylbromide)
Orphenadrine
Otenzepad (AF-DX 116)
Otilonium bromide
Oxapium iodide
Oxitropium bromide
Oxybutynin
Oxyphencyclimine
Oxyphenonium bromide
PD-102,807
PD-0298029
Penthienate
Pethidine
Phenglutarimide
Phenyltoloxamine
Pipenzolate bromide
Piperidolate
Pirenzepine
Piroheptine
Pizotifen
Poldine
Pridinol
Prifinium bromide
Procyclidine
Profenamine (ethopropazine)
Propantheline bromide
Propiverine
Quinidine
3-Quinuclidinyl thiochromane-4-carboxylate
Revefenacin
Rociverine
Scopolamine (hyoscine)
Scopolamine butylbromide (hyoscine butylbromide)
Sofpironium bromide
Solifenacin
SSRIs (e.g., femoxetine , paroxetine )
Telenzepine
Terodiline
Tetracyclic antidepressants (e.g., amoxapine , maprotiline , mianserin , mirtazapine )
Tiemonium iodide
Timepidium bromide
Tiotropium bromide
Tofenacin
Tolterodine
Tricyclic antidepressants (e.g., amitriptyline (+perphenazine ), amitriptylinoxide , butriptyline , cidoxepin , clomipramine , desipramine , , dibenzepin , dosulepin (dothiepin) , doxepin , imipramine , lofepramine , nitroxazepine , northiaden (desmethyldosulepin) , nortriptyline , protriptyline , quinupramine , trimipramine )
Tridihexethyl
Trihexyphenidyl
Trimebutine
Tropatepine
Tropicamide
Trospium chloride
Typical antipsychotics (e.g., chlorpromazine , chlorprothixene , cyamemazine (cyamepromazine) , loxapine , mesoridazine , thioridazine )
Umeclidinium bromide (+vilanterol )
WIN-2299
Xanomeline
Precursors (and prodrugs ) See also: Receptor/signaling modulators • Nicotinic acetylcholine receptor modulators • Acetylcholine metabolism/transport modulators
Categories :
Receptor modulators Trifluoromethoxy compounds Indoles Hidden categories:
Chemical pages without DrugBank identifier Articles without KEGG source Multiple chemicals in Infobox drug Multiple chemicals in an infobox that need indexing Drugs missing an ATC code Drugs with no legal status