From Wikipedia, the free encyclopedia
Chemical compound
VU-0238429
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1-(4-methoxybenzyl)-5-(trifluoromethoxy)indole-2,3-dione
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PubChem
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ChEMBL | |
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CompTox Dashboard (
EPA) | |
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Formula | C17H12F3NO4 |
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Molar mass | 351.281 g·mol−1 |
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3D model (
JSmol) | |
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c2cc(OC)ccc2CN(C(=O)C1=O)c3ccc(cc13)OC(F)(F)F
COc1ccc(cc1)CN2c3ccc(cc3C(=O)C2=O)OC(F)(F)F
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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 YKey:CKLGZXFOLMHCMC-UHFFFAOYSA-N Y
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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
VU-0119498.
[2]
[3] Replacing the
O-methyl- by a
phenyl group further improves the receptor subtype selectivity.
[4]
References
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^ Bridges TM, Marlo JE, Niswender CM, Jones CK, Jadhav SB, Gentry PR, 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): 3445–3448.
doi:
10.1021/jm900286j.
PMC
3875304.
PMID
19438238.
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^ 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): 148–155.
doi:
10.1016/j.tips.2008.12.002.
PMC
2907736.
PMID
19201489.
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^ Bridges TM, Kennedy JP, Hopkins CR, Conn PJ, Lindsley CW (October 2010).
"Heterobiaryl and heterobiaryl ether derived M5 positive allosteric modulators". Bioorganic & Medicinal Chemistry Letters. 20 (19): 5617–5622.
doi:
10.1016/j.bmcl.2010.08.042.
PMC
3179183.
PMID
20801651.
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^ Bridges TM, Phillip Kennedy J, Noetzel MJ, Breininger ML, Gentry PR, Conn PJ, Lindsley CW (March 2010).
"Chemical lead optimization of a pan Gq mAChR M1, M3, M5 positive allosteric modulator (PAM) lead. Part II: development of a 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.
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mAChRsTooltip Muscarinic acetylcholine receptors |
Agonists | |
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Antagonists |
-
3-Quinuclidinyl benzilate
-
4-DAMP
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Aclidinium bromide (
+formoterol)
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Abediterol
-
AF-DX 250
-
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)
-
AQ-RA 741
-
Atropine
-
Atropine methonitrate
-
Atypical antipsychotics (e.g.,
clozapine,
fluperlapine,
olanzapine (
+fluoxetine),
rilapine,
quetiapine,
tenilapine,
zotepine)
-
Benactyzine
-
Benzatropine (benztropine)
-
Benzilone
-
Benzilylcholine mustard
-
Benzydamine
-
BIBN 99
-
Biperiden
-
Bornaprine
-
Camylofin
-
CAR-226,086
-
CAR-301,060
-
CAR-302,196
-
CAR-302,282
-
CAR-302,368
-
CAR-302,537
-
CAR-302,668
-
Caramiphen
-
Cimetropium bromide
-
Clidinium bromide
-
Cloperastine
-
CS-27349
-
Cyclobenzaprine
-
Cyclopentolate
-
Darifenacin
-
DAU-5884
-
Desfesoterodine
-
Dexetimide
-
DIBD
-
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,
+neostigmine)
-
Hexahydrodifenidol
-
Hexahydrosiladifenidol
-
Hexbutinol
-
Hexocyclium
-
Himbacine
-
HL-031,120
-
Homatropine
-
Imidafenacin
-
Ipratropium bromide (
+salbutamol)
-
Isopropamide
-
J-104,129
-
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
-
PBID
-
PD-102,807
-
PD-0298029
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Penthienate
-
Pethidine
-
pFHHSiD
-
Phenglutarimide
-
Phenyltoloxamine
-
Pipenzolate bromide
-
Piperidolate
-
Pirenzepine
-
Piroheptine
-
Pizotifen
-
Poldine
-
Pridinol
-
Prifinium bromide
-
Procyclidine
-
Profenamine (ethopropazine)
-
Propantheline bromide
-
Propiverine
-
Quinidine
-
3-Quinuclidinyl thiochromane-4-carboxylate
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Revefenacin
-
Rociverine
-
RU-47,213
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SCH-57,790
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SCH-72,788
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SCH-217,443
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Scopolamine (hyoscine)
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Scopolamine butylbromide (hyoscine butylbromide)
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Silahexacyclium
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Sofpironium bromide
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Solifenacin
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SSRIsTooltip Selective serotonin reuptake inhibitors (e.g.,
femoxetine,
paroxetine)
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Telenzepine
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Terodiline
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Tetracyclic antidepressants (e.g.,
amoxapine,
maprotiline,
mianserin,
mirtazapine)
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Tiemonium iodide
-
Timepidium bromide
-
Tiotropium bromide
-
Tiquizium bromide
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Tofenacin
-
Tolterodine
-
Tricyclic antidepressants (e.g.,
amitriptyline (
+perphenazine),
amitriptylinoxide,
butriptyline,
cidoxepin,
clomipramine,
desipramine,
desmethyldesipramine,
dibenzepin,
dosulepin (dothiepin),
doxepin,
imipramine,
lofepramine,
nitroxazepine,
northiaden (desmethyldosulepin),
nortriptyline,
protriptyline,
quinupramine,
trimipramine)
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Tridihexethyl
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Trihexyphenidyl
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Trimebutine
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Tripitamine (tripitramine)
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Tropacine
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Tropatepine
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Tropicamide
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Trospium chloride
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Typical antipsychotics (e.g.,
chlorpromazine,
chlorprothixene,
cyamemazine (cyamepromazine),
loxapine,
mesoridazine,
thioridazine)
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Umeclidinium bromide (
+vilanterol)
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WIN-2299
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Xanomeline
-
Zamifenacin
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Precursors (and
prodrugs) | |
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