VU-0238429

VU-0238429
Identifiers
	IUPAC name 1-(4-methoxybenzyl)-5-(trifluoromethoxy)indole-2,3-dione;
CAS Number	1160247-92-6 ;
PubChem CID	42633508;
ChemSpider	24606034 ;
UNII	ZH1ZWF5Q3P;
ChEMBL	ChEMBL466253 ;
CompTox Dashboard (EPA)	DTXSID40655290 ;
Chemical and physical data
Formula	C17H12F3NO4
Molar mass	351.281 g·mol−1
3D model (JSmol)	Interactive image; Interactive image;
	SMILES 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 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 ; Key:CKLGZXFOLMHCMC-UHFFFAOYSA-N ;
(verify)

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

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.

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[pmid19438238-1] 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.

[pmid19201489-2] 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.

[3] 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.

[4] 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.