MK-8189

MK-8189
Legal status
Legal status	Investigational;
Identifiers
	IUPAC name 2-Methyl-6-[[(1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl]methoxy]-N-[(5-methyl-1,3,4-thiadiazol-2-yl)methyl]pyrimidin-4-amine;
CAS Number	1424371-93-6;
PubChem CID	71271414;
ChemSpider	128922007;
Chemical and physical data
Formula	C19H22N6OS
Molar mass	382.49 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1=CN=C(C=C1)[C@H]2C[C@@H]2COC3=NC(=NC(=C3)NCC4=NN=C(S4)C)C;
	InChI InChI=1S/C19H22N6OS/c1-11-4-5-16(20-8-11)15-6-14(15)10-26-18-7-17(22-12(2)23-18)21-9-19-25-24-13(3)27-19/h4-5,7-8,14-15H,6,9-10H2,1-3H3,(H,21,22,23)/t14-,15+/m1/s1; Key:WQKPZDLZRFTMTI-CABCVRRESA-N;

MK-8189 is a selective phosphodiesterase 10A inhibitor being developed for schizophrenia. It is developed by Merck in collaboration with Royalty Pharma.^[1]^[2]^[3]^[4]

References

^ Mukai, Yuki; Lupinacci, Robert; Marder, Stephen; Mackle, Mary; Snow-Adami, Linda; Voss, Tiffini; Smith, Sean; Egan, Michael (May 2022). "P534. Initial Assessment of the Clinical Profile of the PDE10A Inhibitor MK-8189 in Patients With an Acute Episode of Schizophrenia". Biological Psychiatry. 91 (9): S305. doi:10.1016/j.biopsych.2022.02.771. S2CID 248410630.
^ Smith, Sean; Uslaner, Jason; Kandebo, Monika; Hostetler, Eric; Raheem, Izzat; Layton, Mark; Gantert, Liza; Riffel, Kerry; Cox, Christopher; Khalilieh, Sauzanne; De Lepeleire, Inge; Bormans, Guy; Depré, Marleen; de Hoon, Jan; Van Laere, Koen (May 2022). "P546. Preclinical Characterization and Phase 1 Evaluation of the Tolerability, Pharmacokinetics, and Enzyme Occupancy of MK-8189, a Novel PDE10A Inhibitor". Biological Psychiatry. 91 (9): S309–S310. doi:10.1016/j.biopsych.2022.02.783. S2CID 248410556.
^ Layton, Mark E.; Kern, Jeffrey C.; Hartingh, Timothy J.; Shipe, William D.; Raheem, Izzat; Kandebo, Monika; Hayes, Robert P.; Huszar, Sarah; Eddins, Donnie; Ma, Bennett; Fuerst, Joy; Wollenberg, Gordon K.; Li, Jing; Fritzen, Jeff; McGaughey, Georgia B.; Uslaner, Jason M.; Smith, Sean M.; Coleman, Paul J.; Cox, Christopher D. (26 January 2023). "Discovery of MK-8189, a Highly Potent and Selective PDE10A Inhibitor for the Treatment of Schizophrenia". Journal of Medicinal Chemistry. 66 (2): 1157–1171. doi:10.1021/acs.jmedchem.2c01521. PMC 9884086. PMID 36624931. S2CID 255567942.
^ "MK-8189: A Potent and Selective PDE10A Inhibitor for the Treatment of Schizophrenia". Synfacts. 19 (4): 0410. April 2023. doi:10.1055/s-0042-1752651. S2CID 257614478.

[1] Mukai, Yuki; Lupinacci, Robert; Marder, Stephen; Mackle, Mary; Snow-Adami, Linda; Voss, Tiffini; Smith, Sean; Egan, Michael (May 2022). "P534. Initial Assessment of the Clinical Profile of the PDE10A Inhibitor MK-8189 in Patients With an Acute Episode of Schizophrenia". Biological Psychiatry. 91 (9): S305. doi:10.1016/j.biopsych.2022.02.771. S2CID 248410630.

[2] Smith, Sean; Uslaner, Jason; Kandebo, Monika; Hostetler, Eric; Raheem, Izzat; Layton, Mark; Gantert, Liza; Riffel, Kerry; Cox, Christopher; Khalilieh, Sauzanne; De Lepeleire, Inge; Bormans, Guy; Depré, Marleen; de Hoon, Jan; Van Laere, Koen (May 2022). "P546. Preclinical Characterization and Phase 1 Evaluation of the Tolerability, Pharmacokinetics, and Enzyme Occupancy of MK-8189, a Novel PDE10A Inhibitor". Biological Psychiatry. 91 (9): S309–S310. doi:10.1016/j.biopsych.2022.02.783. S2CID 248410556.

[3] Layton, Mark E.; Kern, Jeffrey C.; Hartingh, Timothy J.; Shipe, William D.; Raheem, Izzat; Kandebo, Monika; Hayes, Robert P.; Huszar, Sarah; Eddins, Donnie; Ma, Bennett; Fuerst, Joy; Wollenberg, Gordon K.; Li, Jing; Fritzen, Jeff; McGaughey, Georgia B.; Uslaner, Jason M.; Smith, Sean M.; Coleman, Paul J.; Cox, Christopher D. (26 January 2023). "Discovery of MK-8189, a Highly Potent and Selective PDE10A Inhibitor for the Treatment of Schizophrenia". Journal of Medicinal Chemistry. 66 (2): 1157–1171. doi:10.1021/acs.jmedchem.2c01521. PMC 9884086. PMID 36624931. S2CID 255567942.

[4] "MK-8189: A Potent and Selective PDE10A Inhibitor for the Treatment of Schizophrenia". Synfacts. 19 (4): 0410. April 2023. doi:10.1055/s-0042-1752651. S2CID 257614478.

[1]

[2]

[3]

[4]

See also

References