PF-06412562

❧

Wikipedia

PF-06412562
Clinical data
Other namesPF06412562; PF-6412562; PF6412562; CVL-562; CVL562
Routes of
administration		Oral[1]
Drug classDopamine D1 and D5 receptor agonist
Identifiers
  • 4-[4-(4,6-dimethylpyrimidin-5-yl)-3-methylphenoxy]-1H-pyrazolo[4,5-c]pyridine
CAS Number
PubChem CID
ChemSpider
ChEMBL
Chemical and physical data
FormulaC19H17N5O
Molar mass331.379 g·mol−1
3D model (JSmol)
  • CC1=C(C=CC(=C1)OC2=NC=CC3=C2C=NN3)C4=C(N=CN=C4C)C
  • InChI=1S/C19H17N5O/c1-11-8-14(25-19-16-9-23-24-17(16)6-7-20-19)4-5-15(11)18-12(2)21-10-22-13(18)3/h4-10H,1-3H3,(H,23,24)
  • Key:IDIUJOHYYBNCPC-UHFFFAOYSA-N

PF-06412562, also known as CVL-562, is a moderately potent and highly selective dopamine D1 and D5 receptor partial agonist which is under development for the treatment of the cognitive symptoms of schizophrenia.[1][2][3][4] It is taken orally.[1] The drug has been reported to produce pro-motivational effects in humans.[3][5] PF-06412562 is under development by Pfizer and Cerevel Therapeutics.[1][2] As of August 2025, it is in phase 1/2 clinical trials.[1][2] The drug was also under development for the treatment of Parkinson's disease and cognition disorders, but development for these indications was discontinued.[1][2] Its development for Parkinson's disease was discontinued for business reasons unrelated to safety in 2017.[6]

Chemistry

Synthesis

The chemical synthesis was described (Ex 6):[7]

Protection of 4-Chloro-1H-pyrazolo[4,3-c]pyridine [871836-51-0] (1) with 2,3-Dihydropyran [110-87-2] (2) gives 4-chloro-1-(oxan-2-yl)-1H-pyrazolo[4,3-c]pyridine [1416713-66-0] (3). Suzuki reaction between 4-Methoxy-2-methylphenylboronic acid pinacol ester [214360-68-6] (4) and 5-Bromo-4,6-dimethylpyrimidine [157335-97-2] (5) gives 5-(4-methoxy-2-methylphenyl)-4,6-dimethylpyrimidine [1609259-54-2] (6). Demethylation of the ether gives rise to 4-(4,6-dimethylpyrimidin-5-yl)-3-methylphenol [1609259-55-3] (7). Reaction of this with 3 gives 4-[4-(4,6-dimethylpyrimidin-5-yl)-3-methylphenoxy]-1-(oxan-2-yl)pyrazolo[4,5-c]pyridine, PC90116929 (8). Tetramethyl‑di‑tBuXPhos [857356-94-6] is a bulky, electron‑rich biaryl monophosphine ligand used in palladium‑catalysed cross‑coupling reactions. Deprotection of the THP protecting group in acid completed the synthesis of PF2562 (9).

See also

References

  1. 1 2 3 4 5 6 "PF 6412562". AdisInsight. 5 August 2024. Retrieved 28 January 2026.
  2. 1 2 3 4 Keown A (4 December 2025). "Delving into the Latest Updates on PF-06412562 with Synapse". Synapse. Retrieved 28 January 2026.
  3. 1 2 Abi-Dargham A, Javitch JA, Slifstein M, Anticevic A, Calkins ME, Cho YT, et al. (January 2022). "Dopamine D1R Receptor Stimulation as a Mechanistic Pro-cognitive Target for Schizophrenia". Schizophrenia Bulletin. 48 (1): 199–210. doi:10.1093/schbul/sbab095. PMC 8781338. PMID 34423843.
  4. ↑ Jing XZ, Yang HJ, Taximaimaiti R, Wang XP (2023). "Advances in the Therapeutic Use of Non-Ergot Dopamine Agonists in the Treatment of Motor and Non-Motor Symptoms of Parkinson's Disease". Current Neuropharmacology. 21 (5): 1224–1240. doi:10.2174/1570159X20666220915091022. PMC 10286583. PMID 36111769.
  5. ↑ Soutschek A, Gvozdanovic G, Kozak R, Duvvuri S, de Martinis N, Harel B, et al. (April 2020). "Dopaminergic D1 Receptor Stimulation Affects Effort and Risk Preferences". Biological Psychiatry. 87 (7): 678–685. doi:10.1016/j.biopsych.2019.09.002. PMID 31668477.
  6. ↑ Hall A, Provins L, Valade A (January 2019). "Novel Strategies To Activate the Dopamine D1 Receptor: Recent Advances in Orthosteric Agonism and Positive Allosteric Modulation". Journal of Medicinal Chemistry. 62 (1): 128–140. doi:10.1021/acs.jmedchem.8b01767. PMID 30525590.
  7. ↑ Jennifer E. DAVOREN, et al. WO2014072882 (to Pfizer Corp Belgium, Pfizer Corp SRL).