Tavapadon (PF-6649751; CVL-751) is a partial dopamine receptor agonist with the potential to be used in the treatment of Parkinson's disease and Alzheimer's.

Physicochemical Properties

Molecular Formula	C19H16F3N3O3
Molecular Weight	391.343854904175
Exact Mass	391.114
Elemental Analysis	C, 58.31; H, 4.12; F, 14.56; N, 10.74; O, 12.26
CAS #	1643489-24-0
Related CAS #	(Rac)-Tavapadon; 1643462-64-9
PubChem CID	86764100
Appearance	Solid powder
Density	1.3±0.1 g/cm3
Index of Refraction	1.549
LogP	3.66
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	3
Heavy Atom Count	28
Complexity	665
Defined Atom Stereocenter Count	0
SMILES	FC(C1=CC=CN=C1OC1C=CC(=C(C)C=1)C1=C(C)C(NC(N1C)=O)=O)(F)F
InChi Key	AKQXQLUNFKDZBN-UHFFFAOYSA-N
InChi Code	InChI=1S/C19H16F3N3O3/c1-10-9-12(28-17-14(19(20,21)22)5-4-8-23-17)6-7-13(10)15-11(2)16(26)24-18(27)25(15)3/h4-9H,1-3H3,(H,24,26,27)
Chemical Name	1,5-dimethyl-6-[2-methyl-4-[3-(trifluoromethyl)pyridin-2-yl]oxyphenyl]pyrimidine-2,4-dione
Synonyms	CVL-751; CVL 751; CVL751; PF-6649751; PF 6649751; PF6649751
HS Tariff Code	2934.99.03.00
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	dopamine D1/D5 receptor
ln Vivo	Tavapadon (PF-06649751; 0.02 and 0.04 mg/kg; s.c.) has little to no effect on locomotor activity when administered at the 0.04 mg/kg test dose, in contrast to the 0.02 mg/kg dose[1]. Tavapadon (0.04 mg/kg, s.c.) also reduces parkinsonian disability scores; the greatest reduction in disability was seen 110 minutes after the drug was administered[1]. Increased Tavapadon dosages (0.1 and 0.15 mg/kg; s.c.) result in a statistically significant improvement in locomotor activity when compared to a vehicle[1]. Tavapadon (0.1 mg/kg; s.c.) in captive-bred macaques results in a mean maximal unbound plasma concentration of 8 nM three hours after compound administration[1].
References	[1]. D1 Agonist Improved Movement of Parkinsonian Nonhuman Primates with Limited DyskinesiaSide Effects. ACS Chem Neurosci. 2020 Feb 19;11(4):560-566.
Additional Infomation	Tavapadon is under investigation in clinical trial NCT02262767 (A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of PF-06649751 Co-administered With Trimethobenzamide Hydrochloride in Healthy Subjects). Drug Indication Treatment of Parkinson's disease

Solubility Data

Solubility (In Vitro)

DMSO: ~100 mg/mL (~255.5 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 2.5 mg/mL (6.39 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.5553 mL	12.7766 mL	25.5532 mL
	5 mM	0.5111 mL	2.5553 mL	5.1106 mL
	10 mM	0.2555 mL	1.2777 mL	2.5553 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.