| Synonyms |
(S)-1-(3-Methyl-2-oxobutyl)-8-((R)-3-methylmorpholino)-2-(trifluoromethyl)-3,4-dihydro-1H-pyrimido[1,2-a]pyrimidin-6(2H)-one |
| IUPAC Name |
(8S)-2-[(3R)-3-methylmorpholin-4-yl]-9-(3-methyl-2-oxobutyl)-8-(trifluoromethyl)-7,8-dihydro-6H-pyrimido[1,2-a]pyrimidin-4-one |
| Molecular Weight |
402.41 |
| Molecular Formula |
C18H25F3N4O3 |
| Canonical SMILES |
CC1COCCN1C2=CC(=O)N3CCC(N(C3=N2)CC(=O)C(C)C)C(F)(F)F |
| InChI |
InChI=1S/C18H25F3N4O3/c1-11(2)13(26)9-25-14(18(19,20)21)4-5-24-16(27)8-15(22-17(24)25)23-6-7-28-10-12(23)3/h8,11-12,14H,4-7,9-10H2,1-3H3/t12-,14+/m1/s1 |
| InChIKey |
ITCIAOUZMPREOO-OCCSQVGLSA-N |
| Boiling Point |
466.4±55.0 °C at 760 mmHg |
| Flash Point |
235.9±31.5 °C |
| Purity |
99% |
| Density |
1.4±0.1 g/cm3 |
| Solubility |
In vitro:
10 mM in DMSO |
| Appearance |
White to off-white (Solid) |
| Storage |
Store at -20°C |
| Animal Admin |
For PK/PD studies, 3×106 H1299-GFP-FYVE tumor cells with 50% Matrigel are subcutaneously injected on the dorsal side of SCID mice, one tumor per mouse. When xenografted tumors reach a range of ~200 to 400 mm3, mice are treated with vehicle (98% PEG200/2% PS80) or a single dose of Vps34-IN-2 (compound 31) at 100 and 50 mg/kg via oral gavage. Three mice treated with vehicle alone and three mice treated with Vps34-IN-2 are sacrificed at each time point; tumor tissues are harvested for immunohistochemistry (IHC) analysis and plasma samples are collected to determine the concentration of Vps34-IN-2. |
| Complexity |
705 |
| Exact Mass |
402.18787516 |
| Index Of Refraction |
1.581 |
| In Vitro |
Vps34-IN-2 (Compound 31) displays IC50s of 2 and 82 nM on the Vps34 enzymatic assay and the GFP-FYVE cellular assay, respectively. Vps34-IN-2 exhibits selectivity against mTOR (IC50>10 μM) and class I PI3Ks (IC50 values of 2.7, 4.5, 2.5, and >10 μM on PI3K α, β, δ, γ isoforms, respectively). |
| In Vivo |
After administration by the intravenous (iv) route, Vps34-IN-2 (Compound 31) concentrations are quantifiable up to 6, 8, and 24 h (last sampling time) depending on animals. After oral administration (po), Vps34-IN-2 is rapidly absorbed with maximal plasma concentrations observed at 0.5 h and a bioavailability of 85%. Slight rebounds of concentrations are observed at 4 and 8 h after oral dosing with no obvious explanation. After iv injection of Vps34-IN-2 at 3 mg/kg, plasma clearance is found moderate (i.e., 2.3 L/h/kg), corresponding to 44% of hepatic blood flow in this species, volume of distribution at steady state is moderate, and terminal elimination half-life is short. |
| Target |
Vps34:2 nM (IC50) |
| Vapor Pressure |
0.0±1.2 mmHg at 25°C |
| XLogP3-AA |
2 |
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