P7C3-A20 Chemical Properties

Boiling point:

641.3±55.0 °C(Predicted)

Density 

1.57±0.1 g/cm3(Predicted)

storage temp. 

Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

solubility 

Soluble in DMSO (40 mg/ml)

pka

3.25±0.50(Predicted)

form 

solid

color 

Off-white

Stability:

Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.

InChI

InChI=1S/C22H19Br2FN2O/c1-28-18-4-2-3-17(11-18)26-12-16(25)13-27-21-7-5-14(23)9-19(21)20-10-15(24)6-8-22(20)27/h2-11,16,26H,12-13H2,1H3

InChIKey

XNLTWMQBJFWQOU-UHFFFAOYSA-N

SMILES

N1(CC(F)CNC2=CC=CC(OC)=C2)C2=C(C=C(Br)C=C2)C2=C1C=CC(Br)=C2

P7C3-A20 Usage And Synthesis

Description

P7C3-A20 is a derivative of P7C3 (Item No. 16682) that has proneurogenic and neuroprotective activity. It increases proliferation in the subgranular zone (SGZ) of the adult mouse dentate gyrus in a dose-dependent manner when administered at doses ranging from 0.1 to 10 μM. It also protects U2OS cells from calcium-induced mitochondrial dissolution. In a rat model of traumatic brain injury, P7C3-A20 (10 mg/kg, i.p., twice daily for one week) decreases contusion volume, increases proliferation in the SGZ, and decreases the latency to reach the platform in the Morris water maze to sham surgery control levels. It also prevents or reverses dopaminergic cell death and motor deficits in a 6-OHDA rat model of Parkinson's disease.

Uses

P7C3-A20 is a derivative of P7C3 with potent proneurogenic and neuroprotective activity. P7C3-A20 exerts an antidepressant-like effect. P7C3-A20 can cross the blood-brain barrier and therefore has the potential for brain injury treatment[1][2][3].

Synthesis

To a vial containing N-(3-(3,6-dibromo-9H-carbazol-9-yl)-2-fluoropropyl)-N-(3-methoxyphenyl)-4-nitrobenzenesulfonamide (21.0 mg, 0.030 mmol) were added lithium hydroxide (3.2 mg, 0.134 mmol), N,N-dimethylformamide (0.5 mL, 0.06 M), and mercaptoacetic acid ( 4.2 μL, 0.060 mmol). The reaction mixture was stirred for 1 h at room temperature, then diluted with ethyl acetate and washed sequentially with water, saturated sodium bicarbonate solution, water (3 times) and brine. The organic layer was dried with anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by silica gel column chromatography (eluent: 30% ethyl acetate/hexane containing 0.2% triethylamine) to give 13.6 mg of the target compound in 88% yield. Another synthetic method: DAST (diethylamino sulfur trifluoride, 0.12 mL, 0.916 mmol) was added dropwise to a solution of 1-(3,6-dibromo-9H-carbazol-9-yl)-3-(3-methoxyphenylamino)propan-2-ol (0.102 g, 0.203 mmol) in anhydrous dichloromethane (6.0 mL), and the reaction was carried out at -78 °C. The reaction mixture was stirred at -78 °C for 1 h, then slowly warmed to 0 °C and kept for 5 h. The reaction was carried out at -78 °C. The reaction was quenched by addition of phosphate buffer (pH=8) and extracted with dichloromethane. The aqueous phase was extracted twice with dichloromethane (10 mL). The combined organic phases were dried with anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by silica gel fast column chromatography (eluent: 20% ethyl acetate/hexane containing 0.2% triethylamine) and the fraction containing the desired fluorinated product was further purified with 40% ethyl acetate/hexane containing 0.1% triethylamine to give 5.7 mg of the target compound. Analytical data for 3,6-dibromo-beta-fluoro-N-(3-methoxyphenyl)-9H-carbazole-9-propanamine: 1H NMR (CDCl3, 500 MHz) δ 8.16 (2H, J = 2.0 Hz), 7.56 (dd, 2H, J = 1.9, 8.7 Hz), 7.31 (d, 2H, J = 8.6 Hz), 7.11 (t, 1H, J = 8.1 Hz), 6.36 (dd, 1H, J = 2.2, 8.1 Hz), 6.23 (dd , 1H, J = 2.0, 8.0 Hz), 6.15 (t, 1H, J = 2.3 Hz), 5.11 (ddd, 1H, J = 4.6, 5.8, 10.4, 47.7 Hz), 4.60 (m, 2H), 4.39 (dm, 2H), 3.95 (t, 1H, J = 6.3 Hz), 3.75 (s, 3H). MS (ESI), m/z: 504.9 (M + 1)+. ([M + 1]+ for C22H19Br2FN2O calculated: 505.0).

in vivo

References

[1] PETER M LOCOCO. Pharmacological augmentation of nicotinamide phosphoribosyltransferase (NAMPT) protects against paclitaxel-induced peripheral neuropathy.[J]. eLife, 2017, 6. DOI:10.7554/elife.29626
[2] MEGHAN O BLAYA. Neuroprotective efficacy of a proneurogenic compound after traumatic brain injury.[J]. Journal of neurotrauma, 2014, 31 5: 476-486. DOI:10.1089/neu.2013.3135
[3] EDWIN VÁZQUEZ-ROSA. P7C3-A20 treatment one year after TBI in mice repairs the blood-brain barrier, arrests chronic neurodegeneration, and restores cognition.[J]. Proceedings of the National Academy of Sciences of the United States of America, 2020: 27667-27675. DOI:10.1073/pnas.2010430117
[4] JUNJIE BAI . The Small Molecule P7C3-A20 Exerts Neuroprotective Effects in a Hypoxic–ischemic Encephalopathy Model via Activation of PI3K/AKT/GSK3β Signaling[J]. Neuroscience, 2020, 441: Pages 197-208. DOI:10.1016/j.neuroscience.2020.05.051
[5] HIDEHIRO OKU. P7C3 Suppresses Neuroinflammation and Protects Retinal Ganglion Cells of Rats from Optic Nerve Crush.[J]. Investigative ophthalmology & visual science, 2017: 4877-4888. DOI:10.1167/iovs.17-22179

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