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ChemicalBook--->CAS DataBase List--->1215493-56-3

1215493-56-3

1215493-56-3 Structure

1215493-56-3 Structure
IdentificationBack Directory
[Name]

RGFP 109
[CAS]

1215493-56-3
[Synonyms]

RG2833
RG-2833
RG 2833
RGFP109
CS-2320
RGFP-109
RGFP 109
RG2833(RGFP109)
RG2833; RGFP109; RG-2833; RGFP 109
N-[6-(2-aminoanilino)-6-oxohexyl]-4-methylbenzamide
N-[6-(2-Aminophenylamino)-6-oxohexyl]-4-methylbenzamide
Benzamide, N-[6-[(2-aminophenyl)amino]-6-oxohexyl]-4-methyl-
RGFP 109 N-[6-(2-Aminophenylamino)-6-oxohexyl]-4-methylbenzamide
[Molecular Formula]

C20H25N3O2
[MDL Number]

MFCD25976845
[MOL File]

1215493-56-3.mol
[Molecular Weight]

339.431
Chemical PropertiesBack Directory
[Boiling point ]

620.1±50.0 °C(Predicted)
[density ]

1.163±0.06 g/cm3(Predicted)
[storage temp. ]

Store at -20°C
[solubility ]

insoluble in H2O; ≥16.95 mg/mL in DMSO; ≥8.05 mg/mL in EtOH with gentle warming and ultrasonic
[form ]

Powder
[pka]

14.62±0.70(Predicted)
[color ]

White to off-white
Hazard InformationBack Directory
[Uses]

RGFP 109 is a histone deacetylase (HDAC) inhibitor that has shown to reverse FXN gene silencing in short-term studies of Friedreich ataxia (FRDA) patient cells.
[Synthesis]

o-Phenylenediamine

95-54-5

Hexanoic acid, 6-[(4-Methylbenzoyl)aMino]-

78521-43-4

RGFP 109

1215493-56-3

The general procedure for the synthesis of N-[6-(2-aminophenylamino)-6-oxohexyl]-4-methylbenzamide (R01) from o-phenylenediamine and 6-(4-methylbenzoylamino)hexanoic acid was as follows: under nitrogen protection, 6-(4-methylbenzoylamino)hexanoic acid (498 mg, 2 mmol), o-phenylenediamine (216 mg, 2 mmol), EDCI (383 mg, 2 mmol), HOBt (405 mg, 3 mmol) and triethylamine (404 mg, 4 mmol) were dissolved in dichloromethane (30 mL) and the reaction was stirred at room temperature. After completion of the reaction, the reaction mixture was washed with water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to afford the target compound N-[6-(2-aminophenylamino)-6-oxohexyl]-4-methylbenzamide (227 mg, 33.9% yield) as a white solid. The product was confirmed to be >95% pure by 1H NMR (DMSO-d6) and LC-MS characterization.1H NMR (DMSO-d6) δ: 9.06 (s, 1H), 8.35 (s, 1H), 7.73 (d, J = 8.0 Hz, 2H), 7.24 (d, J = 8.0 Hz, 2H), 7.14 (t, J = 7.5 Hz, 1H), 6.86-6.89 (m, 1H), 6.70 (d, J = 7.5 Hz, 1H), 6.50 (t, J = 7.5 Hz, 1H), 4.80 (s, 2H), 3.22-3.26 (m, 2H), 2.30-2.35 (m, 5H), 1.53-1.65 (m, 4H), 1.36-1.38 (m, 2H). LC-MS (ESI): m/z 340 [M+H]+.

[in vivo]

RG2833 (150 mg/kg) is able to correct frataxin deficiency in the brain and heart of KIKI mice 24 hours after a single injection, but not when lower doses are used. When followed in time, the frataxin mRNA increase induced by RG2833 in the KIKI mouse can be first detected at 12 hours and reach a maximum at 24 hours in both brain and heart[1]. RG2833 (100 mg/kg, s.c.) is well tolerated in chronic dosing of mice without toxicity. RG2833 improves motor coordination of YG8R FRDA mice. RG2833 increases frataxin protein expression in the brain of YG8R FRDA mice[2]. RGFP109 (30 mg/kg, p.o. once daily for 6 days) has no acute effects on dyskinesia after single or 6 days once-daily treatment. One week following cessation of RGFP109, dyskinesia and duration of ON-time with disabling dyskinesia are reduced by 37% and 50%, respectively[3].

[target]

HDAC1
[IC 50]

HDAC3: 50 nM (IC50); HDAC1: 60 nM (IC50); HDAC3: 5 nM (Ki); HDAC1: 32 nM (Ki)
[storage]

Store at -20°C
[References]

[1] Patent: US2012/94971, 2012, A1. Location in patent: Page/Page column 40
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