Uses
5-Amino-2H-isoquinolin-1-one is a reactant used in the synthesis of glucoorticoid receptor agonists as well as PARP inhibitors used in the treatment of tumors.
Definition
ChEBI: 5-amino-2H-isoquinolin-1-one is a member of isoquinolines.
Synthesis
General procedure for the synthesis of 5-amino-1(2H)-isoquinolinone from 5-nitro-1(2H)-isoquinolinone: To a reaction flask was added 378.3 mg (1.51 mmol) of 5-nitroisoquinolin-1(2H)-one, 376.5 mg of ammonium chloride, 2.6 mL of water and a solvent mixture of 14 mL of ethanol and 5.4 mL of tetrahydrofuran. 1.23 g of zinc powder was added in batches at 30 to 35 °C and the reaction was stirred continuously for 2 hours. Upon completion of the reaction, the reaction mixture was filtered by pumping through a glass fiber filter and the filter cake was washed with ethyl acetate. The filtrates were combined and washed sequentially with water and saturated sodium chloride solution, and then the organic phase was treated as usual. Finally, the desiccant was removed by filtration and the solvent was removed by concentration under reduced pressure to afford 196.5 mg (88.1% yield) of the target product 5-amino-1(2H)-isoquinolinone. The product was characterized by 1H-NMR (300 MHz, DMSO-d6): δ=5.6 (2H), 6.68 (1H), 6.87-7.45 (1H), 7.00 (1H), 7.17 (1H), 7.39 (1H), 11.7 (1H).
in vivo
5-AIQ (150 and 250 mg/kg; p.o.; once) possess no significantly genotoxic in vivo system by micronucleus test[1].
5-AIQ (3 mg/kg; p.o.; 5 min prior to onset of liver ischemia) reduces the tissue injury associated with ischemia-reperfusion of the liver[2].
| Animal Model: | Male mice[1] |
| Dosage: | 150 and 250 mg/kg |
| Administration: | Oral administration; 150 and 250 mg/kg; once |
| Result: | Showed no increase of micronucleated polychromatic erythrocytes (MNPCE) in both 24 h and 48 h after both 125 and 250 mg/kg duration exposure as compared to the corresponding control.
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| Animal Model: | Anesthetised male Wistar rats with liver ischemia (for 30 minutes) and reperfusion (for 2 hours) [2] |
| Dosage: | 3 mg/kg |
| Administration: | Intravenous injection; 3 mg/kg; 5 min prior to onset of liver ischemia |
| Result: | Reduced PARP activation and showed less staining for ICAM-1.
|
References
[1] Patent: WO2005/35518, 2005, A1. Location in patent: Page/Page column 24
[2] Patent: WO2005/34939, 2005, A1. Location in patent: Page/Page column 56
[3] Patent: US2005/131226, 2005, A1. Location in patent: Page/Page column 8-9
[4] Patent: US2005/222154, 2005, A1. Location in patent: Page/Page column 16
