| Identification | Back Directory | [Name]
Imidazo[1,5-a]pyrazin-8(7H)-one, 6-[(3S,4S)-4-methyl-1-(2-pyrimidinylmethyl)-3-pyrrolidinyl]-3-(tetrahydro-2H-pyran-4-yl)- | [CAS]
2062661-53-2 | [Synonyms]
IMR-687
TOVINONTRINE
Tovinontrine( IMR-687)
6-[(3S.4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one
Imidazo[1,5-a]pyrazin-8(7H)-one, 6-[(3S,4S)-4-methyl-1-(2-pyrimidinylmethyl)-3-pyrrolidinyl]-3-(tetrahydro-2H-pyran-4-yl)- | [Molecular Formula]
C21H26N6O2 | [MOL File]
2062661-53-2.mol | [Molecular Weight]
394.47 |
| Hazard Information | Back Directory | [Uses]
Tovinontrine (IMR-687) is a highly potent and selective phosphodiesterase-9 (PDE9) inhibitor specifically for the treatment of sickle cell disease. IC50s are 8.19 nM and 9.99 nM for PDE9A1 and PDE9A2, respectively[1]. | [in vivo]
IMR-687 (30 mg/kg/day; after 30 days of treatment) shows a greater than 3-fold in the percent of HbF+ F-cells (8.4% in vehicle treated and 27.3% in IMR-687 treated) and a corresponding 2-fold decrease in sickled red blood cells (56.3% in vehicle treated and 24.4% in IMR-687 treated)[1]. | Animal Model: | HbSS-Townes mice on a 129/B6 background (10-12 weeks old) [1] | | Dosage: | 30 mg/kg | | Administration: | Dosed daily by gavage for 30 days | | Result: | Resulted in fetal hemoglobin (HbF) induction, reduced hemolysis and reduced reticulocytosis. |
| [IC 50]
PDE9A1: 8.19 nM (); PDE9A2: 9.99 nM (); PDE1A3: 88.4 nM (); PDE1B: 8.48 nM (); PDE1C: 12.2 nM (); PDE5A2: 81.9 nM () | [References]
[1] James G McArthur, et al. A novel, highly potent and selective phosphodiesterase-9 inhibitor for the treatment of sickle cell disease. Haematologica. 2020 Mar;105(3):623-631. DOI:10.3324/haematol.2018.213462 |
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