| Identification | Back Directory | [Name]
1H-Pyrrole-2-carboxamide, N-cyclopropyl-3-methyl-4-[[6-(trifluoromethyl)-3-pyridinyl]methyl]- | [CAS]
2426616-55-7 | [Synonyms]
DSM502
1H-Pyrrole-2-carboxamide, N-cyclopropyl-3-methyl-4-[[6-(trifluoromethyl)-3-pyridinyl]methyl]- | [Molecular Formula]
C16H16F3N3O | [MOL File]
2426616-55-7.mol | [Molecular Weight]
323.31 |
| Chemical Properties | Back Directory | [Boiling point ]
447.6±45.0 °C(Predicted) | [density ]
1.35±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 250 mg/mL (773.25 mM; Need ultrasonic) | [form ]
Solid | [pka]
15.60±0.50(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
DSM502 is a pyrrole-based Dihydroorotate Dehydrogenase (DHODH) inhibitor. DSM502 exhibits nanomolar potency againsts Plasmodium DHODH and Plasmodium parasites, with no inhibition of mammalian DHODHs[1]. | [Biological Activity]
DSM502 is a pyrrole-based Dihydroorotate Dehydrogenase (DHODH) inhibitor. DSM502 exhibits nanomolar potency againsts Plasmodium DHODH and Plasmodium parasites, with no inhibition of mammalian DHODHs[1].
DSM502 shows inhibitory activity against P. falciparum DHODH (PfDHODH, IC50=20 nM), P. vivax DHODH (PvDHODH, IC50=14 nM) and Pf3D7 cells (EC50=14 nM), with no inhibition of the human enzyme[1].
DSM502 (10 and 50 mg/kg; p.o. once daily for 4 days) results in 97% parasite clearance in confirmatory SCID study compared to 85% clearance in the GSK study[1].DSM502 (18.3 and 50 mg/kg; a single p.o.) exhibits high oral bioavailability (>100%, >100%), apparent t1/2 (2.6, 3.6 h) and Cmax (8.4, 42.3 μM) in mice[1].DSM502 (2.8 mg/kg; a single i.v.) exhibits apparent t1/2 (2.8 h), plasma clearance (26.1 mL/min/kg), and Vss (1.2 L/kg) in mice[1]. | [in vivo]
DSM502 (10 and 50 mg/kg; p.o. once daily for 4 days) results in 97% parasite clearance in confirmatory SCID study compared to 85% clearance in the GSK study[1].
DSM502 (18.3 and 50 mg/kg; a single p.o.) exhibits high oral bioavailability (>100%, >100%), apparent t1/2 (2.6, 3.6 h) and Cmax (8.4, 42.3 μM) in mice[1].
DSM502 (2.8 mg/kg; a single i.v.) exhibits apparent t1/2 (2.8 h), plasma clearance (26.1 mL/min/kg), and Vss (1.2 L/kg) in mice[1]. | Animal Model: | SCID mice (23-36 g) were inoculated with parasites[1] | | Dosage: | 10 and 50 mg/kg | | Administration: | P.o. once daily for 4 days starting on day 3 after mice had been inoculated with parasites | | Result: | Resulted in 97% parasite clearance compared to 85% clearance in the GSK study.
The 10 mg/kg mouse died on day 5. |
| [IC 50]
Plasmodium | [storage]
Store at -20°C | [References]
[1]. Kokkonda S, et, al. Lead Optimization of a Pyrrole-Based Dihydroorotate Dehydrogenase Inhibitor Series for the Treatment of Malaria. J Med Chem. 2020 May 14;63(9):4929-4956. [2]. Palmer MJ, et, al. Potent Antimalarials with Development Potential Identified by Structure-Guided Computational Optimization of a Pyrrole-Based Dihydroorotate Dehydrogenase Inhibitor Series. J Med Chem. 2021 May 13;64(9):6085-6136. |
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