| Identification | Back Directory | [Name]
Carbamic acid, N-[[2-[[4-(1-piperidinylcarbonyl)benzoyl]amino]-3-thienyl]carbonyl]-, methyl ester | [CAS]
2419160-96-4 | [Synonyms]
DprE1-IN-4
Carbamic acid, N-[[2-[[4-(1-piperidinylcarbonyl)benzoyl]amino]-3-thienyl]carbonyl]-, methyl ester | [Molecular Formula]
C20H21N3O5S | [MOL File]
2419160-96-4.mol | [Molecular Weight]
415.46 |
| Hazard Information | Back Directory | [Uses]
DprE1-IN-4 is a potent and orally active noncovalent DprE1 inhibitor with an IC50 of 0.90 μg/mL. DprE1-IN-4 exhibits potent in vitro activity against M. tuberculosis H37Rv and drug-resistant tuberculosis strain with MIC values of 0.12 μg/mL and 0.24 μg/mL, respectively. DprE1-IN-4 displays acceptable pharmacokinetic property and shows significant bactericidal activity in an acute mouse model of tuberculosis. | [in vivo]
DprE1-IN-4 exhibits acceptable pharmacokinetic property after p.o. and i.v., DprE1-IN-4 (oral administration, 50 mg/kg) exhibits high plasma exposure ((AUC)0-∞=657 ng·h/mL) and high maximum plasma concentration (Cmax=486 ng/mL). It exhibits oral bioavailability (F=7.9%) and is deemed worthy of further evaluation in?in vivo?efficacy studies[1].DprE1-IN-4 (oral gavage; 100 mg/kg; once daily; 3 weeks) showed potent?in vivo?activity, reducing the bacterial burden in the lungs by 2.02?log10?CFU compared with the untreated control group[1]. | [References]
[1] Pengxu Wang, et al. Discovery of Novel Thiophene-arylamide Derivatives as DprE1 Inhibitors with Potent Antimycobacterial Activities. J Med Chem. 2021 May 13;64(9):6241-6261. DOI:10.1021/acs.jmedchem.1c00263 |
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