| Identification | Back Directory | [Name]
4H-Pyrrolo[3,2-d]pyrimidin-4-one, 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-1,2,3,5-tetrahydro-2-thioxo- | [CAS]
1933460-19-5 | [Synonyms]
AZD4831
Mitiperstat
AZD4831(Mitiperstat )
(R)-1-(2-(1-aminoethyl)-4-chlorobenzyl)-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one
4H-Pyrrolo[3,2-d]pyrimidin-4-one, 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-1,2,3,5-tetrahydro-2-thioxo- | [Molecular Formula]
C15H15ClN4OS | [MOL File]
1933460-19-5.mol | [Molecular Weight]
334.82 |
| Chemical Properties | Back Directory | [density ]
1.49±0.1 g/cm3(Predicted) | [form ]
Solid | [pka]
8.11±0.20(Predicted) | [color ]
Off-white to pink | [InChI]
InChI=1S/C15H15ClN4OS/c1-8(17)11-6-10(16)3-2-9(11)7-20-12-4-5-18-13(12)14(21)19-15(20)22/h2-6,8,18H,7,17H2,1H3,(H,19,21,22)/t8-/m1/s1 | [InChIKey]
BHKKSKOHRFHHIN-MRVPVSSYSA-N | [SMILES]
C1(=S)NC(=O)C2NC=CC=2N1CC1=CC=C(Cl)C=C1[C@H](N)C |
| Hazard Information | Back Directory | [Uses]
Mitiperstat (AZD4831) is an effective oral inhibitor of myeloperoxidase (MPO). Mitiperstat inhibits MPO and thyroid peroxidase (TPO) with IC50s of 1.5 nM and 0.69 μM. Mitiperstat exhibits a weak inhibitory activity against CYP3A4 with an IC50 of 6 μM. Mitiperstat can reduce inflammation and improve microvascular function, and it can be used in studies related to heart failure, preserved or mildly reduced ejection fraction, non-alcoholic fatty liver disease, and chronic obstructive pulmonary disease[1][2][3][4]. | [in vivo]
Mitiperstat (0.01-10 μmol/kg, po, single dose) inhibits MPO activity in peritoneal lavage fluid in mouse zymosan-induced neutrophilic peritonitis models, and can be used in research of heart failure and a preserved ejection fraction[4]. | Animal Model: | Mouse zymosan-induced neutrophilic peritonitis models[4] | | Dosage: | 0.01-10 μmol/kg (3.3482 ng/kg-3.3482 μg/kg) | | Administration: | po, single dose | | Result: | Inhibited the peroxidase activity in mouse peritoneal lavage fluid. |
| [References]
[1] Joanna Parkinson， et al. The myeloperoxidase inhibitor mitiperstat (AZD4831) does not prolong the QT interval at expected therapeutic doses. Pharmacol Res Perspect. 2024 Apr;12(2):e1184. DOI:10.1002/prp2.1184
[2] Lars H Lund, et al. Rationale and design of ENDEAVOR: A sequential phase 2b-3 randomized clinical trial to evaluate the effect of myeloperoxidase inhibition on symptoms and exercise capacity in heart failure with preserved or mildly reduced ejection fraction. Eur J Heart Fail. 2023 Sep;25(9):1696-1707. DOI:10.1002/ejhf.2977
[3] Carolyn S P Lam, et al. Myeloperoxidase Inhibition in Heart Failure With Preserved or Mildly Reduced Ejection Fraction: SATELLITE Trial Results. J Card Fail. 2024 Jan;30(1):104-110. DOI:10.1016/j.cardfail.2023.04.003
[4] Inghardt T, et al., Discovery of AZD4831, a Mechanism-Based Irreversible Inhibitor of Myeloperoxidase, As a Potential Treatment for Heart Failure with Preserved Ejection Fraction. J Med Chem. 2022 Sep 8;65(17):11485-11496. DOI:10.1021/acs.jmedchem.1c02141 |
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