1154028-82-6

Basic information

• Product Name: Molidustat(BAY 85-3934)
• Synonyms: Molidustat(BAY 85-3934);BAY 85-3934;2-[6-(4-Morpholinyl)-4-pyrimidinyl]-4-(1H-1,2,3-triazol-1-yl)-1,2-dihydro-3H-pyrazol-3-one;2-[6-(Morpholin-4-yl)pyrimidin-4-yl]-4-(1H-1,2,3-triazol-1-yl)-1,2-dihydro-3H-pyrazol-3-one;Somatoprim;2-(6-morpholinopyrimidin-4-yl)-4-(1H-1,2,3-triazol-1-yl)-1H-pyrazol-3(2H)-one;1,2-dihydro-2-[6-(4-morpholinyl)-4-pyrimidinyl]-4-(1H-1,2,3-triazol-1-yl)-3H-pyrazol-3-one
• CAS NO: 1154028-82-6
• Molecular Formula: C13H14N8O2
• Molecular Weight: 314.30266
• EINECS: -0
• Product Categories: Inhibitors
• Mol File: 1154028-82-6.mol
• Article Data: 0

Chemical Properties

• Boiling Point: 589.2±60.0 °C(Predicted)
• Appearance: /
• Density: 1.67±0.1 g/cm3(Predicted)
• Solubility: insoluble in EtOH; insoluble in H2O; ≥5.68 mg/mL in DMF
• PKA: 5.38±0.37(Predicted)
• CAS DataBase Reference: Molidustat(BAY 85-3934)(CAS DataBase Reference)
• NIST Chemistry Reference: Molidustat(BAY 85-3934)(1154028-82-6)
• EPA Substance Registry System: Molidustat(BAY 85-3934)(1154028-82-6)

Safety Data

• Hazardous Substances Data: 1154028-82-6(Hazardous Substances Data)

Usage

Description

Hypoxia-inducible factor (HIF) is the major transcription factor involved in erythropoietin gene expression. Because oxygen-dependent degradation of the α subunit of HIF suppresses erythropoietin expression, stimulation of erythropoiesis by agents that prevent degradation of HIF has been one strategy for managing anemia. BAY 85-3934 stabilizes HIF from degradation in the proteasome by inhibiting HIF-1α prolyl hydroxylase (IC50 = 0.49 μM). Inhibition of HIF prolyl hydroxylase by BAY 85-3934 has been shown to increase endogenous production of erythropoietin. This compound has been investigated in clinical trial for treatment of patients with anemia associated with chronic kidney disease and/or end-stage renal disease.

in vitro

the ic50 values were found to be dependent on the 2-oxoglutarate concentration in the reaction buffer. by lowering the 2-oxoglutarate concentration from 20 μm to 0.3 μm, the potency of the test compound increased up to 10-fold. variation of the concentrations of fe2+ and ascorbate in the reaction buffer by factors of 30 and 200, respectively, did not alter the potency of the inhibitor by more than 2-fold [1].

in vivo

in repeat dosing of bay 85-3934, hemoglobin levels were increased compared with animals in vehicle group, while endogenous epo remained within the normal physiological range. bay 85-3934 therapy was also effective in the treatment of renal anemia in rats with impaired kidney function and, unlike treatment with rhepo, resulted in normalization of hypertensive blood pressure in a rat model of ckd [1].

IC 50

480 nm, 280 nm, and 450 nm for phd1, phd2, and phd3, respectively.

references

[1] flamme i, oehme f, ellinghaus p, jeske m, keldenich j, thuss u. mimicking hypoxia to treat anemia: hif-stabilizer bay 85-3934 (molidustat) stimulates erythropoietin production without hypertensive effects. plos one. 2014 nov 13;9(11):e111838.