223760-89-2Relevant academic research and scientific papers
Discovery of Molidustat (BAY 85-3934): A Small-Molecule Oral HIF-Prolyl Hydroxylase (HIF-PH) Inhibitor for the Treatment of Renal Anemia
Beck, Hartmut,Jeske, Mario,Thede, Kai,Stoll, Friederike,Flamme, Ingo,Akbaba, Metin,Ergüden, Jens-Kerim,Karig, Gunter,Keldenich, J?rg,Oehme, Felix,Militzer, Hans-Christian,Hartung, Ingo V.,Thuss, Uwe
supporting information, p. 988 - 1003 (2018/04/19)
Small-molecule inhibitors of hypoxia-inducible factor prolyl hydroxylases (HIF-PHs) are currently under clinical development as novel treatment options for chronic kidney disease (CKD) associated anemia. Inhibition of HIF-PH mimics hypoxia and leads to increased erythropoietin (EPO) expression and subsequently increased erythropoiesis. Herein we describe the discovery, synthesis, structure–activity relationship (SAR), and proposed binding mode of novel 2,4-diheteroaryl-1,2-dihydro-3H-pyrazol-3-ones as orally bioavailable HIF-PH inhibitors for the treatment of anemia. High-throughput screening of our corporate compound library identified BAY-908 as a promising hit. The lead optimization program then resulted in the identification of molidustat (BAY 85-3934), a novel small-molecule oral HIF-PH inhibitor. Molidustat is currently being investigated in clinical phase III trials as molidustat sodium for the treatment of anemia in patients with CKD.
Imidazole derivatives and their use as farnesyl protein transferase inhibitors
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Page column 48, (2010/11/29)
The present invention relates to compounds of formula (I), wherein Ar1represents (A) and (B) or (C); R12and R13are independently hydrogen or C1-4alkyl; Ar2is phenyl or heteroaryl; p is 0 or 1; Ar3is phenyl, pyridinyl, pyridazinyl, pyrimidyl or pyrazynyl, the ring being substituted on ring carbon atoms by R2and —(CH2)nR3, and wherein Ar3is attached to Ar1C(R12)R13CH(Ar2)O— by a ring carbon atom; R2is a group of formula (2), or R2represents a lactone of formula (3), the group of formula (2) or (3) havingLorDconfiguration at the chiral alpha carbon in the corresponding free amino acid; n is 0, 1 or 2; R3is phenyl or heteroaryl; and R5-R9, m and n are as defined in the specification; or a pharmaceutically acceptable salt, prodrug or solvate thereof. Processes for their preparation, their use as therapeutic agents and pharmaceutical compositions containing them. A particular use in cancer therapy.
