- Discovery of Novel, Orally Bioavailable Pyrimidine Ether-Based Inhibitors of ELOVL1
-
In our efforts to identify novel small molecule inhibitors for the treatment of adrenoleukodystrophy (ALD), we conducted a high-throughput radiometric screen for inhibitors of elongation of very long chain fatty acid 1 (ELOVL1) enzyme. We developed a seri
- Boyd, Michael J.,Collier, Philip N.,Clark, Michael P.,Deng, Hongbo,Kesavan, Sarathy,Ronkin, Steven M.,Waal, Nathan,Wang, Jian,Cao, Jingrong,Li, Pan,Come, Jon,Davies, Ioana,Duffy, John P.,Cochran, John E.,Court, John J.,Chandupatla, Kishan,Jackson, Katrina L.,Maltais, Francois,O’Dowd, Hardwin,Boucher, Christina,Considine, Tony,Taylor, William P.,Gao, Hong,Chakilam, Ananthisrinivas,Engtrakul, Juntyma,Crawford, Dan,Doyle, Elizabeth,Phillips, Jonathan,Kemper, Raymond,Swett, Rebecca,Empfield, James,Bunnage, Mark E.,Charifson, Paul S.,Magavi, Sanjay Shivayogi
-
p. 17777 - 17794
(2021/12/17)
-
- Discovery of Molidustat (BAY 85-3934): A Small-Molecule Oral HIF-Prolyl Hydroxylase (HIF-PH) Inhibitor for the Treatment of Renal Anemia
-
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.
- 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
-
p. 988 - 1003
(2018/04/19)
-
- Selective mono-amination of dichlorodiazines
-
A mild, easy-to-perform, and versatile method for the formation of aminochlorodiazines from reaction of several types of dichlorodiazines (i.e., pyridazines, pyrimidines, and pyrazines) with primary or secondary amines in ethanol in the presence of trieth
- Sengmany, Stéphane,Lebre, Julie,Le Gall, Ewan,Léonel, Eric
-
p. 4859 - 4867
(2015/08/03)
-
- SUBSTITUTED DIHYDROPYRAZOLONES AND USE THEREOF AS HIF-PROLYL-4 -HYDROXYLASE INHIBITORS
-
The present application relates to novel substituted dihydropyrazolone derivatives, processes for their preparation, their use for treatment and/or prophylaxis of diseases and their use for the preparation of medicaments for treatment and/or prophylaxis of diseases, in particular cardiovascular and hematological diseases and kidney diseases, and for promoting wound healing.
- -
-
Page/Page column 15-16
(2012/10/23)
-
- SUBSTITUTED DIHYDROPYRAZOLONES FOR TREATING CARDIOVASCULAR AND HEMATOLOGICAL DISEASES
-
The invention relates to dihydropyrazolon-derivatives of formula (I), to methods for their production, to their use for treating and/or for preventing diseases and their use for producing medicaments for treating and/or for preventing diseases, in particular cardiovascular and haematological diseases, kidney diseases and for promoting the healing of wounds.
- -
-
Page/Page column 17
(2010/12/29)
-