457051-15-9Relevant articles and documents
Targeting ALK2: An Open Science Approach to Developing Therapeutics for the Treatment of Diffuse Intrinsic Pontine Glioma
Ensan, Deeba,Smil, David,Zepeda-Velázquez, Carlos A.,Panagopoulos, Dimitrios,Wong, Jong Fu,Williams, Eleanor P.,Adamson, Roslin,Bullock, Alex N.,Kiyota, Taira,Aman, Ahmed,Roberts, Owen G.,Edwards, Aled M.,O'meara, Jeff A.,Isaac, Methvin B.,Al-Awar, Rima
, p. 4978 - 4996 (2020/05/18)
Diffuse intrinsic pontine glioma is an aggressive pediatric cancer for which no effective chemotherapeutic drugs exist. Analysis of the genomic landscape of this disease has led to the identification of the serine/threonine kinase ALK2 as a potential target for therapeutic intervention. In this work, we adopted an open science approach to develop a series of potent type I inhibitors of ALK2 which are orally bio-available and brain-penetrant. Initial efforts resulted in the discovery of M4K2009, an analogue of the previously reported ALK2 inhibitor LDN-214117. Although highly selective for ALK2 over the TGF-βR1 receptor ALK5, M4K2009 is also moderately active against the hERG potassium channel. Varying the substituents of the trimethoxyphenyl moiety gave rise to an equipotent benzamide analogue M4K2149 with reduced off-target affinity for the ion channel. Additional modifications yielded 2-fluoro-6-methoxybenzamide derivatives (26a-c), which possess high inhibitory activity against ALK2, excellent selectivity, and superior pharmacokinetic profiles.
SMALL MOLECULE INHIBITORS OF DIHYDROFOLATE REDUCTASE
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Page/Page column 102, (2017/01/31)
The disclosure relates to compositions and methods for the treatment of fungal, bacterial, and parasitic infections and inhibition of fungal, bacterial, and parasitic growth. In particular, such compositions include dihydrofolate reductase (DHFR) inhibito
INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL
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Page/Page column 58, (2014/09/03)
The present invention provides compounds of Formula(I) or a pharmaceutically acceptable salt thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure, kidney disease, edema, and conditions associated with excessive salt and water retention.
SUBSTITUTED 4-AMINOBENZAMIDES AS KCNQ2/3 MODULATORS
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Paragraph 0735, (2013/11/05)
Substituted 4-aminobenzamides, pharmaceutical compositions containing these compounds and also methods of using these compounds in the treatment and/or prophylaxis of pain and further diseases and/or disorders.