1297344-97-8Relevant academic research and scientific papers
IMIDAZOLE-CONTAINING INHIBITORS OF ALK2 KINASE
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Page/Page column 634; 635; 657; 658, (2019/01/08)
Disclosed are compounds of formula (I), (II), (III), and (IV), and pharmaceutically acceptable salts thereof. The compounds are inhibitors of ALK2 kinase. Also provided are pharmaceutical compositions comprising a compound of formula (I), (II), (III), or (IV), or pharmaceutically acceptable salt thereof, and methods involving use of the compounds or pharmaceutically acceptable salts thereof and compositions in the treatment and prevention of various diseases and conditions, such as fibrodysplasia ossificans progressiva.
1-Aryl-4-nitro-1H-imidazoles, a new promising series for the treatment of human African trypanosomiasis
Trunz, Bernadette Bourdin,Jdrysiak, Rafa?,Tweats, David,Brun, Reto,Kaiser, Marcel,Suwiński, Jerzy,Torreele, Els
experimental part, p. 1524 - 1535 (2011/05/06)
Nitroimidazoles are a well-known class of antibacterial and antiprotozoal drugs but in spite of the widespread clinical and veterinary use of these drugs, this family has been stigmatized in part due to associated genotoxicity problems. Here we report the synthesis, the anti-trypanosomal activity and a structure-activity relationship (SAR) study of a series of about fifty 1-aryl-4-nitro-1H-imidazoles, with an emphasis on selected in vivo active molecules. Compounds 4-nitro-1-{4-(trifluoromethoxy)phenyl}-1H-imidazole and 1-(3,4-dichlorophenyl)-4-nitro-1H-imidazole are curative in mouse models of both acute and chronic African trypanosomiasis when given orally at doses of 25-50 mg/kg for 4 days for the acute infection, and 50-100 mg/kg (bid) for 5 days in the chronic model. While both compounds are bacterial mutagens, activity is lost in strains lacking bacterial specific nitro-reductases. Mammalian nitro-reductases do not reduce nitroaromatic compounds with low redox potentials with same avidity as their bacterial counterparts and these compounds were shown to be devoid of genotoxicity in mammalian cells. Both compounds are promising leads for the treatment of human African trypanosomiasis (HAT or sleeping sickness), including the fatal stage 2 of the disease, for which new treatments are urgently needed.
