Selectivity and Physicochemical Optimization of Repurposed Pyrazolo[1,5-b]pyridazines for the Treatment of Human African Trypanosomiasis was written by Tear, Westley F.;Bag, Seema;Diaz-Gonzalez, Rosario;Ceballos-Perez, Gloria;Rojas-Barros, Domingo I.;Cordon-Obras, Carlos;Perez-Moreno, Guiomar;Garcia-Hernandez, Raquel;Martinez-Martinez, Maria Santos;Ruiz-Perez, Luis Miguel;Gamarro, Francisco;Gonzalez Pacanowska, Dolores;Caffrey, Conor R.;Ferrins, Lori;Manzano, Pilar;Navarro, Miguel;Pollastri, Michael P.. And the article was included in Journal of Medicinal Chemistry in 2020.Related Products of 19064-65-4 This article mentions the following:
From a high-throughput screen of 42 444 known human kinases inhibitors, a pyrazolo[1,5-b]pyridazine scaffold was identified to begin optimization for the treatment of human African trypanosomiasis. Previously reported data for analogous compounds against human kinases GSK-3β, CDK-2, and CDK-4 were leveraged to try to improve the selectivity of the series, resulting in 23a which showed selectivity for T. b. brucei over these three human enzymes. In parallel, properties known to influence the absorption, distribution, metabolism, and excretion (ADME) profile of the series were optimized resulting in 20g being progressed into an efficacy study in mice. Though 20g showed toxicity in mice, it also demonstrated CNS penetration in a PK study and significant reduction of parasitemia in four out of the six mice. In the experiment, the researchers used many compounds, for example, 3-Methoxypyridazine (cas: 19064-65-4Related Products of 19064-65-4).
3-Methoxypyridazine (cas: 19064-65-4) belongs to pyridazine derivatives. Pyridazines is a six-membered nitrogen-containing significant heterocycle. It has received considerable interest because of its useful applications as natural products, pharmaceuticals, and various bioactive molecules. Pyridazine can act as a hydrogen bond acceptor to improve the physicochemical properties of drug molecules by increasing their water solubility, and has a high affinity for complexing with targets due to its dipole moment.Related Products of 19064-65-4
Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem