256411-39-9Relevant articles and documents
SUBSTITUTED 1H-IMIDAZO[1, 2-B]PYRAZOLE-3-CARBOXAMIDE AS BRUTON TYROSINE KINASE INHIBITORS
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, (2022/01/24)
This invention relates to a series of compounds 1H-imidazo [1, 2-b] pyrazole-3-carboxamide substituted represented by formula I used as kinase inhibitors, in particular BTK inhibitors (Bruton tyrosine kinase), and the methods of manufacture and use thereof for the treatment of an autoimmune disease, inflammatory disease, cancer and potentially allergies.
Transformation of aldehydes into nitriles in an aqueous medium using O-phenylhydroxylamine as the nitrogen source
Cheewawisuttichai, Thamrongsak,Hurst, Robert D.,Brichacek, Matthew
, (2021/03/24)
The conversion of an aldehyde into a nitrile can be efficiently performed using O-phenylhydroxylamine hydrochloride in buffered aqueous solutions. The reported method is specifically optimized for aqueous-soluble substrates including carbohydrates. Several reducing sugars including monosaccharides, disaccharides, and silyl-protected saccharides were transformed into cyanohydrins in high yields. The reaction conditions are also suitable for the formation of nitriles from various types of hydrophobic aldehyde substrates. Furthermore, cyanide can be eliminated from cyanohydrins, analogous to the Wohl degradation, by utilizing a readily-removed weakly basic resin as a promoter.
Structure-activity relationship study of tryptophan-based butyrylcholinesterase inhibitors
Brazzolotto, Xavier,Gobec, Stanislav,Gro?elj, Uro?,Knez, Damijan,Malikowska-Racia, Natalia,Meden, An?e,Nachon, Florian,Sa?at, Kinga,Svete, Jurij
, (2020/09/15)
A series of tryptophan-based selective nanomolar butyrylcholinesterase (BChE) inhibitors was designed and synthesized. Compounds were optimized in terms of potency, selectivity, and synthetic accessibility. The crystal structure of the inhibitor 18 in complex with BChE revealed the molecular basis for its low nanomolar inhibition (IC50 = 2.8 nM). The favourable in vitro results enabled a first-in-animal in vivo efficacy and safety trial, which demonstrated a positive impact on fear-motivated and spatial long-term memory retrieval without any concomitant adverse motor effects. Altogether, this research culminated in a handful of new lead compounds with promising potential for symptomatic treatment of patients with Alzheimer's disease.