259667-65-7Relevant academic research and scientific papers
Design and synthesis of novel lactate dehydrogenase a inhibitors by fragment-based lead generation
Ward, Richard A.,Brassington, Claire,Breeze, Alexander L.,Caputo, Alessandro,Critchlow, Susan,Davies, Gareth,Goodwin, Louise,Hassall, Giles,Greenwood, Ryan,Holdgate, Geoffrey A.,Mrosek, Michael,Norman, Richard A.,Pearson, Stuart,Tart, Jonathan,Tucker, Julie A.,Vogtherr, Martin,Whittaker, David,Wingfield, Jonathan,Winter, Jon,Hudson, Kevin
, p. 3285 - 3306 (2012)
Lactate dehydrogenase A (LDHA) catalyzes the conversion of pyruvate to lactate, utilizing NADH as a cofactor. It has been identified as a potential therapeutic target in the area of cancer metabolism. In this manuscript we report our progress using fragment-based lead generation (FBLG), assisted by X-ray crystallography to develop small molecule LDHA inhibitors. Fragment hits were identified through NMR and SPR screening and optimized into lead compounds with nanomolar binding affinities via fragment linking. Also reported is their modification into cellular active compounds suitable for target validation work.
6-HETEROARYLOXY BENZIMIDAZOLES AND AZABENZIMIDAZOLES AS JAK2 INHIBITORS
-
Paragraph 0359; 0360, (2021/11/13)
The present disclosure provides 6-heteroaryloxy benzimidazole and azabenzimidazole compounds and compositions thereof useful for inhibiting JAK2.
Oxindole derivative
-
, (2008/06/13)
An oxindole of Formula 1 or a prodrug thereof, or a pharmaceutically acceptable salt thereof is useful for growth hormone releaser: wherein R1, R2, R3and R4are independently hydrogen, optionally substituted alkyl etc; R5is optionally substituted aryl or optionally substituted heteroaryl; Z is —O— or —NH—; one of W1and W2is hydrogen, alkyl or —Y—CON(R10)R11; the other of W1and W2is n is 1, 2 or 3; m is 0, 1, 2 or 3; Y is single bond or C1-C3alkylene; R6and R7are independently hydrogen, optionally substituted alkyl etc; R8and R9are independently hydrogen, optionally substituted alkyl etc; R10and R11are independently hydrogen, alkyl etc.
A concise and regioselective synthesis of 6-iodo-4-trifluoromethylisatin, an intermediate in the synthesis of the novel, non-peptidyl growth hormone secretagogue SM-130686
Ewan Hume,Tokunaga, Teruhisa,Nagata, Ryu
, p. 3605 - 3611 (2007/10/03)
The synthesis of 6-iodo-4-trifluoromethylisatin, an intermediate in the synthesis of the growth hormone secretagogue SM-130686, is disclosed. The synthesis is achieved in seven steps, with an overall yield of 32%, and requires a single recrystallisation as the only purification step. 2-Methyl-3-nitrobenzotrifluoride was converted to (4-iodo-6-nitro-2-trifluoromethylphenyl)acetic acid via iodination, condensation with dimethyloxalate and oxidative decarboxylation. Subsequent esterification followed by reductive cyclisation gave 6-iodo-4-trifluoromethyloxindole. Oxindole 3,3-dibromination followed by hydrolysis gave 6-iodo-4-trifluoromethylisatin.
