1048668-70-7Relevant academic research and scientific papers
A greener approach for the large-scale synthesis of 1,4,5-trisubstituted pyrazole, AZD8329
Rangappa, Paramashivappa,Ghosh, Avipsa,Chitrapadi, Smitha,Kantikar, Gajanan,Ch, Vinod Kumar,Sythana, Sureshkumar,Manjunath, Sulur G.,Nambiar, Sudhir,Sridhran
, p. 947 - 951 (2014)
The development of a convenient, safe and scalable process for AZD8329 manufacturing is reported here. Synthesis was achieved in a two-step telescopic process with an excellent overall yield of 75%. In the first step enamine (6) was synthesized with 90% yield through three chemical transformations. In the next step AZD8329 was synthesized from the reactions of 6 and 4-hydrazinobenzoic acid hydrochloride 7 through two chemical transformations. The process is very efficient and economical, and AZD8329 was manufactured in multikilogram scale. A greener approach is demonstrated through usage of a minimum number of solvents and energy and with process mass intensity (PMI) 60 in the manufacturing process.
Novel acidic 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor with reduced acyl glucuronide liability: The discovery of 4-[4-(2-adamantylcarbamoyl)-5-tert-butyl-pyrazol-1-yl]benzoic acid (AZD8329)
Scott, James S.,Deschoolmeester, Joanne,Kilgour, Elaine,Mayers, Rachel M.,Packer, Martin J.,Hargreaves, David,Gerhardt, Stefan,Ogg, Derek J.,Rees, Amanda,Selmi, Nidhal,Stocker, Andrew,Swales, John G.,Whittamore, Paul R.O.
, p. 10136 - 10147 (2013/01/16)
Inhibition of 11β-HSD1 is viewed as a potential target for the treatment of obesity and other elements of the metabolic syndrome. We report here the optimization of a carboxylic acid class of inhibitors from AZD4017 (1) to the development candidate AZD8329 (27). A structural change from pyridine to pyrazole together with structural optimization led to an improved technical profile in terms of both solubility and pharmacokinetics. The extent of acyl glucuronidation was reduced through structural optimization of both the carboxylic acid and amide substituents, coupled with a reduction in lipophilicity leading to an overall increase in metabolic stability.
NOVEL PROCESS FOR PREPARING CARBOXY-CONTAINING PYRAZOLEAMIDO COMPOUNDS 597
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Page/Page column 25-26, (2010/08/09)
A process for preparing pharmaceutically acceptable compounds of formula (I) wherein R1, R2, R3, X, A and Y are as defined in the specification is described and claimed, together with processes for preparing some key inter
PYRAZOLE DERIVATIVES AS 11-BETA-HSD1 INHIBITORS
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Page/Page column 59-60, (2008/12/08)
A compound of formula (I): and pharmaceutically -acceptable salts thereof wherein the variable groups are defined within; their use in the inhibition of 11βHSD1, processes for making them and pharmaceutical compositions comprising them are also described.
