1048669-31-3

Upstream product

• 15029-38-6 2-cyano-N-cyclohexylacetamide 
• 122-51-0 orthoformic acid triethyl ester 

Downstream Products

• 1048669-32-4 methyl 3-[5-amino-4-(cyclohexylcarbamoyl)pyrazol-1-yl]benzoate 
• 1048669-30-2 methyl 4-[5-amino-4-(cyclohexylcarbamoyl)pyrazol-1-yl]benzoate 
• 1048668-50-3 methyl 3-[4-(cyclohexylcarbamoyl)-5-propylsulfanyl-pyrazol-1-yl]benzoate 
• 1048668-48-9 methyl 4-[4-(cyclohexylcarbamoyl)-5-propylsulfanyl-pyrazol-1-yl]benzoate 
• 1048669-29-9 methyl 3-[5-chloro-4-(cyclohexylcarbamoyl)pyrazol-1-yl]benzoate 
• 1048669-28-8 methyl 4-[5-chloro-4-(cyclohexylcarbamoyl)pyrazol-1-yl]benzoate 
• 1048668-49-0 3-[4-(cyclohexylcarbamoyl)-5-propylsulfanyl-pyrazol-1-yl]benzoic acid 
• 1048668-47-8 4-[4-(cyclohexylcarbamoyl)-5-propylsulfanyl-pyrazol-1-yl]benzoic acid 

Relevant academic research and scientific papers

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)

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.

Synthesis, characterisation and antimicrobial activity of thiazole, bisthiazole, pyridone and bispyridone derivatives

N-cyclohexyl-2-cyano-acetamide was reacted with phenyl isothiocyanates and sulfur to give thiazolidine and bisthiazolidine derivatives. Treatment of N-cyclohexyl-2-cyanoacetamide with phenyl isothiocyanate and KOH followed by in situ heterocyclisation with a-halo compounds gave thiazole derivatives. Treatment of N-cyclohexyl-2-cyanoacetamides with cinnamonitriles gave pyridone and bispyridone derivatives. N-cyclohexyl-2-cyanoacetamide coupled smoothly with benzene-diazonium chloride in pyridine. Cyclocondensation of N-cyclohexyl-2-cyanoacetamide with acetylacetone gave 1,1'-(ethane-1,2-diyl) bis(4,6-dimethyl-2-oxo-1,2-dihydropyridine-3-carbonitrile). Ternary condensation of N-cyclohexyl-2-cyanoacetamide, malononitrile and acetaldehyde gave a bispyridone derivative. Some of the new compounds were tested against bacteria and some fungi.

PYRAZOLE DERIVATIVES AS 11-BETA-HSD1 INHIBITORS

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.