Glucuronide conjugates of Soraprazan (BY359), a new potassium-competitive acid blocker (P-CAB) for the treatment of acid-related diseases

Autor:	Rolf-Peter Hummel, Reinhard Huber, John R. Ferguson, Senn-Bilfinger Joerg, Karl Zech, Michael A. Holmes, Zimmermann Peter Jan, Keith W. Lumbard
Rok vydání:	2006
Předmět:	Organic Chemistry Hydrazine Glucuronidation Biochemistry Combinatorial chemistry chemistry.chemical_compound Hydrolysis Aglycone chemistry Trimethylsilyl trifluoromethanesulfonate Drug Discovery Organic chemistry Reactivity (chemistry) Lewis acids and bases Glucuronide
Zdroj:	Tetrahedron Letters. 47:3321-3323
ISSN:	0040-4039
DOI:	10.1016/j.tetlet.2006.02.156
Popis:	Glucuronide conjugates of Soraprazan (BY359), a potent novel anti-secretory drug (currently in Phase II clinical trials), were not directly accessible synthetically. This was due to the relative instability of Soraprazan under the harsh Lewis acid conditions employed in popular glucuronidation methodologies and a lack of reactivity under alternative, Koenigs–Knorr, coupling conditions. We have now devised a successful synthesis using the novel N-acetylated Soraprazan to access the required glucuronide metabolites on gram scale. Coupling of this novel aglycone with methyl 1- O -trichloroacetimidoyl-2,3,5-tri- O -isobutyryl-α- d -glucopyran-uronate in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) gave the protected glucuronide intermediates. A one-pot two-step deprotection involving hydrolysis of the ester functionalities and removal of the N -acetyl group with alkaline hydrazine delivered the title compounds in satisfactory yield.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::b010f5bd0890f5f5486f10c06aae65ba https://doi.org/10.1016/j.tetlet.2006.02.156 Zobrazit plný text záznamu Full Text from ScienceDirect