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Chem."],"accepted":{"date-parts":[[2024,8,29]]},"abstract":"<jats:p>\n                    The utility of bio-isosteres is broad in drug discovery and methodology herein enables the preparation of deuterium-labeled products is the most fundamental of known bio-isosteric replacements. As such we report the use of both [D\n                    <jats:sub>1<\/jats:sub>\n                    ]-aldehydes and [D\n                    <jats:sub>2<\/jats:sub>\n                    ]-isonitriles across 8 multicomponent reactions (MCRs) to give diverse arrays of deuterated products. A highlight is the synthesis of several FDA-approved calcium channel blockers, selectively deuterated at a\n                    <jats:italic>t<\/jats:italic>\n                    <jats:sub>1\/2<\/jats:sub>\n                    limiting metabolic soft-spot via use of [D\n                    <jats:sub>1<\/jats:sub>\n                    ]-aldehydes. Surrogate pharmacokinetic analyses of microsomal stability confirm prolongation of\n                    <jats:italic>t<\/jats:italic>\n                    <jats:sub>1\/2<\/jats:sub>\n                    of the new deuterated analogs. We also report the first preparation of [D\n                    <jats:sub>2<\/jats:sub>\n                    ]-isonitriles from [D\n                    <jats:sub>3<\/jats:sub>\n                    ]-formamides via a modified Leuckart\u2013Wallach reaction and their use in an MCR to afford products with [D\n                    <jats:sub>2<\/jats:sub>\n                    ]-benzylic positions and likely significantly enhanced metabolic stability, a key parameter for property-based design efforts.\n                  <\/jats:p>","DOI":"10.3762\/bjoc.20.195","type":"journal-article","created":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T07:32:36Z","timestamp":1725607956000},"page":"2270-2279","source":"Crossref","is-referenced-by-count":4,"title":["Deuterated reagents in multicomponent reactions to afford deuterium-labeled 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