{"id":454,"date":"2024-04-28T23:43:13","date_gmt":"2024-04-28T23:43:13","guid":{"rendered":"https:\/\/src.cikeys.com\/2024\/?page_id=454"},"modified":"2024-04-28T23:43:13","modified_gmt":"2024-04-28T23:43:13","slug":"synthesis-and-anti-inflammatory-activity-of-prodrugs-of-dexamethasone-and-related-fluorinated-corticosteroid-analogs","status":"publish","type":"page","link":"https:\/\/src.cikeys.com\/2024\/conference-schedule\/poster-presentations\/poster-presentations-session-2\/synthesis-and-anti-inflammatory-activity-of-prodrugs-of-dexamethasone-and-related-fluorinated-corticosteroid-analogs\/","title":{"rendered":"Synthesis and Anti-Inflammatory Activity of Prodrugs of Dexamethasone and Related Fluorinated Corticosteroid Analogs"},"content":{"rendered":"\n

Grace Yu, Arshia Desarkar, Terry Wang, Jennifer Luo, & Dr. Edward Njoo<\/h2>\n\n\n\n
\n
\n

Since the initial success of fluorinated corticosteroids, many have been investigated for their potent anti-inflammatory activities and improved pharmacokinetic profiles. In particular, dexamethasone received FDA approval in 1958 for the treatment of inflammatory conditions like arthritis, asthma, eczema, and sclerosis. Though fluorination of corticosteroids has demonstrated elongation of metabolic half-life, dosing challenges remain where a prodrug would be useful. As glucocorticosteroids bind to the glucocorticoid receptor at the C-3 ketone, C-11 alcohol, and C-22 alcohol, modification of these locations would hinder binding to the receptor and increase the length of their metabolism. Inspired by prednisolone, a corticosteroid frequently delivered as its C-11 oxidized prodrug prednisone, we attempted a similar synthetic strategy of prodrugging through the oxidation of the secondary alcohol at C-11 into a ketone to increase the half-life of C-9 fluorinated steroids such as dexamethasone, fluocinolone acetonide, triamcinolone acetonide, betamethasone, and fludrocortisone. This prodrugging strategy is atom economical, generalizable to the 11-hydroxysteroid scaffold, and yields no potentially toxic byproducts. Additionally, the structural verification of these oxidized steroids was performed through the use of LCMS, 1H, and 19F Benchtop NMR. These compounds are currently being evaluated for catabolic dehydrogenation through HPLC, where we anticipate dehydrogenase activity by the liver enzyme 11\u03b2-hydroxysteroid dehydrogenase at the aforementioned C-11 scaffold. If successful, the library of five fluorinated steroids presented would be the first successful examples of 11-oxyfluorocorticosteroid prodrugs.<\/p>\n<\/div>\n\n\n\n

\n

Poster Presentation<\/a><\/strong><\/p>\n\n\n\n

Session 2<\/a><\/p>\n\n\n\n

1:00pm \u2013<\/strong> 2:15pm
Grand Salon<\/p>\n\n\n\n

Chemistry<\/strong><\/p>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

Grace Yu, Arshia Desarkar, Terry Wang, Jennifer Luo, & Dr. Edward Njoo Since the initial success of fluorinated corticosteroids, many have been investigated for their potent anti-inflammatory activities and improved pharmacokinetic profiles. In particular, dexamethasone received FDA approval in 1958 for the treatment of inflammatory conditions like arthritis, asthma, eczema, and sclerosis. Though fluorination of […]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":47,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"categories":[5,7],"tags":[29],"class_list":["post-454","page","type-page","status-publish","hentry","category-poster-presentations","category-session-2","tag-chemistry","post"],"_links":{"self":[{"href":"https:\/\/src.cikeys.com\/2024\/wp-json\/wp\/v2\/pages\/454","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/src.cikeys.com\/2024\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/src.cikeys.com\/2024\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/src.cikeys.com\/2024\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/src.cikeys.com\/2024\/wp-json\/wp\/v2\/comments?post=454"}],"version-history":[{"count":1,"href":"https:\/\/src.cikeys.com\/2024\/wp-json\/wp\/v2\/pages\/454\/revisions"}],"predecessor-version":[{"id":552,"href":"https:\/\/src.cikeys.com\/2024\/wp-json\/wp\/v2\/pages\/454\/revisions\/552"}],"up":[{"embeddable":true,"href":"https:\/\/src.cikeys.com\/2024\/wp-json\/wp\/v2\/pages\/47"}],"wp:attachment":[{"href":"https:\/\/src.cikeys.com\/2024\/wp-json\/wp\/v2\/media?parent=454"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/src.cikeys.com\/2024\/wp-json\/wp\/v2\/categories?post=454"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/src.cikeys.com\/2024\/wp-json\/wp\/v2\/tags?post=454"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}