1994
DOI: 10.1002/jps.2600830406
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Novel Fluorinated Antiinflammatory Steroid with Reduced Side Effects: Methyl 9α-Fluoroprednisolone-16-carboxylate

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Cited by 12 publications
(11 citation statements)
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“…Corticosterone was measured as a marker for suppression of the hypothalamo-pituitaryadrenal axis using a radioimmunoassay with rabbit CpdB antibody T54 (antigen: corticosterone 3-carboxymethyloxime-bovine serum albumin; raised in rabbit) (laboratory production) after extraction with dichloromethane. Another marker of adverse systemic effects, which is possible to be monitored in animals, is thymic atrophy [15,16]. Therefore, the thymus was removed to be weighed.…”
Section: Outcome Measuresmentioning
confidence: 99%
“…Corticosterone was measured as a marker for suppression of the hypothalamo-pituitaryadrenal axis using a radioimmunoassay with rabbit CpdB antibody T54 (antigen: corticosterone 3-carboxymethyloxime-bovine serum albumin; raised in rabbit) (laboratory production) after extraction with dichloromethane. Another marker of adverse systemic effects, which is possible to be monitored in animals, is thymic atrophy [15,16]. Therefore, the thymus was removed to be weighed.…”
Section: Outcome Measuresmentioning
confidence: 99%
“…Compound 51 was found not to degrade in rat or human plasma over 30 min at 37 C, indicating that the C-21 methyl ester, which is sterically strongly hindered in these structures, is stable to plasma esterases under these conditions. "Antedrug" Steroids Various, mostly prednisolone-based ester derivatives, were synthesized and investigated in a series of attempts designated as "antedrug" designs [53,54,[211][212][213][214][215][216][217][218][219]. They were aimed to improve the local-to-systemic activity ratio of antiinflammatory steroids and may be considered as SD designs based on hypothetical inactive metabolites.…”
Section: Softmentioning
confidence: 99%
“…They were aimed to improve the local-to-systemic activity ratio of antiinflammatory steroids and may be considered as SD designs based on hypothetical inactive metabolites. Studied compounds include ester derivatives of steroid 21-oic acids [53], a number of 16a-carboxylate analogs (e.g., 52) [54,[211][212][213]216,220], 6-carboxylate analogs [214], and (16a,17a-d) isoxazolines derivatives [215,217,218]. Some of these compounds were found to have relatively low activity, similar to that of hydrocortisone or prednisolone, and they also achieved some, but not very significant, improvement in the local-to-systemic activity ratio.…”
Section: Softmentioning
confidence: 99%
“…Among patients with changes in plasma cortisol, 56% were in the hydrocortisone-17-butyrate group and 27% were in the FP group [29]. Although the 9·-fluorination enhances all the biological activities of glucocorticoids, a concomitant increase in adverse systemic effects could not be reported [4].…”
Section: Potential For Systemic Adverse Eventsmentioning
confidence: 99%
“…1). The two esterifications at position 17 (with a propionate group) and at position 20 (with a fluorized thio ester, named 'carbothioate') highly increase the molecule's natural lipophilicity, its cutaneous drug uptake and its binding to human skin tissue [3] as well as to the glucocorticoid receptor (GR), a 777-aminoacid protein member of the superfamily of ligand-receptor nuclear receptors [4]. X-ray crystallographic investigations revealed that the carbonyl of the 17ß-carbothioate ester substituent lies below the plane of ring D rather than above, as observed for other corticosteroids, and might explain the rapid enzymatic hydrolysis of FP to its inactive metabolite [5].…”
Section: Chemical Structure and Glucocorticoid Receptor Affinitymentioning
confidence: 99%