Detail of "88411-77-2"

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Metabolic pathways of the topical glucocorticoid budesonide in man

Metabolic pathways of the topical glucocorticoid budesonide in man. Edsbaecker, S.; Joensson, S.; Lindberg, C.; Ryrfeldt, A.; Thalen, A. (Res. Dev. Dep., AB Draco, Lund S-221 01, Swed.). Drug Metab.Several reagents with their cas registry numbers 51333-22-3 and 13951-70-7 are used here. Dispos., 11(6), 590-6 (English) 1983. CODEN: DMDSAI. ISSN: 0090-9556. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) The metabolic pathways of budesonide (I) [51333-22-3] in human liver 9000g supernatant fraction were studied. A comparison was made between the in vitro metabolite pattern and the metabolite pattern in plasma obtained after i.v. administration of tritiated I to man. No qual. difference was found, which indicates that the in vitro model is useful to predict results in vivo. The 2 major metabolites formed in vitro were identified by HPLC and mass spectrometry as 6b-hydroxybudesonide [88411-77-2] and 16a-hydroxyprednisolone [13951-70-7]. Loss of the acetal group was not obsd. when desonide was incubated with human liver 9000g supernatant fraction. Neither could 16a-hydroxyprednisolone be detected after incubation of the (22S)-epimer of I with the same medium. The cleavage of the acetal moiety is therefore suggested to be the result of a substrate-selective metabolic pathway. .

Correlation between chemical structure, receptor binding, and biological activity of some novel, highly active, 16a,17a-acetal-substituted glucocorticoids

Correlation between chemical structure, receptor binding, and biological activity of some novel, highly active, 16a,17a-acetal-substituted glucocorticoids. Dahlberg, Erik; Thalen, Arne; Brattsand, Ralph; Gustafsson, Jan Aake; Johansson, Ulf; Roempke, Karin; Saartok, Tonu (Dep. Med. Nutr., Karolinska Inst., Huddinge S-141 86, Swed.). Mol. Pharmacol., 25(1), 70-8 (English) 1984. CODEN: MOPMA3. ISSN: 0026-895X. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) The affinity for the glucocorticoid receptor in rat skeletal muscle of some glucocorticoids with a new type of 16a,17a-acetal substituent was estd. and correlated to the glucocorticoid activities in 3 in vivo systems in rats. Budesonide [51333-22-3] (an approx. 1:1 mixt. of the C(22) epimers of 11b,21-dihydroxy-16a,17a-[(22R,S)-propylmethylenedioxyl]-pregna-1, 4-diene-3,20-dione) and the isolated (22R) [51372-29-3]- and (22S)-epimers [51372-28-2] bound to the same binding site as the potent glucocorticoids dexamethasone (DEX) [50-02-2] or triamcinolone 16a,17a-acetonide (TA) [76-25-5], but with even higher affinity than DEX or TA. The (22R)-epimer was twice as active as the (22S)-epimer, 4 times more active than TA, and 14 times more active than DEX. The introduction of a 9a-fluoro atom slightly decreased the binding affinity of the (22R)-epimer of budesonide, in contrast to the pos. effect of 9a-fluorination of, e.g., 16a,17a-acetonides. The neg. influence of 9a-fluorination of the (22R)-epimer was partially reversed in the 6a,9a-difluorinated (22R)-epimer [51547-52-5]. Nevertheless, the fluorinated compds. were more active than DEX and TA. Budesonide is metabolized mainly to 16a-hydroxyprednisolone [13951-70-7] and 6b-hydroxy-budesonide [88411-77-2]. Both metabolites were very weak competitors for the ligand-binding sites on the receptor. The affinity for the receptor in vitro was closely correlated to the topical glucocorticoid activity in vivo for the 12 steroids compared, which supports the contention that in vitro tests for receptor affinity are useful when screening for agonists among steroids with the present type of structures. The results on receptor-ligand interaction are in accordance with x-ray cyrstallog. data available for some steroids.