17-Heteroaroyl esters of corticosteroids. 2. 11.beta.-Hydroxy series

Abstract

The preparation and topical antiinflammatory potencies of a series of 17-furoyl and -thenoyl esters of 9 alpha-fluoro-11 beta-hydroxy-16 methyl and 9 alpha-chloro-11 beta-hydroxy-16-methyl corticosteroids are described. The 17 alpha-esters were introduced to the 9 alpha-fluoro 11-ketones or to the appropriate delta 9(11) compounds by direct acylation with the appropriate heteroaryl carbonyl chloride in the presence of 4-(dimethylamino)pyridine. Functionalization of the C ring was completed by standard methods. The most extensively studied heterocyclic acyl group was 2-furoyl, but 3-furoyl and 2- and 3-thenoyl derivatives were also investigated. Antiinflammatory potencies were measured in mice by a 5-day modification of the Tonelli croton oil ear assay. The most potent topical antiinflammatory agents were 1e, dexamethasone 17-(2'-furoate) 21-propionate, and 2c, the 21-chloro 17-(2'-furoate) in the 9 alpha-chloro series, both being 6 times as potent as betamethasone 17-valerate. Several other 9 alpha-chloro-11 beta-hydroxy-17-heteroaryl carboxylates (2a, 2b, 2d, and 2g) were at least 4 times as potent as betamethasone 17-valerate. Evaluation of 2c in the clinic confirmed that the compound is a potent topical antiinflammatory agent in humans.

Solid state characterization of mometasone furoate anhydrous and monohydrate forms

“…The X-ray single crystal analysis agrees with the proposed structure and stereochemistry of the mometasone furoate molecule. 9 Bond lengths and bond angles are in the expected ranges. For the molecule structure, both forms have similar conformations.…”

Effects of Mometasone Furoate on Human Keratinocytes and Fibroblasts in vitro

“…In the past, clinical trials have shown that the antiinflammatory potential of MF is similar to triamcinolone [13,14] and stronger than the efficacy of betamethasone [9,10]. Therefore, MF was introduced as a member of the subgroup of glucocorticosteroids with high clinical efficacy.…”

“…In recent years, a number of new corticosteroids have been developed. Mometasone furoate (MF) has been introduced as a very potent corticosteroid associated with a low risk of systemic and topical side effects [9,10]. In the past, many clinical studies confirmed the efficacy in inflammatory skin diseases accompanied by low and rare adverse effects [11][12][13][14][15][16].…”

Mometasone furoate in the treatment of atopic dermatitis in children

“…topical corticosteroid [3] which has been shown to possess high anti-inflammatory activity and improved local and systemic tolerability [4][5].…”