1250-85-7

Usage

Uses

21-Acyloxycorticosteroid derivative. Antiinflammatory.

Upstream product

• 39987-51-4 1,4-pregnane-9α-fluoro-11β,17α,21-triol-3,20-dione 17,21-diacetate 
• 338-95-4 isoflupredone 
• 338-98-7 isoflupredone acetate 
• 3793-90-6 Acetic acid (8S,9R,10S,11S,13S,14S,17R)-9-fluoro-11-hydroxy-17-(2-hydroxy-acetyl)-10,13-dimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl ester 
• 40627-86-9 C₂₅H₃₃FO₆ 

Downstream Products

• 69291-31-2 Acetic acid 2-((1S,3R,4aS,4bS,10aS,10bR,11S,12aS)-10b-fluoro-1,11-dihydroxy-3-methoxy-10a,12a-dimethyl-8-oxo-3,4,4a,4b,5,6,8,10a,10b,11,12,12a-dodecahydro-1H-2-oxa-chrysen-1-yl)-2-oxo-ethyl ester 
• 83291-85-4 Acetic acid 2-((4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS)-8-benzyl-4b-fluoro-5-hydroxy-4a,6a-dimethyl-2-oxo-2,4a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-6b-yl)-2-oxo-ethyl ester 
• 152596-59-3 methyl 9α-fluoro-11β,21-dihydroxy-3,20-dioxo-pregna-1,4-diene-16α-carboxylate 
• 69283-62-1 Acetic acid 2-((1S,3R,4aS,4bS,10aS,10bR,11S,12aS)-10b-fluoro-11-hydroxy-1,3-dimethoxy-10a,12a-dimethyl-8-oxo-3,4,4a,4b,5,6,8,10a,10b,11,12,12a-dodecahydro-1H-2-oxa-chrysen-1-yl)-2-oxo-ethyl ester 
• 3859-65-2 (11β,16α)-21-acetyloxy-9-fluoro-11,16,17-trihydroxypegna-1,4-diene-3,20-dione 
• 911437-91-7 triamcinolone acetonide 

Relevant academic research and scientific papers

New steroidal anti-inflammatory antedrugs: Methyl 3,20-dioxo-9α- fluoro-11β,17α,21-trihydroxy-1,4-pregnadiene-16α-carboxylate and methyl 21-acetyloxy-3,20-dioxo-11β,17α-dihydroxy-9α-fluoro-1,4-pregnadiene-16α- carboxylate

Focused efforts have been made to increase local-to-systemic activity ratios of potent anti-inflammatory steroids for local and/or topical applications. The approach taken in the present investigation is based upon the concept of 'antedrug,' defined as a locally active compound that exerts its action at the application site but rapidly undergoes a predictable biotransformation to an inactive metabolite that is readily excreted upon entry into the systemic circulation. In continuing efforts to synthesize potent, anti-inflammatory steroids without systemic glucocorticoid activities, 9α-flouro-methyl11β,17α,21-trihydroxy-3,20-dioxo-pregna-1,4- diene-16α-carboxylate (FP16CM) and its 21-acetate derivative (FP16CMAc) have been synthesized and screened. Novel antedrugs were evaluated for antiinflammatory activity in the acute croton oil-induced ear edema bioassay, adverse systemic effects in the 5-day croton oil model, receptor binding, and concomitant L-tyrosine-2-oxoglutarate aminotransferase (EC 2.6.1.5) (TAT) enzyme induction in HTC cells in culture. Following a single topical application in the croton oil-induced ear edema bioassay, treatment with all compounds resulted in dose-dependent inhibition of edema. From these dose- response profiles, the following ID50 values (nmol resulting in a 50% reduction of edema) were calculated: 817, 540, 266, and 67 for hydrocortisone (HC), prednisolone (P), FP16CM, and FP16CMAc, respectively. Calculated relative potencies, setting HC = 1.0, were P, 1.5; FP16CM, 3.1, and FP16CMAc, 12.2. Results of the 5-day rat croton oil ear edema bioassay indicated that, in contrast to the parent compound P, the novel steroidal antedrugs did not significantly alter body weight gain, thymus weights, or plasma corticosterone levels. Relative binding potencies for cytosolic HTC glucocorticoid receptors were 1.0, 20.1, 5.4, and 2.5 for HC, P, FP16CM, and FP16CMAc, respectively. As predicted by the antedrug concept, FP16CM and FP16CMAc were very weak agonists for induction of TAT in HTC cells. Collectively, results of these investigations suggest that modifications of P, which included addition of the 9-fluoro and 16-methoxycarbonyl group alone or in conjunction with a 21-acetoxy moiety, increase topical anti- inflammatory activity without significant adverse systemic effects. These new antedrugs may be useful as anti-inflammatory steroids for local applications.

Synthesis method of triamcinolone acetonide

The invention provides a synthesis method of triamcinolone acetonide, and relates to the technical field of chemical synthesis. The synthesis method of triamcinolone acetonide comprises the followingsteps: (a) carrying out dehydration reaction on a compound shown as a formula I under the action of an alkali reagent to obtain a compound shown as a formula II; (b) carrying out oxidation reaction onthe compound shown in the formula II to obtain a compound shown in a formula III; (c) carrying out epoxy reaction on the compound shown in the formula III and acetone under the action of an acid reagent to obtain a compound shown in a formula IV; and (d) carrying out hydrolysis reaction on the compound shown in the formula IV under the action of an alkali reagent to obtain a compound shown in theformula V. According to the synthesis method of triamcinolone acetonide provided by the invention, the triamcinolone acetonide is obtained through dehydration reaction, oxidation reaction, epoxy reaction and hydrolysis reaction by taking the compound shown as the formula I as an initial raw material, the reaction raw materials are cheap and easy to obtain, the reaction conditions are mild, the synthesis route is greatly shortened, and the yield of the product is increased.

Novel fluorinated antiinflammatory steroid with reduced side effects: Methyl 9α-fluoroprednisolone-16-carboxylate

In an effort to test the hypothesis that 9α-fluorination of a steroidal antedrug would enhance receptor binding affinity and local antiinflammatory activity, without concomitantly increasing adverse systemic effects, a fluorinated analog, 10, of methyl 11β,21-dihydroxy-3,20-dioxo-1,4- pregnadiene-16α-carboxylate (DP16CM, 1) was synthesized and evaluated. In the acute rat croton oil-induced ear edema bioassay. 10 was found to be twice as potent as 1. This increase in topical potency was consistent with enhanced binding affinity of 10, relative to 1. The IC50 values for displacement of [3H] dexamethasone from glucocorticoid receptors of rat hepatoma tissue culture cells were 0.16, 1.2, and 0.03 μM for 10, 1, and prednisolone, respectively. Following multiple topical ID50 applications of prednisolone, 1, and its new fluorinated analog, 10, in the rat subacute croton oil- induced ear edema bioassay, only prednisolone exhibited significant untoward effects, such as reduction in relative thymus and adrenal weights, plasma corticosterone levels, and normal body weight gain. Thus, while fluorination of 1 enhanced its topical potency, there was not a concomitant increase in untoward systemic effects. This lack of adverse systemic effects is ostensibly due to the presence of the metabolically labile 16-carboxylate ester moiety.

Synthesis and Topical Antiinflamatory Activity of Some Steroidal Isoxazolidines

1,3-Dipolar cycloaddition of N-methylnitrone, N-benzylnitrone, and pyrroline N-oxide to 1,4,16-pregnatriene-3,20-diones is described.In each case only isoxazolidines were isolated.The pentacyclic adducts 16-19 were active topical antiinflammatory agents in mice, with 18 being more potent than any of the standard compound tested.The hexacyclic adduct 20 was inactive in this assay.