80473-92-3

Usage

Chemical Properties

White solid

InChI:InChI=1/C21H26F2O4S/c1-10-6-12-13-8-15(22)14-7-11(24)4-5-18(14,2)20(13,23)16(25)9-19(12,3)21(10,27)17(26)28/h4-5,7,10,12-13,15-16,25,27H,6,8-9H2,1-3H3,(H,26,28)/t10?,12?,13-,15?,16-,18-,19-,20?,21?/m0/s1

Upstream product

• 2135-17-3 flumetasone 
• 28416-82-2 6α,9α-difluoro-11β,17α-dihydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-carboxylic acid 
• 709002-84-6 17β-N,N-dimethylthiocarbamoyloxycarbonyl-6α,9α-difluoro-11β,17α-dihydroxy-16α-methyl-3-oxoandrosta-1,4-diene 

Downstream Products

• 80474-45-9 17-propionate carbothioic acid 
• 87556-66-9 C₂₂H₂₇ClF₂O₄S 
• 397864-44-7 fluticasone furoate 
• 80474-67-5 S-iodomethyl-6α,9α-difluoro-11β-hydroxy-16α-methyl-17α-propionyloxy-3-oxo-androsta-1,4-diene-17β-carbothioate 
• 80486-69-7 S-chloromethyl 6α,9α-difluoro-11β-hydroxy-16α-methyl-3-oxo-17α-propionyloxyandrosta-1,4-diene-17β-carbothioate 
• 80474-24-4 S-fluoromethyl 17α-acetoxy-6α,9α-difluoro-11β-hydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-carbothioate 
• 80474-14-2 flixotide 

Relevant academic research and scientific papers

GLUCOCORTICOID RECEPTOR AGONIST AND IMMUNOCONJUGATES THEREOF

Provided herein are glucocorticoid receptor agonist immunoconjugates, glucocorticoid receptor agonists, pharmaceutical compositiosn including the same, and methods of using the same.

METHOD FOR PREPARING FLUTICASONE FUROATE

Method for preparing fluticasone furoate (6α,9α-difluoro-11β-hydroxy-16α-methyl-17α-[(2-furoyl)oxy]-3-oxo-androsta-1,4-diene-17β-carbothioic acid S-fluoromethyl ester) by directly subjecting a compound of Formula III and a complex of a fluoromethylating reagent in presence of an organic base to a replacement reaction to obtain the target compound. Generation of impurities in a process via Compound IV is avoided; the method is simple with mild reaction conditions, suitable for industrial production, and yields products with purity of 98% by HPLC.

17.BETA- (ALPHA-HYDROXY) -ESTERS OF ANDROSTANES AS INTERMEDIATES FOR THE PREPARATION FOR THE PREPARATION OF 17Β-FLUORINATED-ANDROSTANE ESTERS

Process for the preparation of polyhalogenated steroids, in particular of androstanic fluoro derivatives corticosteroids by means of the formation of new androstanic S-hydroxy alkyl or aralkyl-17-carbothioate intermediates.

Synthesis and structure-activity relationships in a series of antiinflammatory corticosteroid analogues, halomethyl androstane-17β- carbothioates and -17β-carboselenoates

The preparation and topical antiinflammatory potencies of a series of halomethyl 17α-(acyloxy)-11β-hydroxy-3-oxoandrosta-1,4-diene-17β- carbothioates, carrying combinations of 6α-fluoro, 9α-fluoro, 16-methyl, and 16-methylene substituents, are described. Key synthetic stages were the preparation of carbothioic acids and their reaction with dihalomethanes. The carbothioic acids were formed from 17β-carboxylic acids by initial reaction with dimethylthiocarbamoyl chloride followed by aminolysis of the resulting rearranged mixed anhydride with diethylamine, or by carboxyl activation with 1,1'-carbonyldiimidazole (CDI) or 2-fluoro-N-methylpyridinium tosylate (FMPT) and reaction with hydrogen sulfide, the choice of reagent being governed by the 17α-substituent. Carboxyl activation with FMPT and reaction with sodium hydrogen selenide led to the halomethyl 16-methyleneandrostane-17β- carboselenoate analogues. Anti-inflammatory potencies were measured in humans using the vasoconstriction assay and in rats and mice by a modification the Tonelli croton oil ear assay. Best activities were shown by fluoromethyl and chloromethyl carbothioates with a 17α-propionyloxy group. S-Fluoromethyl 6α,9α-difluoro-11β-hydroxy-16α-methyl-3-oxo-17α-(propionyloxy)androsta- 1,4-diene-17β-carbothioate (fluticasone propionate, FP) was selected for clinical study as it showed high topical antiinflammatory activity but caused little hypothalamic-pituitary-adrenal suppression after topical or oral administration to rodents.

Androstane carbothioic acids

Androstane carbothioic acids of the formula: STR1 wherein R1 represents a hydrogen atom, a hydroxy group in the α-configuration, a methyl group which may be in either the α- or β-configuration, or a methylene group; R2 represents a hydroxy or protected hydroxy group in either the α- or β-configuration or an oxo group; R3 represents a hydrogen, bromine, chlorine or fluorine atom; or R2 and R3 together represent a carbon-carbon bond or an epoxy group in the β-configuration; R4 represents a hydrogen or fluorine atom; and the symbol represents a single or double bond and the salts thereof are useful as intermediates in the preparation of anti-inflammatory androstane 17β-carbothioate esters. The compounds of formula I are prepared by reaction of a reactive derivative of a 17β-carboxylic acid corresponding to the compound of formula I with hydrogen sulphide or a sulphide or hydrosulphide salt.