Flumethasone

Chemical Name 6,9-Difluoro-11,17,21 -trihydroxy-16-methylpregna-l, 4 liene-3,20-dione Common Name 6a-Fluorodexamethasone Structural Formula  

Trede Name Manufacturer Country Year Introduced 

60i-Fluoro-9/3,11/Jepoxy-1 60i-methyl-170i,21 -dihydroxy-1,4-pregnadiene-3,20-dione-21 -acetate Hydrogen fluoride 

To approximately 1.3 g of hydrogen fluoride contained in a polyethylene bottle and maintained at -60°C was added 2.3 ml of tetrahydrofuran and then a solution of 500 mg (0.0012 mol) of 6a-fluoro-9/3,11/3epoxy-160 -methyl-17o ,21 -dihydroxy-l, 4-pregnadiene-3,20-dione 

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Tolrestat (28) is a long-acang aldose reductase inhibitor useful in the prophylaxis of diabetic neuropathy, retinopathy, and cataracts [24 25] Lastly, the intro-ducuon of fluorine into steroids probably ushered in the modem era of fluonnated drugs Many commercial products were introduced [2] Typical of the products are the anti inflammatory glucocorticoids dexamethasone (29 X = F, Y = H), para-methasone (29, X = H, Y = F), and flumethasone (29, X = H, Y = F)... 

Dehydration of 221 affords the corresponding 9,11 olefin, 223. When this compound is subjected to the series of reactions for introduction of the 9,11 fluorohydrin, there is obtained the antiinflammatory steroid flumethasone (224).° As might be expected from the incorporation of a group in almost every posi-tion known to increase potency 224 is an extremely active agent. 

Corticosteroids Cortisone Cortisol Dexamethasone Betamethasone Deoxymethasone Prednisone Prednisolone Flumethasone Growth promoter Anti-inflammatory... 

Immunoaffinity procedures have also been developed to selectively extract corticosteroids from different sample matrices. Thus, Seymour et al. demonstrated the higher efficiency of the immunoaffinity methods compared with the conventional extraction procedures using organic solvents [177]. Immunosorbents have also been used for online procedures followed by HLPC-UV [178, 179], HPLC-APCI-MS [179,180], GC-MS [176,181], or capillary electrophoresis [182]. Poly(hydroxyethyl methacrylate) (HEMA) was evaluated as a support material for the anti-dexamethasone antibodies used in IAC. The online IAC-HPLC-MS allowed determination of dexamethasone and flumethasone in equine urine with LODs in the range 3-4 ng mL-1 [180]. The cross-reactivity values obtained in the ELISA and the recoveries of an IAC-HPLC procedure are presented in Table 7. Bagnati et al. developed an immunoaffinity extraction... 

Flucinolone Acetonide Fludrocortisone Acetate Fludroxycortide Flumethasone Fluocortolone Fluorometholone 9a-Fluoroprednisolone Acetate... 

Reaction of the side chain hydroxyacetone in flumethasone (27-4) with periodic acid leads to cleavage of that function to give carboxylic acid (29-1) with the loss of the carbon atom at C-21. Further reaction of the very hindered acid group requires prior activation. Thus, acylation with diphenyl chlorophosphate leads to the mixed anhydride (29-2) this is not isolated, but treated immediately with methyl mercaptan. The product, tibecasone (29-3), is a quite effective topical anti-inflammatory agent [24]. Cleavage of the ester side chain would lead back to the inactive starting acid (29-1). 

Fredline et al. [18] report an MRM negative-ion ESI method for aldosterone using flumethasone as an internal standard. The MRM transition used was 359—>331. The assay was linear over a 15- to 5000-pg/ml range and the limit of quantitation was 15 pg/ml. A manual extraction was used and recovery and accuracy were excellent. 

Scheme 2. Synthesis of fluticasone propionate (1) from flumethasone (4).

Flumethasone (Fig. 8.3) is primarily indicated for treatment of inflammatory diseases, dermatosis, shock, and primary cattle ketosis. It is administered parenterally at dosages of 2.5-40 g/kg bw. 

Pharmacokinetic data after intravenous, intraruminal, or subcutaneous administration of 0.25-0.5 mg flumethasone/kg bw/day for 8 days in sheep showed that maximum plasma levels were reached within 48 h postdosing. The metabolic clearance was estimated at about one-quarter to three-quarters of that found for cortisol in sheep. 

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