Tixocortol pivalate

N-Benzoyl-DL-tyrosil-di-n-propylamide Sodium methylate 2-Diethylaminoethyl chloride 

8 g (0.1 mol) of N-benzoyl-DL-tyrosil-di-n-propylamide are suspended in 350 cc of toluene there are then added, under agitation, 5.4 g (0.1 mol) of sodium methylate and 50 cc (0.1 mol) of a titrated toluenic solution of 2-diethylamino-ethyl hloride. The temperature is taken up to 105°C and the solution is left at this temperature, in agitation, for 12 hours. The toluenic solution is extracted with HCI 2 N the aqueous acid phase Is alkalized, cold, with sodium carbonate, and then reextracted with successive portions of ethyl acetate. 

The reunited organic phases are anhydrified upon anhydrous N32S04, filtered and dried off. The oily residue which Is obtained crumbles after a few hours of rest. Amount obtained 39.2 g. Yield 84%. Melting point 65°C to 67°C (crystallizes with petroleum ether). 

The free base can be salified so as to render it hydrosoluble. For this purpose, for example, it is dissolved in acetone and precipitated as an oxalate by the addition of a solution of oxalic acid in ethanol. Recrystallizes with ethanol. Melting point (oxalate) 159°C to 162°C. Alternatively it can be dissolved in acetone and precipitated with an acetone solution of HCI. Recrystallizes with acetone-ethanol. Melting point (chlorhydrated) 181°Cto 183°C. 

Makovec, F., Rovati, L. and Senin, P. U.S. Patent 4,004,008 January 18, 1977 assigned to Rotta Research Laboratorium S.p.A. (Italy) 

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Activity is also retained when oxygen at the 21 position is replaced by sulfur. Preparation of one of these compounds follows a route quite analogous to the foregoing thus, displacement of the mesylate group in the cortisone (56) derivative 57 with the anion from thiopivalic acid affords thioester 58. Reduction of the 11-ketone by means of borohydride affords tixocortol pivalate (59)[13j. 

Naflocort Prednicarbate Ticabesone Propionate Timobesone Acetate Tipredane Tixocortol Pivalate... 

Tieabesone propionate, 75 TUomisole, 217 Timefurone, 208 Timobesone acetate, 75 Tinabinol, 210 Tipentosin, 129 Tipredane, 74 Tiprinast, 173 Tixocortol pivalate, 73 Tolgabide, 47 Tolrestat, 56 Tomoxetine, 30 Tranexamie acid, 6 Tranilast, 44 Transcainide, 112 Trepipam, 146,147 Trifenagrel, 89 Trimetrexate, 149 Tripamide, 51 Triprolidine, 105 Tropanserin, 39 Tubulozole, 91... 

A 57-year old Caucasian man with inflammatory bowel disease was given prednisolone metasulfobenzoate sodium enemas twice daily and oral mesalazine 800 mg tds for about 5 months, without improvement. He stopped using the prednisolone enemas but continued to take mesalazine. Within 48 hours of stopping prednisolone his symptoms resolved completely. The theoretical possibility of contact allergy was entertained. Patch tests with a standard battery of contact allergens, including tixocortol pivalate and budesonide, were ++ positive with budesonide. At follow up 3 months later he was symptom free. 

A 58-year-old woman, who had been involved in the manufacturing of glucocorticoid creams and ointments for over 10 years, developed occupational contact sensitization to topical glucocorticoids (472). Patch tests were positive to hydrocortisone, hydrocortisone butyrate, and tixocortol pivalate. Intradermal tests were positive to hydrocortisone succinate, methylpredniso-lone, and prednisolone. An oral challenge with betamethasone 0.75 mg, 2.5 mg, and 8 mg on three consecutive days resulted in no adverse reactions. 

Tixocortol pivalate is a marker for glucocorticoid contact allergy, as a positive patch test suggests established contact allergy to hydrocortisone, prednisolone, and their derivatives (95). A literature search via Medline from 1966 to May 2000 revealed only one patient hypersensitive to tixocortol pivalate and budesonide in a pilot study in 34 patients (10 with asthma, 13 with rhinitis, 11 with both) (96). From case reports, the prevalence of glucocorticoid-induced contact allergy has been estimated at 2.9-5%. 

A woman had received intralesional paramethasone and other topical glucocorticoids several times for alopecia between the ages of 7 and 18 years (381). When she was 30 she was again treated with intralesional paramethasone for a relapse of alopecia. She developed pruritus after the first intralesional injection and erythema, edema, and vesicles 6-8 hours later. A biopsy showed spongiform lymphocytic folliculitis with spongiosis and exocytosis in the sweat gland ducts and in the pilosebaceous unit. She was treated with triamcinolone cream and her skin lesions resolved. Patch tests were positive for paramethasone, with cross-reactivity to tixocortol pivalate, hydrocortisone, and hydrocortisone butyrate. 

Glucocorticoid contact allergy is well known (SEDA-21, 158) and has to be particularly suspected in chronic conditions affecting the perianal area (17), after long-term topical medication, and in cases of failure to ameliorate dermatitis with corticosteroids. Patch tests should then be performed both with the recommended markers, budeso-nide (0.1% petrolatum) and tixocortol pivalate (1% petrolatum), and with the patient s own formulations. 

Dihydroxy-11j3,170 -iodo-21-dloxo-3,20-pregnene-4 Tixocortol pivalate... 

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