68-60-0Relevant academic research and scientific papers
A convenient synthesis of the side chain of loteprednol etabonate - An ocular soft corticosteroid from 20-oxopregnanes using metal-mediated halogenation as a key reaction
Chowdhury, Pritish,Borah, Juri Moni,Goswami, Papori,Das, Archana Moni
experimental part, p. 497 - 501 (2011/05/09)
A facile synthesis of the side chain of loteprednol etabonate, namely, chloromethyl-17α-[(ethoxycarbonyl))oxy]-11β-hydro of loteprednol etabonate, viz., chloromethyl-17α-[(ethoxycarbonyl))oxy]-11xy-3- oxoandrosta-1,4-diene-17β-carboxylate - an ocular soft corticosteroid, has been described starting from a 20-oxopregnane, namely, 3β-acetoxy-pregn- 5(6),16(17)-diene-20-one (16-dehydropregnenolone acetate, i.e., 16-DPA) using our recently developed metal-mediated halogenation as a key reaction.
Potential corticoid metabolites: Chemical synthesis of 3- and 21-monosulfates and their double-conjugates of tetrahydrocorticosteroids in the 5 α- and 5 β-series
Okihara, Rika,Mitamura, Kuniko,Hasegawa, Maki,Mori, Megumi,Muto, Akina,Kakiyama, Genta,Ogawa, Shoujiro,Iida, Takashi,Shimada, Miki,Mano, Nariyasu,Ikegawa, Shigeo
experimental part, p. 344 - 353 (2011/02/22)
Here, we describe the chemical synthesis of the complete sets of 18 novel 3- and 21-monosulfates and their double-conjugated form of tetrahydrocortisol (THF), tetrahydro-11-deoxycortisol (THS), and tetrahydrocortisone (THE) in the 5 α- and 5 β-series. The principal reactions involved are: (1) selective protection of a specific hydroxy group in substrates; (2) catalytic hydrogenation at C-5 of Δ4-3-ketosteroids with 10% Pd(OH) 2/C to yield 3-oxo-5 β-steroids and reductive allomerization with 10% Pd/C to yield 3-oxo-5 α-isomers; (3) reduction of the resulting 3-oxo-5 β- and 3-oxo-5 α-steroids to the corresponding 3 α-hydroxy-compounds with Zn(BH4)2 and K-Selectride, respectively; and (4) sulfation of hydroxy groups at C-3 and/or C-21 in the tetrahydrocorticosteroid derivatives with sulfur trioxide-triethylamine complex.
Phase I and phase II ocular metabolic activities and the role of metabolism in ophthalmic prodrug and codrug design and delivery
Al-Ghananeem, Abeer M.,Crooks, Peter A.
, p. 373 - 388 (2007/10/03)
While the mammalian eye is seldom considered an organ of drug metabolism, the capacity for biotransformation is present. Compared to the liver, the metabolic capabilities of the eye are minuscule; however, phase I and phase II metabolic activities have been detected in various ocular structures. The careful consideration of ocular tissue metabolic processes within the eye has important implications for controlling the detoxification of therapeutic agents and for providing the potential for site-specific bio-activation of certain drug molecules, thus enabling significant improvements in drug efficacy and the minimization of side-effect from either local or systemic drug delivery to the eye. Knowledge of these processes is important to prodrug and codrug development and to researchers involved in the design, delivery and metabolism of ophthalmic drugs. This present article reviews the progress in ocular prodrug and codrug design and delivery in light of ocular metabolic activities.
Permeable, non-irritating prodrugs of nonsteroidal and steroidal agents
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, (2008/06/13)
Prodrugs containing an active drug molecule linked to a polyethylene glycol group, and a method of use thereof are described. Exemplary soluble ester prodrugs contain naproxen, triamcinolone acetonide, gancyclovir, taxol, cyclosporin, dideoxyinosine, trihydroxy steroids, and flurbiprofen molecules linked to polyethylene glycol (PEG) groups. Pharmaceutical compositions containing these prodrugs, and a method of using these esters for treating disease states or symptoms are also described.
The scarlet letter: Reichstein's substance S. A comparison of the angiostatic properties of 5α-tetrahydro S and 5β-tetrahydro S
Hadd, Harry E.
, p. 650 - 655 (2007/10/02)
5β-Tetrahydro-Reichtein's Substance S (3α, 5β-THS) from different sources yielded variable bioassays activity in the chick chorio-allantoic membrane assay system. Physical characterization showed impure products. Synthesis of this compound by two different routes yielded active and inactive 3α,5β-THS. Of the other two epimers, 3β,5β-THS (epi-THS) and 3α,5α-THS (allo-THS), only the latter was active. These results suggest that the impurities present in 3α,5β-THS synthesized by reduction of the α,β-unsaturated ketone of Substance S might be either or both the epi- lallo-epimers (3β,5β-THS and 3α,5α-THS, respectively), with only the latter contributing the positive angiostatic activity to the mixture. Of the two synthetically derived compounds, only the latter was shown to maintain the activity, whereas 3α,5β-THS was not antiangiogenic.
Biotransformation of corticosteroids by Penicillium decumbens ATCC 10436
Holland, Herbert L.
, p. 646 - 649 (2007/10/02)
The biotransformation of a series of corticosteroids by the fungus Penicillium decumbens ATCC 10436 has been investigated. Conversion to the corresponding 5α-dihydroxteroid was observed for all the Δ4-3-ketosteroids studied with the exception of deoxycorticosterone, which was converted to a Δ14-diene. Deoxycorticosterone acetate was, however, converted to a 5α- dihydro product concomitant with ester hydrolysis. Other substrates carrying a C-21 acetoxy group were also hydrolyzed to the alcohol. In two cases (resulting from deoxycorticosterone acetate and 11-deoxycortisone) the 5α- 3-keto-product was further reduced to the 3β-alcohol. No reduction of δ14-dienes was observed.
C-3 GLUCOSIDURONATES OF METABOLITES OF ADRENAL STEROIDS
Mattox, Vernon R.,Goodrich, June E.,Nelson, Albert N.
, p. 23 - 34 (2007/10/02)
On treatment with methyl 2,3,4-tri-O-acetyl-1-bromo-1-deoxy-α-D-glucuronate and silver carbonate, tetrahydrocortisone 21-acetate gave the corresponding 3-glucosiduronate triacetyl methyl ester.This product was converted into the 20-semicarbazone which, by treatment with alkali to hydrolyze the ester functions and acid to hydrolyze the semicarbazone moiety, gave tetrahydrocortisone 3-glucosiduronic acid.The acid was converted into the crystalline barium salt and into the methyl ester.An analogous series of reactions was carried out on tetrahydrocortexolone 21-acetate.Treatment of the 20-semicarbazone of tetrahydrocortisone 3-glucosiduronic acid with potassium borohydride reduced the 11-oxo function to an 11β hydroxyl group; acid-catalyzed removal of the semicarbazone group produced tetrahydrocortisol 3-glucosiduronic acid which also was obtained as the barium salt and the methyl ester.
