- Effect of chirality at C-20 of methyl 11β,17α,20-trihydroxy-3-oxo-1,4-pregnadien-21-oate derivatives on antiinflammatory activity
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In an effort to determine the C-20 chirality effect on the antiinflammatory activity of 17β-glycolate esters, methyl 11β,17α,20-trihydroxy-3-oxo-1,4-pregnadien-21-oate and its 9α-fluoro analog, their acetonide and their carbonate derivatives were synthesized and evaluated. The agents were tested for their binding potency to the macrophage glucocorticoid receptor, and their effect on LPS-induced nitric oxide generation in RAW 264.7 cells. The acetonide derivatives showed the highest binding affinity while the triols and carbonates bound rather poorly to the receptors. With the exception of the triols, the α-isomer in each pair of the agents exhibited higher binding affinity to the receptor than its corresponding β-isomer, clearly indicating that C-20 chirality has a significant effect on antiinflammatory activity. In addition, the α-isomers of the acetonides showed substantially higher binding affinity than the parent compound, prednisolone. In contrast to the high binding activity exhibited by some of the acetonides, all of the agents showed weak inhibitory effect on NO generation. Metabolic inactivation during assessment of NO inhibition may play a role in the divergence noted between receptor affinity and the measured biologic activity resulting from the binding.
- You, Zhengqing,Heiman, Ann S,Hudson, Charles E,Lee, Henry Joung
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- Anti-inflammatory carboxy pregnane derivatives
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Compounds of the formula: STR1 wherein one X is COOR, CH2 COOR, CH(COOR)2, CONHR, CH2 CONHR, or CN remaining X's are H, F, CH3, OH, COOR, CH2 COOR, CH(COOR)2, CONHR, CH2 CONHR, or CN; Y is STR2 R is H, alkyl of 1-5 carbon atoms, or benzyl; R1 is CH2 OR3, COOR, or CONHR; R2 is H, OR3, or BR; R3 is H, COR4, or tetrahydropyranyl; R4 is alkyl of 1-5 carbon atoms or benzyl; R5 is H or COR4 ; represents a single or double bond; represents α-position, β-position, or a mixture of α- and β-positions; and --- represents α-position; and methods for preparing the same.
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- Anti-inflammatory prednisolone steroids
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Derivatives of prednisolone of the formula STR1 wherein CR1 is C=O, α-HCOH, β-HCOH, or a mixture of α-HCOH and β-HCOH CR2 is HC(OH) OR6 or HCO when CR1 is C=O; CR2 is COOR3 or CONHR4 when CR1 is α-HCOH, β-HCOH, or a mixture of α-HCOH and β-HCOH: R3 is alkyl of 1-5 carbon atoms; R4 is alkyl of 1-5 carbon atoms, benzyl, or phenethyl; R5 is hydrogen, acetyl, or benzoyl; R6 is alkyl of 1-5 carbon atoms; R7 is α- or β-position of hydrogen, hydroxyl, methyl, acetate esters of 1-5 carbon atoms, or alkoxy of 1-5 carbon atoms; and X and Y are hydrogen, halogen or methyl; and process for preparing these compounds. The compounds are useful as anti-inflammatory agents which have reduced side effects.
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- OXIDATION OF CORTICOSTEROIDS BY FLAVINS
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The new reaction is reported between corticosteroids and flavins leading to the steroid-21-oic acids.
- Jasiczak, J.,Smoczkiewicz, M. A.
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p. 5221 - 5224
(2007/10/02)
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- Prednisolone derivatives
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Novel prednisolone derivatives modified at C-17,C-20 and/or C-21 positions. Many of the compounds are anti-inflammatory agents which do not significantly suppress the pituitary-adrenal axis.
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