3-Chloro-1,3,5-pregnatriene derivatives with glucocorticoid activity.
Novel synthetic glucocorticoid analogues were tested for receptor binding and glucocorticoid activity. They were of unusual structure, insofar as they had a 3-chloro rather than a 3-oxo function. 3-Chloro analogues of fluorinated glucocorticoids formed extremely stable complexes with the rat liver glucocorticoid receptor. 3-Chloro derivative of fluocinolone acetonide also had in vivo glucocorticoid activity. It induced tyrosine aminotransferase in the liver and repressed thymidine kinase in the thymus very effectively. It is concluded that 3-chloro analogues may retain glucocorticoid activity as well as the ability to bind to the glucocorticoid receptor protein.
D000107:Acetylation; D000315:Adrenalectomy; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D003600:Cytosol / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D005446:Fluocinolone Acetonide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D005938:Glucocorticoids / Q000138:chemical synthesis / Q000494:pharmacology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011494:Protein Kinases / Q000096:biosynthesis / Q000378:metabolism; D011505:Protein-Tyrosine Kinases; D051381:Rats; D011919:Rats, Inbred Strains; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013950:Thymus Gland / Q000187:drug effects; D013997:Time Factors; D014222:Triamcinolone Acetonide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D014444:Tyrosine Transaminase / Q000096:biosynthesis / Q000378:metabolism
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D005446:Fluocinolone Acetonide; C043140:3-chlorotriamcinolone acetonide; C043141:3-chlorofluocinolone acetonide; C043142:3-chlorofluocinolone acetonide 21-acetate; D014444:Tyrosine Transaminase; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D014222:Triamcinolone Acetonide