Steroid glucocorticoid

Several steroidal and non-steroidal glucocorticoid receptor selective dissociated agonists are in development by many pharmaceutical companies and some are now in clinical development. This suggests that the development of dissociated glucocorticoids with a greater margin of safety is possible and may even lead to the development of oral compounds that do not have significant adverse effects. 

Gorodeski GI, Eckert RL, Utian WH, Sheean L, and Rorke EA [1990] Cultured human ectocervical epithelial cell differentiation is regulated by the combined direct actions of sex steroids, glucocorticoids and retinoids. J Clin Endocrinol Metab 70 1624-1630... 

M.E. Wolff, J.D. Baxter, P.A. Kollman, D.L. Lee, I.D. Kuntz, E. Bloom, D.T. Matulich, J. Morris, Nature of steroid-glucocorticoid receptor interactions Thermodynamic analysis of the binding reaction, Biochemistry 16 (1978) 3201-3208. 

Vitamin D is a precursor for a number of compounds that increase intestinal absorption and decrease renal excretion of calcium and phosphate. Metabolites of vitamin D and their pharmacologic analogs are typically used to increase blood calcium and phosphate levels and to enhance bone mineralization in conditions such as osteodystrophy, rickets, or other situations where people lack adequate amounts of vitamin D. Vitamin D analogs such as calcitriol have also been combined with calcium supplements to help treat postmenopausal osteoporosis,4,9 and to treat bone loss caused by antiinflammatory steroids (glucocorticoids see Chapter 29 28.76 Specific vitamin D-related compounds and their clinical applications are listed in Table 31-5. 

Cryotherapy Cold/ice packs Ice massage Cold bath Vapocoolant sprays Decreased pain, edema, and inflammation Muscle relaxation and decreased spasticity Anti-inflammatory steroids (glucocorticoids) nonsteroidal anti-inflammatory analgesics (aspirin and similar NSAIDs) Skeletal muscle relaxants Peripheral vasodilators may exacerbate acute local edema Nonselective cholinergic agonists may stimulate the neuromuscular junction Some forms of cryotherapy may produce local vasoconstriction that temporarily impedes diffusion of drugs to the site of inflammation... 

Allen, J. J., and Shokat, K. M. (2006). Chemical genomics dialed in transcriptional network control with non-steroidal glucocorticoid receptor modulators. ACS Chemical Biology 1, 139-140. 

With this early success the further evolution of the first-generation steroidal glucocorticoids was started, and the stage for later syntheses of potent synthetic steroids such as prednisolone, dexamethasone and fluocortolon was set [13]. 

THERap Cat Glucocorticoid anti-inflammatory. therap cat (vet) Adrenocortical steroid glucocorticoid topical anti -inflammatory. 

Wolff ME, Baxter JD, Kollman PA, Lee DL, Kuntz ID, Bloom E, Matulich DT, Morris J (1978) Nature of steroid-glucocorticoid receptor interactions thermodynamic analysis of the binding reaction. Biochemistry 17 3201-3208... 

Schacke H, Berger M, Hansson TG, McKerrecher D, Rehwinkel H. Dissociated non-steroidal glucocorticoid receptor modulators an update on new compounds. Expert Opin. Iher. Pat 2008 18 339-352. 

SCHEME 30.23. Asymmetric hydrogenation via DKR highly efficient method for the introduction of simultaneously two stereogenic centers application to the syntheses of (+)-codaplmiphylline, non-steroidal glucocorticoid modulator 115, as well as (—)-a-conhydrine and (-l-)-p-conhydrine. 

In 2010, Zhou et al. " demonstrated the utility of RuCl2-SDPs/DPEN-catalyzed asymmetric hydrogenation of racemic ketone 112 via DKR in the enantioselective synthesis of alcohol (1R,25)-114, a chiral key intermediate of non-steroidal glucocorticoid modulator 115. The chiral... 

An example of Ellman s methodology as applied to a chiral reduction has been described in a drug discovery programme undertaken by Merck to develop selective non-steroidal glucocorticoid receptor agonists such as 243. Ketone 238 was converted to ketimine 239 by reaction with (i )-(-l-)-tert-butanesulfinamide and titanium tetraethoxide. Asymmetric reduction was effected by treatment with sodium borohydride followed by deprotection under acidic conditions to afford amine 242. The chiral product was subsequently converted to glucocorticoid receptor agonist 243 (Scheme 14.80). 

Proceeding further down the table, one encounters a cluster based on a triple of uses adrenocortical steroid, glucocorticoid, anti-inflammatory. The parasympathomimetia-miotia cluster occurs alone, followed by a cluster centered on sympathomimetia. 

---