Detail of "338-95-4"

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Role of hydrophobic effects and polar groups in steroid-mineralocorticoid receptor interactions

Role of hydrophobic effects and polar groups in steroid-mineralocorticoid receptor interactions. Genard, P.; Palem-Vliers, M. (Dep. Clin. Pathol. 50-23-7 and 7305-54-6 are also occured in this study. Med., Univ. Liege, Liege, Belg.). J. Steroid Biochem., 19(5), 1639-45 (English) 1983. CODEN: JSTBBK. ISSN: 0022-4731. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) To test whether hydrophobic interactions are the main driving forces in the assocn. of steroids with mineralocorticoid receptors, the binding free energy calcd. (DGc) using the surface area of the steroids accessible to water was compared with the obsd. free energy (DGM) obtained from the Kd at the equil. estd. in the rat cytosol. The results are consistent with a binding process involving principally hydrophobic effects, implying assocn. of both faces of the steroid with the mechanism of H bonding of the polar groups of the steroids to those on the receptor. H bonds in an aq. environment are likely between polar groups of the receptor and the 21-OH, 18-OH, and 11-18 hemiacetal O of the steroids. Strong H bonding in a hydrophobic environment from the 3-CO and 20-CO groups is a possibility (the latter with a dihedral angle C16-C17-C20-O20 of x 7°). Such a strong H bond from the 9a-fluorine atom could account for the obsd. high affinity receptor binding of 9a-fluorocortisol [127-31-1] and 9a-fluoroprednisolone [338-95-4]. The loss of affinity in 11-deoxycortisol [152-58-9] and cortisol [50-23-7] may be explained by modification of the C17 side chain and repulsion forces from the 11b-OH. .

Steroid antagonism of the 'hypertensionogenic' activity of 9a-fluoroprednisolone

Steroid antagonism of the 'hypertensionogenic' activity of 9a-fluoroprednisolone. Coghlan, John P.; Denton, Derek A.; Mills, Eric H.; Nelson, Mark A.; Spence, Campbell D.; Whitworth, Judith A.; Scoggins, Bruce A. (Howard Florey Inst. Exp. Physiol. Med., Parkville 3052, Australia). Life Sci., 35(26), 2609-12 (English) 1984. CODEN: LIFSAK. ISSN: 0024-3205. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) It has been previously reported that adrenocortical steroids raise blood pressure by a hypertensinogenic mechanism of action which is not simply related to their classical mineralocorticoid or glucocorticoid actions. Evidence for specific antagonism of this hypertensinogenic activity is presented. The effects of sep. i.v. infusions of prednisolone (P) [50-24-8] 100 mg/day and 9a-fluoroprednisolone (9aF-P) [338-95-4] 0.6 mg/day on mean arterial pressure (MAP), plasma K+ concn. ([K]), plasma [glucose], and urinary Na+ excretion (UNaV) were studied in sheep after 2 days. In the same group of sheep which received P alone for 2 days, 9aF-P was given for a further 2 days while continuing the P infusion (P + 9aF-P). P alone had no effect on MAP or plasma [K] or UNaV but increased plasma [glucose], effects which are characteristic of glucocorticoid activity. 9aF-P alone increased MAP by 14 mm Hg and reduced plasma [K] and UNaV but had no effect on plasma [glucose]. Thus 9aF-P exhibited both hypertensinogenic and mineralocorticoid activity. In the sheep which received the combined P + 9aF-P infusion, the increase in MAP normally produced by 9aF-P was blocked. Although pretreatment with P blocked the pressor effect of 9aF-P, it did not alter the mineralocorticoid effects, namely hypokalemia and urinary Na retention, produced when 9aF-P was infused alone. These results provide further evidence for the concept of a hypertensinogenic class of steroid activity and are the 1st demonstration of specific antagonism of steroid-induced hypertension.