The Adamantyl Group in Medicinal Agents. II. Anabolic Steroid 17β-Adamantoates

Abstract

h e synthesis of several steroidai liP-adamanloate esters is described. "lie ad:iiiurti!oic ester of 19-iiurlcw tosterotie produce& a profound arid unique effect on anabolic potency as compared Kith other esters. The long diiratiori of high rnyotropic activity with diminished androgeriic.it,y-ma!-be an indication that, the ester is act'irrg in toto as opposed to prior hydrolysis to the parent compound. The action of this anabolic ester over a period of several weeks after a single injection is confirmed by the radioactive :tniirioisobut,yric acid (AIB) C14 uptake data.

The many faces of the adamantyl group in drug design

“…The adamantyl-based sulfonylurea showed a prolonged hypoglycemic effect over a 6-h period, relative to the butyl-or cyclohexyl-based analogues, and was nontoxic in mice when administered as a single oral dose of 2.0 g kg À1 or at daily oral doses of 1.0 g kg À1 over one month [4]. Subsequent to this study, the same team examined steroid 17b-adamantoate esters [5] and nucleoside 5 0 -adamantoates [6]. These studies set the foundation for the future development of diverse adamantyl-based compounds with potential to treat many different conditions.…”

“…Although the major focus has fallen upon 23 and derivatives as anticancer agents, this class of compound also has potential to treat skin and metabolic diseases. The structure of 23, for example, is similar to the clinical anti-acne agent adapalene (5). Subtle modifications to the adamantyl-based retinoid compound prescribe whether it acts as a retinoic acid receptor-g agonist (23), a retinoic acid receptora antagonist (CD2665, structure not shown) or a retinoic acid receptor-b agonist (CD1886, structure not shown) [104].…”

“…[180]. The extended time of activity of steroid 17b-adamantoate esters compared to other aliphatic esters was ascribed to the relative rates of esterase hydrolysis [5].…”

Pharmaceuticals that contain polycyclic hydrocarbon scaffolds

“…The hydrocarbon nature of the adamantane group increases lipophilicity, allowing such molecules to move more easily across biological membranes, as elegantly summarized by Wanka and Schreiner. 252,[255][256][257] These favourable properties have prompted studies investigating the potential for use of adamantyl containing compounds in cancer and CNS diseases, such as those involving the AMPA and KATP channels View Article Online and the GABAergic system. 253,254 Furthermore, this lipophilic moiety can be added to pharmaceutically active compounds and known pharmacophors to improve pharmacokinetic properties or to exploit a lipophilic pocket in the target in order to increase selectivity.…”

Stereoselective synthesis and pharmacological evaluation of [4.3.3]propellan-8-amines as analogs of adamantanamines

“…[1][2][3] Exemplarily, introduction of the adamantane system into cannabinoid receptor subtype 2 (CB 2 ) ligands leads to increased CB 2 affinity and penetration into the central nervous system. 4 The adamantanamines amantadine (1) and memantine (2) display anti-Parkinson, antiAlzheimer and antiviral activities.…”