Androgen Receptor Affinity of 5'-Acyl Furanosteroids

Abstract

Syntheses of 5'-acyl furanosteroids are described from the corresponding unsubstituted [3,2-b]furanosteroids using acid anhydrides and acid chlorides in the presence or absence of Lewis acids. New methods have been developed to prepare 5'-acetyl derivatives: reduction of a 5'-trichloroacetyl intermediate either by sodium formaldehyde sulfoxylate or with 10% Pd/C. Most of these 5'-acyl derivatives bind to the rat ventral prostate androgen receptor. However the antiandrogenic activity was diminished when compared with 4,5'-methylsulfonyl furanosteroid. Biological studies revealed that 5'-acyl furanosteroids were either androgens or modest antiandrogens. The electrostatic potential maps of the substructures of 3, 4, and 5'-acetyl syn- and anti-furanosteroids showed striking differences which may explain, to some extent, the lack of significant antiandrogenic activity of 5'-acyl furanosteroids.

Cu and Cu-Based Nanoparticles: Synthesis and Applications in Catalysis

“…Benzofuran and its derivatives, including substituted oxygen heterocyclic compounds, play an important role in various pharmaceutically active molecules, − as antioxidative, , anticancer, , and anti-inflammatory , agents. Copper­(I) oxide NPs (CuO NPs) have been employed in multicomponent coupling/cycloisomerization reactions leading to the synthesis of 2,3-disubstituted 1-benzofurans, showing that Cu promoted a vital step in this methodology, namely, C–H activation and an O -annulation protocol.…”

A Facile and Scaleable Synthesis of ABT-239, A Benzofuranoid H3 Antagonist

“…This compound belongs to a recently described class of structurally novel benzo[ b ]furan derivatives that are of great interest due to their remarkable biological and pharmacological properties, including modulation of androgen biosynthesis, inhibition of 5-lipoxygenase, and the blood coagulation factor Xa . Of the several general and versatile methodologies considered for the synthesis of 2-substituted benzo[ b ]furans, the palladium-catalyzed Sonogashira reaction of o -halophenol ( 3 ) with substituted 1-alkynes ( 4 ) represents a very efficient procedure and was deemed best suited for our purposes (eq 1) …”

Palladium-Catalyzed Reaction of o-Ethynylphenols, o-((Trimethylsilyl)ethynyl)phenyl Acetates, and o-Alkynylphenols with Unsaturated Triflates or Halides: A Route to 2-Substituted-, 2,3-Disubstituted-, and 2-Substituted-3-acylbenzo[b]furans

“…Considering the structural similarity between indoles and benzo[ b ]furans, it appeared to us that an analogous chemistry might be used to generate the benzo[ b ]furan skeleton. On the other hand, its occurrence in natural substances and the growing interest in the activity of benzo[ b ]furan derivatives as modulators of androgen biosynthesis (furanosteroids), as inhibitors of 5-lipoxygenase and of the blood coagulation factor Xa, as antagonists of the angiotensin II receptor, as calcium entry blockers, as ligands of adenosine A 1 receptor, as antitumor agents, and as inhibitors of the E-selectin-mediated cell adhesion appear to justify efforts to develop more general and versatile synthetic methodologies to this class of compounds, particularly when these methodologies accommodate considerable functionality and are broad in scope.…”