Nucleophilic Aromatic Substitution of Methacrylamide Anion and Its Application to the Synthesis of the Anticancer Drug Bicalutamide

Abstract

The anticancer drug (R,S)-biscaltamide was prepared in three steps in >90% overall yield. A key step in the new synthesis involved a new nucleophilic aromatic substitution reaction of methacrylamide anion.

Rational design and synthesis of novel anti-prostate cancer agents bearing a 3,5-bis-trifluoromethylphenyl moiety

“…[8][9][10][11][12] Reagents and conditions: All newly synthesised compounds were evaluated for their antiproliferative effect in an in vitro 2D monolayer assay using four human prostate cancer cell lines ( Table 1, absolute IC50 in µM). LNCaP, 5 VCaP and 22Rv1 cell lines exhibit some androgen sensitivity, whereas DU-145 is hormone-insensitive (Supporting Information, section S.3).…”

“…All planned modifications were carried out according to an optimised three or four-step synthetic pathway, adapted from literature procedures, [8][9][10][11][12][13][14] summarised in Schemes 1 and…”

Synthesis and biological activity of ferrocenyl derivatives of the non-steroidal antiandrogens flutamide and bicalutamide

“…The new compounds 4 and 5 were prepared via the reaction of sodium ferrocenylmethoxide with epoxides 8 and 9, respectively, which were themselves obtained by following the literature procedure reported by Chen and coworkers [26] (Scheme 2). The reaction of 4-nitro-3-trifluoromethyl-fluorobenzene with sodium methacrylamide, generated in situ from the addition of NaH to methacrylamide, secured 6 in 88% yield.…”

“…The synthesis of SARM S-1 was carried out following the literature procedure [14] as well as (R)-10 and (S)-10 [27,29], 1 [25], 6 and 7 [8,26] and hydroxy-flutamide [35].…”

Nonsteroidal Androgen Receptor Ligands: Versatile Syntheses and Biological Data

“…Their synthesis should also allow us to study the relationship between stereochemistry and pharmacological activity, the importance of stereochemistry already having been demonstrated for bicalutamide. 14 To the best of our knowledge, no examples of highly derivatizated N-tert-butane-sulfinyl ketimines bearing an electron poor aryl propanamide skeleton have been reported so far. Sulfinylimino propanamides S (S) -and S (R) -6 were obtained by reaction of oxopropanamide (5) 15,16 with (S)/ (R)-4 with acceptable isolated yield (56%), and they represent the key starting materials for the preparation of the new AR ligands.…”