92572-52-6Relevant academic research and scientific papers
A new avenue toward androgen receptor pan-antagonists: C2 sterically hindered substitution of hydroxy-propanamides
Guerrini, Andrea,Tesei, Anna,Ferroni, Claudia,Paganelli, Giulia,Zamagni, Alice,Carloni, Silvia,Di Donato, Marzia,Castoria, Gabriella,Leonetti, Carlo,Porru, Manuela,De Cesare, Michelandrea,Zaffaroni, Nadia,Beretta, Giovanni Luca,Del Rio, Alberto,Varchi, Greta
supporting information, p. 7263 - 7279 (2015/01/30)
The androgen receptor (AR) represents the primary target for prostate cancer (PC) treatment even when the disease progresses toward androgen-independent (AIPC) or castration-resistant (CRPC) forms. Because small chemical changes in the structure of nonsteroidal AR ligands determine the pharmacological responses of AR, we developed a novel stereoselective synthetic strategy that allows sterically hindered C2-substituted bicalutamide analogues to be obtained. Biological and theoretical evaluations demonstrate that C2-substitution with benzyl and phenyl moieties is a new, valuable option toward improving pan-antagonist behavior. Among the synthesized compounds, (R)-16m, when compared to casodex, (R)-bicalutamide, and enzalutamide, displayed very promising in vitro activity toward five different prostate cancer cell lines, all representative of CPRC and AIPC typical mutations. Despite being less active than (R)-bicalutamide, (R)-16m also displayed marked in vivo antitumor activity on VCaP xenografts and thus it may serve as starting point for developing novel AR pan-antagonists.
A concise synthesis of (R)- and (S)-α-alkyl isoserines from d- and l-malic acids
Huang, Yan,Zhang, Yong-Bo,Chen, Zhi-Ce,Xu, Peng-Fei
, p. 3152 - 3157 (2007/10/03)
A simple and diastereoselective method for the synthesis of (R)- and (S)-α-alkyl isoserines has been developed in four steps starting from commercially available d- and l-malic acid, respectively. This approach features stereocontrolled alkylation of 2-(2
α-ALKYLATION OF α-HETEROSUBSTITUTED CARBOXYLIC ACIDS WITHOUT RACEMIZATION; EPC-SYNTHESES OF TERTIARY ALCOHOLS AND THIOLS
Seebach, Dieter,Naef, Reto,Calderari, Giorgio
, p. 1313 - 1324 (2007/10/02)
α-Hydroxy- and α-mercapto-carboxylic acids are condensed with pivalaldehyde to give 2-t-butyl-5-substituted-1,3-dioxolanones or 1,3-oxathiolanones (2); the predominate cis-isomers are separeted by crystallization.The cis-disubstituted heterocycles 2 derived from lactic, mandelic and malic acid funish, after deprotonation with LDA, reaction with electrophiles such as alkyl halides, aldehydes and ketones, and hydrolysis α-branched α-hydroxy-carboxylic acids (3, 6, 8, 9, 10).These result from an overall substitution of the proton in the α-CO position with retention of configuration.The optically active carboxylic acids are α-alkylated without racemization and without employment of a chiral auxiliary ("self-reproduction of chirality", Scheme 1).The diastereoselectivities (ds) are generally >95percent (Table 1, 2, and 20-25).
