61985-25-9Relevant articles and documents
Balanced dual acting compounds targeting aromatase and estrogen receptor α as an emerging therapeutic opportunity to counteract estrogen responsive breast cancer
Belluti, Federica,Bisi, Alessandra,Caciolla, Jessica,Fimognari, Carmela,Gobbi, Silvia,Magistrato, Alessandra,Martini, Silvia,Pavlin, Matic,Rampa, Angela,Simonelli, Federica,Spinello, Angelo,Turrini, Eleonora,Zaffaroni, Nadia
supporting information, (2021/08/09)
Breast Cancer (BC) is a leading cause of death in women, currently affecting 13% of female population worldwide. First-line clinical treatments against Estrogen Receptor positive (ER+) BC rely on suppressing estrogen production, by inhibiting the aromatase (AR) enzyme, or on blocking estrogen-dependent pro-oncogenic signaling, by targeting Estrogen Receptor (ER) α with selective Modulators/Degraders (SERMs/SERDs). The development of dual acting molecules targeting AR and ERα represents a tantalizing alternative strategy to fight ER + BC, reducing the incidence of adverse effects and resistance onset that limit the effectiveness of these gold-standard therapies. Here, in silico design, synthesis, biological evaluation and an atomic-level characterization of the binding and inhibition mechanism of twelve structurally related drug-candidates enable the discovery of multiple compounds active on both AR and ERα in the sub-μM range. The best drug-candidate 3a displayed a balanced low-nanomolar IC50 towards the two targets, SERM activity and moderate selectivity towards a BC cell line. Moreover, most of the studied compounds reduced ERα levels, suggesting a potential SERD activity. This study dissects the key structural traits needed to obtain optimal dual acting drug-candidates, showing that multitarget compounds may be a viable therapeutic option to counteract ER + BC.
SUBSTITUTED BIARYLS, PROCESS FOR THEIR MANUFACTURE AND USE THEREOF AS MEDICAMENTS
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Page/Page column 48, (2010/11/30)
The present invention relates to compounds of general formula (I) wherein A, B, L, R1, R2, R3a and R3b are defined as in the specification, the tautomers, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, which have valuable properties.
A GENERAL SYNTHESIS OF 4(5)-ACYLIMIDAZOLES FROM 4-ACYLAMINOISOXAZOLES.
Reiter, Lawrence A.
, p. 3423 - 3426 (2007/10/02)
2-Substituted-4(5)-acyl, 1,2-disubstituted 4-acyl and 1,2-disubstituted-5-acylimidazoles can be specifically prepared from 4-aminoisoxazoles.
