55161-19-8Relevant academic research and scientific papers
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
, (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.
Selective C(sp3)?H Aerobic Oxidation Enabled by Decatungstate Photocatalysis in Flow
Laudadio, Gabriele,Govaerts, Sebastian,Wang, Ying,Ravelli, Davide,Koolman, Hannes F.,Fagnoni, Maurizio,Djuric, Stevan W.,No?l, Timothy
supporting information, p. 4078 - 4082 (2018/03/21)
A mild and selective C(sp3)?H aerobic oxidation enabled by decatungstate photocatalysis has been developed. The reaction can be significantly improved in a microflow reactor enabling the safe use of oxygen and enhanced irradiation of the reaction mixture. Our method allows for the oxidation of both activated and unactivated C?H bonds (30 examples). The ability to selectively oxidize natural scaffolds, such as (?)-ambroxide, pregnenolone acetate, (+)-sclareolide, and artemisinin, exemplifies the utility of this new method.
Synthesis of β-heteroaryl carbonyl compounds via direct cross-coupling of allyl alcohols with heteroaryl boronic acids under cooperative bimetallic catalysis
Zhu, Mingxiang,Du, Hongli,Li, Jingya,Zou, Dapeng,Wu, Yusheng,Wu, Yangjie
supporting information, p. 1352 - 1355 (2018/03/06)
The eco-friendly cooperative Cu/Pd-catalyzed oxidative Heck reaction of allyl alcohols with heteroaryl boronic acids under air was described. The ready availability of starting materials and the mild reaction conditions made this protocol a safe and operationally convenient strategy for the efficient synthesis of β-heteroaryl carbonyl compounds.
Nickel catalyzed electrochemical heteroarylation of activated olefins
Condon, Sylvie,Dupre, Daniel,Lachaise, Isabelle,Nedelec, Jean-Yves
, p. 1752 - 1758 (2007/10/03)
Conjugate addition reaction of heteroaryl halides to activated olefins has been successfully achieved by nickel catalysis combined with the consumable anode procedure and provides access to various functionalized heteroaryl compounds with potential biolog
PHOTOCHEMICAL GENERATION OF ALIPHATIC RADICALS FROM BENZOPHENONE OXIME ESTERS: SIMPLE SYNTHESIS OF ALKYLBENZENES AND ALKYLPYRIDINES
Hasebe, Masato,Tsuchiya, Takashi
, p. 3239 - 3242 (2007/10/02)
Photolysis of benzophenone oxime esters, prepared with aliphatic carboxylic acids and benzophenone oxime, in benzene and pyridine generates various primary, secondary and tertiary aliphatic radicals selectively, and corresponding alkylbenzenes and alkylpyridines are produced in good yields, respectively.
REACTION OF 1-PYRIDYL-1,3-BUTANEDIONES AND 1,3-DIPYRIDYL-1,3-PROPANEDIONES
Ferles, Miloslav,Kafka, Stanislav,Silhankova, Alexandra,Sputova, Michaela
, p. 1167 - 1172 (2007/10/02)
Reduction of diketones I with zinc and formic acid gives monoketones II.Diketones Ia, IIIb, IIIc are converted with hydrazines to pyrazoles VIa, IVa, IVb, V.Methiodides VII are reduced with sodium borohydride to derivatives of 1-methyl-3-piperideine VIII-
GENERAL METHODS OF SYNTHESIS OF INDOLE ALKALOIDS - 14. SHORT ROUTES OF CONSTRUCTION OF YOHIMBOID AND AJMALICINOID ALKALOID SYSTEMS AND THEIR 13C NUCLEAR MAGNETIC RESONANCE SPECTRAL ANALYSIS.
Wenkert,Chang,Chawla,Cochran,Hagaman,King,orito
, p. 3645 - 3661 (2007/10/04)
Conceptually new schemes of synthesis of indole alkaloids are introduced. The yohimboid ring system is constructed by the sequential treatment of 1-tryptophyl-3-( beta -ketobutyl)pyridinium bromide with base and acid. Hydrogenation of the product yields d,l-pseudoyohimbone. The ajmalicinoid ring system is formed by the exposure of 1-tryptophyl-3-acetylpyridinium bromide to sodio dimethyl malonate and then to acid, followed by hydrogenation. Subsequent reduction and dehydration of the products lead to the racemates of the alkaloids tetrahydroalstonine and akuammigine as well as isomers of ajmalicine. Shifts of specific carbons are found to be of stereochemically diagnostic value.
