23434-37-9Relevant academic research and scientific papers
Combined inhibition of the EGFR/AKT pathways by a novel conjugate of quinazoline with isothiocyanate
Tarozzi, Andrea,Marchetti, Chiara,Nicolini, Benedetta,D'Amico, Massimo,Ticchi, Nicole,Pruccoli, Letizia,Tumiatti, Vincenzo,Simoni, Elena,Lodola, Alessio,Mor, Marco,Milelli, Andrea,Minarini, Anna
, p. 283 - 291 (2016/05/10)
Epidermal growth factor receptor inhibitors (EGFR-TKIs) represent a class of compounds widely used in anticancer therapy. An increasing number of studies reports on combination therapies in which the block of the EGFR-TK activity is associated with inhibition of its downstream pathways, as PI3K-Akt. Sulforaphane targets the PI3K-Akt pathway whose dysregulation is implicated in many functions of cancer cells. According to these considerations, a series of multitarget molecules have been designed by combining key structural features derived from an EGFR-TKI, PD168393, and the isothiocyanate sulforaphane. Among the obtained molecules 1-6, compound 6 emerges as a promising lead compound able to exert antiproliferative and proapoptotic effects in A431 epithelial cancer cell line by covalently binding to EGFR-TK, and reducing the phosphorylation of Akt without affecting the total Akt levels.
Total synthesis of (±)-gephyrotoxin by amide-selective reductive nucleophilic addition
Shirokane, Kenji,Wada, Takamasa,Yoritate, Makoto,Minamikawa, Ryo,Takayama, Nobuaki,Sato, Takaaki,Chida, Noritaka
, p. 512 - 516 (2014/01/23)
A chemoselective approach for the total synthesis of (±)- gephyrotoxin has been developed. The key to success was the utilization of N-methoxyamides, which enabled the direct coupling of the amide with an aldehyde and selective reductive nucleophilic addition to the amide in the presence of a variety of sensitive and electrophilic functional groups, such as a methyl ester. This chemoselective approach minimized the use of protecting-group manipulations and redox reactions, which resulted in the most concise and efficient total synthesis of (±)-gephyrotoxin described to date. Aim for selectivity: A chemoselective approach that utilizes N-methoxyamides has been developed for the total synthesis of (±)-gephyrotoxin. The N-methoxy group enabled the direct coupling of the amide with an aldehyde and amide-selective reductive allylation in the presence of a more electrophilic methyl ester, which resulted in the most concise and efficient total synthesis of (±)-gephyrotoxin described to date.
Chemoselective reductive nucleophilic addition to tertiary amides, secondary amides, and N-methoxyamides
Nakajima, Minami,Oda, Yukiko,Wada, Takamasa,Minamikawa, Ryo,Shirokane, Kenji,Sato, Takaaki,Chida, Noritaka
, p. 17565 - 17571 (2015/02/19)
As the complexity of targeted molecules increases in modern organic synthesis, chemoselectivity is recognized as an important factor in the development of new methodologies. Chemoselective nucleophilic addition to amide car-bonyl centers is a challenge because classical methods require harsh reaction conditions to overcome the poor elec-trophilicity of the amide carbonyl group. We have successfully developed a reductive nucleophilic addition of mild nu-cleophiles to tertiary amides, secondary amides, and N-methoxyamides that uses the Schwartz reagent [Cp2ZrHCl]. The reaction took place in a highly chemoselective fashion in the presence of a variety of sensitive functional groups, such as methyl esters, which conventionally require protection prior to nucleophilic addition. The reaction will be applicable to the concise synthesis of complex natural alkaloids from readily available amide groups.
5,6-Bicyclic glycoprotein IIb IIIa antagonists useful in inhibition of platelet aggregation
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, (2008/06/13)
This invention relates to 5,6 fused ring bicyclic compounds inclusive of indoles, benzofurans, and benzothiophenes, and corresponding to the formula (I) substituted with both basic (B) and acidic (A) functionality, which are useful in inhibition of platelet aggregation.
