10602-06-9Relevant academic research and scientific papers
A fragment-based approach for the development of g-quadruplex ligands: Role of the amidoxime moiety
Tassinari, Martina,Lena, Alberto,Butovskaya, Elena,Pirota, Valentina,Nadai, Matteo,Freccero, Mauro,Doria, Filippo,Richter, Sara N.
, (2018)
G-quadruplex (G4) nucleic acid structures have been reported to be involved in several human pathologies, including cancer, neurodegenerative disorders and infectious diseases; however, G4 targeting compounds still need implementation in terms of drug-lik
Design, synthesis and biological evaluation of 3-(imidazo[1,2-a]pyrazin-3-ylethynyl)-2-methylbenzamides as potent and selective pan-tropomyosin receptor kinase (TRK) inhibitors
Cui, Shengyang,Wang, Yongjin,Wang, Yuting,Tang, Xia,Ren, Xiaomei,Zhang, Lei,Xu, Yong,Zhang, Zhang,Zhang, Zhi-Min,Lu, Xiaoyun,Ding, Ke
, p. 470 - 482 (2019)
A series of 3-(imidazo[1,2-a]pyrazin-3-ylethynyl)-2-methylbenzamides was designed and synthesized as new tropomyosin receptor kinases (Trks) inhibitors by utilizing a structure-guided optimization strategy. One of the most potent compounds 9o suppressed TrkA/B/C with IC50 values of 2.65, 10.47 and 2.95 nM, respectively. The compound dose-dependently inhibited brain-derived neurotrophic factor (BDNF)-mediated TrkB activation and suppressed migration and invasion of SH-SY5Y-TrkB neuroblastoma cells expressing high level of TrkB. Inhibitor 9o also inhibited the proliferation of SH-SY5Y-TrkB cells with an IC50 value of 58 nM, which was comparable to that of an US FDA recently approved drug LOXO-101. Compound 9o may serve as a new lead compound for further anti-cancer drug discovery.
Iron-Catalyzed Vinylzincation of Terminal Alkynes
Huang, Qiang,Su, Yu-Xuan,Sun, Wei,Hu, Meng-Yang,Wang, Wei-Na,Zhu, Shou-Fei
supporting information, p. 515 - 526 (2022/01/08)
Organozinc reagents are among the most commonly used organometallic reagents in modern synthetic chemistry, and multifunctionalized organozinc reagents can be synthesized from structurally simple, readily available ones by means of alkyne carbozincation. However, this method suffers from poor tolerance for terminal alkynes, and transformation of the newly introduced organic groups is difficult, which limits its applications. Herein, we report a method for vinylzincation of terminal alkynes catalyzed by newly developed iron catalysts bearing 1,10-phenanthroline-imine ligands. This method provides efficient access to novel organozinc reagents with a diverse array of structures and functional groups from readily available vinylzinc reagents and terminal alkynes. The method features excellent functional group tolerance (tolerated functional groups include amino, amide, cyano, ester, hydroxyl, sulfonyl, acetal, phosphono, pyridyl), a good substrate scope (suitable terminal alkynes include aryl, alkenyl, and alkyl acetylenes bearing various functional groups), and high chemoselectivity, regioselectivity, and stereoselectivity. The method could significantly improve the synthetic efficiency of various important bioactive molecules, including vitamin A. Mechanistic studies indicate that the new iron-1,10-phenanthroline-imine catalysts developed in this study have an extremely crowded reaction pocket, which promotes efficient transfer of the vinyl group to the alkynes, disfavors substitution reactions between the zinc reagent and the terminal C–H bond of the alkynes, and prevents the further reactions of the products. Our findings show that iron catalysts can be superior to other metal catalysts in terms of activity, chemoselectivity, regioselectivity, and stereoselectivity when suitable ligands are used.
COMBINATION PRODUCT FOR THE TREATMENT OF CANCEROUS DISEASES
-
, (2021/12/31)
The present invention relates to a product for combination therapies useful for the treatment of cancer diseases. In particular, the invention relates to the combination of an anti-PD-Ll antibody and an MCT4 inhibitor of Formula (I). The therapeutic combination may be utilized for the use in treating a subject having a cancer disease that tests positive for PD-L1 and/or MCT4 expression.
DISUBSTITUTED ALKYNE DERIVATIVES
-
Page/Page column 143-146, (2020/07/14)
The present invention relates to disubstituted alkyne derivatives. These compounds are useful for the prevention and/or treatment of several medical conditions including hyperproliferative disorders and diseases.
Palladium-Catalyzed Cascade Intramolecular Cyclization and Allylation of Enynoates with Allylic Alcohols
Qiu, Sheng-Qi,Ahmad, Tanveer,Xu, Yun-He,Loh, Teck-Peng
, p. 6729 - 6736 (2019/06/14)
A Pd(II)-catalyzed mild and highly regioselective 6-endo cyclization/allylation reaction of enynoates with simple allylic alcohols has been developed. Under mild reaction conditions, the vinyl palladium species generated in situ after cyclization could insert C-C double bond of allylic alcohol through cross-coupling reaction and lead to the formation of allyl pyrone via β-OH elimination. This cascade cross-coupling reaction represents a direct and atom economic methodology for the construction of novel allyl pyrones in moderate to good yields.
Pyrtriazoles, a Novel Class of Store-Operated Calcium Entry Modulators: Discovery, Biological Profiling, and in Vivo Proof-of-Concept Efficacy in Acute Pancreatitis
Riva, Beatrice,Griglio, Alessia,Serafini, Marta,Cordero-Sanchez, Celia,Aprile, Silvio,Di Paola, Rosanna,Gugliandolo, Enrico,Alansary, Dalia,Biocotino, Isabella,Lim, Dmitry,Grosa, Giorgio,Galli, Ubaldina,Niemeyer, Barbara,Sorba, Giovanni,Canonico, Pier Luigi,Cuzzocrea, Salvatore,Genazzani, Armando A.,Pirali, Tracey
supporting information, p. 9756 - 9783 (2018/11/23)
In recent years, channels that mediate store-operated calcium entry (SOCE, i.e., the ability of cells to sense a decrease in endoplasmic reticulum luminal calcium and induce calcium entry across the plasma membrane) have been associated with a number of d
FAK AND FLT3 INHIBITORS
-
, (2014/03/22)
The use of a compound of the formula (I): (Formula (I)) in the preparation of a medicament for treating Acute Myeloid Leukemia or a disease ameliorated by the inhibition of Flt3, or Flt3 and FAK.
Discovery and optimization of 3-(2-(Pyrazolo[1,5- a ]pyrimidin-6-yl) ethynyl)benzamides as novel selective and orally bioavailable discoidin domain receptor 1 (DDR1) inhibitors
Gao, Mingshan,Duan, Lei,Luo, Jinfeng,Zhang, Lianwen,Lu, Xiaoyun,Zhang, Yan,Zhang, Zhang,Tu, Zhengchao,Xu, Yong,Ren, Xiaomei,Ding, Ke
supporting information, p. 3281 - 3295 (2013/06/04)
Discoidin domain receptor 1 (DDR1) is an emerging potential molecular target for new anticancer drug discovery. We have discovered a series of 3-(2-(pyrazolo[1,5-a]pyrimidin-6-yl) ethynyl)benzamides that are selective and orally bioavailable DDR1 inhibitors. The two most promising compounds (7rh and 7rj) inhibited the enzymatic activity of DDR1, with IC50 values of 6.8 and 7.0 nM, respectively, but were significantly less potent in suppressing the kinase activities of DDR2, Bcr-Abl, and c-Kit. Further study revealed that 7rh bound with DDR1 with a Kd value of 0.6 nM, while it was significantly less potent to the other 455 kinases tested. The S(35) and S(10) selectivity scores of 7rh were 0.035 and 0.008, respectively. The compounds also potently inhibited the proliferation of cancer cells expressing high levels of DDR1 and strongly suppressed cancer cell invasion, adhesion, and tumorigenicity. Preliminary pharmacokinetic studies suggested that they possessed good PK profiles, with oral bioavailabilities of 67.4% and 56.2%, respectively.
Palladium-catalyzed trifluoroethylation of terminal alkynes with 1,1,1-trifluoro-2-iodoethane
Feng, Yi-Si,Xie, Chuan-Qi,Qiao, Wen-Long,Xu, Hua-Jian
supporting information, p. 936 - 939 (2013/03/28)
An efficient Csp-CH2CF3 bond-forming reaction via Pd-catalyzed 2,2,2-trifluoroethylation of aryl and alkyl terminal alkynes has been developed. This protocol proceeds under mild conditions using the readily available and cheap reagent CF3CH2I as the source of the CH2CF3 group. Various terminal aryl alkynes as well as alkylacetylenes can be transformed into the corresponding trifluoroethylated products in good-to-excellent yields. The method is tolerant of carbonyl, nitro, ester, cyano, and even formyl groups.
