1240912-19-9Relevant academic research and scientific papers
Design, synthesis and anticancer activity of 5-aryl-4-(4-arylpiperazine-1-carbonyl)-1,2,3-thiadiazoles as microtubule-destabilizing agents
Wang, Chao,Wang, Zeyu,Gao, Minghuan,Li, Yuelin,Zhang, Yujing,Bao, Kai,Wu, Yingliang,Guan, Qi,Zuo, Daiying,Zhang, Weige
, (2020/12/21)
Hereby, we report our efforts on discovery and optimization of a new series of 5-aryl-4-(4-arylpiperazine-1-carbonyl)-1,2,3-thiadiazoles as new microtubule-destabilizing agents along our previous study. Guided by docking model analysis, we introduced the 1,2,3-thiadiazole moiety containing the hydrogen-bond acceptors as B-ring of XRP44X analogues. Extensive structure modifications were performed to investigate the detailed structure and activity relationships (SARs). Some compounds exhibited potent antiproliferative activities against three human cancer cell lines (SGC-7901, A549 and HeLa). The compound 5m exhibited the highest potency against the three cancer cell lines. The tubulin polymerization experiments indicated that compound 5m effectively inhibited the tubulin polymerization, and immunostaining assay revealed that it significantly disrupted microtubule dynamics. Moreover, cell cycle studies revealed that compound 5m dramatically arrested cell cycle progression at G2/M phase.
2,5-Disubstituted Pyrazolo[4,3-c]cinnolin-3-ones
Beshore, Douglas C.,Johnson, Adam W.,DiPardo, Robert M.,Pitts, Daniel R.,Cofre, Victoria,Kuduk, Scott D.
, p. 1558 - 1571 (2017/03/27)
Complementary strategies to 2,5-disubstituted pyrazolo[4,3-c]cinnolin-3-ones are reported herein, providing late stage substituent introduction at either the 2- or the 5-position. Treating a readily prepared 4-thiocinnoline ester with substituted hydrazines afforded late stage access to the 2-position, while late stage substituent introduction at the 5-position was achieved via two different strategies: alkylation of 4-hydrazonopyrazol-3-ones, followed by a ring-closing intramolecular SNAr tactic and direct reaction of 5-(2-fluorophenyl)-2,4-dihydro-3H-pyrazol-3-ones with aryl diazonium salts, followed by cyclization. The strategies described herein provide practical and general methods to prepare 2,5-disubstituted pyrazolo[4,3-c]cinnolin-3-ones.
C-H Activation-Based Traceless Synthesis via Electrophilic Removal of a Directing Group. Rhodium(III)-Catalyzed Entry into Indoles from N-Nitroso and α-Diazo-β-keto Compounds
Wang, Jie,Wang, Mingyang,Chen, Kehao,Zha, Shanke,Song, Chao,Zhu, Jin
supporting information, p. 1178 - 1181 (2016/03/15)
A distinct C-H activation-based traceless synthetic protocol via electrophilic removal of a directing group is reported, complementing the currently exclusively used nucleophilic strategy. Rh(III)-catalyzed, N-nitroso-directed C-H activation allows the development of a traceless, atom- and step-economic, cascade approach for the synthesis of indole skeletons, starting from readily available N-nitroso and α-diazo-β-keto compounds. Importantly, the cyclization/denitrosation reaction represents a hitherto unobserved reactivity pattern for the N-nitroso group.
PYRAZOLO [4,3-c] CINNOLIN-3-ONE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS
-
Page/Page column 51, (2010/09/17)
The present invention is directed to pyrazolo [4,3-c] cinnolin-3-one compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.
