20474-37-7Relevant articles and documents
Design, synthesis and biological evaluation of novel N-sulfonylamidine-based derivatives as c-Met inhibitors via Cu-catalyzed three-component reaction
Fang, Sen-Biao,Li, Hui-Jing,Nan, Xiang,Wu, Rui,Wu, Yan-Chao,Zhang, Jing,Zhang, Zhi-Zhou
, (2020/06/04)
In our continuing efforts to develop novel c-Met inhibitors as potential anticancer candidates, a series of new N-sulfonylamidine derivatives were designed, synthesized via Cu-catalyzed multicomponent reaction (MCR) as the key step, and evaluated for their in vitro biological activities against c-Met kinase and four cancer cell lines (A549, HT-29, MKN-45 and MDA-MB-231). Most of the target compounds showed moderate to significant potency at both the enzyme-based and cell-based assay and possessed selectivity for A549 and HT-29 cancer cell lines. The preliminary SAR studies demonstrated that compound 26af (c-Met IC50 = 2.89 nM) was the most promising compound compared with the positive foretinib, which exhibited the remarkable antiproliferative activities, with IC50 values ranging from 0.28 to 0.72 μM. Mechanistic studies of 26af showed the anticancer activity was closely related to the blocking phosphorylation of c-Met, leading to cell cycle arresting at G2/M phase and apoptosis of A549 cells by a concentration-dependent manner. The promising compound 26af was further identified as a relatively selective inhibitor of c-Met kinase, which also possessed an acceptable safety profile and favorable pharmacokinetic properties in BALB/c mouse. The favorable drug-likeness of 26af suggested that N-sulfonylamidines may be used as a promising scaffold for antitumor drug development. Additionally, the docking study and molecular dynamics simulations of 26af revealed a common mode of interaction with the binding site of c-Met. These positive results indicated that compound 26af is a potential anti-cancer candidate for clinical trials, and deserves further development as a selective c-Met inhibitor.
Rh(III)-Catalyzed C(8)-H Activation of Quinoline N-Oxides: Regioselective C-Br and C-N Bond Formation
Dhiman, Ankit Kumar,Gupta, Shiv Shankar,Sharma, Ritika,Kumar, Rakesh,Sharma, Upendra
, p. 12871 - 12880 (2019/11/02)
A highly efficient and regioselective Rh(III)-catalyzed protocol for C8-bromination and amidation of quinoline N-oxide was developed. The transformation was found to be successful up to gram scale with excellent functional group tolerance and wide substrate scope. The mechanistic study revealed five-membered rhodacycle with quinoline N-oxide as a key intermediate for regioselective C8-functionalization. In addition, NFSI (N-fluorobis(phenylsulfonyl)-imide) was explored as an amidating reagent for C8-amidation of quinoline N-oxide for the first time.
Palladium(0)-Catalyzed Carbonylative Synthesis of N-Acylsulfonamides via Regioselective Acylation
Schembri, Luke S.,Eriksson, Jonas,Odell, Luke R.
, p. 6970 - 6981 (2019/06/14)
N-Acylsulfonamides represent an important bioisostere of carboxylic acids that allow for greater molecular elaboration and enhanced hydrogen bonding capabilities. Herein, we present a mild and convenient palladium(0)-catalyzed synthesis of N-acylsulfonamides via the carbonylative coupling of sulfonyl azides and electron-rich heterocycles. The reaction proceeds via in situ generation of a sulfonyl isocyanate followed by regioselective acylation of an indole or pyrrole nucleophile. This approach has been used to synthesize 34 indole- and pyrrole-substituted N-acylsulfonamides in yields of up to 95%. Importantly, this process is ligand-free and compatible with an ex situ solid CO source and requires only slightly elevated temperatures, making it a highly attractive method for the preparation of this important class of compounds. This study further investigated the possibility of labeling N-acylsulfonamides with carbon-11 to facilitate biological evaluation and in vivo studies with positron emission tomography.
