1008450-83-6Relevant academic research and scientific papers
Rational drug design of benzothiazole-based derivatives as potent signal transducer and activator of transcription 3 (STAT3) signaling pathway inhibitors
Gao, Dingding,Jin, Nan,Fu, Yixian,Zhu, Yueyue,Wang, Yujie,Wang, Ting,Chen, Yuehong,Zhang, Mingming,Xiao, Qiang,Huang, Min,Li, Yingxia
, (2021/03/14)
The cumulative evidence supports STAT3, a transcriptional mediator of oncogenic signaling, as a therapeutic target in cancer. The development of STAT3 inhibitors remain an active area of research as no inhibitors have yet to be approved for cancer treatment. In a continuing effort to develop more potent STAT3 inhibitors based on our previously identified hit compound 16w, a series of benzothiazole derivatives with unique binding mode in SH2 domain of STAT3 were designed, synthesized and biologically evaluated. Of note, compound B19 demonstrated excellent activity against IL-6/STAT3 signaling pathway with the IC50 value as low as 0.067 μM as determined by a luciferase reporter assay. Moreover, multiple compounds displayed potent antiproliferative activity against MDA-MB-468 and JAK2 mutant HEL cell lines. Further biochemical study using Western blot assay indicated that B19 blocked the phosphorylation of STAT3 at Tyr 705 and Ser 727 and thus suppressed STAT3-mediated gene expression of c-MYC and MCL-1. Simultaneously, it induced cancer cell G2/M phase arrest and apoptosis both in MDA-MB-468 and HEL cell lines. Finally, molecular docking study along with surface plasmon resonance (SPR) and fluorescence polarization (FP) assays disclosed the binding mode of B19 in STAT3 SH2 domain. Taken together, our finding suggests that B19 is a promising therapeutic STAT3 inhibitor for cancer treatment.
A concise synthetic approach to the sorbicillactones: Total synthesis of sorbicillactone A and 9-epi-sorbicillactone A
Volp, Kelly A.,Johnson, Diane M.,Harned, Andrew M.
, p. 4486 - 4489 (2011/10/09)
A concise (12 step) total synthesis of sorbicillactone A and 9-epi-sorbicillactone A is reported. Unlike typical routes to the sorbicillinoids, this strategy does not start from sorbicillin and allows for the production of the bicyclic core on a multigram scale. The intramolecular conjugate addition of a tethered malonate serves as an effective means of introducing the lactone ring and provides a synthetic handle for installing the amide nitrogen.
Regioselective and stereoselective cyclizations of cyclohexadienones tethered to active methylene groups
Tello-Aburto, Rodolfo,Kalstabakken, Kyle A.,Volp, Kelly A.,Harned, Andrew M.
, p. 7849 - 7859 (2011/12/04)
The cyclization of 2,5-cyclohexadienones tethered to activated methylene groups was studied. The substitution around the cyclohexadienone ring serves to regioselectively direct these cyclizations based primarily on electronic effects. In the case of brominated substrates, these reactions proceed to give highly unusual electron-deficient tricyclic cyclopropanes. By using a Cinchona alkaloid-based phase-transfer catalyst, prochiral cyclohexadienones can be desymmetrized with moderate stereoselectivity.
Biaryl formation using the Suzuki protocol: Considerations of base, halide, and protecting group
Benbow, John W.,Martinez, Bonnie L.
, p. 8829 - 8832 (2007/10/03)
The generation of aryl anions prior to quenching with a trialkyl berate has been shown to be sensitive to the composition of the aryl substrate. Aryl iodides containing remote benzyl ether substituents undergo trans-metallation with sec-BuLi to cleanly give the desired aryl anions whereas the corresponding bromides afford appreciable quantities of dianionic intermediates. The aryl boronic acids derived from alkylation of these anions subsequently undergo a palladium mediated coupling with aryl halides to provide good yields of the desired biaryls. Copyright (C) 1996 Elsevier Science Ltd.
