748183-46-2

Upstream product

• 1400584-71-5 1-[3-fluoro-4-(1-methylbutoxy)-phenyl]-ethanone 
• 107-81-3 2-bromopentane 
• 350-29-8 3-fluoro-4-hydroxybenzoic acid 

Relevant 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

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.

SUBSTITUTED N-ARYLHETEROCYCLES, METHOD FOR PRODUCTION AND USE THEREOF AS MEDICAMENTS

The invention relates to N-arylheterocycles and the physiologically-acceptable salts and physiologically-functional derivatives thereof. Compounds of formula (I), where the groups have the given meanings, the N-oxides and the physiologically-acceptable salts and methods for production thereof are disclosed. The compounds are suitable as anorectics for example.

Substituted N-aryl heterocycles, process for their preparation and their use as medicaments

The invention relates to substituted N-aryl heterocycles and to the physiologically tolerated salts and physiologically functional derivatives thereof. Compounds of the formula I in which the radicals have the stated meanings, the N-oxides and the physiologically tolerated salts thereof and process for the preparation thereof are described. The compounds are suitable for example as anorectic agents.