1008450-80-3

Upstream product

• 6248-20-0 2,4-dihydroxy-3-methylbenzaldehyde 
• 100-39-0 benzyl bromide 
• 608-25-3 2-methylbenzene-1,3-diol 
• 100-44-7 benzyl chloride 

Downstream Products

• 81633-95-6 3-methoxy-2,4-dimethylphenol 
• 1318760-76-7 4-hydroxy-3-methoxy-2,4-dimethylcyclohexa-2,5-dienone 
• 1318760-77-8 tert-butyl (2-methoxy-1,3-dimethyl-4-oxocyclohexa-2,5-dien-1-yl) malonate 
• 1008450-83-6 4-(benzyloxy)-2-methoxy-3-methylbenzaldehyde 
• 1349842-72-3 6-bromo-3-methoxy-2,4-dimethylphenol 
• 1349842-76-7 6-bromo-4-hydroxy-3-methoxy-2,4-dimethylcyclohexa-2,5-dienone 
• 1349842-79-0 5-bromo-2-methoxy-1,3-dimethyl-4-oxocyclohexa-2,5-dien-1-yl-tert-butyl malonate 
• 185981-91-3 2,5,2'-Tris-benzyloxy-4,4',5'-trimethoxy-3,3'-dimethyl-biphenyl 
• 185981-80-0 1,4-Bis-benzyloxy-5-bromo-2-methoxy-3-methyl-benzene 

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.

Benzoxaborole Antimalarial Agents. Part 5. Lead Optimization of Novel Amide Pyrazinyloxy Benzoxaboroles and Identification of a Preclinical Candidate

Carboxamide pyrazinyloxy benzoxaboroles were investigated with the goal to identify a molecule with satisfactory antimalarial activity, physicochemical properties, pharmacokinetic profile, in vivo efficacy, and safety profile. This optimization effort discovered 46, which met our target candidate profile. Compound 46 had excellent activity against cultured Plasmodium falciparum, and in vivo against P. falciparum and P. berghei in infected mice. It exhibited good PK properties in mice, rats, and dogs. It was highly active against the other 11 P. falciparum strains, which are mostly resistant to chloroquine and pyrimethamine. The rapid parasite in vitro reduction and in vivo parasite clearance profile of 46 were similar to those of artemisinin and chloroquine, two rapid-acting antimalarials. It was nongenotoxic in an Ames assay, an in vitro micronucleus assay, and an in vivo rat micronucleus assay when dosed orally up to 2000 mg/kg. The combined properties of this novel benzoxaborole support its progression to preclinical development.

Modified biphenyl Hsp90 C-terminal inhibitors for the treatment of cancer

Heat Shock Protein 90 (Hsp90) is a molecular chaperone under clinical investigation for the treatment of neurodegenerative diseases and cancer. Neuroprotective Hsp90 C-terminal inhibitors (novologues) contain a biaryl ring system, and include KU-596, which was modified and investigated for potential anti-cancer activity. Incorporation of a benzamide group onto the biaryl novologues in lieu of the acetamide yielded compounds that manifest anti-cancer activity. Further exploration of the central phenyl ring led to compounds with enhanced anti-proliferative activity. The design, synthesis, and evaluation of these new analogs against breast and prostate cancer cell lines is reported herein, where it was found that 8b and 10 manifest potent anti-proliferative activity and a robust degradation of Hsp90 client-dependent proteins.

1 -HYDROXY-BENZOOXABOROLES AS ANTIPARASITIC AGENTS

Provided are compounds useful for controlling endoparasites both in animals and agriculture. Further provided are methods for controlling endoparasite infestations of an animal by administering an effective amount of a compound as described above, or a pharmaceutically acceptable salt thereof, to an animal, as well as formulations for controlling endoparasite infestations using the compounds described above or an acceptable salt thereof, and an acceptable carrier. The claimed compounds are described by the following Markush formula:A typical example for a compound according to above formula is: A typical example for a compound according to above formula is:

A concise synthetic approach to the sorbicillactones: Total synthesis of sorbicillactone A and 9-epi-sorbicillactone A

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

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

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.