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Type | HazMat fee for 500 gram (Estimated) |
Excepted Quantity | USD 0.00 |
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Inaccessible (Haz class 6.1), Domestic | USD 80+ |
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Structure of 622-59-3
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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Design and Development of CARP-1-NEMO Binding Inhibitors for Breast Cancer
DEEPTI PANDEY ;
Abstract: Cancer continues to be a leading global health concern. Despite notable progress in current chemotherapeutics, drug resistance often contributes to treatment failure and poor prognosis. NF-κB signaling pathway has been long considered a prime regulator of normal biological processes and tumor cell survival, proliferation, and growth, which often contributes to resistant phenotypes. One reason for the resistance is the activation of DNA damage-induced canonical NF-κB that is transduced in part by interaction of CARP-1 protein with NF-κB activating kinase subunit gamma or NEMO. High throughput screening (HTS) of the chemical library yielded a selective NF-κB inhibitor (SNI)-1 that showed remarkable inhibition of CARP-1 and NEMO interaction in vitro, and consequent loss of canonical NF-κB activation that resulted in elevated cytotoxicity of chemotherapeutics adriamycin or cisplatin in vitro and in vivo. We aimed to synthesize and evaluate the selective NF-κB inhibitor (SNI)-1 analogs to improve their solubility, stability, and efficacy of cytotoxic chemotherapy. We are utilized Structure-Activity Relationship (SAR) strategies to identify a series of compounds. Several modifications and changes in specific moieties in SNI-1 were predicted to enhance compound drug-like properties such as solubility and biological activity. To date, we identified a few lead compounds that showed better potential to inhibit cell viability of different breast cancer cell lines compared to the parent compound. Our lead compounds GL-213, GL-216, GL-252, GL-269, and GL-340, GL-341, GL-342, and GL-343 have shown an effect on cell viability on their own, and in some instances, greater enhancement of chemotherapeutic efficacies in vitro assays. Thus, targeting of CARP-1 binding with NEMO has the potential to offer novel tools or strategies to combat various breast cancer and their drug-resistant variants. Outcomes of our current SAR studies are expected to identify additional potent drug-like lead compounds that will function in part by abrogating chemotherapy-induced NF-κB signaling activation and help minimize the development of drug-induced resistance and toxicities in breast cancers.
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CAS No. : | 622-59-3 |
Formula : | C8H7NS |
M.W : | 149.21 |
SMILES Code : | CC1=CC=C(N=C=S)C=C1 |
MDL No. : | MFCD00004813 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H315-H319-H335-H317-H334 |
Precautionary Statements: | P261-P264-P271-P272-P280-P285-P302+P352-P304+P340-P305+P351+P338-P332+P313-P337+P313-P342+P311-P362-P403+P233-P405-P501 |
Class: | 6.1 |
UN#: | 2811 |
Packing Group: | Ⅱ |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethyl acetate; | Example 69 4-Methoxy-N-phenyl-3-(-3-p-tolyl-thioureido)-benzamide Prepared according to the procedure described for Example 60 using 3-amino-4-methoxy-N-phenyl-benzamide (0.243 g, 1.0 mmol) and 4-methylphenyl isothiocyanate (0.205 g, 1.38 mmol). The reaction was incomplete after 2 days, so the mixture was diluted to 30 mL with ethyl acetate, and a small additional portion of 4-methylphenyl isothiocyanate was added. The mixture was boiled on a steambath until no solvent remained and the residue triturated in hexanes/ethyl acetate (4:1) and filtered to afford the product (0.255 g); m.p. 156-158 C. CI Mass Spectrum: [M+H+]+=392. Calculated for C22H21N3O2S.0.5 H2O: C, 65.97; H, 5.54; N, 10.49. Found: C, 66.16; H, 5.60; N, 10.31. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With pyridine;Reflux; | General procedure: To a solution of the thiazole 1 (0.93 g, 5 mmol) in pyridine (10 mL) was added the appropriate isothiocyanate (6 mmol). The reaction mixture was heated under reflux for 5-6 h then allowed to attain room temperature. Working up of the reaction mixture was carried out as described under 9a,b. Physicochemical and analytical data are recorded in Table 3. IR (cm-1): 3470-2935 (NH), 1730- 1718 (C=O), 982-958 (NCS). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With montmorillonite K10 Clay; In acetonitrile; at 20℃; for 1h; | General procedure: A round bottom flask containing commercially available montmorillonite K10 (10 molpercent) was placed in an oven at 120-130°C for 30 minutes and then it was cooled to room temperature under nitrogen protection. To the activated montmorillonite K10 was added isothiocyanate (3.4 mmol) and <strong>[25475-67-6]3-aminoisoquinoline</strong> (3.4 mmol) followed by acetonitrile (2 mL) at room temperature. The resulting suspension was stirred at room temperature for 1-3 hour. When the reaction was completed (detected by TLC), ethyl acetate (30 mL) was added and the catalyst was filtered off to recover. The organic layer was washed with water (3×30 mL), and finally with half saturated brine, dried over anhydrous Na2SO4 and concentrated by rotary evaporator. Finally, the residue was purified by recrystallization from ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With 1,8-diazabicyclo[5.4.0]undec-7-ene; In tetrahydrofuran; at 0℃; for 0.333333h;Inert atmosphere; | General procedure: A4 (100mg, 0.6mmol) was combined with 2-chloro-4-nitrophenyl isothiocyanate (129mg, 0.6mmol) in anhydrous THF (30mL) at 0C, followed by the addition of DBU (106mg, 0.7mmol). The resultant mixture was stirred at 0C for 20min, after which the ice bath was removed, and the reaction mixture was stirred at room temperature until the completion of the reaction indicated by TLC. The crude product was purified by column chromatography (chloroform/methanol, 30/1). |