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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.
Synonyms: 3-Hydroxybenzeneboronic acid
4.5
*For Research Use Only !
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Wen Ren ; Yuling Deng ; Jacob D. Ward ; Rebecca Vairin ; Ruoli Bai b ; Hashini I. Wanniarachchi , et al.
Abstract: The synthesis and evaluation of small-molecule inhibitors of tubulin polymerization remains a promising approach for the development of new therapeutic agents for cancer treatment. The natural products colchicine and combretastatin A-4 (CA4) inspired significant drug discovery campaigns targeting the colchicine site located on the beta-subunit of the tubulin heterodimer, but so far these efforts have not yielded an approved drug for cancer treatment in human patients. Interest in the colchicine site was enhanced by the discovery that a subset of colchicine site agents demonstrated dual functionality as both potent antiproliferative agents and effective vascular disrupting agents (VDAs). Our previous studies led to the discovery and development of a 2-aryl-3-aroyl-indole analogue (OXi8006) that inhibited tubulin polymerization and demonstrated low nM IC50 values against a variety of human cancer cell lines. A water-soluble phosphate prodrug salt (OXi8007), synthesized from OXi8006, displayed promising vascular disrupting activity in mouse models of cancer. To further extend structure-activity relationship correlations, a series of 6-aryl-3-aroyl-indole analogues was synthesized and evaluated for their inhibition of tubulin polymerization and cytotoxicity against human cancer cell lines. Several structurally diverse molecules in this small library were strong inhibitors of tubulin polymerization and of MCF-7 and MDA-MB-231 human breast cancer cells. One of the most promising analogues (KGP591) caused significant G2/M arrest of MDA-MB-231 cells, disrupted microtubule structure and cell morphology in MDA-MB-231 cells, and demonstrated significant inhibition of MDA-MB-231 cell migration in a wound healing (scratch) assay. A phosphate prodrug salt, KGP618, synthesized from its parent phenolic precursor, KGP591, demonstrated significant reduction in bioluminescence signal when evaluated in vivo against an orthotopic model of kidney cancer (RENCA-luc) in BALB/c mice, indicative of VDA efficacy. The most active compounds from this series offer promise as anticancer therapeutic agents.
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Keywords: Inhibitors of tubulin polymerization ; Vascular disrupting agents ; Indole synthesis ; Molecular docking ; Antiproliferative agents ; Inhibitors of cell migration
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Purchased from AmBeed: 128796-39-4 ; 10365-98-7 ; 98-80-6 ; 98437-24-2 ; 5720-05-8 ; 64-86-8 ; 13331-27-6 ; 206551-43-1 ; 63139-21-9 ; 622864-48-6 ; 5720-07-0 ; 87199-18-6 ; 30418-59-8 ; 4521-61-3 ; 4521-61-3 ; 87199-18-6 ; 64-86-8 ; 64-86-8 ; 128796-39-4 ; 5720-05-8 ; 64-86-8
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Pieterse, Lianie ; Beteck, Richard M. ; Baratte, Blandine ; Jesumoroti, Omobolanle J. ; Robert, Thomas ; Ruchaud, Sandrine , et al.
Abstract: Protein kinases, including CDK9/CyclinT and Haspin, are regarded as potential drug targets in cancer therapy. Findings from a previous study suggested 7-azaindole as a privileged scaffold for producing inhibitors of CDK9/CyclinT and Haspin. Inspired by these findings, the current study synthesized and evaluated thirteen (13) C6-substituted 7-azaindole and twenty (20) C4-substituted structurally related 7H-pyrrolo[2,3-d]pyrimidine derivatives against a panel of protein kinases, including CDK9/CyclinT and Haspin. Eleven of the 7H-pyrrolo[2,3-d]pyrimidine derivatives exhibited activity toward CDK9/CyclinT, while 4 of compounds had activity against Haspin. The best CDK9/CyclinT (IC50 of 0.38 μM) and Haspin (IC50 of 0.11 μM) activities were achieved by compounds 7d and 7f, resp. Hence, these compounds may be valuable starting points for development of new anti-cancer drugs.
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Keywords: 7-Deazapurine ; Anticancer ; CDK9/CylinT ; Haspin ; Protein kinase
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Purchased from AmBeed: 98437-24-2 ; 71597-85-8 ; 3680-69-1 ; 6165-68-0 ; 51067-38-0 ; 87199-18-6
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CAS No. : | 87199-18-6 |
Formula : | C6H7BO3 |
M.W : | 137.93 |
SMILES Code : | OB(C1=CC=CC(O)=C1)O |
Synonyms : |
3-Hydroxybenzeneboronic acid
|
MDL No. : | MFCD01074603 |
InChI Key : | WFWQWTPAPNEOFE-UHFFFAOYSA-N |
Pubchem ID : | 2734359 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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 |
---|---|---|
With sodium carbonate; tricyclohexylphosphine;palladium diacetate; In 1,4-dioxane; water; at 90℃; for 3h;Micro wave conditions; | A mixture of [2-(4-bromo-phenyl)-ethyl]-carbamic acid tert-butyl ester (500 mg), 3-hydroxy- benzeneboronic acid (296 mg), sodium carbonate (265 mg), palladium (II) acetate (7 mg) and tricyclohexylphosphine (10 mg) in water (3 ml) and dioxane (12 ml) is kept at 90C under micro wave conditions for 180 min. The mixture is cooled down to rt and is filtered through an EXTUBE extraction column (Varian) with EtOAc ( 200 ml). The filtrate is evaporated and the resulting crude product is purified on silica (15Og) with cyclohexane /EtOAc 5/1 to afford pure [2-(3'-hydroxy-biphenyl-4-yl)-ethyl]-carbamic acid tert-butyl ester.MS (ESI+): 336 [M+Na]; Rf: (EtOAc/hexane = 1/2): 0.28. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With palladium diacetate; potassium carbonate; In 2-methoxy-ethanol; water; at 20℃; for 15h; | General procedure: To a solution of the corresponding boronic acid (1.2mmol) in EGME/H2O (3:1, 0.25M) were added Pd(OAc)2 (0.05mmol) and K2CO3 (1.2mmol), followed by the addition of the corresponding phenyl iodide (1.0mmol). The dark reaction mixture was stirred at rt for 15h, then diluted with EtOAc (40mL) and filtered through a pad of Celite. The resulting filtrate was washed with H2O (20mL) and a 1M solution of Na2SO3 (20mL). After separation, the organic phase was dried over Na2SO4 and concentrated under reduced pressure. The residues were purified by column chromatography (Cy/EtOAc). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85.5% | With palladium diacetate; cesium fluoride; In toluene; at 25℃; for 6h; | 3-hydroxyphenyl boronic acid (formula 87-A, 12 mmol, 1.66 g), 2-bromo-5-trifluoromethyl-pyridine (formula 87-B, 10 mmol, 2.26 g), cesium fluoride (25 mmol, 3.80 g), palladium acetate (0.2 mmol, 45 mg), toluene (50 ml) were successively added to a 25 ml, three-necked reaction flask to react at room temperature (25° C.) for 6 hours. When the reaction was finished, the solution was extracted with ethyl acetate (40 ml×3) and water (40 ml), the organic phase was dried, filtered, desolventized, crystallized and dried to obtain 2.09 g of pale yellow solid, i.e. compound of formula 87-C, with the content of 97.8percent (HPLC) and the yield of 85.5percent. |
Tags: (3-Hydroxyphenyl)boronic acid | 3-Hydroxybenzeneboronic acid | Benzene Compounds | Organoboron | Aryls | Boronic Acids | Fluorinated Building Blocks | Organic Building Blocks | Organometallic Reagents | Boronic Acids/Esters | 87199-18-6
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P270 | Do not eat, drink or smoke when using this product. |
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P272 | Contaminated work clothing should not be allowed out of the workplace. |
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P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
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P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
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P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
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P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
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H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
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H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
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H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
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H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
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H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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