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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.
3,5-Dimethylbenzaldehyde is an aromatic aldehyde commonly used in organic synthesis and the fragrance industry, serving as a building block in chemical synthesis.
4.5
*For Research Use Only !
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Selective and Cell-Active PBRM1 Bromodomain Inhibitors Discovered through NMR Fragment Screening
Shifali Shishodia ; Raymundo Nuñez ; Brayden P. Strohmier ; Karina L. Bursch ; Christopher J. Goetz ; Michael D. Olp , et al.
Abstract: PBRM1 is a subunit of the PBAF chromatin remodeling complex that uniquely contains six bromodomains. PBRM1 can operate as a tumor suppressor or tumor promoter. PBRM1 is a tumor promoter in prostate cancer, contributing to migratory and immunosuppressive phenotypes. Selective chemical probes targeting PBRM1 bromodomains are desired to elucidate the association between aberrant PBRM1 chromatin binding and cancer pathogenesis and the contributions of PBRM1 to immunotherapy. Previous PBRM1 inhibitors unselectively bind SMARCA2 and SMARCA4 bromodomains with nanomolar potency. We used our protein-detected NMR screening pipeline to screen 1968 fragments against the second PBRM1 bromodomain, identifying 17 hits with Kd values from 45 μM to >2 mM. Structure–activity relationship studies on the tightest-binding hit resulted in nanomolar inhibitors with selectivity for PBRM1 over SMARCA2 and SMARCA4. These chemical probes inhibit the association of full-length PBRM1 to acetylated histone peptides and selectively inhibit growth of a PBRM1-dependent prostate cancer cell line.
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Purchased from AmBeed: 77326-36-4 ; 104-87-0 ; 2148-56-3 ; 63329-53-3 ; 1591-37-3 ; 387-45-1 ; 936-08-3 ; 1123-56-4 ; 2819989-75-6 ; 703-80-0 ; 1885-29-6 ; 115643-59-9 ; 15764-16-6 ; 487-68-3 ; 145737-61-7 ; 5779-95-3 ; 88-68-6 ; 6575-11-7 ; 77326-62-6 ; 88-65-3 ; 4635-59-0 ; 5779-94-2 ; 56043-01-7 ; 5779-93-1 ; 1591-38-4 ; 446-52-6 ; 62803-47-8 ; 1885-31-0 ; 620-23-5 ; 54166-95-9 ; 22179-72-2 ; 529-20-4 ; 100-52-7 ; 123-11-5 ; 1711-06-4 ; 454-89-7 ; 170875-01-1 ; 883032-29-9 ; 2819989-61-0 ; 1915012-21-3 ; 2819989-58-5 ; 2819989-60-9 ; 2819989-57-4 ; 2819989-68-7 ; 2819989-67-6 ; 111478-13-8 ; 73096-42-1 ; 2835-78-1 ; 118-92-3 ; 22458-07-7 ; 80258-99-7 ; 24782-64-7 ; 1108790-90-4 ; 175204-03-2 ; 97-96-1 ; 780802-33-7 ; 89-98-5
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CAS No. : | 5779-95-3 |
Formula : | C9H10O |
M.W : | 134.17 |
SMILES Code : | C1=C(C=C(C)C=C1C)C=O |
MDL No. : | MFCD00082777 |
InChI Key : | NBEFMISJJNGCIZ-UHFFFAOYSA-N |
Pubchem ID : | 34225 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H227-H315-H319-H335 |
Precautionary Statements: | 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 |
---|---|---|
Example 218 4-Methoxy-3-(3,5-dimethyl-benzylamino)-N-phenyl-benzamide The title compound has been made using the procedure of Example 50, but using 3-amino-4-methoxy-N-phenyl benzamide and 3,5-dimethylbenzaldehyde as starting materials, which are commercially available from Aldrich or Lancaster; m.p. 168-170 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With hydrogenchloride; In water; at 35 - 50℃; for 6h;Inert atmosphere; Reflux; | Equipped with a mechanical stirrer, a condenser and a nitrogen gas through the mouth of the three-necked flask, were added 61.28g (0.40mol) 2,6- dimethoxy aniline and 135.00mL distilled water, stir under a nitrogen atmosphere.40.50mL slowly added dropwise concentrated hydrochloric acid (37% mass fraction), the temperature of the system was maintained at 35 , then portionwise added 28.14g (0.21mol) 3,5- dimethylbenzaldehyde.System under reflux with vigorous stirring After 6h, the reaction system temperature was lowered to 50 , added in portions with stirring 16.40g sodium hydroxide powder.The solution was subjected to steam distillation, after suction filtration to obtain a solid powder.A solid powder with hot water, and dried dioxane was recrystallized, and dried to give α, α- bis (4-amino-3,5-dimethoxyphenyl) -1- (3 ', 5'-A phenyl) methane solid powder 77.56g (92% yield) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | In ethanol; at 80℃; for 8h; | General procedure: ZrO2-Al2O3 solid acid catalytic material was added to the stirred solution of O-phenylenediamines and different substituted aromatic aldehydes in a suitable solvent, and the resulting mixture was heated at a particular temperature and monitored by TLC. After the completion of the reaction, the reaction mixture was cooled and filtered and the residue was washed with ethanol to recover the solid acid catalyst. Filtrate was evaporated in vacuum to get the crude reaction product, which was then purified by silica-gel column chromatography using a suitable mobile phase to separate the desired product. The reaction products were characterized by melting point, 1H NMR and 13C NMR spectroscopy (Bruker, 400 MHz), LC-MS (Varian), and HPLC (Waters) techniques |
Tags: 3,5-Dimethylbenzaldehyde | Benzene Compounds | Aryls | Aldehydes | Organic Building Blocks | 5779-95-3
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P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
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P305 | IF IN EYES: |
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P310 | Immediately call a POISON CENTER or doctor/physician. |
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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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P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
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 |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
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 |
H261 | In contact with water releases flammable gas |
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Health hazards | |
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H301 | Toxic if swallowed |
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H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
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H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
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H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
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H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
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H371 | May cause damage to organs |
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H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
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H400 | Very toxic to aquatic life |
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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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