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Chemical Structure| 54166-95-9 Chemical Structure| 54166-95-9

Structure of 54166-95-9

Chemical Structure| 54166-95-9

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Product Citations

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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Product Details of [ 54166-95-9 ]

CAS No. :54166-95-9
Formula : C7H7ClN2O
M.W : 170.60
SMILES Code : O=C(N)C1=C(Cl)C=CC=C1N
MDL No. :MFCD00234296
InChI Key :RMDBIAFBDRRSOK-UHFFFAOYSA-N
Pubchem ID :13675968

Safety of [ 54166-95-9 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H312-H315-H319-H332-H335
Precautionary Statements:P261-P264-P270-P271-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338-P330-P332+P313-P337+P313-P362-P403+P233-P405-P501

Application In Synthesis of [ 54166-95-9 ]

* 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.

  • Downstream synthetic route of [ 54166-95-9 ]

[ 54166-95-9 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 1039948-89-4 ]
  • [ 54166-95-9 ]
  • [ 1246250-77-0 ]
YieldReaction ConditionsOperation in experiment
64% With toluene-4-sulfonic acid; sodium hydrogensulfite; In N,N-dimethyl acetamide; at 120℃; for 23.0h;Inert atmosphere; <strong>[1039948-89-4]4-(2-hydroxyethoxy)-3,5-dimethylbenzaldehyde</strong> (0.70 g, 3.58 mmol), 2-amino-6-chlorobenzamide (0.60 g, 3.51 mmol), sodium bisulfite (0.71 g, 3.86 mmol) and p-toluenesulfonic acid monohydrate (0.133 g, 0.699 mmol) in anhydrous N,N-dimethyl acetamide (14 mL) were heated at 120 C. under nitrogen for 23 hours. The solvent was evaporated and the white solid was triturated with water (50 mL), filtered, and washed with water (20 mL). The solid was dried in vacuo and triturated with Et2O (20 mL), filtered, and dried to give 5-chloro-2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)quinazolin-4(3H)-one as a white solid. Yield: 0.77 g, (64%)
64% With toluene-4-sulfonic acid; sodium hydrogensulfite; In N,N-dimethyl acetamide; at 120℃; for 23.0h;Inert atmosphere; 4-(2-Hydroxyethoxy)-3,5-dimethylbenzaldehyde (0.70 g, 3.58 mmol), 2-amino-6-chlorobenzamide (0.60 g, 3.51 mmol), sodium bisulfite (0.71 g, 3.86 mmol) and p-toluenesulfonic acid monohydrate (0.133 g, 0.699 mmol) in anhydrous N,N-dimethyl acetamide (14 mL) were heated at 120 C. under nitrogen for 23 hours. The solvent was evaporated and the white solid was triturated with water (50 mL), filtered, and washed with water (20 mL). The solid was dried in vacuo and triturated with Et2O (20 mL), filtered, and dried to give 5-chloro-2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)quinazolin-4(3H)-one as a white solid. Yield: 0.77 g, (64%).
 

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