| Identification | Back Directory | [Name]
HA14-1 | [CAS]
65673-63-4 | [Synonyms]
CS-392
HA14-1
HA14-1 USP/EP/BP
HA14-1;HA-14-1; HA 14-1
ethyl 6-broMo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chroMene-3-carboxylate
[Ethyl 2-amino-6-bromo-4-(1cyano-2-ethoxy-2-oxoethyl)-4H-chromene3-3carboxylate]
2-Amino-6-bromo-α-cyano-3-(ethoxycarbonyl)-4H-1-benzopyran-4-aceticacidethylester
ETHYL [2-AMINO-6-BROMO-4-(1-CYANO-2-ETHOXY-2-OXOETHYL)]-4H-CHROMENE-3-CARBOXYLATE
Ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-1-benzopyran-3-carboxylate
Ethyl2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-1-benzopyran-3-carboxylate97%
(R)-ethyl 2-amino-6-bromo-4-((R)-1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate
Ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-1-benzopyran-3-carboxylate 97%
2-Amino-6-bromo-alpha-cyano-3-(ethoxycarbonyl)-(4H)-1-benzopyrane-4-aceticacidethylester
ethyl (4S)-2-amino-6-bromo-4-[(R)-cyano-ethoxycarbonyl-methyl]-4H-chromene-3-carboxylate
2-AMINO-6-BROMO-ALPHA-CYANO-3-(ETHOXYCARBONYL)-4H-1-BENZOPYRAN-4-ACETIC ACID ETHYL ESTER
4H-1-Benzopyran-4-acetic acid, 2-amino-6-bromo-α-cyano-3-(ethoxycarbonyl)-, ethyl ester, (αR,4R)-rel-
rel-(R)-Ethyl 2-amino-6-bromo-4-((R)-1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate(relative)
2-Amino-6-bromo-alpha-cyano-3-(ethoxycarbonyl)-(alphaR,4R)-rel-4H-1-benzopyran-4-acetic acid ethyl ester
HA 14-1 2-Amino-6-bromo-alpha-cyano-3-(ethoxycarbonyl)-(alphaR,4R)-rel-4H-1-benzopyran-4-acetic acid ethyl ester
2-Amino-6-bromo-alpha-cyano-3-(ethoxycarbonyl)-(alphaR,4R)-rel-4H-1-benzopyran-4-acetic acid ethyl ester HA 14-1
[Ethyl 2-amino-6-bromo-4-(1cyano-2-ethoxy-2-oxoethyl)-4H-chromene3-3carboxylate], Ethyl [2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)]-4H-chromene-3-carboxylate
2-Amino-6-bromo-α-cyano-3-(ethoxycarbonyl)-4H-1-benzopyran-4-acetic acid ethyl ester, Ethyl [2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)]-4H-chromene-3-carboxylate
HA 14-1, Ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate, 2-[2-Amino-6-bromo-3-(ethoxycarbonyl)-4H-chromen-4-yl]-3-ethoxy-3-oxopropanenitrile | [Molecular Formula]
C17H17BrN2O5 | [MDL Number]
MFCD00218213 | [MOL File]
65673-63-4.mol | [Molecular Weight]
409.23 |
| Chemical Properties | Back Directory | [Melting point ]
105 °C | [density ]
1.480 | [storage temp. ]
−20°C
| [solubility ]
DMSO: 26 mg/mL
| [form ]
powder
| [color ]
White to light yellow | [InChI]
1S/C17H17BrN2O5/c1-3-23-16(21)11(8-19)13-10-7-9(18)5-6-12(10)25-15(20)14(13)17(22)24-4-2/h5-7,11,13H,3-4,20H2,1-2H3 | [InChIKey]
SXJDCULZDFWMJC-UHFFFAOYSA-N | [SMILES]
CCOC(=O)C(C#N)C1c2cc(Br)ccc2OC(N)=C1C(=O)OCC | [CAS DataBase Reference]
65673-63-4 |
| Hazard Information | Back Directory | [Uses]
Cell permeable, low molecular weight Bcl-2 ligand. Antagonizes the function of Bcl-2 and induces apoptosis. In HL-60 cells, HA4-1 (50μM and 4h incubation) induced apoptosis of more than 90% of the cells. Apoptosis is blocked by ZVAD-FM. IC50 = ~9μM for competition with Flu-BakBH3 binding to Bcl-2. | [Definition]
ChEBI: 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-1-benzopyran-3-carboxylic acid ethyl ester is a 1-benzopyran. | [Biological Activity]
Cell-permeable inhibitor of Bcl-2 protein (IC 50 ~ 9 μ M); acts by binding to the surface pocket. Disrupts Bax/Bcl-2 interaction and induces apoptosis of tumor cells. | [Biochem/physiol Actions]
HA 14-1 is a nonpeptide apoptosis inducer; Bcl-2 antagonist. | [Synthesis]
GENERAL METHODS: 1,1,3,3-Tetramethylguanidine (TMG, 3.5 mmol) was added to a mixture of 5-bromosalicylaldehyde (SA, 1 mmol), ethyl cyanoacetate (MN, 1 mmol), and 2,3-diaminopyridine (DAP, 1 mmol) under pure conditions. The reaction mixture was stirred at room temperature and the reaction process was monitored by thin layer chromatography (TLC). Upon completion of the reaction, distilled water (15 mL) was added to the reaction mixture and stirring was continued until a free-flowing solid was formed. The solid was collected by filtration and washed sequentially with water and hexane. The crude product was purified by recrystallization from ethanol solution: the crude product was dissolved in boiling ethanol to saturation and hot filtered to remove undissolved solid. The hot filtrate was cooled to room temperature to give an elementally analytically pure crystalline product, rel-(αR,4R)-2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-carbonyl)-4H-benzofuran-3-carboxylic acid. Similar experimental procedures were used to synthesize all 2-amino-4H-benzofuran derivatives. | [in vivo]
Swiss nude mice are challenged with BeGBM cells (104 injected s.c.). HA14-1 (400 nmol) in 100 μL free RPMI 1640-50% DMSO, or the carrier alone, is given at the site of injection once weekly from day 2 following cell injection. HA14-1 treatment does not have any significant effect on the growth of glioblastoma tumors in immunodeficient mice as monitored twice weekly by measuring the volume of the expanding tumors. Moreover, no gross organ toxicity or weight loss can be detected in mice receiving such treatment. To analyze whether HA14-1 treatment might enhance the efficiency of another antitumoral treatment, Swiss nude mice challenged with human glioblastoma multiforme cells are also given i.p. low doses of Etoposide (2.5 mg/kg in 200 μL of 0.9% NaCl 5 days a week from day 2 following cell injection) together with HA14-1 or mock treatment. Whereas Etoposide treatment is insufficient by itself to restrain the growth of glioblastoma cells, its combination with HA14-1 leads to a significant restrain on tumor growth as judged by the ability of the combined treatment to increase the doubling time of the tumor volume[3]. | [IC 50]
Bcl-2: 9 μM (IC50); Bcl-xL | [storage]
Desiccate at -20°C | [References]
[1] Tetrahedron Letters, 2005, vol. 46, # 20, p. 3497 - 3499
[2] RSC Advances, 2015, vol. 5, # 80, p. 65526 - 65531
[3] Tetrahedron, 2013, vol. 69, # 49, p. 10544 - 10551
[4] Tetrahedron Letters, 2006, vol. 47, # 43, p. 7629 - 7633
[5] Russian Chemical Bulletin, 2008, vol. 57, # 3, p. 595 - 600 |
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| Company Name: |
J & K SCIENTIFIC LTD.
|
| Telephone: |
18210857532 18210857532 |
| Website: |
https://www.jkchemical.com |
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