| Identification | Back Directory | [Name]
KD 5170 | [CAS]
940943-37-3 | [Synonyms]
KD 5170
KD5170; KD-5170
S-(2-(6-(4-(3-(DiMethylaMino)propoxy)phenylsulfonaMido)pyridin-3-yl)-2-oxoethyl) ethanethioate
S-(2-{6-[({4-[3-(dimethylamino)propoxy]phenyl}sulfonyl)amino]-3-p Yridinyl}-2-oxoethyl) Ethanethioate
Ethanethioic acid, S-[2-[6-[[[4-[3-(dimethylamino)propoxy]phenyl]sulfonyl]amino]-3-pyridinyl]-2-oxoethyl] ester | [Molecular Formula]
C20H25N3O5S2 | [MOL File]
940943-37-3.mol | [Molecular Weight]
451.56 |
| Chemical Properties | Back Directory | [Boiling point ]
637.9±65.0 °C(Predicted) | [density ]
1.310±0.06 g/cm3(Predicted) | [storage temp. ]
Sealed in dry,Room Temperature | [solubility ]
≥21.2 mg/mL in DMSO with gentle warming; insoluble in H2O; insoluble in EtOH | [form ]
solid | [pka]
9.29±0.28(Predicted) | [color ]
White to yellow |
| Hazard Information | Back Directory | [Description]
KD 5170 is a mercaptoketone-based inhibitor of class I and II histone deacetylases (HDACs; IC50s = 20, 2,060, 75, 26, 950, 14, 85, 2,500, 150, and 18 nM for HDAC1-10, respectively). It exhibits broad spectrum antitumor activity in vitro and in vivo. KD 5170 increases the acetylation of histones and activates caspases 3, 8, and 9, leading to apoptosis in primary myeloma cells. | [Uses]
KD 5170 is a pan inhibitor of histone deacetylases (HDACs) and exhibits broad spectrum antitumor activity in vitro and in vivo[1]. | [Synthesis]
1. N-(5-acetylpyridin-2-yl)-4-(3-dimethylaminopropoxy)benzenesulfonamide (100 g, 0.265 mol) and dimethylformamide (400 mL) were added to the reaction vial under nitrogen protection and stirring was initiated.
2. Acetic acid solution of 32% HBr (98 mL, 0.53 mol) was added slowly dropwise, and the reaction temperature was raised to 45 °C during the dropwise addition.
3. pyrrolidone hydrobromide (130 g, 0.262 mol) was added in a single addition, and after addition, the reaction mixture was heated to 50 °C and maintained for 1 hour.
4. Upon completion of the reaction, the mixture was cooled to 35 °C, followed by a one-time addition of potassium thioacetate (60.5 g, 0.53 mol).
5. Stirring was continued at room temperature for 1 h. The reaction mixture was filtered through a medium porosity glass filter to remove inorganic salts.
6. The filtrate was poured into 2 L of isopropanol and the resulting turbid mixture was placed in a refrigerator at -20°C overnight.
7. On the following day, the mixture was allowed to stand at room temperature for 30 minutes and a clarified light yellow supernatant was decanted.
8. The insoluble residue was suspended with 500 mL of dichloromethane and stirred vigorously, and an aqueous solution (700 mL) of potassium hydrogen phosphate trihydrate (140 g, 0.53 mol) was added.
9. After stirring for 15 minutes, most of the target product precipitated out of solution and adhered to the vessel wall.
10. The aqueous layer was separated and extracted with dichloromethane to combine the organic phase and insoluble residue.
11. The combined organic phases were chromatographed on a 900 g dried silica gel column, eluting with a dichloromethane solution (1 L) containing 20% methanol.
12. Fractions 3 to 20 were collected and concentrated to give S-(2-(6-(4-(3-dimethylaminopropoxy)benzenesulfonylamino)pyridin-3-yl)-2-oxoethyl)ethanethioate as a tan solid (32.1 g, 27% yield).
13. The product was characterized by 1H-NMR (400 MHz, DMSO): δ 8.66 (s, 1H), 7.94 (d, 1H), 7.77 (d, 2H), 6.98 (d, 2H), 6.90 (d, 1H), 4.34 (s, 2H), 4.03 (t, 2H), 2.68 (t, 2H), 2.40 (s, 6H). 2.33 (s, 3H), 1.88-1.98 (m, 2H); MS: [M + H]+ 452. | [References]
[1]. hassig ca, symons kt, guo x, et al. kd5170, a novel mercaptoketone-based histone deacetylase inhibitor that exhibits broad spectrum antitumor activity in vitro and in vivo. mol cancer ther, 2008, 7(5): 1054-1065.
[2]. payne je, bonnefous c, hassig ca, et al. identification of kd5170: a novel mercaptoketone-based histone deacetylase inhibitor. bioorg med chem lett, 2008, 18(23): 6093-6096.
[3]. feng r, ma h, hassig ca, et al. kd5170, a novel mercaptoketone-based histone deacetylase inhibitor, exerts antimyeloma effects by dna damage and mitochondrial signaling. mol cancer ther, 2008, 7(6): 1494-1505. |
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