| Identification | Back Directory | [Name]
6-CHLORO-2,3,4,9-TETRAHYDRO-1H-CARBAZOLE-1-CARBOXAMIDE | [CAS]
49843-98-3 | [Synonyms]
CS-1862
(S)-EX-527
Selisistat
SEN0014196
EX 527, >=98%
EX 527; EX527
EX 527 (Selisistat)
EX 527 (SEN0014196)
SIRT1 Inhibitor III
Selisistat - EX 527
Selisistat (SEN0014196
SELISISTAT;EX 527;EX527;SEN0014196
EX-527; EX-527; EX-527; SELISISTAT.
6-CHLORO-2,3,4,9-TETRAHYDRO-1H-CARBAZOLE-1-CARBOXAMIDE
1H-Carbazole-1-carboxamide, 6-chloro-2,3,4,9-tetrahydro-
6-Chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide >
(S)-6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide
6-CHLORO-2,3,4,9-TETRAHYDRO-1H-CARBAZOLE-1-CARBOXAMIDE, >95%
6-CHLORO-2,3,4,9-TETRAHYDRO-1H-CARBAZOLE-1-CARBOXAMIDE USP/EP/BP
Selisistat 6-Chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxaMide
6-Chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide EX-527 Selisistat | [Molecular Formula]
C13H13ClN2O | [MDL Number]
MFCD03009471 | [MOL File]
49843-98-3.mol | [Molecular Weight]
248.71 |
| Chemical Properties | Back Directory | [Melting point ]
179.0 to 183.0 °C | [Boiling point ]
531.7±38.0 °C(Predicted) | [density ]
1.388 | [storage temp. ]
Store at +4°C | [solubility ]
Soluble in dimethyl sulfoxide, ethanol and dimethyl formamide. | [form ]
powder | [pka]
16.12±0.40(Predicted) | [color ]
white to beige | [Stability:]
Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months | [InChI]
InChI=1S/C13H13ClN2O/c14-7-4-5-11-10(6-7)8-2-1-3-9(13(15)17)12(8)16-11/h4-6,9,16H,1-3H2,(H2,15,17) | [InChIKey]
FUZYTVDVLBBXDL-UHFFFAOYSA-N | [SMILES]
N1C2=C(C=C(Cl)C=C2)C2=C1C(C(N)=O)CCC2 |
| Hazard Information | Back Directory | [Description]
EX-527 (49843-98-3) is a selective SIRT1 inhibitor (IC50=98 nM). Does not inhibit other HDACs or SIRT family members. Increases p53 acetylation following DNA damage. Cell permeable. | [Uses]
A selective inhibitor of SIRT1 over SIRT2 and SIRT3 | [Definition]
ChEBI: 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide is a member of the class of carbazoles that is 2,3,4,9-tetrahydro-1H-carbazole which is substituted at position 1 by an aminocarbohyl group and at position 6 by a chlorine. It is a member of carbazoles, a monocarboxylic acid amide and an organochlorine compound. | [General Description]
A cell-permeable indole compound that acts as a potent and highly selective inhibitor of SIRT1 (IC50 = 98 nM). It inhibits other sirtuin family deacetylases only at much higher concentrations (IC50 = 19.6 and 48.7 μM for SIRT2 and SIRT3, respectively) and shows no inhibitory effect against class I and II HDACs or NAD glycohydrolase even at concentrations as high as 100 μM. Shown to be orally bioavailable with a serum half-life of 136 minutes in mice in vivo. | [Biological Activity]
Selective inhibitor of SIRT1 that does not inhibit histone deacetylase (HDAC) or other sirtuin deacetylase family members (IC 50 values are 98, 19600, 48700, > 100000 and > 100000 nM for SIRT1, SIRT2, SIRT3, HDAC and NADase respectively). Enhances p53 acetylation in response to DNA damaging agents. | [Biochem/physiol Actions]
Primary TargetSIRT1 | [Synthesis]
Step 3: Ethyl 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxylate (1 g, 3.60 mmol, 1.00 eq.) was added to a 30 mL high-pressure reactor with a methanol solution of NH3 (7 M, 15 mL). The reactor was sealed and the reaction was stirred at 100 °C for 15 hours. Upon completion of the reaction, the reaction mixture was concentrated under reduced pressure to remove the solvent. The crude product was purified by preparative high performance liquid chromatography (HPLC) under the following conditions: the column was a Bridge Shield RP18 OBD column (5 μm, 19×150 mm); the mobile phases were water (containing 0.05% trifluoroacetic acid) and acetonitrile (acetonitrile ratio was increased from 31.0% to 42.0% in 10 min); the detection wavelength was UV 254/ 220 nm.The final product was 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide 400 mg (45% yield) as a white solid. The structure of the product was confirmed by NMR hydrogen spectroscopy (400 MHz, DMSO-d6): δ 10.81 (s, 1H), 7.44-7.36 (m, 2H), 7.29 (m, 1H), 7.10 (s, 1H), 7.00 (m, 1H), 3.66 (m, 1H), 2.64-2.56 (m, 2H), 2.11-1.89 (m , 3H), 1.70 (m, 1H). Liquid chromatography-mass spectrometry (LC-MS) analysis showed m/z = 249 [M + H]+. | [storage]
Store at +4°C | [References]
1) Napper et al. (2005), Discovery of indoles as potent and selective inhibitors of the deacetylase SIRT1; J. Med. Chem., 48 8045
2) Solomon et al. (2006) Inhibition of SIRT1 catalytic activity increases p53 acetylation but does not alter cell survival following DNA damage; Mol. Cell, 26 28
3) Gertz et al. (2013) EX-527 inhibits Sirtuins by exploiting their unique NAD+-dependent deacetylation mechanism; Proc. Natl. Acad. Sci. USA, 110 e2772 |
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