743420-02-2 Usage
Description
Chidamide, also known as Epidaza, CS055, and HBI-8000, is an orally bioavailable benzamide type inhibitor of HDAC isoenzymes class I 1–3, as well as class IIb 10, with potential antineoplastic activity. It selectively binds to and inhibits HDAC, leading to an increase in acetylation levels of histone protein H3.74. This agent also inhibits the expression of signaling kinases in the PI3K/Akt and MAPK/Ras pathways and may result in cell cycle arrest and the induction of tumor cell apoptosis.
Uses
Used in Oncology:
Chidamide is used as an antineoplastic agent for the treatment of recurrent or refractory peripheral T-cell lymphoma, as approved by the CFDA in December 2014. It is also being evaluated in phases I and II clinical trials for the treatment of non-small cell lung cancer and breast cancer, respectively.
Used in Drug Development:
De-5-fluoro 4-Fluorochidamide is an analogue of Chidamide, which is a histone deacetylase inhibitor (HDACI) that enhances gemcitabine cytotoxicity in pancreatic cancer cells. This suggests potential applications in the development of novel therapeutic agents for pancreatic cancer treatment.
Synthesis
The scalable synthetic approach to chidamide very closely follows
the discovery route. The
sequence began with the condensation of commercial nicotinaldehyde
(52) and malonic acid (53) in a mixture of pyridine and
piperidine. Next, activation of acid 54 with N,N0-carbonyldiimidazole
(CDI) and subsequent reaction with 4-aminomethyl benzoic
acid (55) under basic conditions afforded amide 56 in 82% yield.
Finally, activation of 56 with CDI prior to treatment with 4-fluorobenzene-
1,2-diamine (57) and subsequent treatment with TFA
and THF yielded chidamide (VIII) in 38% overall yield from 52.
However, no publication reported that mono-N-Boc-protected
bis-aniline was used to approach Chidamide.
references
[1] gong k, xie j, yi h, li w. cs055 (chidamide/hbi-8000), a novel histone deacetylase inhibitor, induces g1 arrest, ros-dependent apoptosisand differentiation in human leukaemia cells. biochem j. 2012 may 1;443(3):735-46.[2] wang h1, guo y, fu m, liang x, etal. , antitumor activity of chidamide in hepatocellular carcinoma cell lines. mol med rep. 2012 jun;5(6):1503-8.
Check Digit Verification of cas no
The CAS Registry Mumber 743420-02-2 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 7,4,3,4,2 and 0 respectively; the second part has 2 digits, 0 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 743420-02:
(8*7)+(7*4)+(6*3)+(5*4)+(4*2)+(3*0)+(2*0)+(1*2)=132
132 % 10 = 2
So 743420-02-2 is a valid CAS Registry Number.
743420-02-2Relevant articles and documents
Benzamide Derivative as Histone Deacetylase Inhibitor with Potent Differentiation and Anti-Proliferation Activity
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Paragraph 0040; 0041, (2017/12/27)
The present invention is related to the preparation and pharmaceutical use of novel benzamide derivatives as defined in the specification of formula (I) as histone deacetylase inhibitors (HDACI), their preparations and the methods of using these compounds
