눈에 묻으면 몇 분간 물로 조심해서 씻으시오. 가능하면 콘택트렌즈를 제거하시오. 계속 씻으시오.
P312
불편함을 느끼면 의료기관(의사)의 진찰을 받으시오.
P321
(…) 처치를 하시오.
P332+P313
피부 자극이 생기면 의학적인 조치· 조언을 구하시오.
P337+P313
눈에 대한 자극이 지속되면 의학적인 조치· 조언를 구하시오.
P362
오염된 의복을 벗고 세척 후에 재사용하기
P403+P233
용기는 환기가 잘 되는 곳에 단단히 밀폐하여 저장하시오.
P405
밀봉하여 저장하시오.
P501
...에 내용물 / 용기를 폐기 하시오.
키다마이드 C화학적 특성, 용도, 생산
개요
Chidamide (Epidaza®), a class I HDAC inhibitor, was discovered
and developed by ChipScreen and approved by the CFDA in
December 2014 for the treatment of recurrent of refractory peripheral
T-cell lymphoma. Chidamide, also known as 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. Currently, phases I and II
clinical trials are underway for the treatment of non-small cell lung
cancer and for the treatment of breast cancer, respectively.
용도
De-5-fluoro 4-Fluorochidamide is an analogue of Chidamide (CAS 743420-02-0), a hitsone deacetylase inhibitor (HDACI) that enhances gemcitabine (G305000) cytotoxicity in pancreatic cancer cells.
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.
