암을 일으킬 것으로 의심됨 (노출되어도 암을 일으키지 않는다는 결정적인 증거가 있는 노출경로가 있다면 노출경로 기재)
발암성 물질
구분 2
경고
P201, P202, P281, P308+P313, P405,P501
H360
태아 또는 생식능력에 손상을 일으킬 수 있음
생식독성 물질
구분 1A, 1B
위험
H413
장기적 영향에 의해 수생생물에 유해의 우려가 있음
수생 환경유해성 물질 - 만성
구분 4
예방조치문구:
P201
사용 전 취급 설명서를 확보하시오.
P202
모든 안전 조치 문구를 읽고 이해하기 전에는 취급하지 마시오.
P281
요구되는 개인 보호구를 착용하시오
P308+P313
노출 또는 접촉이 우려되면 의학적인 조치· 조언를 구하시오.
P405
밀봉하여 저장하시오.
P501
...에 내용물 / 용기를 폐기 하시오.
BMS 201038-04 C화학적 특성, 용도, 생산
개요
Lomitapide is an orally active microsomal triglyceride transfer
protein (MTP) inhibitor for the treatment of hypercholesterolemia.
The drug was developed by Aegerion
Pharmaceuticals Inc. and licensed to Bristol–Myers Squibb Co.
and the University of Pennsylvania. Lomitapide effectively lowered
LDL–cholesterol, both as a single agent and in combination
with commonly prescribed lipid-lowering therapies. Sold under
the trade name Juxtapid, the drug offers a new treatment option
to patients who cannot tolerate statin therapy or who experience
insufficient LDL–cholesterol reduction with the currently available
therapies, such as patients with homozygous familial hypercholesterolemia
caused by mutations in the LDLR gene.
정의
ChEBI: A methanesulfonate (mesylate) salt prepared from equimolar amounts of lomitapide and methanesulfonic acid. Used as a complement to a low-fat diet and other lipid-lowering treatments in patients with homozygous familial hypercholesterolemia.
Synthesis
Commercial 9H-fluorene-9-carboxylic acid (105) was alkylated
with 1,4-dibromobutane in the presence of n-butyl lithium in
THF to give 9-(4-bromobutyl)-9H-fluorene-9-carboxylic acid
(106) in 85% yield. Next, activation of the acid as the acid chloride
followed by coupling with (2,2,2-trifluoroethylamine) provided
amide 107 in 71% yield for the two-step sequence. Displacement
of the terminal bromide with the appropriate 4-carbamoyl
piperidine followed by removal of the Boc group furnished piperidinyl
fluorine 108 in high yield. Amine 108 was then reacted with
the acid chloride derived from acid 109 (derived from the Suzuki
coupling of boronic acid 110 and o-iodobenzoic acid 111) to give
lomitapide, and this was followed by salt formation with methanesulfonic
acid to afford lomitapide mesylate (XIV).
