≥16.6 mg/mL in DMSO; ≥57.4 mg/mL in H2O; ≥94.2 mg/mL in EtOH
물리적 상태
고체
물리적 상태
단단한 모양
색상
White to off-white
안전
위험 및 안전 성명
그림문자(GHS):
신호 어:
Warning
유해·위험 문구:
암호
유해·위험 문구
위험 등급
범주
신호 어
그림 문자
P- 코드
예방조치문구:
P201
사용 전 취급 설명서를 확보하시오.
P308+P313
노출 또는 접촉이 우려되면 의학적인 조치· 조언를 구하시오.
NFPA 704
0
2
0
1-[3-[3-(4-클로로페닐)프로폭시]프로필]-피페리딘염산염 C화학적 특성, 용도, 생산
개요
Pitolisant hydrochloride,
a first-in-class inverse agonist of the histamine H3
receptor, was approved in the EU for the treatment of excessive
daytime sleepiness (EDS) in adults with narcolepsy with or
without cataplexy. The drug, which was developed by
Bioprojet and has orphan drug designation in the EU and
US, enhances wakefulness by increasing histaminergic neuron
activity. With once daily oral administration in the morning,
patients taking pitolisant exhibited significantly reduced EDS
versus placebo but not versus modafinil. Plasma levels of the
drug are reduced at the end of the day such that its waking
effect is minimized at night (plasma t1/2 10-12 h). Several
articles have been published detailing the discovery of
pitolisant.
Synthesis
The most likely scale preparation of pitolisant hydrochloride
consists of only four synthetic steps starting with the mesylation
of commercial 3-(4-chlorophenyl)propan-1-ol (132). Displacement of the mesylate with the sodium salt of
commercial 3-(piperidin-1-yl)propan-1-ol (133) in warm DMA
assembled the parent drug in 97% yield over two steps. Salt
formation was affected by pH adjustment to 3-4 using HCl gas
in EtOAc. Recrystallization from ethyl acetate and isopropanol
provided pitolisant hydrochloride (XII) on kilogram scale in
78% overall yield across the short four-step protocol.
![1-[3-[3-(4-클로로페닐)프로폭시]프로필]-피페리딘염산염](CAS/GIF/903576-44-3.gif)
