눈에 묻으면 몇 분간 물로 조심해서 씻으시오. 가능하면 콘택트렌즈를 제거하시오. 계속 씻으시오.
P312
불편함을 느끼면 의료기관(의사)의 진찰을 받으시오.
P321
(…) 처치를 하시오.
P322
특정 조치(라벨의 … 참조)
P330
입을 씻어내시오.
P332+P313
피부 자극이 생기면 의학적인 조치· 조언을 구하시오.
P362
오염된 의복을 벗고 세척 후에 재사용하기
P363
다시 사용전 오염된 의류는 세척하시오.
P501
...에 내용물 / 용기를 폐기 하시오.
베르나칼란트염화물 C화학적 특성, 용도, 생산
용도
Vernakalant Hydrochloride is a novel, relatively atrial-selective antiarrhythmic drug that effectively and rapidly terminates atrial fibrillation (AF).
Clinical Use
Vernakalant is an investigational drug under regulatory review for the acute conversion of atrial
fibrillation. The drug was initially developed by Cardiome Pharma under the trade names Kynapid ®
and Brinavess ® and its intravenous formulation was further developed by Merck in April 2009. Like other class III antiarrhythmics, vernakalant blocks atrial potassium channels, thereby
prolonging repolarization. It differs from typical class III agents by blocking the cardiac
transient outward potassium current, with increased potency as the heart rate increases. It also slightly
blocks the hERG potassium channel, leading to a prolonged QT interval, which may theoretically
increase the risk of ventricular tachycardia.
Synthesis
The preparation of vernakalant entails the union of a
prolinol derivative 150 with a 3,4-dimethoxyphenethyl alcohol (148) across a cyclohexanyl lynchpin
152 and is described in the scheme. Decarboxylation of commercially available (2S,4R)-4-
hydroxyprolinol (150) was effected using cyclohexanol and cyclohexanone at elevated temperatures.
Subsequent protection of the nitrogen atom and the oxygen atom within this system resulted in
carbamate 151. Acid-mediated removal of the N-protective functionality preceded nucleophilic attack on epoxide 152 in hot water, and the ensuing mixture of diastereomers was separated by classical
resolution via the tartrate salt. O-Benzylated vernakalant 154 was obtained when enantiomerically pure
alcohol 153 was subjected to trichloroacetimidate 149 (which arose from the corresponding alcohol 148
under modified Williamson conditions. Acidic hydrogenolysis, which the authors report as
separate steps, furnished vernakalant hydrochloride (XIV) in excellent overall yield.
