Pochodna chromanylu, tiochromanylu lub naftalenylu, sposób wytwarzania jej pojedynczych enancjomerów (R) i (S) albo mieszanin tych enancjomerów i farmaceutycznie dopuszczalnych soli i związków pośrednich, zawierająca ją kompozycja oraz zastosowanie tej pochodnej
LEARMONTH DAVID ALEXANDER,DAVID ALEXANDER LEARMONTH,SOARES DA SILVA PATRICIO MANUEL VIEIRA ARAUJO,PATRICIO MANUEL VIEIRA ARAUJO SOARES DA SILVA,BELIAEV ALEXANDER,ALEXANDER BELIAEV
申请号：
PL376224
公开号：
PL218537B1
申请日:
2003.10.10
申请国别(地区):
PL
年份:
2014
代理人:
摘要：
Imidazole derivatives (I), their salts and (R) enantiomers and/or (S) enantiomers are new. Imidazole derivatives of formula (I), their salts and (R) enantiomers and/or (S) enantiomers are new. [Image] R 1, R 2, R 3H, halo, alkyl, alkyloxy, OH, NO 2, NH 2, alkylcarbonylamino, alkylamino or dialkylamino； R 4H, alkyl or alkylaryl； X : CH 2, O or S； n : 1-3； halo : F, Cl, Br or I； alkyl : 1-6C hydrocarbon chains optionally substituted by aryl, alkoxy, halo, alkoxycarbonyl or hydroxycarbonyl； aryl : phenyl or naphthyl optionally substituted by alkyloxy, halo or NO 2； provided that when n is 1, X is not CH 2. Independent claims are also included for: (1) a carbonyl compound of formula (III)； (2) compound (III； n' = 3 and NR 4'R 6= phthalimido) (3) an amine of formula (II)； and (4) preparation of (R) enantiomers and/or (S) enantiomers and salts of (I). [Image] R 1', R 2', R 3'F or H (provided that at least one of R 1', R 2' and R 3' is F)； R 4'H or alkyl； R 5hydroxyl protecting group selected from trialkylsilyl, triphenylsilyl, phenyldialkylsilyl or alkyldiphenylsilyl； R 6amino protecting group selected from an alkyl carbamate or alkylaryl carbamate； and n' : 2. ACTIVITY : Cardiovascular-Gen.； Hypotensive； Cardiant. MECHANISM OF ACTION : Peripheral selective dopamine-beta-hydroxylase inhibitors； Dopamine-beta-hydroxylase inhibitor (claimed). The dopamine-beta-hydroxylase inhibitory activity of compounds (I) was determined in SK-N-SH cells. (R)-5-Aminomethyl-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrochloride (Ia) exhibited a median inhibitory concentration value of 91 nM.
