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Compounds and their use as bace inhibitors
专利权人:
ASTRAZENECA AB
发明人:
CSJERNYIK GABOR,KARLSTRÖM SOFIA,KERS ANNIKA,KOLMODIN KARIN,NYLÖF MARTIN,ÖHBERG LISELOTTE,RAKOS LASZLO,SANDBERG LARS,SEHGELMEBLE FERNANDO,SÖDERMAN PETER,SWAHN BRITT-MARIE,VON BERG STEFAN
申请号:
NZ61204111
公开号:
NZ612041A
申请日:
2011.12.21
申请国别(地区):
NZ
年份:
2015
代理人:
摘要:
Disclosed are compounds of general formula (I) such as 4-methoxy-5&rsquo&rsquo-methyl-6&rsquo-[5-(prop-1-yn-1-yl)pyridin-3-yl]-3&rsquoH-dispiro-[cyclohexane-1,2&rsquo-indene-1&rsquo,2&rsquo&rsquo-imidazol]-4&rsquo&rsquo-amine and its analogues, wherein: A is -O- or -CH2- n is 0 or 1 R1 is alkyl or haloalkyl R2 is hydrogen, alkylaryl, alkylheteroaryl, alkynyl, alkenyl, alkyl, halogen, cyano, haloalkyl, NHC(O)R9 or OR8 R5 and R6 are independently hydrogen, heterocyclyl, cycloalkyl, aryl, heteroaryl or alkyl, or R5 and R6 25 together with the carbon to which they are attached, form a ring B, which is a 3-14 membered cycloalkyl or heterocyclyl monocyclic ring, or a 9-14 membered bicyclic cycloalkyl or heterocyclyl ring. Representative compounds include 4-methoxy-5&rsquo&rsquo-methyl-6&rsquo-[5-(prop-1-yn-1-yl)pyridin-3-yl]-3&rsquoH-dispiro-[cyclohexane-1,2&rsquo-indene-1&rsquo,2&rsquo&rsquo-imidazol]-4&rsquo&rsquo-amine, 3-[4&rsquo&rsquo-amino-4-methoxy-5&rsquo&rsquo-methyl-3&rsquoH-dispiro[cyclohexane-1,2&rsquo-indene-1&rsquo,2&rsquo&rsquo-imidazol]-6&rsquo-yl]-5-chlorobenzonitrile, 4-methoxy-5&rsquo&rsquo-methyl-6&rsquo-(2-methylpropoxy)-3&rsquoH-dispiro[cyclohexane-1,2&rsquo-indene-1&rsquo,2&rsquo&rsquo-imidazol]-4&rsquo&rsquo-amine, N-(4&rsquo-amino-5&rsquo-methyl-spiro[chromane-4,2&rsquo-imidazole]-6-yl)-5-(trifluoromethyl)pyridine-2-carboxamide, 5-(4&rsquo&rsquo-amino-4-methoxy-5&rsquo&rsquo-methyl-3&rsquoH-dispiro[cyclohexane-1,2&rsquo-indene-1&rsquo,2&rsquo&rsquo-imidazol]-6&rsquo-yl)benzene-1,3-dicarbonitrile, 6&rsquo-(3-chlorophenyl)-5-methyl-2&rsquo&rsquo,3&rsquo&rsquo,5&rsquo&rsquo,6&rsquo&rsquo-tetrahydro-3&rsquoH-dispiro[imidazole-2,1&rsquo-indene-2&rsquo,4&rsquo&rsquo-pyran]-4-amine and 5&rsquo-bromo-4-methoxy-5&rsquo&rsquo-methyldispiro[cyclohexane-1,2&rsquo-[1]benzofuran-3&rsquo,2&rsquo&rsquo-imidazol]-4&rsquo&rsquo-amine. Also disclosed is a pharmaceutical composition comprising as active ingredient a therapeutically effective amount of a compound as d
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