EP1912999A1 — Macrocyclic inhibitors of hepatitis c virus

USPTO Abstract

Inhibitors of HCV replication of formula (I) and the N-oxides, salts, and stereoisomers, wherein each dashed line represents an optional double bond; X is N, CH and where X bears a double bond it is C; R<SUP>1</SUP> is -OR<SUP>7</SUP>, -NH-SO<SUB>2</SUB>R<SUP>8</SUP>; R<SUP>2</SUP> is hydrogen, and where X is C or CH, R<SUP>2</SUP> may also be C<SUB>1-6</SUB>alkyl; R<SUP>3</SUP> is hydrogen, C<SUB>1-6</SUB>alkyl, C<SUB>1-6</SUB>alkoxyC<SUB>1-6</SUB>alkyl, C<SUB>3-7</SUB>cycloalkyl; R<SUP>4</SUP> is aryl or Het; n is 3, 4, 5, or 6; R<SUP>5</SUP> is halo, C<SUB>1-6</SUB>alkyl, hydroxy, C<SUB>1-6</SUB>alkoxy, phenyl, or Het; R<SUP>6</SUP> is C<SUB>1-6</SUB>alkoxy, or dimethylamino; R<SUP>7</SUP> is hydrogen; aryl; Het; C<SUB>3-7</SUB>cycloalkyl optionally substituted with C<SUB>1-6</SUB>alkyl; or C<SUB>1-6</SUB>alkyl optionally substituted with C<SUB>3-7</SUB>cycloalkyl, aryl or with Het; R<SUP>8</SUP> is aryl; Het; C<SUB>3-7</SUB>cycloalkyl optionally substituted with C<SUB>1-6</SUB>alkyl; or C<SUB>1-6</SUB>alkyl optionally substituted with C<SUB>3-7</SUB>cycloalkyl, aryl or with Het; aryl is phenyl optionally substituted with one, two or three substituents; Het is a 5 or 6 membered saturated, partially unsaturated or completely unsaturated heterocyclic ring containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and being optionally substituted with one, two or three substituents ; pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I). Bioavailable combinations of the inhibitors of HCV of formula (I) with ritonavir are also provided.