Disubstituted bicyclic heterocycles, the preparation thereof, and their use as pharmaceutical compositions

A compound of the formula I

• Ra—A—Het—B—Ar—E (I)
• wherein:
• A is a carbonyl or sulfonyl group linked to the benzo moiety of the group Het, wherein the benzo moiety may not contain an R1 group;
• B is an ethylene group, wherein a methylene group, linked either to the group Het or Ar, is optionally replaced by an oxygen or sulfur atom or by a sulfinyl, sulfonyl, carbonyl, or —NR1— group, wherein
• R1 is a hydrogen atom or a C1-6-alkyl group;
• E is a cyano or RbNH—C(═NH)— group, wherein
• Rb is a hydrogen atom or a hydroxy, C1-9-alkoxycarbonyl, cyclohexyloxycarbonyl, phenyl-C1-3-alkoxycarbonyl, benzoyl, p-C1-3-alkyl-benzoyl, or pyridinoyl group, wherein the ethoxy moiety in the 2-position of the abovementioned C1-9-alkoxycarbonyl group is unsubstituted or additionally substituted by a C1-3-alkylsulfonyl or 2-(C1-3-alkoxy)-ethyl group;
• Ar is a phenylene or naphthylene group optionally substituted by a fluorine, chlorine, or bromine atom or by a trifluoromethyl, C1-3-alkyl, or C1-3-alkoxy group, or a thienylene, thiazolylene, pyridinylene, pyrimidinylene, pyrazinylene, or pyridazinylene group optionally substituted in the carbon skeleton by a C1-3-alkyl group;
• Het is a bicyclic heterocycle of formula
• wherein
• X is a nitrogen atom, and
• Y is an oxygen or sulfur atom or an imino group optionally substituted by a C1-6-alkyl or C3-7-cycloalkyl group whilst additionally one or two non-angular methyne groups in the phenyl moiety of the above-mentioned bicyclic heterocycle may each be replaced by a nitrogen atom;
• or
• X is a methyne group optionally substituted by the group R1, wherein R1 is as hereinbefore defined, and
• Y is a nitrogen atom optionally substituted by a C1-6-alkyl or C3-7-cycloalkyl group;
• Ra is a C1-6-alkyl group, a C3-7-cycloalkyl group optionally substituted by a C1-3-alkyl group, wherein the C1-3-alkyl group may additionally be substituted by a carboxyl group or by a group which may be converted in vivo into a carboxy group, or
• Ra is a R2NR3— group, wherein
• R2 is a C1-4-alkyl group optionally substituted by a carboxy, C1-6-alkyloxycarbonyl, benzyloxycarbonyl, C1-3-alkylsulfonylaminocarbonyl, phenylsulfonylaminocarbonyl, trifluorosulfonylamino, trifluorosulfonylaminocarbonyl, or 1H-tetrazolyl group, or
• a C2-4-alkyl group substituted at a carbon which is other than the one in the α-position relative to the adjacent nitrogen atom, by a hydroxy, phenyl-C1-3-alkoxy, carboxy-C1-3-alkylamino, C1-3-alkoxycarbonyl-C1-3-alkylamino, N—(C1-3-alkyl)-carboxy-C1-3-alkylamino or N—(C1-3-alkyl)-C1-3-alkoxycarbonyl-C1-3-alkylamino group, or
• a piperidinyl group optionally substituted by a C1-3-alkyl group;
• and
• R3 is a hydrogen atom, a C1-6-alkyl group, a C3-7-cycloalkyl group optionally substituted by a C1-3-alkyl group or a C3-6-alkenyl or alkynyl group, wherein the unsaturated part may not be linked directly to the nitrogen atom of the R2NR3— group, or a oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, thienyl, or imidazolyl group, or
• R2 and R3 together with the nitrogen atom between them are a 5- to 7-membered cycloalkyleneimino group, optionally substituted by a carboxymethyl or C1-4-alkoxycarbonyl group, onto which a phenyl ring may additionally be fused,
• or, if E is a group of the formula RbNH—C(═NH)—, a physiologically acceptable salt thereof or, if E is a cyano group, a salt thereof.