Benzodiazepin derivatives useful as CCK-receptor antagonists

A process for preparing a benzodiazepine compound of formula I, or a pharmaceutically acceptable salt thereof:

• ##STR12## wherein (a) R.sup.1 is --CH.sub.2 CO(CH.sub.2).sub.a R.sup.5 in which a is 0 or 1 and R.sup.5 is selected from (C.sub.1 -C.sub.8)alkyl groups, (C.sub.3 -C.sub.8)cycloalkyl and adamantyl groups, which may be unsubstituted or substituted by one or two (C.sub.1 -C.sub.8)alkyl groups, and groups of formulae II and III;
• ##STR13## in which R.sup.6 is H or (C.sub.1 -C.sub.8)alkyl or --CO--(C.sub.1 -C.sub.6)alkyl and b is 1 or 2;
• (b) R.sup.2 and R.sup.3 are independently selected from 5- and 6-membered aromatic carbocyclic and 5- and 6-membered heterocyclic groups with one heteroatom selected from the groups consisting of N, O and S, where R.sup.2 and R.sup.3 each may have 1 or 2 substituents selected from the group consisting of a halogen atom, an amino group, a hydroxyl group, a nitro group, a cyano group, an alkyl group, an alkoxy group, a hydroxyamino group, an alkylamino group and a dialkylamino group, a carbamoyl group, a formylamino group, an alkylaminoalkyl group, a dialkylaminoalkyl group, a --(CH.sub.2).sub.c --CO.sub.2 H group in which c is 0-2 and a --(CH.sub.2).sub.c --SO.sub.3 H in which c is 0-2, wherein alkyl portions of the recited groups consist of 1 to 6 carbon atoms;
• and
• (c) W and X are selected independently from halogen and hydrogen atoms and (C.sub.1 -C.sub.8)alkyl and (C.sub.1 -C.sub.8)alkoxy groups, comprising the step of reacting 3-aminobenzodiazepine V with organic isocyanate R.sup.2 --NCO according to the following reaction scheme:
• ##STR14##

A process for preparing a benzodiazepine compound of formula I, or a pharmaceutically acceptable salt thereof:

• wherein
• (a) R.sup.1 is --CH.sub.2 CO(CH.sub.2).sub.a R.sup.5 in which a is 0 or 1 and R.sup.5 is selected from (C.sub.1 -C.sub.8)alkyl groups, (C.sub.3 -C.sub.8)cycloalkyl and adamantyl groups, which may be unsubstituted or substituted by one or two (C.sub.1 -C.sub.8)alkyl groups, and groups of formulae II and III;
• ##STR15## in which R.sup.6 is H or (C.sub.1 -C.sub.8)alkyl or --CO--(C.sub.1 -C.sub.6)alkyl and b is 1 or 2;
• (b) R.sup.2 and R.sup.3 are independently selected from 5- and 6-membered aromatic carbocyclic and 5- and 6-membered heterocyclic groups with one heteroatom selected from the groups consisting of N, O and S, where R.sup.2 and R.sup.3 each may have 1 or 2 substituents selected from the group consisting of a halogen atom, an amino group, a hydroxyl group, a nitro group, a cyano group, an alkyl group, an alkoxy group, a hydroxyamino group, an alkylamino group and a dialkylamino group, a carbamoyl group, a formylamino group, an alkylaminoalkyl group, a dialkylaminoalkyl group, a --(CH.sub.2).sub.c --CO.sub.2 H group in which c is 0-2 and a --(CH.sub.2).sub.c --SO.sub.3 H in which c is 0-2, wherein alkyl portions of the recited groups consist of 1 to 6 carbon atoms;
• and
• (c) W and X are selected independently from halogen and hydrogen atoms and (C.sub.1 -C.sub.8)alkyl and (C.sub.1 -C.sub.8)alkoxy groups,
• comprising the step of reacting 3-p-nitrophenyloxycarbonylaminobenzodiazepine VI with amine R.sup.2 --NH.sub.2, according to the following reaction scheme ##STR16##

A process for preparing a benzodiazepine compound of formula I, or a pharmaceutically acceptable salt thereof:

• wherein
• (a) R.sup.1 is --CH.sub.2 CHOH(CH.sub.2).sub.a R.sup.4, in which a is 0 or 1 and R.sup.4 is selected from (C.sub.1 -C.sub.8)alkyl groups, (C.sub.3 -C.sub.8)cycloalkyl and adamantyl groups, which may be unsubstituted or substituted by one or two (C.sub.1 -C.sub.8)alkyl groups, and groups of formulae II and III;
• ##STR17## in which R.sup.6 is H or (C.sub.1 -C.sub.8)alkyl or --CO--(C.sup.1 -C.sub.6)alkyl and b is 1 or 2;
• (b) R.sup.2 and R.sup.3 are independently selected from 5- and 6-membered aromatic carbocyclic and 5- and 6-membered heterocyclic groups with one heteroatom selected from the groups consisting of N, O and S, where R.sup.2 and R.sup.3 each may have 1 or 2 substituents selected from the group consisting of a halogen atom, an amino group, a hydroxyl group, a nitro group, a cyano group, an alkyl group, an alkoxy group, a hydroxyamino group, an alkylamino group and a dialkylamino group, a carbamoyl group, a formylamino group, an alkylaminoalkyl group, a dialkylaminoalkyl group, a --(CH.sub.2).sub.c --CO.sub.2 H group in which c is 0-2 and a --(CH.sub.2).sub.c --SO.sub.3 H in which c is 0-2, wherein alkyl portions of the recited groups consist of 1 to 6 carbon atoms;
• and
• (c) W and X are selected independently from halogen and hydrogen atoms and (C.sub.1 -C.sub.8)alkyl and (C.sub.1 -C.sub.8)alkoxy groups,
• comprising the step of reacting a compound of general formula I with a reducing agent.