8-arylalkyl- and 8-arylheteroalkyl-5,11-dihydro-6H-dipyrido›3,2-B:2',3'-e!›1!diazepines and their use in the treatment of HIV-1 infection

A compound of formula 1 ##STR12## wherein, A is a connecting chain of 1 to 3 atoms, wherein one of the atoms is oxygen, phosphorous or sulfur (optionally oxidized or unoxidized), or nitrogen (unsubstituted or substituted with methyl or acetyl), and the remaining atoms are carbon;

• or,
• all of the atoms are carbon atoms, wherein two of the atoms form an unsaturated alkynyl or cis- or trans-alkenyl bond, or all of the atoms are connected by single bonds and one of the atoms is optionally unsubstituted or substituted with oxo, methyl, hydroxy, amino, or halogen wherein halogen is defined as fluoro, chloro bromo or iodo;
• or,
• A is a connecting chain of 2 atoms, wherein one of the atoms is nitrogen (unsubstituted or substituted with methyl) or oxygen, and the adjacent position is carbonyl;
• or,
• A is a 1,2-disubstituted cyclopropyl or oxiranyl ring;
• D, E, G, and L form a five-membered heteroaromatic ring of type I, wherein the dotted bonds represent either double or single bonds depending on the valency of the atoms, either D or E is nitrogen (unsubstituted or substituted with methyl, ethyl, or acetyl), oxygen, or sulfur, and the three remaining positions are carbon, wherein one or two of these carbon atoms are optionally unsubstituted or substituted with alkyl, alkyloxy, or alkylmercapto of 1 to 4 carbon atoms, trifluoromethyl, hydroxymethyl, hydroxyethyl, halogen, acetyl, methoxy- or ethoxycarbonyl, carboxy, hydroxy, amino, methyl- or ethylamino, acetamido, ureido, methylsulfonamido, mono- or dimethylaminosulfonyl, aminosulfonyl, mono- or dimethylaminocarbonyl, aminocarbonyl, methyl- or ethylsulfinyl, methyl- or ethylsulfonyl, cyano, or nitro;
• or,
• one of D, E, G, and L is nitrogen, one is oxygen or sulfur, and the two remaining positions are carbon optionally unsubstituted or substituted with alkyl, alkyloxy, or alkylmercapto of 1 to 4 carbon atoms, trifluoromethyl, hydroxymethyl, hydroxyethyl, halogen, acetyl, methoxy or ethoxycarbonyl, carboxy, hydroxy, amino, methyl- or ethylamino, acetamido, ureido, methylsulfonamido, mono- or dimethylaminosulfonyl, aminosulfonyl, mono- or dimethylaminocarbonyl, aminocarbonyl, methyl- or ethylsulfinyl, methyl- or ethylsulfonyl, cyano, or nitro;
• or,
• two of D, E, G, and L are nitrogen (wherein one of the nitrogen atoms is unsubstituted or substituted with methyl, ethyl, acetyl, mono- or dimethylaminosulfonyl, methoxy- or ethoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, or phenylaminocarbonyl), and the two remaining positions are carbon optionally unsubstituted or substituted with alkyl, alkyloxy, or alkylmercapto of 1 to 4 carbon atoms, trifluoromethyl, hydroxymethyl, hydroxyethyl, halogen, acetyl, methoxy- or ethoxycarbonyl, carboxy, hydroxy, amino, methyl- or ethylamino, acetamido, ureido, methylsulfonamido, mono- or dimethylaminosulfonyl, aminosulfonyl, mono- or dimethylaminocarbonyl, aminocarbonyl, methyl- or ethylsulfinyl, methyl- or ethylsulfonyl, cyano, or nitro;
• or,
• two of D, E, G, and L are nitrogen, one is oxygen or sulfur, and the remaining position is carbon optionally unsubstituted or substituted with alkyl, alkyloxy, or alkylmercapto of 1 to 4 carbon atoms, trifluoromethyl, hydroxymethyl, hydroxyethyl, halogen, acetyl, methoxy- or ethoxycarbonyl, carboxy, hydroxy, amino, methyl- or ethylamino, acetamido, ureido, methylsulfonamido, mono- or dimethylaminosulfonyl, aminosulfonyl, mono- or dimethylaminocarbonyl, aminocarbonyl, methyl- or ethylsulfinyl, methyl- or ethylsulfonyl, cyano, or nitro;
• or,
• three of D, E, G, and L are nitrogen (wherein one of the nitrogen atoms is unsubstituted or substituted with methyl, ethyl, acetyl, mono- or dimethylaminosulfonyl, methoxy- or ethoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, or phenylaminocarbonyl), and the remaining position is carbon optionally unsubstituted or substituted with alkyl, alkyloxy, or alkylmercapto of 1 to 4 carbon atoms, trifluoromethyl, hydroxymethyl, hydroxyethyl, halogen, acetyl, methoxy- or ethoxycarbonyl, carboxy, hydroxy, amino, methyl- or ethylamino, acetamido, ureido, methylsulfonamido, mono- or dimethylaminosulfonyl, aminosulfonyl, mono- or dimethylaminocarbonyl, aminocarbonyl, methyl- or ethylsulfinyl, methyl- or ethylsulfonyl, cyano, or nitro;
• or,
• D, E, G, and L are nitrogen, wherein one of the nitrogen atoms is unsubstituted or substituted with methyl, ethyl, acetyl, mono- or dimethylaminosulfonyl, methoxy- or ethoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, or phenylaminocarbonyl;
• or,
• D is nitrogen (wherein the nitrogen atom is unsubstituted or substituted with methyl, ethyl, acetyl, mono- or dimethylaminosulfonyl, methoxy- or ethoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, or phenylaminocarbonyl), oxygen, or sulfur, L is carbon (optionally unsubstituted or substituted with methyl or ethyl) or nitrogen, and E and G together form one side of a fused phenyl or pyridyl ring (which is either unsubstituted or substituted by alkyl, alkyloxy, or alkylmercapto of 1 to 4 carbon atoms, amino, hydroxy, carboxy, or aminocarbonyl);
• or,
• D is carbon (optionally unsubstituted or substituted with methyl or ethyl) or nitrogen, E is nitrogen (wherein the nitrogen atom is unsubstituted or substituted with methyl, ethyl, acetyl, mono- or dimethylaminosulfonyl, methoxy- or ethoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, or phenylaminocarbonyl), oxygen, or sulfur, G and L together form one side of a fused phenyl or pyridyl ring (which is either unsubstituted or substituted by alkyl, alkyloxy, or alkylmercapto of 1 to 4 carbon atoms, amino, hydroxy, carboxy, or aminocarbonyl);
• or,
• D, E, G, L and M form a six-membered aromatic ring of type II, wherein D, E, G, L, and M are carbon, of which one or two of these carbon atoms are optionally unsubstituted or substituted with methyl, ethyl, trifluoromethyl, hydroxymethyl, hydroxyethyl, halogen, acetyl, acetyloxy, methoxy- or ethoxycarbonyl, carboxy, hydroxy, amino, methyl- or ethylamino, acetamido, ureido, methylsulfonamido, alkyloxy of 1 to 4 carbon atoms, methyl- or ethylmercapto, mono- or dimethylaminosulfonyl, aminosulfonyl, mono- or dimethylaminocarbonyl, aminocarbonyl, methyl- or ethylsulfinyl, methyl- or ethylsulfonyl, cyano, or nitro;
• or,
• D, E, G, L and M are carbon, wherein D and E form one side of a fused phenyl, pyridyl, pyrrolyl, thienyl, or furanyl ring (which is either unsubstituted or substituted by alkyl, alkyloxy, or alkylmercapto of 1 to 4 carbon atoms, amino, hydroxy, carboxy, or aminocarbonyl) and one of G, L, or M is optionally unsubstituted or substituted with alkyl, alkyloxy, or alkylmercapto of 1 to 4 carbon atoms, trifluoromethyl, hydroxymethyl, hydroxyethyl, halogen, acetyl, methoxy- or ethoxycarbonyl, carboxy, hydroxy, amino, methyl- or ethylamino, acetamido, ureido, methylsulfonamido, mono- or dimethylaminosulfonyl, aminosulfonyl, mono- or dimethylaminocarbonyl, aminocarbonyl, methyl- or ethylsulfinyl, methyl- or ethylsulfonyl, cyano, or nitro;
• or,
• D, E, G, L and M are carbon, wherein E and G form one side of a fused phenyl, pyridyl, pyrrolyl, thienyl, or furanyl ring (which is either unsubstituted or substituted by alkyl, alkyloxy, or alkylmercapto of 1 to 4 carbon atoms, amino, hydroxy, carboxy, or aminocarbonyl) and one of D, L, or M is optionally unsubstituted or substituted with alkyl, alkyloxy, or alkylmercapto of 1 to 4 carbon atoms, trifluoromethyl, hydroxymethyl, hydroxyethyl, halogen, acetyl, methoxy- or ethoxycarbonyl, carboxy, hydroxy, amino, methyl- or ethylamino, acetamido, ureido, methylsulfonamido, mono- or dimethylaminosulfonyl, aminosulfonyl, mono- or dimethylaminocarbonyl, aminocarbonyl, methyl- or ethylsulfinyl, methyl- or ethylsulfonyl, cyano, or nitro;
• or,
• D, E, G, L and M form a six-membered heteroaromatic ring of type II, wherein one of D, E, or G is nitrogen (optionally unoxidized or oxidized to the corresponding N-oxide), and the four remaining positions are carbon, of which one of these carbon atoms is optionally unsubstituted or substituted with alkyl, alkyloxy, or alkylmercapto of 1 to 4 carbon atoms, trifluoromethyl, hydroxymethyl, hydroxyethyl, halogen, acetyl, methoxy- or ethoxycarbonyl, carboxy, hydroxy, amino, methyl- or ethylamino, acetamido, ureido, methylsulfonamido, mono- or dimethylaminosulfonyl, aminosulfonyl, mono- or dimethylaminocarbonyl, aminocarbonyl, methyl- or ethylsulfinyl, methyl- or ethylsulfonyl, cyano, or nitro, and of which a second of these carbon atoms is optionally unsubstituted or substituted with methyl, ethyl, hydroxy, or amino;
• or,
• one of D, E, or G is nitrogen, L and M form one side of a fused phenyl, pyridyl, pyrrolyl, thienyl, or furanyl ring (which is either unsubstituted or substituted by alkyl, alkyloxy, or alkylmercapto of 1 to 4 carbon atoms, amino, hydroxy, carboxy, or aminocarbonyl), and the remaining two positions are carbon, of which one of these carbon atoms is optionally unsubstituted or substituted with alkyl, alkyloxy, or alkylmercapto of 1 to 4 carbon atoms, trifluoromethyl, hydroxymethyl, hydroxyethyl, halogen, acetyl, methoxy- or ethoxycarbonyl, carboxy, hydroxy, amino, methyl- or ethylamino, acetamido, ureido, methylsulfonamido, mono- or dimethylaminosulfonyl, aminosulfonyl, mono- or dimethylaminocarbonyl, aminocarbonyl, methyl- or ethylsulfinyl, methyl- or ethylsulfonyl, cyano, or nitro;
• or,
• one of D, E or M is nitrogen, G and L form one side of a fused phenyl, pyridyl, pyrrolyl, thienyl, or furanyl ring (which is either unsubstituted or substituted by alkyl, alkyloxy, or alkylmercapto of 1 to 4 carbon atoms, amino, hydroxy, carboxy, or aminocarbonyl), and the remaining two positions are carbon, of which one of these carbon atoms is optionally unsubstituted or substituted with alkyl, alkyloxy, or alkylmercapto of 1 to 4 carbon atoms, trifluoromethyl, hydroxymethyl, hydroxyethyl, halogen, acetyl, methoxy- or ethoxycarbonyl, carboxy, hydroxy, amino, methyl- or ethylamino, acetamido, ureido, methylsulfonamido, mono- or dimethylaminosulfonyl, aminosulfonyl, mono- or dimethylaminocarbonyl, aminocarbonyl, methyl- or ethylsulfinyl, methyl- or ethylsulfonyl, cyano, or nitro;
• or,
• D is nitrogen, E and G form one side of a fused phenyl, pyridyl, pyrrolyl, thienyl, or furanyl ring (which is either unsubstituted or substituted by alkyl, alkyloxy, or alkylmercapto of 1 to 4 carbon atoms, amino, hydroxy, carboxy, or aminocarbonyl), and the remaining two positions are carbon, of which one of these carbon atoms is optionally unsubstituted or substituted with alkyl, alkyloxy, or alkylmercapto of 1 to 4 carbon atoms, trifluoromethyl, hydroxymethyl, hydroxyethyl, halogen, acetyl, methoxy- or ethoxycarbonyl, carboxy, hydroxy, amino, methyl- or ethylamino, acetamido, ureido, methylsulfonamido, mono- or dimethylaminosulfonyl, aminosulfonyl, mono- or dimethylaminocarbonyl, aminocarbonyl, methyl- or ethylsulfinyl, methyl- or ethylsulfonyl, cyano, or nitro;
• or,
• two of D, E, G, L, and M are nitrogen, and the three remaining positions are carbon, of which one of these carbon atoms is optionally unsubstituted or substituted with methyl, ethyl, trifluoromethyl, hydroxy, acetoxy, hydroxymethyl, hydroxyethyl, halogen, acetyl, methoxy- or ethoxycarbonyl, carboxy, hydroxy, amino, methyl- or ethylamino, acetamido, ureido, methylsulfonamido, alkyloxy of 1 to 4 carbon atoms, methyl- or ethylmercapto, mono- or dimethylaminosulfonyl, aminosulfonyl, mono- or dimethylaminocarbonyl, aminocarbonyl, methyl- or ethylsulfinyl, methyl- or ethylsulfonyl, cyano, or nitro, and of which a second of these carbon atoms is optionally unsubstituted or substituted with methyl, ethyl, hydroxy, or amino;
• or,
• two of D, E, and G are nitrogen, and L and M together form one side of a fused phenyl, pyridyl, imidazolyl, pyrazolyl, or triazolyl ring (the carbon atoms of which are either unsubstituted or substituted by alkyl, alkyloxy, or alkylmercapto of 1 to 4 carbon atoms, amino, hydroxy, carboxy, or aminocarbonyl);
• or,
• two of D, L, and M are nitrogen, and E and G together form one side of a fused phenyl, pyridyl, imidazolyl, pyrazolyl, or triazolyl ring (the carbon atoms of which are either unsubstituted or substituted by alkyl, alkyloxy, or alkylmercapto of 1 to 4 carbon atoms, amino, hydroxy, carboxy, or aminocarbonyl);
• R.sup.1 is hydrogen, alkyl of 1 to 6 carbon atoms, fluoroalkyl of 1 to 6 carbon atoms and 1 to 3 fluorine atoms, alkenylmethyl or alkynylmethyl of 3 to 6 carbon atoms, aryl or arylmethyl (wherein the aryl moiety is phenyl, thienyl or furanyl, which is either unsubstituted or substituted by methyl, methoxy or halogen), alkanoyl or thioalkanoyl of 2 to 4 carbon atoms, alkylsulfonyl of 1 to 4 carbon atoms, mono- or dimethylaminosulfonyl, aminosulfonyl, aminocarbonyl, mono- or di-alkylaminocarbonyl wherein each alkyl moiety contains 1 to 2 carbon atoms, aminoethyl, mono- or di-alkylaminoethyl wherein each alkyl moiety contains 1 to 2 carbon atoms, alkyloxyalkyl or alkylthioalkyl of 2 to 4 carbon atoms, alkyloxycarbonyl wherein the alkyl moiety contains 1 to 4 carbon atoms, alkenyloxycarbonyl wherein the alkenyl moiety contains 2 to 4 carbon atoms, hydroxy, alkyloxy of 1 to 4 carbon atoms, cyano, amino, mono- or di-alkylamino wherein each alkyl moiety contains 1 to 4 carbon atoms, aminocarbonylmethyl, mono- or di-alkylaminocarbonylmethyl wherein the alkyl moiety contains 1 to 2 carbon atoms;
• Z is oxygen, sulfur, .dbd.NCN or a group of the formula .dbd.NOR.sup.8 wherein R.sup.8 is alkyl of 1 to 3 carbon atoms;
• R.sup.2 is hydrogen, alkyl of 1 to 6 carbon atoms, fluoroalkyl of 1 to 6 carbon atoms and 1 to 3 fluorine atoms, cycloalkyl of 3 to 6 carbon atoms, oxetanyl, thietanyl, tetrahydrofuranyl, tetrahydrothienyl, tetrahydropyranyl, tetrahydrothiopyranyl, alkenylmethyl or alkynylmethyl of 3 to 6 carbon atoms, alkyloxyalkyl or alkylthioalkyl of 2 to 5 carbon atoms, alkanoyl or thioalkanoyl of 2 to 5 carbon atoms, cyano, cyanoalkyl of 2 to 5 carbon atoms, hydroxyalkyl or acyloxyalkyl wherein the alkyl moiety contains 2 to 6 carbon atoms and the acyl moiety contains 2 to 3 carbon atoms, oxazolyl, isoxazolyl, thiazolyl, aryl or arylmethyl (wherein the aryl moiety is phenyl, thienyl or furanyl, which is either unsubstituted or substituted by alkyl or alkyloxy of 1 to 3 carbon atoms, hydroxy or halogen), or alkyloxycarbonylmethyl wherein the alkyl moiety contains 1 to 5 carbon atoms;
• R.sup.3 is alkyl of 1 to 6 carbon atoms, alkenyl or alkynyl of 2 to 6 carbon atoms, trihalomethyl, hydroxyalkyl of 1 to 6 carbon atoms, alkyloxyalkyl or alkylthioalkyl of 2 to 6 carbon atoms, or halogen;
• R.sup.4 is hydrogen, methyl, or halogen, and R.sup.5 is hydrogen;
• or,
• R.sup.3 and R.sup.5 are each hydrogen and R.sup.4 is methyl or halogen;
• or
• R.sup.3 and R.sup.4 are each hydrogen and R.sup.5 is alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, alkenyl or alkynyl of 2 to 6 carbon atoms, trihalomethyl, hydroxyalkyl of 1 to 6 carbon atoms, alkyloxyalkyl or alkylthioalkyl of 2 to 6 carbon atoms, aryloxy(or thio)methyl (wherein the aryl moiety is phenyl, thienyl or furanyl, which is either unsubstituted or substituted by alkyl or alkyloxy of 1 to 3 carbon atoms, hydroxy or halogen), arylmethyloxy(or thio)methyl or arylethyloxy(or thio)methyl (wherein the aryl moiety is phenyl, thienyl or furanyl, which is either unsubstituted or substituted by alkyl or alkyloxy of 1 to 3 carbon atoms, hydroxy or halogen), alkyloxycarbonylalkyl wherein the alkyl moieties each contain 1 to 2 carbon atoms, carboxyalkyl or cyanoalkyl wherein the alkyl moieties each contain 1 to 5 carbon atoms, mono- or di-alkylaminocarbonylalkyl wherein the alkyl moieties each contain 1 to 2 carbon atoms, hydroxy, mercapto, alkyloxy or alkylthio of 1 to 5 carbon atoms, hydroxyalkyloxy of 2 to 4 carbon atoms, alkanoyloxy of 2 to 4 carbon atoms, alkylsulfinyl or alkylsulfonyl of 1 to 4 carbon atoms, alkanoyl of 2 to 6 carbon atoms, alkyloxycarbonyl wherein the alkyl moiety contains 1 to 3 carbon atoms, mono- or di-alkylaminocarbonyl wherein each alkyl moiety contains 1 to 3 carbon atoms, aminoalkyl of 1 to 4 carbon atoms, mono- or di-alkylamino wherein each alkyl moiety contains 1 to 3 carbon atoms mono- or di-alkylaminoalkyl wherein each alkyl moiety contains 1 to 3 carbon atoms, N-pyrrolidino, N-piperidino, N-morpholino, aryl or arylalkyl (wherein the aryl moiety is phenyl, pyridyl, or a 5-membered heteroaromatic ring which is either unsubstituted or substituted by alkyl or alkyloxy of 1 to 3 carbon atoms, hydroxy, amino, or halogen, and the alkyl moiety contains 1 to 3 carbon atoms which may be unsubstituted or substituted with a methyl, hydroxy, or amino groups), halogen, cyano, nitro, azido or carboxy;
• or,
• R.sup.5 is hydrogen and R.sup.3 and R.sup.4 are joined to form a cycloalkyl with a 3 or 4 carbon bridge;
• or,
• R.sup.3 is hydrogen and R.sup.4 and R.sup.5 are joined to form a cycloalkyl with a 3 or 4 carbon bridge;
• or,
• R.sup.3, R.sup.4, and R.sup.5 are each hydrogen;
• R.sup.6 and R.sup.7 are each hydrogen;
• or a pharmaceutically acceptable salt thereof.