Novel multifunctional peptidase inhibitors, especially for medical use

Compounds of the general formula (1)

• wherein
• —X1, X2, X3, X4 and X5 may be identical to or different from each other and are selected from the group consisting of —H, —OH, —NO2, -halogens, —NH2, —OR4, —NHR4, —NR4R5, —CH2NHR4, —CH2NR4R5, —SH, —SR4, —CH2(C═O)R4, —P(═O)(OH)2, —P(═O)(OH)(OR4), —P(═O)(OR4)(OR5), —P(═O)(═O)(OH), —P(═O)(═O)(OR4), —P(═O)(═O)(H) and —P(═O)(═O)(R4), homocyclic and heterocyclic, aromatic and non-aromatic, condensed and non-condensed ring systems, in the case of heterocyclic moieties being allowed to have one, two or several heteroatoms selected from the group consisting of N, O, S, P, substituted with substituents R4 and R5;
• wherein R4 and R5 may be identical to or different from each other and are selected from the group consisting of —H, —OH, —NH2, —NO2, substituted and unsubstituted straight-chain or once- or multiple-branched aliphatic hydrocarbon, ester, amide, carbonate and carbamate residues having no, one or multiple double or triple carbon-carbon bonds and having from 1 to 29 carbon atoms which may bear O, S, NH or a secondary amino moiety at any chemically possible position of the chain between two chain carbon atoms, with the one or two sub-chains at the secondary amino group being built up according to the definition of the main chain described here;
• homoaromatic or heteroaromatic or non-aromatic homocyclic or heterocyclic condensed or non-condensed aliphatic hydrocarbon residues having 3 to 10 ring members, and, in the case of heterocyclic moieties, including one or several identical or different hetero atoms selected from O, N, S, and P and, in the case of non-aromatic cyclic systems, having no or one or several carbon-carbon or carbon-heteroatom double bonds or having no, one or several carbon-carbon triple bonds;
• said R4 and R5 residues optionally bearing one, two or more substituents independently selected from X1, X2, X2, X4 and X5 or optionally bearing, at each possible position, one or more moieties selected from the group consisting of carbonyl, carbonic acid, carbonic acid ester, carbonic acid amide, carbonate and carbamate;
• with the proviso that substituents defined according to the definition of R4 and R5, which are allowed to occupy positions only that avoid direct —N—N— and —O—O— grouping;
• and with the further proviso that, if R4 and R5 are bound to the same carbon atom or hetero atom and the valence situation allows, the R4 and R5 substituents may be part of a spiro ring system and form a homocyclic or heterocyclic, condensed or uncondensed ring which is unsubstituted or is substituted by one, two or more substituents selected from the group consisting of X1, X2, X3, X4 and X5;
• R1, R2, R6 and R7 may vary independently and represent residues as defined above for R4 and R5, or all permutatively possible pairs of the substituents R1, R2, R6 and R7 may form, together with the atom(s) of the basic structure (1) to which they are bound, a 5- to 14-membered heterocyclic aromatic (if chemically possible) or non-aromatic ring structure which may be condensed or non-condensed and unsubstituted or substituted with one or more substituent(s) R4 as defined above;
• Sp represents an aliphatic hydrocarbon chain having 2 to 8 carbon atoms in the main chain and bearing no, one or several substituents R4 defined as above, a non-aromatic homocyclic or heterocyclic or homoaromatic or heteroaromatic non-condensed or condensed ring system consisting of 3 to 10 ring atoms and bearing no, one or several substituents R4 defined as above or bearing —O—, —S—, —NH— and —NR4— substituents, wherein R4 is defined as above;
• L represents —CR13, >C═O or >C═NR13, wherein R13 represents a residue having the same meanings as R4 above, with the proviso that, if L represents >C═O or >C═NR13 (wherein R13 is defined as R4 above), R2 is not existent, or L may be nitrogen or oxygen, respectively, provided that the bond with the respective part of the molecule causes no directly bound —N—N— or —O—O— units;
• R3 represents one of the following substituents of (a), (b), (c) or (d):
• wherein
• A is a structural element directly bound to the substituent L and represents a single bond or a substituent selected from >C═O, >C═NR4, or >C═CR4R5, an aliphatic straight or once or several times branched hydrocarbon chain having 1 to 6 carbon atoms, having none or one or several carbon-carbon double or triple bonds and being unsubstituted or substituted with one or several R4 substituents, wherein R4 and R5 have the meaning as defined above, or A may be —NR4, —O— or —S—, with the proviso that the bond between A and L forms no —N—N— or —O—O-bond, and n is an integer selected from 0, 1 and 2;
• B1 and B2 are identical to or different from each other and represent a residue selected from the group consisting of —H, —CH3, -halogens, —OH, —OR9, —NH2, —NHR9, —NR9R10 or all meanings of R4 defined above, wherein R9 and R10 may be identical to or different from each other and may be selected from the group consisting of all substituents defined above as R4;
• or B1 and B2 together may be part of or together form a 3- to 10-membered homocyclic or heterocyclic aromatic or non-aromatic saturated or once or several times unsaturated, non-condensed or condensed ring having none or one or several hetero atoms selected from >N—, O—, —S— and >P<, which ring is unsubstituted or may be substituted with one or several substituent(s) selected from all substituents defined above as R4;
• R8 represents a substituent selected from the group consisting of all substituents represented by R4 above or may be a hydrocarbon chain bridging to the above substituent A or to a carbon or hetero atom contained in the above substituent Sp, said hydrocarbon chain having 1 to 6 carbon atoms in a straight chain, having none or one or several carbon-carbon double or triple bond(s) and being unsubstituted or substituted with one or several R4 substituents, wherein R4 has the meaning defined above, or containing, within said straight hydrocarbon chain, one or several hetero atom(s) selected from the group consisting of —O—, —S—, >NH and >NR12 wherein R12 may have all meanings as R4 defined above, or represents a homoaromatic or heteroaromatic ring or non-aromatic homocyclic or heterocyclic ring having none, one or multiple double or triple bond(s) and bearing no, one or multiple substituent(s) selected from all meanings of R4;
• and
• Y1, Y2, Y3, Y4 and Y5 may be identical to or different from each other and may be selected from substituents having the same meaning as the substituents X1, X2, X3, X4 and X5;
• wherein Y-substituents having consecutive numbers may be may be bound via atoms selected from the group consisting of C, N, O, S or P being part of a condensed or non-condensed, homocyclic or heterocyclic, non-aromatic or homoaromatic or, provided that the chemical situation allows, heteroaromatic ring system having 3 to 10 ring members which may be non-substituted or substituted with one, two or several residues represented by R4 and R5 as defined above so that the phenyl ring is a part of a condensed system;
• wherein A, B1, B2, and Y1 to Y5 may have the same meaning as the corresponding substituents of the above formula (a), n is an integer selected from the range of between 0 and 3, and Z represents —H, a residue having the meaning selected from all meanings of R4 or may be a hydrocarbon chain selected from those meanings of hydrocarbon chains found above for R8 and bridging to B1, B2, R2 or to a carbon atom or hetero atom of Sp;
• wherein A, B1, B2, Y1 to Y5 and Z may have the same meaning as the corresponding substituents of the formulae (a) and (b), n is an integer selected from the range of between 0 and 3;
• or
• wherein Y1 to Y5 and Z may have the same meaning as the corresponding substituents of the formulae (a), (b) and (c), n is an integer selected from the range of between 0 and 6;
• for the four representations of R3, (a), (b), (c) and (d), bridgings connecting the structural elements A, B1, B2, R8 and L are allowed between two or more of these elements, so that, in the case of more than two moieties connected, bridged condensed and basket-like sub-structures can be formed, respectively;
• as bridging moieties, unsubstituted and, with substituents according to the definition of R4 and R5, substituted, continuous or interrupted with O, S and NR4, straight and once or multiple branched carbon chains with none, one or several double and triple bond(s), respectively, are possible;
• or the salts thereof with organic and/or inorganic acids.