PIRIDO (3 ', 2': 4,5) HAVING (3,2-D) PYRIMIDINES AND PIRIDO (3 ', 2': 4,5) FURO (3,2-D) PIRIMIDINES REPLACED FOR USE AS INHIBITORS OF THE RELEASE OF PDA-4 AND / OR TNF-ALFA.

摘要

Compounds of general formulas 1a, 1b, 1c and 1d ** (See formula) ** where Y means S, O or N-H; R1 means hydrogen; (C1-10) alkyl, (C2-12) alkenyl, (C2-12) alkynyl, in each case straight, branched or cyclic chain and, if necessary, substituted simply, double or triple with independently selected R NAK groups ; aralkyl with aryl (C6-12) and alkyl (C1-5), if necessary substituted simply, double or triple with independently selected R NAK groups; phenyl, if any substituted simply, double or triple with independently selected R NAK groups; 1-naphthyl, 2-naphthyl; pyridyl-N-oxide (if appropriate substituted with R NAK); mono or bicyclic heterocycles, saturated or unsaturated in a single or multiple way, with 5-14 ring atoms, including 1-4 heteroatoms that preferably consist of N, O and S, and if necessary substituted simply, double or triple with independently selected R NAK groups; (C1-10) straight chain, branched or cyclic alkoxy and, where appropriate, substituted simply, double or triple with independently selected R NAK groups; aralkyloxy with aryl (C6-12) and alkyl (C1-5), if necessary substituted simply, double or triple with independently selected R NAK groups; (C2-12) alkylacil (if any substituted with R NAK); benzoyl, 1- and 2-naphthoyl (in each case optionally substituted with R NAK); hydroxyl, sulfhydryl, formyl, carboxyl, CONH2, cyano, rhodan, nitro, SO3H; alkylthio, alkylsulfinyl, SO2O-alk and alkylsulfonyl, in each case a straight, branched or cyclic chain (C1-6) and, where appropriate, substituted simply, double or triple with independently selected R NAK groups; arylthio, arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl and heteroarylsulfonyl, in each case optionally substituted simply, double or triple with independently selected R NAK groups; alkoxycarbonyl, CONHalq and CONalq2, in each case of straight, branched or cyclic chain (C1-6), and if necessary substituted in a simple, double or triple way with independently selected R NAK groups; aryloxycarbonyl, arylcarbamoyl, arylamido, N-aryl-N-alkylamido, N-aryl-N-alkylcarbamoyl, aralkyloxycarbonyl and aralkylcarbamoyl, with (C1-5) alkyl, aryl (C6-10), and if substituted simply, double or triple with independently selected R NAK groups; heterocyclylcarbonyl, heterocyclylcarbamoyl, heterocyclylamido, N-heterocyclyl-N-alkylcarbamoyl, N-heterocyclyl-N-alkylamido, heterocyclylalkyloxycarbonyl and heterocyclic mono or bicyclic, single- or multi-ring, 5- or double-heteroatty, mono- or bicyclic, heterocycle they 1-4 heteroatoms that preferably consist of N, O and S, if necessary substituted simply, double or triple with independently selected R NAK groups and (C1-5) alkyl; chlorine, bromine, iodine, fluorine; amino, (C1-6) alkylamino, dialkyl (C1-5) amino, in each case straight, branched or cyclic chain, and if necessary substituted simply, double or triple with independently selected R NAK groups; arylamino (C6-10), if necessary substituted simply, double or triple with independently selected R NAK groups; mono or bicyclic heterocyclylamino, saturated or unsaturated in a single or multiple way, with 5-14 ring atoms, including 1-4 heteroatoms that preferably consist of N, O and S, if necessary substituted simply, double or triple with independently selected R NAK groups; arylhydrazino, if necessary substituted simply, double or triple with independently selected R NAK groups; LA-A-LB-B, formula in which: LA means a simple link; NR, O, S, SO, SO2; A means phenyl, if any substituted simply, double or triple with independently selected R NAK groups; naphthyl, naphthyl substituted simply or multiplely with R NAK; mono or bicyclic heterocycles, saturated or unsaturated in a single or multiple way, with 4-14 ring atoms, including 1-5 heteroatoms that preferably consist of N, O and S, which can carry one or more oxygen atoms in C , N and / or S and, where appropriate, are substituted simply, double or triple with independently selected R NAK groups; LA-A can also mean a tricycle-LB direct link, in which case LB n does not represent a single link; LB means a simple link; NR, O, S, SO, SO2, -CHR NAK-, -CH2-O-, -O-CH2; the following functional groups: ** (See formula) ** B means hydrogen; alkyl, if any substituted simply, double or triple, independently of each other, with R NAK; -CONH2, -CONHalq (alq where appropriate substituted with R NAK), -CONHaryl (aryl if appropriate substituted with R NAK), -CONH-het-aryl (het-aryl if appropriate substituted with R NAK) , -COOH, -COOalq (if any, substituted with R NAK); -COalq (alq where appropriate substituted with R NAK), -CO-aryl (aryl if appropriate substituted with R NAK), -CO-het-aryl (het-aryl if appropriate substituted with R NAK); -CH2-CONH2, -CH2-CONHalq (alq where appropriate substituted with R NAK), -CH2-CONHaryl (aryl if appropriate substituted with R NAK); CH2-CONH-het-aryl (het-aryl if appropriate substituted with R NAK), -CH2-COOH, -CH2-COOalq (alq where appropriate substituted with R NAK); -CH2-COalq (alq where appropriate substituted with R NAK); CH2-COaryl (aryl if appropriate substituted with R NAK), -CH2-CO-het-aryl (het-aryl if appropriate substituted with R NAK); phenyl, if any substituted simply, double or triple with independently selected R NAK groups; naphthyl, if necessary substituted simply, double or triple with independently selected R NAK groups; single or multiple saturated or unsaturated mono or bicyclic heterocycles with 4-14 ring atoms, including 1-5 heteroatoms that preferably consist of N, O and S, which can carry one or more oxygen atoms in C, N and / or S and, where appropriate, are substituted simply, double or triple with independently selected R NAK groups; R means hydrogen, alkyl, if any substituted with R NAK; R2 means hydrogen; (C1-12) alkyl; (C2-12) alkenyl and (C2-12) alkynyl; benzyl, phenylalkyl (C2-6) (if any substituted with R NAK in a single or multiple way, the same or different, in the aromatic and / or aliphatic part of the molecule); phenacyl (if necessary substituted with R NAK in a single or multiple way, the same or different, in the aliphatic aromatic part of the molecule); carboxyl, alkoxycarbonyl (C1-4), -CONH2, -CONHalq and CONalq2 (with "alq" in each case (C1-6)); R C (O) - (R having the meaning indicated above); cyano, nitro, amino, (C1-6) alkylamino, dialkyl (C1-6) amino, -N = N-C6H5, -N = N-C6H4-R NAK; 1,3-diphenylpyrazol-4-yl, thiazolin-2-yl, imidazolin-2-yl and 3,4,5,6-tetrahydro-pyrimidinyl. R3 means hydrogen; (C1-10) alkyl; (C2-12) alkenyl and (C2-12) alkynyl, in each case straight, branched or cyclic chain, and if necessary substituted in a simple, double or triple way with independently selected R NAK groups; aralkyl with aryl (C6-12) and alkyl (C1-5), if necessary substituted simply, double or triple with independently selected R NAK groups; phenyl, if any substituted simply, double or triple with independently selected R NAK groups; 1-naphthyl, 2-naphthyl; pyridyl-N-oxide (if appropriate substituted with R NAK); (C1-10) straight chain, branched or cyclic alkoxy, and if necessary substituted simply, double or triple with independently selected R NAK groups; aralkyloxy with aryl (C6-12) and alkyl (C1-5), if necessary substituted simply, double or triple with independently selected R NAK groups; (C2-12) alkylacil (if any substituted with R NAK); benzoyl, 1- and 2-naphthoyl (in each case optionally substituted with R NAK); hydroxyl, sulfhydryl, formyl, carboxyl, CONH2, cyano, rhodan, nitro, SO3H; alkylthio, alkylsulfinyl, SO2Oalq and alkylsulfonyl, in each case a straight, branched or cyclic chain (C1-6) and, where appropriate, substituted simply, double or triple with independently selected R NAK groups; arylthio, arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl and heteroarylsulfonyl, in each case optionally substituted simply, double or triple with independently selected R NAK groups; alkoxycarbonyl, CONHalq and CONalq2, in each case of straight, branched or cyclic chain (C1-6), and if necessary substituted in a simple, double or triple way with independently selected R NAK groups; aryloxycarbonyl, arylcarbamoyl, arylamido, N-aryl-N-alkylamido, N-aryl-N-alkylcarbamoyl, aralkyloxycarbonyl and aralkylcarbamoyl, with (C1-5) alkyl, aryl (C6-10), and if substituted simply, double or triple with independently selected R NAK groups; chlorine, bromine, iodine, fluorine; amino, (C1-6) alkyl amino, dialkyl (C1-5) amino, in each case straight, branched or cyclic chain, and if necessary substituted simply, double or triple with independently selected R NAK groups; arylamino (C6-10), if necessary substituted simply, double or triple with independently selected R NAK groups; arylhydrazino, if necessary substituted simply, double or triple with independently selected R NAK groups; R4 means (C2-14) alkyl; cycloalkyl (C3-14), alkenyl (C2-14), cycloalkenyl (C3-14) and alkynyl (C2-14) (in each case optionally substituted with R NAK in skeleton C of the aliphatic groups mentioned above); phenyl, 4-R NAK-phenyl, 3-R NAK-phenyl, 2-R NAK-phenyl (but except: 2-NO2-phenyl), 3-R NAK, 4-R NAK-phenyl, 3-R NAK, 4-R NAK-, 5-R NAK-phenyl; 1-naphthyl, 2-naphthyl (in each case optionally substituted with R NAK); S-alkyl, SO-alkyl, SO2-alkyl (in each case (C1-C8)), S-alkenyl, SO-alkenyl, SO2-alkenyl (in each case (C2-C8)), S-alkynyl, SO-