Patent IL-100899-A (IL)
Title: Beta-amino-alpha- hydroxycarboxylic acid derivatives, processes for the preparation thereof and pharmaceutical compositions containing the same
IPC: C07D403/12
Filed: 1992-02-07
Abstract: A compound for treatment of retroviral infection, in particular AIDS of the formula R2OR4O NCCHC R1CHNCHR5 HR3OH wherein: R1 represents a group of the formula R(Z)xA- wherein R represents a hydrogen atom, an alkyl, alkenyl or alkynyl group optionally substituted by at least one substitutent selected from a cycloalkyl group, carbocyclic aryl group having from six to fourteen carbon atoms or a heterocyclic group having from 3 to 10 ring atoms of which from 1 to 4 are nitrogen, oxygen or sulfur heteroatoms, said cycloalkyl, aryl or heterocylic groups being unsubstituted or substituted by at least one substituent selected from the group consisting of substituents (b) or R represents a group of formula -NRaRb wherein Ra and Rb are independently selected from the group consisting of hydrogen, alkyl groups having from 1 to 4 carbon atoms, cycloalkyl, heterocylic or carbocyclic groups as defined above or from aralkenyl groups in which the aryl group has from 6 to 14 carbon atoms and the alkenyl group has from 2 to 7 carbon atoms. or aralkyl groups in which the aryl group has from 6 to 14 carbon atoms and the alkyl group has from 1 to 3 carbon atoms; Z represents oxygen or sulfur; A represents a group of formula -CO-, -COCO-, -SO-, -SO2- or -CS-; and x is the cipher 0 or the integer 1; R2 represents a hydrogen atom, an alkyl group having from one to six carbon atoms substituted with at least one of substitutents (a); R3 represents a hydrogen atom, an alkyl group having from one to six carbon atoms, being optionally substituted by at least one of substitutents (c), a cycloalkyl, carbocyclic aryl or a heterocyclic group optionally being substituted by at least one substituent selected from the group consisting of substituents (b) or an alkenyl or allkynyl group having from two to seven carbon atoms, and being optionally substituted by at least one substituent selected from the group consisting of substituents (a), R4 represents a hydrogen atom, an alkyl group having from one to six carbon atoms and optionally being substituted by at least one of substituents (a), or a cycloalkyl, carbocyclic aryl or a heterocyclic group optionally being substituted by at least one substituent selected from the group consisting of substituents (b) and R5 represents a group of formula -B-(CO)- Y-Rcy, wherein B represents a heterocyclic group having from 3 to 10 ring atoms of which from 1 to 4 are heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur heteroatoms, at least one of which is a nitrogen heteroatom, said heterocyclic group being unsubstituted or substituted with at least one alkyl group having from one to six carbon atoms; Y represents an oxygen atom, a nitrogen atom or a sulfur atom; y is the integer 1 when Y represents an oxygen atom or a sulfur atom, and 2 when Y represents a nitrogen atom; and Rc represents a hydrogen atom, an alkyl, alkenyl or alkynyl group optionally being substituted by at least one substitutent selected from the group consisting of substituents (a), a cycloalkyl, carbocyclic aryl or heterocyclic group optionally being substituted by at least one substituent selected from the group consisting of substituents (b); and, where there are two groups or atoms represented by Rc, they are the same or different; and substituents (a) are selected from: hydroxy groups, C3-C10 cycloalkyl groups, C1-C6 alkoxy groups, C1-C6 aliphatic acyloxy groups, C1-C6 aliphatic acyl groups, carboxy groups, C2-C6 alkoxycarbonyl groups, sulfo groups, halogen atoms, amino groups, C2-C5 aliphatic acylamino groups, alkylamino groups in which the alkyl part is C1-C6 alkyl, dialkylamino groups in which each alkyl part is C1-C3 alkyl, carbocyclic aryl groups having from six to fourteen carbon atoms, carbocyclic aryl groups having from six to fourteen carbon atoms and being substituted by at least one substituent selected from the group consisting of substituents (b) below, carbocyclic aryloxy groups having from six to fourteen carbon atoms, carbocyclic aryloxy groups having from six to fourteen carbon atoms and being substituted by at least one substituent selected from the group consisting of substituents (b) below, and heterocyclic groups having from 3 to 10 ring atoms of which from 1 to 4 are heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur heteroatoms, said heterocyclic group being unsubstituted or substituted by at least one substituent selected from the group consisting of substituents (b) below; substituents (b) are selected from C1-C6 alkyl groups having from 0 to 3 of substituents (a), C1-C6 haloalkyl groups, C1-C6 aliphatic acyl groups having from 0 to 3 of substituents (a), C1-C6 alkylenedioxy groups, aralkyl groups wherein the alkyl part is C1-C6 alkyl and the aryl part is C6-C14 carbocyclic aryl which has from 0 to 3 of substituents (b), aralkyloxycarbonyl groups wherein the alkyl part is C1-C6 alkyl and the aryl part is C6-C14 carbocyclic aryl which has from 0 to 3 of substituents (b), hydroxy groups, C1-C6 alkoxy groups, C6-C14 carbocyclic aryl groups having from 0 to 3 of substituents (b), aralkyloxy groups where the alkyl part is C1-C6 alkyl and the aryl part is C6-C14 carbocyclic aryl which has from 0 to 3 of substituents (b), C6-C14 carbocyclic aryloxy groups having from 0-3 of substituents (b), heterocyclic groups having from 3 to 10 ring atoms of which 1 to 4 are heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, said heterocyclic group being unsubstituted or substituted by at least one of substituents (b), halogen atoms, nitro groups, cyano groups, carboxy groups, alkoxycarbonyl groups having a total of from 2 to 7 carbon atoms, amino groups, C1-C6 alkylamino groups, dialkylamino groups wherein each alkyl part is C1-C6 alkyl, aliphatic or carbocyclic aromatic carboxylic acylamino groups, carbamoyl groups, alkylcarbamoyl groups where the alkyl part is C1-C6 alkyl, dialkylcarbamoyl groups where each alkyl part is C1-C6 alkyl, mercapto groups, C1-C6 alkylthio groups, C6-C14 carbocyclic arylthio groups, C1-C6 alkylsulfonyl groups, C6-C14 carbocylic arylsulfonyl groups wherein the aryl part has from 0 to 3 C1-C6 alkyl substituents, aminosulfonyl groups, C1-C6 alkylsulfinyl groups and C6-C14 carbocyclic arylsulfinyl groups wherein the aryl part has from 0 to 3 C1-C6 alkyl substituents; substituents (c) are selected from: hydroxy groups, C1-C6 alkoxy groups, C6-C14 carbocyclic aryl groups having from 0 to 3 of substituents (b), aralkyloxy groups where the alkyl part is C1-C6 alkyl and the carbocyclic aryl part is C6-C14 carbocyclic aryl which has from 0 to 3 of substituents (b), C6-C14 carbocyclic aryloxy groups having from 0-3 of substituents (b), heterocyclic groups having from 3 to 10 ring atoms of which 1 to 4 are heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, said heterocyclic group being unsubstituted or substituted by at least one of substituents (b), halogen atoms, nitro groups, cyano groups, carboxy groups, alkoxycarbonyl groups having a total of from 2 to 7 carbon atoms, amino groups, C1-C6 alkylamino groups, dialkylamino groups wherein each alkyl part is C1-C6 alkyl, aliphatic or carbocyclic aromatic carboxylic acylamino groups, carbamoyl groups, alkylcarbamoyl groups where the alkyl part is C1-C6 alkyl, dialkylcarbamoyl groups where each alkyl part is C1-C6 alkyl, mercapto groups, C1-C6 alkylthio groups, C6-C14 carbocyclic arylthio groups, C1-C6 alkylsulfonyl groups, C6-C14 carbocyclic arylsulfonyl groups wherein the aryl part has from 0 to 3 C1-C6 alkyl substituents, aminosulfonyl groups, C1-C6 alkylsulfinyl groups and C6-C14 carbocyclic arylsulfinyl groups wherein the aryl part has from 0 to 3 C1-C6 alkyl substituents; provided that, where a substituent (a) is substituted by a substituent (b), then substituent (b) is not further substituted by a substituent (a); that where a substituent (b) is substituted by a substituent (a), then substituent (a) is not further substituted by a substituent (b); that, where substituent (b) is group which is itself substituted by a further substituent (b), that further substituent (b) is not itself substituted; and that where a substituent (c) is substituted by a substitutent (b), that further substituent (b) is not itself substituted, and pharmaceutically acceptable salts and esters thereof.