4″-deoxy-4″-(S)-amido avermectin derivatives

A compound of formula

• that has the S-configuration at the 4″-position and wherein
• the bond between carbon atoms 22 and 23 is a single or a double bond;
• R1 is C1-C12alkyl, C3-C8cycloalkyl;
• or C2-C12alkenyl;
• R2 is H, C2-C12alkenyl, C2-C12alkynyl, —C(═O)—R5, aryl;
• wherein the C2-C12alkenyl, C2-C12alkynyl, aryl substituents may be unsubstituted or mono-to penta-substituted;
• R3 is H, C2-C12alkenyl or C2-C12alkynyl;
• wherein the C2-C12alkynyl and C2-C12alkynyl substituents may be unsubstituted or mono-to penta-substituted;
• X is a bond, O, NR4 or S;
• Z is C═O, C═S or SO2;
• R4 is H, C1-C8alkyl, C3-C8Cycloaklkyl, C2-C8alkenyl, C2-C8alkynyl benzyl or —C(═O)-R5;
• or
• R2 and R4 together are a three-to seven membered alkylene or alkenylene bridge, wherein the alkylene or elkenylene bridges are unsubstituted or mono to tri-substituted;
• and wherein one of the methylene groups of the three-to seven membered alkylene-or alkenylene-bridge may be replaced by O, NH, S, S(═O) or SO2;
• and
• wherein the substituents of the mentioned alkyl, alkeny, alkynyl, cycloalkyl, alkylene, alkenylene, aryl radicals as defined under R2, R3 and R4 are selected from the group consisting of OH, ═O, halogen, halo-C1-C2alkyl, CN, NO2, —N3, C3-C8cycloalkyl that is unsubstituted or substituted by from one to three methyl groups;
• norbornylenyl;
• C3-C8cycloalkenyl that is unsubstituted or substituted by from one to three methyl groups;
• C3-C8halocycloalkyl, C1-C12alkoxy, C1-C6alkoxy-C1-C6alkyl, C3-C8cycloalkoxy, C1-C12haloalkoxy, C1-C12alkythio, C3-C8cycloalkylthio, C1-C12haloalkylthio, C1-C12alkylsulfinyl, C3-C8cycloalkylsulfinyl, C1-C12haloalkylsulfinyl, C3-C8halocycloalkylsulfinyl, C1-C12alkylsulfonyl, C3-C8cycloalkylsulfonyl, C1-C12haloalkylsulfonyl, C3-C8halocycloalkylsulfonyl, C2-C8alkenyl, C2-C8alkynyl, NH(C1-C6alkyl), —N(C1-C6alkyl)2, —C(═O)R5, —NHC(═O)R6, ═NO—C1-C6alkyl, —P(═O)(OC1-C6alkyl)2;
• aryl, pyridyl, pyrimidyl, s-triazinyl, 1,2,4-triazinyl, thienyl, furyl, tetrahydrofuranyl, pyranyl, tetrahydropyranyl, pyrrolyl, pyrazolyl, imidazolyl, thiazolyl, triazolyl, oxazolyl, thiadiazolyl, oxadiazolyl, benzothienyl, quinolinyl, quinoxalinyl, benzofuranyl, benzimidazolyl, benzopyrrolyl, benzothiazolyl, indolyl, coumarinyl, indazolyl, aryloxy;
• and aryl, pyridyl, pyrimidyl, s-triazinyl, 1,2,4-triazinyl, thienyl, furyl, tetrahydrofuranyl, pyranyl, tetrahydropyranyl, pyrrolyl, pyrazolyl, imidazolyl, thiazolyl, oxazolyl, thiadiazolyl, oxadiazolyl, benzothienyl, quinolinyl, quinoxalinyl, benzofuranyl, benzimidazolyl, benzopyrrolyl, benzothiazolyl, indolyl, coumarinyl, indazolyl, and aryloxy that, depending upon the possibilities of substitution at the ring, are mono- to penta-substituted by substituents selected from the group consisting of OH, ═O, halogen, CN, NO2, —N3, C1-C12alkyl, C3-C8cycloalkyl, C1-C12haloalkyl, C1-C12alkoxy, C1-C12haloalkoxy, C1-C12alkylthio, C1-C12haloalkylthio, C1-C6alkoxy-C1-C6alkyl, dimethylamino-C1-C6alkoxy, C2-C8alkenyl, C2-C8alkynyl, phenoxy and phenyl-C1-C6alkyl;
• phenoxy that is unsubstituted or substituted by from one to three substituents selected independently of one another from halogen, methoxy, trifluoromethyl and trifluoromethoxy;
• phenyl-C1-C6alkoxy that is unsubstituted or substituted in the aromatic ring by from one to three substituents selected independently of one another from halogen, methoxy, trifluoromethyl and trifluoromethoxy;
• phenyl-C2-C6alkenyl, phenyl-C2-C6alkynyl, methylenedioxy, —C(═O)R5,—O—C(═O)R8, —NH—C(═O)R6, NH2, NH(C1-C12alkyl), N(C1C12alkyl)2, C1-C6alkylsulfinyl, C3-C8cycloalkylsulfinyl, C1-C6haloalkylsulfinyl, C3-C8halocycloalkylsulfinyl, C1-C6alkylsulfonyl, C3-C8cycloalkylsulfonyl, C1-C6haloalkylsulfonyl and C3-C8halocycloalkylsulfonyl;
• R5 is H, OH, SH, NH2, NH(C1-C12alkyl), N(C1-C12alkyl)2, C1-C12alkyl, C3-C8cycloalkyl, C1-C12haloalkyl, C1-C12alkoxy, C1-C12haloalkoxy, C1-C6alkoxy-C1-C12alkoxy, C1-C12alkylthio, C2-C8alkenyloxy, C2-C8alkynyloxy;
• phenyl, phenoxy, benzyloxy, NH-phenyl, —N(C1-C6alkyl)-phenyl, NH—C1-C6alkyl-C(═O)—R7, —N(C1-C6alkyl)-C1-C6alkyl-C(═O)—R7;
• or phenyl, phenoxy, benzyloxy, NH-phenyl or —N(C1-C6alkyl)-phenyl each of which is substituted in the aromatic ring by from one to three substituents selected independently of one another from halogen, C1-C6alkoxy, C1-C6haloalkyl and C1-C6haloalkoxy;
• R6 is H, C1-C12alkyl, C1-C12haloalkyl, C2-C8alkenyl, C2-C6alkynyl, phenyl, benzyl, NH2, NH(C1-C12alkyl), N(C1-C12alkyl)2, —NH-phenyl or —N(C1-C12alkyl)-phenyl;
• and
• R7 is H, OH, C1-C12alkyl, C,-C12alkoxy, C1-C6alkoxy-C1-C6alkoxy, C2-C8alkenyloxy, phenyl, phenoxy, benzyloxy, NH2, NH(C1-C12alkyl), N(C1-C12alkyl)2, —NH-phenyl or —N(C1-C12alkyl)-phenyl;
• or, where applicable, an E/Z isomer, a mixture of E/Z isomers and/or a tautomer, in each case in free form or in salt form;
• with the proviso that Z is not C═O when X is a bond, R2 is H, R3 is hydrogen, the bond between carbon atoms 22 and 23 is a double bond and R1 is i-propyl or sec-butyl.