Patent GB-880752-A (GB)
Title: Substituted amides
IPC: C07D213/81
Filed: 1959-05-20
Abstract: The invention comprises compounds of the formula A-NHNHZCONR1R2 in which Z is an alkylene radical of 1 to 5 carbon atoms, R1 is hydrogen or an alkyl group of at most 5 carbon atoms, R2 is alkyl, alkenyl, cycloalkyl of 3 to 6 carbon atoms, or pyridyl, pyridyl alkyl, furylalkyl or thienylalkyl in which the alkylene group contains at most 5 carbon atoms and which may be ring-substituted by an alkyl group of at most 5 carbon atoms, or an aryl or aralkyl group of the formula <FORM:0880752/IV (b)/1> (wherein X is hydrogen, halogen or alkyl or alkoxy of at most 5 carbon atoms, Y is hydrogen, halogen, alkyl or alkoxy of at most 5 carbon atoms, trifluoromethyl, cyano or alkanoyl of at most 4 carbon atoms and n is zero or an integer of from 1 to 4), and A is hydrogen or an aryl group of the formula RCO (wherein R is an alkyl or alkenyl group of at most 20 carbon atoms which may be substituted by one or two hydroxy or mercapto groups or alkylamino, alkoxy or alkylmercapto groups containing at most 5 carbon atoms, or alkanoylamino, alkanoyloxy or alkanoylmercapto groups containing at most 4 carbon atoms, or R is the group E-(CH2)m-, E being cycloalkyl of 3 to 6 carbon atoms, pyridyl, furyl, thienyl, thiazolyl, oxazolyl or isooxazoyl which may be ring-substituted by an alkyl group of at most 5 carbon atoms and m being zero or an integer from 1 to 4, or R is an aryl or aralkyl group of the general formula indicated above); and pharmaceutically acceptable acid-addition salts thereof; and their preparation by (1) reacting an amine NHR1R2 with an acid ANHNHZCOOH or an ester, amide, nitrile, halide or anhydride thereof; or (2) hydrogenating the corresponding hydrazone of the formula ANHN=CHZ1CONR1R2 wherein Z1 is an alkylene group of at most 4 carbon atoms; or (3) reacting a hydrazine ANHNH2 with an amide halogen -ZCONR1R2; or (4) where A is RCO, acylating the corresponding compound where A is H; or (5) where A is RCO, reacting a hydrazide RCONHNH2 with an amide R3CH=CHCONR1R2, wherein R3 is hydrogen or an alkyl group of at most 3 carbon atoms. The subject-matter of Specification 880,753 is disclaimed.  Many examples and lists of starting materials and final products are given, and a list of mineral and sulphonic salt forming acids is provided.  Esters of the formula RCONHNHCH(R3) CH2COOR4 (wherein R and R3 are as defined above and R4 is an alkyl group) are prepared by reacting a hydrazide RCONHNH2 with an ester R3CH=CHCOOR4 in an inert organic solvent; or by acylating esters of the formula NH2NHCH(R3)CH2COOR4.  Hydrazones of the formula ANHN=CHZ1 CONR1R2 are prepared by condensing a hydrazine ANHNH2 with the appropriate carbonyl compound.  Esters of the formula ANHNHZCOOR4 are prepared by condensing a hydrazine ANHNH2 with the appropriate carbonyl compound to give a hydrazone of the formula ANHN=CHZ1COOR4 and then reducing this; or, where A is RCO, acylating the esters where A is hydrogen.ALSO:Therapeutic compositions comprise compounds of the formula A-NHNHZCONR1R2 in which Z is an alkylene radical of 1 to 5 carbon atoms, R1 is hydrogen or an alkyl group of at most 5 carbon atoms, R2 is alkyl, alkenyl, cycloalkyl of 3 to 6 carbon atoms, or pyridyl, pyridylalkyl, furylalkyl or thienylalkyl in which the alkylene group contains at most 5 carbon atoms and which may be ring-substituted by an alkyl group of at most 5 carbon atoms, or an aryl or aralkyl group of the formula <FORM:0880752/VI/1> (wherein X is hydrogen, halogen or alkyl or alkoxy of at most 5 carbon atoms, Y is hydrogen, halogen, alkyl or alkoxy of at most 5 carbon atoms, trifluoromethyl, cyano or alkaroyl of at most 4 carbon atoms and n is zero or an integer of from 1 to 4), and A is hydrogen or an acyl group of the formula RCO (wherein R is an alkyl or alkenyl group of at most 20 carbon atoms which may be substituted by one or two hydroxy or mercapto groups or alkylamino, alkoxy or alkylmercapto groups containing at most 5 carbon atoms, or alkanoylamino, alkanoyloxy or alkanoylmercapto groups containing at most 4 carbon atoms, or R is the group E-(CH2)m-, E being cycloalkyl of 3 to 6 carbon atoms, pyridyl, furyl, thienyl, thiazolyl, oxazolyl or iso-oxazolyl which may be ring-substituted by an alkyl group of at most 5 carbon atoms and m is zero or an integer of from 1 to 4, or R is an aryl or aralkyl group of the general formula indicated above) or acid-addition salts thereof, and pharmaceutically acceptable carriers therefor.  They may take the form of tablets, capsules or liquid preparations which may contain flavouring and colouring agents.  Salts with mineral acids and sulphonic acids are referred to.  Specification 880,753 is referred to.