Patent ES-274343-A1 (ES)
Title: Compositions and method of treating mycobacterium tuberculosis with 2,2'-(ethylenediimino)-di-1-butanols
IPC: C07D213/30
Filed: 1962-02-06
Abstract: The invention comprises compounds of the formula <FORM:0981818/C2/1> (wherein R1 is lower alkyl R2 and R3 are hydrogen, lower alkyl or hydroxy lower alkyl R4 is lower alkyl, lower haloalkyl, lower hydroxyalkyl, lower alkoxy lower alkyl, phenyl lower alkoxy lower alkyl, phenoxy lower alkyl optionally substituted by amino, alkoxy, alkylenedioxy or nitro groups, pyridoxy lower alkyl, pyridyl lower alkoxy lower alkyl, benzoyloxy lower alkyl optionally substituted by halogen, amino, alkoxy or alkylenedioxy groups, pyridylcarbonyloxy lower alkyl or lower alkanoyloxy lower alkyl X is an alkylene chain of 2 or 3 carbon atoms and Y is halogen, lower alkoxy, phenyl lower alkoxy, phenoxy optionally substituted by amino, alkoxy, alkylenedioxy or nitro groups, pyridoxy, pyridyl lower alkoxy, lower alkanoyloxy, benzoyloxy optionally substituted by halogen, amino, alkoxy or alkylenedioxy groups, or pyridylcarbonyloxy: the word "lower" referring to groups containing at most 6 carbon atoms) and acid-addition salts thereof and their preparation (1) by condensing 2 mols. of <FORM:0981818/C2/2> (wherein Y is an ether group as defined above) with one mol. of R2.NH.X.NH.R3 or (2) by condensing 2 mols. of R1.CO.CH2Y or the ketal thereof under acidic reducing conditions with one mol. of R2.NH.X.NH.R3 or (3) by condensing 2 mols. of <FORM:0981818/C2/3> (wherein Y is an ether group as defined above) which may be produced in situ by reduction of the corresponding nitro compound, with 1 mol. of Halogen-X-Halogen or (4) by condensing 2 mols. of compound IID with 1 mol. of Z.CO. CO.Z (wherein Z is OH, substituted OH or halogen) to form a compound of the formula <FORM:0981818/C2/4> and reducing thio or (5) condensing 2 mols. of compound IID (wherein Y has any of the values assigned for compounds I) under acidic reducing. conditions with OHC.COR6 (wherein R6 is hydrogen or methyl) or the acetal thereof or (6) by condensing 2 mols. of compound IIA with 1 mol. of a salt of R2.NH.CO.CO.NH.R3 to form compound IVC, and reducing thio or (7) by condensing 1 mol. of compound IIA with 1 mol. of R2.NH.X.NR3R4 or (8) by condensing 1 mol. of compound IID with 1 mol. of Halogen. CH.R6.CO.NR3R4 to form <FORM:0981818/C2/5> and reducing thio or (9) by condensing 1 mol. of compound IID with 1 mol. of Halogen. X.NR3R4 or (10) by condensing 1 mol. of compound IID with 1 mol. of Z.CO.CH.R6. NR3R4 to form <FORM:0981818/C2/6> and reducing thio or (11) by condensing 1 mol. of compound IID (wherein Y has the values as in (5)) under acidic reducing conditions with 1 mol. of OHC.CH.R6.NR3R4 or (12) by treating a compound <FORM:0981818/C2/7> (prepared by replacing an OH group in the appropriate compound by the group A) with a base to form <FORM:0981818/C2/8> and treating this with a suitable anion, such as a methoxide, acetate or halide or (13) by condensing OHC.CH2.Y (wherein Y is defined as in (1)) or an acetal thereof with H2N.X.NR3R4 to form Y.CH2.CH = NH.X.NR3R4 and reacting this with an organo metallic reagent containing R1. If the product is a compound wherein Y is a hydroxy group, then it may be halogenated, and the compound wherein Y is halogen thus produced, or the hydroxy compound, may then be converted into a compound wherein Y is an ester or ether group. Compounds IIA and other halogenated reagents may utilize other displaceable groups besides halogen which groups may be united in a reactive ring such as an epoxide or an imine, or in a multiple bond such as in acetylene. In (2), the diamine reagent may be produced in situ from Z-X-Z, wherein Z is nitro, oximino or hydroxylamino possible intermediates being <FORM:0981818/C2/9> R2 and R3 being introduced, if desired, by reductive alkylation. A large number of other similar starting materials and intermediate are also referred to. Examples are given. Specification 961,317 is referred to.ALSO:Pharmaceutical compositions, useful in the treatment of tuberculosis, contain compounds of the formula <FORM:0981818/A5-A6/1> (wherein R1 is lower alkyl R2 and R3 are hydrogen, lower alkyl or hydroxy lower alkyl R4 is lower alkyl, lower haloalkyl, lower hydroxyalkyl, lower alkoxy lower alkyl, phenyl lower alkoxy lower alkyl, phenoxy lower alkyl optionally substituted by amino, alkoxy, alkylenedioxy or nitro groups, pyridoxy lower alkyl, pyridyl lower alkoxy lower alkyl, benzoyloxy lower alkyl optionally substituted by halogen, amino, alkoxy or alkylenedioxy groups, pyridyl carbonyloxy lower alkyl or lower alkanoyloxy lower alkyl X is an alkylene chain of 2 or 3 carbon atoms and Y is halogen, lower alkoxy, phenyl lower alkoxy, phenoxy optionally substituted by amino, alkoxy, alkylenedioxy or nitro groups, pyridoxy, pyridyl lower alkoxy, lower alkanoyloxy, benzoyloxy optionally substituted by halogen, amino, alkoxy or alkylenedioxy groups, or pyridylcarbonyloxy the word "lower" referring to groups containing at most 6 carbon atoms), or acid-addition salts (including p-aminosalicylates) thereof, and carriers. They may also contain isonicotinic acid hydrazide and p-aminosalicylic acid. Tablets and capsules are referred to. Specification 961,317 is referred to.