Claims
- 1. A method for the prevention, treatment or control of bacterial infections in a warm-blooded animal "in need of such prophylaxis, treatment or control" which comprises administering to said animal a pharmacologically effective amount of a compound of the formula: ##STR27## wherein: X is halogen or trifluoromethanesulfonyloxy, the halogen is selected from bromine, chlorine, fluorine and iodine;
- R is selected from hydrogen; halogen selected from bromine, chlorine, fluorine and iodine; or R=--NR.sup.1 R.sup.2 and R.sup.1 is selected from hydrogen, methyl, ethyl, n-propyl, 1-methylethyl, n-butyl or 1-methylpropyl and R.sup.2 is selected from methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl or 1,1-dimethylethyl with the proviso that when R.sup.1 =hydrogen,
- R.sup.2 =methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl or 1,1-dimethylethyl; and when R.sup.1 =methyl or ethyl,
- R.sup.2 =methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl or 2-methylpropyl;
- and when R.sup.1 =n-propyl,
- R.sup.2 =n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl or 2-methylpropyl;
- and when R.sup.1 =1-methylethyl,
- R.sup.2 =n-butyl, 1-methylpropyl or 2-methylpropyl;
- and when R.sup.1 =n-butyl,
- R.sup.2 =n-butyl, 1-methylpropyl or 2-methylpropyl;
- and when R.sup.1 =1-methylpropyl,
- R.sup.2 =2-methylpropyl;
- R.sup.3 is selected from hydrogen; straight or branched (C.sub.1 -C.sub.8)alkyl group selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, hexyl, heptyl and octyl; .alpha.-mercapto(C.sub.1 -C.sub.4)alkyl group selected from mercaptomethyl, .alpha.-mercaptoethyl, .alpha.-mercapto-1-methylethyl, .alpha.-mercaptopropyl and .alpha.-mercaptobutyl; .alpha.-hydroxy-(C.sub.1 -C.sub.4)alkyl group selected from hydroxymethyl, .alpha.-hydroxyethyl, .alpha.-hydroxy-1-methylethyl, .alpha.-hydroxypropyl and .alpha.-hydroxybutyl; carboxyl (C.sub.1 -C.sub.8)alkyl group; (C.sub.6 -C.sub.10)aryl group selected from phenyl, .alpha.-naphthyl and .beta.-naphthyl; substituted(C.sub.6 -C.sub.10)aryl group with substitution selected from hydroxy, halogen, (C.sub.1 -C.sub.4)alkoxy, trihalo(C.sub.1 -C.sub.3)alkyl, nitro, amino, cyano, (C.sub.1 -C.sub.4)-alkoxycarbonyl, (C.sub.1 -C.sub.3)alkylamino and carboxy; (C.sub.7 -C.sub.9)aralkyl group selected from benzyl, 1-phenylethyl, 2-phenylethyl and phenylpropyl; substituted (C.sub.7 -C.sub.9)aralkyl group with substitution selected from halo, (C.sub.1 -C.sub.4)alkyl, nitro, hydroxy, amino, mono- or di-substituted (C.sub.1 -C.sub.4) alkylamino, (C.sub.1 -C.sub.4)alkoxy, (C.sub.1 -C.sub. 4)alkylsulfonyl, cyano and carboxy; R.sup.4 is selected from hydrogen and (C.sub.1 -C.sub.6)alkyl selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl and hexyl;
- when R.sup.3 does not equal R.sup.4 the stereochemistry of the carbon bearing the W substituent may be either the racemate (DL) or the individual enantiomers (n or D);
- W is selected from amino; hydroxylamino; (C.sub.1 -C.sub.12) straight or branched alkyl monosubstituted amino group with substitution selected from methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, n-pentyl, 2-methylbutyl, 1,1-dimethylpropyl, 2,2-dimethylpropyl, 3-methylbutyl, n-hexyl, 1-methylpentyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3-methylpentyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 1-methyl-1-ethylpropyl, heptyl, octyl, nonyl, decyl, undecyl and dodecyl and the diastereomers and enantiomers of said branched alkyl monosubstituted amino group; (C.sub.3 -C.sub.8)cycloalkyl mono-substituted amino group with substitution selected from cyclopropyl, trans-1,2-dimethylcyclopropyl, cic-1,2-dimethylcyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclo[2.2.1]hept-2-yl, and bicyclo[2.2.2]oct-2-yl and the diastereomers and enantiomers of said (C.sub.3 -C.sub.8)cycloalkyl monosubstituted amino; [(C.sub.4 -C.sub.10)]cycloalkyl]alkyl monosubstituted amino group with substitution selected from (cyclopropyl)methyl, (cyclopropyl)ethyl, (cyclobutyl)methyl, (trans-2-methylcyclopropyl)methyl, and (cis-2-methyl-cyclobutyl)methyl; (C.sub.3 -C.sub.10)alkenyl monosubstituted amino group with substitution selected from allyl, 3-butenyl, 2-butenyl (cis or trans), 2-pentenyl, 4-octenyl, 2,3-dimethyl-2-butenyl, 3-methyl-2-butenyl, 2-cyclopentenyl and 2-cyclohexenyl; (C.sub.6 -C.sub.10)aryl monosubstituted amino group with substitution selected from phenyl and naphthyl; (C.sub.7 -C.sub.10)aralkylamino group selected from benzylamino, 2-phenylethylamino, 1-phenylethylamino, 2-(naphthyl)methylamino, 1-(naphthyl)methylamino and phenylpropylamino; substituted (C.sub. 6 -C.sub.10)aryl monosubstituted amino group with substitution for the (C.sub.6 -C.sub.10)aryl group selected from (C.sub.1 -C.sub.5)acyl, (C.sub.1 -C.sub.5) acylamino, (C.sub.1 -C.sub.4)alkyl, mono or disubstituted (C.sub.1 -C.sub.8)alkylamino, (C.sub.1 -C.sub.4) alkoxy, (C.sub.1 -C.sub.4)alkoxycarbonyl, (C.sub.1 -C.sub.4)alkylsulfonyl, amino, carboxy, cyano, halogen, hydroxy, nitro and trihalo(C.sub.1 -C.sub.3)alkyl; straight or branched symmetrical disubstituted (C.sub.2 -C.sub.14) alkylamino group with substitution selected from dimethyl, diethyl, diisopropyl, di-n-propyl, dibutyl and diisobutyl; symmetrical disubstituted (C.sub.3 -C.sub.14)cycloalkylamino group with substitution selected from dicyclopropyl, dicyclobutyl, dicyclopentyl, dicylohexyl and dicycloheptyl; straight or branched unsymmetrical disubstituted (C.sub.3 -C.sub.14)alkylamino group wherein the total number of carbons in the substitution is not more than 14; unsymmetrical disubstituted (C.sub.4 -C.sub.14)cycloalkylamino group wherein the total number of carbons in the substitution is not more than 14; (C.sub.2 -C.sub.8)azacyclo- alkyl and substituted (C.sub.2 -C.sub.8)azacycloalkyl group selected from aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, 4-methylpiperidinyl, 2-methylpyrrolidinyl, cis-3,4-dimethylpyrrolidinyl, trans-3,4-dimethylpyrrolidinyl, 2-azabicyclo[2.1.1]-hex-2-yl, 5-azabicyclo[2.1.1]hex-5-yl, 2-azabicyclo[2.2.1]hept-2-yl, 7-azabicyclo[2.2.1]hept-7-yl, 2-azabicyclo[2.2.2]oct-2-yl and the diastereomers and enantiomers of said (C.sub.2 -C.sub.8)azacycloalkyl and substituted (C.sub.2 -C.sub.8)azacycloalkyl group; 1-azaoxacycloalkyl selected from morpholinyl and 1-aza-5-oxocycloheptane; substituted 1-azaoxacycloalkyl group selected from 2-(C.sub.1 -C.sub.3)alkylmorpholinyl, 3-(C.sub.1 -C.sub.3)alkylisoxazolidinyl, tetrahydrooxazinyl and 3,4-dihydrooxazinyl; [1,n]-diazacycloalkyl and substituted [1,n]-diazacycloalkyl group selected from piperazinyl, 2-(C.sub.1 -C.sub.3)alkylpiperazinyl, 4-(C.sub.1 -C.sub.3)alkylpiperazinyl, 2,4-dimethylpiperazinyl, 4-(C.sub.1 -C.sub.4) alkoxypiperazinyl, 4-(C.sub.6 -C.sub.10)aryloxypiperazinyl, 4-hydroxypiperazinyl, 2,5-diazabicyclo[ 2.2.1]hept-2-yl, 2,5-diaza-5- methylbicyclo-[2.2.1]hept-2-yl, 2,3-diaza-3-methylbicyclo[2.2.2]oct-2-yl, 2,5-diaza-5,7-dimethylbicyclo[2.2.2]oct-2-yl and the diastereomers or enantiomers of said [1,n]-diazacycloalkyl and substituted [1,n]-diazacycloalkyl group;
- 1-azathiacycloalkyl and substituted 1-azathiacycloalkyl group selected from thiomorpholinyl, 2-(C.sub.1 -C.sub.3)-alkylthiomorpholinyl and 3-(C.sub.3 -C.sub.6)cycloalkylthiomorpholinyl; N-azolyl and substituted N-azolyl group selected from 1-imidazolyl, 2-(C.sub.1 -C.sub.3)alkyl-1-imidazolyl, 3-(C.sub.1 -C.sub.3)alkyl-1-imidazolyl, 1-pyrazolyl, 2-(C.sub.1 -C.sub.3) alkyl-1-pyrrolyl, 3-(C.sub.1 -C.sub.3)alkyl-1-pyrazolyl, indolyl, 1-(1,2,3-triazolyl), 4-(C.sub.1 -C.sub.3)alkyl-1-(1,2,3-triazolyl), 5-(C.sub.1 -C.sub.3)alkyl-1-(1,2,3-triazolyl), 4-(1,2,4-triazolyl), 1-tetrazolyl, 2-tetrazolyl and benzimidazolyl; (heterocycle)amino group selected from 2- or 3-furanylamino, 2- or 3-thienylamino, 2-, 3- or 4-pyridylamino, 2- or 5-pyridazinylamino, 2-pyrazinylamino, 2-(imidazolyl)amino, (benzimidazolyl)amino, and (benzothiazolyl)amino and substituted (heterocycle)amino group as defined above with substitution selected from straight or branched (C.sub.1 -C.sub.6)alkyl; (heterocycle) methylamino group selected from 2- or 3-furylmethylamino, 2- or 3-thienylmethylamino, 2-, 3- or 4-pyridylmethylamino, 2- or 5-pyridazinylmethylamino, 2-pyrazinylmethylamino, 2-(imidazolyl) methylamino, (benzimidazolyl)methylamino, and (benzothiazolyl) methylamino and substituted (heterocycle)-methylamino as defined above with substitution selected from straight or branched (C.sub.1 -C.sub.6)alkyl; carboxy (C.sub.2 -C.sub.4) alkylamino group selected from aminoacetic acid, .alpha.-aminopropionic acid, .beta.-aminopropionic acid, .alpha.-butyric acid, and .beta.-aminobutyric acid and the enantiomers of said carboxy-(C.sub.2 -C.sub.4) alkylamino group; (C.sub.1 -C.sub.4)alkoxycarbonylamino group selected from methoxycarbonylamino, ethoxycarbonylamino, allyloxycarbonylamino, propoxycarbonylamino, isoproproxycarbonylamino, 1,1-dimethylethoxycarbonylamino, n-butoxycarbonylamino, and 2-methylpropoxycarbonylamino; (C.sub.1 -C.sub.4)alkoxyamino group selected from methoxyamino, ethoxyamino, n-propoxyamino, 1-methylethoxyamino, n -butoxyamino, 2-methylpropoxyamino, and 1,1-dimethylethoxyamino; (C.sub.3 -C.sub.8) cycloalkoxyamino group selected from cyclopropoxyamino, trans-1,2-dimethylcyclopropoxyamino, cis-1,2-dimethyl cyclopropoxyamino, cyclobutoxyamino, cyclopentoxyamino, cyclohexoxyamino, cycloheptoxyamino, cyclooctoxyamino, bicyclo[2.2.1]hept-2-yloxyamino, bicyclo-[2.2.2]oct-2-yloxyamino and the diastereomers and enantiomers of said (C.sub.3 -C.sub.8)cycloalkoxyamino group; (C.sub.6 -C.sub.10) aryloxyamino group selected from phenoxyamino, 1-naphthyloxyamino and 2-naphthyloxyamino; (C.sub.7 -C.sub.11) arylalkoxyamino group selected from benzyloxyamino, 2-phenylethoxyamino, 1-phenylethoxyamino, 2-(naphthyl) methoxyamino, 1-(naphthyl) methoxyamino and phenylpropoxyamino;
- R.sup.5 is selected from hydrogen; straight or branched (C.sub.1 -C.sub.3)alkyl group selected from methyl, ethyl, n-propyl or 1-methylethyl; (C.sub.6 -C.sub.10)aryl group selected from phenyl, .alpha.-naphthyl or .beta.-naphthyl; (C.sub.7 -C.sub.9 ) aralkyl group selected from benzyl, 1-phenylethyl, 2-phenylethyl or phenylpropyl; a heterocycle group selected from a five membered aromatic or saturated ring with one N, O, S or Se heteroatom optionally having a benzo or pyrido ring fused thereto selected from pyrrolyl, N-methylindolyl, indolyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 2-pyrrolinyl, tetrahydrofuranyl, furanyl, benzofuranyl, tetrahydrothienyl, thienyl benzothienyl or selenazolyl, or a five membered aromatic ring with two N, O, S or Se heteroatoms optionally having a benzo or pyrido ring fused thereto selected from imidazolyl, pyrazolyl, benzimidazolyl, oxazolyl, benzoxazolyl, indazolyl, thiazolyl, benzothiazolyl, 3-alkyl-3H-imidazo[4,5-b]pyridyl or pyridylimidazolyl, or a five membered saturated ring with one or two N, O, S or Se heteroatoms and an adjacent appended O heteroatom selected from .gamma.-butyrolactam, .gamma.-butyrolactone, imidazolidinone or N-aminoimidazolidinone, or a six membered aromatic ring with one to three N heteroatoms selected from pyridyl, pyridazinyl, pyrazinyl, sym-triazinyl, unsymtriazinyl, pyrimidinyl or (C.sub.1 -C.sub.3) alkylthio-pyridazinyl, or a six membered saturated ring with one or two N, O, S or Se heteroatoms and an adjacent appended O heteroatom selected from 2,3-dioxo-1-dioxo1-piperazinyl, 4-ethyl-2,3-dioxo-1-piperazinyl, 4-methyl-2,3,-dioxo-1-piperazinyl, 4-cyclopropyl-2-dioxo-1-piperazinyl, 2-dioxomorpholinyl, 2-dioxothiomorpholinyl; or --(CH.sub.2).sub.n COOR.sup.7 where n=0-4 and R.sup.7 is selected from hydrogen; straight or branched (C.sub.1 -C.sub.3)alkyl group selected from methyl, ethyl, n-propyl or 1-methylethyl; or (C.sub.6 -C.sub.10)aryl group selected from phenyl, .alpha.-naphthyl, or .beta.-naphthyl;
- R.sup.6 is selected from hydrogen; straight or branched (C.sub.1 -C.sub.3)alkyl group selected from methyl, ethyl, n-propyl or 1-methylethyl; (C.sub.6 -C.sub.10)aryl group selected from phenyl, .alpha.-naphthyl or .beta.-naphthyl; (C.sub.7 -C.sub.9)aralkyl group selected from benzyl, 1-phenylethyl, 2-phenylethyl or phenylpropyl; a heterocycle group selected from a five membered aromatic or saturated ring with one N, O, S or Se heteroatom optionally having a benzo or pyrido ring fused thereto selected from pyrrolyl, N-methylindolyl, indolyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 2-pyrrolinyl, tetrahydrofuranyl, furanyl, benzofuranyl, tetrahydrothienyl, thienyl, benzothienyl or selenazolyl, or a five membered aromatic ring with two N, O, S or Se heteroatoms optionally having a benzo or pyrido ring fused thereto selected from imidazolyl, pyrazolyl, benzimidazolyl, oxazolyl, benzoxazolyl, indazolyl, thiazolyl, benzothiazoly, 3-alkyl-3H-imidazo[4,5-b]pyridyl or pyridylimidazolyl, or a five membered saturated ring with one or two N, O, S or Se heteroatoms and an adjacent appended O heteroatom selected from .gamma.-butyrolactam, .gamma.-butyrolactone, imidazolidinone or N-aminoimidazolidinone, or a six membered aromatic ring with one to three N heteroatoms selected from pyridyl, pyridazinyl, pyrazinyl, symtriazinyl, unsymtriazinyl, pyrimidinyl or (C.sub.1 -C.sub.3)alkylthiopyridazinyl, or a six membered saturated ring with one or two N, O, S or Se heteroatoms and an adjacent appended O heteroatom such as 2,3-dioxo-1-piperazinyl, 4-ethyl-2,3-dioxo-1-piperazinyl, 4-methyl-2,3-dioxo-1-piperazinyl, 4-cyclopropyl-2-dioxo-1-piperazinyl, 2-dioxomorpholinyl, 2-dioxothiomorpholinyl; or --(CH.sub.2).sub.n COOR.sup.7 where n=0-4 and R.sup.7 is selected from hydrogen; straight or branched (C.sub.1 -C.sub.3)alkyl selected from methyl, ethyl, n-propyl or 1-methylethyl; or (C.sub.6 -C.sub.10)aryl selected from phenyl, .alpha.-naphthyl or .beta.-naphthyl; with the proviso that R.sup.5 and R.sup.6 cannot both be hydrogen; or R.sup.5 and R.sup.6 taken together are --(CH.sub.2).sub.2 B(CH.sub.2).sub.2 --, wherein B is selected from (CH.sub.2).sub.m and m=0-1 --NH, --N(C.sub.1 -C.sub.3)alkyl, straight or branched, --N(C.sub.1 -C.sub.4)alkoxy, oxygen, sulfur or substituted congeners selected from (L or D) proline, ethyl(L or D)prolinate, morpholine, pyrrolidine or piperidine; and the pharmacologically acceptable organic and inorganic salts or metal complexes.
- 2. A method for the prevention, treatment or control of bacterial infections in a warm-blooded animal "in need of such prophylaxis, treatment or control" caused by bacteria having the TetM or TetK resistant determinant which comprises administering to said animal a pharmacologically evvective amount of a compound of the formula: ##STR28## wherein: X is halogen or trifluoromethanesulfonyloxy, the halogen is selected from bromine, chlorine, fluorine and iodine;
- R is selected from hydrogen; halogen selected from bromine, chlorine, fluorine and iodine;
- or R=--NR.sup.1 R.sup.2 and R.sup.1 is selected from hydrogen, methyl, ethyl, n-propyl, 1-methylethyl, n-butyl or 1-methylpropyl and R.sup.2 is selected from methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl or 1,1-dimethylethyl with the proviso that when R.sup.1 =hydrogen,
- R.sup.2 =methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl or 1,1-dimethylethyl;
- and when R.sup.1 =methyl or ethyl,
- R.sup.2 =methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl or 2-methylpropyl;
- and when R.sup.1 =n-propyl,
- R.sup.2 =n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl or 2-methylpropyl;
- and when R.sup.1 =1-methylethyl,
- R.sup.2 =n-butyl, 1-methylpropyl or 2-methylpropyl;
- and when R.sup.1 =n-butyl,
- R.sup.2 =n-butyl, 1-methylpropyl or 2-methylpropyl;
- and when R.sup.1 =1-methylpropyl,
- R.sup.2 =2-methylpropyl;
- R.sup.3 is selected from hydrogen; straight or branched (C.sub.1 -C.sub.8)alkyl group selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, hexyl, heptyl and octyl; .alpha.-mercapto(C.sub.1 -C.sub.4)alkyl group selected from mercaptomethyl, .alpha.-mercaptoethyl, .alpha.-mercapto-1-methylethyl, .alpha.-mercaptopropyl and .alpha.-mercaptobutyl; .alpha.-hydroxy-(C.sub.1 -C.sub.4)alkyl group selected from hydroxymethyl, .alpha.-hydroxyethyl, .alpha.-hydroxy-1-methylethyl, .alpha.-hydroxypropyl and .alpha.-hydroxybutyl; carboxyl (C.sub.1 -C.sub.8)alkyl group; (C.sub.6 -C.sub.10)aryl group selected from phenyl, .alpha.-naphthyl and .beta.-naphthyl; substituted(C.sub.6 -C.sub.10)aryl group with substitution selected from hydroxy, halogen, (C.sub.1 -C.sub.4)alkoxy, trihalo(C.sub.1 -C.sub.3)alkyl, nitro, amino, cyano, (C.sub.1 -C.sub.4)alkoxycarbonyl, (C.sub.1 -C.sub.3)alkylamino and carboxy; (C.sub.7 -C.sub.9)aralkyl group selected from benzyl, 1-phenylethyl, 2-phenylethyl and phenylpropyl; substituted (C.sub.7 -C.sub.9)aralkyl group with substitution selected from halo, (C.sub.1 C.sub.4)alkyl, nitro, hydroxy, amino, mono- or di-substituted (C.sub.1 -C.sub.4) alkylamino, (C.sub.1 -C.sub.4)alkoxy, (C.sub.1 -C.sub.4)alkylsulfonyl, cyano and carboxy;
- R.sup.4 is selected from hydrogen and (C.sub.1 -C.sub.6)alkyl selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl and hexyl;
- when R.sup.3 does not equal R.sup.4 the stereochemistry of the carbon bearing the W substituent may be either the racemate (DL) or the individual enantiomers (L or D);
- W is selected from amino; hydroxylamino; (C.sub.1 -C.sub.12) straight or branched alkyl monosubstituted amino group with substitution selected from methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, n-pentyl, 2-methylbutyl, 1,1-dimethylpropyl, 2,2-dimethylpropyl, 3-methylbutyl, n-hexyl, 1-methylpentyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3-methylpentyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 1-methyl-1-ethylpropyl, heptyl, octyl, nonyl, decyl, undecyl and dodecyl and the diastereomers and enantiomers of said branched alkyl monosubstituted amino group; (C.sub.3 --C.sub.8)cycloalkyl mono-substituted amino group with substitution selected from cyclopropyl, trans-1,2-dimethylcyclopropyl, cic-1,2-dimethylcyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclo[2.2.1]hept-2-yl, and bicyclo[2.2.2]oct-2-yl and the diastereomers and enantiomers of said (C.sub.3 -C.sub.8)cycloalkyl monosubstituted amino; [(C.sub.4 -C.sub.10)]cycloalkyl]alkyl monosubstituted amino group with substitution selected from (cyclopropyl)methyl, (cyclopropyl)ethyl, (cyclobutyl)methyl, (trans-2-methylcyclopropyl)methyl, and (cis-2-methyl-cyclobutyl)methyl; (C.sub.3 -C.sub.10)alkenyl monosubstituted amino group with substitution selected from allyl, 3-butenyl, 2-butenyl (cis or trans), 2-pentenyl, 4-octenyl, 2,3-dimethyl-2-butenyl, 3-methyl-2-butenyl, 2-cyclopentenyl and 2-cyclohexenyl; (C.sub.6 -C.sub.10)aryl monosubstituted amino group with substitution selected from phenyl and naphthyl; (C.sub.7 -C.sub.10)aralkylamino group selected from benzylamino, 2-phenylethylamino, 1-phenylethylamino, 2-(naphthyl)methylamino, 1-(naphthyl)methylamino and phenylpropylamino; substituted (C.sub.6 -C.sub.10)aryl monosubstitutedamino group with substitution for the (C.sub.6 -C.sub.10) aryl group selected from (C.sub.1 -C.sub.5) acyl, (C.sub.1 -C.sub.5) acylamino, (C.sub.1 -C.sub.4) alkyl, mono or disubstituted (C.sub.1 -C.sub.8) alkylamino, (C.sub.1 -C.sub.4) alkoxy, (C.sub.1 -C.sub.4 ) alkoxycarbonyl, (C.sub.1 -C.sub.4 ) alkylsulfonyl, amino, carboxy, cyano, halogen, hydroxy, nitro and trihalo(C.sub.1 -C.sub.3)alkyl; straight or branched symmetrical disubstituted (C.sub.2 -C.sub.14) alkylamino group with substitution selected from dimethyl, diethyl, diisopropyl, di-n-propyl, dibutyl and diisobutyl; symmetrical disubstituted (C.sub.3 -C.sub.14)cycloalkylamino group with substitution selected from dicyclopropyl, dicyclobutyl, dicyclopentyl, dicylohexyl and dicycloheptyl; straight or branched unsymmetrical disubstituted (C.sub.3 -C.sub.14)alkylamino group wherein the total number of carbons in the substitution is not more than 14; unsymmetrical disubstituted (C.sub.4 -C.sub.14)cycloalkylamino group wherein the total number of carbons in the substitution is not more than 14; (C.sub.2 -C.sub.8)azacyclo- alkyl and substituted (C.sub.2 -C.sub.8)azacycloalkyl group selected from aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, 4-methylpiperidinyl, 2-methylpyrrolidinyl, cis-3,4-dimethylpyrrolidinyl, trans-3,4-dimethylpyrrolidinyl, 2-azabicyclo[2.1.1]-hex-2-yl, 5-azabicyclo[2.1.1]hex-5-yl, 2-azabicyclo[2.2.1]hept-2-yl, 7-azabicyclo[2.2.1]hept-7-yl, 2-azabicyclo[2.2.2]oct-2-yl and the diastereomers and enantiomers of said (C.sub.2 -C.sub.8)azacycloalkyl and substituted (C.sub.2 -C.sub.8)azacycloalkyl group; 1-azaoxacycloalkyl selected from morpholinyl and 1-aza-5-oxocycloheptane; substituted 1-azaoxacycloalkyl group selected from 2-(C.sub.1 -C.sub.3)alkylmorpholinyl, 3-(C.sub.1 -C.sub.3)alkylisoxazolidinyl, tetrahydrooxazinyl and 3,4-dihydrooxazinyl; [1,n]-diazacycloalkyl and substituted [1,n]-diazacycloalkyl group selected from piperazinyl, 2-(C.sub.1 -C.sub.3)alkylpiperazinyl, 4-(C.sub.1 -C.sub.3 ) alkylpiperazinyl, 2,4-dimethylpiperazinyl, 4-(C.sub.1 -C.sub.4) alkoxypiperazinyl, 4-(C.sub.6 -C.sub.10)aryloxypiperazinyl, 4-hydroxypiperazinyl, 2,5-diazabicyclo[2.2.1]hept-2-yl, 2,5-diaza-5- methylbicyclo-[2.2.1]hept-2-yl, 2,3-diaza-3-methylbicyclo[2.2.2]oct-2-yl, 2,5-diaza-5,7-dimethylbicyclo[2.2.2]oct-2-yl and the diastereomers or enantiomers of said [1,n]-diazacycloalkyl and substituted [1,n]-diazacycloalkyl group; 1-azathiacycloalkyl and substituted 1-azathiacycloalkyl group selected from thiomorpholinyl, 2-(C.sub.1 -C.sub.3)-alkylthiomorpholinyl and 3-(C.sub.3 -C.sub.6)cycloalkylthiomorpholinyl; N-azolyl and substituted N-azolyl group selected from 1-imidazolyl, 2-(C.sub.1 -C.sub.3)alkyl-1-imidazolyl, 3-(C.sub.1 -C.sub.3)alkyl-1-imidazolyl, 1-pyrazolyl, 2-(C.sub.1 -C.sub.3) alkyl-1-pyrrolyl, 3-(C.sub.1 -C.sub.3)alkyl-1-pyrazolyl, indolyl, 1-(1,2,3-triazolyl), 4-(C.sub.1 -C.sub.3)alkyl-1-(1,2,3-triazolyl), 5-(C.sub.1 -C.sub.3)alkyl-1-(1,2,3-triazolyl), 4-(1,2,4-triazolyl), 1-tetrazolyl, 2-tetrazolyl and benzimidazolyl; (heterocycle)amino group selected from 2- or 3-furanylamino, 2- or 3-thienylamino, 2-, 3- or 4-pyridylamino, 2- or 5-pyridazinylamino, 2-pyrazinylamino, 2-(imidazolyl)amino, (benzimidazolyl)amino, and (benzothiazolyl)amino and substituted (heterocycle) amino group as defined above with substitution selected from straight or branched (C.sub.1 -C.sub.6)alkyl; (heterocycle) methylamino group selected from 2- or 3-furylmethylamino, 2- or 3-thienylmethylamino, 2-, 3- or 4-pyridylmethylamino, 2- or 5-pyridazinylmethylamino, 2-pyrazinylmethylamino, 2-(imidazolyl) methylamino, (benzimidazolyl)methylamino, and (benzothiazolyl) methylamino and substituted (heterocycle)-methylamino as defined above with substitution selected from straight or branched (C.sub.1 -C.sub.6)alkyl; carboxy(C.sub.2 -C.sub.4)alkylamino group selected from aminoacetic acid, .alpha.-aminopropionic acid, .beta.-aminopropionic acid, .alpha.-butyric acid, and .beta.-aminobutyric acid and the enantiomers of said carboxy-(C.sub.2 -C.sub.4) alkylamino group; (C.sub.1 -C.sub.4)alkoxycarbonylamino group selected from methoxycarbonylamino, ethoxycarbonylamino, allyloxycarbonylamino, propoxycarbonylamino, isoproproxycarbonylamino, 1,1-dimethylethoxycarbonylamino, n-butoxycarbonylamino, and 2-methylpropoxycarbonylamino; (C.sub.1 -C.sub.4)alkoxyamino group selected from methoxyamino, ethoxyamino, n-propoxyamino, 1-methylethoxyamino, n-butoxyamino, 2-methylpropoxyamino, and 1,1-dimethylethoxyamino; (C.sub.3 -C.sub.8)cycloalkoxyamino group selected from cyclopropoxyamino, trans-1,2-dimethylcyclopropoxyamino,cis-1,2-dimethylcyclopropoxyamino, cyclobutoxyamino, cyclopentoxyamino, cyclohexoxyamino, cycloheptoxyamino, cyclocctoxyamino, bicyclo[2.2.1]hept-2-yloxyamino, bicyclo-[2.2.2]oct-2-yloxyamino and the diastereomers and enantiomers of said (C.sub.3 -C.sub.8)cycloalkoxyamino group; (C.sub.6 -C.sub.10) aryloxyamino group selected from phenoxyamino, 1-naphthyloxyamino and 2-naphthyloxyamino; (C.sub.7 - C.sub.11)arylalkoxyamino group selected from benzyloxyamino, 2-phenylethoxyamino, 1-phenylethoxyamino, 2-(naphthyl) methoxyamino, 1-(naphthyl)methoxyamino and phenylpropoxyamino;
- R.sup.5 is selected from hydrogen; straight or branched (C.sub.1 -C.sub.3)alkyl group selected from methyl, ethyl, n-propyl or 1-methylethyl; (C.sub.6 -C.sub.10)aryl group selected from phenyl, .alpha.-naphthyl or .beta.-naphthyl; (C.sub.7 -C.sub.9)aralkyl group selected from benzyl, 1-phenylethyl, 2-phenylethyl or phenylpropyl; a heterocycle group selected from a five membered aromatic or saturated ring with one N, O, S or Se heteroatom optionally having a benzo or pyrido ring fused thereto selected from pyrrolyl, N-methylindolyl, indolyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 2-pyrrolinyl, tetrahydrofuranyl, furanyl, benzofuranyl, tetrahydrothienyl, thienyl benzothienyl or selenazolyl, or a five membered aromatic ring with two N, O, S or Se heteroatoms optionally having a benzo or pyrido ring fused thereto selected from imidazolyl, pyrazolyl, benzimidazolyl, oxazolyl, benzoxazolyl, indazolyl, thiazolyl, benzothiazolyl, 3-alkyl-3H-imidazo[4,5-b]pyridyl or pyridylimidazolyl, or a five membered saturated ring with one or two N, O, S or Se heteroatoms and an adjacent appended O heteroatom selected from .gamma.-butyrolactam, .gamma.-butyrolactone, imidazolidinone or N-aminoimidazolidinone, or a six membered aromatic ring with one to three N heteroatoms selected from pyridyl, pyridazinyl, pyrazinyl, sym-triazinyl, unsymtriazinyl, pyrimidinyl or (C.sub.1 -C.sub.3) alkylthio-pyridazinyl, or a six membered saturated ring with one or two N, O, S or Se heteroatoms and an adjacent appended O heteroatom selected from 2,3-dioxo-1-piperazinyl, 4-ethyl-2,3-dioxo-1-piperazinyl, 4-methyl-2,3-dioxo-1-piperazinyl, 4-cyclopropyl-2-dioxo-1-piperazinyl, 2-dioxomorpholinyl, 2-dioxothiomorpholinyl; or --(CH.sub.2).sub.n COOR.sup.7 where n=0-4 and R.sup.7 is selected from hydrogen; straight or branched (C.sub.1 -C.sub.3)alkyl group selected from methyl, ethyl, n-propyl or 1-methylethyl; or (C.sub.6 -C.sub.10)aryl group selected from phenyl, .alpha.-naphthyl, or .beta.-naphthyl;
- R.sup.6 is selected from hydrogen; straight or branched (C.sub.1 -C.sub.3)alkyl group selected from methyl, ethyl, n-propyl or 1-methylethyl; (C.sub.6 -C.sub.10)aryl group selected from phenyl, .alpha.-naphthyl or .beta.-naphthyl; (C.sub.7 -C.sub.9)aralkyl group selected from benzyl, 1-phenylethyl, 2-phenylethyl or phenylpropyl; a heterocycle group selected from a five membered aromatic or saturated ring with one N, O, S or Se heteroatom optionally having a benzo or pyrido ring fused thereto selected from pyrrolyl, N-methylindolyl, indolyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 2-pyrrolinyl, tetrahydrofuranyl, furanyl, benzofuranyl, tetrahydrothienyl, thienyl, benzothienyl or selenazolyl, or a five membered aromatic ring with two N, O, S or Se heteroatoms optionally having a benzo or pyrido ring fused thereto selected from imidazolyl, pyrazolyl, benzimidazolyl, oxazolyl, benzoxazolyl, indazolyl, thiazolyl, benzothiazoly, 3-alkyl-3H-imidazo[4,5-b]pyridyl or pyridylimidazolyl, or a five membered saturated ring with one or two N, O, S or Se heteroatoms and an adjacent appended O heteroatom selected from .gamma.-butyrolactam, .gamma.-butyrolactone, imidazolidinone or N-aminoimidazolidinone, or a six membered aromatic ring with one to three N heteroatoms selected from pyridyl, pyridazinyl, pyrazinyl, symtriazinyl, unsymtriazinyl, pyrimidinyl or (C.sub.1 -C.sub.3)alkylthiopyridazinyl, or a six membered saturated ring with one or two N, O, S or Se heteroatoms and an adjacent appended O heteroatom such as 2,3-dioxo-1-piperazinyl, 4-ethyl-2,3-dioxo-1-piperazinyl, 4-methyl-2,3-dioxo-1-piperazinyl, 4-cyclopropyl-2-dioxo-1-piperazinyl, 2-dioxomorpholinyl, 2-dioxothiomorpholinyl; or --(CH.sub.2).sub.n COOR.sup.7 where n=0-4 and R.sup.7 is selected from hydrogen; straight or branched (C.sub.1 -C.sub.3)alkyl selected from methyl, ethyl, n-propyl or 1-methylethyl; or (C.sub.6 -C.sub.10)aryl selected from phenyl, .alpha.-naphthyl or .beta.-naphthyl; with the proviso that R.sup.5 and R.sup.6 cannot both be hydrogen; or R.sup.5 and R.sup.6 taken together are --(CH.sub.2).sub.2 B(CH.sub.2).sub.2 --, wherein B is selected from (CH.sub.2).sub.m and m=0-1, --NH, --N (C.sub.1 -C.sub.3)alkyl, straight or branched, --N(C.sub.1 -C.sub.4)alkoxy, oxygen, sulfur or substituted congeners selected from (L or D) proline, ethyl(L or D)prolinate, morpholine, pyrrolidine or piperidine; and the pharmacologically acceptable organic and inorganic salts or metal complexes.
Parent Case Info
This is a divisional of application Ser. No. 08/193,828 filed on Feb. 8, 1994, now U.S. Pat. No. 5,386,041, which in turn is a divisional of application Ser. No. 07/928,578 filed on Aug. 13, 1992, now U.S. Pat. No. 5,420,272.
US Referenced Citations (4)
Divisions (2)
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Number |
Date |
Country |
Parent |
193828 |
Feb 1994 |
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Parent |
928578 |
Aug 1992 |
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