7-(substituted)-8-(substituted)-9-(substitued amino)-6-demethyl-6-deoxytetracyclines

A compound of the formula:

• ##STR225## wherein Y is selected from --N.sub.2.sup.+ Cl.sup.- or N.sub.3 ;
• X is selected from halogen or trifluoromethanesulfonyloxy;
• the halogen is selected from bromine, chlorine, fluorine or iodine;
• R or R.sup.1 is selected from nitro;
• amino;
• halogen selected from chlorine, bromine, fluorine, or iodine;
• cyano;
• hydroxy;
• or --NR.sup.2 R.sup.3 ;
• R.sup.2 is selected from hydrogen, methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, and 1-methylpropyl;
• R.sup.3 is selected from methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, R.sup.4 (CH.sub.2).sub.n CO-- or R.sup.4' (CH.sub.2).sub.n SO.sub.2 --;
• where n=0-4;
• with the proviso that when R or R.sup.1 =--NR.sup.2 R.sup.3 and R.sup.2 =hydrogen,
• R.sup.3 =methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, R.sup.4 (CH.sub.2).sub.n CO-- or R.sup.4' (CH.sub.2).sub.n SO.sub.2 --;
• and when R.sup.2 =methyl or ethyl,
• R.sup.3 =methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, or 2-methylpropyl;
• and when R.sup.2 =n-propyl,
• R.sup.3 =n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, or 2-methylpropy;
• and when R.sup.2 =1-methylethyl,
• R.sup.3 =n-butyl, 1-methylpropyl, or 2-methylpropy;
• and when R.sup.2 =n-butyl,
• R.sup.3 =n-butyl, 1-methylpropyl, or 2-methylpropy;
• and when R.sup.2 =1-methylpropyl,
• R.sup.3 =2-methylpropyl;
• and when R.sup.3 is selected from R.sup.4 (CH.sub.2).sub.n CO-- and n=0,
• R.sup.4 is selected from hydrogen;
• amino;
• hydroyamino;
• straight or branched mono(C.sub.1 -C.sub.6)alkylamino group where (C.sub.1 -C.sub.6)alkyl is 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 and the diastereomers and enantiomers of said straight or branched mono(C.sub.1 -C.sub.6)alkylamino group;
• (C.sub.3 -C.sub.8)cycloalkylamino group where (C.sub.3 -C.sub.8)cycloalkyl is selected from cyclopropyl, trans-1,2-dimethylcyclopropyl, cis-1,2-dimethylcyclopropyl, trans-2,3-dimethylcyclopropyl, cis-2,3-dimethylcyclopropyl, cyclobutyl, trans-2,3-dimethylcyclobutyl, cis-2,3-dimethylcyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclo›2.2.1!hept-2-yl, bicyclo›2.2.2!oct-2-yl and the diastereomers and enantiomers of said (C.sub.3 -C.sub.8)cycloalkylamino group;
• straight or branched chain di-(C.sub.1 -C.sub.6)alkylamino group selected from dimethylamino, diethylamino, methyl(ethyl)amino, ethyl(1-methylethyl)amino or where each (C.sub.1 -C.sub.6)alkyl is independently 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-ethylpropyl and the diastereomers and enantiomers of said straight or branched chain di-(C.sub.1 -C.sub.6)alkylamino group;
• (C.sub.1 -C.sub.6)alkoxyamino group where (C.sub.1 -C.sub.6)alkoxy is selected from methoxy, ethoxy, propoxy, butoxy, pentoxy, or hexoxy;
• (C.sub.3 -C.sub.8)cycloalkoxyamino group where (C.sub.3 -C.sub.8)alkoxy is selected from cyclopropoxy, trans-1,2-dimethylcyclopropoxy, cis-1,2-dimethylcyclopropoxy, trans-2,3-dimethylcyclopropoxy, cis-2,3-dimethylcyclopropoxy, cyclobutoxy, trans-2,3-dimethylcyclobutoxy, cis-2,3-dimethylcyclobutoxy, cyclopentoxy, cyclohexoxy, cycloheptoxy, cyclooctoxy, bicyclo›2.2.1!hept-2-yloxy, bicyclo›2.2.1!oct-2-yloxy and the diastereomers and enantiomers of said (C.sub.3 -C.sub.8)cycloalkyloxyamino group;
• (C.sub.7 -C.sub.10 l)aralkoxyamino group where (C.sub.7 -C.sub.10) is selected from benzyloxy, 2-phenylethoxy, .alpha.-phenylethoxy, (2-naphthyl)methoxy, (1-naphthyl)methoxy, or phenylpropoxy;
• (C.sub.2 -C.sub.8)azacycloalkyl group selected from aziridinyl, azetidinyl, pyrrolidinyl, pyrrolinyl, piperidinyl, 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-2-yl, 2-azabicyclo›2.2.2!oct-2-yl and the diastereomers and enantiomers of said (C.sub.2 -C.sub.8)azacycloalkyl group;
• azaheterocycloalkyl group selected from morpholinyl, piperazinyl, 4-methylpiperazinyl, 4-hydroxypiperazinyl, 4-(C.sub.1 -C.sub.4)alkoxy-piperazinyl, thiamorphinyl, tetrahydro-1,2-oxazinyl, isoxazolidinyl, pyrazolidinyl, 2-methylpyrazolidinyl, 2,5-diazabicyclo›2.2.2!hept-2-yl, 2,5-diaza-5-methylbicyclo›2.2.1!hept-2-yl, and diastereomers and enantiomers of said azaheterocycloalkyl group;
• (C.sub.6 -C.sub.10)arylamino group selected from phenylamino or naphthylamino;
• (C.sub.7 -C.sub.10)aralkylamino group where (C.sub.7 -C.sub.10)aralkyl is selected from benzyl, 2-phenylethyl, .alpha.-phenylethyl, (2-naphthyl)methyl, (1-naphthyl)methyl, or phenylpropyl;
• straight or branched (C.sub.1 -C.sub.4)alkyl group selected from methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl, or 1,1-dimethylethyl;
• (C.sub.3 -C.sub.6)cycloalkyl group selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl;
• substituted (C.sub.3 -C.sub.6)cycloalkyl group where the substitution is selected from (C.sub.1 -C.sub.3)alkyl, cyano, amino or (C.sub.1 -C.sub.3)acyl;
• (C.sub.6 -C.sub.10)aryl group selected from phenyl, .alpha.-naphthyl or .beta.-naphthyl;
• substituted (C.sub.6 -C.sub.10)aryl group where the substitution is selected from halo, (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 or carboxy;
• (C.sub.7 -C.sub.9)aralkyl group selected from benzyl, 1-phenylethyl, 2-phenylethyl, or phenylpropyl;
• .alpha.-hydroxy-(C.sub.1 -C.sub.3)alkyl group selected from hydroxymethyl, .alpha.-hydroxyethyl, .alpha.-hydroxy-1-methylethyl, or .alpha.-hydroxypropyl;
• .alpha.-mercapto(C.sub.1 -C.sub.3)alkyl group selected from mercaptomethyl, .alpha.-mercaptoethyl, .alpha.-mercapto-1-methylethyl, or .alpha.-mercaptopropyl;
• halo(C.sub.1 -C.sub.3)alkyl group;
• 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 ##STR226## where Z=N, O, S or Se;
• 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 ##STR227## wherein Z and Z.sup.1 are independently N, O, S or Se;
• or a five membered saturated ring with one or two N, O, S or Se heteroatoms and an adjacent appended O heteroatom selected from ##STR228## wherein A is selected from hydrogen;
• straight or branched (C.sub.1 -C.sub.4)alkyl;
• C.sub.6 -aryl;
• substituted C.sub.6 -aryl where the substitution is selected from halo, (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 or carboxy;
• (C.sub.7 -C.sub.9)aralkyl group selected from benzyl, 1-phenylethyl, 2-phenylethyl or phenylpropyl;
• or a six membered aromatic ring with one to three N heteroatoms, or a six membered saturated ring with one or two N, O, S, or Se heteroatoms and an adjacent appended O heteroatom;
• acyl or haloacyl group selected from acetyl, propionyl, chloroacetyl, trifluoroacetyl, (C.sub.3 -C.sub.6)cycloalkylcarbonyl, (C.sub.6 -C.sub.10)aroyl selected from benzoyl or naphthoyl, halo substituted (C.sub.6 -C.sub.10)aroyl, (C.sub.1 -C.sub.4)alkylbenzoyl, or (heterocycle)carbonyl, the heterocycle 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 ##STR229## where Z=N, O, S or Se;
• 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 ##STR230## wherein Z and Z.sup.1 are independently N, O, S or Se;
• or a five membered saturated ring with one or two N, O, S or Se heteroatoms and an adjacent appended O heteroatom selected from ##STR231## wherein A is selected from hydrogen;
• straight or branched (C.sub.1 -C.sub.4)alkyl;
• C.sub.6 -aryl;
• substituted C.sub.6 -aryl where the substitution is selected from halo, (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 or carboxy;
• (C.sub.7 -C.sub.9)aralkyl group selected from benzyl, 1-phenylethyl, 2-phenylethyl or phenylpropyl;
• or a six membered aromatic ring with one to three N heteroatoms, or a six membered saturated ring with one or two N, O, S, or Se heteroatoms and an adjacent appended O heteroatom;
• (C.sub.1 -C.sub.4)alkoxycarbonyl group selected from methoxycarbonyl, ethoxycarbonyl, straight or branched propoxycarbonyl, straight butoxycarbonyl, or allyloxycarbonyl;
• vinyl or substituted vinyl group where the substitution is selected from (C.sub.1 -C.sub.3)alkyl group, halogen, (C.sub.6 -C.sub.10)aryl group selected from phenyl, .alpha.-naphthyl, .beta.-naphthyl, substituted (C.sub.6 -C.sub.10)aryl group where the substitution is selected from halo, (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 or carboxy;
• halo(C.sub.1 -C.sub.3)alkyl group, 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 ##STR232## where Z=N, O, S or Se;
• (C.sub.1 -C.sub.4)alkoxy group;
• C.sub.6 -aryloxy group selected from phenoxy or substituted phenoxy where the substitution is selected from halo, (C.sub.1 -C.sub.4)alkyl, nitro, cyano, thiol, amino, carboxy, or di-(C.sub.1 -C.sub.3)alkylamino;
• (C.sub.7 -C.sub.10)aralkoxy group;
• vinyloxy or substituted vinyloxy group where the substitution is selected from (C.sub.1 -C.sub.4)alkyl, cyano, carboxy or (C.sub.6 -C.sub.10)aryl selected from phenyl, .alpha.-naphthyl or .beta.-naphthyl;
• R.sup.a R.sup.b amino(C.sub.1 -C.sub.4)alkoxy group or R.sup.a R.sup.b aminoxy group, wherein R.sup.a R.sup.b is a straight or branched (C.sub.1 -C.sub.4)alkyl selected from methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, (CH.sub.2).sub.n where n=2-6, or --(CH.sub.2).sub.2 W(CH.sub.2).sub.2 -- where W is selected from --N(C.sub.1 -C.sub.3)alkyl where the alkyl is straight or branched, --NH, O, S, or --NOB where B is selected from hydrogen or (C.sub.1 -C.sub.4)alkyl;
• and when R.sup.3 =R.sup.4 (CH.sub.2).sub.n CO-- and n=1-4,
• R.sup.4 is selected from hydrogen;
• straight or branched (C.sub.1 -C.sub.4)alkyl group selected from methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl, or 1,1-dimethylethyl;
• (C.sub.3 -C.sub.6)cycloalkyl group selected from cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl;
• substituted (C.sub.3 -C.sub.6)cycloalkyl group where the substitution is selected from (C.sub.1 -C.sub.3)alkyl, cyano, amino or (C.sub.1 -C.sub.3)acyl;
• (C.sub.6 -C.sub.10)aryl group selected from phenyl, .alpha.-naphthyl or .beta.-naphthyl;
• substituted (C.sub.6 -C.sub.10)aryl group where the substitution is selected from halo, (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 or carboxy;
• (C.sub.7 -C.sub.9)aralkyl group;
• acyloxy or haloacyloxy group where acyl or haloacyl is selected from acetyl, propionyl, chloroacetyl, trichloroacetyl, (C.sub.3 -C.sub.6)cycloalkylcarbonyl, (C.sub.6 -C.sub.10)aroyl selected from benzoyl or naphthoyl, halo substituted(C.sub.6 -C.sub.10)aroyl, (C.sub.1 -C.sub.4)alkylbenzoyl, (heterocycle)carbonyl, the heterocycle 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 ##STR233## where Z=N, O, S or Se;
• 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 ##STR234## wherein Z and Z.sup.1 are independently N, O, S or Se;
• or a five membered saturated ring with one or two N, O, S or Se heteroatoms and an adjacent appended O heteroatom selected from ##STR235## wherein A is selected from hydrogen;
• straight or branched (C.sub.1 -C.sub.4)alkyl;
• C.sub.6 -aryl;
• substituted C.sub.6 -aryl where the substitution is selected from halo, (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 or carboxy;
• (C.sub.7 -C.sub.9)aralkyl group selected from benzyl, 1-phenylethyl, 2-phenylethyl or phenylpropyl;
• or a six membered aromatic ring with one to three N heteroatoms, or a six membered saturated ring with one or two N, O, S, or Se heteroatoms and an adjacent appended O heteroatom;
• (C.sub.1 -C.sub.4)alkoxy group;
• C.sub.6 -aryl group selected from phenoxy or substituted phenoxy where the substitution is selected from halo, (C.sub.1 -C.sub.4)alkyl, nitro, cyano, thiol, amino, carboxy, or di-(C.sub.1 -C.sub.3)alkylamino;
• (C.sub.7 -C.sub.10)aralkoxy group;
• (C.sub.1 -C.sub.3)alkylthio group selected from methylthio, ethylthio, propylthio or allylthio;
• C.sub.6 -arylthio group selected from phenylthio or substituted phenylthio where the substitution is selected from halo (C.sub.1 -C.sub.4)alkyl, nitro, cyano, thio, amino, carboxy, di-(C.sub.1 -C.sub.3)alkylamino;
• C.sub.6 -arylsulfonyl group selected from phenylsulfonyl or substituted phenylsulfonyl where the substitution is selected from halo, (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 or carboxy;
• (C.sub.7 -C.sub.8)aralkylthio group;
• 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 ##STR236## where Z=N, O, S or Se;
• 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 ##STR237## wherein Z and Z.sup.1 are independently N, O, S or Se;
• or a five membered saturated ring with one or two N, O, S or Se heteroatoms and an adjacent appended O heteroatom selected from ##STR238## wherein A is selected from hydrogen;
• straight or branched (C.sub.1 -C.sub.4)alkyl;
• C.sub.6 -aryl;
• substituted C.sub.6 -aryl where the substitution is selected from halo, (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 or carboxy;
• (C.sub.7 -C.sub.9)aralkyl group selected from benzyl, 1-phenylethyl, 2-phenylethyl or phenylpropyl;
• or a six membered aromatic ring with one to three N heteroatoms, or a six membered saturated ring with one or two N, O, S, or Se heteroatoms and an adjacent appended O heteroatom;
• hydroxy group, mercapto group;
• .alpha.-hydroxy(C.sub.1 -C.sub.3)alkyl group selected from hydroxymethy, .alpha.-hydroxyethyl, .alpha.-hydroxy-1-methylethyl or .alpha.-hydroxypropyl;
• halo(C.sub.1 -C.sub.3)alkyl group;
• acyl or haloacyl group selected from acetyl, propionyl, chloroacetyl, trifluoroacetyl, (C.sub.3 -C.sub.6)cycloalkylcarbonyl, (C.sub.6 -C.sub.10)aroyl selected from benzoyl or naphthoyl, halo substituted (C.sub.6 -C.sub.10)aroyl, (C.sub.1 -C.sub.4)alkylbenzoyl, or (heterocycle)carbonyl, the heterocycle 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 ##STR239## where Z=N, O, S or Se;
• 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 ##STR240## wherein Z and Z.sup.1 are independently N, O, S or Se;
• or a five membered saturated ring with one or two N, O, S or Se heteroatoms and an adjacent appended O heteroatom selected from ##STR241## wherein A is selected from hydrogen;
• straight or branched (C.sub.1 -C.sub.4)alkyl;
• C.sub.6 -aryl;
• substituted C.sub.6 -aryl where the substitution is selected from halo, (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 or carboxy;
• (C.sub.7 -C.sub.9)aralkyl group selected from benzyl, 1-phenylethyl, 2-phenylethyl or phenylpropyl;
• or a six membered aromatic ring with one to three N heteroatoms, or a six membered saturated ring with one or two N, O, S, or Se heteroatoms and an adjacent appended O heteroatom;
• (C.sub.1 -C.sub.4)alkoxycarbonyl group selected from methoxycarbonyl, ethoxycarbonyl, straight or branched propoxycarbonyl, allyloxycarbonyl, or straight or branched butoxycarbonyl;
• R.sup.a R.sup.b amino(C.sub.1 -C.sub.4)alkoxy group or R.sup.a R.sup.b aminoxy group, wherein R.sup.a R.sup.b is a straight or branched (C.sub.1 -C.sub.4)alkyl selected from methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, (CH.sub.2).sub.n where n=2-6, or --(CH.sub.2).sub.2 W(CH.sub.2).sub.2 -- where W is selected from --N(C.sub.1 -C.sub.3)alkyl where the alkyl is straight or branched, --NH, O, S, or --NOB where B is selected from hydrogen or (C.sub.1 -C.sub.4)alkyl;
• and when R.sup.3 =R.sup.4 (CH.sub.2).sub.n CO-- and n=2-4,
• R.sup.4 is additionally selected from amino;
• hydroyamino;
• straight or branched mono(C.sub.1 -C.sub.6)alkylamino group where (C.sub.1 -C.sub.6)alkyl is 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-methyl-1-ethylpropyl and the diastereomers and enantiomers of said straight or branched mono(C.sub.1 -C.sub.6)alkylamino group;
• (C.sub.3 -C.sub.8)cycloalkylamino group where (C.sub.3 -C.sub.8)cycloalkyl is selected from cyclopropyl, trans-1,2-dimethylcyclopropyl, cis-1,2-dimethylcyclopropyl, trans-2,3-dimethylcyclopropyl, cis-2,3-dimethylcyclopropyl, cyclobutyl, trans-2,3-dimethylcyclobutyl, cis-2,3-dimethylcyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclo›2.2.1!hept-2-yl, bicyclo›2.2.2!oct-2-yl and the diastereomers and enantiomers of said (C.sub.3 -C.sub.8)cycloalkylamino group;
• straight or branched chain di-(C.sub.1 -C.sub.6)alkylamino group selected from dimethylamino, diethylamino, methyl(ethyl)amino, ethyl(1-methylethyl)amino or where each (C.sub.1 -C.sub.6)alkyl is independently 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-ethylpropyl and the diastereomers and enantiomers of said straight or branched chain di-(C.sub.1 -C.sub.6)alkylamino group;
• (C.sub.1 -C.sub.6)alkoxyamino group where (C.sub.1 -C.sub.6)alkoxy is selected from methoxy, ethoxy, propoxy, butoxy, pentoxy, or hexoxy;
• (C.sub.3 -C.sub.8)cycloalkoxyamino group where (C.sub.3 -C.sub.8)alkoxy is selected from cyclopropoxy, trans-1,2-dimethylcyclopropoxy, cis-1,2-dimethylcyclopropoxy, trans-2,3-dimethylcyclopropoxy, cis-2,3-dimethylcyclopropoxy, cyclobutoxy, trans-2,3-dimethylcyclobutoxy, cis-2,3-dimethylcyclobutoxy, cyclopentoxy, cyclohexoxy, cycloheptoxy, cyclooctoxy, bicyclo›2.2.1!hept-2-yloxy, bicyclo›2.2.1!oct-2-yloxy and the diastereomers and enantiomers of said (C.sub.3 -C.sub.8)cycloalkyloxyamino group;
• (C.sub.7 -C.sub.10)aralkoxyamino group where (C.sub.7 -C.sub.10) is selected from benzyloxy, 2-phenylethoxy, .alpha.-phenylethoxy, (2-naphthyl)methoxy, (1-naphthyl)methoxy, or phenylpropoxy;
• (C.sub.2 -C.sub.8)azacycloalkyl group selected from aziridinyl, azetidinyl, pyrrolidinyl, pyrrolinyl, piperidinyl, 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-2-yl, 2-azabicyclo›2.2.2!oct-2-yl and the diastereomers and enantiomers of said (C.sub.2 -C.sub.8)azacycloalkyl group;
• azaheterocycloalkyl group selected from morpholinyl, piperazinyl, 4-methylpiperazinyl, 4-hydroxypiperazinyl, 4-(C.sub.1 -C.sub.4)alkoxy-piperazinyl, thiamorphinyl, tetrahydro-1,2-oxazinyl, isoxazolidinyl, pyrazolidinyl, 2-methylpyrazolidinyl, 2,5-diazabicyclo›2.2.2!hept-2-yl, 2,5-diaza-5-methylbicyclo›2.2.1!hept-2-yl, and diastereomers and enantiomers of said azaheterocycloalkyl group;
• (C.sub.6 -C.sub.10)arylamino group selected from phenylamino or naphthylamino;
• (C.sub.7 -C.sub.10)aralkylamino group where (C.sub.7 -C.sub.10)aralkyl is selected from benzyl, 2-phenylethyl, .alpha.-phenylethyl, (2-naphthyl)methyl, (1-naphthyl)methyl, or phenylpropyl;
• (C.sub.1 -C.sub.4)alkoxycarbonylamino group selected from n-butoxycarbonylamino, allyloxycarbonylamino, methoxycarbonylamino, ethoxycarbonylamino, or propoxycarbonylamino;
• and when R.sup.3 =R.sup.4' (CH.sub.2).sub.n SO.sub.2 -- and n=0,
• R.sup.4' is selected from amino;
• hydroyamino;
• straight or branched mono(C.sub.1 -C.sub.6)alkylamino group where (C.sub.1 -C.sub.6)alkyl is 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 and the diastereomers and enantiomers of said straight or branched mono(C.sub.1 -C.sub.6)alkylamino group;
• (C.sub.3 -C.sub.8)cycloalkylamino group where (C.sub.3 -C.sub.8)cycloalkyl is selected from cyclopropyl, trans-1,2-dimethylcyclopropyl, cis-1,2-dimethylcyclopropyl, trans-2,3-dimethylcyclopropyl, cis-2,3-dimethylcyclopropyl, cyclobutyl, trans-2,3-dimethylcyclobutyl, cis-2,3-dimethylcyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclo›2.2.1!hept-2-yl, bicyclo›2.2.2!oct-2-yl and the diastereomers and enantiomers of said (C.sub.3 -C.sub.8)cycloalkylamino group;
• straight or branched chain di-(C.sub.1 -C.sub.6)alkylamino group selected from dimethylamino, diethylamino, methyl(ethyl)amino, ethyl(1-methylethyl)amino or where each (C.sub.1 -C.sub.6)alkyl is independently 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-ethylpropyl and the diastereomers and enantiomers of said straight or branched chain di-(C.sub.1 -C.sub.6)alkylamino group;
• (C.sub.1 -C.sub.6)alkoxyamino group where (C.sub.1 -C.sub.6)alkoxy is selected from methoxy, ethoxy, propoxy, butoxy, pentoxy, or hexoxy;
• (C.sub.3 -C.sub.8)cycloalkoxyamino group where (C.sub.3 -C.sub.8)alkoxy is selected from cyclopropoxy, trans-1,2-dimethylcyclopropoxy, cis- 1,2-dimethylcyclopropoxy, trans-2,3-dimethylcyclopropoxy, cis-2,3-dimethylcyclopropoxy, cyclobutoxy, trans-2,3-dimethylcyclobutoxy, cis-2,3-dimethylcyclobutoxy, cyclopentoxy, cyclohexoxy, cycloheptoxy, cyclooctoxy, bicyclo›2.2.1!hept-2-yloxy, bicyclo›2.2.1!oct-2-yloxy and the diastereomers and enantiomers of said (C.sub.3 -C.sub.8)cycloalkyloxyamino group;
• (C.sub.7 -C.sub.10)aralkoxyamino group where (C.sub.7 -C.sub.10) is selected from benzyloxy, 2-phenylethoxy, .alpha.-phenylethoxy, (2-naphthyl)methoxy, (1-naphthyl)methoxy, or phenylpropoxy;
• straight or branched (C.sub.1 -C.sub.4)alkyl group selected from methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl, or 1,1-dimethylethyl;
• (C.sub.3 -C.sub.6)cycloalkyl group selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl;
• substituted (C.sub.3 -C.sub.6)cycloalkyl group where the substitution is selected from (C.sub.1 -C.sub.3)alkyl, cyano, amino or (C.sub.1 -C.sub.3)acyl;
• (C.sub.6 -C.sub.10)aryl group selected from phenyl, .alpha.-naphthyl or, .beta.-naphthyl;
• substituted (C.sub.6 -C.sub.10)aryl group where the substitution is selected from halo, (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 or carboxy;
• (C.sub.7 -C.sub.9)aralkyl group;
• halo (C.sub.1 -C.sub.3)alkyl group;
• 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 ##STR242## where Z=N, O, S or Se;
• 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 ##STR243## wherein Z and Z.sup.1 are independently N, O, S or Se;
• or a five membered saturated ring with one or two N, O, S or Se heteroatoms and an adjacent appended O heteroatom selected from ##STR244## wherein A is selected from hydrogen;
• straight or branched (C.sub.1 -C.sub.4)alkyl;
• C.sub.6 -aryl;
• substituted C.sub.6 -aryl where the substitution is selected from halo, (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 or carboxy;
• (C.sub.7 -C.sub.9)aralkyl group selected from benzyl, 1-phenylethyl, 2-phenylethyl or phenylpropyl;
• or a six membered aromatic ring with one to three N heteroatoms, or a six membered saturated ring with one or two N, O, S, or Se heteroatoms and an adjacent appended O heteroatom;
• R.sup.a R.sup.b amino(C.sub.1 -C.sub.4)alkoxy group or R.sup.a R.sup.b aminoxy group, wherein R.sup.a R.sup.b is a straight or branched (C.sub.1 -C.sub.4)alkyl selected from methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, (CH.sub.2).sub.n where n=2-6, or --(CH.sub.2).sub.2 W(CH.sub.2).sub.2 -- where W is selected from --N(C.sub.1 -C.sub.3)alkyl where the alkyl is straight or branched, --NH, O, S, or --NOB where B is selected from hydrogen or (C.sub.1 -C.sub.4)alkyl;
• and when R.sup.3 =R.sup.4' (CH.sub.2).sub.n SO.sub.2 -- and n=1-4,
• R.sup.4' is selected from hydrogen;
• amino;
• straight or branched (C.sub.1 -C.sub.4)alkyl group selected from methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl, or 1,1-dimethylethyl;
• (C.sub.1 -C.sub.4)carboxyalkyl;
• (C.sub.3 -C.sub.6)cycloalkyl group selected from cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl;
• substituted (C.sub.3 -C.sub.6)cycloalkyl group where the substitution is selected from (C.sub.1 -C.sub.3)alkyl, cyano, amino or (C.sub.1 -C.sub.3)acyl;
• (C.sub.6 -C.sub.10)aryl group selected from phenyl, .alpha.-naphthyl or .beta.-naphthyl;
• substituted (C.sub.6 -C.sub.10)aryl group where the substitution is selected from halo, (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 or carboxy;
• (C.sub.7 -C.sub.9)aralkyl group selected from benzyl, 1-phenylethyl, 2-phenylethyl, or phenylpropyl;
• (C.sub.1 -C.sub.4)alkoxy group;
• C.sub.6 -aryloxy group selected from phenoxy or substituted phenoxy where the substitution is selected from halo, (C.sub.1 -C.sub.4)alkyl, nitro, cyano, thiol, amino, carboxy, or di-(C.sub.1 -C.sub.3)alkylamino;
• (C.sub.7 -C.sub.10)aralkoxy group;
• R.sup.a R.sup.b amino(C.sub.1 -C.sub.4)alkoxy group or R.sup.a R.sup.b aminoxy group, wherein R.sup.a R.sup.b is a straight or branched (C.sub.1 -C.sub.4)alkyl selected from methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, (CH.sub.2).sub.n where n=2-6, or --(CH.sub.2).sub.2 W(CH.sub.2).sub.2 -- where W is selected from --N(C.sub.1 -C.sub.3)alkyl where the alkyl is straight or branched, --NH, O, S, or --NOB where B is selected from hydrogen or (C.sub.1 -C.sub.4)alkyl;
• (C.sub.1 -C.sub.3)alkylthio group selected from methylthio, ethylthio, or n-propylthio;
• C.sub.6 -arylthio group selected from phenylthio or substituted phenylthio where the substitution is selected from halo (C.sub.1 -C.sub.4)alkyl, nitro, cyano, thio, amino, carboxy, di-(C.sub.1 -C.sub.3)alkylamino;
• (C.sub.7 -C.sub.8)aralkylthio group;
• 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 ##STR245## where Z=N, O, S or Se;
• 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 ##STR246## wherein Z and Z.sup.1 are independently N, O, S or Se;
• or a five membered saturated ring with one or two N, O, S or Se heteroatoms and an adjacent appended O heteroatom selected from ##STR247## wherein A is selected from hydrogen;
• straight or branched (C.sub.1 -C.sub.4)alkyl;
• C.sub.6 -aryl;
• substituted C.sub.6 -aryl where the substitution is selected from halo, (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 or carboxy;
• (C.sub.7 -C.sub.9)aralkyl group selected from benzyl, 1-phenylethyl, 2-phenylethyl or phenylpropyl;
• or a six membered aromatic ring with one to three N heteroatoms, or a six membered saturated ring with one or two N, O, S, or Se heteroatoms and an adjacent appended O heteroatom;
• hydroxy group;
• mercapto group;
• halo (C.sub.1 -C.sub.3)alkyl group;
• acyl or haloacyl group selected from acetyl, propionyl, chloroacetyl, trifluoroacetyl, (C.sub.3 -C.sub.6)cycloalkylcarbonyl, (C.sub.6 -C.sub.10)aroyl selected from benzoyl or naphthoyl, halo substituted (C.sub.6 -C.sub.10)aroyl, (C.sub.1 -C.sub.4)alkylbenzoyl, or (heterocycle)carbonyl, the heterocycle 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 ##STR248## where Z=N, O, S or Se;
• 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 ##STR249## wherein Z and Z.sup.1 are independently N, O, S or Se;
• or a five membered saturated ring with one or two N, O, S or Se heteroatoms and an adjacent appended O heteroatom selected from ##STR250## wherein A is selected from hydrogen;
• straight or branched (C.sub.1 -C.sub.4)alkyl;
• C.sub.6 -aryl;
• substituted C.sub.6 -aryl where the substitution is selected from halo, (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 or carboxy;
• (C.sub.7 -C.sub.9)aralkyl group selected from benzyl, 1-phenylethyl, 2-phenylethyl or phenylpropyl;
• or a six membered aromatic ring with one to three N heteroatoms, or a six membered saturated ring with one or two N, O, S, or Se heteroatoms and an adjacent appended O heteroatom;
• (C.sub.1 -C.sub.4)alkoxycarbonyl group selected from methoxycarbonyl, ethoxycarbonyl, straight or branched propoxycarbonyl, allyloxycarbonyl or straight butoxycarbonyl;
• or a pharmacologically acceptable organic or inorganic salt or metal complex thereof.