T 0574/96 (Deoxytetracyclines/AMERICAN CYANAMID) 30-07-1999

I. The appeal lodged on 28 March 1996 lies from the decision of the Examining Division posted on 30. January 1996 refusing European patent application No. 92 114 281.6 (European publication No. 0 536 515).

II. The decision of the Examining Division was based on claims 1 to 20 of the application as filed and annexed thereto. Claims 1 and 11 read as follows:

"1. A compound of the formula:

FORMULA

wherein:

X is selected from amino, NR1R2, or halogen; the halogen is selected from bromine, chlorine, fluorine or iodine; and when X = NR1R2 and R1 = hydrogen,

R2 = methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl or 1,1-dimethylethyl;

and when R1 = methyl or ethyl,

R2 = methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl or 2-methylpropyl;

and when R1 = n-propyl,

R2 = n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl or 2-methylpropyl;

and when R1 = 1-methylethyl,

R2 = n-butyl, 1-methylpropyl or 2-methylpropyl;

and when R1 = n-butyl,

R2 = n-butyl, 1-methylpropyl or 2-methylpropyl;

and when R1 = 1-methylpropyl,

R2 = 2-methylpropyl;

R is selected from R4(CH2)nCO- or R4'(CH2)nSO2-;

and when R = R4(CH2)nCO- and n=0,

R4 is selected from hydrogen; amino; monosubstituted amino selected from straight or branched (C1-C6)alkylamino, cyclopropylamino, cyclobutylamino, benzylamino or phenylamino; disubstituted amino selected from dimethylamino, diethylamino, ethyl(1-methylethyl)amino, monomethylbenzylamino, piperidinyl, morpholinyl, 1-imidazolyl, 1-pyrrolyl, 1-(1,2,3-triazolyl) or 4-(1,2,4-triazolyl); straight or branched (C1-C4)alkyl group selected from methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl or 1,1-dimethylethyl; (C3-C6)cycloalkyl group selected from cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; substituted (C3-C6)cycloalkyl group (substitution selected from (C1-C3)alkyl, cyano, amino or (C1-C3)acyl); (C6-C10)aryl group selected from phenyl, alpha-naphthyl or beta-naphthyl; substituted (C6-C10)aryl group (substitution selected from halo, (C1-C4)alkoxy, trihalo(C1-C3)alkyl, nitro, amino, cyano, (C1-C4)alkoxycarbonyl, (C1-C3)alkylamino or carboxy); (C7-C9)aralkyl group selected from benzyl, 1-phenylethyl, 2-phenylethyl or phenylpropyl; alpha-amino-(C1-C4)alkyl group selected from aminomethyl, alpha-aminoethyl, alpha-aminopropyl or alpha-aminobutyl; carboxy(C2-C4)-alkylamino group selected from aminoacetic acid, alpha-aminobutyric acid or alpha-aminopropionic acid and their optical isomers; (C7-C9)aralkylamino group; (C1-C4)alkoxycarbonylamino substituted (C1-C4)alkyl group, substitution selected from phenyl or p-hydroxyphenyl; alpha-hydroxy(C1-C3)alkyl group selected from hydroxymethyl, alpha-hydroxyethyl or alpha-hydroxy-1-methylethyl or alpha-hydroxypropyl; alpha-mercapto(C1-C3)alkyl group selected from mercaptomethyl, alpha-mercaptoethyl, alpha-mercapto-1-methylethyl or alpha-mercaptopropyl; halo(C1-C3)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:

FORMULA

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:

FORMULA

Z or Z1 = 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:

FORMULA

(A is selected from hydrogen; straight or branched (C1-C4)alkyl; C6-aryl; substituted C6-aryl (substitution selected from halo,(C1-C4)alkoxy, trihalo(C1-C3)alkyl, nitro, amino, cyano, (C1-C4)alkoxycarbonyl, (C1-C3)alkylamino or carboxy); (C7-C9)aralkyl group selected from benzyl, 1-phenylethyl, 2-phenylethyl or phenylpropyl)

or a six membered aromatic ring with one to three N, O, S or Se 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, (C3-C6)cycloalkylcarbonyl, (C6-C10)aroyl selected from benzoyl or naphthoyl, halo substituted (C6-C10)aroyl, (C1-C4)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: FORMULA

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:

FORMULA

Z or Z1 = 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:

FORMULA

(A is selected from hydrogen; straight or branched (C1-C4)alkyl; C6-aryl; substituted C6-aryl (substitution selected from halo,(C1-C4)alkoxy, trihalo(C1-C3)alkyl, nitro, amino, cyano, (C1-C4)alkoxycarbonyl, (C1-C3)alkylamino or carboxy); (C7-C9)aralkyl group selected from benzyl, 1-phenylethyl, 2-phenylethyl or phenylpropyl)

or a six membered aromatic ring with one to three N, O, S or Se heteroatoms, or a six membered saturated ring with one or two N, O, S or Se heteroatoms and an adjacent appended O heteroatom; (C1-C4)alkoxycarbonyl group selected from methoxycarbonyl, ethoxycarbonyl, straight or branched propoxylcarbonyl, straight or branched butoxycarbonyl or allyloxycarbonyl; vinyl or substituted vinyl group [substitution selected from (C1-C3)alkyl group, halogen, (C6-C10)aryl group selected from phenyl, alpha-naphthyl, beta-naphthyl, substituted (C6-C10)aryl group (substitution selected from halo, (C1-C4)alkoxy, trihalo(C1-C3)alkyl, nitro, amino, cyano, (C1-C4)alkoxycarbonyl, (C1-C3)alkylamino or carboxy), halo(C1-C3)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:

FORMULA

Z = N, O, S or Se ]; (C1-C4)alkoxy group; C6-aryloxy group selected from phenoxy or substituted phenoxy (substitution selected from halo, (C1-C4)alkyl, nitro, cyano, thiol, amino, carboxy, di(C1-C3)alkylamino); (C7-C10)aralkyloxy group; vinyloxy or substituted vinyloxy group (substitution selected from (C1-C4)alkyl, cyano, carboxy, or (C6-C10)aryl selected from phenyl, alpha-naphthyl or beta-naphthyl); RaRbamino(C1-C4)alkoxy group, wherein RaRb is a straight or branched (C1-C4)alkyl selected from methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, or 2-methylpropyl or RaRb is (CH2)n, n=2-6, or -(CH2)2W(CH2)2- wherein W is selected from -N(C1-C3)alkyl [straight or branched], -NH, -NOB [B is selected from hydrogen or (C1-C3)alkyl], O or S; or RaRbaminoxy group, wherein RaRb is a straight or branched (C1-C4)alkyl selected from methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl, or 1,1-dimethylethyl or RaRb is (CH2)n, n=2-6, or -(CH2)2W(CH2)2- wherein W is selected from -N(C1-C3)alkyl [straight or branched], -NH, -NOB [B is selected from hydrogen or (C1-C3)alkyl], O or S; and when R = R4(CH2)nCO- and n=1-4, R4 is selected from hydrogen; amino; straight or branched (C1-C4)alkyl group selected from methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl or 1,1-dimethylethyl; (C3-C6)cycloalkyl group selected from cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; substituted (C3-C6)cycloalkyl group (substitution selected from (C1-C3)alkyl, cyano, amino or (C1-C3)acyl); (C6-C10)aryl group selected from phenyl, alpha-naphthyl or beta-naphthyl; substituted(C6-C10)aryl group (substitution selected from halo, (C1-C4)alkoxy, trihalo(C1-C3)alkyl, nitro, amino, cyano, (C1-C4)alkoxycarbonyl, (C1-C3)alkylamino or carboxy); (C7-C9)aralkyl group; acyloxy or haloacyloxy group selected from acetyl, propionyl, chloroacetyl, trichloroacetyl, (C3-C6)cycloalkylcar- bonyl, (C6-C10)aroyl selected from benzoyl or naphthoyl, halo substituted (C6-C10)aroyl, (C1-C4)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:

FORMULA

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:

FORMULA

Z or Z1 = 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:

FORMULA

(A is selected from hydrogen; straight or branched (C1-C4)alkyl; C6-aryl; substituted C6-aryl (substitution selected from halo,(C1-C4)alkoxy, trihalo(C1-C3)alkyl, nitro, amino, cyano, (C1-C4)alkoxycarbonyl, (C1-C3)alkylamino or carboxy); (C7-C9)aralkyl group selected from benzyl, 1-phenylethyl, 2-phenylethyl or phenylpropyl)

or a six membered aromatic ring with one to three N, O, S or Se heteroatoms, or a six membered saturated ring with one or two N, O, S or Se heteroatoms and an adjacent appended O heteroatom; (C1-C4)alkoxy group; C6-aryloxy group selected from phenoxy or substituted phenoxy (substitution selected from halo, (C1-C4)alkyl, nitro, cyano, thiol, amino, carboxy, di(C1-C3) alkylamino); (C7-C10)aralkyloxy group; (C1-C3)alkylthio group selected from methylthio, ethylthio, propylthio or allylthio; C6-arylthio group selected from phenylthio or substituted phenylthio (substitution selected from halo, (C1-C4)alkyl, nitro, cyano, thiol, amino, carboxy, di(C1-C3)alkylamino); C6-arylsulfonyl group selected from phenylsulfonyl or substituted phenylsulfonyl (substitution selected from halo, (C1-C4)alkoxy, trihalo(C1-C3)alkyl, nitro, amino, cyano, (C1-C4)alkoxycarbonyl, (C1-C3)alkylamino or carboxy); (C7-C8)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:

FORMULA

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:

FORMULA

Z or Z1 = 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:

FORMULA

(A is selected from hydrogen; straight or branched (C1-C4)alkyl; C6-aryl; substituted C6-aryl (substitution selected from halo,(C1-C4)alkoxy, trihalo(C1-C3)alkyl, nitro, amino, cyano, (C1-C4)alkoxycarbonyl, (C1-C3)alkylamino or carboxy); (C7-C9)aralkyl group selected from benzyl, 1-phenylethyl, 2-phenylethyl or phenylpropyl)

or a six membered aromatic ring with one to three N, O, S or Se 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; mono- or di-straight or branched chain (C1-C6)alkylamino group selected from methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, 2-methylbutyl, 1,1-dimethylpropyl, 2,2-dimethylpropyl, 3-methylbutyl, n-hexyl, 1-methylpentyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 2-methylpentyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl or 1-methyl-1-ethylpropyl amino; (C2-C5)azacycloalkyl group; carboxy(C2-C4)alkylamino group selected from aminoacetic acid, alpha-aminopropionic acid, alpha-aminobutyric acid and their optical isomers; alpha-hydroxy(C1-C3)alkyl group selected from hydroxymethyl, alpha-hydroxyethyl or alpha-hydroxy-1-methylethyl or alpha-hydroxypropyl; halo(C1-C3) alkyl group; acyl or haloacyl group selected from acetyl, propionyl, chloroacetyl, trifluoroacetyl, (C3-C6)cycloalkylcarbonyl, (C6-C10)aroyl selected from benzoyl or naphthoyl, halo substituted (C6-C10)aroyl, (C1-C4)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:

FORMULA

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:

FORMULA

Z or Z1 = 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:

FORMULA (A is selected from hydrogen; straight or branched (C1-C4)alkyl; C6-ar yl; substituted C6-aryl (substitution selected from halo,(C1-C4)alkoxy, trihalo(C1-C3)alkyl, nitro, amino, cyano, (C1-C4)alkoxycarbonyl, (C1-C3)alkylamino or carboxy); (C7-C9)aralkyl group selected from benzyl, 1-phenylethyl, 2-phenylethyl or phenylpropyl)

or a six membered aromatic ring with one to three N, O, S or Se heteroatoms, or a six membered saturated ring with one or two N, O, S or Se heteroatoms and an adjacent appended O heteroatom; (C1-C4)alkoxycarbonylamino group selected from tert-butoxycarbonylamino, allyloxycarbonylamino, methoxycarbonylamino, ethoxycarbonylamino or propoxycarbonylamino; (C1-C4)alkoxycarbonyl group selected from methoxycarbonyl, ethoxycarbonyl, straight or branched propoxycarbonyl, allyloxycarbonyl or straight or branched butoxycarbonyl; RaRbamino(C1-C4)alkoxy group, wherein RaRb is a straight or branched (C1-C4)alkyl selected from methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, or 2-methylpropyl or RaRb is (CH2)n, n=2-6, or

-(CH2)2W(CH2)2- wherein W is selected from -N(C1-C3)alkyl [straight or branched], -NH, -NOB [B is selected from hydrogen or (C1-C3)alkyl], O or S; or RaRbaminoxy group, wherein RaRb is a straight or branched (C1-C4)alkyl selected from methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl or RaRb is (CH2)n, n=2-6, or

-(CH2)2W(CH2)2- wherein W is selected from -N(C1-C3)alkyl [straight or branched], -NH, -NOB [B is selected from hydrogen or (C1-C3)alkyl], O or S; and when R = R4'(CH2)nSO2- and n = 0, R4' is selected from amino; monosubstituted amino selected from straight or branched (C1-C6)alkylamino, cyclopropylamino, cyclobutylamino, benzylamino or phenylamino; disubstituted amino selected from dimethylamino, diethylamino, ethyl(1-methylethyl)amino, monomethylbenzylamino, piperidinyl, morpholinyl, 1-imidazolyl, 1-pyrrolyl, 1-(1,2,3-triazolyl) or 4-(1,2,4-triazolyl); straight or branched (C1-C4)alkyl group selected from methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl or 1,1-dimethylethyl; (C3-C6)cycloalkyl group selected from cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; substituted (C3-C6)cycloalkyl group (substitution selected from (C1-C3)alkyl, cyano, amino or (C1-C3)acyl); (C6-C10)aryl group selected from phenyl, alpha-naphthyl or beta-naphthyl; substituted (C6-C10)aryl group (substitution selected from halo, (C1-C4)alkoxy, trihalo(C1-C3)alkyl, nitro, amino, cyano, (C1-C4)alkoxycarbonyl, (C1-C3)alkylamino or carboxy); (C7-C9)aralkyl group; halo(C1-C3)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: FORMULA

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:

FORMULA

Z or Z1 = 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:

FORMULA

(A is selected from hydrogen; straight or branched (C1-C4)alkyl; C6-aryl; substituted C6-aryl (substitution selected from halo,(C1-C4)alkoxy, trihalo(C1-C3)alkyl, nitro, amino, cyano, (C1-C4)alkoxycarbonyl, (C1-C3)alkylamino or carboxy); (C7-C9)aralkyl group selected from benzyl, 1-phenylethyl, 2-phenylethyl or phenylpropyl)

or a six membered aromatic ring with one to three N, O, S or Se heteroatoms, or a six membered saturated ring with one or two N, O, S or Se heteroatoms and an adjacent appended O heteroatom; RaRbamino(C1-C4)alkoxy group, wherein RaRb is a straight or branched (C1-C4)alkyl selected from methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, or 2-methylpropyl or RaRb is (CH2)n, n=2-6, or

-(CH2)2W-(CH2)2- wherein W is selected from -N(C1-C3)alkyl [straight or branched], -NH, -NOB [B is selected from hydrogen or (C1-C3)alkyl], O or S; or RaRbaminoxy group, wherein RaRb is a straight or branched (C1-C4)alkyl selected from methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, or 2-methylpropyl or RaRb is (CH2)n, n=2-6, or -(CH2)2W(CH2)2- wherein W is selected from -N(C1-C3)alkyl [straight or branched], -NH, -NOB [B is selected from hydrogen or (C1-C3)alkyl], O or S; and when R = R4'(CH2)nSO2- and n= 1-4, R4' is selected from hydrogen; straight or branched (C1-C4)alkyl group selected from methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl or 1,1-dimethylethyl; (C1-C4)carboxyalkyl group; (C3-C6)cycloalkyl group selected from cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; substituted (C3-C6)cycloalkyl group (substitution selected from (C1-C3)alkyl, cyano, amino or (C1-C3)acyl); (C6-C10)aryl group selected from phenyl, alpha-naphthyl or beta-naphthyl; substituted (C6-C10)aryl group (substitution selected from halo, (C1-C4)alkoxy, trihalo(C1-C3)alkyl, nitro, amino, cyano, (C1-C4)alkoxycarbonyl, (C1-C3)alkylamino or carboxy); (C7-C9)aralkyl group selected from benzyl, 1-phenylethyl, 2-phenylethyl or phenylpropyl; (C1-C4)alkoxy group; C6-aryloxy group selected from phenoxy or substituted phenoxy (substitution selected from halo, (C1-C3)alkyl, nitro, cyano, thiol, amino, carboxy, di(C1-C3)alkylamino); (C7-C10)aralkyloxy group; RaRbamino(C1-C4)alkoxy group, wherein RaRb is a straight or branched (C1-C4)alkyl selected from methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, or 2-methylpropyl or RaRb is (CH2)n, n=2-6, or -(CH2)2W(CH2)n- wherein W is selected from -N(C1-C3)alkyl [straight or branched], -NH, -NOB [B is selected from hydrogen or (C1-C3)alkyl], O or S; or RaRbaminoxy group, wherein RaRb is a straight or branched (C1-C4)alkyl selected from methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, or 2-methylpropyl or RaRb is (CH2)n, n=2-6, or -(CH2)2W(CH2)2- wherein W is selected from -N(C1-C3)alkyl [straight or branched], -NH, -NOB [B is selected from hydrogen or (C1-C3)alkyl], O or S; (C1-C3)alkylthio group selected from methylthio, ethylthio or n-propylthio; C6-arylthio group selected from phenylthio or substituted phenylthio (substitution selected from halo, (C1-C3)alkyl, nitro, cyano, thiol, amino, carboxy, di(C1-C3)alkylamino); (C7-C8)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:

FORMULA

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:

FORMULA

Z or Z1 = 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:

FORMULA

(A is selected from hydrogen; straight or branched (C1-C4)alkyl; C6-aryl; substituted C6-aryl (substitution selected from halo,(C1-C4)alkoxy, trihalo(C1-C3)alkyl, nitro, amino, cyano, (C1-C4)alkoxycarbonyl, (C1-C3)alkylamino or carboxy); (C7-C9)aralkyl group selected from benzyl, 1-phenylethyl, 2-phenylethyl or phenylpropyl)

or a six membered aromatic ring with one to three N, O,S or Se 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; mono- or di- straight or branched (C1-C6)alkylamino group selected from methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, 2-methylbutyl, 1,1-dimethylpropyl, 2,2-dimethylpropyl, 3-methylbutyl, n-hexyl, 1-methylpentyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 2-methylpentyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl or 1-methyl-1-ethylpropyl amino; halo(C1-C3)alkyl group; acyl or haloacyl group selected from acetyl, propionyl, chloroacetyl, trifluoroacetyl, (C3-C6)cycloalkylcarbonyl, (C6-C10)aroyl selected from benzoyl or naphthoyl, halo substituted (C6-C10)aroyl, (C1-C4)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:

FORMULA

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:

FORMULA

Z or Z1 = 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:

FORMULA

(A is selected from hydrogen; straight or branched (C1-C4)alkyl; C6-aryl; substituted C6-aryl (substitution selected from halo,(C1-C4)alkoxy, trihalo(C1-C3)alkyl, nitro, amino, cyano, (C1-C4)alkoxycarbonyl, (C1-C3)alkylamino or carboxy); (C7-C9)aralkyl group selected from benzyl, 1-phenylethyl, 2-phenylethyl or phenylpropyl)

or a six membered aromatic ring with one to three N, O, S or Se heteroatoms, or a six membered saturated ring with one or two N, O, S or Se heteroatoms and an adjacent appended O heteroatom; (C1-C4)alkoxycarbonyl group selected from methoxycarbonyl, ethoxycarbonyl, straight or branched propoxycarbonyl, allyloxycarbonyl or straight or branched butoxycarbonyl; R5 is selected from hydrogen; straight or branched (C1-C3)alkyl group selected from methyl, ethyl, n-propyl or 1-methylethyl; (C6-C10)aryl group selected from phenyl, alpha-naphthyl or beta-naphthyl; (C7-C9)aralkyl 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:

FORMULA

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:

FORMULA

Z or Z1 = 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: FORMULA

(A is selected from hydrogen; straight or branched (C1-C4)alkyl; C6-aryl; substituted C6-aryl (substitution selected from halo,(C1-C4)alkoxy, trihalo(C1-C3)alkyl, nitro, amino, cyano, (C1-C4)alkoxycarbonyl, (C1-C3)alkylamino or carboxy); (C7-C9)aralkyl group selected from benzyl, 1-phenylethyl, 2-phenylethyl or phenylpropyl)

or a six membered aromatic ring with one to three N, O, S or Se heteroatoms, or a six membered saturated ring with one or two N, O, S or Se heteroatoms and an adjacent appended O heteroatom; or -(CH2)nCOOR7 where n=0-4 and R7 is selected from hydrogen; straight or branched (C1-C3)alkyl group selected from methyl, ethyl, n-propyl or 1-methylethyl; or (C6-C10)aryl group selected from phenyl, alpha-naphthyl or beta-naphthyl; R6 is selected from hydrogen; straight or branched (C1-C3)alkyl group selected from methyl, ethyl, n-propyl or 1-methylethyl; (C6-C10)aryl group selected from phenyl, alpha-naphthyl or beta-naphthyl; (C7-C9)aralkyl 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:

FORMULA

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:

FORMULA

Z or Z1 = 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:

FORMULA

(A is selected from hydrogen; straight or branched (C1-C4)alkyl; C6-aryl; substituted C6-aryl (substitution selected from halo,(C1-C4)alkoxy, trihalo(C1-C3)alkyl, nitro, amino, cyano, (C1-C4)alkoxycarbonyl, (C1-C3)alkylamino or carboxy); (C7-C9)aralkyl group selected from benzyl, 1-phenylethyl, 2-phenylethyl or phenylpropyl)

or a six membered aromatic ring with one to three N, O, S or Se heteroatoms, or a six membered saturated ring with one or two N, O, S or Se heteroatoms and an adjacent appended O heteroatom; or -(CH2)nCOOR7' where n=0-4 and R7' is selected from hydrogen; straight or branched (C1-C3)alkyl selected from methyl, ethyl, n-propyl or 1-methylethyl; or (C6-C10)aryl selected from phenyl, alpha-naphthyl or beta-naphthyl; with the proviso that R5 and R6 cannot both be hydrogen; or R5 and R6 taken together are -(CH2)2W(CH2)2-, wherein W is selected from (CH2)n and n=0-1, -NH, -N(C1-C3)alkyl [straight or branched], -N(C1-C4)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.

11. The compound according to Claim 1, [4S-(4alpha,12aalpha)]-4,7-Bis(dimethylamino)-9- (formylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3, 10,12,12a-tetrahydroxy-1,11-dioxo-2- naphthacenecarboxamide; [4S-(4alpha,12aalpha)]-4,7-Bis(dimethylamino)-9- (formylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3, 10,12,12a-tetrahydroxy-1,11-dioxo-2- naphthacenecarboxamide sulfate; [4S-(4alpha,12aalpha)]-4,7-Bis(dimethylamino)-9- (formylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3, 10,12,12a-tetrahydroxy-1,11-dioxo-2- naphthacenecarboxamide monohydrochloride; [4S-(4alpha,12aalpha)]-9-(Acetylamino)-4,7-bis (dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro- 3,10,12,12a-tetrahydroxy-1,11-dioxo-2- naphthacenecarboxamide; [4S-(4alpha,12aalpha)] -4,7-Bis(dimethylamino)-1,4,4a,5,5a,6,11,12a- octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-9- [(trifluoroacetyl)amino]-2- naphthacenecarboxamide sulfate; [4S-(4alpha, 12aalpha)]-7-(Diethylamino)-4-(dimethylamino)-9- (formylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3, 10,12,12a-tetrahydroxy-1,11-dioxo-2- naphthacenecarboxamidesulfate (1:2); [4S-(4alpha,12aalpha)]-9-(Acetylamino)-7- (diethylamino)-4-(dimethylamino)-1,4,4a,5,5a,6, 11,12a-octahydro-3,10,12,12a-tetrahydroxy-1, 11-dioxo-2-naphthacenecarboxamide sulfate (1:2); [4S-(4alpha,12aalpha)]-7-(Diethylamino)-4- (dimethylamino)-9-(formylamino)-1,4,4a,5,5a,6, 11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11- dioxo-2-naphthacenecarboxamide; [4S-(4alpha, 12aalpha)]-9-(Acetylamino)-7-(diethylamino)-4- (dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro- 3,10,12,12a-tetrahydrox y-1,11-dioxo-2- naphthacenecarboxamide; [4S-(4alpha,12aalpha)] -4-(Dimethylamino)-9-(formylamino)-1,4,4a,5,5a, 6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-7- iodo-1,11-dioxo-2-naphthacenecarboxamide; [4S-(4alpha,12aalpha)]-4-(Dimethylamino)-9- (formylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3, 10,12,12a-tetrahydroxy-7-iodo-1,11-dioxo-2- naphthacenecarboxamide sulfate; [4S-(4alpha, 12aalpha)]-4,7-Bis(dimethylamino)-1,4,4a,5,5a,6, 11,12a-octahydro-3,10,12,12a-tetrahydroxy-9- [(methoxyacetyl)amino]-1,11-dioxo-2- naphthacenecarboxamide; 4S-(4alpha,12aalpha)]-9- [(4-Bromo-1-oxobutyl)amino]-4,7-bis (dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro- 3,10,12,12a-tetrahydroxy-1,11-dioxo-2- naphthacenecarboxamide; 4S-(4alpha,12aalpha)]- 4,7-Bis(dimethylamino)-1,4,4a,5,5a,6,11,12a- octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-9- [(1-oxo-2-propenyl)amino]-2- naphthacenecarboxamide; 4S-(4alpha,12aalpha)]-9- [[(Acetyloxy)acetyl]amino]-4,7-bis (dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro- 3,10,12,12a-tetrahydroxy-1,11-dioxo-2- naphthacenecarboxamide sulfate; 4S-(4alpha, 12aalpha)]-9-(Benzoylamino)-4,7-bis (dimethylamino)-1,4,4a,5,5a,6,11, 2a-octahydro- 3,10,12,12a-tetrahydroxy-1,11-dioxo-2- naphthacenecarboxamide; 4S-(4alpha,12aalpha)]- 4,7-Bis(dimethylamino)-1,4,4a,5,5a,6,11,12a- octahydro-3,10,12,12a-tetrahydroxy-9- [(4-methoxybenzoyl)amino]-1,11-dioxo-2- naphthacenecarboxamide; [4S-(4alpha,12aalpha))]- 4,7-Bis(dimethylamino)-1,4,4a,5,5a,6,11,12a- octahydro-3,10,12,12a-tetrahydroxy-9- [(2-methylbenzoyl)amino]-1,11-dioxo-2- naphthacenecarboxamide; [4S-(4alpha,12aalpha)]- 4,7-Bis(dimethylamino)-9-[(2-fluorobenzoyl) amino]-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12, 12a-tetrahydroxy-1,11-dioxo-2- naphthacenecarboxamide; [4S-(4alpha,12aalpha)]- 4,7-Bis(dimethylamino)-1,4,4a,5,5a,6,11,12a- octahydro-3,10,12,12a-tetrahydroxy-9- [(pentafluorobenzoyl)amino]-1,11-dioxo-2- naphthacenecarboxamide hydrochloride; [4S-(4alpha,12aalpha)]-4,7-Bis(dimethylamino)- 1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a- tetrahydroxy-1,11-dioxo-9-[[3-(trifluoromethyl) benzoyl]amino]-2-naphthacenecarboxamide;

[4S-(4alpha,12aalpha)]-4,7-Bis(dimethylamino)-9- [(2-furanylcarbonyl)amino]-1,4,4a,5,5a,6,11,12a- octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2- naphthacenecarboxamide; [4S-(4alpha,12aalpha)]- 4,7-Bis(dimethylamino)-1,4,4a,5,5a,6,11,12a- octahydro-3,10,12,12a-tetrahydroxy1,11-dioxo-9- [(2-thienylcarbonyl)amino]-2- naphthacenecarboxamide; [4S-(4alpha,12aalpha)]- 4,7-Bis(dimethylamino)-1,4,4a,5,5a,6,11,12a- octahydro-3,10,12,12a-tetrahydroxy-9- [(4-nitrobenzoyl)amino]-1,11-dioxo-2- naphthacenecarboxamide; [4S-(4alpha,12aalpha)]- 9-[(4-Aminobenzoyl)amino]-4,7-bis- dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro- 3,10,12,12a-tetrahydroxy-1,11-dioxo-2- naphthacenecarboxamidesulfate; [4S-(4alpha, 12aalpha)]-4,7-Bis(dimethylamino)-9-[[(4- dimethylamino)benzoyl]amino]-1,4,4a,5,5a,6,11, 12a-octahydro-3,10,12,12a-tetrahydroxy-1,11- dioxo-2-naphthacenecarboxamide; [7S-(7alpha, 10aalpha)]-[2-[[9-(Aminocarbonyl)-4,7-bis (dimethylamino)-5,5a,6,6a,7,10,10a,12-octahydro- 1,8,10a,11-tetrahydroxy-10,12-dioxo-2- naphthacenyl]amino]-2-oxoethyl]carbamic acid 1,1-dimethylethyl ester; [4S-(4alpha,12aalpha)]- 9-[(Aminoacetyl)amino]-4,7-bis(dimethylamino)- 1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a- tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide mono(trifluoroacetate); [4S-(4alpha,12aalpha)]- 4,7-Bis(dimethylamino)-1,4,4a,5,5a,6,11,12a- octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-9- [(phenylsulfonyl)amino]-2-naphthacenecarboxamide; [4S-(4alpha,12aalpha)]-9-[[(4-Chlorophenyl) sulfonyl]amino]-4,7-bis(dimethylamino)-1,4,4a,5, 5a,6,11,12a-tetrahydroxy-1,11-dioxo-2- naphthacenecarboxamide; [4S-(4alpha,12aalpha)]- 4,7-Bis(dimethylamino)-1,4,4a,5,5a,6,11,12a- octahydro-3,10,12,12a-tetrahydroxy-9-[(3- nitrophenyl)sulfonyl]amino-1,11-dioxo-2- naphthacenecaboxamide; [4S-(4alpha,12aalpha)]- 4,7-Bis(dimethylamino)-1,4,4a,5a,6,11,12a- octahydro-3,10,12,12a-tetrahydroxy-9-[[(4- nitrophenyl)sulfonyl]amino]-1,11-dioxo-2-naphthacenecarboxamide; [4S-(4alpha,12a alpha)]- 4,7-Bis(dimethylamino)-1,4,4a,5,5a,6,11,12a- octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-9- [(2-thienylsulfon [4S-(4alpha,12aalpha)]-9[[(2- (Acetylamino)-4-methyl-5-thiazolylsulfonyl]amino]-4,7-bis (dimethylamino)-1,4,4a,5,5a,6,11,12a- octahydro- 3,10,12,12a-tetrahydroxy-1,11-dioxo-2- naphthacenecarboxamide; [4S-(4alpha,12aalpha)]- 4,7-Bis(dimethylamino)-9-[(ethylsulfonyl)amino]- 1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a- tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide; [4S-(4alpha,12aalpha)]-4,7-Bis(dimethylamino)-9- (formylamino)-1,4,4a,5a,6,11,12a-octahydro-3,10, 12,12a-tetrahydroxy-1,11-dioxo-N-(1- pyrrolidinylmethyl)-2-naphthacenecarboxamide; [4S-(4alpha,12aalpha)]-4,7-Bis(dimethylamino)- 1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a- tetrahydroxy-9-[(methanesulfonyl)amino]-1,11- dioxo-2-naphthacenecarboxamide; [4S-(4alpha, 12aalpha)]-4,7-Bis(dimethylamino)-1,4,4a,5,5a,6, 11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11- dioxo-9-[[(phenylmethoxy)acetyl]amino]-2- naphthacenecarboxamide; [7S-(7alpha,10aalpha)]- [[9-(Aminocarbonyl)-4,7-bis(dimethylamino)-5,5a, 6,6a,7,10,10a,12-octahydro-1,8,10a,11- tetrahydroxy-10,12-dioxo-2-naphthacenyl]amino]oxoacetic acid ethyl ester; [4S-(4alpha,12aalpha)]- 4,7-Bis(dimethylamino)-1,4,4a,5,5a,6,11,12a- octahydro-3,10,12,12a-tetrahydroxy-9- [(hydroxyacetyl)amino]-1,11-dioxo-2- naphthacenecarboxamide; [4S-(4alpha,12aalpha)]- 4,7-Bis(dimethylamino)-9-[[(methylamino)acetyl] amino]-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12, 12a-tetrahydroxy-1,11-dioxo-2- naphthacenecarboximide hydrochloride; [4S-(4alpha,12aalpha)]-4-(Dimethylamino)-9- (acetylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3, 10,12,12a-tetrahydroxy-7-iodo-1,11-dioxo-2- naphthacenecarboxamide sulfate; [7S(7alpha, 10aalpha)]-[9-(Aminocarbonyl)-4,7-bis (dimethylamino)-5,5a,6,6a,7,10,10a,12-octahydro- 1,8,10a,11-tetrahydroxy-10,12-dioxo-2- naphthacenyl]carbamic acid methyl ester; [7S-(7alpha,10aalpha)]-[9-(Aminocarbonyl)-4,7- bis(dimethylamino)-5,5a,6,6a,7,10,10a,12- octahydro-1,8,10a,11-tetrahydroxy-10,12-dioxo-2- naphthacenyl]carbamic acid (2-diethylamino)ethyl ester; [7S-(7alpha,10aalpha)][9-(Aminocarbonyl)- 4,7-bis(dimethylamino)-5,5a,6,6a,7,10,10a,12- octahydro-1,8,10a,11-tetrahydroxy-10,12-dioxo-2- naphthacenyl]carbamic acid ethenyl ester; [7S- (7alpha,10aalpha)]-[9-(Aminocarbonyl)-4,7-bis (dimethylamino)-5,5a,6,6a,7,10,10a,12-octahydro- 1,8,10a,11-tetrahydroxy-10,12-dioxo-2- naphthacenyl]carbamic acid 2-propenyl ester; [4S-(4alpha,12aalpha)]-4,7-Bis(dimethylamino)-9- [[(dimethylamino)acetyl]amino]-1,4,4a,5,5a,6,11, 12a-octahydro-3,10,12,12a-tetrahydroxy-1,11- dioxo-2-naphthacenecarboxamide sulfate; [4S-(4alpha,12aalpha)]-4,7-Bis(dimethylamino)- 1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a- tetrahydroxy-9-[(methoxyacetyl)amino]-1,11-dioxo- 2-naphthacenecarboxamide hydrochloride; [4S-(4alpha,12aalpha)]-9-[(4-Bromo-1-oxobutyl) amino]-4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11, 12a-octahydro-3,10,12,12a-tetrahydroxy-1, 11-dioxo-2-naphthacenecarboxamide sulfate; [4S-(4alpha,12aalpha)]-9-[[(Acetyloxy)acetyl] amino]-4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11, 12a-octahydro-3,10,12,12a-tetrahydroxy-1,11- dioxo-2-naphthacenecarboxamide; [4S-(4alpha, 12aalpha)]-9-(Benzoylamino)-4,7-bis (dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro- 3,10,12,12a-tetrahydroxy-1,11-dioxo-2- naphthacenecarboxamide sulfate; [4S-(4alpha, 12aalpha)]-4,7-Bis(dimethylamino)-1,4,4a,5,5a,6, 11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11- dioxo-9-[[3-(trifluoromethyl)benzoyl]amino]-2- naphthacenecarboxamide hydrochloride; [4S- (4alpha,12aalpha)]-9-[(4-Aminobenzoyl)amino]-4,7-bis (dimethylamino)-1,4,4a,5,5a,6,11,12a- octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2- naphthacenecarboxamide; [4S-(4alpha,12aalpha)]- 4,7-Bis(dimethylamino)-9-[[(4-dimethylamino) benzoyl]amino]-1,4,4a,5,5a,6,11,12a-octahydro- 3,10,12,12a-tetrahydroxy-1,11-dioxo-2- naphthacenecarboxamide hydrochloride; [7S- (7alpha,10aalpha)]-[2-[[9-(Aminocarbonyl)-4, 7-bis(dimethylamino)-5,5a,6,6a,7,10,10a,12- octahydro-1,8,10a,11-tetrahydroxy-10,12-dioxo-2- naphthacenyl]amino]-2-oxoethyl]carbamic acid 1,1-dimethylethyl ester hydrochloride; [4S- (4alpha,12aalpha]-9-[(Aminoacetyl)amino]-4,7-bis- dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro- 3,10,12,12a-tetrahydroxy-1,11-dioxo-2- naphthacenecarboxamide; [4S-(4alpha,12aalpha)]- 4,7-Bis(dimethylamino)-9-[(ethylsulfonyl)amino]- 1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a- tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide hydrochloride; [4S-(4alpha,12aalpha)]-4,7-Bis (dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro- 3,10,12,12a-tetrahydroxy-9-[(methanesulfonyl) amino]-1,11-dioxo-2-naphthacenecarboxamide sulfate; [4S-(4alpha,12aalpha)]-4,7-Bis (dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro- 3,10,12,12a-tetrahydroxy-1,11-dioxo-9- [[(phenylmethoxy)acetyl]amino]-2- naphthacenecarboxamide hydrochloride; [4S- (4alpha,12aalpha)]-4,7-Bis(dimethylamino)-1,4,4a, 5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy- 9-[(hydroxyacetyl)amino]-1,11-dioxo-2- naphthacenecarboxamide sulfate; [4S-(4alpha, 12aalpha)]-4-(Dimethylamino)-9-(acetylamino)-1,4, 4a,5,5a,6,11,12a-octahydro-3,10,12,12a- tetrahydroxy-7-iodo-1,11-dioxo-2- naphthacenecarboxamide; [4S-(4alpha,12aalpha)]- 4,7-Bis(dimethylamino)-9-[[(dimethylamino)acetyl] amino]-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12, 12a-tetrahydroxy-1,11-dioxo-2- naphthacenecarboxamide; [7S-(7alpha,10aalpha)]- [9-(Aminocarbonyl)-4,7-bis(dimethylamino)-5,5a,6, 6a,7,10,10a,12-octahydro-1,8,10a,11-tetrahydroxy- 10,12-dioxo-2-naphthacenyl]carbamic acid methyl ester sulfate; [7S-(7alpha,10aalpha)]-[9- (Aminocarbonyl)-4,7-bis(dimethylamino)-5,5a,6,6a, 7,10,10a,12-octahydro-1,8,10a,11-tetrahydroxy-10, 12-dioxo-2-naphthacenyl]carbamic acid (2-diethylamino)ethyl ester hydrochloride; [7S-(7alpha,10aalpha)]-[9-(Aminocarbonyl)-4,7-bis (dimethylamino)-5,5a,6,6a,7,10,10a,12-octahydro- 1,8,10a,11-tetrahydroxy-10,12-dioxo-2- naphthacenyl]carbamic acid ethenyl ester sulfate; [7S-(7alpha,10aalpha)]-[9-(Aminocarbonyl)-4,7-bis (dimethylamino)-5,5a,6,6a,7,10,10a,12-octahydro- 1,8,10a,11-tetrahydroxy-10,12-dioxo-2- naphthacenyl]carbamic acid 2-propenyl ester hydrochloride; [4S-(4alpha,12aalpha]-4,7-Bis (dimethylamino)-9-[[(diethylamino)acetyl]amino]- 1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a- tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide sulfate; [4S(4alpha,12aalpha]-4,7-Bis (dimethylamino)-9-[[(diethylamino)acetyl]amino]- 1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a- tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide hydrochloride; [4S-(4alpha,12aalpha]-4,7-Bis (dimethylamino)-9-[[(diethylamino)acetyl]amino]- 1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a- tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide; [4S-(4alpha,12aalpha)]-4,7-Bis(dimethylamino)-9- [[(dimethylamino)acetyl]amino]-1,4,4a,5,5a,6,11, 12a-octahydro-3,10,12,12a-tetrahydroxy-1,11- dioxo-2-naphthacenecarboxamide dihydrochloride; [4S-(4alpha,12aalpha)]-4,7-Bis(dimethylamino)-9- (chloroacetylamino)-1,4,4a,5,5a,6,11,12a- octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2- naphthacenecarboxamide; [4S-(4alpha,12aalpha)]-9- [(Chloroacetyl)amino]-4,7-bis(dimethylamino)-1,4, 4a,5,5a,6,11,12a-octahydro-3,10,12,12a- tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide dihydrochloride; [4S-(4alpha,12aalpha)]-9- [(Bromoacetyl)amino]-4,7-bis(dimethylamino)-1,4, 4a,5,5a,6,11,12a-octahydro-3,10,12,12a- tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide dihydrochloride; [4S-(4alpha,12aalpha)]-9- [(Bromoacetyl)amino]-4,7-bis(dimethylamino)-1,4, 4a,5,5a,6,11,12a-octahydro-3,10,12,12a- tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide (free base); [4S-(4alpha,12aalpha)]-9- [(Bromoacetyl)amino]-4,7-bis(dimethylamino)-1,4, 4a,5,5a,6,11,12a-octahydro-3,10,12,12a- tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide monohydrobromide; [4S-(4alpha,12aalpha)]-9- [(2-Bromo-1-oxopropyl)amino]-4,7-bis (dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro- 3,10,12,12a-tetrahydroxy-1,11-dioxo-2- naphthacenecarboxamide hydrobromide; [4S- (4alpha,12aalpha)]-9-[(2-Bromo-1-oxopropyl)amino]-4,7-bis (dimethylamino)-1,4,4a,5,5a,6,11,12a- octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2- naphthacenecarboxamide hydrobromide; [4S-(4alpha, 12aalpha)]-4,7-Bis(dimethylamino)-1,4,4a,5,5a,6, 11,12a-octahydro-3,10,12,12a-tetrahydroxy-9- [[(methylamino)acetyl]amino]-1,11-dioxo-2- naphthacenecarboxamide dihydrochloride; [7S- (7alpha,10aalpha)]-N-[9-(Aminocarbonyl)-4,7- bis(dimethylamino)-5,5a,6,6a,7,10,10a,12- octahydro-1,8,10a,11-tetrahydroxy-10,12-dioxo-2- naphthacenyl]-4-morpholineacetamide dihydrochloride; [4S-(4alpha,12aalpha)]-4,7- Bis(dimethylamino)-9-[[(ethylamino)acetyl]amino]- 1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a- tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide dihydrochloride; [4S-(4alpha,12aalpha)]-9- [[(Cyclopropylamino)acetyl]amino]-4,7- bis(dimethylamino)-1,4,4a,5,5a,6,11,12aoctahydro- 3,10,12,12a-tetrahydroxy-1,11-dioxo-2- naphthacenecarboxamide dihydrochloride; [4S- (4alpha,12aalpha)]-4,7-Bis(dimethylamino)-9- [[(butylamino)acetyl]amino]-1,4,4a,5,5a,6,11,12a- octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2- naphthacenecarboxamide dihydrochloride; [4S- (4alpha,12aalpha)]-9-[[(Diethylamino)acetyl] amino]-4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11, 12a-octahydro-3,10,12,12a-tetrahydroxy-1,11- dioxo-2-naphthacenecarboxamide dihydrochloride; [7S-(7alpha,10aalpha)]-N-[9-(Aminocarbonyl)-4,7- bis(dimethylamino)-5,5a,6,6a,7,10,10a,12- octahydro-1,8,10a,11-tetrahydroxy-10,12-dioxo-2- naphthacenyl]-1-pyrrolidineacetamide dihydrochloride; [4S-(4alpha,12aalpha)]-4,7- Bis(dimethylamino)-1,4,4a,5,5a,6,11,12a- octahydro-3,10,12,12a-tetrahydroxy-9- [[[(2-methylpropyl)amino]acetyl]amino]-1,11- dioxo-2-naphthacenecarboxamide dihydrochloride; [7S-(7alpha,10aalpha)]-N-[9-(Aminocarbonyl)-4,7- bis(dimethylamino)-5,5a,6,6a,7,10,10a,12- octahydro-1,8,10a,11-tetrahydroxy-10,12-dioxo-2- naphthacenyl]-1-piperidineacetamide dihydrochloride; [7S-(7alpha,10aalpha)]-N-[9- (Aminocarbonyl)-4,7-bis(dimethylamino)-5,5a,6,6a, 7,10,10a,12-octahydro-1,8,10a,11-tetrahydroxy-10, 12-dioxo-2-naphthacenyl]-1H-imidazole-1-acetamide dihydrochloride; [4S-(4alpha,12aalpha)]-4,7- Bis(dimethylamino)-1,4,4a,5,5a,6,11,12a- octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-9- [[(propylamino)acetyl]amino]-2- naphthacenecarboxamide dihydrochloride; [4S- (4alpha,12aalpha)]-4,7-Bis(dimethylamino)-9- [[dimethylamino)acetyl]amino]-1,4,4a,5,5a,6,11, 12a-octahydro-3,10,12,12a-tetrahydroxy-1,11- dioxo-2-naphthacenecarboxamide; [4S- (4alpha,12aalpha)]-4,7-Bis(dimethylamino)-9- [[(hexylamino)acetyl]amino]-1,4,4a,5,5a,6,11,12a- octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2- naphthacenecarboxamide dihydrochloride; [4S- (4alpha,12aalpha)]-4,7-Bis(dimethylamino)-9- [[2-(dimethylamino)-1-oxopropyl]amino]-1,4,4a,5, 5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy- 1,11-dioxo-2-napthacenecarboxamide dihydrochloride; [4S-(4alpha,12aalpha)]-4,7- Bis(dimethylamino)-1,4,4a,5,5a,6,11,12a- octahydro-3,10,12,12a-tetrahydroxy-9- [[2-(methylamino)-1-oxopropyl]amino]-1,11-dioxo- 2-naphthacenecarboxamide dihydrochloride; [7S-(7alpha,10aalpha)]-N-[9-(Aminocarbonyl)-4,7- bis(dimethylamino)-5,5a,6,6a,7,10,10a,12- octahydro-1,8,10a,11-tetrahydroxy-10,12-dioxo-2- naphthacenyl]-alpha-methyl-1-pyrrolidineacetamide dihydrochloride; [4S-(4alpha,12aalpha)]-4,7- Bis(dimethylamino)-9-[[4-(dimethylamino)-1- oxobutyl]amino]-1,4,4a,5,5a,6,11,12a-octahydro- 3,10,12,12a-tetrahydroxy-1,11-dioxo-2- napthacenecarboxamide dihydrochloride; [4S- (4alpha,12aalpha)]-9-[[(Butylmethylamino)acetyl] amino]-4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11, 12a-octahydro-3,10,12,12a-tetrahydroxy-1,11- dioxo-2-naphthacenecarboxamide dihydrochloride; [4S-(4alpha,12aalpha)]-4,7-Bis(dimethylamino)- 1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a- tetrahydroxy-1,11-dioxo-9-[[(pentylamino)acetyl] amino]-2-naphthacenecarboxamide dihydrochloride; [4S-(4alpha,12aalpha)]-4,7-Bis(dimethylamino)- 1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a- tetrahydroxy-1,11-dioxo-9-[[[(phenylmethyl)amino]acetyl]amino] -2-naphthacenecarboxamide dihydrochloride; [7S-(7alpha,10aalpha)]-N-[2-[[9- (Aminocarbonyl)-4,7-bis(dimethylamino)-5,5a,6,6a, 7,10a,12-octahydro-1,8,10a,11-tetrahydroxy-10,12- dioxo-2-naphthacenyl]amino]-2-oxoethyl]glycine; [4S-(4alpha,12aalpha)]-4,7-Bis(dimethylamino)-9- [[(dimethylamino)acetyl]amino]-1,4,4a,5,5a,6,11, 12a-octahydro-3,10,12,12a-tetrahydroxy-1,11- dioxo-N-(1-pyrrolidinylmethyl)-2- naphthacenecarboxamide; [4S-(4alpha,12aalpha)]- 4,7-Bis(dimethylamino)-9-[[(dimethylamino)acetyl] amino]-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12, 12a-tetrahydroxy-1,11-dioxo-N-(4- morpholinylmethyl)-2-naphthacenecarboxamide; [4S-(4alpha,12aalpha)]-4,7-Bis(dimethylamino)-9- [[(dimethylamino)acetyl]amino]-1,4,4a,5,5a,6,11, 12a-octahydro-3,10,12,12a-tetrahydroxy-1,11- dioxo-N-(1-piperidinylmethyl)-2- naphthacenecarboxamide; [7S-(7alpha,10aalpha)]-N- [9-(Aminocarbonyl-4,7-bis(dimethylamino)-5,5a,6, 6a,7,10,10a,12-octahydro-1,8,10a,11-tetrahydroxy- 10,12-dioxo-2-napthacenyl]-1-azetidineacetamide; [4S-(4alpha,12aalpha)]-9-[[(Cyclobutylamino) acetyl]amino]-4,7-bis(dimethylamino)-1,4,4a,5,5a, 6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11- dioxo-2-naphthacenecarboxamide hydrochloride."

III. The Examining Division held that claims 1 and 11 did not meet the requirements of Article 84 EPC. More particularly, the Examining Division considered claim 1 to be unclear since it was not possible to establish with absolute certainty within a reasonable time whether any single compound fell within the scope of that claim due to Markush formulae formulated in a complex manner. Problems arose from the enormous length of the claim, the large number of variables often defined in terms of further variables and the manifold provisos. To combine these features caused the mental processes, which determined whether a compound was covered by the claim, to break down in confusion rendering it impossible for the claim to define the matter for which protection is sought. The complexity of a claim could not be increased indefinitely and still meet the requirements of Article 84 EPC. In such a case it must be possible to declare the claim prima facie unclear. With regard to claim 11 the long list of complex chemical names in that claim presented an undue burden on the person trying to establish whether a compound fell within the scope of that claim.

IV. The Appellant (Applicant) submitted that claims 1 and 11. did not lack clarity as stipulated by Article 84 EPC. More particularly, neither the complexity of the claims nor the time needed by a reader to establish whether or not a single compound fell within the scope of the claims were issues to be considered pursuant to Article 84 EPC. Claim 1 showed a clear and concise hierarchical construction which prevented any confusion of the skilled reader. The two polycyclic formulae of claim 1 had only four substituents (R, X, R5, R6). The substituent X had a very brief definition over 13 lines. The substituent R was defined hierarchically on the basis of the provisos:

(A) R = R4(CH2)nCO- and n=0, or

(B) R = R4(CH2)nCO- and n=1-4, or

(C) R = R4'(CH2)nSO2- and n = 0, or

(D) R = R4'(CH2)nSO2- and n= 1-4.

Those provisos were further defined on one to two pages each. Finally the substituents R5 and R6 were then defined on 3/4 of a page. Claim 11 had been written in accordance with standard chemical nomenclature which could not cause any lack of clarity.

V. The Appellant requested that the decision under appeal be set aside and that the case be remitted to the Examining Division for further prosecution. Auxiliarily he requested that oral proceedings be appointed in case the request was not held allowable.