Claims
- 1. A compound of the formula: ##STR28## wherein: Y is selected from (CH.sub.2).sub.n X, n=0-5, X is halogen selected from bromine, chlorine, fluorine and iodine;
- R 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 wherein the substitution is 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 wherein the 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.1 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 does not equal R.sup.1 the stereochemistry of the asymmetric carbon (i.e. the carbon bearing the Y substituent) maybe be either the racemate (DL) or the individual enantiomers (L or D); or a pharmacologically acceptable organic or inorganic salt or metal complex thereof.
- 2. The compound according to claim 1, wherein:
- Y is selected from (CH.sub.2).sub.n X, n=0-5, X is halogen selected from bromine, chlorine, fluorine and iodine;
- R 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; (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 wherein the substitution is 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.1 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 does not equal R.sup.1 the stereochemistry of the asymmetric carbon (i.e. the carbon bearing the Y substituent) maybe be either the racemate (DL) or the individual enantiomers (L or D); or a pharmacologically acceptable organic or inorganic salt or metal complex thereof.
- 3. The compound according to claim 1, wherein:
- Y is selected from (CH.sub.2).sub.n X, n=0-5, X is halogen selected from bromine, chlorine, fluorine and iodine;
- R 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 and .alpha.-mercaptopropyl; .alpha.-hydroxy(C.sub.1 -C.sub.4)alkyl group selected from hydroxymethyl, .alpha.-hydroxyethyl, .alpha.-hydroxy-1-methylethyl and .alpha.-hydroxypropyl; 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; (C.sub.7 -C.sub.9)aralkyl group selected from benzyl, 1-phenylethyl, 2-phenylethyl and phenylpropyl; R.sup.1 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 does not equal R.sup.1 the stereochemistry of the asymmetric carbon (i.e. the carbon bearing the Y substituent) maybe be either the racemate (DL) or the individual enantiomers (L or D); or a pharmacologically acceptable organic or inorganic salt or metal complex thereof.
- 4. The compound according to claim 1, wherein:
- Y is selected from (CH.sub.2).sub.n X, n=0-5, X is halogen selected from bromine, chlorine, fluorine and iodine; R is selected from hydrogen; straight or branched (C.sub.1 -C.sub.2)alkyl group selected from methyl and ethyl; R.sup.1 is selected from hydrogen and (C.sub.1 -C.sub.2)alkyl selected from methyl and ethyl;
- when R does not equal R.sup.1 the stereochemistry of the asymmetric carbon (i.e. the carbon bearing the Y substituent) maybe be either the racemate (DL) or the individual enantiomers (L or D); or a pharmacologically acceptable organic or inorganic salt or metal complex thereof.
- 5. The compound according to claim 1 wherein said inorganic salts comprise hydrochloric, hydrobromic, hydroiodic, phosphoric, nitric or sulfate.
- 6. The compound according to claim 1 wherein said organic salts comprise acetate, benzoate, citrate, cysteine or other amino acid, fumarate, glycolate, maleate, succinate, tartrate, alkylsulfonate or arylsulfonate.
- 7. The compound according to claim 1 wherein said metal complexes comprise aluminum, calcium, iron, magnesium, manganese or complex salts.
- 8. A compound according to claim 1, which is [4S-(4alpha,12aalpha)]-9-[(bromoacetyl)amino]-4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide monohydrochloride.
- 9. A compound according to claim 1, which is [4S-(4alpha,12aalpha)]-9-[(chloroacetyl)amino]-4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide monohydrochloride.
- 10. A compound according to claim 1, which is [4S-(4alpha,12aalpha)]-9-[(bromoacetyl)amino]-4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide monohydrobromide.
- 11. A compound according to claim 1, which is [4S-(4alpha,12aalpha)]-9-[(bromoacetyl)amino]-4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12.12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide monosulfate.
- 12. A compound according to claim 1, which is [4S-(4alpha,12aalpha)]-9-[(2-bromo-1-oxopropyl)amino]-4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10-12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide monohydrobromide.
- 13. A compound according to claim 1, which is [4S-(4alpha,12aalpha)]-9-[(2-Bromo-2-methyl-1-oxopropyl)amino]-4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide hydrobromide.
- 14. A compound according to claim 1, which is [4S-(4alpha,12aalpha)]-9-[(2-Bromo-1-oxobutyl)amino]-4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide hydrobromide.
- 15. A compound according to claim 1, which is [4S-(4alpha,12aalpha)]-9-[(2-Bromo-1-oxopentyl)amino]-4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide hydrobromide.
- 16. A compound according to claim 1, which is [4S-(4alpha,12aalpha)]-9-[(2-Bromo-1-oxobutyl)amino]-4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide hydrobromide.
- 17. A compound according to claim 1, which is [4S-(4alpha,12aalpha)]-9-[(2-Bromo-3-hydroxy-1-oxopropyl)amino]-4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide hydrobromide.
- 18. A compound according to claim 1, which is [4S-(4alpha,12aalpha)]-9-[(2-Bromo-3-mercapto-1-oxopropyl)amino]-4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide hydrobromide.
- 19. A compound according to claim 1, which is [7S-(7alpha,10aalpha)]-4-[[9-(Aminocarbonyl)-7-(dimethylamino)-5,5a,6,6a,7,10,10a,12-octahydro-1,8,10a,11-tetrahydroxy-10-12-dioxo-2-naphthacenyl]amino]-3-bromo-4-oxobutanoic acid hydrobromide.
- 20. A compound according to claim 1, which is [7S-(7alpha,10aalpha)]-5-[[9-(Aminocarbonyl)-7-(dimethylamino)-5,5a,6,6a,7,10,10a,12-octahydro-1,8,10a-11-tetrahydroxy-10,12-dioxo-2-naphthacenyl]amino]-4-bromo-5-oxopentanoic acid hydrobromide.
- 21. A compound according to claim 1, which is [4S-(4alpha,12aalpha)]-9-[(Bromophenylacetyl)amino]-4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide hydrobromide.
- 22. A compound according to claim 1, which is [4S-(4alpha,12aalpha)]-9-[[Bromo(4-hydroxyphenyl)acetyl]amino]-4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide hydrobromide.
- 23. A compound according to claim 1, which is [4S-(4alpha,12aalpha)]-9-[[Bromo(4-methoxyphenyl)acetyl]amino]-4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide hydrobromide.
- 24. A compound according to claim 1, which is [4S-(4alpha,12aalpha)]-9-[[Bromo[4-(trifluoromethyl)phenyl]acetyl]amino]-4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide hydrobromide.
- 25. A compound according to claim 1, which is [4-S-(4alpha,12aalpha)]-9-[[Bromo[4-(dimethylamino)phenyl]acetyl]amino]-4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide hydrobromide.
Parent Case Info
This is a divisional of application Ser. No. 07/928,590 filed on Aug. 13, 1992 now U.S. Pat. No. 5,442,059.
US Referenced Citations (33)
Divisions (1)
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Number |
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928590 |
Aug 1992 |
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