Claims
- 1. A compound having the formula:
- 2. The compound according to claim 1, wherein segment P is a nucleoside base or analog or derivative thereof.
- 3. The compound according to claim 2, wherein segment P is selected from the group consisting of uracil linked through the 3-position; isocytosine linked through the 3-position; guanine linked through the 7-, 8- or 9-position; adenine linked through the 7-, 8- or 9-position; 3-deazaguanine linked through the 7-, 8- or 9-position; 2-pyridone linked through the 3- or 4-position, and the 2-aminopyridine linked through the 3- or 4-position to the L linking segment or, in the absence of L, directly to the T segment.
- 4. The compound according to claim 2, wherein the segment P is selected from the group consisting of uracil substituted with an optionally substituted phenylamino or benzylamino at the 6-position; isocytosine substituted with an optionally substituted phenylamino or benzylamino in the 6-position; guanine substituted with an optionally substituted phenyl or benzyl on the N2-position; adenine substituted with an optionally substituted phenylamino or benzylamino in the 2-position, and 2-aminopyridine linked through the 3- or 4-position to the L linking segment or, in the absence of L, directly to the T segment.
- 5. The compound according to claim 4, wherein the optionally substituted phenylamino, phenyl, benzylamino, or benzyl is substituted in the 3-position by lower alkyl, lower alkenyl, lower alkynyl or halo and/or substituted in the 4-position by lower alkyl, lower alkenyl, lower alkynyl or halo, or positions 3 and 4 are linked to form a fused 5 or 6 membered carbocyclic ring, which is saturated, unsaturated, or aromatic.
- 6. A compound having formula (1) or (2):
- 7. A compound having any one of the formulas (3), (4), (5), (6), (7), and (8), as indicated below:
- 8. The compound of any one of formulas (3)-(8) according to claim 7, wherein:
Y is absent or CH2; and Z is phenyl optionally substituted with 1-3 substituents independently selected from the group of substituents consisting of aryl, lower alkyl, lower alkenyl, lower alkynyl, lower alkoxy, lower alkyloxyalkyl, lower arylalkyl, halo, hydroxy, nitro, amino, and a substituent formed by two adjacent positions linked to form a fused 4, 5, or 6 membered carbocyclic ring, which may be saturated, unsaturated, or aromatic.
- 9. The compound according to claim 8, wherein:
Z is phenyl substituted with 1 or 2 substituents independently selected from the group consisting of lower alkyl, lower alkenyl, lower alknyl, halo, hydroxy, and amino, and a substituent formed by two adjacent positions linked to form a fused 4, 5, or 6 membered carbocyclic ring, which may be saturated, unsaturated, or aromatic.
- 10. The compound according to claim 9, wherein:
Z is a phenyl substituted in the 3- and 4-position with substituents independently selected from the group consisting of aryl, lower alkyl, lower alkenyl, lower alkynyl, lower alkoxy, lower alkyloxyalkyl, lower arylalkyl, halo, hydroxy, and amino.
- 11. The compound according to claim 10, wherein:
Z is phenyl substituted in the 3- and 4-position with independently selected lower alkyl substituents.
- 12. The compound according to claim 11, wherein Z is 3-ethyl, 4-methyl phenyl.
- 13. The compound according to claim 7, wherein the compound has formula (3) or (4), wherein:
Y is CH2 and Z is phenyl substituted with 1 or 2 substituents independently selected from lower alkyl, lower alkenyl, lower alknyl, halo, hydroxy and amino; or wherein two adjacent positions may be linked to form a fused 4, 5, or 6 membered carbocyclic ring which may be saturated, unsaturated, or aromatic.
- 14. The compound according to claim 13, wherein the compound has formula (3) or (4), wherein Z is 3-methyl, 4-ethyl phenyl.
- 15. The compound according to claim 7, wherein the pyridone of segment of A-B is a quinolone.
- 16. The compound according to claim 15, wherein the quinolone is selected from the group consisting of consisting of a 4-quinolone-3-carboxylic acid; 4-pyridone-3-carboxylic acid; 8-aza-4-quinolone-3-carboxylic acid; 6-aza-4-quinolone-3-carboxylic acid; 6,8-diaza-4-quinolone-3-carboxylic acid; 4-quinazolinone-3-carboxylic acid; halo substituted forms thereof; and esters thereof.
- 17. The compound according to claim 15, wherein the quinolone is a fluoroquinolone.
- 18. The compound according to claim 7, wherein the compound has any one of the formulas (1)-(8), wherein the segment A-B- is any one of the pyridone radicals of formulas (9), (10), and (11), below:
- 19. The compound according to claim 18, wherein R8 and R9 are, independently, halo.
- 20. The compound according to claim 19, wherein the halogen is is fluorine (F).
- 21. The compound according to claim 18, wherein the lower alkyl is methyl.
- 22. The compound according to claim 18, wherein an amino group is NH2.
- 23. The compound according to claim 18, wherein the compound has any one of (1)-(8), wherein the segment A-B is a pyridone radical having any one of formulas (9), (10), or (11), wherein:
X is N; R1 is selected from the group consisting of optionally substituted lower alkyl, lower cycloalkyl and phenyl; R2 is selected from the group consisting of optionally substituted piperidinyl, pyrrolidinyl and piperazinyl heterocycles optionally fused with a 3-6 membered carbocycle or heterocycle; R3 is N or a ring carbon substituted with substituent R8, wherein R8 is selected from the group consisting of H, amino, halo, unsubstituted aryl, aryl substituted with halo, unsubstituted alkyl, alkyl substituted with halo; or R1 and R8 are joined to form an optionally substituted, fused 4-6 membered heterocyclic or carbocyclic ring, which is saturated, unsaturated, or aromatic, wherein the heterocyclic ring comprises 1-3 heteroatoms selected from the group consisting of S, N and O; R4 is N or a ring carbon substituted with substituent R9, wherein R9 is selected from the group consisting of H, amino, halo, unsubstituted aryl, aryl substituted with halo, unsubstituted alkyl, alkyl substituted with halo; or R1 and R8 may be joined to form an optionally substituted, fused 4-6 membered heterocyclic or carbocyclic ring, which is saturated, unsaturated, or aromatic, wherein the heterocyclic ring comprises 1-3 heteroatoms selected from the group consisting of S, N and O; R5 is selected from the group consisting of H, halo, NH2, and lower alkyl; and R6 is N or a ring carbon substituted with substituent R7, wherein R7 is selected from the group consisting of H, halo and lower alkyl; or R1 and R7 are joined to form an optionally substituted 5-6 membered heterocycle comprising 1-3 heteroatoms selected from the group consisting of S, N and O.
- 24. The compound according to claim 23, wherein R8 and R9 are, independently, halo.
- 25. The compound according to claim 24, wherein the halogen is fluorine (F).
- 26. The compound according to claim 23, wherein the lower alkyl of R5 is methyl.
- 27. The compound according to claim 18, wherein the compound has any one of formulas (1)-(8), wherein the segment A-B which is a pyridone radical having any one of formulas (9), (10), or (11), wherein:
X is N; R1 is selected from the group consisting of ethyl, fluoroethyl, cyclopropyl, 4-fluorophenyl or 2,4-difluorophenyl; R2 is selected from the group consisting of: 67optionally fused with a 3-6 membered carbocycle or heterocycle, and wherein each Ra and Rb is independently selected from the group consisting of H and lower alkyl, and Rc is selected from the group consisting of H, lower alkyl, and a chain of 1-6 amino acid residues; R3 is N or a ring carbon substituted with substituent R8, wherein R8 is selected from the group consisting of H, halo, unsubstituted alkyl, aryl substituted with halo, unsubstituted alkyl, alkyl substituted with halo; R4 is N or a ring carbon substituted with substituent R9, wherein R9 is selected from the group consisting of H, halo, unsubstituted alkyl, aryl substituted with halo, unsubstituted alkyl, alkyl substituted with halo; R5 is selected from the group consisting of H, halo, NH2, and methyl; and R6 is N or a ring carbon substituted with substituent R7, wherein R7 is selected from the group consisting of H, halo and lower alkyl; or R1 and R7 are joined to form an optionally substituted 6 membered heterocycle comprising 1-3 heteroatoms selected from the group consisting of S, N and O.
- 28. The compound according to claim 27, wherein R2 of the compound is selected from the group consisting of:
- 29. A compound selected from the group consisting of:
3-{4-[1-(1-ethyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[1-(1-ethyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl]butyl}-6-(3-ethyl-4-methylanilino)uracil hydrochloride 3-{4-[1-(1-ethyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl]butyl}-6-(3-ethyl-4-methylanilino)uracil methanesulfonate 3-{4-[1-(1-ethyl-3-carboxy-4-oxo-6-fluoro-8-chloro-7-quinolyl)-4-piperazinyl]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[1-(1-ethyl-3-carboxy-4-oxo-6-fluoro-8-aza-7-quinolyl)-4-piperazinyl]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[1-(1-ethyl-3-carboxy-4-oxo-6,8-difluoro-7-quinolyl)-4-piperazinyl]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{7-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl]heptyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-amino]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl]butyl}-6-(3-ethyl-4-methylanilino)uracil methanesulfonate 3-{2-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl]ethoxyethyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[1-(1-{2,4-difluorophenyl}-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[1-(1-{2-hydroxyethyl}-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[1-(1-{4-fluorophenyl}-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{5-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl]pentyl}-6-(3-ethyl-4-methylanilino)uracil 3-{5-[1-(1-ethyl-3-carboxy-4-oxo-6-fluoro-8-aza-7-quinolyl)-4-piperazinyl]pentyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[1-(1-tert-butyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[1-(1-{2,4-difluorophenyl}-3-carboxyl-4-oxo-6-fluoro-8-methoxy-7-quinolyl)-4-piperazinyl]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl]butyl}-6-(3-ethyl-4-methylanilino)isocytosine 9-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl]butyl}-N2-(3-ethyl-4-methylphenyl)guanine 3-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl]butyl}-6-(3-ethyl-4-methylanilino)uracil hydrochloride 3-{4-[1-(1-{ethyl}-3-carboxy-4-oxo-6-fluoro-8-methoxy-7-quinolyl)-4-piperazinyl]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[1-(1-{cyclopropyl}-3-carboxy-4-oxo-6-fluoro-8-methoxy-7-quinolyl)-4-piperazinyl]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[3-(1-ethyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)aminomethyl-1-pyrrolidinyl]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[3-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)aminomethyl-1-pyrrolidinyl]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[3-(1-(2,4-difluorophenyl)-3-carboxy-4-oxo-6-fluoro-7-quinolyl)aminomethyl-1-pyrrolidinyl]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[1-(1-ethyl-3-carboxy-4-oxo-6-pyridyl)-4-piperazinyl]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-pyridyl)-4-piperazinyl]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[1-(1-{2,4-difluorophenyl}-3-carboxy-4-oxo-6-pyridyl)-4-piperazinyl]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[3-(1-ethyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)aminomethyl-1-pyrrolidinyl]butyl}-6-(3-ethyl-4-methylanilino)isocytosine 3-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)aminomethyl-1-pyrrolidinyl]butyl}-6-(3-ethyl-4-methylanilino)isocytosine 3-{4-[1-(1-{2,4-difluorophenyl}-3-carboxy-4-oxo-6-fluoro-7-quinolyl)aminomethyl-1-pyrrolidinyl]butyl}-6-(3-ethyl-4-methylanilino)isocytosine 3-{4-[1-(1-ethyl-3-carboxy-4-oxo-6-pyridyl)-4-piperazinyl]butyl}-6-(3-ethyl-4-methylanilino)isocytosine 3-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-pyridyl)-4-piperazinyl]butyl}-6-(3-ethyl-4-methylanilino)isocytosine 3-{4-[1-(1-{2,4-difluorophenyl}-3-carboxy-4-oxo-6-pyridyl)-4-piperazinyl]butyl}-6-(3-ethyl-4-methylanilino)isocytosine 9-{4-[1-(1-ethyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl]butyl}-N2-(3-ethyl-4-methylphenyl)guanine 9-{5-[1-(1-[2,4-difluorophenyl}-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl]pentyl}-N-2-(3-ethyl-4-methylphenyl)guanine 9-{5-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-8-aza-7-quinolyl)-4-piperazinyl]pentyl}-N2-(3-ethyl-4-methylphenyl)guanine 9-{5-[1-(1-ethyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl]pentyl}-2-(3-ethyl-4-methylanilino)adenine 9-{5-[1-(1-[2,4-difluorophenyl}-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl]pentyl}-2-(3-ethyl-4-methylanilino)adenine 9-{5-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-8-aza-7-quinolyl)-4-piperazinyl]pentyl}-2-(3-ethyl-4-methylanilino)adenine 3-{5-[1-(1-ethyl-3-carboxy-4-oxo-6-fluoro-8-methoxy-7-quinolyl)-4-piperazinyl]pentyl}-6-(3-ethyl-4-methylanilino)uracil 3-{5-[1-(1-{cyclopropyl}-3-carboxy-4-oxo-6-fluoro-8-methoxy-7-quinolyl)-4-piperazinyl]pentyl}-6-(3-ethyl-4-methylanilino)uracil 3-{5-[3-(1-ethyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)aminomethyl-1-pyrrolidinyl]pentyl}-6-(3-ethyl-4-methylanilino)uracil 3-{5-[3-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)aminomethyl-1-pyrrolidinyl]pentyl}-6-(3-ethyl-4-methylanilino)uracil 3-{5-[3-(1-(2,4-difluorophenyl)-3-carboxy-4-oxo-6-fluoro-7-quinolyl)aminomethyl-1-pyrrolidinyl]pentyl}-6-(3-ethyl-4-methylanilino)uracil 3-{5-[1-(1-ethyl-3-carboxy-4-oxo-6-pyridyl)-4-piperazinyl]pentyl}-6-(3-ethyl-4-methylanilino)uracil 3-{5-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-pyridyl)-4-piperazinyl]pentyl}-6-(3-ethyl-4-methylanilino)uracil 3-{5-[1-(1-{2,4-difluorophenyl}-3-carboxy-4-oxo-6-pyridyl)-4-piperazinyl]pentyl}-6-(3-ethyl-4-methylanilino)uracil 3-{5-[3-(1-ethyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)aminomethyl-1-pyrrolidinyl]pentyl}-6-(3-ethyl-4-methylanilino)isocytosine 3-{5-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)aminomethyl-1-pyrrolidinyl]pentyl}-6-(3-ethyl-4-methylanilino)isocytosine 3-{5-[1-(1-{2,4-difluorophenyl}-3-carboxy-4-oxo-6-fluoro-7-quinolyl)aminomethyl-1-pyrrolidinyl]pentyl}-6-(3-ethyl-4-methylanilino)isocytosine 3-{5-[1-(1-ethyl-3-carboxy-4-oxo-6-pyridyl)-4-piperazinyl]pentyl}-6-(3-ethyl-4-methylanilino)isocytosine 3-{5-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-pyridyl)-4-piperazinyl]pentyl}-6-(3-ethyl-4-methylanilino)isocytosine 3-{5-[1-(1-{2,4-difluorophenyl}-3-carboxy-4-oxo-6-pyridyl)-4-piperazinyl]pentyl}-6-(3-ethyl-4-methylanilino)isocytosine. 3-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl]butyl}-6-(3-chloro-4-methylanilino)uracil 3-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl]butyl}-6-(3,4-dimethylanilino)uracil 3-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl]butyl}-6-(3-ethylanilino)uracil 3-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl]butyl}-6-(5-indanylamino)uracil 3-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl]butyl}-6-(3,4-dichlorobenzylamino)uracil 3-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-(2-methylpiperazinyl)]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6,8-difluoro-7-quinolyl)-4-(3-methylpiperazinyl)]butyl}-6-(3-ethyl-4-methylanilino)uracil (S)-3-{4-[-(1-cyclopropyl-3-carboxy-4-oxo-6,8-difluoro-7-quinolyl)-4-(3-methylpiperazinyl)]butyl}-6-(3-ethyl-4-methylanilino)uracil (R)-3-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6,8-difluoro-7-quinolyl)-4-(3-methylpiperazinyl)]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-8-methoxy-7-quinolyl)-4-(3-methylpiperazinyl)]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[1-(1-{2,4-difluorophenyl}-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-(3-methyl)piperazinyl]butyl}-6-(3-ethyl-4-methylanilino)uracil 7-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl]butyl}-N2-(3-ethyl-4-methylphenyl)guanine 7-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl]butyl}-2-(3-ethyl-4-methylanilino)adenine 3-{[1-(1-ethyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl]carboxamido}-6-(3-ethyl-4-methylanilino)-2-pyridone 3-{4-[1-(1-ethyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl]butyl}-6-(3-ethyl-4-methylanilino)-2-pyridone 3-{4-[1-(1-ethyl-3-carboxy-4-oxo-6,8-diaza-7-quinolyl)-4-piperazinyl]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{5-[1-(1-ethyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-3-(1,3-diazabicyclononyl)]pentyl}-6-(3-ethyl-4-methylanilino)uracil 3-{5-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-3-(1,3-diazabicyclooctyl)]pentyl}-6-(3-ethyl-4-methylanilino)uracil 3-{5-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-3-(1,3-diazabicyclononyl)]pentyl}-6-(3-ethyl-4-methylanilino)uracil 3-{5-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-3-(pyrrolidinylamino)]pentyl}-6-(3-ethyl-4-methylanilino)uracil 3-{5-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-3-(5-oxa-1,3-diazabicyclononyl)]pentyl}-6-(3-ethyl-4-methylanilino)uracil 3-{5-[1-(1-ethyl-3-carboxy-4-oxo-6,8-difluoro-7-quinolyl)-3-(5-oxa-1,3-diazabicyclononyl)]pentyl}-6-(3-ethyl-4-methylanilino)uracil 3-{5-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-(1,4-diazabicyclooctyl)]pentyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-3-(5-oxa-1,3-diazabicyclononyl)]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{5-[1-(1-ethyl-3-carboxy-4-oxo-6,8-difluoro-7-quinolyl)-3-(1,3-diazabicyclononyl)]pentyl}-6-(3-ethyl-4-methylanilino)uracil. 3-{4-[1-(1-{2,4-difluorophenyl}-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-(3-methylpiperazinyl)]butyl}-6-(3-ethyl-4-methylanilino)uracil (R)-3-{4-[1-(1-{2,4-difluorophenyl}-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-(3-methylpiperazinyl)]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6,8-difluoro-7-quinolyl)-4-(3-hydroxymethylpiperazinyl)]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6,8-difluoro-7-quinolyl)-4-(3-methylpiperazinyl)]butyl}-6-(5-indanylamino)uracil 3-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6,8-difluoro-7-quinolyl)-4-(3-methylpiperazinyl)]butyl}-6-(3-chloro-4-methylanilino)uracil 3-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6,8-difluoro-7-quinolyl)-4-(3-methylpiperazinyl)]butyl}-6-(3,4-dimethylanilino)uracil (R)-3-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-(3-methylpiperazinyl)]butyl}-6-(3-ethyl-4-methylanilino)uracil (R)-3-{4-[-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-(3-methylpiperazinyl)]butyl}-6-(3,4-dimethylanilino)uracil (S)-3-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-(3-methylpiperazinyl)]butyl}-6-(3,4-dimethylanilino)uracil (R)-3-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6,8-difluoro-7-quinolyl)-4-(3-methylpiperazinyl)]butyl}-6-(3,4-dimethylanilino)uracil (S)-3-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6,8-difluoro-7-quinolyl)-4-(3-methylpiperazinyl)]butyl}-6-(3,4-dimethylanilino)uracil (S)-3-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-7-quinolyl)-4-(3-methylpiperazinyl)]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6,8-difluoro-7-quinolyl)-4-(piperazinyl)]butyl}-6-(3,4-dimethylanilino)uracil 3-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-8-methoxy)-7-quinolyl)-4-(3-methylpiperazinyl)]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6-fluoro-8-methoxy)-7-quinolyl)-4-(3-methylpiperazinyl)]butyl}-6-(3,4-dimethylanilino)uracil 3-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-6,8-difluoro-7-quinolyl)-4-(3-carboxypiperazinyl)]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-7-quinolyl)-4-piperazinyl]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[1-(1-allyl-3-carboxy-4-oxo-7-quinolyl)-4-piperazinyl]butyl}-6-(3-ethyl-4-methylanilino)uracil (R)-3-{4-[1-(1-cyclopropyl-3-carboxy-4-oxo-7-quinolyl-8-difluoromethoxy)-4-(3-methylpiperazinyl)]butyl}-6-(3-ethyl-4-methylanilino)uracil (R)-3-{4-[2-(1-cyclopropyl-3-carboxy-4-oxo-7-quinolyl-8-difluoromethoxy)-2,3-dihydro-1-methyl-isoindol-5-yl)]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[1-(1-ethyl-3-carboxy-4-oxo-6,8-diaza-7-quinolyl)-4-(3-methyl piperazinyl)]butyl}-6-(3-ethyl-4-methylanilino)uracil.
- 30. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier.
- 31. The pharmaceutical composition according to claim 30, further comprising an additional compound selected from the group consisting of an antibiotic, an antiviral compound, anti-cancer compound, a vitamin, a trace metal, and combinations thereof.
- 32. A method of therapeutically treating a bacterial disease in a patient in need of treatment thereof comprising administering to the patient a pharmaceutical composition according to claim 30.
- 33. A method of treating a patient to prevent a bacterial disease comprising administering to the patient a pharmaceutical composition according to claim 30.
- 34. A method of inhibiting or reducing the activity of DNA polymerase IIIC in a patient in need of treatment thereof comprising administering to the patient a pharmaceutical composition according to claim 30.
- 35. A method of inhibiting or reducing the activity of bacterial type II topoisomerase in a patient in need of treatment thereof comprising administering to the patient a pharmaceutical composition according to claim 30.
- 36. A method of determining the antibiotic resistance profile of a bacterial species of interest comprising testing the ability of cells of the bacterial species of interest to grow on a growth medium supplemented with a compound according to claim 1.
- 37. A kit comprising a compound according to claim 1 and instructions describing use of the compound in treating a bacterial disease.
- 38. A kit comprising a compound according to claim 1 and instructions describing use of the compound for inhibiting a DNA polymerase IIIC and/or type II topoisomerase.
- 39. A compound selected from the group consisting of:
3-{4-[1-(1-cyclopropyl-3-ethoxycarbonyl-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{2-[1-(1-cyclopropyl-3-benzyloxycarbonyl-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl] ethoxyethyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[1-(1-cyclopropyl-3-ethoxycarbonyl-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl]butyl}-6-anilinouracil 3-{4-[1-(1-{2,4-difluorophenyl}-3-ethoxycarbonyl-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[1-(1-{2-hydroxyethyl}-3-ethoxycarbonyl-4-oxo-6,8-difluoro-7-quinolyl)-4-piperazinyl]butyl}-6-(3-ethyl-4-methylanilino)uracil 3-{4-[1-(1-{4-fluorophenyl}-3-ethoxycarbonyl-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl]butyl}-6-(3-ethyl-4-methylanilino)uracil and 9-{4-[1-(1-cyclopropyl-3-ethoxycarbonyl-4-oxo-6-fluoro-7-quinolyl)-4-piperazinyl]butyl}-2-(3-ethyl-4-methylanilino)-6-iodopurine.
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit under 35 U.S.C. §119(e) of U.S. provisional application No. 60/298,534, filed Jun. 15, 2001; U.S. provisional application No. 60/348,839, filed Jan. 14, 2002; and U.S. provisional application No. 60/349,837, filed Jan. 17, 2002.
STATEMENT AS TO FEDERALLY SPONSORED RESEARCH
[0002] The invention described herein was supported in whole or in part by SBIR grant number 1 R43 GM60828-01 from the National Institutes of Health. The United States Government may have certain rights in the invention.
Provisional Applications (3)
|
Number |
Date |
Country |
|
60298534 |
Jun 2001 |
US |
|
60348839 |
Jan 2002 |
US |
|
60349837 |
Jan 2002 |
US |