Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1995-03-01
1997-04-29
Trinh, Ba K.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
548525, 549285, 549287, 549289, A61K 3140, C07D40502, C07D40510
Patent
active
056249519
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/U.S. 93/06308, dated Jul. 7, 1993.
The present application relates to 4-hydroxycoumarin derivatives and pharmaceutical compositions comprising such compounds. The compounds are useful as antibacterial agents.
U.S. Pat. No. 4,078,075 refers to a 3-N-(4-trifluoromethylphenyl)-carbamoyl-4-hydroxy-coumarin compound useful in combating insect pests particularly of the species Hellothis virescens.
U.S. Pat. No. 3,511,892 refers to a 3-(4-aminophenyl)carbamoyl)-4-hydroxycoumarin compound useful as bactericides and fungicides for the control of a wide variety of organisms such as Staphylococcus aureus, Bacillus subtilis, Mycobacterium phlet, Salmonella typhosa, Aerobacter aerogenes, Escherichia coli, Trichophyton mentagrophytes, Pullularia pullulans and Cundida alpicans and other fungal organisms such as downey mildew and tomato late blight.
U.S. Pat. No. 3,112,557 refers to 4,5,7-trihydroxycoumarin-3-N-phenylcarboxamide and 4-hydroxy-6-methyl-2-alpha-pyrone-3-(N-p-hydroxyphenyl)-carboxamide, 4-hydroxy-5:6-benzo-2-alpha-pyrone-3-(N-p-hydroxyphenyl)-carboxamide compounds useful for their antibacterial or fungicidal activity in human or veterinary therapy.
The present invention relates to compounds of the formula ##STR2## wherein R.sup.1 is hydrogen, (C.sub.1 -C.sub.6)alkyl or halogen; R.sup.2 is hydrogen, halogen, nitro, amino, (C.sub.1 -C.sub.6)alkoxy or (C.sub.1 -C.sub.6)alkylthio; R.sup.3 is hydrogen, halogen, hydroxy, nitro, amino or (C.sub.1 -C.sub.6)alkoxy; R.sup.4 is hydrogen, halogen, (C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkoxy, amino or nitro; R.sup.5, R.sup.6, R.sup.7, and R.sup.8 are each independently selected from the group consisting of hydrogen, halogen, (C.sub.1 -C.sub.6)alkenyl, (C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)haloalkyl, (C.sub.1 -C.sub.3)alkoxy, phenyl(C.sub.1 -C.sub.6)alkoxy, (C.sub.2 -C.sub.8)acyl, (C.sub.1 -C.sub.6)thioalkoxy, pyrrolyl, 2,5-dimethylpyrrolyl, imidazolyl, pyridinyl, pyrimidinyl or pyrazinyl with the proviso that when R.sup.6 is other than acyl, pyrrolyl, (C.sub.1 -C.sub.3)alkoxy or 2,5-dimethylpyrrolyl, or R.sup.8 is trifluoromethyl, at least one of R.sup.1, R.sup.2, R.sup.3 and R.sup.4 is not hydrogen.
More specific compounds of formula V are those wherein at least one of R.sup.5, R.sup.6, R.sup.7, and R.sup.8 is halogen, hydroxy, acyl or nitro, and at least one of R.sup.1, R.sup.2, R.sup.3 and R.sup.4 is not hydrogen, halogen, hydroxy or nitro.
Preferred compounds of the invention include 4-hydroxy-3-[4'-chlorophenyl)carbamoyl-4-hydroxy-6-methoxycoumarin, 4-hydroxy-3-[4'-methoxy-3'-(3"-methyl-2"-butenyl)phenyl]carbamoylcoumarin, 4-hydroxy-3-(4'-pyrrolyl-3'-trifluoromethylphenyl)carbamoylcoumarin, 7-chloro-4-hydroxy-3-(4'-trifluoromethylphenyl)carbamoylcoumarin.
More specific compounds of formula V are those wherein R.sup.6 is pyrrolyl, 2,5-dimethylpyrrolyl, imidazolyl, pyridinyl, pyrimidinyl or pyrazinyl.
More specific compounds of formula V are those wherein R.sup.1, R.sup.2, R.sup.4, R.sup.5 and R.sup.8 are hydrogen; those wherein R.sup.3 is hydrogen or chloro; those wherein R.sup.6 is trifluoromethyl, 2,5-dimethylpyrrolyl, pyrrolyl or methoxy and R.sup.7 is hydrogen, trifluoromethyl or 3-methyl-2-butenyl.
More specific compounds of formula V are those wherein R.sup.1, R.sup.2, R.sup.4, R.sup.5 and R.sup.8 are hydrogen.
The present invention also relates to an antibacterial composition comprising a compound of the formula V wherein R.sup.1 is hydrogen, (C.sub.1 -C.sub.6)alkyl or halogen; R.sup.2 is hydrogen, halogen, nitro, amino, (C.sub.1 -C.sub.6)alkoxyl or (C.sub.1 -C.sub.6)alkylthio; R.sup.3 is hydrogen, halogen, hydroxy, nitro, amino or (C.sub.1 -C.sub.6)alkoxy; R.sup.4 is hydrogen, halogen, (C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkoxy, amino or nitro; R.sup.5, R.sup.6, R.sup.7, and R.sup.8 are each independently selected from the group consisting of hydrogen, halogen, (C.sub.1 -C.sub.6)alkenyl, (C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)haloalkyl, (C.sub.1 -C.sub.3)alkoxy, phenyl(C.sub.1 -C.sub.6)alkoxy, (C.sub.2 -C
REFERENCES:
patent: 3511856 (1970-05-01), McIntyre et al.
Chemical Abstracts, No. 90675j, vol. 67, 1967.
Chemical Abstracts, No. 90676k, vol. 67, 1967.
Dutton Chris J.
Sutcliffe Joyce
Yang Bingwei
Creagan B. Timothy
Holtrust Gezina
Pfizer Inc.
Richardson Peter C.
Trinh Ba K.
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