Organic compounds -- part of the class 532-570 series – Organic compounds – Unsubstituted hydrocarbyl chain between the ring and the -c-...
Patent
1989-08-24
1991-03-19
Berch, Mark L.
Organic compounds -- part of the class 532-570 series
Organic compounds
Unsubstituted hydrocarbyl chain between the ring and the -c-...
540364, A61K 3164, C07D20585, C07D40114
Patent
active
050012355
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention encompasses novel 2-azetidinone compounds which have useful antimicrobial activity.
INFORMATION DISCLOSURE
Derivatives of 2-azetidinone which have antimicrobial and .beta.-lactamase inhibitory activity are known in the art. European Patent Applications Nos. 0053815, 0053816, 0076758, and 0096297 disclose .beta.-lactams with various substituents at the C.sub.4 position of the ring. European Patent Application No. 0053816 discloses 2-azetidinone compounds substituted at the C.sub.4 position with an organic residue.
Abstracts from papers presented by Squibb Institute for Medical Research at the 25th and 26th Interscience Conferences on Antimicrobial Agents and Chemotherapy disclose antibacterial compounds with a substituted-sulfonylaminocarbonyl group at the N-1 position and a 2-(2-amino-4-thiazolyl)-2-(1-carboxy-1-methylethoxy)-iminoacetamido group at the C.sub.3 position.
U.S. Pat. No. 4,587,047, filed Apr. 1, 1982, issued May 6, 1986, discloses substituted sulfonylaminocarbonyl-2-azetidinones. U.S. patent application Ser. No. 444,771, filed Nov. 26, 1982 and European Patent Application No. 0085291, filed Mar. 1, 1983, published Oct. 8, 1983, disclose substituted sulfonylaminocarbonyl-2-azetidinones containing a terminal substituted heterocycle in the sulfonylaminocarbonyl activating group. U.K. Patent Application No. 8623151, filed Sept. 26, 1986, and Belgium Patent No. 905502A disclose sulfonylaminocarbonyl-2-azetidinones containing an imidazolidonylaminocarbonyl-1,4-dihydro-5-hydroxy-4-oxo-2-pyridinone in the activating group.
SUMMARY OF THE INVENTION
The present invention teaches novel 2-azetidinone analogs useful as microbial growth inhibitors. This invention includes enantiomers, diastereomeric and racemic mixtures of these compounds. Intermediates and processes for preparing these compounds are also disclosed.
Novel 2-azetidinone analogs within the scope of this invention are represented by Formula I and pharmacologically acceptable salts thereof; wherein R.sub.10 and R.sub.15 are the same or different and are hydrogen, (C.sub.1 -C.sub.8) alkyl, (C.sub.2 -C.sub.8) alkenyl, (C.sub.2 -C.sub.8) alkynyl, (C.sub.3 -C.sub.8) cycloalkyl, phenyl optionally substituted with between 1 and 3 substituents selected from the group consisting of halogen, nitro, (C.sub.1 -C.sub.4)-alkyl, and (C.sub.1 -C.sub.4)alkoxy, benzyl optionally substituted with between 1 and 3 substituents selected from the group consisting of halogen, nitro, (C.sub.1 -C.sub.4)alkyl, and (C.sub.1 -C.sub.4)alkoxy, --CH.sub.2 OCOCH.sub.2 NHR.sub.4, --CH.sub.2 OCO.sub.2 R.sub.30, --CH.sub.2 F, or --CHF.sub.2 ; wherein R.sub.4 is hydrogen, --COH or --CO--O--C(CH.sub.3).sub.3 ; wherein R.sub.30 is (C.sub.1 -C.sub.8)alkyl, --(CH.sub.2).sub.2 NH.sub.2, --(CH.sub.2).sub.2 NH(CH.sub.3), --(CH.sub.2).sub.2 NH--CO--O--C(CH.sub.3).sub.3, --(CH.sub.2).sub.2 N(CH.sub.3)--CO--O--C(CH.sub.3).sub.3, --(CH.sub.2).sub.2 OC(O)NH.sub.2, --(CH.sub.2).sub.2 Cl, --(CH.sub.2).sub.2 OCH.sub.3 or --(CH.sub.2).sub.2 NHCOH; wherein R.sub.20 is an acyl group derived from a carboxylic acid; wherein R.sub.80 is --CO.sub.2 R.sub.5 or --CONR.sub.6 R.sub.7 ; wherein R.sub.5 is hydrogen or (C.sub.1 -C.sub.4) alkyl; and wherein R.sub.6 and R.sub.7 are the same or different and are hydrogen, (C.sub.1 -C.sub.4) alkyl, or --OH with the proviso that when R.sub.6 is OH, R.sub.7 is other than --OH.
Novel compounds within the scope of this invention which are useful as intermediates to 2-azetidinone analogs having microbial growth inhibition include compounds of Formula I wherein R.sub.4 is --COH and --CO--O--C(CH.sub.3).sub.3 ; and wherein R.sub.30 is --(CH.sub.2).sub.2 NH--CO--O--(CH.sub.3).sub.3 and --(CH.sub.2).sub.2 N(CH.sub.3)--CO--O--(CH.sub.3).sub.3.
A detailed description of the acyl groups included in R.sub.20 is found in U.S. Pat. No. 4,478,749, column 8, line 41 to column 12, line 50, as those terms are defined at column 7, line 34 through column 8, line 22, all of which is incorporated by reference herein.
Preferred acyl groups
REFERENCES:
patent: 4587047 (1986-05-01), Breuer
patent: 4670553 (1987-06-01), Breuer et al.
patent: 4743685 (1988-03-01), Breuer
Breuer, H. et al., Abstract 371, Sep. 29-Oct. 2, 1985, XXV Interscience Conference on Antimicrobial Agents and Chemotherapy, Minneapolis, Minnesota.
Tanaka, S. K. et al., Abstract 372, Sep. 29-Oct. 2, 1985, XXV Interscience Conference on Antimicrobial Agents and Chemotherapy, Minneapolis, Minnesota.
Clark, J. M. et al., Abstract 373, Sep. 29-Oct. 2, 1985, XXV Interscience Conference on Antimicrobial Agents and Chemotherapy, Minneapolis, Minnesota.
Breuer, H. et al., Abstract 847, Sep. 28-Oct. 1, 1986, XXVI Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, Louisiana.
Whitney, R. R. et al., Abstract 848, Sep. 28-Oct. 1, 1986, XXVI Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, Louisiana.
Pilkiewicz, F. G. and Remsburg, B. J., Abstract 849, Sep. 28-Oct. 1, 1986, XXVI Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, Louisiana.
Berch Mark L.
Corneglio Donald L.
The Upjohn Company
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