Organic compounds -- part of the class 532-570 series – Organic compounds – Unsubstituted hydrocarbyl chain between the ring and the -c-...
Patent
1989-08-25
1990-12-04
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, C07D40114, C07D41314, C07D205085
Patent
active
049755382
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention encompasses novel antibiotic substituted sulfonylaminocarbonyl-2-azetidinones having a heterocyclic activating group.
INFORMATION DISCLOSURE
Derivatives of 2-azetidinone which have antimicrobial and .beta.-lactamase inhibitory activity are known in the art. European Patent Application 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 However, the documents do not suggest the specific substituents disclosed herein and do not suggest or teach how to make the specific compounds of this application.
Abstracts from papers presented by Squibb Institute for Medical Research at the 25th and 26th Interscience Conferences on Antimicrobial Agents and Chemotherapy disclose antibacterial substituted sulfonylaminocarbonyl-2-azetidinones containing a substituted heterocycle in the sulfonylaminocarbonyl activating 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 substituted heterocycle in the sulfonylaminocarbonyl activating group. U. K. Patent Application No. 8623151, filed Sept. 26, 1986 and Belgium Pat. No. 905502A disclose sulfonylaminocarbonyl-2-azetidinones containing an imidazolidonylaminocarbonyl-2-(1,4-dihydro-5-hydroxy-4-oxo)pyridine in the activating group. None of the above documents discloses a substituted sulfonylaminocarbonyl-2-azetidinone which has a heterocyclic activating group claimed in this invention.
Mochida, K., et al. Journal of Antibiotics, 182-189 (1987) disclose cephalosporins containing N-hydroxyl and N-methyl pyridinones and 5-hydroxypyridinones.
SUMMARY OF THE INVENTION
The present invention teaches novel 2-azetidinone analogs containing heterocyclic activating groups which are 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 1 and pharmaceutically acceptable salts thereof; wherein R.sub.401 and R.sub.402 are the same or different and are (a) hydrogen, (b) (C.sub.1 -C.sub.12) alkyl (c) (C.sub.2 -C.sub.8) alkenyl, (d) (C.sub.2 -C.sub.8) alkynyl, (e) (C.sub.3 -C.sub.10) cycloalkyl, (f) phenyl optionally substituted with from one to 3 substituents selected from the group consisting of halogen, hydroxy amino, nitro, (C.sub.1 -C.sub.4)alkyl, and (C.sub.1 -C.sub.4)alkoxy, (g) benzyl optionally substituted with from one to 3 substituents selected from the group consisting of halogen, hydroxy, amino, nitro, (C.sub.1 -C.sub.4)alkyl, and (C.sub.1 -C.sub.4)alkoxy, (h) --CH.sub.2 --O--CO--CH.sub.2 --NHR.sub.420, (i) --CH.sub.2 --O--CO.sub.2 --R.sub.430, (j) --CH.sub.2 F, or (k) --CHF.sub.2 ; wherein R.sub.420 is (a) hydrogen, (b) --COH, or (c) --CO--O--C(CH.sub.3).sub.3 ; wherein R.sub.430 is (C.sub.1 -C.sub.8)alkyl, --(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.300 is an acyl group derived from a carboxylic acid; wherein R.sub.100 is a heterocyclic compound of Formulas 2, 3, 4 or 5; wherein R.sub.121 and R.sub.122 are hydrogen; wherein R.sub.123 is methylene or carbonyl; wherein R.sub.131 and R.sub.132 are hydrogen or (C.sub.1 -C.sub.3) alkyl with the proviso that if one of R.sub.131 or R.sub.132 is alkyl the other is hydrogen; wherein R.sub.133, R.sub.134 and R.sub.135 are the same or different and are
REFERENCES:
patent: 4587047 (1986-05-01), Breuer
patent: 4670553 (1987-06-01), Breuer et al.
Breuer, H., et al., Abstract 371, Sept. 29-Oct. 2, 1985, XXV Interscience Conference on Antimicrobial Agents and Chemotherapy, Minneapolis, Minn.
Tanaka, S. K., et al., Abstract 372, Sept. 29-Oct. 2, 1985, XXV Interscience Conference on Antimicrobial Agents and Chemotherapy, Minneapolis, Minn.
Clark, J. M., et al., Abstract 373, Sept. 29-Oct. 2, 1985, XXV Interscience Conference on Antimicrobial Agents and Chemotherapy, Minneapolis, Minn.
Breuer, H. et al., Abstract 847, Sept. 28-Oct. 1, 1986, XXVI Interscience Conference on Amtimicrobial Agents and Chemotherapy, New Orleans, La.
Whitney, R. R., et al., Abstract 848, Sept. 28-Oct. 1, 1986, XXVI Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, La.
Pilkiewicz, F. G. and Remsburg, B. J., Abstract 849, Sept. 28-Oct. 1, 1986, XXVI Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, La.
Mochida, K. et al., Journal of Antibiotics, 182-189 (1987).
Barbachyn Michael R.
Brickner Steven J.
Thomas Richard C.
Berch Mark L.
Busse Paul W.
Corneglio Donald L.
The Upjohn Company
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