Organic compounds -- part of the class 532-570 series – Organic compounds – Unsubstituted hydrocarbyl chain between the ring and the -c-...
Patent
1990-01-25
1991-05-14
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, C07D41714
Patent
active
050157370
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention encompasses novel 2-azetidinone compounds containing chiral aminopyrazolidinones 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 0053815, 0053816, 0076758 and 0096297 disclose .beta.-lactams with various substituents at the C.sub.4 position of the ring.
European Patent Application 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 C3 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 sulfonylaminocarbonl activating group. U.K. Patent Application No. 8623151, filed Sept. 26, 1986, and Belgium Patent 905502A disclose sulfonylaminocarbonyl-2-azetidinones containing an imidazolidonylaminocarbonyl-2(1,4-dihydro-5-hydroxy4-oxo)pyridine in the activating group. None of the above documents discloses a substituted sulfonylaminocarbonyl-2-azetidinone which has a chiral aminopyrazolidinone in the activating group.
SUMMARY OF THE INVENTION
The present invention teaches novel 2-azetidinone analogs containing chiral aminopyrazolidinones 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 I and pharmaceutically acceptable salts thereof. from the group consisting of halogen, hydroxy, amino, nitro, (C.sub.1 -C.sub.4)alkyl, and (C.sub.1 -C.sub.4)alkoxy. from the group consisting of halogen, hydroxy, amino, nitro, (C.sub.1 -C.sub.4)alkyl, and (C.sub.1 -C.sub.4)alkoxy, --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 NHCHO;
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 --CHO and --CO--O--C(CH.sub.3).sub.3 ; wherein R.sub.5 is --(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 and wherein R.sub.11 is --O--CH.sub.2 --(C.sub.6 H.sub.5).
A detailed description of the acyl groups included in R.sub.3 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 of R.sub.3 include those which have been used to acylate 6-aminopenicillanic acid, 7-aminocephalosporic acid and their derivatives which can be found in "Chemistry and Biology of .beta.-Lactam Antibiotics Vol. 1, R. B. Morin and M. Gorham, ed., Academic Press, N.Y. 1982 and include the following list: 2-Cyanoacetyl, Aminophenylacetyl Amino(4-hydroxyphenyl)acetyl, .alpha.(Thien-2-yl)acetyl, .alpha.(Thien-3-yl)acetyl, Phenylacetyl, Hydroxyphenylacetyl (F
REFERENCES:
patent: 4587047 (1986-05-01), Breuer
patent: 4670553 (1987-06-01), 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 Bemsburg, B. J., Abstract 849, Sep. 28-Oct. 1, 1986, XXVI Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, Louisiana.
Berch Mark L.
Busse Paul W.
Corneglio Donald L.
The Upjohn Company
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