Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1995-06-26
1997-09-16
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514211, 5142305, 540468, 540552, 544 91, C07D26512, C07D26712, C07D26722
Patent
active
056681275
ABSTRACT:
Methods, compounds and compositions are provided for inhibiting the growth of pathogenic mycobacteria in vitro and of treatment of pathogenic bacterial infections, such as mycobacterial and clostridium infections, in vivo using bicyclic nitroimidazole compounds of the formula (II): ##STR1## wherein R.sub.1 is hydrogen, halogen, loweralkyl, haloloweralkyl, cycloalkyl, heterocycle, substituted heterocycle and heterocyclicalkyl; X is oxygen, sulfur or NK.sub.2, where R.sub.2 is hydrogen, loweralkyl, aryl, cycloalkyl, heterocycle, substituted heterocycle, heterocyclicalkyl, COR.sub.3 or SO.sub.2 R.sub.4 CONR.sub.4 R.sub.5, where R.sub.4 and R.sub.5 are independently selected from hydrogen, loweralkyl, aryl, alkylaryl, alkoxyalkyl, alkoxyaryl, alkoxyalkoxyaryl, alkylheterocycle, and alkoxyheterocycle; n is 1, 2 or 3; Y and Z are independently selected CH.sub.2, CO, CR.sub.4 R.sub.5 or NR.sub.4, where R.sub.4 and R.sub.5 are as defined above; provided that when n is 2 or 3, the compounds of formula II can be additionally substituted as follows: ##STR2## wherein R.sub.6, R.sub.7, R.sub.8 and R.sub.9 are independently selected from hydrogen, loweralkyl, aryl, alkylaryl, alkoxyalkyl, alkoxyaryl, alkoxyalkoxyaryl, alkylheterocycle, and alkoxyheterocycle; and the pharmaceutically acceptable salts thereof. The methods, compounds and compositons are particularly useful for inhibiting the growth of Mycobacterium tuberculosis and Clostridium difficile.
REFERENCES:
patent: 3978211 (1976-08-01), Coronelli et al.
patent: 5317019 (1994-05-01), Bender et al.
Sehgal, R.K. and Agrawal, K.C., "Novel Nitroimidazo[2,1-b]oxazole Formation Reaction of 2,4(5)-Dinitroimidazole with Oxiranes (1)," J. Heterocyclic Chem. 16:1499-1500 (1979).
Agrawal, K.C. et al., "Potential Radiosensitizing Agents. Dinitroimidazoles," J. Chem. 22(5):583-586 (1979).
Sehgal, R.K. et al, "Potential Radiosensitizing Agents. 2. Synthesis and Biologica Activity of Derivatives of Dinitroimidazole with Oxiranes," J. Med. Chem. 24:601-604 (1981).
Nagarajan, K. et al., "Nitroimidazoles XXI. 2,3-dihydro-6-nitroimidazo [2.1-b]oxazoles with antitubercular activity," Eur. J. Med. Chem. 24:631-633 (1989).
Ashtekar, D.R. et al, "In Vitro and In Vivo Activities of the Nitroimidazole CGI 17341 against Mycobacterium tuberculosis," Antimicrob. Agents Chemother., 37(2):183-186 (1993).
Aronsson, B. et al., J. Infect. Dis. 151:476-481 (1985).
Dosik, G.M. et al., Am. J. Med. 67:646-656 (1979).
Bartlett, J., see Clostridium difficle: Its role in Intestinal Disease. R.D. Rolfe an S.M. Finegold, eds., Academic Press Inc., New York, 1988 pp. 1-13.
Swannson, B. et. al., Antimicrob. Agents Chemother., 35:1108-1111 (1991).
Bartlett, J.G. et al., Clin. Infect. Dis. (S4) S265-72 (1994).
Physician's Desk Reference, 48th Edition, pp. 1704-1706 (1994).
IUPAC 1974 Recommendations for Section E, Fundamental Stereochemistry, Pure Appl. Chem., 45:13-30 (1976).
Chemical Abstracts Index Guide-Appendix IV, paragraph 203 (1987).
Bundle, D.R. et al., J. Chem. Soc., Perkin Trans. I, 11:2247-2250 (1985).
Liu, H. et al., J. Org. Chem., 57:2471 (1992).
Pandey, G.D. et al., Pol. J. Chem., 54:763 (1980).
Spangler, S.K. et al. "Oxyrase, a method which avoids CO.sub.2 in the incubation atmosphere for anaerobic susceptibility testing of antibiotics affected by CO.sub.2," J. Microbiol. 31:460-462 (1993).
Spangler, S.K. et al., "Susceptibilities of 201 anaerobes to erythromycin, azithromycin, clarithromycin, and roxithromycin by Oxyrase agar dilution and E-t methodologies," J. Clin. Microbiol. 33:1366-1367 (1995).
Barry, A.L. et al., "In-vitro potency of azithromycin against gram-negative bacilli method-dependent," J. Antimicrob. Chemother. 28: 607-610 (1991).
Hansen, S.L. et al., "Effect of carbon dioxide and pH on susceptibility of Bactero fragilis group to erythromycin," Antimicrob. Agents Chemother., 19: 335-336 (1990).
Retsema, J.A. et al., "Significance of environmental factors on the in vitro potenc azithromycin," Eur. J. Clin. Microbiol. Infect. Dis. 10:834-842 (1991).
Bartlett, J.G., "Clostridium difficile: History of Its Role as an Enteric Pathogen the Current State of Knowledge About the Organism," Clin. Infect. Dis., 18(Suppl. 4):S265-S272 (1994).
Ahmad, S.H. et at., "Antibiotic Associated Colitis," Indian J. Pediatri., 60:591-5 (1993).
Anand, A., et al., "Epidemiology, Clinical Manifestations, and Outcome of Clostridium difficile-Associated Diarrhea," Am. J. Gastro., 89(4):519-523 (1994.
Mitty, Roger D. and Lamont, J.T., "Clostridium difficile Colitis: Epidemiology, Pathophysiology, and Treatment," Mt. Sinai J. Med., 61(4):329-335 (1994).
Samore, M.H. et al., "Clostridium difficile Colonization and Diarrhea at a Tertiar Care Hospital," Clin. Infect. Dis., 18:181-187 (1994).
Fekety, R., "Antibiotic-Associated Colitis," In: Mandell G.L., ed., Principles and Practice of Infectious Diseases, Part II, Major Clinical Syndromes, Ch. 78, pp. 978-987. (1995).
Fekety, R. and Shah., A.B., "Diagnosis and Treatment of Clostridium difficile Colitis," JAMA, 269(1):71-75 (1993).
Gorbach, S.L., "Clostridium difficile Settles In a Nursing Home," Hospital Practice, pp. 145-160 (Feb. 15, 1989).
Kofman, T.P. et al., ".alpha.-Oxides in Reactions with NH Acids of the Heterocyclic Series. II. Alkylation of 3,5-Dinitro-l,2,4-Triazole with Olefin Oxides," (translat from Khimiya Geterotsiklicheskih Soedinenii, 5:705-707 (1975)), Plenum Publishing Corporation, pp. 612-614 (1976).
Nagarajan, K. et at., "Nitroimidazoles: Part XIX--Structure-activity Relationship" Indian J. Chem., 23:342-362 (1984).
Nagarajan, K. and Shenoy, S.J., "Nitroimidazoles: Part XX--Reactions of 2,4-Dinitroimidazole with 2-Haloethanols, 3-Chloropropionitrile & Propylene Oxide", Indian J. Chem., 23:363-368 (1984).
Baker William R.
Keeler Eric L.
Shaopei Cai
Ngo Tamthom T.
PathoGenesis Corporation
Shah Mukund J.
LandOfFree
Nitroimidazole antibacterial compounds and methods of use thereo does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Nitroimidazole antibacterial compounds and methods of use thereo, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Nitroimidazole antibacterial compounds and methods of use thereo will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-218354