Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1999-01-13
2000-04-11
Gerstl, Robert
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514197, A61K 31195
Patent
active
060488522
DESCRIPTION:
BRIEF SUMMARY
This invention relates to chemical compounds having metallo-.beta.-lactamase inhibitory and antibacterial properties. The invention also relates to methods for the preparation of such compounds, to pharmaceutical compositions containing them, and to uses thereof.
Metallo-.beta.-lactamases confer resistance to the vast majority of .beta.-lactam based therapies, including carbapenems and jeopardise the future use of all such agents. As a result of the increased use of carbapenems and other .beta.-lactam antibiotics the clinical climate is becoming more favourable for the survival of clinical strains which produce metallo-.beta.-lactamases, and metallo-.beta.-lactamases have now been identified in common pathogens such as Bacillus fragilis, Klebsiella, Pseudomonas aeruginosa and Serratia marcescens. Emerging knowledge emphasises that metallo-.beta.-lactamases have the potential to present a crisis situation for antimicrobial chemotherapy.
U.S. Pat. No. 4,513,009 discloses amino acid derivatives including thiorphan having enkephalinase-inhibiting, antalgic, antidiarrhea and hypotensive. Analgesic effects are disclosed for thiorphan (B. P. Roques et al, Nature, 1980, 288, 286) and for other mercapto amino acid derivatives (JO 3002-117-A). Mercapto amino acid derivatives are disclosed as inhibitors of angiotensin-converting enzyme (ACE) (J. L. Stanton, et al, J. Med. Chem, 1983, 26, 1257, U.S. Pat. No. 4,053,651 and GB 2090-591); as conferring antihypotensive effects (WO 9308162); as enkephalinase (neutral endopeptidase (NEP)) inhibitors (U.S. Pat. No. 4,474,799 and Mimura et al, J. Med. Chem., 1992, 35, 602 and references cited therein); as dual inhibitors of ACE and NEP (Fournie-Zaluski et al., J. Med. Chem., 1994, 37(8), 1070, WO 9417036); as inhibitors of endothelin-converting enzyme (ECE) (WO 9311154, Burtenshaw, et al, Bioorg. Med. Chem. Lett., 1993, 3(10), 1953 and Deprez et al., Bioorg. Med. Chem. Lett., 1996, 6(19), 2317); as metalloproteinase inhibitors (WO 9425435); and having radioprotective action and cytotoxicity (M. Hikita et al, J. Radiat. Res., 1975, 16(3), 162 and DE2,349,707). DE3819539 (Squibb) discloses amino acids and peptide derivatives as inhibitors of neutral endopeptidase and their use as antihypertensives and diuretics.
Other references to amino acid derivatives having the abovementioned activities include: Gordon et al., Life Sciences 1983, 33 (Supp. I), 113-6; Waller et al., J, Med. Chem. 1993, 36, 2390-2403; Saunders et al., J. Comp. Aided Mole. Des. 1987, 1, 133-42; Gomez-Monterrey et al., J. Med. Chem. 1993, 36, 87-94; Oya et al., Chem. Pharm. Bull. 1981, 29(4), 940-7; Trapani et al., Biochem. Mol. Biol. Int 1993, 31(5), 861-7; Baxter et al., J. Med. Chem. 1992, 35(20), 3718-20; Condon et al., J. Med. Chem. 1982, 25(3), 250-8; Cheung et al., J. Biol. Chem. 1980, 255(2), 401-7; Cushman et al., Biochemistry 1977, 16(25), 5484-91; EP0539848, EP0419327, EP0254032, EP0355784, EP0449523, EP0153755, U.S. Pat. No. 5,061,710, U.S. Pat. No. 4,339,600, U.S. Pat. No. 4,401,677, U.S. Pat. No. 4,199,512, DE2717548, DE2711225, JP54052073, JP54063017, JP54092937, JP55055165, JP54063017, W09407481, W08202890 and BE890398.
Other amino acid derivatives are described by: Fuchs et al., Arzneim.-Forsch. 1985, 35(9)1394-402, having mitochondrial dysfunction and postischemic myocardial damage activity; Rajkovic et al., Biochem. Pharmacol. 1984, 33(8), 1249-50, having enhancement of neutrophil response and modulation of superoxide and hydrogen peroxide production; Sakurai et al., Chem. Pharam. Bull. 1979, 27(12), 3022-8 forming a peptide/cytochrome P-450 heme system; and Sugiura et al., J. Am. Chem. Soc. 1977, 99(5), 1581-5, forming copper(II) and nickel(II) complexes.
According to the present invention there is provided a method of treatment of bacterial infections in humans or animals which comprises administering, in combination with a .beta.-lactam antibiotic, a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt, solvate or in vivo hydrolysable ester th
REFERENCES:
Chemical Abstract. vol.: 120, No.:17, p. 1075, Abstract No.: 217613h, Apr. 25, 1994.
Ito, et al., "Synthesis and Pharmacological Activities of Novel Cyclic Disulfide and Cyclic Sulfide Derivatives as Hepatoprotective Agents," Chem. Pharm. Bull. 41(6): pp. 1066-1073 (1993).
Walker, et al., "Effect of Redox Environment on the in Vivo and in Vitro Folding of RTEM-1 .beta.-Lactamase and Escherichia coli Alkaline Phosphatase," The Journal of Biological Chemistry, 269(45), pp. 28487-28493 (1994).
Bateson John Hargreaves
Best Desmond John
Gasson Brian Charles
Payne David John
Witty David R
Gerstl Robert
Kanagy James M.
Kinzig Charles M.
SmithKline Beecham p.l.c.
LandOfFree
.beta.-thiopropionyl-aminoacid derivatives and their use as .bet does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with .beta.-thiopropionyl-aminoacid derivatives and their use as .bet, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and .beta.-thiopropionyl-aminoacid derivatives and their use as .bet will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1176709