Cyclic homopentapeptides 1. Analogs of tuberactinomycins and capreomycin with activity against vancomycin-resistant enterococci and Pasteurella

Bioorganic and Medicinal Chemistry Letters

Volumn 7, Issue 9, 1997, Pages 1139-1144

  Dirlam, J P ^a   Belton, A M ^a   Birsner, N C ^a   Brooks, R R ^a   Chang, S P ^a   Chandrasekaran, R Y ^a   Clancy, J ^a   Cronin, B J ^a   Dirlam, B P ^a   Finegan, S M ^a   Froshauer, S A ^a   Girard, A E ^a   Hayashi, S F ^a   Howe, R J ^a   Kane, J C ^a   Kamicker, B J ^a   Kaufman, S A ^a   Kolosko, N L ^a   LeMay, M A ^a   Linde II, R G ^a   Lyssikatos, J P ^a   MacLelland, C P ^a   Magee, T V ^a   Massa, M A ^a   Miller, S A ^a   Minich, M L ^a   Perry, D A ^a   Petitpas, J W ^a   Reese, C P ^a   Seibel, S B ^a   Su, W G ^a   Sweeney, K T ^a   Whipple, D A ^a   Yang, B V ^a   more..

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBIOTIC AGENT; CAPREOMYCIN; METICILLIN; PENTAPEPTIDE; VANCOMYCIN;

ANIMAL MODEL; ANTIBACTERIAL ACTIVITY; ARTICLE; BACTERIAL INFECTION; CONTROLLED STUDY; DRUG RESISTANCE; DRUG SYNTHESIS; ESCHERICHIA COLI; IN VITRO STUDY; MANNHEIMIA HAEMOLYTICA; MASS SPECTROMETRY; MINIMUM INHIBITORY CONCENTRATION; MOUSE; MULTIDRUG RESISTANCE; NONHUMAN; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PASTEURELLA MULTOCIDA; STAPHYLOCOCCUS AUREUS; STRUCTURE ACTIVITY RELATION; SUBCUTANEOUS DRUG ADMINISTRATION;

ANIMALIA; BACTERIA (MICROORGANISMS); ESCHERICHIA COLI; MANNHEIMIA HAEMOLYTICA; METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS; PASTEURELLA; PASTEURELLA MULTOCIDA; STAPHYLOCOCCUS AUREUS;

EID: 18744422288     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(97)00186-8     Document Type: Article

References (17)

1. Marsh, W. S.; Mayer, R. L.; Mull, R. P.; Scholz, C. R.; Townley, R. W.; U.S. Patent 2,633,445 (1953).
2. Herr, E. B., Jr.; Haney, M. E.; Pittenger, G. E. Proc. Ind. Acad. Sci. 1960, 69, 134.
3. Stark, W. M.; Boeck, L. D. Antimicrob. Agents Chemother. 1965, 157.
4. (a)Gould, S. J.; Minott, D. A. J. Org. Chem. 1992, 57, 5214.
5. (b) Wang, M.; Gould, S. J. J. Org. Chem. 1993, 58, 5176.
6. Herr, E. B., Jr., Redstone, M. O. Annal. N. Y. Acad. Sci. 1966, 135, 940.
7. In a search for potential tuberculostatic agents, a number of viomycin and capreomycin analogs were first prepared using this exchange reaction with anilines and phenyl ureas at Pfizer Central Research, Sandwich, UK, in the 1960s in a joint collaboration with A. W. Johnson, B. W. Bycroft, and A. Hassanali - Walji of the Univ. of Nottingham, England, and J. D. Hardstone and J. E. Thorpe, Pfizer Ltd; however, purification and characterization were very difficult without modern analytical and spectroscopic methods (private communication with J. D. Hardstone).
8. Nomoto, S.; Shiba, T. J. Antibiot. 1977, 30, 1008.
9. Mitsubishi Kasei Corp.; a high porous polymer absorption resin that was pre-swollen in methanol for 0.75 to 12 h and rinsed well with water prior to use.
10. R Sulfate, Eli Lilly and Co.) in 20 mL 2 N HCl solution and 20 mL dioxane. The reaction mixture was allowed to stir at 65 °C for 4 h, and then cooled to room temperature. Water (600 mL) was added and the reaction mixture was adjusted to a pH of 8.5 with sodium bicarbonate. The resulting precipitate (excess 3,4-dichloroaniline) was removed by suction filtration and the filtrate was washed with methylene chloride (8X with 500 mL), ether (2X with 300 mL) and hexane (1X with 300 mL). The aqueous layer was adjusted to a pH of 3 with 2 N HCl solution and treated with 250 g of activated Diaion HP-21; the mixture was stirred with an overhead paddle stirrer for 2 h. The resin was removed by suction filtration and washed with water (4X with 1 L; which eluted unreacted antibiotic starting material) and then methanol (4X with 500 mL). The methanol washes were combined and evaporated under vacuum to a volume of about 5 mL. The addition of a small amount of methanol resulted in precipitation of 4.7 g (the salt contained 75% active material based on C,H,N analysis; 75 % corrected yield) of the desired product as an HCl salt. The positive FAB MS of 2 gave diagnostic cationized molecules at m/z 770 (M+1) for the IA analog, and at m/z 754 (M+1) for the IB analog. The syntheses of corresponding phenyl urea analogs were performed in a similar manner in 2 N HCl/dioxane solution, but required only 2-10 equiv of the phenyl urea starting material. These reactions were typically heated at 65 °C overnight, and then allowed to cool to ambient temperature. The precipitated urea was filtered off and the mixture was poured into water. The aqueous layer was then washed 4X with ethyl acetate before pouring onto activated HP-21 resin in a beaker, covered with a watch glass, and gently shaken (orbital shaker) for 7 h. The resin was filtered (coarse frit), rinsed thoroughly with water (5X), and transferred into a beaker before adding methanol:water (in a 9:1 ratio), shaking for 3 h, and pouring through a frit to collect the extract. After solvent removal the sample was lyophilized to yield the desired product (ca. 60-80% yield).
11. Magnus, P.; Gallagher, T.; Schultz, J.; Or, Y.-S.; Ananthanarayan, T. P. J. Am. Chem. Soc. 1987, 109, 2706.
12. Reduction of the C-19 OH group of viomycin by catalytic hydrogenation is accompanied by formation of a C-6 methyl derivative (with loss of the urea moiety): Kitagawa, T.; Miura, T.; Tanaka, S.; Taniyama, H. J. Antibiot. 1973, 26, 528.
13. Tuberactinomycin O is produced as a minor component in a mixture of fermentation products; thus, the present semisynthetic procedure allows easy entry to this antibiotic: Izumi, R.; Noda, T.; Take, T.; Nagata, A.J. Antibiot. 1972, 25, 201.
14. The gram-negative acute murine infection models were conducted in a manner described previously: Dirlam; J. P.; Presslitz, J. E.; Williams, B. J. J. Med Chem. 1983, 26, 1122.
15. The gram-positive acute murine infection models were performed in a manner described previously: Girard, A. E.; Girard, D.; Gootz, T. D., Faiella, J. A., Cimochowski, C. R. Antimicrob. Agents Chemother. 1995, 39, 2210; additional in vivo data for these compounds will be provided in a full paper.
16. MICs against P. multocida and E. coli were analyzed by a microdilution method similar to that described in the NCCLS document M7-A3 (Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically, 3rd Edition, Villanova, PA, 1993), with the exception that the total volume of the well was 200 μL instead of 100 μL, and BHI (brain-heart infusion) broth was used in place of CAMH broth.
17. MICs against E. faecalis and E. faecium were analyzed according to the procedures described in NCCLS document M7-A3, cited in ref 15.