Synthesis and activity of 2-(sulfonamido)methylcarbapenems: Discovery of a novel, anti-MRSA 1,8-naphthosultam pharmacophore

Bioorganic and Medicinal Chemistry Letters

Volumn 9, Issue 5, 1999, Pages 673-678

  Wilkening, R R ^a   Ratcliffe, R W ^a   Wildonger, K J ^a   Cama, L D ^a   Dykstra, K D ^a   DiNinno, F P ^a   Blizzard, T A ^a   Hammond, M L ^a   Heck, J V ^a   Dorso, K L ^a   St Rose, E ^a   Kohler, J ^a   Hammond, G G ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,8 NAPHTHOSULTAM DERIVATIVE; 2 (SULFONAMIDO)METHYLCARBAPENEM DERIVATIVE; CARBAPENEM DERIVATIVE; IMIPENEM; PENICILLIN BINDING PROTEIN; UNCLASSIFIED DRUG; VANCOMYCIN;

ANTIBACTERIAL ACTIVITY; ARTICLE; BACTERIAL INFECTION; DRUG PROTEIN BINDING; DRUG STRUCTURE; DRUG SYNTHESIS; GRAM POSITIVE BACTERIUM; METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS; MINIMUM INHIBITORY CONCENTRATION; PHARMACOPHORE;

BACTERIAL PROTEINS; CARBAPENEMS; CARRIER PROTEINS; DRUG RESISTANCE, MICROBIAL; GRAM-POSITIVE BACTERIA; HEXOSYLTRANSFERASES; MICROBIAL SENSITIVITY TESTS; MURAMOYLPENTAPEPTIDE CARBOXYPEPTIDASE; PENICILLIN-BINDING PROTEINS; PEPTIDYL TRANSFERASES;

BACTERIA (MICROORGANISMS); METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS; POSIBACTERIA; STAPHYLOCOCCUS AUREUS;

EID: 0033535443     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(99)00070-0     Document Type: Article

References (47)

1. (a) Cormican, M. G.; Jones, R. N. Drugs 1996 51 Suppl. 1, 61.
2. (b) Cars, O. Drugs 1997, 54 Suppl. 6, 4.
3. (c) Baquero, F. J. Antimicrob. Chemother. 1997, 39 Suppl. A, 1.
4. (d) Michel, M.; Gutmann, L. Lancet 1997, 349, 1901.
5. (a) Maranan, M. C.; Moreira, B.; Boyle-Vavra, S.; Daum, R. S. Infect. Dis. Clin. North Am. 1997, 11, 813.
6. (b) Chambers, H. F. Clin. Microbiol. Rev. 1997, 10, 781.
7. Gruneberg, R. N. Drugs 1997, 54 Suppl. 6, 29.
8. (a) Murray, B. E. Am. J. Med. 1997, 102, 284.
9. (b) Moellering, R. C. Clin. Inf. Dis. 1998, 26. 1196.
10. The transfer of vancomycin resistance from E. faecalis to S. aureus has been demonstrated in the laboratory. Noble, W. C.; Virani, Z.; Cree, R. G. A. FEMS Microbiol. Lett. 1992, 93, 195.
11. (a) Edmond, M. B.; Wenzel, R. P.; Pasculle, A. W. Ann. Int. Med. 1996, 724, 329.
12. (b) Tabaqchali, S. Lancet 1997, 350, 1644.
13. (a) Hanaki, H.; Akagi, H.; Nomura, S.; Unemi, N.; Hiramatsu, K. J. Antibiot. 1996, 49, 402.
14. (b) Kim, O. K.; Ueda, Y.; Mansuri, M. M.; Russell, J. W.; Bidwell, V. W. Bioorg. Med. Chem. Lett. 1997, 7, 1945.
15. Ternansky, R. J.; Draheim, S. E.; Pike, A. J.; Bell, F. W.; West, S. J.; Jordan, C. L.; Wu, C. Y. E.; Preston, D. A.; Alborn, W.; Kasher, J. S.; Hawkins, B. L. J. Med. Chem. 1993, 36, 1971.
16. Tsubouchi, H.; Ishikawa, H. Bioorg. Med. Chem. 1995, 3, 143.
17. Hanaki, H.; Akagi, H.; Yasui, M.; Otani, T. J. Antibiot. 1995, 48, 901.
18. (a) Jabes, D.; Rossi, R.; Brunna, C. D.; Perrone, E.; Alpegiani, M.; Andreini, B. P.; Visentin, G.; Zarini, F.; Franceschi, G. Bioorg, Med. Chem. Lett. 1993, 3, 2165.
19. (b) Ishiguro, M.; Tanaka, R.; Namikawa, K.; Nasu, T.; Inoue, H.; Nakatsuka, T.; Oyama, Y.; Imajo, S. J. Med. Chem. 1997, 40, 2126.
20. (a) Shinagawa, H.; Yamaga, H.; Houchigai, H.; Sumita, Y.; Sunagawa, M. Bioorg. Med. Chem. 1997, 5, 601.
21. (b) Arnould, J. C.; Illingworth, R. N.; Nichols, W. W.; Wilson, R. G. Bioorg. Med. Chem. Lett. 1996, 6, 2449.
22. (c) Ohtake, N.; Imamura, H.; Jona, H.; Kiyonaga, H.; Shimizu, A.; Moriya, M.; Sato, H.; Nakano, M.; Ushijima, R.; Nakagawa, S. Bioorg. Med. Chem. 1998, 6, 1089.
23. (d) Azami, H.; Matsuda, K.; Tsutsumi, H.; Kamimura, T.; Murata, M. J. Antibiot. 1998, 51, 374.
24. (a) Meurer, L. C.; Guthikonda, R. N.; Huber; J. L.; DiNinno, F. Bioorg. Med. Chem. Lett. 1995, 5, 767.
25. (b) DiNinno, F.; Muthard, D. A.; Salzmann, T. N. Bioorg. Med. Chem. Lett. 1995, 5, 945.
26. Waddell, S. T.; Ratcliffe, R. W.; Szumiloski, S. P.; Wildonger, K. J.; Wilkening, R. R.; Blizzard, T. A.; Huber, J.; Kohler, J.; Dorso, K.; St. Rose, E.; Sundelof, J. G.; Hammond, G. G. Bioorg. Med. Chem. Lett. 1995, 5, 1427.
27. (a) Chambers, H. F. Antimicrob. Agents Chemother. 1995, 39, 462.
28. (b) Malanoski, G.; Collins, L.; Eliopoulos, C. T.; Moellering, R. C.; Eliopoulos, G. M. Antimicrob. Agents Chemother. 1995, 39, 990.
29. Yasuda, N.; Huffman, M. A.; Ho, G.; Xavier, L. C.; Yang, C.; Emerson, K. M.; Tsay, F.; Li, Y.; Kress, M. H.; Rieger, D. L.; Karady, S.; Sohar, P.; Abramson, N. L.; DeCamp, A. E.; Mathre, D.; Douglas, A. W.; Dolling, U. H.; Grabowski, E. J. J.; Reider, P. J. J. Org. Chem. 1998, 63, 5438.
30. (a) Chambers, H. F.; Sachdeva, M. J. Inf. Dis. 1990, 161, 1170.
31. (b) de Lencastre, H.; de Jonge, B. L. M.; Matthews, P. R.; Tomasz, A. J. Antimicrob. Chemother. 1994, 33, 7.
32. Fontana, R.; Aldegheri, M.; Ligozzi, M.; Lopez, H.; Sucari, A.; Satta, G. Antimicrob. Agents Chemother. 1994, 38, 1980.
33. Lankas, G. R.; Coleman, J. B.; Klein, H. J.; Bailly, Y. Toxicology 1996, 108, 207.
34. (a) Faraci, W. S.; Pratt, R. F. Biochem. 1985, 24, 903.
35. (b) Grabowski, E. J. J.; Douglas, A. W.; Smith, G. B. J. Am. Chem. Soc. 1985, 107, 268.
36. Perrone, E.; Jabes, D.; Alpegiani, M.; Andreini, B. P.; Bruna, C. D.; Nero, S. D.; Rossi, R.; Visentin, G.; Zarini, F.; Franceschi, G. J. Antibiot. 1992, 45, 589.
37. 2O-EtOH ranged from 10.1-10.5 for alkyl substituted derivatives to 6.0-8.7 for nitro substituted derivatives; Dauphin, G.; Kergomard, A.; Veschambre, H. Bull. Soc. Chim. Fr. 1967, 3395. The pKa of 1,8-naphthosultam was determined to be 6.2 by a photometric method; Kanety, H.; Kosower, E. M. J. Phys. Chem. 1982, 86, 3776.
38. 2O-EtOH ranged from 10.1-10.5 for alkyl substituted derivatives to 6.0-8.7 for nitro substituted derivatives; Dauphin, G.; Kergomard, A.; Veschambre, H. Bull. Soc. Chim. Fr. 1967, 3395. The pKa of 1,8-naphthosultam was determined to be 6.2 by a photometric method; Kanety, H.; Kosower, E. M. J. Phys. Chem. 1982, 86, 3776.
39. Mitsunobu reactions involving aryl sulfonamides are well documented. See, for example (a) Edwards, M. L.; Stemerick, D. M.; McCarthy, J. R. Tetrahedron Lett. 1990, 31, 3417.
40. (b) Jones, R. J.; Rapoport, H. J. Org. Chem. 1990, 55, 1144. Mitsunobu reactions of a 2-hydroxymethyl carbapenem with N-nucleophiles have been reported; Arnould, J. C.; Landier, F.; Pasquet, M. J. Tetrahedron Lett. 1992, 33, 7133.
41. (b) Jones, R. J.; Rapoport, H. J. Org. Chem. 1990, 55, 1144. Mitsunobu reactions of a 2-hydroxymethyl carbapenem with N-nucleophiles have been reported; Arnould, J. C.; Landier, F.; Pasquet, M. J. Tetrahedron Lett. 1992, 33, 7133.
42. Sulfonamides 5a, 5b, 5d-5k, 5m, and 5o, lactam 5l, and imide 5q were prepared by literature procedures. The acyclic sulfonamide 5c was prepared by the reaction of MsCl with a pyridine solution of 4-aminofluorenone. Sulfonamides 5n and 5p were prepared by the borane reduction of the corresponding acylsulfonamides 5m and 5o. Sulfam 5r was prepared by the methylation (NaH, MeI) of the parent sulfam.
43. Bis(allyl)-protected carbapenem 4 was prepared according to a Merck route (see a) or by a Shionogi route (see b) in which the protection scheme was modified. (a) Schmitt, S. M.; Salzmann, T. N.; Shih, D. H.; Christensen, B. G. J. Antibiot. 1988, 41, 780.
44. (b) Uyeo, S.; Itani, H. Tetrahedron Lett. 1994, 35, 4377.
45. Jeffrey, P. D.; McCombie, S. W. J. Org. Chem. 1982, 47, 587.
46. Toney, J. H.; Hammond, G. G.; Leiting, B.; Pryor, K. D.; Wu, J. K.; Cuca, G. C.; Pompliano, D. L. Anal. Biochem. 1998, 255, 113.
47. Ratcliffe, R. W.; Wilkening, R. R.; Wildonger, K. J.; Waddell, S. T.; Santorelli, G. M.; Parker, D. L.; Morgan, J. D.; Blizzard, T. A.; Hammond, M. L.; Heck, J. V.; Huber, J.; Kohler, J.; Dorso, K. L.; St. Rose, E.; Sundelof, J. G.; May, W. J.; Hammond, G. G. Bioorg. Med. Chem. Lett. 1999, 9, 679.