Conformational analysis of meropenem and desmethyl meropenem: The effect of 1β-methyl group on carbapenem antibiotics

Bioorganic and Medicinal Chemistry Letters

Volumn 6, Issue 16, 1996, Pages 1881-1886

  Igarashi, Jun Etsu ^a   Nishimura, Tamiki ^a   Sasaki, Akira ^a   Sunagawa, Makoto ^a  

^a DAINIPPON SUMITOMO PHARMA CO LTD   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

CARBAPENEM DERIVATIVE; MEROPENEM; NORMEROPENEM; UNCLASSIFIED DRUG;

ARTICLE; CALCULATION; DRUG STRUCTURE; MOLECULAR DYNAMICS; NUCLEAR MAGNETIC RESONANCE; THEORY;

EID: 0030594997     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/0960-894X(96)00341-1     Document Type: Article

References (16)

1. 1) Portions of this work have been presented previously: Igarashi, J.; Nishimura, T.; Sasaki, A.; Sunagawa, M. Conformational Analysis of Meropenem and Desmethyl Meropenem: The Effect of 1β-Methyl Group on Carbapenem Antibiotics. The 37th Experimental NMR Conference, March 17-22, 1996, Abstract pp 123.
2. 2) Albers-Schoenberg, G.; Arison, B. H.; Hensens, O. D.; Hirshfield, J.; Hoogsteen, K; Kaczka, E. A.; Rhodes, R. E.; Kahan, J. S.; Kahan, F. M.; Ratcliffe, R. W.; Walton, E.; Ruswinkle, L. J.; Morin, R. B. Christensen, B. G. J. Am. Chem. Soc., 1978, 100, 6491. Kahan, J. S.; Kahan, F. M.; Goegelman, R.; Currie, S. A.; Jackson, M.; Stapley, E. O.; Miller, T. W.; Miller, A. K.; Hendlin, D.; Mochales, S.; Hernandez, S.; Woodruff, H. B.; Birnbaum, J. J. Antibiotics, 1979, 32, 1.
3. 2) Albers-Schoenberg, G.; Arison, B. H.; Hensens, O. D.; Hirshfield, J.; Hoogsteen, K; Kaczka, E. A.; Rhodes, R. E.; Kahan, J. S.; Kahan, F. M.; Ratcliffe, R. W.; Walton, E.; Ruswinkle, L. J.; Morin, R. B. Christensen, B. G. J. Am. Chem. Soc., 1978, 100, 6491. Kahan, J. S.; Kahan, F. M.; Goegelman, R.; Currie, S. A.; Jackson, M.; Stapley, E. O.; Miller, T. W.; Miller, A. K.; Hendlin, D.; Mochales, S.; Hernandez, S.; Woodruff, H. B.; Birnbaum, J. J. Antibiotics, 1979, 32, 1.
4. 3) Sunagawa, M.; Matsumura, H.; Inoue, T.; Fukasawa, M.; Kato, M. J. Antibiotics, 1990, 43, 519.
5. 4) Sumita,Y.; Eguchi, Y.; Fukasawa, M.; Okuda, T.; Yamaga, H.; Matsumura, H.; Sunagawa, M. J. Antibiots, 1993, 46, 1629.
6. 5) Takeuchi, Y.; Sunagawa, M.; Isobe, Y.; Hamazume, Y.; Noguchi, T. Chem. Pharm. Bull., 1995, 43, 689.
7. 6) Fukasawa, M.; Sumita, Y.; Harabe, E. T.; Tanio, T.; Nouda, H.; Kohzuki, T.; Okuda, T.; Matsumura, H.; Sunagawa, M. Antimicrob. Agents Chemother., 1992, 36, 1577.
8. 7) Sunagawa, M.; Matsumura, H.; Sumita, Y.; Nouda, H. J. Antibiotics, 1995, 48, 408. Sunagawa, M.; Nouda, H. Japanese J. Antibiotics, 1996, 49, 1.
9. 7) Sunagawa, M.; Matsumura, H.; Sumita, Y.; Nouda, H. J. Antibiotics, 1995, 48, 408. Sunagawa, M.; Nouda, H. Japanese J. Antibiotics, 1996, 49, 1.
10. 8) Shih, D. H.; Baker, F.; Cama, L.; Christensen, B. G.; Heterocycles, 1984, 21, 29. Cama, L. D.; Wildonger, K. J.; Guthikonda, R.; Ratcliffe, R. N.; Christensen, B. G. Tetrahedron, 1983, 39, 2531.
11. 8) Shih, D. H.; Baker, F.; Cama, L.; Christensen, B. G.; Heterocycles, 1984, 21, 29. Cama, L. D.; Wildonger, K. J.; Guthikonda, R.; Ratcliffe, R. N.; Christensen, B. G. Tetrahedron, 1983, 39, 2531.
12. 9) Guthikonda, R. N.; Cama, L. D.; Quesada, M.; Woods, M. F.; Salzmann, T. N.; Christensen, B. G. J. Med. Chem., 1987, 30, 871.
13. 10) Takeuchi, Y.; Inoue, T.; Sunagawa, M. J. Antibiotics, 1993, 46, 827.
14. 11) Macromodel ver. 4.5: Mohamadi, F.; Richards, N. G. J.; Guida, W. C.; Liskamp, R.; Canfield, C.; Chang, G. Hendrickson, T.; Still, W. C. J. Comput. Chem., 11, 440 (1990). Molecular modeling studies were carried out on a Silicon Graphics Indigo 2 workstation using the Macromodel. Initial structures were derived from the X-ray crystal structure of meropenem and 1000 steps of Monte Carlo conformational searches were conducted. All flexible bonds except the carbapenem ring system were allowed to rotate and minimizations were performed for each structure up to 2000 iterations using the MM3* force field with parameters implemented in the modeling program. Conformations within 10 KJ of the lowest energy were examined.
15. 12) Yanagi, K.; Takeuchi, Y.; Sunagawa, M. Acta Crystallogr. Sect. C : Cryst. Struct. Commun., 1992, C48 (9), 1737.
16. 1 dimension were zero-filled to 512 points prior to the FT.