Antiviral and tumor cell antiproliferative SAR studies on tetracyclic eudistomins-II

Bioorganic and Medicinal Chemistry

Volumn 5, Issue 5, 1997, Pages 955-970

  Van Maarseveen, Jan H ^a   Scheeren, Hans W ^a   De Clercq, Erik ^b   Balzarini, Jan ^b   Kruse, Chris G ^c  

^a RADBOUD UNIVERSITY NIJMEGEN   (Netherlands)

^b REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

^c Solvay Pharmaceuticals Inc   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIVIRUS AGENT; EUDISTOMIN DERIVATIVE;

ANTINEOPLASTIC ACTIVITY; ANTIVIRAL ACTIVITY; ARTICLE; CANCER CELL; CYTOTOXICITY; DIASTEREOISOMER; DRUG ACTIVITY; DRUG SYNTHESIS; HUMAN; NONHUMAN; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; STRUCTURE ACTIVITY RELATION; VIRUS REPLICATION;

ANIMALS; ANTINEOPLASTIC AGENTS; ANTIVIRAL AGENTS; CARBOLINES; DRUG DESIGN; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; MICROBIAL SENSITIVITY TESTS; STRUCTURE-ACTIVITY RELATIONSHIP; TUMOR CELLS, CULTURED; VIRUSES;

HUMAN HERPESVIRUS 1; HUMAN HERPESVIRUS 2; VACCINIA; VACCINIA VIRUS; VESICULAR STOMATITIS VIRUS;

EID: 0030954510     PISSN: 09680896     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0968-0896(97)00034-5     Document Type: Article

References (38)

1. Davidson, B. S. Chem. Rev. 1993, 93, 1771.
2. (a) Rinehart Jr., K. L.; Kobayashi, J.; Harbour, C. G.; Gilmore, J.; Mascal, M.; Holt, T. G.; Shield, L. S.; Lafargue, F. J. Am. Chem. Soc. 1987, 109, 3378.
3. (b) Blunt, J. W.; Lake, R. J.; Munro, M. H. G.; Toyokuni, T. Tetrahedron Lett. 1987, 28, 1825.
4. Lake, R. J.; Brennan, M. M.; Blunt, J. W.; Munro, M. H. G.; Pannell, L. K. Tetrahedron Lett. 1988, 29, 2255.
5. Lake, R. J.; Blunt, J. W.; Munro, M. H. G. Aust. J. Chem. 1989, 42, 1201.
6. (a) Hermkens, P. H. H. Thesis, Catholic University of Nijmegen, 1990.
7. (b) Hermkens, P. H. H.; Maarseveen, J. H. van; Ottenheijm, H. C. J.; Kruse, C. G.; Scheeren, J. W. J. Org. Chem. 1990, 55, 3998.
8. Nakagawa, M.; Liu, J. J.; Hino, T. J. Am. Chem. Soc. 1989, 111, 2721.
9. Liu, J. J.; Nakagawa, M.; Harada, N.; Tsuruoka, A.; Hasegawa, A.; Ma, J.; Hino, T. 1990, 31, 229.
10. (e) Still, I. W. J.; Strautmanis, J. Tetrahedron Lett. 1989, 30, 1041.
11. (f) Still, I. W. J.; Strautmanis, J. Can. J. Chem. 1990, 68, 1408.
12. (a) Maarseveen, J. H. van; Hermkens, P. H. H.; De Clercq, E.; Balzarini, J.; Scheeren, J. W.; Kruse, C. G. J. Med. Chem. 1992, 35, 3223.
13. (b) Recently a paper appeared describing an SAR study of some tetracyclic eudistomin desthia carba derivatives: Kurihara, T.; Sakamoto, Y.; Kimura, T.; Ohishi, H.; Harusawa, S.; Yoneda, R.; Suzutani, T.; Azuma, M. Chem. Pharm. Bull. 1996, 44, 900.
14. Maarseveen, J. H. van; Kruse, C. G.; Scheeren, J. W. Tetrahedron 1993, 49, 2325.
15. (a) Tietze, L. F.; Schimpf, R.; Wichmann, J. Chem. Ber. 1992, 125, 2571.
16. (b) Maryanoff, B. E.; Rebarchak, M. C. Synthesis 1992, 1245.
17. Maurer, P. J.; Miller, M. J. J. Am. Chem. Soc. 1982, 104, 3096.
18. We also successfully used O-TBDMS-N-Aloc-hydroxylamine in the Mitsunobu reaction-based approach towards N-hydroxy-2(3,4-dimethoxyphenyl)ethylamine derivatives from 2-(3,4-dimethoxyphenyl)ethanol. Similar carbamate-protected hydroxylamines have recently also been used for the Mitsunobu reaction-mediated synthesis of N-hydroxy-α-amino acids from α-hydroxy acids; Hanessian, S.; Yang, R-Y. Synlett 1995, 633.
19. McNulty, J.; Still, I. W. J. Synth.Comm. 1992, 22, 979.
20. Dijkstra, G. D. H.; Tulp, M. Th. M.; Hermkens, P. H. H.; Maarseveen, J. H. van; Scheeren, H. W.; Kruse, C. G. Recl. Trav. Chim. Pays-Bas 1993, 112 , 131.
21. Liu, J.-J.; Nakagawa, M.; Hino, T. Tetrahedron 1989, 45, 7729.
22. Liu, J.-J.; Nakagawa, M.; Ogata, K.; Hino, T. Chem. Pharm. Bull. 1991, 39, 1672.
23. The NMR data of the trans diastereomer 7 were obtained at 58 °C to give a sharp spectrum. At this temperature two conformers existed in a 4:1 ratio. These conformers result from inversion of the N(2) nitrogen atom. Peak-broadening due to a nitrogen inversion process occurring at the NMR timescale is known for cyclic 1,2-oxaza compounds. See: Riddel, F.G. Tetrahedron 1981, 37, 849.
24. In the literature two successful approaches to the eudistomin desthia carba skeleton have been described (see also ref 15). During our synthetic investigations towards the cis desthia carba derivative, Kurihara and coworkers succeeded in the synthesis using an efficient approach. This strategy included the Meisenheimer [2,3]-sigmatropic rearrangement followed by base-induced epimerization, reduction of the obtained double bond, and a Curtius reaction for introduction of the C(1)-amino group to give the desthia carba eudistomin derivative as a racemate in good yields: Kurihara, T.; Sakamoto, Y.; Matsumoto, H.; Kawabata, N.; Harusawa, S.; Yoneda, R. Chem. Pharm. Bull. 1994, 42, 475 (see also ref 4b).
25. Kirkup, M. P.; Shankar, N. B.; McCombie, S.; Ganguly, A. K. Tetrahedron Lett. 1989, 30, 6809.
26. We also attempted the synthesis of 22 by selective reduction of the carboxyl group in (D)-Trt-Glu(OH)-OMe. (D)-Trt-Glu(OH)-OMe was synthesized in 76% yield by selective saponification of the γ-ester in (D)-Trt-Glu(OMe)-OMe 21 following a modified literature procedure; Amiard, G.; Heyms, R.; Velluz, L. Bull. Soc. Chim. Fr. 1956, 97. Selective reduction of the terminal carboxyl group with borane dimethylsulfide surprisingly gave Trt-Pro-OMe in a nearly quantitative yield instead of the anticipated γ-alcohol. This can be explained by the formation of a cyclic iminium ion from the intermediate aldehyde, probably catalyzed by the borane reagent. The highly electrophilic iminium ion is then reduced by the borane dimethylsulfide complex to yield the proline derivative. Substitution of the trityl amino protective group by BOC or Cbz protective groups also gave the prolines in nearly quantitative yields.
27. Attempted transformation of the alcohol into the tosylate also gave Trt-Pro-OMe as the main product (see ref 15). Although the tosylate was visible on TLC as an intermediate, it was not possible to optimize the reaction conditions.
28. Dr B. B. Shankar of Schering Plough Research Institute (New Jersey, U.S.A.) is greatly acknowledged for providing the X-ray crystallography and NMR data of several desthia carba eudistomin analogues.
29. (a) De Clercq, E.; Descamps, J.; Verhelst, G.; Walker, R. T.; Jones, A. S.; Torrence, P. F.; Shugar, D. J. Infect. Dis. 1980, 5, 563.
30. (b) De Clercq, E.; Montgomery, J. A. Antiviral Res. 1983, 3, 17.
31. Balzarini, J.; Naesens, L.; Herdewijn, P.; Rosenberg, I.; Holy, A.; Pauwels, R.; Baba, M.; Johns, D. G.; De Clercq, E. Proc. Natl. Acad. Sci. U.S.A. 1989, 86, 332.
32. 50 values, this does not exclude its potential use as an antiviral agent as it may be perfectly well applicable as a topical drug (i.e., ointments, drops, aerosol, etc.) in the treatment of virus infections of not actively dividing cells (i.e. on the skin, cornea, respiratory epithelium, etc.). In fact, all antiviral agents that are targeted at cellular enzymes (e.g., ribavirin, neplanocin, pyrazofurin, etc.) may be expected to inhibit both virus replication and cell proliferation. Therefore, the MCC:MIC ratio is a proven parameter for the prediction of clinical antiviral efficacy. The exception to the rule is HIV which replicates in actively dividing cells (i.e., T-lymphocytes). Thus compounds that interfere with the proliferation of the T-cells may not show up as selective anti-HIV agents, as these compounds would be active against HIV only at concentrations that inhibit host cell proliferation as well.
33. (a) De Clercq, E.; Balzarini, J.; Torrence, P. F.; Mertes, M. P.; Schmidt, C. L.; Shugar, D.; Barr, P. J.; Jones, A. S.; Verhelst, G.; Walker, R. T. Mol. Pharmacol. 1981, 19, 321.
34. (b) Balzarini, J.; De Clercq, E.; Torrence, P. F.; Mertes, M. P.; Park, J. S.; Schmidt, C. L.; Shugar, D.; Barr, P. J.; Jones, A. S.; Verhelst, G.; Walker, R. T. Biochem. Pharmacol. 1982, 31, 1089.
35. (a) Kepers, Y. P.; Pizao, P. E.; Peters, G. J.; Van Ark-Otte, J.; Winograd, B.; Pinedo, H. M. Eur. J. Cancer. 1991, 27, 897.
36. (b) Boyd, M. R. Status of the NCI preclinical antitumor drug discovery screen. Principles and practice of oncology. 1989, 3, 1.
37. De Clercq, E.; Murase, J.; Marquez, V. E. Biochem. Pharmacol. 1991, 41, 1821.
38. Arx, E. v.; Faupel, M.; Brugger, M. J. J.Chromatogr. 1976, 120, 224.