Synthesis and structure-activity relationships of thienylcyanoguanidine derivatives as potassium channel openers

Chemical and Pharmaceutical Bulletin

Volumn 45, Issue 12, 1997, Pages 2005-2010

  Yoshiizumi, Kazuya ^a   Ikeda, Shoji ^a   Nishimura, Noriyasu ^a   Yoshino, Kohichiro ^a  

^a KANEBO LTD   (Japan)

Author keywords

Pinacidil; Potassium channel opener; Smooth muscle relaxation activity; Thienylcyanoguanidine

Indexed keywords

BENZENE DERIVATIVE; PINACIDIL; POTASSIUM CHANNEL; POTASSIUM CHANNEL STIMULATING AGENT; POTASSIUM ION; THIOPHENE DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIHYPERTENSIVE ACTIVITY; ARTICLE; CECUM; DOG; DRUG ACTIVITY; DRUG SYNTHESIS; GUINEA PIG; MEAN ARTERIAL PRESSURE; NONHUMAN; SMOOTH MUSCLE RELAXATION; STEREOISOMERISM; STRUCTURE ACTIVITY RELATION;

EID: 0031471693     PISSN: 00092363     EISSN: None     Source Type: Journal    
DOI: 10.1248/cpb.45.2005     Document Type: Article

References (36)

1. Previous paper : Yoshiizumi K., Ikeda S., Goto K., Morita T., Nishimura N., Sukamoto T., Yoshino K., Chem. Pharm. Bull., 44, 2042-2050 (1996).
2. Robertson D. W., Steinberg M. I., J. Med. Chem., 33, 1529-1541 (1990).
3. Longman S. D., Hamilton T. C., Med. Res. Rev., 12, 73-148 (1992).
4. Petersen H. J., Nielsen C. K., Arrigoni-Martelli E., J. Med. Chem., 21, 773-781 (1978).
5. Goldberg M. R., Rockhold F. W., Offen W. W., Dornseif B. E., Clin. Pharmacol. Ther., 46, 208-218 (1989).
6. Atwal K. S., Moreland S., McCullough J. R., O'Reilly B. C., Ahmed S. Z., Normandin D. E., Bioorg. Med. Chem. Lett., 2, 83-86 (1992).
7. Manley P. W., Quast U., J. Med. Chem., 35, 2327-2340 (1992).
8. Takemoto T., Eda M., Okada T., Sakashita H., Matzno S., Gohda M., Ebisu H., Nakamura N., Fukaya C., Hihara M., Eiraku M., Yamanouchi K., Yokoyama K., J. Med. Chem., 37, 18-25 (1994).
9. Goldberg M. R., Sushak C. S., Rockhold F. W., Thompson W. L., Clin. Pharmacol. Ther., 44, 78-92 (1988).
10. Sterndorff B., Johansen P., Acta Med. Scand., 224, 329-336 (1988).
11. Ramsey L. E., Freestone S., Br. J. Clin. Pharmcol., 16, 336-338 (1983).
12. Reports describing bioisosterism, see; a) Russell R. K., Press J. B., Rumpulla R. A., McNally J. J., Falotico R. F., Keiser J. A., Bright D. A., Tobia A., J. Med. Chem., 31, 1786-1793 (1988); b) Press J. B., Russell R. K., McNally J. J., Rampulla R. A., Falotico R., Scott C., Moore J. B., Offord S. J., Tobia J., Eur. J. Med. Chem., 26, 807-813 (1991); c) Wong G., Skolnick P., Eur. J. Pharm. Mol. Pharm. Sec., 225, 63-68 (1992).
13. Reports describing bioisosterism, see; a) Russell R. K., Press J. B., Rumpulla R. A., McNally J. J., Falotico R. F., Keiser J. A., Bright D. A., Tobia A., J. Med. Chem., 31, 1786-1793 (1988); b) Press J. B., Russell R. K., McNally J. J., Rampulla R. A., Falotico R., Scott C., Moore J. B., Offord S. J., Tobia J., Eur. J. Med. Chem., 26, 807-813 (1991); c) Wong G., Skolnick P., Eur. J. Pharm. Mol. Pharm. Sec., 225, 63-68 (1992).
14. Reports describing bioisosterism, see; a) Russell R. K., Press J. B., Rumpulla R. A., McNally J. J., Falotico R. F., Keiser J. A., Bright D. A., Tobia A., J. Med. Chem., 31, 1786-1793 (1988); b) Press J. B., Russell R. K., McNally J. J., Rampulla R. A., Falotico R., Scott C., Moore J. B., Offord S. J., Tobia J., Eur. J. Med. Chem., 26, 807-813 (1991); c) Wong G., Skolnick P., Eur. J. Pharm. Mol. Pharm. Sec., 225, 63-68 (1992).
15. Reports describing absence of bioisosterism, see; a) Estenne G., Dodey P., Renaut P., Leclerc G., Bioorg. Med. Chem. Lett., 5, 15-18 (1995); b) Binder D., Koch A., Rocvenszky F., Stroissnig H., Arch. Pharm. Weinheim., 325, 797-801 (1992); c) Schove L. T., Chen S.-W., Beatty M. B., Maguire P. A., Davies M. F., Loew G. H., Bioorg. Med. Chem., 3, 1547-1561 (1995).
16. Reports describing absence of bioisosterism, see; a) Estenne G., Dodey P., Renaut P., Leclerc G., Bioorg. Med. Chem. Lett., 5, 15-18 (1995); b) Binder D., Koch A., Rocvenszky F., Stroissnig H., Arch. Pharm. Weinheim., 325, 797-801 (1992); c) Schove L. T., Chen S.-W., Beatty M. B., Maguire P. A., Davies M. F., Loew G. H., Bioorg. Med. Chem., 3, 1547-1561 (1995).
17. Reports describing absence of bioisosterism, see; a) Estenne G., Dodey P., Renaut P., Leclerc G., Bioorg. Med. Chem. Lett., 5, 15-18 (1995); b) Binder D., Koch A., Rocvenszky F., Stroissnig H., Arch. Pharm. Weinheim., 325, 797-801 (1992); c) Schove L. T., Chen S.-W., Beatty M. B., Maguire P. A., Davies M. F., Loew G. H., Bioorg. Med. Chem., 3, 1547-1561 (1995).
18. Pharmacologically active compounds containing a thiophene ring prior to 1985, see: Press J. B., "The Chemistry of Heterocyclic Compounds," Vol. 44. Thiophene and Its Derivatives Part 1 ed. by Weissberger A., Taylor E. C., John Wiley and Sons, Inc., New York. 1985, pp. 353-456 (Chapter V).
19. Sanfilippo P. J., McNally J. J., Press J. B., Fitzpatrick L. J., Urbanski M. J., Katz L. B., Giardino E., Falotico R., Salata J., Moore J. B., Miller W., J. Med. Chem., 35, 4425-4433 (1992).
20. Buschauer A., Schunack W., J. Heterocycl. Chem., 21, 753-757 (1984).
21. a) Ito Y., Hirao T., Saegusa T., J. Org. Chem., 40, 2981-2982 (1975);
22. b) Kiyoi T., Seko N., Yoshino K., Ito Y., ibid., 58, 5118-5120 (1993);
23. c) Baumagarten H. E. (ed.), "Organic Synthesis," Coll. Vol. 5, John Wiley and Sons, Inc., New York, 1973, p. 300.
24. Weir S. W., Weston A. H., Br. J. Pharmacol., 88, 113-120 (1986).
25. a) Thiophene is not a perfect pentagon as reported in reference 19b. Nevertheless, the orientation of the cyano group in 4b is thought to be almost the same as that of the cyano group in 4c, because 4b and 4c are isomers in which the cyano group and the cyanoguanidine moiety are exchanged on the thiophene ring;
26. b) Bak B., Christensen D., Hansen-Nygaard L., Rasrup-Andersen J., J. Mol. Spectrosc., 7, 58-63 (1961).
27. In the monosubstituted phenylcyanoguanidine derivatives, the most favorable substituent was chloro, but the synthesis of 4-amino-2-chlorothiophene is known to be more difficult than that of 4-amino-2-bromothiophene. So, we chose the bromo atom as the halogen substituent.
28. Calcium antagonists also relax taeniae cecum of guinea pig. See; Matsui K., Ogawa Y., Imai S., Arch. Int. Pharmacodyn., 283, 124-133 (1986).
29. a) Schmid-Antomarch H., Weille J. D., Fosset M., Lazdunski M., J. Biol. Chem., 262, 15840-15844 (1987);
30. b) Cavero I., Mondot S., Mestre M., Escande D., Br. J. Pharmacol., 95, 643P (1988).
31. Hansch C., Kiens K., Lawrence G. L., J. Am. Chem. Soc., 87, 5770-5773 (1965).
32. Hammond M. L., Zambias R. A., Chang M. N., Jensen N. P., McDonald J., Thompson K., Baulton D. A., Kopka I. E., Hand K. M., Opas E. E., Luell S., Bach T., Davies P., MacIntyre D. E., Bonney R. J., Humes J. L., J. Med. Chem., 33, 908-918 (1990).
33. Motoyama Y., Nishimura S., Imoto E., Nihon Kagaku Zasshi, 78, 788-792 (1957).
34. Maybridge Chemical Co., Ltd.
35. a) Reference 27b, mp 150-151 °C;
36. b) Tsuzuki R., Matsumoto Y., Kondo Y., Fujikura T., Uchida W., Asano M. (Yamanouchi Pharmaceutical Co., Ltd.), Japan. Patent 2-172984 (1990).