Synthesis and evaluation of 1-arylsulfonyl-3-piperazinone derivatives as factor Xa inhibitors1-4 V. A series of new derivatives containing a spiro[imidazo[1,2-a]pyrazine-2(3H),4′-piperidin]-5(1H)-one scaffold

Chemical and Pharmaceutical Bulletin

Volumn 54, Issue 11, 2006, Pages 1535-1544

  Saitoh, Fumihiko ^a   Mukaihira, Takafumi ^a   Nishida, Hidemitsu ^a   Satoh, Tsutomu ^a   Okano, Akihiro ^a   Yumiya, Yasunobu ^a   Ohkouchi, Munetaka ^a   Johka, Rumi ^a   Matsusue, Tomokazu ^a   Shiromizu, Ikuya ^a   Hosaka, Yoshitaka ^a   Matsumoto, Miwa ^a   Ohnishi, Shuhei ^a  

^a MOCHIDA PHARMACEUTICAL CO   (Japan)

Author keywords

Factor Xa inhibitor; Intramolecular cyclization; M58163; M58169; N,N spiro acetal; Structure activity relationship

Indexed keywords

1 SULFONYL 3 PIPERAZINONE DERIVATIVE; ACETAL DERIVATIVE; BLOOD CLOTTING FACTOR 10A INHIBITOR; ESTER DERIVATIVE; M 58163; M 58169; SPIRO[IMIDAZOL[1,2 ALPHA]PYRAZINE 2(3HH),4' PIPERIDIN] 5(1H) ONE; UNCLASSIFIED DRUG;

ARTICLE; CONTROLLED STUDY; CRYSTALLOGRAPHY; DRUG INHIBITION; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; IC 50; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY;

CRYSTALLOGRAPHY, X-RAY; FACTOR XA; MAGNETIC RESONANCE SPECTROSCOPY; MODELS, MOLECULAR; MOLECULAR STRUCTURE; NAPHTHALENES; PIPERAZINES; PIPERIDONES; SENSITIVITY AND SPECIFICITY; SPIRO COMPOUNDS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 33750732286     PISSN: 00092363     EISSN: 13475223     Source Type: Journal    
DOI: 10.1248/cpb.54.1535     Document Type: Article

References (43)

1. Part 1: Nishida H., Miyazaki Y., Kitamura Y., Ohashi M., Matsusue T., Okamoto A., Hosaka Y., Ohnishi S., Mochizuki H., Chem. Pharm. Bull., 49, 1237-1244 (2001).
2. Part 2: Nishida H., Miyazaki Y., Mukaihira T., Saitoh F., Fukui M., Harada K., Itoh M., Muraoka A., Matsusue T., Okamoto A., Hosaka Y., Matsumoto M., Ohnishi S., Mochizuki H., Chem. Pharm. Bull., 50, 1187-1194 (2002).
3. Part 3: Nishida H., Miyazaki Y., Mukaihira T., Shimada H., Suzuki K., Saitoh F., Mizuno M., Matsusue T., Okamoto A., Hosaka Y., Matsumoto M., Ohnishi S., Mochizuki H., Chem. Pharm. Bull., 52, 459-462 (2004).
4. Part 4: Nishida H., Mukaihira T., Saitoh F., Harada K., Fukui M., Matsusue T., Okamoto A., Hosaka Y., Matsumoto M., Shiromizu I., Ohnishi S., Mochizuki H., Chem. Pharm. Bull., 52, 406-412 (2004).
5. Hosaka Y., Matsumoto M., Shinozaki M., Ohno T., Yatagai Y., Kamiya M., Kurokawa M., Nishida H., Matsusue T., Mizuguchi K., Ishi H., Eur. J. Pharmacol., 529, 164-171 (2006).
6. Davie E. W., Fujikawa K., Kisiel W., Biochemistry, 30, 10363-10370 (1991).
7. Mann K. G., Nesheim M. E., Church W. R., Haley P., Krishnaswamy S., Blood, 76, 1-16 (1990).
8. Rosenberg J. S., Beeler D. L., Rosenberg R. D., J. Biol. Chem., 250, 1607-1617 (1995).
9. Harker L. A., Hanson S. R., Kelly A. B., Thromb. Haemost., 78, 736-741 (1997).
10. Elodi S., Varadi K., Thromb. Res., 15, 617-629 (1979).
11. Markwardt F., Nowak G., Sturzebecher J., Vogel G., Thromb. Res., 52, 393-400 (1988).
12. Heras M., Chesbro J. H., Penny W. J., Bailey K. R., Badimon L., Fuster V., Circulation, 79, 657-665 (1989).
13. Markwardt F., Thromb. Haemost., 66, 141-152 (1991).
14. Markwardt F., Thromb. Res., 74, 1-23 (1994).
15. Kaplan K. L., Francis C. W., Semin. Hematol., 39, 187-196 (2002).
16. Waxman L., Smith D. E., Arcuri K. E., Vlasuk G. P., Science, 248, 593-596 (1990).
17. Jordan S. P., Waxman L., Smith D. E., Vlasuk G. P., Biochemisyry, 29, 11095-11100 (1990).
18. Neper M. P., Waxman L., Smith D. E., Schulman C. A., Sardana M., Ellis R. W., Schaffer L. W., Siegel P. K. S., Vlasuk G. P., J. Biol. Chem., 265, 17746-17752 (1990).
19. Schaffer L. W., Davidson J. T., Vlasuk G. P., Siegl P. K. S., Circulation, 84, 1741-1748 (1991).
20. Dunwiddie C. T., Neeper M. P., Nutt E. M., Waxman L., Smith D. E., Hofmann K. J., Lumma P. K., Garsky V. M., Vlasuk G. P., Biochemistry, 31, 12126-12131 (1992).
21. Vlasuk G. P., Thromb. Haemost., 70, 212-216 (1993).
22. Ragosta M., Gimple L. W., Gertz D., Dunwiddie C. T., Vlasuk G. P., Haber H. L., Powers E. R., Roberts W. C., Sarembock I. J., Circulation, 89, 1262-1271 (1994).
23. Fevig J. M., Wexler R. R., Ann. Rep. Med. Chem., 34, 81-100 (1999).
24. Sanderson P. E. J., Med. Res. Rev., 19, 179-197 (1999).
25. Hauptmann J., Sturzebecher J., Thromb. Res., 93, 203-241 (1999).
26. Weitz J. I., Hirsh J., Chest., 119, 95S-107S (2001).
27. Eisenberg P. R., Siegel J. E., Abendschein D. R., Miletich J. P., J. Clin. Invest., 91, 1877-1883 (1993).
28. Kaiser B., Hauptmann J., Cardiovasc. Drug. Rev., 12, 225-236 (1994).
29. Prager N. A., Abendschein D. R., McKenzie C. R., Eisenberg P. R., Circulation, 92, 962-967 (1995).
30. Wong P. C., Crain E. J., Jr., Nguan O., Watson C. A., Racanelli A., Thromb. Res., 83, 117-126 (1996).
31. Herault J. P., Bernat A., Pflieger A. M., Lormeau J. C., Herbert J. M., J. Pharmacol. Exp. Ther., 283, 16-22 (1997).
32. Scarborough R. M., J. Enzym. Inhib., 14, 15-25 (1998).
33. Kunitada S., Therap. Res., 19, 7-12 (1998).
34. MOPAC PM3 calculation was used in SYBYL7.1 (Tripos Inc.)
35. Anell P. L., Biffi C., Montanari F., Quici S., J. Org. Chem., 52, 2559-2662 (1987).
36. Araki K., Kuroda T., Tsutsumi K., Isoshima H., WO 9313191 (1993).
37. Pauling L., J. Am. Chem. Soc., 54, 3570-3582 (1932).
38. teXan: Single Crystal Structure Analysis Software, Version 1.6 (1993). Molecular Structure Corporation, The Woodlands, TX. 77381.
39. Ψ-Scan Absorption Correction: North A. C. T., Phillips D. C., Mathews F. S., Acta Crystallogr., A24, 351-359 (1968).
40. Full Matrix Least Squares : Busing W. R., Mratin K. O., Levy H. A., ORFLS, A FORTRAN Crystallographic Least Squares Program, Report ORNL-TM-305, Oak Ridge National Laboratory, Oak Ridge, Tennesee, 1962.
41. FLACK X-PARAMETER: Flack H. D., Acta Crystallogr., A39, 876-881 (1983).
42. FLACK X-PARAMETER: Bernardinelli G., Flack H. D., Acta Crystallogr., A41, 500-511 (1985).
43. SIR92: A program for crystal structure solution. Altomare A., Cascarano G., Giacovazzo C., Guagliardi A., J. Appl. Crystallogr., 26, 343-350 (1993).