Novel renin inhibitors containing (2S,3S,5S)-2-amino-1-cyclohexyl-6- methyl-3,5-heptanediol fragment as a transition-state mimic at the P1-P1' cleavage site

Chemical and Pharmaceutical Bulletin

Volumn 45, Issue 10, 1997, Pages 1631-1641

  Yamada, Yasuki ^a   Ando, Koji ^a   Ikemoto, Yukishige ^a   Tada, Hiroki ^a   Shirakawa, Eiji ^a   Inagaki, Eiji ^a   Shibata, Saizo ^a   Nakamura, Ikuro ^b   Hayashi, Yoshiharu ^b   Ikegami, Kiyoteru ^b   Uchida, Itsuo ^a  

^a JAPAN TOBACCO INC   (Japan)

^b Yoshitomi Pharmaceutical Industries Ltd   (Japan)

Author keywords

(2S,3S,5S) 2 amino 1 cyclohexyl 6 methyl 3,5 heptanediol; Blood pressure lowering effect; Renin inhibitor; Transition state mimic

Indexed keywords

2 AMINO 1 CYCLOHEXYL 6 METHYL 3,5 HEPTANEDIOL (2 AMINO 3,5 ANTI DIOL); DIPEPTIDYL CARBOXYPEPTIDASE; JTP 2724; RENIN; RENIN INHIBITOR; UNCLASSIFIED DRUG;

ANIMAL MODEL; ARTICLE; BLOOD PRESSURE REGULATION; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME SPECIFICITY; MARMOSET; NONHUMAN; ORAL DRUG ADMINISTRATION; PROTON NUCLEAR MAGNETIC RESONANCE; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; STRUCTURE ACTIVITY RELATION;

EID: 0030668574     PISSN: 00092363     EISSN: None     Source Type: Journal    
DOI: 10.1248/cpb.45.1631     Document Type: Article

References (35)

1. Shibata S., Yamada Y., Ikemoto Y., Tada H., Shirakawa E., Ando K., Tsuji H., Uchida I., Nakamura I., Hayashi Y., Inui J., Ikegami K., Part of this work has been presented at the 111th Annual Meeting of the Pharmaceutical Society of Japan, Tokyo, March 1991.
2. Zannad F., J. Cardiovasc. Pharmacol., 15 (Suppl. 2), S1-S5 (1990).
3. Petrillo E. W., Jr., Ondetti M. A., Med. Res. Rev., 2, 1-41 (1982).
4. Israili Z. H., Hall W. D., Ann. Intern. Med., 117, 234-242 (1992).
5. Erdos E. G., Hypertension, 16, 363-370 (1990).
6. Ocain T. D., Abou-Gharbia M., Drugs Fut., 16, 37-51 (1991).
7. Umezawa H., Aoyagi T., Morishima H., Matsuzaki M., Hamada M., Takeuchi T., J. Antibiot., 23, 259-262 (1970).
8. Boger J., Payne L. S., Perlow D. S., Lohr N. S., Poe M., Blaine E. H., Ulm E. H., Schorn T. W., LaMont B. I., Lin T-Y., Kawai M., Rich D. H., Veber D. F., J. Med. Chem., 28, 1779-1790 (1985).
9. The P4, P3, P2, P1 and P1′ positions correspond to the followig amino acid residues of human angiotensinogen: -Pro(P4)-Phe-(P3)-His(P2)-Leu(P1)-Val(P1′). Schechter I., Berger A., Biochem. Biophys. Res. Commun., 27, 157-162 (1967).
10. -10 M order against purified human renal renin. Luly J. R., BaMaung N., Soderquist J., Fung A. K. L., Stein H., Kleinert H. D., Marcotte P. A., Egan D. A., Bopp B., Mertis I., Bolis G., Greer J., Perun T. J., Plattner J. J., J. Med. Chem., 31, 2264-2276 (1988).
11. Sawyer T. K., Pals D. T., Mao B., Staples D. J., deVax A. E., Maggiora L. L., Affholter J. A., Kati W., Duchamp D., Hester J. B., Smith C. W., Saneii H. H., Kinner J., Handschumachar M., Carlson W., J. Med. Chem., 31, 18-30 (1988).
12. Rosenberg S. H., Dellaria J. F., Kempf D. J., Hutchins C. W., Woods K. W., Maki R. G., Lara E. de, Spina K. P., Stein H. H., Cohen J., Baker W. R., Plattner J. J., Kleinert H. D., Perun T. J., J. Med. Chem., 33, 1582-1590 (1990).
13. a) Iizuka K., Kamijo T., Harada H., Akahane K., Kubota T., Umeyama H., Kiso Y., J. Chem. Soc., Chem. Commun., 1989, 1678-1680;
14. b) Iizuka K., Kamijo T., Harada H., Akahane K., Kubota T., Etoh Y., Shimaoka I., Tsubaki A., Murakami M., Yamaguchi T., Iyobe A., Umeyama H., Kiso Y., Chem. Pharm. Bull., 38, 2487-2493 (1990);
15. c) Iizuka K., Kamijo T., Harada H., Akahane K., Kubota T., Umeyama H., Ishida T., Kiso Y., J. Med. Chem., 33, 2707-2714 (1990).
16. The stereoselective aldol reaction using O-silyl enol ether and Lewis acid is under examination. The results will be reported in due course.
17. Takemoto Y., Matsumoto T., Ito Y., Terashima S., Chem. Pharm. Bull., 39, 2425-2428 (1991).
18. The 2D NOESY spectra of compounds 9 and 10 were measured under the same conditions. The volume integrations of the counter plot of Ha to Hb for compounds 9 and 10 were 15 and 45, respectively, (volume integrations of the counter plot of Hcl to Hc2 for compounds 9 and 10 were both 135). a) Derome A. W., "Modern NMR Techniques for Chemistry Research," Organic Chemistry series Vol. 6, ed. by Baldwin J. E., Pergamon Books Ltd. New York, 1987, chapter 5, pp. 97-127; b) Lim M. S. L., Johnston E. R., Kettner C. A., J. Med. Chem., 36, 1831-1838 (1993).
19. The 2D NOESY spectra of compounds 9 and 10 were measured under the same conditions. The volume integrations of the counter plot of Ha to Hb for compounds 9 and 10 were 15 and 45, respectively, (volume integrations of the counter plot of Hcl to Hc2 for compounds 9 and 10 were both 135). a) Derome A. W., "Modern NMR Techniques for Chemistry Research," Organic Chemistry series Vol. 6, ed. by Baldwin J. E., Pergamon Books Ltd. New York, 1987, chapter 5, pp. 97-127; b) Lim M. S. L., Johnston E. R., Kettner C. A., J. Med. Chem., 36, 1831-1838 (1993).
20. The anti (twist boat) 1,3-diol acetonides generally display carbon resonances at 24.6±0.76 ppm for acetonide methyl groups and at 100.6±0.25 ppm for acetal carbon, while the syn isomers generally display methyl resonance at 19.4±0.21 ppm and 30.0±0.15 ppm, and acetal carbon resonance at 98.1±0.83 ppm. a) Rychnovsky S. D., Skalitzky D. J., Tetrahedron Lett., 31, 945-948 (1990); b) Evans D. A., Rieger D. L., Gage J. R., ibid., 31, 7099-7100 (1990).
21. The anti (twist boat) 1,3-diol acetonides generally display carbon resonances at 24.6±0.76 ppm for acetonide methyl groups and at 100.6±0.25 ppm for acetal carbon, while the syn isomers generally display methyl resonance at 19.4±0.21 ppm and 30.0±0.15 ppm, and acetal carbon resonance at 98.1±0.83 ppm. a) Rychnovsky S. D., Skalitzky D. J., Tetrahedron Lett., 31, 945-948 (1990); b) Evans D. A., Rieger D. L., Gage J. R., ibid., 31, 7099-7100 (1990).
22. Fujii T., Sakakibara S., Bull. Chem. Soc. Jpn., 47, 3146-3151 (1974).
23. During the N-methylation of 42, racemization occurred to the extent of 10±5%. Optically pure 43 was obtained by repeated recrystallization.
24. 8 packed column (Nakarai, Japan), 4.6 I.D. × 150mm; mobile phase, 20mM phosphate buffer (pH 2.2)/acetonitrile (3/2); flow rate, 1.0ml/min; temperature, 40 °C. Retention times of compound 21 and its D-phenylalanyl derivative were 6.4 and 10.0 min, respectively.
25. 50 value of FK906 against human plasma renin is 3.0 nM. a) Drugs Fut., 18, 312-315 (1993); b) Japan Kokai Tokkyo Koho, Japan. Patent 64-19071 (1989) [Chem. Abstr., 112, 669 f]; c) Ogihara T., Nagano M., Higaki J, Higashimori K., Masuo K., Mikami H., Clinical Therapeutics, 15, 539-548 (1993).
26. 50 value of FK906 against human plasma renin is 3.0 nM. a) Drugs Fut., 18, 312-315 (1993); b) Japan Kokai Tokkyo Koho, Japan. Patent 64-19071 (1989) [Chem. Abstr., 112, 669 f]; c) Ogihara T., Nagano M., Higaki J, Higashimori K., Masuo K., Mikami H., Clinical Therapeutics, 15, 539-548 (1993).
27. 50 value of FK906 against human plasma renin is 3.0 nM. a) Drugs Fut., 18, 312-315 (1993); b) Japan Kokai Tokkyo Koho, Japan. Patent 64-19071 (1989) [Chem. Abstr., 112, 669 f]; c) Ogihara T., Nagano M., Higaki J, Higashimori K., Masuo K., Mikami H., Clinical Therapeutics, 15, 539-548 (1993).
28. Miyazaki M., Drugs Fut., 13, 1042-1044 (1988).
29. Thaisrivongs S., Pals D. T., Harris D. W., Kati W. M., Turner S. R., J. Med. Chem., 29, 2088-2093 (1986).
30. Kleinert H. D., Martin D., Chekal M. A., Kadam J., Luly J. R., Plattner J. J., Perun T. J., Luther R. R., Hypertension, 11, 613-619 (1988).
31. Rosenberg S. H., Woods K. W., Sham H. L., Kleinert H. D., Martin D. L., Stein H., Cohen J., Egan D. A., Bopp B., Mertis I., Garren K. W., Hoffman D. J., Plattner J. J., J. Med. Chem., 33, 1962-1969 (1990).
32. North A. C. T., Phillips D. C., Mathews F. S., Acta Cryst., A24, 351-359 (1968).
33. Fan H. M., SAPI-91, Structure Analysis Programs with Intelligent Control, Rigaku Corporation, Tokyo Japan, 1991.
34. Sheldrick G. M., SHELXL-93, Program for the Refinement of Crystal Structures, University of Göttingen, Germany, 1993.
35. Flack H. D., Acta Cryst., A39, 876-881 (1983).