Synthesis and pharmacological evaluation of 1-Alkyl-N-[(1R)-1-(4- fluorophenyl)-2-methylpropyl]piperidine-4-carboxamide derivatives as novel antihypertensive agents

Chemical and Pharmaceutical Bulletin

Volumn 59, Issue 11, 2011, Pages 1376-1385

  Watanuki, Susumu ^a   Matsuura, Keisuke ^a   Tomura, Yuichi ^a   Okada, Minoru ^a   Okazaki, Toshio ^a   Ohta, Mitsuaki ^a   Tsukamoto, Shin Ichi ^a  

^a ASTELLAS PHARMA INC   (Japan)

Author keywords

Antihypertensive agent; Mibefradil; Piperidine 4 carboxamide; T type Ca2+ channel

Indexed keywords

1 [2 (2,3 DIMETHOXYLPHENYL)ETHYL] N [1 (4 FLUOROPHENYL) 2 METHYLPROPYL]PIPERIDINE 4 CARBOXAMIDE OXALATE; 1 [2 (2,5 DIMETHOXYLPHENYL)ETHYL] N [1 (4 FLUOROPHENYL) 2 METHYLPROPYL]PIPERIDINE 4 CARBOXAMIDE OXALATE; 1 [2 (3,4 DIMETHOXYLPHENYL)ETHYL] N [1 (4 FLUOROPHENYL) 2 METHYLPROPYL]PIPERIDINE 4 CARBOXAMIDE OXALATE; 1 [2 (3,5 DIMETHOXYLPHENYL)ETHYL] N [1 (4 FLUOROPHENYL) 2 METHYLPROPYL]PIPERIDINE 4 CARBOXAMIDE OXALATE; ANTIHYPERTENSIVE AGENT; CALCIUM CHANNEL BLOCKING AGENT; CALCIUM CHANNEL T TYPE; ETHYL [3 [2 [4 [[1 (4 FLUOROPHENYL) 2 METHYLPROPYL]CARBAMOYL]PIPERIDIN 1 YL]ETHYL]PHENOXY]ACETATE OXALATE; MIBEFRADIL; N (3 PHENYLPENTAN 3 YL) 1 (2 PHENYLETHYL)PIPERIDINE 4 CARBOXAMIDE FUMARATE; N [1 (4 FLUOROPHENYL) 2 METHYLPROPYL] 1 (2 PHENYLETHYL)PIPERIDINE 4 CARBOXAMIDE; N [1 (4 FLUOROPHENYL) 2 METHYLPROPYL] 1 [2 (2 METHOXYLPHENYL)ETHYL]PIPERIDINE 4 CARBOXAMIDE FUMARATE; N [1 (4 FLUOROPHENYL) 2 METHYLPROPYL] 1 [2 (3 METHOXYLPHENYL)ETHYL]PIPERIDINE 4 CARBOXAMIDE OXALATE; N [1 (4 FLUOROPHENYL) 2 METHYLPROPYL] 1 [2 (3 METHOXYPHENYL)ETHYL]PIPERIDINE 4 CARBOXAMIDE; N [1 (4 FLUOROPHENYL) 2 METHYLPROPYL] 1 [2 (4 METHOXYLPHENYL)ETHYL]PIPERIDINE 4 CARBOXAMIDE FUMARATE; N [1 (4 FLUOROPHENYL) 2 METHYLPROPYL] 1 [2 [2 (TRIFLUOROMETHYL)PHENYL]ETHYL]PIPERIDINE 4 CARBOXAMIDE OXALATE; N [1 (4 FLUOROPHENYL) 2 METHYLPROPYL] 1 [2 [3 (2 HYDROXYETHOXY)PHENYL]ETHYL]PIPERIDINE 4 CARBOXAMIDE; N [1 (4 FLUOROPHENYL) 2 METHYLPROPYL] 1 [2 [3 (2 METHOXYETHOXY)PHENYL]ETHYL]PIPERIDINE 4 CARBOXAMIDE; N [1 (4 FLUOROPHENYL) 2 METHYLPROPYL] 1 [2 [3 (TRIFLUOROMETHYL)PHENYL]ETHYL]PIPERIDINE 4 CARBOXAMIDE OXALATE; N [1 (4 FLUOROPHENYL) 2 METHYLPROPYL] 1 [2 [4 (TRIFLUOROMETHYL)PHENYL]ETHYL]PIPERIDINE 4 CARBOXAMIDE OXALATE; N [3 (2 FLUOROPHENYL)PENTAN 3 YL] 1 (2 PHENYLETHYL)PIPERIDINE 4 CARBOXAMIDE FUMARATE; N [3 (2 METHOXYPHENYL)PENTAN 3 YL] 1 (2 PHENYLETHYL)PIPERIDINE 4 CARBOXAMIDE FUMARATE; N [3 (3 FLUOROPHENYL)PENTAN 3 YL] 1 (2 PHENYLETHYL)PIPERIDINE 4 CARBOXAMIDE FUMARATE; N [3 (3 METHOXYPHENYL)PENTAN 3 YL] 1 (2 PHENYLETHYL)PIPERIDINE 4 CARBOXAMIDE FUMARATE; N [3 (4 FLUOROPHENYL)PENTAN 3 YL] 1 (2 PHENYLETHYL)PIPERIDINE 4 CARBOXAMIDE FUMARATE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BLOOD PRESSURE; DRUG SYNTHESIS; ESSENTIAL HYPERTENSION; HUMAN; HUMAN CELL; MALE; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION; TACHYCARDIA;

AMIDES; ANIMALS; ANTIHYPERTENSIVE AGENTS; BLOOD PRESSURE; CALCIUM CHANNEL BLOCKERS; CALCIUM CHANNELS, T-TYPE; CELL LINE; GUINEA PIGS; HUMANS; HYPERTENSION; MALE; PIPERIDINES; RATS; RATS, INBRED SHR; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 81455128899     PISSN: 00092363     EISSN: 13475223     Source Type: Journal    
DOI: 10.1248/cpb.59.1376     Document Type: Article

References (44)

1. Brini M., Carafoli E., Cell. Mol. Life Sci., 57, 354-370 (2000).
2. Catterall W. A., Perez-Reyes E., Snutch T. P., Striessnig J., Pharmacol. Rev., 57, 411-425 (2005).
3. Yamakage M., Namiki A., Can. J. Anesth., 49, 151-164 (2002).
4. Mangoni M. E., Traboulsie A., Leoni A.-L., Couette B., Marger L., Le Quang K., Kupfer E., Cohen-Solal A., Vilar J., Shin H.-S., Escande D., Charpentier F., Nargeot J., Lory P., Circ. Res., 98, 1422-1430 (2006).
5. Ernst M. E., Kelly M. W., Pharmacotherapy, 18, 463-485 (1998).
6. Portegies M. C. M., Schmitt R., Kraaij C. J., Braat S. H. J. G., Gassner A., Hagemeijer F., Pozenel H., Prager G., Viersma J. W., van der Wall E. E., Kleinbloesem C. H., Lie K. I., J. Cardiovasc. Pharmacol., 18, 746-751 (1991).
7. Cremers B., Flesch M., Südkamp M., Böhm M., J. Cardiovasc. Pharmacol., 29, 692-696 (1997).
8. Mullins M. E., Horowitz B. Z., Linden D. H. J., Smith G. W., Norton R. L., Stump J., JAMA, 280, 157-158 (1998).
9. SoRelle R., Circulation, 98, 831-832 (1998).
10. Kumar P. P., Stotz S. C., Paramashivappa R., Beedle A. M., Zamponi G. W., Rao A. S., Mol. Pharmacol., 61, 649-658 (2002).
11. Schenck H. A., Lenkowski P. W., Choudhury-Mukherjee I., Ko S.-H., Stables J. P., Patel M. K., Brown M. L., Bioorg. Med. Chem., 12, 979-993 (2004).
12. Doddareddy M. R., Jung H. K., Lee J. Y., Lee Y. S., Cho Y. S., Koh H. Y., Pae A. N., Bioorg. Med. Chem., 12, 1605-1611 (2004).
13. Doddareddy M. R., Jung H. K., Cha J. H., Cho Y. S., Koh H. Y., Chang M. H., Pae A. N., Bioorg. Med. Chem., 12, 1613-1621 (2004).
14. Lee Y. S., Lee B. H., Park S. J., Kang S. B., Rhim H., Park J.-Y., Lee J.-H., Jeong S.-W., Lee J. Y., Bioorg. Med. Chem. Lett., 14, 3379-3384 (2004).
15. McCalmont W. F., Heady T. N., Patterson J. R., Lindenmuth M. A., Haverstick D. M., Gray L. S., Macdonald T. L., Bioorg. Med. Chem. Lett., 14, 3691-3695 (2004).
16. Jung H. K., Doddareddy M. R., Cha J. H., Rhim H., Cho Y. S., Koh H. Y., Jung B. Y., Pae A. N., Bioorg. Med. Chem., 12, 3965-3970 (2004).
17. Rhim H., Lee Y. S., Park S. J., Chung B. Y., Lee J. Y., Bioorg. Med. Chem. Lett., 15, 283-286 (2005).
18. McCalmont W. F., Patterson J. R., Lindenmuth M. A., Heady T. N., Haverstick D. M., Gray L. S., Macdonald T. L., Bioorg. Med. Chem., 13, 3821-3839 (2005).
19. Park Se. J., Park Su. J., Lee M. J., Rhim H., Kim Y., Lee J.-H., Chung B. Y., Lee J. Y., Bioorg. Med. Chem., 14, 3502-3511 (2006).
20. Ku I. W., Cho S., Doddareddy M. R., Jang M. S., Keum G., Lee J.-H., Chung B. Y., Kim Y., Rhim H., Kang S. B., Bioorg. Med. Chem. Lett., 16, 5244-5248 (2006).
21. Choi J. Y., Seo H. N., Lee M. J., Park Se. J., Park Su. J., Jeon J. Y., Kang J. H., Pae A. N., Rhim H., Lee J. Y., Bioorg. Med. Chem. Lett., 17, 471-475 (2007).
22. Kim H. S., Kim Y., Doddareddy M. R., Seo S. H., Rhim H., Tae J., Pae A. N., Choo H., Cho Y. S., Bioorg. Med. Chem. Lett., 17, 476-481 (2007).
23. Doddareddy M. R., Choo H., Cho Y. S., Rhim H., Koh H. Y., Lee J.-H., Jeong S.-W., Pae A. N., Bioorg. Med. Chem., 15, 1091-1105 (2007).
24. Park J. H., Choi J. K., Lee E., Lee J. K., Rhim H., Seo S. H., Kim Y., Doddareddy M. R., Pae A. N., Kang J., Roh E. J., Bioorg. Med. Chem., 15, 1409-1419 (2007).
25. Seo H. N., Choi J. Y., Choe Y. J., Kim Y., Rhim H., Lee S. H., Kim J., Joo D. J., Lee J. Y., Bioorg. Med. Chem. Lett., 17, 5740-5743 (2007).
26. Hangeland J. J., Cheney D. L., Friends T. J., Swartz S., Levesque P. C., Rich A. J., Sun L., Bridal T. R., Adam L. P., Normandin D. E., Murugesan N., Ewing W. R., Bioorg. Med. Chem. Lett., 18, 474-478 (2008).
27. Oh Y., Kim Y., Seo S. H., Lee J. K., Rhim H., Pae A. N., Jeong K.-S., Choo H., Cho Y. S., Bull. Korean Chem. Soc., 29, 1881-1882 (2008).
28. Shipe W. D., Barrow J. C., Yang Z.-Q., Lindsley C. W., Yang F. V., Schlegel K.-A. S., Shu Y., Rittle K. E., Bock M. G., Hartman G. D., Tang C., Ballard J. E., Kuo Y., Adarayan E. D., Prueksaritanont T., Zrada M. M., Uebele V. N., Nuss C. E., Connolly T. M., Doran S. M., Fox S. V., Kraus R. L., Marino M. J., Graufelds V. K., Vargas H. M., Bunting P. B., Hasbun-Manning M., Evans R. M., Koblan K. S., Renger J. J., J. Med. Chem., 51, 3692-3695 (2008).
29. Heo J. H., Seo H. N., Choe Y. J., Kim S., Oh C. R., Kim Y. D., Rhim H., Choo D. J., Kim J., Lee J. Y., Bioorg. Med. Chem. Lett., 18, 3899-3901 (2008).
30. Lee H. K., Lee Y. S., Roh E. J., Rhim H., Lee J. Y., Shin K. J., Bioorg. Med. Chem. Lett., 18, 4424-4427 (2008).
31. Yang Z.-Q., Barrow J. C., Shipe W. D., Schlegel K.-A. S., Shu Y., Yang F. V., Lindsley C. W., Rittle K. E., Bock M. G., Hartman G. D., Uebele V. N., Nuss C. E., Fox S. V., Kraus R. L., Doran S. M., Connolly T. M., Tang C., Ballard J. E., Kuo Y., Adarayan E. D., Prueksaritanont T., Zrada M. M., Marino M. J., Graufelds V. K., DiLella A. G., Reynolds I. J., Vargas H. M., Bunting P. B., Woltmann R. F., Magee M. M., Koblan K. S., Renger J. J., J. Med. Chem., 51, 6471-6477 (2008).
32. Jeong J. A., Cho H., Jung S. Y., Kang H. B., Park J. Y., Kim J., Choo D. J., Lee J. Y., Bioorg. Med. Chem. Lett., 20, 38-41 (2010).
33. Gu S. J., Lee J. K., Pae A. N., Chung H. J., Rhim H., Han S. Y., Min S.-J., Cho Y. S., Bioorg. Med. Chem. Lett., 20, 2705-2708 (2010).
34. Lee J. E., Koh H. Y., Seo S. H., Baek Y. Y., Rhim H., Cho Y. S., Choo H., Pae A. N., Bioorg. Med. Chem. Lett., 20, 4219-4222 (2010).
35. Smith E. M., Sorota S., Kim H. M., McKittrick B. A., Nechuta T. L., Bennett C., Knutson C., Burnett D. A., Kieselgof J., Tan Z., Rindgen D., Bridal T., Zhou X., Jia Y.-P., Dong Z., Mullins D., Zhang X., Priestley T., Correll C. C., Tulshian D., Czarniecki M., Greenlee W. J., Bioorg. Med. Chem. Lett., 20, 4602-4606 (2010).
36. Schlegel K.-A. S., Yang Z.-Q., Reger T. S., Shu Y., Cube R., Rittle K. E., Bondiskey P., Bock M. G., Hartman G. D., Tang C., Ballard J., Kuo Y., Prueksaritanont T., Nuss C. E., Doran S. M., Fox S. V., Garson S. L., Kraus R. L., Li Y., Uebele V. N., Renger J. J., Barrow J. C., Bioorg. Med. Chem. Lett., 20, 5147-5152 (2010).
37. Kam Y. L., Rhee H.-K., Rhim H., Back S. K., Na H. S., Choo H.-Y. P., Bioorg. Med. Chem., 18, 5938-5944 (2010).
38. Fritch P. C., Krajewski J., Bioorg. Med. Chem. Lett., 20, 6375-6378 (2010).
39. Choi Y.-H., Baek J., Seo S. H., Lee J. K., Pae A. N., Cho Y. S., Min S.-J., Bioorg. Med. Chem. Lett., 21, 215-219 (2011).
40. Reger T. S., Yang Z.-Q., Schlegel K.-A. S., Shu Y., Mattern C., Cube R., Rittle K. E., McGaughey G. B., Hartman G. D., Tang C., Ballard J., Kuo Y., Prueksaritanont T., Nuss C. E., Doran S. M., Fox S. V., Garson S. L., Li Y., Kraus R. L., Uebele V. N., Renger J. J., Barrow J. C., Bioorg. Med. Chem. Lett., 21, 1692-1696 (2011).
41. Watanuki S., Matsuura K., Tomura Y., Okada M., Okazaki T., Ohta M., Tsukamoto S., Chem. Pharm. Bull., 59, 1029-1037 (2011).
42. Watanuki S., Matsuura K., Tomura Y., Okada M., Okazaki T., Ohta M., Tsukamoto S., Bioorg. Med. Chem., 19, 5628-5638 (2011).
43. Jirgensons A., Kauss V., Kalvinsh I., Gold M. R., Synthesis, 2000, 1709-1712 (2000).
44. Hengartner U., Ramuz H., E. P. Patent, 388739 (1990) [Chem. Abstr., 114, 732 (1991)].