Substituted bridged phenyl piperidines: Orally active growth hormone secretagogues

Bioorganic and Medicinal Chemistry Letters

Volumn 13, Issue 10, 2003, Pages 1817-1820

  Lu, Zhijian ^a   Tata, James R ^a   Cheng, Kang ^a   Wei, Liente ^a   Chan, Wanda W S ^a   Butler, Bridget ^a   Schleim, Klaus D ^a   Jacks, Thomas M ^a   Hickey, Gerard ^a   Patchett, Arthur A ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BRIDGED COMPOUND; GROWTH HORMONE; GROWTH HORMONE SECRETAGOGUE; METHYL GROUP; PIPERIDINE DERIVATIVE;

ANIMAL CELL; ARTICLE; CIS ISOMER; CONTROLLED STUDY; CORRELATION ANALYSIS; DOG; DRUG ACTIVITY; DRUG POTENCY; DRUG SYNTHESIS; GROWTH HORMONE RELEASE; HYPOPHYSIS CELL; LOW DRUG DOSE; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION; SUBSTITUTION REACTION; TRANS ISOMER; X RAY CRYSTALLOGRAPHY;

EID: 0038743127     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(03)00261-0     Document Type: Article

References (16)

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5. For recent reviews on GHS, see: (a) Smith, R. G.; Sun, Y.; Smith, A. G. A.; Howard, A.; Feighner, S.; Dean, D.; Narguard, R. P.; Patchett, A. A. 222nd ACS National Meeting, Chicago, IL, Aug. 26-30, 2001. (b) Jungheim, L. N. 222nd ACS National Meeting, Chicago, IL, Aug. 26-30, 2001. (c) Nargund, R. P.; Ye, Z.; Tata, J. R.; Lu, Z.; Barakat, K.; Hong, Q.; Bakshi, R.; Gao, Y.; Tamvakopoulos, C.; Colwell, L.; Feighner, S.; Hreniuk, D.; Pong, S.; Cheng, K.; Schleim, K.; Jacks, T.; Strack, A.; Hickey, G.; Howard, A.; Van der Ploeg, L.; Bailey, A.; Smith, R.; and Patchett, A. A. 222nd ACS National Meeting, Chicago, IL, Aug. 26-30, 2001. (d) Carpino, P. A.; Lefker, B. A.; Toler, S. M.; Pan, L. C.; Hadcock, J. R.; Murray, M. C.; Cook, E. R.; Dibrino, J. N.; DeNinno, S. L.; Chidsey-Frink, K. L.; Hada, W. A.; Inthavongsay, J.; Lewis, S. K.; Mangano, F. M.; Mullins, M. A.; Nickerson, D. F.; Ng, O.; Pirie, C. M.; Ragan, J. A.; Rose, C. R.; Tess, D. A.; Wright, A. S.; Yu, L.; Zawistoski, M. P.; MacLean, D, B.; Pettersen, J. C.; DaSilva-Jardine, P. A.; Wilson, T. C.; Thompson, D. D. 222nd ACS National Meeting, Chicago, IL, Aug. 26-30, 2001. (e) Nagata, R.; Tokunaga, T.; Hume, W. E.; Umezome, T.; Okazaki, K.; Ueki, Y.; Kumagai, K.; Nagamine, J.; Seki, H.; Taiji, M.; and Noguchi, H. 222nd ACS National Meeting, Chicago, IL, Aug. 26-30, 2001. (f) Carpino, P. A.; Mangano, F. M.; Lefker, B. A.; Toler, S. M.; Pan, L. C.; Cook, E. R.; Dibrino, J. N.; Chidsey-Frink, K. L.; Hada, W. A.; Inthavongsay, J.; Mullins, M. A.; Nickerson, D. F.; Ng, O.; Pirie, C. M.; Rose, C. R.; Tess, D. A.; Wright, A. S.; Zawistoski, M. P.; DaSilva-Jardine, P. A.; Thompson, D. D. 222nd ACS National Meeting, Chicago, IL, Aug. 23-27, 1999. (g) Chen M.-H., Pollard P.P., Cheng K., Wei L., Chan W.W.-S., Butler B., Jacks T.M., Smith R.G., Patchett A.A. Bioorg. Med. Chem. Lett. 9:1999;1261 (a) . For recent reviews on GHS, see: Ghigo E., Arvat E., Broglio F., Giordano R., Gianotti L., Muccioli G., Papotti M., Graziani A., Bisi G., Deghenghi R., Camanni F. Horm. Res. 51:1999;9 (b) Nargund R.P., Patchett A.A., Bach M.A., Murphy M.G., Smith R.G. J. Med. Chem. 41:1998;3103 (c) Nargund, R. P.; Van der Ploeg, L. H. T. In Annual Reports in Medicinal Chemistry; Bristol, J. A., Ed.; Academic: San Diego, 1997; Vol. 32, p 221 and references cited therein. (d) DeVita R.J., Wyvratt M.J. Drugs Future. 21:1996;273.
6. For recent reviews on GHS, see: (a) Smith, R. G.; Sun, Y.; Smith, A. G. A.; Howard, A.; Feighner, S.; Dean, D.; Narguard, R. P.; Patchett, A. A. 222nd ACS National Meeting, Chicago, IL, Aug. 26-30, 2001. (b) Jungheim, L. N. 222nd ACS National Meeting, Chicago, IL, Aug. 26-30, 2001. (c) Nargund, R. P.; Ye, Z.; Tata, J. R.; Lu, Z.; Barakat, K.; Hong, Q.; Bakshi, R.; Gao, Y.; Tamvakopoulos, C.; Colwell, L.; Feighner, S.; Hreniuk, D.; Pong, S.; Cheng, K.; Schleim, K.; Jacks, T.; Strack, A.; Hickey, G.; Howard, A.; Van der Ploeg, L.; Bailey, A.; Smith, R.; and Patchett, A. A. 222nd ACS National Meeting, Chicago, IL, Aug. 26-30, 2001. (d) Carpino, P. A.; Lefker, B. A.; Toler, S. M.; Pan, L. C.; Hadcock, J. R.; Murray, M. C.; Cook, E. R.; Dibrino, J. N.; DeNinno, S. L.; Chidsey-Frink, K. L.; Hada, W. A.; Inthavongsay, J.; Lewis, S. K.; Mangano, F. M.; Mullins, M. A.; Nickerson, D. F.; Ng, O.; Pirie, C. M.; Ragan, J. A.; Rose, C. R.; Tess, D. A.; Wright, A. S.; Yu, L.; Zawistoski, M. P.; MacLean, D, B.; Pettersen, J. C.; DaSilva-Jardine, P. A.; Wilson, T. C.; Thompson, D. D. 222nd ACS National Meeting, Chicago, IL, Aug. 26-30, 2001. (e) Nagata, R.; Tokunaga, T.; Hume, W. E.; Umezome, T.; Okazaki, K.; Ueki, Y.; Kumagai, K.; Nagamine, J.; Seki, H.; Taiji, M.; and Noguchi, H. 222nd ACS National Meeting, Chicago, IL, Aug. 26-30, 2001. (f) Carpino, P. A.; Mangano, F. M.; Lefker, B. A.; Toler, S. M.; Pan, L. C.; Cook, E. R.; Dibrino, J. N.; Chidsey-Frink, K. L.; Hada, W. A.; Inthavongsay, J.; Mullins, M. A.; Nickerson, D. F.; Ng, O.; Pirie, C. M.; Rose, C. R.; Tess, D. A.; Wright, A. S.; Zawistoski, M. P.; DaSilva-Jardine, P. A.; Thompson, D. D. 222nd ACS National Meeting, Chicago, IL, Aug. 23-27, 1999. (g) Chen M.-H., Pollard P.P., Cheng K., Wei L., Chan W.W.-S., Butler B., Jacks T.M., Smith R.G., Patchett A.A. Bioorg. Med. Chem. Lett. 9:1999;1261 (a) . For recent reviews on GHS, see: Ghigo E., Arvat E., Broglio F., Giordano R., Gianotti L., Muccioli G., Papotti M., Graziani A., Bisi G., Deghenghi R., Camanni F. Horm. Res. 51:1999;9 (b) Nargund R.P., Patchett A.A., Bach M.A., Murphy M.G., Smith R.G. J. Med. Chem. 41:1998;3103 (c) Nargund, R. P.; Van der Ploeg, L. H. T. In Annual Reports in Medicinal Chemistry; Bristol, J. A., Ed.; Academic: San Diego, 1997; Vol. 32, p 221 and references cited therein. (d) DeVita R.J., Wyvratt M.J. Drugs Future. 21:1996;273.
7. For recent reviews on GHS, see: (a) Smith, R. G.; Sun, Y.; Smith, A. G. A.; Howard, A.; Feighner, S.; Dean, D.; Narguard, R. P.; Patchett, A. A. 222nd ACS National Meeting, Chicago, IL, Aug. 26-30, 2001. (b) Jungheim, L. N. 222nd ACS National Meeting, Chicago, IL, Aug. 26-30, 2001. (c) Nargund, R. P.; Ye, Z.; Tata, J. R.; Lu, Z.; Barakat, K.; Hong, Q.; Bakshi, R.; Gao, Y.; Tamvakopoulos, C.; Colwell, L.; Feighner, S.; Hreniuk, D.; Pong, S.; Cheng, K.; Schleim, K.; Jacks, T.; Strack, A.; Hickey, G.; Howard, A.; Van der Ploeg, L.; Bailey, A.; Smith, R.; and Patchett, A. A. 222nd ACS National Meeting, Chicago, IL, Aug. 26-30, 2001. (d) Carpino, P. A.; Lefker, B. A.; Toler, S. M.; Pan, L. C.; Hadcock, J. R.; Murray, M. C.; Cook, E. R.; Dibrino, J. N.; DeNinno, S. L.; Chidsey-Frink, K. L.; Hada, W. A.; Inthavongsay, J.; Lewis, S. K.; Mangano, F. M.; Mullins, M. A.; Nickerson, D. F.; Ng, O.; Pirie, C. M.; Ragan, J. A.; Rose, C. R.; Tess, D. A.; Wright, A. S.; Yu, L.; Zawistoski, M. P.; MacLean, D, B.; Pettersen, J. C.; DaSilva-Jardine, P. A.; Wilson, T. C.; Thompson, D. D. 222nd ACS National Meeting, Chicago, IL, Aug. 26-30, 2001. (e) Nagata, R.; Tokunaga, T.; Hume, W. E.; Umezome, T.; Okazaki, K.; Ueki, Y.; Kumagai, K.; Nagamine, J.; Seki, H.; Taiji, M.; and Noguchi, H. 222nd ACS National Meeting, Chicago, IL, Aug. 26-30, 2001. (f) Carpino, P. A.; Mangano, F. M.; Lefker, B. A.; Toler, S. M.; Pan, L. C.; Cook, E. R.; Dibrino, J. N.; Chidsey-Frink, K. L.; Hada, W. A.; Inthavongsay, J.; Mullins, M. A.; Nickerson, D. F.; Ng, O.; Pirie, C. M.; Rose, C. R.; Tess, D. A.; Wright, A. S.; Zawistoski, M. P.; DaSilva-Jardine, P. A.; Thompson, D. D. 222nd ACS National Meeting, Chicago, IL, Aug. 23-27, 1999. (g) Chen M.-H., Pollard P.P., Cheng K., Wei L., Chan W.W.-S., Butler B., Jacks T.M., Smith R.G., Patchett A.A. Bioorg. Med. Chem. Lett. 9:1999;1261 (a) . For recent reviews on GHS, see: Ghigo E., Arvat E., Broglio F., Giordano R., Gianotti L., Muccioli G., Papotti M., Graziani A., Bisi G., Deghenghi R., Camanni F. Horm. Res. 51:1999;9 (b) Nargund R.P., Patchett A.A., Bach M.A., Murphy M.G., Smith R.G. J. Med. Chem. 41:1998;3103 (c) Nargund, R. P.; Van der Ploeg, L. H. T. In Annual Reports in Medicinal Chemistry; Bristol, J. A., Ed.; Academic: San Diego, 1997; Vol. 32, p 221 and references cited therein. (d) DeVita R.J., Wyvratt M.J. Drugs Future. 21:1996;273.
8. For recent reviews on GHS, see: (a) Smith, R. G.; Sun, Y.; Smith, A. G. A.; Howard, A.; Feighner, S.; Dean, D.; Narguard, R. P.; Patchett, A. A. 222nd ACS National Meeting, Chicago, IL, Aug. 26-30, 2001. (b) Jungheim, L. N. 222nd ACS National Meeting, Chicago, IL, Aug. 26-30, 2001. (c) Nargund, R. P.; Ye, Z.; Tata, J. R.; Lu, Z.; Barakat, K.; Hong, Q.; Bakshi, R.; Gao, Y.; Tamvakopoulos, C.; Colwell, L.; Feighner, S.; Hreniuk, D.; Pong, S.; Cheng, K.; Schleim, K.; Jacks, T.; Strack, A.; Hickey, G.; Howard, A.; Van der Ploeg, L.; Bailey, A.; Smith, R.; and Patchett, A. A. 222nd ACS National Meeting, Chicago, IL, Aug. 26-30, 2001. (d) Carpino, P. A.; Lefker, B. A.; Toler, S. M.; Pan, L. C.; Hadcock, J. R.; Murray, M. C.; Cook, E. R.; Dibrino, J. N.; DeNinno, S. L.; Chidsey-Frink, K. L.; Hada, W. A.; Inthavongsay, J.; Lewis, S. K.; Mangano, F. M.; Mullins, M. A.; Nickerson, D. F.; Ng, O.; Pirie, C. M.; Ragan, J. A.; Rose, C. R.; Tess, D. A.; Wright, A. S.; Yu, L.; Zawistoski, M. P.; MacLean, D, B.; Pettersen, J. C.; DaSilva-Jardine, P. A.; Wilson, T. C.; Thompson, D. D. 222nd ACS National Meeting, Chicago, IL, Aug. 26-30, 2001. (e) Nagata, R.; Tokunaga, T.; Hume, W. E.; Umezome, T.; Okazaki, K.; Ueki, Y.; Kumagai, K.; Nagamine, J.; Seki, H.; Taiji, M.; and Noguchi, H. 222nd ACS National Meeting, Chicago, IL, Aug. 26-30, 2001. (f) Carpino, P. A.; Mangano, F. M.; Lefker, B. A.; Toler, S. M.; Pan, L. C.; Cook, E. R.; Dibrino, J. N.; Chidsey-Frink, K. L.; Hada, W. A.; Inthavongsay, J.; Mullins, M. A.; Nickerson, D. F.; Ng, O.; Pirie, C. M.; Rose, C. R.; Tess, D. A.; Wright, A. S.; Zawistoski, M. P.; DaSilva-Jardine, P. A.; Thompson, D. D. 222nd ACS National Meeting, Chicago, IL, Aug. 23-27, 1999. (g) Chen M.-H., Pollard P.P., Cheng K., Wei L., Chan W.W.-S., Butler B., Jacks T.M., Smith R.G., Patchett A.A. Bioorg. Med. Chem. Lett. 9:1999;1261 (a) . For recent reviews on GHS, see: Ghigo E., Arvat E., Broglio F., Giordano R., Gianotti L., Muccioli G., Papotti M., Graziani A., Bisi G., Deghenghi R., Camanni F. Horm. Res. 51:1999;9 (b) Nargund R.P., Patchett A.A., Bach M.A., Murphy M.G., Smith R.G. J. Med. Chem. 41:1998;3103 (c) Nargund, R. P.; Van der Ploeg, L. H. T. In Annual Reports in Medicinal Chemistry; Bristol, J. A., Ed.; Academic: San Diego, 1997; Vol. 32, p 221 and references cited therein. (d) DeVita R.J., Wyvratt M.J. Drugs Future. 21:1996;273.
9. (a) Shoen W.R., Pisano J.M., Prendergast K., Wyvratt M.J., Fisher M.H., Cheng K., Chan W.-S., Butler B., Smith R.G., Ball R.G. J. Med. Chem. 37:1994;897
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11. Patchett A.A., Nargund R.P., Tata J.R., Chen M.H., Barakat K.J., Johnston D.B.R., Cheng K., Chan W.-S., Butler J.B., Hickey G.J., Jacks T.M., Schleim K., Pong S.-S., Chaung L.-Y.P., Chen H.Y., Frazier E., Leung K.H., Chiu S.-H., Smith R.G. Proc. Natl. Acad. Sci. U.S.A. 92:1995;7001.
12. Tata J.R., Lu Z., Jacks T.M., Schleim K.D., Cheng K., Wei L., Chan W.-S., Butler B., Tsou N., Leung K., Chiu S.-H.L., Hickey G.J., Smith R.G., Patchett A.A. Bioorg. Med. Chem. Lett. 7:1997;2319.
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15. 3): 22a 7.74 (d, J=7.94 Hz, 1H), 7.40 (t, J=7.94 Hz, 1H), 7.31 (d, J=7.77 Hz, 1H), 7.22 (t, J=7.77 Hz, 1H), 4.35 (m, 2H), 4.22 (m, 2H), 4.08 (m, 1H), 2.50 (m, 2H), 2.00 (m, 2H), 1.80 (m, 2H), 1.70 (m, 2H), 1.50 (s, 9H), 1.35 (t, J=7.1 Hz, 3H); 22b 7.60 (d, J=7.94 Hz, 1H), 7.38 (t, J=7.93 Hz, 1H), 7.31 (d, J=7.7 Hz, 1H), 7.18 (t, J=7.7 Hz, 1H), 4.32 (m, 2H), 4.22 (m, 2H), 3.25 (m, 1H), 2.50 (m, 2H), 2.06 (m, 2H), 1.62 (m, 2H), 1.48 (s, 9H), 1.35 (t, J=7.1 Hz, 3H), 1.28 (m, 2H).
16. Cheng K., Chan W.-S., Barreto A., Convey E.M., Smith R.G. Endocrinology. 124:1989;2791.