A potent, orally bioavailable benzazepinone growth hormone secretagogue

Journal of Medicinal Chemistry

Volumn 41, Issue 10, 1998, Pages 1716-1728

  DeVita, Robert J ^a   Bochis, Richard ^a   Frontier, Alison J ^a   Kotliar, Andrew ^a   Fisher, Michael H ^a   Schoen, William R ^a,b   Wyvratt, Matthew J ^a   Cheng, Kang ^a   Chan, Wanda W S ^a   Butler, Bridget ^a   Jacks, Thomas M ^a   Hickey, Gerard J ^a   Schleim, Klaus D ^a   Leung, Kwan ^a   Chen, Zhesheng ^a   Lee Chiu, S H ^a   Feeney, William P ^a   Cunningham, Paul K ^a   Smith, Roy G ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

^b BAYER CORPORATION   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 AMINO 2 METHYL N [2,3,4,5 TETRAHYDRO 1 [[2' [[[(METHYLAMINO)CARBONYL]AMINO]METHYL][1,1' BIPHENYL] 4 YL]METHYL] 2 OXO 1H BENZAZEPIN 3 YL]PROPIONAMIDE; GROWTH HORMONE RELEASING FACTOR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; CONFORMATIONAL TRANSITION; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG CONFORMATION; DRUG EFFECT; DRUG POTENCY; GROWTH HORMONE RELEASE; NONHUMAN; ORAL DRUG ADMINISTRATION; STRUCTURE ACTIVITY RELATION;

ADMINISTRATION, ORAL; ANIMALS; BENZAZEPINES; BIOLOGICAL AVAILABILITY; CELLS, CULTURED; DOGS; FEMALE; GROWTH HORMONE; MALE; METHYLUREA COMPOUNDS; PITUITARY GLAND; RATS; RATS, WISTAR; STRUCTURE-ACTIVITY RELATIONSHIP; TETRAZOLES;

EID: 15644383589     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm970816j     Document Type: Article

References (25)

1. Thorner, M. O. On the discovery of growth hormone-releasing hormone. Acta Paediatr. Suppl. 1993, 388, 2-7.
2. Schoen, W. R.; Wyvratt, M. J. Jr.; Smith, R. G. Growth hormone secretagogues. In Annual Reports in Medicinal Chemistry Vol. 28; Bristol, J. A., Ed.; Academic Press: California, 1993; Chapter 19.
3. DeVita, R. J.; Wyvratt, M. J. Benzolactam growth hormone secretagogues. Drugs Future 1996, 21, 273-281.
4. Nargund, R. P.; Van der Ploeg, L. H. T. Growth hormone secretagogues. In Annual Reports in Medicinal Chemistry Vol. 32; Bristol, J. A., Ed.; Academic Press: California, 1997; Chapter 22.
5. Pong, S.-S,; Chaung, L.-Y.; Dean, D. C.; Nargund, R. P.; Patchett, A. A.; Smith, R. G. Identification of a new G-protein-linked receptor for growth hormone secretagogues. Mol. Endocrinol. 1996, 10, 57-61.
6. Howard, A. D.; Feighner, S. D.; Cully, D. F.; Arena, J. P.; Liberator, P. A.; Rosenblum, C. I.; Hamelin, M.; Hreniuk, D. L.; Palyha, O. C.; Anderson, J.; Paress, P. S.; Diaz, C.; Chou, M.; Liu, K. K.; McKee, K. K; Pong, S.-S.; Chaung, L.-Y.; Eibrecht, A.; Dashkevicz, M.; Heavens, R.; Rigby, M.; Sirinathsinghji, D. J. S.; Dean, D. C.; Melillo, D. G.; Patchett, A. A.; Nargund, R.; Griffen, P. R.; Demartino, J. A.; Gupta, S. K.; Schaeffer, J. M.; Smith, R. G.; Van der Ploeg, L. H. T. A receptor in the pituitary and hypothalamus that functions in growth hormone release. Science 1996, 273, 974-977.
7. Bowers, C. Y. GH releasing peptide-structure and kinetics. J. Pediatr. Endocrinol 1993, 6, 21-31.
8. Smith, R. G.; Cheng, K.; Schoen, W. R.; Pong, S.-S,; Hickey, G.; Jacks, T.; Butler, B.; Chan, W. W.-S.; Chaung, L.-Y. P.; Judith, F.; Taylor, J.; Wyvratt, M. J.; Fisher, M. H. A nonpeptidyl growth hormone secretagogue. Science 1993, 260, 1640-1643.
9. Schoen, W. R.; Pisano, J. M.; Prendergast, K.; Wyvratt, M. J.; Fisher, M. H.; Cheng, K.; Chan, W. W.-S.; Butler, B.; Smith, R. G.; Ball, R. G. A novel 3-substituted benzazepinone growth hormone secretagogue (L-692, 429). J. Med. Chem. 1994, 37, 897-906.
10. Gertz, B. J.; Barrett, J. S.; Eisenhandler, R.; Krupa, D. A.; Wittreich, J. M.; Seibold, J. R.; Schneider, S. H. Growth hormone response in Man to L-692,429, a novel non-peptide mimic of growth hormone-releasing peptide-6. J. Clin. Endocrinol. Metab. 1993, 77, 1393-1397.
11. Patchett, A. A.; Nargund, R. P.; Tata, J. R.; Chen, M.-H.; Barakat, K. J.; Johnston, D. B. R.; Cheng, K.; Chan, W. W.-S.; Butler, B.; Hickey, G.; Jacks, T.; Schleim, K; Pong, S.-S.; Chaung, L.-Y. P.; Chen, H. Y.; Frazier, E.; Leung, K. H.; Chiu, S.-H. L.; Smith, R. G, Design and biological activities of L-163,191 (MK-0677): a potent orally active growth hormone secretagogue. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 7001-7005.
12. Chapman, I. M.; Bach, M. A.; Van Cauter, E.; Farmer, M.; Krupa, D.; Taylor, A. M.; Schilling, L. M.; Cole, K Y.; Skiles, E. H.; Pezzoli, S. S.; Hartman, M. L.; Veldhuis, J. D.; Gormley, G. J.; Thorner, M. O. Stimulation of the growth hormone (GH)-insulinlike growth factor I axis by daily oral administration of a GH secretagogue (MK-677) in healthy elderly subjects. J. Clin. Endocrinol. Metab. 1996, 81, 4249-4257.
13. DeVita, R. J.; Schoen, W. R.; Ok, D.; Barash, L.; Brown, J. E.; Fisher, M. H.; Hodges, P.; Wyvratt, M. J.; Cheng, K.; Chan, W. W.-S.; Butler, B. S.; Smith, R. G. Benzolactam growth hormone secretagogues: Replacements for the 2′-tetrazole moiety of L-692, 429. Bioorg. Med. Chem. Lett. 1994, 4, 1807-1812.
14. DeVita, R. J.; Schoen, W. R.; Fisher, M. H.; Frontier, A. J.; Pisano, J. M.; Wyvratt, M. J.; Cheng, K.; Chan, W. W.-S.; Butler, B. S.; Hickey, G. J.; Jacks, T. M.; Smith, R. G. Benzolactam growth hormone secretagogues: carboxamides au replacements for the 2′-tetrazole moiety of L-692,429. Bioorg. Med. Chem. Lett. 1994, 4, 2249-2254.
15. Pearlman, W. M. Noble metal hydroxides on carbon nonpyrophoric catalysts. Tetrahedron Lett. 1967, 8, 1663-1664.
16. Miyaura, N.; Yanagi, T.; Suzuki, A. The palladium-catalyzed cross-coupling reaction of phenyl boronic acid with haloarenes in the presence of bases. Synth. Commun. 1981, 11, 513-519.
17. Watanabe, T.; Miyaura, N.; Suzuki, A. Synthesis of sterically hindered biaryls via the palladium-catalyzed cross-coupling reaction of arylboronic acids or their esters with haloarenes. Synlett. 1992, 207-210.
18. Cheng, K.; Chan, W. W.-S.; Butler, B.; Wei, L.; Schoen, W. R.; Wyvratt, M. J.; Fisher, M. H.; Smith, R. G. Stimulation of growth hormone release from rat primary pituitary cells by L-692,429, a novel non-peptidyl growth hormone secretagogue. Endocrinology 1993, 132, 2729-2731.
19. Schoen, W. R.; Ok, D.; DeVita, R. J.; Pisano, J. M.; Hodges, P.; Cheng, K.; Chan, W. W.-S.; Butler, B. S.; Smith, R. G.; Wyvratt, M. J.; Fisher, M. H. Structure activity relationships in the amino acid side-chain of L-692,429. Bioorg. Med. Chem. Lett. 1994, 4, 1117-1122.
20. Bowers, C. Y.; Reynolds, G. A.; Durham, D.; Barrera, C. M.; Pezzoli, S. S.; Thorner, M. O. Growth hormone (GH)-releasing peptide stimulates GH release in normal men and acts synergistically with GH-releasing hormone. J. Clin, Endocrinol. Metab. 1990, 70, 975-982.
21. Leung, K. H.; Cohn, D. A.; Miller, R. R.; Doss, M. A.; Stearns, R. A.; Simpson, R. E.; Feeney, W. P.; Chiu, S.-H. L. Pharmacokinetics and dispostion of L-692,429, a novel non-peptidyl growth hormone secretagogue, in preclinical species. Drug Metab. Dispos. 1996, 24, 753-760.
22. 2 on growth hormone (GH)-releasing factor-stimulated GH release and intracellular adenosine 3′ ,5′-monophosphate accumulation in rat primary pituitary cell culture. Endocrinology 1989, 124, 2791-2798.
23. Rodbard, D.; Frazier, G. R. Statistical Analysis of Radioligand Assay Data. Methods Enzymol. 1975, 37, 3-22.
24. Bates, D.; Watts, D. Nonlinear Regression Analysis and its Applications; John Wiley and Sons: New York, 1988.
25. Yeh, K. C.; Small, R. D. Pharmacokinetic evaluation of stable piecewise cubic polynomials as numerical integration functions. J. Pharmacokinet. Biopharmaceut. 1989, 17, 721-740.