Analogs of the orally active growth hormone secretagogue L-162,752

Bioorganic and Medicinal Chemistry Letters

Volumn 6, Issue 18, 1996, Pages 2163-2168

  Chen, Meng Hsin ^a   Steiner, Mark G ^a   Patchett, Arthur A ^a   Cheng, Kang ^a   Wei, Liente ^a   Chan, Wanda W S ^a   Butler, Bridget ^a   Jacks, Thomas M ^a   Smith, Roy G ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GROWTH HORMONE; INDAN DERIVATIVE; L 162752; SPIRO COMPOUND; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CELL CULTURE; CONTROLLED STUDY; DOG; DRUG DESIGN; HYPOPHYSIS; IN VITRO STUDY; INTRAVENOUS DRUG ADMINISTRATION; NONHUMAN; ORAL DRUG ADMINISTRATION; RAT; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION;

ANIMALIA; CANIS FAMILIARIS;

EID: 0030591697     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/0960-894X(96)00394-0     Document Type: Article

References (15)

1. 1. (a) Jaffe, C. A.; Ho, P. J.; Demott-Friberg, R.; Bower, C. Y.; Barkan, A. L. J. Clin. Endocrinol. Metab. 1993, 77, 1641.
2. (b) Ghigo, E.; Awat, E.; Gianotti, L.; Imbimbo, B. P.; Lenaerts, V. Deghenghi, R.; Camanni, F. J. Clin. Endrocrinol Metab. 1994, 78, 693.
3. 2. Gertz, B. J.; Barrett, J. S.; Eisenhandler, R.; Krupa, D. A; Wittreich, J. M.; Seibold, J. R.; Scheneider, S. H. J. Clin. Endocrinol. Metab. 1993, 77, 1393.
4. 3. 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. Proc. Natl. Acad. Sci. 1995, 92, 7001.
5. 4. Cheng, K.; Chan, W. W. S.; Barreto, A.; Convey, E. M.; Smith, R. G. Endocrinology 1989, 124, 2791.
6. 5. Compounds were administered orally at the appropiate levels in water solution to male and female beagle 1.2-2.5 years old, weighing 8-16 kg. GH levels in plasma were determined by RIA at -5, 0 and +5 and every 10 minutes thereafter for 2 hours.
7. 6. Compound 1 was effective i.v. at 0.1 mg/kg (1/1) but inactive at p.o. at 5.0 mg/kg (0/2).
8. 7. (a) 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. J. Med. Chem. 1994, 37, 897.
9. (b) 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. Bioorg. Med. Chem. Lett. 1994, 4, 1117.
10. 8. Chambers, M. S.; Baker, R.; Billington, D. C.; Knight, A. K.; Middlemiss, D. N.; Wong, E. H. F. J. Med. Chem. 1992, 35, 2033.
11. 9. Bodanszky, M. and Bodanszky, A. The Practice of Peptide Synthesis Springer-Verlag, Berlin and Heidelberg, 1984.
12. 10. Hanessian, S; Kloss, H. Tetrahedron Lett. 1985, 26, 1261.
13. 11. Kuszmann, J.; Tomori, E.; Meerwald I. Carbohydr. Res. 1984, 128, 87.
14. 12. pKa's were determined by direct titration in 50% aqueous methanol.
15. 12