Discovery, synthesis, and structure-activity studies of tetrazole based growth hormone secretagogues

Bioorganic and Medicinal Chemistry Letters

Volumn 17, Issue 21, 2007, Pages 5928-5933

  Hernández, Andrés S ^a   Cheng, Peter T W ^a   Musial, Christa M ^a   Swartz, Stephen G ^a   George, Rocco J ^a   Grover, Gary ^a   Slusarchyk, Dorothy ^a   Seethala, R Krishna ^a   Smith, Mark ^a   Dickinson, Kenneth ^a   Giupponi, Leah ^a   Longhi, Daniel A ^a   Flynn, Neil ^a   Murphy, Brian J ^a   Gordon, David A ^a   Biller, Scott A ^a   Robl, Jeffrey A ^a   Tino, Joseph A ^a  

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

Growth hormone secretagogues; Tetrazole

Indexed keywords

GROWTH HORMONE SECRETAGOGUE; GROWTH HORMONE SECRETAGOGUE RECEPTOR; IBUTAMOREN; TETRAZOLE DERIVATIVE;

ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DOG; DRUG BIOAVAILABILITY; DRUG STRUCTURE; DRUG SYNTHESIS; GROWTH HORMONE RELEASE; NONHUMAN; RAT; REACTION ANALYSIS; STRUCTURE ACTIVITY RELATION;

ANIMALS; DOGS; GROWTH HORMONE; STRUCTURE-ACTIVITY RELATIONSHIP; TETRAZOLES;

CANIS FAMILIARIS; RATTUS;

EID: 34548851728     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2007.07.099     Document Type: Article

References (20)

1. Bowers C.Y., Momany F.A., Reynolds G.A., and Hong A. Endocrinology 114 (1984) 1537
2. DeVita R.J., Schoen W.R., Fischer M.H., Fontier A.J., Pisano J.M., Wyvratt M.J., Cheng K., Chan W.-S., Butler B.S., Hickey G.J., Jacks T.M., and Smith R.G. Bioorg. Med. Chem. Lett. 4 (1994) 2229
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., and Smith R.G. Proc. Natl. Acad. Sci. U.S.A. 92 (1995) 7001
4. Ghrelin is a 28-amino acid peptide that displays a unique octanoyl-serine residue and is secreted in the stomach.
5. Kojima M., Hosoda H., and Date Y. Nature 402 (1999) 656
6. Svensson J. Exp. Opin. Ther. Patents 10 (2000) 1071
7. Carpino P.A. Exp. Opin. Ther. Patents 12 (2002) 1599
8. Dodge J.A., and Heiman M.L. Annu. Rep. Med. Chem. 38 (2003) 81
9. Thornber C.W. Chem. Soc. Revs. 8 (1979) 563
10. Singh H., Chawla A.S., Kapoor V.K., Paul D., and Malhotra R.K. Prog. Med. Chem. 17 (1980) 151
11. De Lombaert S., Blanchard L., Tan J., Sakane Y., and Berry C. Bioorg. Med. Chem. Lett. 5 (1995) 145
12. Duncia J.V., Pierce M.E., and Santella III J.B. J. Org. Chem. 56 (1991) 2395
13. 1HNMR easily distinguished between the 1H and 2H isomers by comparison of the Δδ between the methyls of the 2-aminoisobutyric fragment. The Δδ is significantly larger in the 1H isomer than in the 2H isomer.
14. 50 values are averages of at least three measurements
15. i values were determined using the Cheng-Prusoff equation. Compounds were routinely tested on three separate occasions.
16. Full experimental details will be disclosed in a manuscript which is in preparation.
17. Hernández A.S., and Hodges J.C. J. Org. Chem. 62 (1997) 3153
18. Wilson M.W., Hernández A.S., Calvet A.P., and Hodges J.C. Mol. Diversity 3 (1998) 95
19. 3 = OMe).
20. max for GH in this model), 1.5 mL blood samples were drawn from the abdominal aorta. Plasma samples were then analyzed for rat GH by radioimmunoassay using a modification of the kit supplied by the National Pituitary hormone Center (Dr. A. Parlow, Harbor-UCLA Medical Center, Los Angeles, CA).