Tetrazole based amides as growth hormone secretagogues

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 8, 2008, Pages 2536-2539

  Li, James J ^a   Wang, Haixia ^a   Li, Jun ^a   Qu, Fucheng ^a   Swartz, Stephen G ^a   Hernández, Andrés S ^a   Biller, Scott A ^a   Robl, Jeffrey A ^a   Tino, Joseph A ^a   Slusarchyk, Dorothy ^a   Seethala, Ramakrishna ^a   Sleph, Paul ^a   Yan, Mujing ^a   Grover, Gary ^a   Flynn, Neil ^a   Murphy, Brian J ^a   Gordon, David ^a  

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

GHS; growth hormone secretagogues; Tetrazole amide

Indexed keywords

GROWTH HORMONE; GROWTH HORMONE SECRETAGOGUE; HYDROXYL GROUP; TETRAZOLE DERIVATIVE;

ANESTHESIA INDUCTION; ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DRUG ACTIVITY; DRUG BIOAVAILABILITY; DRUG POTENCY; DRUG SYNTHESIS; FEMALE; GROWTH HORMONE BLOOD LEVEL; IN VITRO STUDY; IN VIVO STUDY; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION; WISTAR RAT;

AMIDES; ANIMALS; CELL LINE; GLIOMA; GROWTH HORMONE; MOLECULAR STRUCTURE; RATS; STRUCTURE-ACTIVITY RELATIONSHIP; TETRAZOLES;

RATTUS;

EID: 41849151129     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.03.059     Document Type: Article

References (17)

1. Rudman D., Feller A.G., Nagraj H.S., Gergans G.A., Lalitha P.Y., Goldberg A.F., Schlenker R.A., Cohn L., Rudman I.W., and Mattson D.E. N. Engl. J. Med. 323 (1990) 1
2. Hintz R.L. Horm. Res. 38 (1992) 44
3. Chapman I.M., Bach M.A., Van Cauter E., Farmar 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., and Thorner M.O. J. Clin. Endocrinol. Metab. 81 (1996) 4249
4. For a review on GHS, see:. Nargund R.P., Patchett A.A., Bach M.A., Murphy M.G., and Smith R.G. J. Med. Chem. 41 (1998) 3103
5. 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., Schleim K., Pong S.S., Chaung L.-Y.P., Chen H.Y., Frazier E., Leung K.H., Chiu S.H., and Smith R.G. Proc. Natl. Acad. Sci. U.S.A. 92 (1995) 7001
6. Pan L.C. Endocrine 14 (2001) 121
7. Carpino P.A., et al. Bioorg. Med. Chem. Lett. 12 (2002) 3279
8. Seyler D.E., Dodge J.A., Osborne J.J., Cox K.L., Viswanath D., Wilmot A.F., Keaton M.J., Heiman M.L., Bryant H.U., and Cutler Jr. G.B. Drug Dev. Res. 49 (2000) 260
9. Li J., Chen S., Li J.J., Wang H., Hernandez A., Tao S., Musial C., Qu F., Swartz S., Chao S., Flynn N., Murphy B., Slusarchyk D., Seethala R., Yan M., Sleph P., Grover G., Smith M., Beehler B., Giupponi L., Dickinson K., Zhang H., Humphreys W.G., Patel B., Schwinden M., Stouch T., Cheng P.W., Biller S., Ewing W., Gordon D., Robl J., and Tino J. J. Med. Chem. 50 (2007) 5890
10. Hernandez A.S., Cheng P.T.W., Musial C.M., Swartz S.G., George R.J., Grover G., Slusarchyk D., Seethala R.K., Smith M., Dickinson K., Giupponi L., Longhi D.A., Flynn N., Murphy B.J., Gordon D.A., Biller S.A., Robl J.A., and Tino J. Bioorg. Med. Chem. Lett. 17 (2007) 5928
11. Duncia J.V., Pierce M.E., and Santella III J.B. J. Org. Chem. 56 (1991) 2395
12. Lawrence R.M., Biller S.A., Fryszman O.M., and Poss M.A. Synthesis (1997) 553
13. For details about FLIPR, see:. Sullivan E., Tucker E.M., and Dale I.L. Methods Mol. Biol. 114 (1999) 125
14. Schroeder K.S., and Neagle B.D. J. Biomol. Screen. 1 (1996) 75
15. Expression of the endogenous human GHS receptor was enhanced by Random Activation of Gene Expression (RAGE)™ technology (Athersys, Inc.), see:. Harrington J.J., Sherf B., Rundlett S., Jackson P.D., Perry R., Cain S., Leventhal C., Thornton M., Ramachandran R., Whittington J., Lerner L., Costanzo D., McElligott K., Boozer S., Mays R., Smith E., Veloso N., Klika A., Hess J., Cothren K., Lo K., Offenbacher J., Danzig J., and Ducar M. Nat. Biotechnol. 19 (2001) 440
16. 50 values are the average of at least three measurements.
17. Fasted male Wistar rats (200-250 g) were anesthetized via intraperitoneal injection with ketamine (30 mg) and xylazine (10 mg) per kg body weight. The drug or vehicle (10% ethanol, 0.09% saline V/V) was administered intravenously at a volume of 10 mL/kg to a group of five rats, respectively. After 15 min, a 1.5 mL of blood sample was drawn from the abdominal aorta. Plasma samples were then assayed for rat growth hormone 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).