Tetrahydroisoquinoline 1-carboxamides as growth hormone secretagogues

Bioorganic and Medicinal Chemistry Letters

Volumn 15, Issue 7, 2005, Pages 1799-1802

  Li, James J ^a   Wang, Haixia ^a   Qu, Fucheng ^a   Musial, Christa ^a   Tino, Joseph A ^a   Robl, Jeffrey A ^a   Slusarchyk, Dorothy ^a   Golla, Rajasree ^a   Seethala, Ramakrishna ^a   Dickinson, Kenneth ^a   Giupponi, Leah ^a   Grover, Gary ^a   Sleph, Paul ^a   Flynn, Neil ^a   Murphy, Brian J ^a   Gordon, David ^a   Kung, Melissa ^a   Stoffel, Robert ^a  

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

Growth hormone secretagogues

Indexed keywords

CAPROMORELIN; GROWTH HORMONE SECRETAGOGUE; IBUTAMOREN; LY 444711; TETRAHYDROISOQUINOLINE 1 CARBOXAMIDE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; DRUG ACTIVITY; DRUG POTENCY; DRUG SYNTHESIS; HORMONE BLOOD LEVEL; IN VIVO STUDY; NONHUMAN; PLASMA; RAT; STRUCTURE ACTIVITY RELATION;

EID: 20144380823     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.02.040     Document Type: Article

References (24)

1. D. Rudman, A.G. Feller, H.S. Nagraj, G.A. Gergans, P.Y. Lalitha, A.F. Goldberg, R.A. Schlenker, L. Cohn, I.W. Rudman, and D.E. Mattson N. Engl. J. Med. 323 1990 1
2. R.L. Hintz Horm. Res. 38 Suppl. 1 1992 44
3. C.Y. Bowers, F.A. Momany, G.A. Reynolds, and A. Hong Endocrinology 114 1984 1537
4. R.G. Smith, L.H. Van Der Ploeg, A.D. Howard, S.D. Feighner, K. Cheng, G.J. Hickey, M.J. Wyvratt Jr., M.H. Fisher, R.P. Nargund, and A.A. Patchett Endocr. Rev. 18 5 1997 621
5. For a review on GHS, see: R.P. Nargund, A.A. Patchett, M.A. Bach, M.G. Murphy, and R.G. Smith J. Med. Chem. 41 1998 3103
6. I.M. Chapman, M.A. Bach, E. Van Cauter, M. Farmar, D. Krupa, A.M. Taylor, L.M. Schilling, K.Y. Cole, E.H. Skiles, S.S. Pezzoli, M.L. Hartman, J.D. Veldhuis, G.J. Gormley, and M.O. Thorner J. Clin. Endocrinol. Metab. 81 1996 4249
7. A.A. Patchett, R.P. Nargund, J.R. Tata, M.H. Chen, K.J. Barakat, D.B.R. Johnston, K. Cheng, W.S. Chan, J.B. Butler, G.J. Hickey, T. Jacks, K. Schleim, S.S. Pong, L.-Y.P. Chaung, H.Y. Chen, E. Frazier, K.H. Leung, S.H. Chiu, and R.G. Smith Proc. Natl. Acad. Sci. U.S.A. 92 1995 7001
8. L.C. Pan Endocrine 14 2001 121
9. P.A. Carpino Bioorg. Med. Chem. Lett. 12 2002 3279
10. C.W. Lugar, M.P. Clay, T.D. Lindstrom, A.L. Woodson, D. Smiley, M.L. Heiman, and J.A. Dodge Bioorg. Med. Chem. Lett. 14 2004 5873 5876
11. D.E. Seyler, J.A. Dodge, J.J. Osborne, K.L. Cox, D. Viswanath, A.F. Wilmot, M.J. Keaton, M.L. Heiman, H.U. Bryant, and G.B. Cutler Jr. Drug Dev. Res. 49 2000 260
12. A.D. Howard, and S.D. Feighner Science 273 1996 974
13. S.S. Pong, L.-Y.P. Chuang, D.C. Dean, R.P. Nargund, A.A. Patchett, and R.G. Smith Mol. Endocrinol. 10 1996 57
14. E. Sullivan, E.M. Tucker, and I.L. Dale Methods Mol. Biol. 114 1999 125 133
15. K.S. Schroeder, and B.D. Neagle J. Biomol. Screen. 1 1996 75
16. 50 values are the averages of multiple measurements
17. TM technology (Athersys, Inc.), see: J.J. Harrington, B. Sherf, S. Rundlett, P.D. Jackson, R. Perry, S. Cain, C. Leventhal, M. Thornton, R. Ramachandran, J. Whittington, L. Lerner, D. Costanzo, K. McElligott, S. Boozer, R. Mays, E. Smith, N. Veloso, A. Klika, J. Hess, K. Cothren, K. Lo, J. Offenbacher, J. Danzig, and M. Ducar Nat. Biotechnol. 19 2001 440
18. For details, see Li, J. J.; Tino, J. A. US 6,469,024, 2002
19. R.M. Lawrence, S.A. Biller, O.M. Fryszman, and M.A. Poss Synthesis 1997 553
20. D.A. Evans, J.L. Katz, and T.R. West Tetrahedron Lett. 39 1998 2937
21. The enantiomers were later separated for several analogs (unpublished results). It was typically observed that one enantiomer is about 5- to 15-fold more potent than the other, and both enantiomers are full GHS agonists
22. 18 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, 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)
23. K. Chihara, A. Arimura, and A.V. Schally Endocrinology 104 1979 1434
24. Chiral separations were performed on a preparative ChiralPakAD Column (5 × 50 cm) with 20% isopropanol/hexanes. The first eluting isomer is assigned as 12a-E1, and second one is assigned as 12a-E2, but absolute configurations have not been assigned