Highly potent growth hormone secretagogues.
During an effort to search for more potent growth hormone secretagogues, we discovered a class of compounds of which the best compound 8 was 7-fold more active in vitro than the best compound in the series we revealed before [Tata, J. R.; Lu, Z.; Jacks, T. M.; Schleim, K. D.; Cheng, K.; Wei, L.; Chan, W.-S.; Butler, B.; Tsou, N.; Leung, K.; Chiu, S.-H. L.; Hickey, G. J.; Smith, R. G.; Patchett, A. A. Bioorg. Med. Chem. Lett.1997, 7, 2319.]. Animal studies show that compound 8 can stimulate growth hormone release at the oral dose as low as 0.06 mpk. Chemistry and biological studies are discussed.
Lu
Zhijian
Z
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. Zhijian_lu@merck.com <Zhijian_lu@merck.com>
Tata
James R
JR
Cheng
Kang
K
Wei
Liente
L
Chan
Wanda W-S
WW
Butler
Bridget
B
Schleim
Klaus D
KD
Jacks
Thomas M
TM
Hickey
Gerard
G
Patchett
Arthur A
AA
D000284:Administration, Oral; D000577:Amides / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004285:Dogs; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D013006:Growth Hormone / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D008956:Models, Chemical; D010902:Pituitary Gland / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D051381:Rats; D013141:Spiro Compounds / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000577:Amides; D000588:Amines; D007211:Indoles; D013141:Spiro Compounds; D013006:Growth Hormone; C094817:ibutamoren mesylate