Synthesis and biological activities of spiroheterocyclic growth hormone secretagogues.
The synthesis and biological activities of a series of spiroheterocyclic growth hormone secretagogues are reported. Modification of the spiroindane part-structure of the prototypal secretagogue L-162,752 revealed that the spiroindane could be replaced with spirobenzodihydrothiophen derivatives to enhance not only in vitro potency but also oral activity. In this study non-aromatic D-2-amino-4-cyclohexylbutanoic analogs (8a-8d) were also identified to be active secretagogues.
Chen
M H
MH
Medicinal Chemistry Department, Merck Research Laboratories, Rahway, NJ 07065, USA.
Pollard
P P
PP
Patchett
A A
AA
Cheng
K
K
Wei
L
L
Chan
W W
WW
Butler
B
B
Jacks
T M
TM
Smith
R G
RG
D000818:Animals; D004285:Dogs; D013006:Growth Hormone / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D007700:Kinetics; D008956:Models, Chemical; D051381:Rats; D013141:Spiro Compounds / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology
D007211:Indoles; C116595:L 162752; D013141:Spiro Compounds; D013006:Growth Hormone