Structure-activity relationships of the oxindole growth hormone secretagogues.
A series of substituted oxindole derivatives of SM-130686 was synthesized and evaluated as ghrelin receptor agonists. Modification of the substituents on the C3-aromatic part of the oxindole led to compounds with subnanomolar binding affinities. Compound 4i (IC(50)=0.02 nM) was orally active at low doses and showed in vivo activity when orally administered, 2 mg/kg twice a day for 4 days, as evidenced by significant body weight gain.
Tokunaga
Teruhisa
T
Research Division, Sumitomo Pharmaceuticals Co., Ltd, 1-98 Kasugade Naka 3-chome, Konohana-ku, Osaka 554-0022, Japan.
Hume
W Ewan
WE
Nagamine
Jun
J
Kawamura
Tetsuya
T
Taiji
Mutsuo
M
Nagata
Ryu
R
D000284:Administration, Oral; D000818:Animals; D005021:Ethylamines / Q000138:chemical synthesis / Q000494:pharmacology*; D013006:Growth Hormone / Q000378:metabolism*; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism*; D054440:Receptors, Ghrelin; D013329:Structure-Activity Relationship; D013997:Time Factors; D015430:Weight Gain / Q000187:drug effects
D005021:Ethylamines; D007211:Indoles; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; C443685:SM 130686; D013006:Growth Hormone