Synthesis of a small library of phenylalkylamide derivatives as melatoninergic ligands for human mt1 and MT2 receptors.
Focused small libraries of melatonin receptor ligands from arylalkylamine derivatives were synthesised by combinatorial chemistry using the mix and split method in the solid phase. A library of 108 compounds was then synthesised from 12 arylalkyl amines and nine carboxylic acids. The compound mixtures were evaluated on chicken brain melatonin and recombinant human mt1 and MT2 receptors. Deconvolution of the most potent mixture demonstrated the superiority of 3-methoxy and 2,5-dimethoxy substitution on the phenyl ring with isopropyl, propyl and ethyl amido chains. Several compounds with nanomolar affinity for human melatonin receptors were obtained.
Pégurier
C
C
CNRS-BIOCIS (URA 1843), Université de Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry, France.
Curtet
S
S
Nicolas
J P
JP
Boutin
J A
JA
Delagrange
P
P
Renard
P
P
Langlois
M
M
D000577:Amides / Q000138:chemical synthesis* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D002645:Chickens; D020650:Combinatorial Chemistry Techniques; D005260:Female; D006801:Humans; D008024:Ligands; D008297:Male; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D044094:Receptors, Melatonin; D011994:Recombinant Proteins / Q000378:metabolism; D013057:Spectrum Analysis
D000577:Amides; D008024:Ligands; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; D011994:Recombinant Proteins