Design and synthesis of benzoxazole derivatives as novel melatoninergic ligands.
A novel series of benzoxazole derivatives was synthesized and evaluated as melatoninergic ligands. The binding affinity of these compounds for human MT(1) and MT(2) receptors was determined using 2-[(125)I]-iodomelatonin as the radioligand. The results of the SAR studies in this series led to the identification of compound 28, which exhibited better MT(1) and MT(2) receptor affinities than melatonin itself. This work also established the benzoxazole nucleus as a melatoninergic pharmacophore, which served as an isosteric replacement to the previously established alkoxyaryl core.
Sun
Li-Qiang
LQ
Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA. sunl@bms.com
Chen
Jie
J
Takaki
Katherine
K
Johnson
Graham
G
Iben
Lawrence
L
Mahle
Cathy D
CD
Ryan
Elaine
E
Xu
Cen
C
D001583:Benzoxazoles / Q000138:chemical synthesis* / Q000378:metabolism*; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008550:Melatonin / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D044094:Receptors, Melatonin / Q000502:physiology*
D001583:Benzoxazoles; D008024:Ligands; D044094:Receptors, Melatonin; D008550:Melatonin