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.
Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA. sunl@bms.com
Li-Qiang
LQ
Sun
Jie
J
Chen
Katherine
K
Takaki
Graham
G
Johnson
Lawrence
L
Iben
Cathy D
CD
Mahle
Elaine
E
Ryan
Cen
C
Xu
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