A three-dimensional pharmacophore model for 5-hydroxytryptamine6 (5-HT6) receptor antagonists.
Forty-five structurally diverse 5-hydroxytryptamine(6) receptor (5-HT(6)R) antagonists were selected to develop a 3D pharmacophore model with the Catalyst software. The structural features for antagonism at this receptor are a positive ionizable atom interacting with Asp(3.32), a hydrogen bond acceptor group interacting with Ser(5.43) and Asn(6.55), a hydrophobic site interacting with residues in a hydrophobic pocket between transmembranes 3, 4, and 5, and an aromatic-ring hydrophobic site interacting with Phe(6.52).
López-Rodríguez
María L
ML
Departamento de Química Orgánica I, Facultad de Ciencias Químicas, Universidad Complutense, E-28040 Madrid, Spain. mluzlr@quim.ucm.es
Benhamú
Bellinda
B
de la Fuente
Tania
T
Sanz
Arantxa
A
Pardo
Leonardo
L
Campillo
Mercedes
M
D000818:Animals; D001216:Asparagine; D001224:Aspartic Acid; D001665:Binding Sites; D002417:Cattle; D015195:Drug Design; D006860:Hydrogen Bonding; D008958:Models, Molecular; D011487:Protein Conformation; D011985:Receptors, Serotonin / Q000378:metabolism*; D012243:Rhodopsin / Q000737:chemistry; D012694:Serine; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C097216:serotonin 6 receptor; D001224:Aspartic Acid; D012694:Serine; D001216:Asparagine; D012243:Rhodopsin