Structure-activity relationship studies on a series of piperazinebenzylalcohols and their ketone and amine analogs as melanocortin-4 receptor ligands.
A series of piperazinebenzylalcohols were prepared and studied to compare with their ketone and amine analogs as MC4R antagonists. Several benzylalcohols such as 14a and 14g displayed low nanomolar binding affinities (K(i)<10 nM), and high selectivities over other melanocortin receptor subtypes.
Marinkovic
Dragan
D
Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., 12790 El Camino Real, San Diego, CA 92121, USA.
Tucci
Fabio C
FC
Tran
Joe A
JA
Fleck
Beth A
BA
Wen
Jenny
J
Chen
Chen
C
D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D019943:Amino Acid Substitution; D000818:Animals; D001592:Benzyl Alcohols / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D001667:Binding, Competitive; D002460:Cell Line; D006801:Humans; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D053486:Melanocortins / Q000037:antagonists & inhibitors / Q000378:metabolism; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D044105:Receptor, Melanocortin, Type 4 / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000588:Amines; D001592:Benzyl Alcohols; D007659:Ketones; D008024:Ligands; D053486:Melanocortins; D010879:Piperazines; D044105:Receptor, Melanocortin, Type 4