Synthesis of diphenylmethyl analogues and their affinity for the melanocortin-4 receptor and the serotonin transporter.
While examining antagonists of the melanocortin-4 receptor (MC4 receptor), we found that compound 12b, containing a diphenylmethyl moiety, had a relatively high affinity for the MC4 receptor. When diphenylmethyl analogues were further examined, compounds 12c and 18 were also found to exhibit a high affinity for the MC4 receptor (IC(50)=46.7 nM and 33.2 nM, respectively). Furthermore, compound 12c was also found to show a high affinity for the serotonin transporter (IC(50)=10.7 nM). Here, we describe the synthesis and biological evaluation of various diphenylmethyl analogues in relation to their actions on the MC4 receptor and the serotonin transporter.
Nozawa
Dai
D
Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd, Saitama, Japan. dai.nozawa@po.rd.taisho.co.jp
Okubo
Taketoshi
T
Ishii
Takaaki
T
Chaki
Shigeyuki
S
Okuyama
Shigeru
S
Nakazato
Atsuro
A
D000818:Animals; D001559:Benzhydryl Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D019556:COS Cells; D002522:Chlorocebus aethiops; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D044105:Receptor, Melanocortin, Type 4 / Q000187:drug effects* / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship
D001559:Benzhydryl Compounds; D044105:Receptor, Melanocortin, Type 4; D050486:Serotonin Plasma Membrane Transport Proteins