Structure-activity relationships of novel piperazines as antagonists for the melanocortin-4 receptor.
During the investigation of antagonists for the MC4 receptor, we found that 10ab having a naphthyl group showed almost the same binding affinity for the MC4 receptor as that of the lead compound 1 with a benzoyl group. We also developed a new type of compounds, namely, bis-piperazines, and found that the bis-piperazines 10 exhibited a high affinity for the MC4 receptor. In particular, (-)-10bg exhibited the highest affinity for the MC4 receptor with an IC50 value of 8.13nM. In this paper, we present the design, synthesis, and structure-activity relationships of the novel bis-piperazines as MC4 receptor antagonists.
Nozawa
Dai
D
Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd, 1-403 Yoshino-cho, Kita-ku, Saitama, Saitama 331-9530, Japan. dai.nozawa@po.rd.taisho.co.jp
Okubo
Taketoshi
T
Ishii
Takaaki
T
Kakinuma
Hiroyuki
H
Chaki
Shigeyuki
S
Okuyama
Shigeru
S
Nakazato
Atsuro
A
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D009682:Magnetic Resonance Spectroscopy; D010879:Piperazines / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D044105:Receptor, Melanocortin, Type 4 / Q000037:antagonists & inhibitors*; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
D010879:Piperazines; D044105:Receptor, Melanocortin, Type 4