Structure-activity relationships of novel piperazines as antagonists for the melanocortin-4 receptor

Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd, 1-403 Yoshino-cho, Kita-ku, Saitama, Saitama 331-9530, Japan.
Bioorganic & Medicinal Chemistry (Impact Factor: 2.95). 04/2007; 15(5):1989-2005. DOI: 10.1016/j.bmc.2006.12.039
Source: PubMed

ABSTRACT 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.

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