Synthesis, Structure–Activity Relationship, and Pharmacological Studies of Novel Melanin-Concentrating Hormone Receptor 1 Antagonists 3-Aminomethylquinolines: …

S Kasai, M Kamata, S Masada, J Kunitomo…

Index: Kasai, Shizuo; Kamata, Makoto; Masada, Shinichi; Kunitomo, Jun; Kamaura, Masahiro; Okawa, Tomohiro; Takami, Kazuaki; Ogino, Hitomi; Nakano, Yoshihide; Ashina, Shuntarou; Watanabe, Kaoru; Kaisho, Tomoko; Imai, Yumi N.; Ryu, Sunghi; Nakayama, Masaharu; Nagisa, Yasutaka; Takekawa, Shiro; Kato, Koki; Murata, Toshiki; Suzuki, Nobuhiro; Ishihara, Yuji Journal of Medicinal Chemistry, 2012 , vol. 55, # 9 p. 4336 - 4351

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Citation Number: 13

Abstract

Recently, we discovered 3-aminomethylquinoline derivative 1, a selective, highly potent, centrally acting, and orally bioavailable human MCH receptor 1 (hMCHR1) antagonist, that inhibited food intake in F344 rats with diet-induced obesity (DIO). Subsequent investigation of 1 was discontinued because 1 showed potent hERG K+ channel inhibition in a patch- clamp study. To decrease hERG K+ channel inhibition, experiments with ligand-based ...