Li Jun, Chen Stephanie Y, Tao Shiwei, Wang Haixia, Li James J, Swartz Steve, Musial Christa, Hernandez Andres A, Flynn Neil, Murphy Brian J, Beehler Blake, Dickinson Kenneth E, Giupponi Leah, Grover Gary, Seethala Ramakrishna, Sleph Paul, Slusarchyk Dorothy, Yan Mujing, Humphreys William G, Zhang Hongjian, Ewing William R, Robl Jeffrey A, Gordon David, Tino Joseph A
Discovery Chemistry, Bristol Myers Squibb, Princeton, NJ 08543, USA.
Bioorg Med Chem Lett. 2008 Mar 15;18(6):1825-9. doi: 10.1016/j.bmcl.2008.02.021. Epub 2008 Feb 13.
The structure-activity relationship of the O-benzyl serine side chain was investigated based on the tetrazole-based growth hormone secretagogue BMS-317180 (2). The ortho position of the benzyl moiety was found to be favorable for introduction of substituents. A series of ortho-substituted compounds were synthesized with improved in-vitro and in-vivo activity. Among them, the biphenyl compound 2p shows twofold improvement in potency compared to its parent compound BMS-317180 (2).
基于四氮唑类生长激素促分泌剂BMS-317180（2），对O-苄基丝氨酸侧链的构效关系进行了研究。发现苄基部分的邻位有利于引入取代基。合成了一系列邻位取代的化合物，其体外和体内活性均有所提高。其中，联苯化合物2p与其母体化合物BMS-317180（2）相比，效价提高了两倍。
