Discovery of VU0409551/JNJ-46778212: An mGlu5 Positive Allosteric Modulator Clinical Candidate Targeting Schizophrenia
Discovery of VU0409551/JNJ-46778212: An mGlu5 Positive Allosteric Modulator Clinical Candidate Targeting Schizophrenia
复制标题
DOI：
10.1021/acsmedchemlett.5b00181
复制
发表时间：
2015-06-01
影响因子：
4.2
通讯作者：
Lindsley, Craig W.
中科院分区：
文献类型：
--
作者：
Conde-Ceide, Susana;Martinez-Viturro, Carlos M.;Lindsley, Craig W.
在此，我们报道了一系列新的(2(phenoxymethyl)-6，7-dihydrooxazolo[5，4-c]pyridine-5(4H)-yl(aryl)methanones作为有效的、选择性的和口服生物可用的代谢性谷氨酸受体亚型5(mGlu(5))阳性变构调节剂(PAM)的构效关系。基于17a(VU0409551/JNJ-46778212)在精神分裂症多个领域的多个临床前模型中的强大体外效力和体内疗效，再加上良好的DMPK谱和可接受的治疗窗口，17a被选为进一步开发的候选药物。
Herein, we report the structure activity relationship of a novel series of (2(phenoxymethyl)-6,7-dihydrooxazolo[5,4-c]pyridine-5(4H)-yl(aryl)methanones as potent, selective, and orally bioavailable metabotropic glutamate receptor subtype 5 (mGlu(5)) positive allosteric modulators (PAMs). On the basis of its robust in vitro potency and in vivo efficacy in multiple preclinical models of multiple domains of schizophrenia, coupled with a good DMPK profile and an acceptable therapeutic window, 17a (VU0409551/JNJ-46778212) was selected as a candidate for further development.