双杂环异恶唑基甲基和异恶唑啉基甲基吡唑的平行合成

Parallel Synthesis of bis-heterocyclic isoxazolylmethyl- and isoxazolinylmethylpyrazoles.

作者信息

Meng Liping, Lorsbach Beth A, Sparks Thomas C, Fettinger James C, Kurth Mark J

机构信息

Department of Chemistry, University of California, Davis, Davis, California 95616, USA.

出版信息

J Comb Chem. 2010 Jan-Feb;12(1):129-36. doi: 10.1021/cc900133k.

DOI:10.1021/cc900133k

PMID:20000375

Abstract

The solution-phase parallel synthesis of a 136-member library of isoxazol(in)e-CH(2)-pyrazoles is described. X-ray crystallographic structure determination verified the regioselectivities of the N-alkylation and nitrile oxide 1,3-dipolar cycloaddition steps. The construction of these pharmaceutically relevant heterocycles on solid support under microwave irradiation is also demonstrated. The resulting library of drug-like compounds has been added to the National Institutes of Health repository (approximately 10 mg of each with >or=90% purity) for pilot-scale biomedical studies with bioassay data available at the National Center for Biotechnology Information PubChem database. A subset of these compounds has been broadly screened by Dow AgroSciences for herbicidal, fungicidal, and insecticidal activity.

摘要

描述了异恶唑（啉）-CH₂-吡唑136元库的溶液相平行合成。X射线晶体结构测定验证了N-烷基化和腈氧化物1,3-偶极环加成步骤的区域选择性。还展示了在微波辐射下在固体载体上构建这些与药物相关的杂环。所得的类药物化合物库已添加到美国国立卫生研究院储存库（每种约10毫克，纯度≥90%），用于在国家生物技术信息中心PubChem数据库可获得生物测定数据的中试规模生物医学研究。陶氏益农公司对这些化合物的一个子集进行了广泛的除草、杀菌和杀虫活性筛选。