Tolmachev Andrey, Bogolubsky Andrey V, Pipko Sergey E, Grishchenko Alexander V, Ushakov Dmytro V, Zhemera Anton V, Viniychuk Oleksandr O, Konovets Anzhelika I, Zaporozhets Olga A, Mykhailiuk Pavel K, Moroz Yurii S
Enamine Ltd. , 78 Chervonotkatska Street, Kyiv, 02094, Ukraine.
ChemBioCenter, Kyiv National Taras Shevchenko University , 61 Chervonotkatska Street, Kyiv, 02094, Ukraine.
ACS Comb Sci. 2016 Oct 10;18(10):616-624. doi: 10.1021/acscombsci.6b00103. Epub 2016 Sep 7.
One-pot synthesis of 3,5-disubstituted 1,2,4-oxadiazoles from carboxylic acids and nitriles was optimized to parallel chemistry. The method was validated on a 141 member library; the desired products were recovered with a high success rate and in moderate yields. Practical application of the approach was demonstrated in the synthesis of bioactive compound pifexole and agonists of free fatty acid receptor 1. A library of 4 948 100 synthesizable drug-like 3,5-disubstituted 1,2,4-oxadiazoles was enumerated based on the method and available validated reagents.
将由羧酸和腈类化合物一锅法合成3,5-二取代-1,2,4-恶二唑的方法优化为平行化学方法。该方法在一个包含141个成员的文库上得到验证；目标产物的回收率很高，产率适中。该方法在生物活性化合物匹非克索和游离脂肪酸受体1激动剂的合成中得到了实际应用。基于该方法和可用的经过验证的试剂，列举了一个包含4948100种可合成的类药物3,5-二取代-1,2,4-恶二唑的文库。
