Abstract

The one-pot three-component reaction of 3-methyl-1-phenyl-1,6,7,8-tetrahydro-5H-pyrazolo[3,4-b]quinolin-5-one, aromatic aldehydes, and malononitrile in the presence of piperidine in ethanol has been carried out. The reaction proceeded through domino Knoevenagel condensation – Michael addition – O-cyclization sequence of reactions in a single transformation affording structurally intriguing novel pyrano[2,3-f]pyrazolo[3,4-b]quinoline-3-carbonitriles in excellent yields in short reaction time. The high-throughput AChE inhibition studies of these pyrano[2,3-f]pyrazolo[3,4-b]quinoline-3-carbonitriles disclosed one compound with maximum potency with an IC₅₀ value of 2.6 µM/L. The structure–activity relationship revealed that the pyrano[2,3-f]pyrazolo[3,4-b]quinoline-3-carbonitriles bearing alkyl or alkoxy substituted phenyl ring at C-4 exhibited more potency than the compounds with halogen-substituted phenyl ring.

抽象的

3-甲基-1-苯基-1,6,7,8-四氢-5 H-吡唑并[3,4- b ]喹啉-5-酮，芳族醛和丙二腈的一锅三组分反应已经进行了哌啶在乙醇中的存在。该反应通过多米诺Knoevenagel缩合反应-迈克尔加成反应-在单个转化中的O环化顺序进行，从而在结构上提供了极具吸引力的新型吡喃并[2,3- f ]吡唑并[3,4- b ]喹啉3-腈。反应时间短。这些吡喃并[2,3- f ]吡唑并[3,4- b ]喹啉-3-甲腈的高通量AChE抑制作用研究表明，一种化合物具有最大的IC效价。₅₀值为2.6 µM / L。结构-活性关系表明，在C-4处带有烷基或烷氧基取代的苯环的吡喃并[2,3- f ]吡唑并[3,4- b ]喹啉-3-腈比具有卤素取代的化合物表现出更高的效能苯环。