Recent developments in anticancer kinase inhibitors based on the pyrazolo[3,4-d]pyrimidine scaffold,RSC Medicinal Chemistry

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Recent developments in anticancer kinase inhibitors based on the pyrazolo[3,4-d]pyrimidine scaffold
RSC Medicinal Chemistry ( IF 4.1 ) Pub Date : 2020-09-08 , DOI: 10.1039/d0md00227e
Daniel J Baillache ₁ , Asier Unciti-Broceta ₁

Affiliation

Pyrazolo[3,4-d]pyrimidines have become of significant interest for the medicinal chemistry community as a privileged scaffold for the development of kinase inhibitors to treat a range of diseases, including cancer. This fused nitrogen-containing heterocycle is an isostere of the adenine ring of ATP, allowing the molecules to mimic hinge region binding interactions in kinase active sites. Similarities in kinase ATP sites can be exploited to direct the activity and selectivity of pyrazolo[3,4-d]pyrimidines to multiple oncogenic targets through focussed chemical modification. As a result, pharma and academic efforts have succeeded in progressing several pyrazolo[3,4-d]pyrimidines to clinical trials, including the BTK inhibitor ibrutinib, which has been approved for the treatment of several B-cell cancers. In this review, we examine the pyrazolo[3,4-d]pyrimidines currently in clinical trials for oncology patients, as well as those published in the literature during the last 5 years for different anticancer indications.

中文翻译：

基于吡唑并[3,4-d]嘧啶支架的抗癌激酶抑制剂的最新进展

吡唑并[3,4- d ]嘧啶作为开发激酶抑制剂以治疗包括癌症在内的一系列疾病的特殊支架，已引起药物化学界的极大兴趣。这种融合的含氮杂环是 ATP 腺嘌呤环的等排体，允许分子模拟激酶活性位点中铰链区的结合相互作用。可以利用激酶 ATP 位点的相似性，通过集中化学修饰将吡唑并[3,4- d ]嘧啶的活性和选择性引导至多个致癌靶点。因此，制药界和学术界的努力已成功将几种吡唑并[3,4- d ]嘧啶类药物推进到临床试验，其中包括 BTK 抑制剂伊布替尼（ibrutinib），该药物已被批准用于治疗多种 B 细胞癌症。在这篇综述中，我们检查了目前正在对肿瘤患者进行临床试验的吡唑并[3,4- d ]嘧啶类药物，以及过去5年中针对不同抗癌适应症在文献中发表的药物。

更新日期：2020-09-08

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