Structural features and functional activities of benzimidazoles as NOD2 antagonists.,European Journal of Medicinal Chemistry

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Structural features and functional activities of benzimidazoles as NOD2 antagonists.
European Journal of Medicinal Chemistry ( IF 6.0 ) Pub Date : 2020-01-24 , DOI: 10.1016/j.ejmech.2020.112089
Samo Guzelj ₁ , Martina Gobec ₁ , Dunja Urbančič ₁ , Irena Mlinarič-Raščan ₁ , Emanuela Corsini ₂ , Žiga Jakopin ₁

Affiliation

NOD1 and NOD2 are pattern recognition receptors that have important roles in innate immune responses. Although their overactivation has been linked to a number of diseases, NOD2 in particular remains a virtually unexploited target in this respect, with only one structural class of antagonist reported. To gain insight into the structure-activity relationships of NOD2 antagonists, a series of novel analogs was designed and synthesized, and then screened for antagonist activity versus NOD2, and counter-screened versus NOD1. Compounds 32 and 38 were identified as potent and moderately selective NOD2 antagonists, and 33 and 42 as dual NOD1/NOD2 antagonists, with balanced activities against both targets in the low micromolar range. These data enable in-depth exploration of their structure-activity relationships and provide deeper understanding of the structural features required for NOD2 antagonism.

中文翻译：

苯并咪唑作为NOD2拮抗剂的结构特征和功能活性。

NOD1和NOD2是模式识别受体，在先天免疫反应中具有重要作用。尽管它们的过度活化与多种疾病有关，但在这方面，NOD2尤其仍是未开发的靶标，仅报道了一种结构拮抗剂。为了深入了解NOD2拮抗剂的结构-活性关系，设计并合成了一系列新型类似物，然后筛选了与NOD2相对的拮抗剂活性，以及与NOD1相对的拮抗活性。化合物32和38被鉴定为有效的和中等选择性的NOD2拮抗剂，化合物33和42被鉴定为双重NOD1 / NOD2拮抗剂，对低微摩尔范围内的两个靶标均具有平衡的活性。

更新日期：2020-01-24

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