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1-咪唑并[1,2 -]吡唑支架的选择性官能团化。一种新型潜在的非经典吲哚电子等排体及推拉型染料的前体。

Selective functionalization of the 1-imidazo[1,2-]pyrazole scaffold. A new potential non-classical isostere of indole and a precursor of push-pull dyes.

作者信息

Schwärzer Kuno, Rout Saroj K, Bessinger Derya, Lima Fabio, Brocklehurst Cara E, Karaghiosoff Konstantin, Bein Thomas, Knochel Paul

机构信息

Department Chemie, Ludwig-Maximilians-Universität München Munich 81377 Germany

Global Discovery Chemistry, Novartis Institutes of BioMedical Research Basel 4057 Switzerland.

出版信息

Chem Sci. 2021 Aug 30;12(39):12993-13000. doi: 10.1039/d1sc04155j. eCollection 2021 Oct 13.

DOI:10.1039/d1sc04155j
PMID:34745530
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8513920/
Abstract

We report the selective functionalization of the 1-imidazo[1,2-]pyrazole scaffold using a Br/Mg-exchange, as well as regioselective magnesiations and zincations with TMP-bases (TMP = 2,2,6,6-tetramethylpiperidyl), followed by trapping reactions with various electrophiles. In addition, we report a fragmentation of the pyrazole ring, giving access to push-pull dyes with a proaromatic (1,3-dihydro-2-imidazol-2-ylidene)malononitrile core. These functionalization methods were used in the synthesis of an isostere of the indolyl drug pruvanserin. Comparative assays between the original drug and the isostere showed that a substitution of the indole ring with a 1-imidazo[1,2-]pyrazole results in a significantly improved solubility in aqueous media.

摘要

我们报道了使用溴/镁交换对1-咪唑并[1,2 -]吡唑骨架进行选择性官能团化，以及用TMP碱（TMP = 2,2,6,6 - 四甲基哌啶基）进行区域选择性镁化和锌化，随后与各种亲电试剂进行捕获反应。此外，我们报道了吡唑环的碎片化反应，可得到具有准芳香性（1,3 - 二氢 - 2 - 咪唑 - 2 - 亚基）丙二腈核心的推拉型染料。这些官能团化方法被用于合成吲哚类药物普鲁万色林的等排体。原药物与等排体之间的对比试验表明，用1 - 咪唑并[1,2 -]吡唑取代吲哚环可显著提高在水性介质中的溶解度。

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3
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Phys Chem Chem Phys. 2021 Apr 22;23(15):9139-9146. doi: 10.1039/d1cp00831e.
4
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Org Lett. 2020 Mar 6;22(5):1899-1902. doi: 10.1021/acs.orglett.0c00238. Epub 2020 Feb 12.
5
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Chemistry. 2019 Feb 21;25(11):2695-2703. doi: 10.1002/chem.201803904. Epub 2018 Dec 17.
6
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