基于磺酰脲的哌嗪哒嗪酮系列葡聚糖合酶抑制剂的先导优化。

Lead optimization of a sulfonylurea-based piperazine pyridazinone series of glucan synthase inhibitors.

机构信息

Medicinal Chemistry Department, Albany Molecular Research, Inc. (AMRI), 26 Corporate Circle, Albany, NY 12203, USA.

出版信息

Bioorg Med Chem Lett. 2012 Jul 15;22(14):4896-9. doi: 10.1016/j.bmcl.2012.04.127. Epub 2012 May 17.

DOI:10.1016/j.bmcl.2012.04.127

Abstract

The structure-activity relationship studies of a novel sulfonylurea series of piperazine pyridazine-based small molecule glucan synthase inhibitors is described. The optimization of PK profiles within the series led to the discovery of several compounds with improved pharmacokinetic profiles which demonstrated in vitro potency against clinically relevant strains. However, the advancement of compounds from this series into a non-lethal systemic fungal infection model failed to show in vivo efficacy.

摘要

描述了新型磺酰脲系列哌嗪哒嗪基小分子葡聚糖合酶抑制剂的构效关系研究。该系列化合物的 PK 特性优化导致发现了几种具有改善的药代动力学特性的化合物，这些化合物对临床上相关的菌株具有体外活性。然而，该系列化合物在非致死性系统性真菌感染模型中的进展未能显示出体内疗效。

相似文献

Lead optimization of a sulfonylurea-based piperazine pyridazinone series of glucan synthase inhibitors.基于磺酰脲的哌嗪哒嗪酮系列葡聚糖合酶抑制剂的先导优化。

Bioorg Med Chem Lett. 2012 Jul 15;22(14):4896-9. doi: 10.1016/j.bmcl.2012.04.127. Epub 2012 May 17.

The optimization of pyridazinone series of glucan synthase inhibitors.吡嗪酮类葡聚糖合成酶抑制剂的优化。

Bioorg Med Chem Lett. 2012 Aug 15;22(16):5268-71. doi: 10.1016/j.bmcl.2012.06.091. Epub 2012 Jul 4.

SAR studies of pyridazinone derivatives as novel glucan synthase inhibitors.作为新型葡聚糖合成酶抑制剂的哒嗪酮衍生物的 SAR 研究。

Bioorg Med Chem Lett. 2011 May 15;21(10):2890-3. doi: 10.1016/j.bmcl.2011.03.083. Epub 2011 Mar 30.

The synthesis and structure-activity relationship of pyridazinones as glucan synthase inhibitors.哒嗪酮类作为葡聚糖合成酶抑制剂的合成及构效关系。

Bioorg Med Chem Lett. 2011 Mar 15;21(6):1819-22. doi: 10.1016/j.bmcl.2011.01.058. Epub 2011 Jan 21.

Synthesis, anti-fungal and 1,3-β-D-glucan synthase inhibitory activities of caffeic and quinic acid derivatives.咖啡酸和奎宁酸衍生物的合成、抗真菌和 1,3-β-D-葡聚糖合酶抑制活性。

Bioorg Med Chem. 2010 Oct 1;18(19):7009-14. doi: 10.1016/j.bmc.2010.08.022. Epub 2010 Aug 13.

Discovery of a novel class of orally active antifungal beta-1,3-D-glucan synthase inhibitors.发现一类新型的具有口服活性的抗真菌β-1,3-D-葡聚糖合酶抑制剂。

Antimicrob Agents Chemother. 2011 Nov;55(11):5099-106. doi: 10.1128/AAC.00432-11. Epub 2011 Aug 15.

Quinazolinone fungal efflux pump inhibitors. Part 3: (N-methyl)piperazine variants and pharmacokinetic optimization.喹唑啉酮类真菌外排泵抑制剂。第3部分：（N-甲基）哌嗪变体与药代动力学优化。

Bioorg Med Chem Lett. 2007 May 15;17(10):2802-6. doi: 10.1016/j.bmcl.2007.02.047. Epub 2007 Feb 27.

Novel dendrimeric lipopeptides with antifungal activity.具有抗真菌活性的新型树枝状脂肽。

Bioorg Med Chem Lett. 2012 Feb 1;22(3):1388-93. doi: 10.1016/j.bmcl.2011.12.051. Epub 2011 Dec 17.

N-Phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amines as potent and selective inhibitors of glycogen synthase kinase 3 with good cellular efficacy.N-苯基-4-吡唑并[1,5-b]哒嗪-3-基嘧啶-2-胺作为糖原合酶激酶3的强效选择性抑制剂，具有良好的细胞活性。

J Med Chem. 2004 Sep 9;47(19):4716-30. doi: 10.1021/jm040063i.

Discovery of a new class of glucosylceramide synthase inhibitors.发现一类新型的葡萄糖神经酰胺合酶抑制剂。

Bioorg Med Chem Lett. 2011 Nov 15;21(22):6773-7. doi: 10.1016/j.bmcl.2011.09.037. Epub 2011 Sep 17.

文献AI研究员

20分钟写一篇综述，助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型，支持多种主流文档格式。