Synthesis and Biology of Bengazole Analogs

苯并唑类似物的合成与生物学

• 批准号: 6639962
• 负责人: Peter Wipf
• 金额: $ 3.97万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6639962
• 关键词: Nippostrongylus; South America; analog; anthelmintics; antibiotics; antifungal agents; antineoplastics; antiviral agents; cell line; chemical structure function; chemical synthesis; colon neoplasms; drug design /synthesis /production; drug screening /evaluation; lymphocytic leukemia; melanoma; neoplasm /cancer pharmacology; oxazoles; thiazoles

This is an application for a Fogarty International Research Collaboration Award (FIRCA) between the research groups of Dr. Gloria Serra (Assistant Professor of Medicinal Chemistry, UniversIdad de Ia Republica, Montevideo, Uruguay) and Dr. Peter Wipf (Professor of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA). Our specific aims in this collaborative project are: - Synthesis of bis-oxazoles, bis-oxazolines, bis-thiazoles and bis-thiazolines analogs of the anthelminthic marine natural product bengazole. This is the primary goal of this application. - Evaluation of biological activities, e.g. i) In vitro anthelmintic activity against Nippostrongylus brassiliensis by Prof. Laura DomInguez from the Pharmacology Department of the Faculty of Chemistry (Uruguay); ii) cytotoxic activity in cancer cell lines by Dr. Adriana Baz at the Immunology Department of the Faculty of Chemistry (Uruguay); iii) if the results of the in vitro anthelminthic activity assays are significant, the Pharmacology Department will perform an in vivo evaluation. - SAR analysis of compounds of type 1: i) esterification with fatty acids of some of the 0H groups on the lateral chain; ii) preparation of 0/S heterocycle analogs for structures of type 1; iii) preparation of analogs differing in the level of polyhydroxylation at the lateral chain R. Chemotherapy has been a long-standing effective instrument for battling parasitic infections in both human and veterinary medicine. Although there have been major advances in the clinical treatment of anthelmintic diseases, there are still no ideal broad-spectrum anthelminthics. Moreover, the field has suffered major setbacks, since resistance of nematodes to the anthelminthic drugs of general use such as benzimidazoles levamizole and praziquantel has emerged. The proposed project will provide a wide range of bengazole analogs for testing of their anthelminthic properties which represents a crucial step in the development of new antiparasitic pharmaceuticals.

这是福格蒂国际研究合作奖的申请 （FIRCA）格洛丽亚·塞拉博士（助理教授）的研究小组之间 药物化学，UniversIdad de Ia Republica，蒙得维的亚，乌拉圭）和博士。 Peter Wipf（匹兹堡大学化学教授，宾夕法尼亚州匹兹堡， 美国）。我们在这个合作项目中的具体目标是： - 双恶唑、双恶唑啉、双噻唑和双噻唑啉的合成 驱虫海洋天然产物苯唑的类似物。这是 此应用程序的主要目标。 - 生物活性评估，例如i) 体外驱虫活性 来自巴西科学院的 Laura DomInguez 教授针对巴西白圆线虫 化学系药理学系（乌拉圭）； ii) 细胞毒性 免疫学系的 Adriana Baz 博士对癌细胞系的活性 化学学院（乌拉圭）； iii) 如果体外实验的结果 驱虫活性测定很重要，药理学部门将 进行体内评估。 - 1 类化合物的 SAR 分析：i) 与脂肪酸的酯化反应 侧链上的一些0H基团； ii) 0/S杂环的制备 1 型结构的类似物； iii) 不同的类似物的制备 侧链 R 的多羟基化水平。 化疗长期以来一直是对抗癌症的有效手段 人类和兽医中的寄生虫感染。虽然有 驱虫疾病的临床治疗取得了重大进展 目前尚无理想的广谱驱虫药。此外，该领域还有 由于线虫对驱虫药的抗药性，遭受了重大挫折 常用药物如苯并咪唑、左旋咪唑和吡喹酮 出现了。拟议项目将提供广泛的苯唑类似物 用于测试其驱虫特性，这是关键的一步 开发新的抗寄生虫药物。

项目成果

Toward the Total Synthesis of Scleritodermin A: Preparation of the C(1)-N(15) Fragment.

Scleritodermin A 的全合成：C(1)-N(15) 片段的制备。

• 发表时间: 2007-03-05
• 影响因子: 1.8
• 作者: Sellanes, Diver;Manta, Eduardo;Serra, Gloria
• 通讯作者: Serra, Gloria

Synthesis and Structure-Activity Relationships of Benzothienothiazepinone Inhibitors of Protein Kinase D.

蛋白激酶 D 苯并噻吩并噻嗪酮抑制剂的合成及构效关系。

• 发表时间: 2011-02-14
• 影响因子: 4.2
• 作者: Bravo;George, Kara M;Frantz, Marie;Lavalle, Courtney R;Tandon, Manuj;Leimgruber, Stephanie;Sharlow, Elizabeth R;Lazo, John S;Wang, Q Jane;Wipf, Peter
• 通讯作者: Wipf, Peter