公开(公告)号：US08853228B2

公开(公告)日：2014-10-07

申请号：US13290741

申请日：2011-11-07

申请人： Amy C. Anderson ,  Dennis L. Wright ,  Kathleen Mary Frey ,  Janet Leigh Paulsen ,  Eric William Scocchera ,  Kishore Viswanathan

发明人： Amy C. Anderson ,  Dennis L. Wright ,  Kathleen Mary Frey ,  Janet Leigh Paulsen ,  Eric William Scocchera ,  Kishore Viswanathan

IPC分类号： A01N43/54 ,  A61K31/505 ,  C07D239/02

CPC分类号： C07D239/42 ,  C07D239/48 ,  C07D401/10 ,  C07D403/10 ,  C07D413/10 ,  C07D487/10 ,  C07D491/107 ,  Y02A50/488

摘要： The compositions and methods described herein disclose the design, synthesis and testing of compounds that act as inhibitors of DHFR. The basic scaffold of these inhibitors includes a 2,4-diaminopyrimidine ring with a propargyl linker to another substituted aryl, bicyclo or heteroaryl ring. These DHFR inhibitors are potent and selective for many different pathogenic organisms, including the DHFR enzyme from bacteria such as Bacillus anthracis and methicillin-resistant Staphylococcus aureus, fungi such as Candida glabrata, Candida albicans and Cryptococcus neoformans and protozoa such as Cryptosporidium hominis and Toxoplasma gondii. These compounds and other similar compounds are also potent against the mammalian enzyme and may be useful as anti-cancer therapeutics.

摘要翻译： 本文所述的组合物和方法公开了用作DHFR抑制剂的化合物的设计，合成和测试。 这些抑制剂的基本支架包括具有炔丙基接头的2,4-二氨基嘧啶环与另一个取代的芳基，双环或杂芳基环。 这些DHFR抑制剂对于许多不同的致病生物体是有效的和选择性的，包括来自细菌如炭疽芽孢杆菌和耐甲氧西林金黄色葡萄球菌的DHFR酶，真菌如光滑假丝酵母，白色念珠菌和新型隐球酵母以及原生动物如人隐孢子虫和弓形虫 。 这些化合物和其它类似化合物对哺乳动物酶也是有效的，并且可用作抗癌治疗剂。

公开(公告)号：US20120196859A1

公开(公告)日：2012-08-02

申请号：US13290741

申请日：2011-11-07

申请人： Amy C. Anderson ,  Dennis L. Wright ,  Kathleen Mary Frey ,  Janet Leigh Paulsen ,  Eric William Scocchera ,  Kishore Viswanathan

发明人： Amy C. Anderson ,  Dennis L. Wright ,  Kathleen Mary Frey ,  Janet Leigh Paulsen ,  Eric William Scocchera ,  Kishore Viswanathan

IPC分类号： A61K31/505 ,  C07D401/06 ,  A61K31/506 ,  C07D413/06 ,  A61P35/00 ,  C07D403/06 ,  A61P31/04 ,  A61P31/10 ,  A61P33/02 ,  C07D239/49 ,  A61K31/5377

CPC分类号： C07D239/42 ,  C07D239/48 ,  C07D401/10 ,  C07D403/10 ,  C07D413/10 ,  C07D487/10 ,  C07D491/107 ,  Y02A50/488

摘要： The compositions and methods described herein disclose the design, synthesis and testing of compounds that act as inhibitors of DHFR. The basic scaffold of these inhibitors includes a 2,4-diaminopyrimidine ring with a propargyl linker to another substituted aryl, bicyclo or heteroaryl ring. These DHFR inhibitors are potent and selective for many different pathogenic organisms, including the DHFR enzyme from bacteria such as Bacillus anthracis and methicillin-resistant Staphylococcus aureus, fungi such as Candida glabrata, Candida albicans and Cryptococcus neoformans and protozoa such as Cryptosporidium hominis and Toxoplasma gondii. These compounds and other similar compounds are also potent against the mammalian enzyme and may be useful as anti-cancer therapeutics.

摘要翻译： 本文所述的组合物和方法公开了用作DHFR抑制剂的化合物的设计，合成和测试。 这些抑制剂的基本支架包括具有炔丙基接头的2,4-二氨基嘧啶环与另一个取代的芳基，双环或杂芳基环。 这些DHFR抑制剂对于许多不同的致病生物体是有效的和选择性的，包括来自细菌如炭疽芽孢杆菌和耐甲氧西林金黄色葡萄球菌的DHFR酶，真菌如光滑假丝酵母，白色念珠菌和新型隐球酵母以及原生动物如人隐孢子虫和弓形虫 。 这些化合物和其它类似化合物对哺乳动物酶也是有效的，并且可用作抗癌治疗剂。