公开(公告)号：US20070021384A1

公开(公告)日：2007-01-25

申请号：US11455889

申请日：2006-06-20

申请人： James Anderson ,  Catherine Headley ,  Paul Stapleton ,  Peter Taylor

发明人： James Anderson ,  Catherine Headley ,  Paul Stapleton ,  Peter Taylor

IPC分类号： A61K31/695 ,  A61K31/353 ,  C07F7/02

CPC分类号： C07D311/62 ,  C07D311/60

摘要： There is provided a novel compound of the general formula I in which each of R8 to R10 is hydrogen, aryl, C1-6 alkyl, trialkylsilyl or acyl; R1 to R5 are individually selected from hydrogen, hydroxy, C1-6 alkoxy and acyloxy; R6 and R7 are H, C1-4 alkyl, trialkylsilyl or acyl; X is O or NR, and R is H or Me; in which any of the alkyl groups including alkyl groups in alkoxy, acyl and acyloxy groups may be substituted by aryl, C1-4 alkyl, C1-4 alkoxy, hydroxyl, trialkylsiloxy or acyloxy groups; with the proviso that R2 and R3 are not both OH when R4 is H or OH, R1 and R5 are both H, and X is O. The amide compounds (X is NR) are analogues of epigallocatechin gallate or epicatechin galate, with an amide bond in place of the natural ester bond, with resistance to hydrolysis by esterase enzymes. The ester compounds (X is O) have a different hydroxylation pattern on the B ring as compared to the natural products. The compounds may be used to modulate the resistance to β-lactam antibiotics of various infections, especially methicillin resistant Staphylococcus aureus (MRSA). Pharmaceutical compositions containing the novel compounds and combinations of the novel compounds and β-lactam antibiotics are described.

摘要翻译： 提供了通式I的新化合物，其中R 8和R 10各自为氢，芳基，C 1-6烷基， 烷基，三烷基甲硅烷基或酰基; R 1至R 5各自独立地选自氢，羟基，C 1-6烷氧基和酰氧基; R 6和R 7是H，C 1-4烷基，三烷基甲硅烷基或酰基; X是O或NR，R是H或Me; 其中包括烷氧基，酰基和酰氧基中的烷基的任何烷基可以被芳基，C 1-4烷基，C 1-4烷氧基，羟基 三烷基甲硅烷氧基或酰氧基; 条件是当R 4为H或OH时，R 2和R 3不同时为OH，R 1为H >和R 5都是H，X是O.酰胺化合物（X是NR）是表没食子儿茶素没食子酸酯或表儿茶素加成酸酯的类似物，酰胺键代替天然酯键，与 耐酯酶水解。 与天然产物相比，酯化合物（X为O）在B环上具有不同的羟基化模式。 该化合物可用于调节对各种感染的β-内酰胺抗生素的抗性，特别是耐甲氧西林金黄色葡萄球菌（MRSA）。 描述了含有新化合物和新化合物和β-内酰胺抗生素的组合的药物组合物。

公开(公告)号：US07700646B2

公开(公告)日：2010-04-20

申请号：US11455889

申请日：2006-06-20

申请人： James C. Anderson ,  Catherine Headley ,  Paul D. Stapleton ,  Peter W. Taylor

发明人： James C. Anderson ,  Catherine Headley ,  Paul D. Stapleton ,  Peter W. Taylor

IPC分类号： A61K31/353 ,  C07D311/60 ,  C07D311/62

CPC分类号： C07D311/62 ,  C07D311/60

摘要： There is provided a novel compound of the general formula I in which each of R8 to R10 is hydrogen, aryl, C1-6 alkyl, trialkylsilyl or acyl; R1 to R5 are individually selected from hydrogen, hydroxy, C1-6 alkoxy and acyloxy; R6 and R7 are H, C1-4 alkyl, trialkylsilyl or acyl; X is O or NR, and R is H or Me; in which any of the alkyl groups including alkyl groups in alkoxy, acyl and acyloxy groups may be substituted by aryl, C1-4 alkyl, C1-4 alkoxy, hydroxyl, trialkylsiloxy or acyloxy groups; with the proviso that R2 and R3 are not both OH when R4 is H or OH, R1 and R5 are both H, and X is O. The amide compounds (X is NR) are analogues of epigallocatechin gallate or epicatechin galate, with an amide bond in place of the natural ester bond, with resistance to hydrolysis by esterase enzymes. The ester compounds (X is O) have a different hydroxylation pattern on the B ring as compared to the natural products. The compounds may be used to modulate the resistance to β-lactam antibiotics of various infections, especially methicillin resistant Staphylococcus aureus (MRSA). Pharmaceutical compositions containing the novel compounds and combinations of the novel compounds and β-lactam antibiotics are described.

摘要翻译： 提供了通式I的新化合物，其中R 8至R 10各自为氢，芳基，C 1-6烷基，三烷基甲硅烷基或酰基; R 1至R 5分别选自氢，羟基，C 1-6烷氧基和酰氧基; R6和R7是H，C1-4烷基，三烷基甲硅烷基或酰基; X是O或NR，R是H或Me; 其中包括烷氧基，酰基和酰氧基中的烷基的任何烷基可以被芳基，C 1-4烷基，C 1-4烷氧基，羟基，三烷基甲硅烷氧基或酰氧基取代; 条件是当R 4为H或OH时，R 2和R 3不同时为OH，R 1和R 5都为H，且X为O.酰胺化合物（X为NR）为表没食子儿茶素没食子酸没食子酸酯或表儿茶素加成酸盐的类似物，具有酰胺 键代替天然酯键，具有抗酯酶的水解作用。 与天然产物相比，酯化合物（X为O）在B环上具有不同的羟基化模式。 这些化合物可用于调节对各种感染，特别是耐甲氧西林金黄色葡萄球菌（MRSA）的β-内酰胺抗生素的抗性。 描述了含有新化合物和新化合物和β-内酰胺抗生素的组合的药物组合物。