公开(公告)号：US6147076A

公开(公告)日：2000-11-14

申请号：US749908

申请日：1996-11-15

申请人： Samuel J. Danishefsky ,  Kristopher Depew ,  Stephen P. Marsden ,  William Bornmann ,  Ting Chao Chou ,  Andrej Zatorski

发明人： Samuel J. Danishefsky ,  Kristopher Depew ,  Stephen P. Marsden ,  William Bornmann ,  Ting Chao Chou ,  Andrej Zatorski

IPC分类号： C07D487/14 ,  A61K31/495 ,  A61K31/505 ,  A61P35/02 ,  C07D487/22

CPC分类号： C07D487/22

摘要： The present invention provides a compound having the structure: ##STR1## wherein R.sub.1 R.sub.6 and R.sub.7 are independently hydrogen, OH, NH.sub.2, SH, halogen, C.sub.1 -C.sub.9 linear or branched chain alkyl, alkylmercapto, alkylamino, dialkylamino, alkoxy, phenyl, etc.; wherein R.sub.0 and R.sub.2 are independently hydrogen, OH, linear or branched chain alkyl, --CR.sub.3 R.sub.3 --CH(O)CH.sub.2, --CR.sub.3 R.sub.3 --CH.sub.2 CH.sub.3, --CR.sub.3 R.sub.3 --CH.sub.2 CH.sub.2 OH, --CR.sub.3 R.sub.3 --CH(OH)R.sub.4 or --CR.sub.3 R.sub.3 --CH.dbd.CHR.sub.4 ; wherein R.sub.3 and R.sub.4 are independently hydrogen, halogen, C.sub.1 -C.sub.9 linear or branched chain alkyl, phenyl, etc.; wherein R.sub.5 is hydrogen, C.sub.1 -C.sub.9 linear or branched chain alkyl, phenyl, etc.; and wherein R.sub.8 is hydrogen, C.sub.1 -C.sub.9 linear or branched chain acyl, benzoyl, etc.; with the proviso that (a) when R.sub.2 is --CR.sub.3 R.sub.3 --CH(O)CH.sub.2, --CR.sub.3 R.sub.3 --CH.sub.2 CH.sub.3, --CR.sub.3 R.sub.3 --CH.sub.2 CH.sub.2 OH, --CR.sub.3 R.sub.3 --CH(OH)R.sub.4 or --CR.sub.3 R.sub.3 --CH.dbd.CHR.sub.4, then R.sub.2 is hydrogen; (b) when R.sub.0 is --CR.sub.3 R.sub.3 --CH(O)CH.sub.2, --CR.sub.3 R.sub.3 --CH.sub.2 CH.sub.3, --CR.sub.3 R.sub.3 --CH.sub.2 CH.sub.2 OH, --CR.sub.3 R.sub.3 --CH(OH)R.sub.4 or --CR.sub.3 R.sub.3 --CH.dbd.CHR.sub.4, then R.sub.2 is OH; and (c) when (i) R.sub.0 or R.sub.2 is --CR.sub.3 R.sub.3 --CH.dbd.CHR.sub.4, (ii) R.sub.3 and R.sub.5 are CH.sub.3 and (iii) R.sub.4 is hydrogen, then R.sub.1, R.sub.6 and R.sub.7 are not all hydrogen. Also provided are related compounds and compositions, and methods of inhibiting the growth of multidrug resistant cells by means of MDR reversal, collateral sensitivity and quantitative synergism.

摘要翻译： 本发明提供具有以下结构的化合物：其中R 1 R 6和R 7独立地为氢，OH，NH 2，SH，卤素，C 1 -C 9直链或支链烷基，烷基巯基，烷基氨基，二烷基氨基，烷氧基，苯基等; 其中R 0和R 2独立地是氢，OH，直链或支链烷基，-CR 3 R 3 -CH（O）CH 2，-CR 3 R 3 -CH 2 CH 3，-CR 3 R 3 -CH 2 CH 2 OH，-CR 3 R 3 -CH（OH）R 4或-CR 3 R 3 -CH = CHR 4 ; 其中R 3和R 4独立地是氢，卤素，C 1 -C 9直链或支链烷基，苯基等; 其中R5是氢，C1-C9直链或支链烷基，苯基等; 并且其中R8是氢，C1-C9直链或支链酰基，苯甲酰基等; 条件是（a）当R 2为-CR 3 R 3 -CH（O）CH 2，-CR 3 R 3 -CH 2 CH 3，-CR 3 R 3 -CH 2 CH 2 OH，-CR 3 R 3 -CH（OH）R 4或-CR 3 R 3 -CH = CHR 4时，则R2为氢; （b）当R 0是-CR 3 R 3 -CH（O）CH 2，-CR 3 R 3 -CH 2 CH 3，-CR 3 R 3 -CH 2 CH 2 OH，-CR 3 R 3 -CH（OH）R 4或-CR 3 R 3 -CH = CHR 4时，则R2是OH; 和（c）当（i）R 0或R 2为-CR 3 R 3 -CH = CHR 4时，（ⅱ）R 3和R 5为CH 3，（ⅲ）R 4为氢，则R 1，R 6和R 7不全为氢。 还提供了相关的化合物和组合物，以及通过MDR逆转，附着敏感性和定量协同作用抑制多药耐药细胞生长的方法。