申请人：——
公开号：US20020165201A1
公开（公告）日：2002-11-07
The invention relates to compounds of the formula I
1
wherein X
1
and X
2
independently represent a bond; a straight, branched and/or cyclic hydrocarbon diradical, optionally substituted with one or more hydroxy, halogen, nitro, amino, cyano, aminosulfonyl, alkylsulfonylamino, alkylcarbonyl, formyl, aminocarbonyl or alkylcarbonylamino; a heteroarylene or non-aromatic heterocyclic hydrocarbon diradical, all of which are optionally substituted with one or more straight, branched and/or cyclic non-aromatic hydrocarbon radical, hydroxyl, halogen, amino, nitro, cyano, aminosulfonyl, alkylsulfonylamino, alkylcarbonyl, formyl, aminocarbonyl or alkylcarbonylamino;
Y
1
and Y
2
independently represent a bond, an ether diradical (R′—O—R″), an amine diradical (R′—N—R″), O, S, S(O), S(O)
2
, C(O), NH—CO, CO—NH, SO
2
—N(R′), methylene or N(R′)—SO
2
wherein R′ and R″ independently represent straight or branched hydrocarbon diradicals containing up to 4 carbon atoms;
Y
3
represents O, O—C(O), C(O)—O, N(R
8
), R
8
being hydrogen or C
1-4
alkyl
R
1
represents hydrogen or straight, branched and/or cyclic alkyl, optionally substituted with phenyl; or an aromatic hydrocarbon radical;
R
2
represents aryl, heteroaryl or a non-aromatic heterocyclic hydrocarbon radical, all of which are optionally substituted; tetrahydropyranyloxy, di-(C
1-4
alkoxy)phosphinoyloxy or C
1-4
alkoxycarbonylamino;
R
3
represents hydrogen; a straight, branched and/or cyclic hydrocarbon radical, optionally substituted with one or more amino, hydroxy, carboxy, halogen, nitro, cyano, alkoxy, aminocarbonyl, C
1-4
alkoxycarbonyl, C
1-4
alkoxycarbonylamino, sulfo, hydroxysulfonyloxy, dihydroxyphosphinoyloxy, phosphono, sulfamino, aminosulfonyl, aminoacylamino or dialkoxyphosphinoyl; heteroaryl or a non-aromatic heterocyclic hydrocarbon radical, all of which are optionally substituted with one or more straight, branched and/or cyclic hydrocarbon radical, amino, hydroxy, carboxy, halogen, nitro, cyano, alkoxy, aminocarbonyl, C
1-4
alkoxycarbonyl, C
1-4
alkoxycarbonylamino, sulfo, hydroxysulfonyloxy, dihydroxyphosphinoyloxy, phosphono, sulfamino, aminosulfonyl, aminoacylamino or dialkoxyphosphinoyl;
2
wherein s is an integer from 1 to 200; R
6
is hydrogen or an optionally substituted non-aromatic hydrocarbon radical; R
7
is independently hydrogen or methyl;
R
4
and R
5
independently represent hydrogen; a straight, branched and/or cyclic hydrocarbon radical, optionally substituted with halogen, hydroxyl, halogen, amino, nitro or cyano;
A represents hydrogen, an optionally substituted, straight, branched and/or cyclic hydrocarbon radical, hydroxy, halogen, nitro, cyano, heteroaryl, heteroaralkyl or thiol; m and r are independently integers from 0 to 4; and n is 0 or 1;
Z
−
is a pharmaceutically acceptable anion, such as chloride, bromide, iodide, sulfate, methanesulfonate, p-toluenesulfonate, nitrate or phosphate. The compounds are well suited as prodrugs in human and veterinary therapy.
该发明涉及以下式I的化合物：
其中X1和X2分别表示键；一种直链、支链和/或环烃二自由基，可选择地取代一个或多个羟基、卤素、硝基、氨基、氰基、氨基磺酰基、烷基磺酰胺基、烷基羰基、甲酰基、氨基羰基或烷基羰基氨基；一种杂芳烃基或非芳香杂环烃二自由基，均可选择地取代一个或多个直链、支链和/或环非芳香烃基、羟基、卤素、氨基、硝基、氰基、氨基磺酰基、烷基磺酰胺基、烷基羰基、甲酰基、氨基羰基或烷基羰基氨基；
Y1和Y2分别表示键、醚二自由基（R′—O—R″）、胺二自由基（R′—N—R″）、O、S、S(O)、S(O)2、C(O)、NH—CO、CO—NH、SO2—N(R′)、亚甲基或N(R′)—SO2，其中R′和R″分别表示含有最多4个碳原子的直链或支链烃基；
Y3表示O、O—C(O)、C(O)—O、N(R8)，其中R8为氢或C1-4烷基
R1表示氢或直链、支链和/或环烷基，可选择地取代苯基；或芳香烃基；
R2表示芳基、杂芳基或非芳香杂环烃基，均可选择地取代；四氢吡喃氧基、二-(C1-4烷氧)磷酰氧基或C1-4烷氧羰基氨基；
R3表示氢；一种直链、支链和/或环烃基，可选择地取代一个或多个氨基、羟基、羧基、卤素、硝基、氰基、烷氧基、氨基羰基、C1-4烷氧羰基、C1-4烷氧羰基氨基、磺酰基、羟基磺酰氧基、二羟基磷酰氧基、磷酸酯、磺胺基、氨基磺酰基、氨基酰氨基或二烷氧基磷酰基；杂芳基或非芳香杂环烃基，均可选择地取代一个或多个直链、支链和/或环烃基、氨基、羟基、羧基、卤素、硝基、氰基、烷氧基、氨基羰基、C1-4烷氧羰基、C1-4烷氧羰基氨基、磺酰基、羟基磺酰氧基、二羟基磷酰氧基、磷酸酯、磺胺基、氨基磺酰基、氨基酰氨基或二烷氧基磷酰基；
其中s为1至200的整数；R6为氢或可选择地取代的非芳香烃基；R7独立地为氢或甲基；
R4和R5独立地表示氢；一种直链、支链和/或环烃基，可选择地取代卤素、羟基、卤素、氨基、硝基或氰基；
A表示氢、可选择地取代的直链、支链和/或环烃基、羟基、卤素、硝基、氰基、杂芳基、杂芳基烷基或硫醇；m和r独立地为0至4的整数；n为0或1；
Z-为药用可接受的阴离子，如氯化物、溴化物、碘化物、硫酸盐、甲磺酸盐、对甲苯磺酸盐、硝酸盐或磷酸盐。这些化合物非常适用于人类和兽医治疗中作为前药。
