申请人:——
公开号:US20030195173A1
公开(公告)日:2003-10-16
The invention related to colchinol derivatives of the formula (I): Wherein: R
1
, R
2
and R
3
are each independently hydroxy, phosphoryloxy (—OPO
3
H
2
), C
1-4
alkoxy or an in vivo hydrolysable ester of hydroxy, with the proviso that at least 2 of R
1
, R
2
and R
3
are C
1-4
alkoxy; A is —CO—, —C(O)O—, —CON(R
8
)— (wherein R
8
is hydrogen, C
1-4
alkyl, C
1-3
alkoxyC
1-3
alkyl, aminoC
1-3
alkyl or hydroxyC
1-3
alkyl); a is an integer from 1 to 4 inclusive; R
a
and R
b
are independently selected from hydrogen, hydroxy and amino; B is —O—, —CO—, N(R
9
)CO—, —CON(R
9
)—, —N(R
9
)C(O)O—, —N(R
9
)CON(R
10
)—, —N(R
9
)SO
2
—, —SO
2
N(R
9
)— or a direct single blond (wherein R
9
and R
10
are independently selected from hydrogen, C
1-4
alkyl, C
1-3
alkoxyC
1-3
alkyl,aminoC
1-3
alkyl and hydroxyC
1-3
alkyl); b is O or an integer from 1 to 4 inclusive, (provided that when bis O, B is a single direct bond); D is carboxy, sulpho, tetrazolyl, imidazolyl, phosphoryloxy, hydroxy, amino, N-(C
1-4
alkyl)amino, N,N-di(C
1-3
alkyl)amino, or of the formula-Y
1
(CH
2
)
0
R
11
or —NHCH(R
12
)COOH;[wherein Y
1
is a direct single bond, —O—, —C(O)—, —N(R
13
)C(O)— or —C(O)N(R
13
)— (wherein R
13
is hydrogen, C
1-4
alkyl,C
1-3
alkoxyC
2-3
alkyl, aminoC
2-3
alkyl or hydroxyC
2-3
alkyl); e is O or an integer from 1 to 4 inclusive.
与化学相关的发明,涉及公式(I)的秋水仙碱衍生物:其中:R1、R2和R3分别独立地为羟基、磷酸酯基(—OPO3H2)、C1-4烷氧基或羟基的体内可水解酯,但至少其中2个为C1-4烷氧基;A为—CO—、—C(O)O—、—CON(R8)—(其中R8为氢、C1-4烷基、C1-3烷氧基烷基、氨基烷基或羟基烷基);a为1到4的整数;Ra和Rb分别独立地选自氢、羟基和氨基;B为—O—、—CO—、N(R9)CO—、—CON(R9)—、—N(R9)C(O)O—、—N(R9)CON(R10)—、—N(R9)SO2—、—SO2N(R9)—或直接单键(其中R9和R10分别独立地选自氢、C1-4烷基、C1-3烷氧基烷基、氨基烷基和羟基烷基);b为O或1到4的整数,(当b为O时,B为单一直接键);D为羧基、磺酸基、四唑基、咪唑基、磷酸酯基、羟基、氨基、N-(C1-4烷基)氨基、N,N-二(C1-3烷基)氨基,或公式-Y1(CH2)0R11或—NHCH(R12)COOH;[其中Y1为直接单键、—O—、—C(O)—、—N(R13)C(O)—或—C(O)N(R13)—(其中R13为氢、C1-4烷基、C1-3烷氧基烷基、氨基烷基或羟基烷基);e为O或1到4的整数。