申请人:THE WELLCOME FOUNDATION LIMITED
公开号:EP0409406A2
公开(公告)日:1991-01-23
Use of compounds of formula (I)
wherein A represents a group selected from:
X represents -CH- or -N-;
R¹ represents a hydrogen or halogen atom, a C₁₋₄ alkoxy group, a C₁₋₄ alkyl group, or a C₁₋₄ alkyl group substituted by 1 to 3 halogen atoms;
R² represents a hydrogen or halogen atom, a C₁₋₄ alkoxy group, benzyloxy or a group -R⁷COOR⁸ (wherein R⁷ represents a single bond or a C₁₋₇ bivalent aliphatic hydrocarbon group and R⁸ represents a hydrogen atom or a C₁₋₄ alkyl group) or a group R⁷CONR8aR8b (wherein R8a and R8b each represent a hydrogen atom or a C₁₋₄ alkyl group, or together with the nitrogen atom to which they are attached form a 4-6 membered saturated heterocyclic ring);
R³ and R⁴, which may be the same or different each represent a hydrogen atom or a C₁₋₄ alkyl group,
or R³ and R⁴ together with the nitrogen atom to which they are attached form a 4-6 membered saturated heterocyclic ring, which may optionally contain an oxygen atom or a further nitrogen atom, which may itself be substituted by a C₁₋₄ alkyl group;
R⁵ and R⁶ each represent a hydrogen atom or together form a linking group between the aromatic rings, said group being selected from -CH₂CH₂-, -CH₂O-, -OCH₂-, -NHCH₂, or -CH₂NH;
n is zero or an integer from 1 to 3; and
p and q are each independently an integer from 1 to 4,
with the provisos that
(a) when R⁵ and R⁶ form a linking group, A is not -CH₂-(CH₂)n-
and
(b) when A represents a group
C=CH(CH₂)n- and n is 1, R¹ is methyl, NR³R⁴ is pyrrolidino and R⁵ and R⁶ are both hydrogen then R² is not hydrogen or -CH=CHCO₂H,
and pharmaceutically acceptable salts thereof in the manufacture of a medicament for enhancing the therapeutic effect of an antineoplastic agent.
使用式(I)化合物
其中 A 代表选自以下的基团
X 代表-CH-或-N-;
R¹ 代表氢原子或卤素原子、C₁₋₄ 烷氧基、C₁₋₄ 烷基或被 1 至 3 个卤素原子取代的 C₁₋₄ 烷基;
R² 代表氢原子或卤素原子、C₁₋₄ 烷氧基、苄氧基或一个基团R⁷COOR⁸(其中 R⁷ 代表单键或 C₁₋₇二价脂肪族烃基,R⁸ 代表氢原子或 C₁₋₄烷氧基,苄氧基或以下基团原子或 C₁₋₄ 烷基)或基团 R⁷CONR8aR8b(其中 R8a 和 R8b 各自代表氢原子或 C₁₋₄ 烷基、或与所连接的氮原子一起形成 4-6 个成员的饱和杂环);
R³ 和 R⁴,可以相同或不同,各自代表一个氢原子或一个 C₁₋₄ 烷基、
或 R³ 和 R⁴ 与它们所连接的氮原子一起形成一个 4-6 个成员的饱和杂环,该杂环可任选含有一个氧原子或另一个氮原子,其本身可被一个 C₁₋₄ 烷基取代;
R⁵ 和 R⁶ 各自代表一个氢原子或共同构成芳环之间的连接基团,所述基团选自 -CH₂CH₂-、-CH₂O-、-OCH₂-、-NHCH₂或 -CH₂NH;
n 是零或 1 至 3 的整数;以及
p 和 q 各自独立地为 1 至 4 的整数、
但书为
(a) 当 R⁵ 和 R⁶ 构成连接基团时,A 不是 -CH₂-(CH₂)n-
且
(b) 当 A 代表一个基团时
C=CH(CH₂)n-且 n 为 1,R¹ 为甲基,NR³R⁴ 为吡咯烷基,且 R⁵ 和 R⁶ 均为氢时,R² 不是氢或 -CH=CHCO₂H、
及其药学上可接受的盐,用于制造增强抗肿瘤药物治疗效果的药物。