5-Halo-pyrimidin-2-ones, the salts thereof, processes for their preparation and pharmaceutical compositions containing them
申请人:NYEGAARD & CO. A/S
公开号:EP0032131A1
公开(公告)日:1981-07-15
Compounds of the formula :-
(wherein
X represents a halogen atom;
R' and R2, which may be the same or different, each represents a hydrogen atom, or a C1-4 alkyl group;
Het represents a C-attached 3-9 membered, saturated, unsaturated or aromatic heterocyclic ring containing one or more hetero atoms selected from 0,N and S and optionally carrying a fused ring and/or optionally substituted by one or more substituents; and
alk represents a C1-4 saturated or unsaturated, straight or branched chain, divalent aliphatic hydrocarbyl group optionally substituted and, where an acidic or basic group is present, the salts thereof have been found to possess metaphase arresting ability which by virtue of its reversibility is of use in combating abnormal cell proliferation. Thus a knowledge of the cell division cycles of the normal and abnormal cells enables a cytotoxic drug to be administered whilst the abnormal cells are in a phase susceptible to attack and whilst the normal cells are in a non-susceptible phase.
The compounds of the invention are prepared by alkylation, ring closure of the pyrimidine ring, halogenation, ring closure of the heterocyclic ring Het or dehydrazination.
式中的化合物
其中
X 代表卤素原子;
R'和 R2(可以相同或不同)分别代表氢原子或 C1-4 烷基;
Het 代表与 C 相连的 3-9 分子、饱和、不饱和或芳香杂环,含有一个或多个选自 0、N 和 S 的杂原子,可选带熔合环和/或可选被一个或多个取代基取代;以及
烷基代表 C1-4 饱和或不饱和、直链或支链、可选择被取代的二价脂族烃基,在存在酸性或碱性基团的情况下,其盐类已被发现具有抑制分裂期的能力,由于其可逆性,可用于抑制异常细胞增殖。因此,了解了正常细胞和异常细胞的细胞分裂周期,就可以在异常细胞处于易受攻击阶段而正常细胞处于非易受攻击阶段时施用细胞毒性药物。
本发明的化合物是通过烷基化、嘧啶环闭环、卤化、杂环闭环 Het 或脱氮来制备的。