5-halo-pyrimid-2-ones, the salts thereof, processes for...

C - Chemistry – Metallurgy – 07 – D

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C07D 239/30 (2006.01) C07D 243/08 (2006.01) C07D 277/42 (2006.01) C07D 277/56 (2006.01) C07D 333/16 (2006.01) C07D 333/28 (2006.01) C07D 403/06 (2006.01)

Patent

CA 1168239

ABSTRACT "5-Halo-pyrimidin-2-ones, the salts thereof, processes for their preparation, pharmaceutical compositions containing them and a method therefor" Compounds of the formula :- Image (I) (wherein X represents a halogen atom; R1 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 selected from halogen atoms and hydroxy, C1-4 alkoxy, amino, acylamino, nitro, oxo, C1-4 alkyl groups and monocyclic carbocyclic and heterocyclic aryl groups having 5 to 8 ring members; such a heterocyclic ring being saturated and having only a single heteroatom when there are 3 or 4 ring members; and alk represents a C1-4 saturated or unsaturated, straight or branched chain, divalent aliphatic hydrocarbyl group optionally substituted by one or more groups selected from carbocyclic aryl groups and heterocyclic groups as defined for Het above) and, where an acidic or basic group is present, the salts thereof have been found to possess metaphase arresting ability which by virtue of 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 or ring closure of the heterocyclic` ring Het.

367958

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