公开(公告)号：US6043228A

公开(公告)日：2000-03-28

申请号：US568576

申请日：1995-12-07

申请人： Thomas Brian McMurry ,  Robert Stanley McBlhinney ,  Joan Elizabeth McCormick ,  Rhoderick Hugh Elder ,  Jane Kelly ,  Geoffrey Margison ,  Joseph Anthony Rafferty ,  Amanda Jean Watson ,  Mark Andrew Willington ,  Dorothy Josephine Donnelly

发明人： Thomas Brian McMurry ,  Robert Stanley McBlhinney ,  Joan Elizabeth McCormick ,  Rhoderick Hugh Elder ,  Jane Kelly ,  Geoffrey Margison ,  Joseph Anthony Rafferty ,  Amanda Jean Watson ,  Mark Andrew Willington ,  Dorothy Josephine Donnelly

IPC分类号： A01N43/54 ,  A01N43/90 ,  A61K31/70

CPC分类号： A01N43/54 ,  A01N43/90 ,  A61K31/70

摘要： O.sup.6 -hetarylalkyl- or naphthylalkylguanine derivatives of the formula ##STR1## wherein Y is H, ribosyl, deoxyribosyl, or R"XCHR',wherein X is O or S, R" and R"' are alkyl, or substituted derivatives thereof,R' is H, or alkyl or hydroxyalkylR is(i) a cyclic group having at least one 5- or 6-membered heterocyclic ring, optionally with a carbocylic or heterocyclic ring fused thereto, the or each heterocyclic ring having at least one hereto atom chosen from O, N, or S, or a substituted derivative thereof; or(ii) naphthyl or a substituted derivative thereofand pharmaceutically acceptable salts thereof, exhibit the ability to deplete O.sup.6 -alkylguanine-DNA alkyltransferase (ATase) activity.A process for preparation of the compounds is described. The compounds have utility in combination with alkylating agents in the chemotherapeutic treatment of tumour cells.

摘要翻译： 其中Y是H，核糖基，脱氧核糖基或R''XCHR'，其中X是O或S，R“和R”'是烷基，C 1 -C 6烷基或萘基烷基鸟嘌呤衍生物， 或其取代衍生物，R'为H，或烷基或羟基烷基R为（i）具有至少一个5-或6-元杂环的环状基团，任选具有与其稠合的碳环或杂环，所述或各杂环 具有至少一个选自O，N或S的原子或其取代的衍生物的环; 或（ii）萘基或其取代的衍生物及其药学上可接受的盐，具有消耗+ E，非O + EE6-烷基鸟嘌呤-DNA烷基转移酶（ATase）活性的能力。 描述了制备该化合物的方法。 化合物在肿瘤细胞的化学治疗中具有与烷化剂组合的效用。