2-amino-4-(benzyloxy)-5-nitropyrimidine | 160948-26-5

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 2-amino-4-(benzyloxy)-5-nitropyrimidine
• 英文别名: 2-Amino-4-benzyloxy-5-nitropyrimidine；5-nitro-4-phenylmethoxypyrimidin-2-amine
• CAS: 160948-26-5
• 化学式: C₁₁H₁₀N₄O₃
• 分子量: 246.225
• InChiKey: DSIVLMKQNTVXOD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-氨基-4-氯-5-硝基嘧啶 、 苯甲醇 在 sodium 作用下， 反应 3.0h， 以13%的产率得到2-amino-4-(benzyloxy)-5-nitropyrimidine
  参考文献：
  名称：

  8-取代的O6-苄基鸟嘌呤，取代的6（4）-（苄氧基）嘧啶和相关衍生物作为人O6-烷基鸟嘌呤-DNA烷基转移酶的灭活剂。

  摘要：

  测试了几种8-取代的O6-苄基鸟嘌呤，2-和/或8-取代的6-（苄氧基）嘌呤，取代的6（4）-（苄氧基）嘧啶和6-（苄氧基）-s-三嗪的能力。使人类DNA修复蛋白O6-烷基鸟嘌呤-DNA烷基转移酶（AGT，烷基转移酶）失活。已鉴定出两种类型的化合物在使人HT29结肠肿瘤细胞提取物中的AGT失活方面比O6-苄基鸟嘌呤（原型低分子量灭活剂）明显更有效。它们是在8位带有吸电子基团的8-取代的O6-苄基鸟嘌呤（例如8-氮杂-O6-苄基鸟嘌呤和O6-苄基-8-溴鸟嘌呤）和5-取代的2,4-二氨基-6-（苄氧基）在5位带有吸电子基团的嘧啶（例如2,4-二氨基-6-（苄氧基）-5-亚硝基和2，4-二氨基-6-（苄氧基）-5-硝基嘧啶）。在完整的HT29结肠肿瘤细胞中，后者的衍生物在灭活AGT方面比O6-苄基鸟嘌呤更有效。如果这些类型的嘌呤和嘧啶没有表现出不希望的毒性，则它们可以优于O6-苄基鸟嘌呤作为用

  DOI：

  10.1021/jm00002a018

文献信息

• Substituted O6-benzyl-8-aza-guanines
  申请人：The Government of the United States of America, Department of Health and Human Services

  公开号：US20020013299A1

  公开（公告）日：2002-01-31

  The present invention provides AGT inactivating compounds such as substituted O 6 -benzylguanines of the formula 1 7- or 9-substituted 8-aza-O 6 -benzylguanines, 7,8-disubstituted O 6 -benzylguanines, 7,9-disubstituted O 6 -benzylguanines, 4(6)-substituted 2-amino-5-nitro-6 (4) -benzyloxypyrimidines, and 4 (6) -substituted 2-amino-5-nitroso-6(4)-benzyloxypyrimidines, as well as pharmaceutical compositions comprising such compounds along with a pharmaceutically acceptable carrier. The present invention further provides a method of enhancing the chemotherapeutic treatment of tumor cells in a mammal with an antineoplastic alkylating agent, which causes cytotoxic lesions at the O 6 -position of guanine, by administering to a mammal an effective amount of one of the aforesaid compounds, 2,4-diamino-6-benzyloxy-s-triazine, 5-substituted 2,4-diamino-6-benzyloxypyrimidines, or 8-aza-O 6 -benzylguanine, and administering to the mammal an effective amount of an antineoplastic alkylating agent which causes cytotoxic lesions at the Deposition of guanine.

  本发明提供了AGT失活化合物，例如公式17-或9-取代的8-aza-O6-苄基鸟嘌呤、7,8-二取代的O6-苄基鸟嘌呤、7,9-二取代的O6-苄基鸟嘌呤、4（6）-取代的2-氨基-5-硝基-6（4）-苄氧嘧啶和4（6）-取代的2-氨基-5-亚硝基-6（4）-苄氧嘧啶，以及包含这些化合物和药用载体的制药组合物。本发明还提供了一种增强抗肿瘤烷化剂治疗哺乳动物肿瘤细胞的方法，该方法通过向哺乳动物投与上述化合物、2,4-二氨基-6-苄氧基-s-三嗪、5-取代的2,4-二氨基-6-苄氧基嘧啶或8-aza-O6-苄基鸟嘌呤的有效量，并向哺乳动物投与一种在鸟嘌呤O6位引起细胞毒性损伤的抗肿瘤烷化剂的有效量。
• Substituted 06-benzylguanines and 6(4)-benzyloxypyrimidines
  申请人：The United States of America as represented by the Department of Health

  公开号：US05525606A1

  公开（公告）日：1996-06-11

  The present invention provides 8-substituted O.sup.6 -benzylguanines of the formula ##STR1## wherein R.sub.1, R.sub.2, and R.sub.3 are as defined in the specification, and 4(6)-substituted 2-amino-5-nitro-6(4)-benzyloxypyrimidine, and 4(6)-substituted 2-amino-5-nitroso-6(4)-benzyloxypyrimidine derivatives which have been found to be effective AGT inactivators, as well as pharmaceutical compositions comprising such derivatives along with a pharmaceutically acceptable carrier. The present invention further provides a method of enhancing the chemotherapeutic treatment of tumor cells in a mammal with an antineoplastic alkylating agent which causes cytotoxic lesions at the O.sup.6 -position of guanine, by administering to a mammal an effective amount of one of the aforesaid derivatives, 2,4-diamino-6-benzyloxy-s-triazine, 5-substituted 2,4-diamino-6-benzyloxypyrimidines, or 8-aza-O.sup.6 -benzylguanine, and administering to the mammal an effective amount of an antineoplastic alkylating agent which causes cytotoxic lesions at the O.sup.6 -position of guanine.

  本发明提供了式子如下的8-取代O.sup.6-苄基鸟嘌呤：##STR1##其中R.sub.1，R.sub.2和R.sub.3如规范中定义的，以及4（6）-取代的2-氨基-5-硝基-6（4）-苄氧基嘧啶，以及已发现有效的AGT失活剂的4（6）-取代2-氨基-5-亚硝基-6（4）-苄氧基嘧啶衍生物，以及包含这些衍生物和药用可接受载体的制药组合物。本发明还提供了一种增强哺乳动物体内肿瘤细胞化疗治疗的方法，该方法使用一种抗肿瘤烷基化剂，该烷基化剂在鸟嘌呤的O.sup.6-位置引起细胞毒性损伤，通过向哺乳动物体内投与上述衍生物，2,4-二氨基-6-苄氧基-s-三嗪，5-取代的2,4-二氨基-6-苄氧基嘧啶，或8-氮杂-O.sup.6-苄基鸟嘌呤的有效量，并向哺乳动物体内投与引起鸟嘌呤的O.sup.6-位置细胞毒性损伤的抗肿瘤烷基化剂的有效量。
• Substituted benzyloxypyrimidines and their inactivation of O.sup.6
  申请人：The United States of America as represented by the Department of Health

  公开号：US05753668A1

  公开（公告）日：1998-05-19

  The present invention provides certain novel nitro or nitroso substituted benzyloxy pyrimidines useful as AGT inactivators. An example of such a pyrimidine is a compound of the formula ##STR1## wherein R.sub.1, is NO.sub.2 or NO, and R.sub.2 is hydrogen, halo, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 hydroxyalkyl, thiol, C.sub.1 -C.sub.4 alkythio, trifluoromethoxy, oxymethanesulfonyl, oxytrifluoromethanesulfonyl, or C.sub.1 -C.sub.4 oxyacyl. The present invention further provides pharmaceutical compositions comprising these compounds, and a method of enhancing the chemotherapeutic treatment of tumor cells in a mammal with an antineoplastic alkylating agent which causes cytotoxic lesions at the O.sup.6 -position of guanine.

  本发明提供了某些新型的硝基或亚硝基取代的苄氧基嘧啶，可用作AGT失活剂。这样的嘧啶的一个例子是式子##STR1##中的化合物，其中R.sub.1是NO.sub.2或NO，R.sub.2是氢、卤素、C.sub.1-C.sub.4烷基、C.sub.1-C.sub.4羟基烷基、硫醇、C.sub.1-C.sub.4烷硫基、三氟甲氧基、氧甲烷磺酰基、氧三氟甲烷磺酰基或C.sub.1-C.sub.4氧酰基。本发明还提供了包含这些化合物的药物组合物，以及一种增强哺乳动物中肿瘤细胞的化疗治疗的方法，该方法使用一种抗肿瘤烷基化剂，在鸟嘌呤的O.sup.6位引起细胞毒性损伤。
• Pharmaceutical composition comprising 2,4-diamino-6-benzyloxy-s-triazine and inactivation of O6-alkylguanine-DNA-alkyltransferase
  申请人：The United States of America as represented by the Department of Health and Human Services

  公开号：US06303604B1

  公开（公告）日：2001-10-16

  The present invention provides 8-substituted O6-benzylguanine, 4(6)-substituted 2-amino-5-nitro-6(4)-benzyloxypyrimidine, and 4(6)-substituted 2-amino-5-nitroso-6(4)-benzyloxypyrimidine derivatives which have been found to be effective AGT inactivators, as well as pharmaceutical compositions comprising such derivatives along with a pharmaceutically acceptable carrier. The present invention further provides a method of enhancing the chemotherapeutic treatment of tumor cells in a mammal with an antineoplastic alkylating agent which causes cytotoxic lesions at the O6-position of quanine, by administering to a mammal an effective amount of one of the aforesaid derivatives, 2,4-diamino-6-benzyloxy-s-triazine, 5-substituted 2,4-diamino-6-benzyloxypyrimidines, or 8-aza-O6-benzylguanine, and administering to the mammal an effective amount of an antineoplastic alkylating agent which causes cytotoxic lesions at the O6-position of guanine.

  本发明提供了8-取代的O6-苄基鸟嘌呤，4(6)-取代的2-氨基-5-硝基-6(4)-苄氧基嘧啶和4(6)-取代的2-氨基-5-亚硝基-6(4)-苄氧基嘧啶衍生物，发现它们是有效的AGT失活剂，以及包含这些衍生物和药学上可接受的载体的制药组合物。本发明还提供了一种增强哺乳动物体内抗肿瘤烷基化剂治疗肿瘤细胞的方法，该烷基化剂在鸟嘌呤的O6位引起细胞毒性损伤，通过向哺乳动物体内投与上述衍生物、2,4-二氨基-6-苄氧基-s-三嗪、5-取代的2,4-二氨基-6-苄氧基嘧啶或8-氮杂-O6-苄基鸟嘌呤的有效量，并向哺乳动物体内投与一种在鸟嘌呤的O6位引起细胞毒性损伤的抗肿瘤烷基化剂的有效量。
• Substituted O6-benzylguanines
  申请人：The United States of America as represented by the Department of Health and Human Services

  公开号：US06333331B1

  公开（公告）日：2001-12-25

  The present invention provides AGT inactivating compounds such as substituted O6-benzylguanines of the formula 7- or 9-substituted 8-aza-O6-benzylguanines, 7,8-disubstituted O6-benzylguanines, 7,9-disubstituted O6-benzylguanines, 4(6)-substituted 2-amino-5-nitro-6(4)-benzyloxypyrimidines, and 4(6)-substituted 2-amino-5-nitroso-6(4)-benzyloxypyrimidines, as well as pharmaceutical compositions comprising such compounds along with a pharmaceutically acceptable carrier. The present invention further provides a method of enhancing the chemotherapeutic treatment of tumor cells in a mammal with an antineoplastic alkylating agent which causes cytotoxic lesions at the O6-position of guanine, by administering to a mammal an effective amount of one of the aforesaid compounds, 2,4-diamino-6-benzyloxy-s-triazine, 5-substituted 2,4-diamino-6-benzyloxypyrimidines, or 8-aza-O6-benzylguanine, and administering to the mammal an effective amount of an antineoplastic alkylating agent which causes cytotoxic lesions at the O6-position of guanine.

  本发明提供了AGT失活化合物，例如公式7-或9-取代的8-氮杂-O6-苄基鸟嘌呤，7,8-二取代的O6-苄基鸟嘌呤，7,9-二取代的O6-苄基鸟嘌呤，4（6）-取代的2-氨基-5-硝基-6（4）-苄氧嘧啶和4（6）-取代的2-氨基-5-亚硝基-6（4）-苄氧嘧啶，以及包含这些化合物和药学上可接受的载体的制药组合物。本发明还提供了一种方法，在哺乳动物中通过向哺乳动物施用上述化合物之一，2,4-二氨基-6-苄氧基-s-三嗪，5-取代的2,4-二氨基-6-苄氧基嘧啶，或8-氮杂-O6-苄基鸟嘌呤的有效量，并向哺乳动物施用在鸟嘌呤的O6位引起细胞毒性损伤的抗肿瘤烷基化剂的有效量，以增强肿瘤细胞的化疗治疗。