E2GG

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: E2GG
• 英文别名: 5-(4-methoxybenzyl)amino-7-(4-methoxybenzyl)amino-3-isopropylpyrazolo[4,3-d]pyrimidine；5,7-di[(4-methoxybenzyl)amino]-3-isopropylpyrazolo[4,3-d]pyrimidine；E2GG,7-bis[(4-methoxybenzyl)amino]-3-isopropylpyrazolo[4,3-d]py rimidine；5-N,7-N-bis[(4-methoxyphenyl)methyl]-3-propan-2-yl-2H-pyrazolo[4,3-d]pyrimidine-5,7-diamine
• 化学式: C₂₄H₂₈N₆O₂
• 分子量: 432.525
• InChiKey: JLVOUKYHCMDIQP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  97
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  5-异丙基-4-硝基-1H-吡唑-3-羧酸 在 镍 苯膦酰二氯 、 氯化亚砜 、 氨 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 水 、 丙酮 为溶剂， 反应 25.5h， 生成 E2GG
  参考文献：
  名称：

  肌球蛋白的8-氮杂嘌呤和吡唑并[4,3-d]嘧啶类似物的合成及生物活性。

  摘要：

  三取代嘌呤肌球蛋白最近已被鉴定为微管组装的新型抑制剂。为了分析修饰其杂环骨架的效果，我们制备了肌球蛋白的8-氮杂嘌呤和吡唑并[4,3-d]嘧啶类似物，并比较了它们的生物学活性。聚合测定的结果表明，杂环中氮原子的重排改变了化合物对纯化微管蛋白的亲和力，并影响了癌细胞系的增殖。令人惊讶的是，化合物E2GG，一种肌球蛋白的吡唑并[4,3-d]嘧啶类似物，显示出对微管蛋白聚合的抑制活性和细胞周期蛋白依赖性激酶1、2和7的活性。这种双重特异性抑制剂提供了一个起点。用于开发一类新型的抗增殖剂。

  DOI：

  10.1016/j.ejmech.2006.07.004

文献信息

• Pyrazolo[4,3-D]pyrimidines, processes for their preparation and methods for therapy
  申请人：Moravcova Daniela

  公开号：US20050080097A1

  公开（公告）日：2005-04-14

  The invention relates to 3-, 5-, 7-trisubstituted pyrazolo[4,3-d]pyrimidines represented by the general formula I and pharmaceutically acceptable salts thereof, wherein R3 is an optionally substituted alkyl, cycloalkyl, cycloheteroalkyl, cycloalkyl alkyl, aryl or alkylaryl group; R5 is halogen, —NHNH 2 , —NHOH, NHCONH 2 , guanylo (NH—C(NH)NH 2 ) an optionally substituted C 1 -C 6 alkyl, alkenyl, alkinyl, C 3 -C 15 cycloalkyl, R f (C 3 -C 15 cycloalkyl), heterocycle, heteroalkyl, aryl, heteroaryl, arylalkyl, cycloheteroalkyl, cycloheteroalkyl alkyl, heteroarylalkyl group, the group —C(O)—R a , —C(O)NR b R c , —SO 3 R d , or —NHC(O)R e , wherein R a and R f are an optionally substituted C 1 -C 6 alkyl, alkenyl, or alkinyl group, R b , R c and R d are independently selected from the group consisting of H, optionally substituted C 1 -C 6 alkyl, alkenyl, or alkinyl group, and R e is a hydroxy, amino, alkoxy, alkylamino, optionally substituted C 1 -C 6 alkyl, alkenyl or alkinyl group; or the group —X—R 5′ , wherein X is —NH—, —O—, —S— or —N(alkyl)- and R 5 ′ is hydrogen, an optionally substituted C 1 -C 6 alkyl, alkenyl, alkinyl, C 3 -C 15 cycloalkyl, Rf(C 3 -C 15 cycloalkyl), aryl, heterocycle, hetero C 1 -C 6 alkyl, arylalkyl, heteroaryl, cycloheteroalkyl, cycloheteroalkyl alkyl, or heteroarylalkyl group, the group —C(O)—R a , —C(O)NR b R c , —SO 3 R d , or —NHC(O)R e , wherein R a , R b , R c , R d , R e and R f have the above meaning, and R7 is halogen, —NHNH 2 , NHOH, NHCONH 2 , guanylo (NH—C(NH)NH 2 ) or the group —X—R 7′ , wherein X has the above meaning and the meaning of R 7′ is as defined for R 5′ .

  本发明涉及一种由通式I表示的3-，5-，7-三取代吡唑并[4,3-d]嘧啶及其药学上可接受的盐，其中R3是可选取代的烷基，环烷基，环杂烷基，环烷基烷基，芳基或烷基芳基基团；R5是卤素，—NHNH2，—NHOH，NHCONH2，鸟苷基（NH—C(NH)NH2）可选取代的C1-C6烷基，烯基，炔基，C3-C15环烷基，Rf（C3-C15环烷基），杂环，杂烷基，芳基，杂芳基，芳基烷基，环杂烷基，环杂烷基烷基，杂芳基烷基基团，基团—C(O)—Ra，—C(O)NRbRc，—SO3Rd，或—NHC(O)Re，其中Ra和Rf是可选取代的C1-C6烷基，烯基或炔基，Rb，Rc和Rd是独立选择自H，可选取代的C1-C6烷基，烯基或炔基，Re是羟基，氨基，烷氧基，烷基氨基，可选取代的C1-C6烷基，烯基或炔基；或基团—X—R5′，其中X是—NH—，—O—，—S—或—N（烷基）-，R5′是氢，可选取代的C1-C6烷基，烯基，炔基，C3-C15环烷基，Rf（C3-C15环烷基），芳基，杂环，杂C1-C6烷基，芳基烷基，杂芳基，环杂烷基，环杂烷基烷基，或杂芳基烷基基团，基团—C(O)—Ra，—C(O)NRbRc，—SO3Rd，或—NHC(O)Re，其中Ra，Rb，Rc，Rd，Re和Rf具有上述含义，R7是卤素，—NHNH2，NHOH，NHCONH2，鸟苷基（NH—C(NH)NH2）或基团—X—R7′，其中X具有上述含义，R7′的含义如R5′所定义。
• Pyrazolo[4,3-d]pyrimidines, processes for their preparation and methods for therapy
  申请人：Ustav Experimentalni Botaniky AV CR, v.v.i. (Institute of Experimental Botany Academy of Sciences of the Czech Republic, PRO)

  公开号：EP1348707B1

  公开（公告）日：2010-08-25
• US7745450B2
  申请人：——

  公开号：US7745450B2

  公开（公告）日：2010-06-29
• [EN] NOVEL PYRAZOLO[4,3-D]PYRIMIDINES, PROCESSES FOR THEIR PREPARATION AND METHODS FOR THERAPY<br/>[FR] NOUVEAUX PYRAZOLO[4,3-D]PYRIMIDINES, PROCEDES POUR LEUR PREPARATION ET METHODES POUR UNE THERAPIE
  申请人：USTAV EX BOTAN AV CR I OF EX B

  公开号：WO2003082872A1

  公开（公告）日：2003-10-09

  The invention relates to 3-, 5-, 7-trisubstituted pyrazolo[4,3-d]pyrimidines represented by the general formula (I), and pharmaceutically acceptable salts thereof, wherein, R3 is an optionally substituted alkyl, cycloalkyl, cycloheteroalkyl, cycloalkyl alkyl, aryl or alkylaryl group; R5 is halogen, -NHNH2, -NHOH, NHCONH2, guanylo (NH-C(NH)NH2) an optionally substituted C1-C6 alkyl, alkenyl, alkinyl, C3-C15 cycloalkyl, Rf (C3-C15 cycloalkyl), heterocycle, heteroalkyl, aryl, heteroaryl, arylalkyl, cycloheteroalkyl, cycloheteroalkyl alkyl, heteroarylalkyl group, the group -C(O)-Ra, -C(O)NRbRc - SO3Rd, or -NHC(O)Re, wherein Ra and Rf are an optionally substituted C1-C6 alkyl, alkenyl, or alkinyl group, Rb, Rc and Rd are independently selected from the group consisting of H, optionally substituted C1-C6 alkyl, alkenyl, or alkinyl group, and Re is a hydroxy, amino, alkoxy, alkylamino, optionally substituted C1-C6 alkyl, alkenyl or alkinyl group; or the group -X-R5', wherein X is -NH-, -O-, -S- or -N(alkyl)- and R5' is hydrogen, an optionally substituted C1-C6 alkyl, alkenyl, alkinyl, C3-C15 cycloalkyl, Rf(C3-C15 cycloalkyl), aryl, heterocycle, hetero C1-C6 alkyl, arylalkyl, heteroaryl, cycloheteroalkyl, cycloheteroalkyl alkyl, or heteroarylalkyl group, the group -C(O)-Ra, -C(O)NRbRc, -SO3Rd, or -NHC(O)Re, wherein Ra, Rb, Rc, Rd, Re and Rf have the above meaning, and R7 is halogen, -NHNH2, NHOH, NHCONH2, guanylo (NH-C(NH)NH2) or the group -X-R7, wherein X has the above meaning and the meaning of R7, is as defined for R5'.
• Synthesis and biological activity of 8-azapurine and pyrazolo[4,3-d]pyrimidine analogues of myoseverin
  作者：Vladimír Kryštof、Daniela Moravcová、Martina Paprskářová、Pascale Barbier、Vincent Peyrot、Alice Hlobilková、Libor Havlíček、Miroslav Strnad

  DOI：10.1016/j.ejmech.2006.07.004

  日期：2006.12

  8-azapurine and pyrazolo[4,3-d]pyrimidine analogues of myoseverin and compared their biological activities. Rearrangement of nitrogen atoms in the heterocycle changes the affinity of the compounds to purified tubulin, as demonstrated by the results of polymerization assays, and affects the proliferation of cancer cell lines. Surprisingly, compound E2GG, a pyrazolo[4,3-d]pyrimidine analogue of myoseverin

  三取代嘌呤肌球蛋白最近已被鉴定为微管组装的新型抑制剂。为了分析修饰其杂环骨架的效果，我们制备了肌球蛋白的8-氮杂嘌呤和吡唑并[4,3-d]嘧啶类似物，并比较了它们的生物学活性。聚合测定的结果表明，杂环中氮原子的重排改变了化合物对纯化微管蛋白的亲和力，并影响了癌细胞系的增殖。令人惊讶的是，化合物E2GG，一种肌球蛋白的吡唑并[4,3-d]嘧啶类似物，显示出对微管蛋白聚合的抑制活性和细胞周期蛋白依赖性激酶1、2和7的活性。这种双重特异性抑制剂提供了一个起点。用于开发一类新型的抗增殖剂。