1-(5-methyl-1-pyrimidin-2-yl-1H-pyrazol-4-yl)-ethanone | 33453-25-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(5-methyl-1-pyrimidin-2-yl-1H-pyrazol-4-yl)-ethanone
• 英文别名: 1-(2-pyrimidinyl)-4-acetyl-5-methylpyrazole；1-(5-methyl-1-pyrimidin-2-ylpyrazol-4-yl)ethanone
• CAS: 33453-25-7
• 化学式: C₁₀H₁₀N₄O
• 分子量: 202.216
• InChiKey: UMOPUYQHCRDESJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  60.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(5-methyl-1-pyrimidin-2-yl-1H-pyrazol-4-yl)-ethanone 在 sodium hydride 、 碳酸二乙酯 作用下， 以 甲苯 为溶剂， 反应 3.0h， 以78%的产率得到1-(3-Methyl-1-pyrimidin-2-yl-1H-pyrazol-4-yl)-ethanone
  参考文献：
  名称：

  Synthesis and Antitumor Activity of Novel Pyrimidinyl Pyrazole Derivatives. III. Synthesis and Antitumor Activity of 3-Phenylpiperazinyl-1-trans-propenes

  摘要：

  一系列新型的3-[4-苯基-1-哌嗪基]-1-[5-甲基-1-(2-嘧啶基)-4-吡唑基]-1-反式丙烯及其相关化合物被合成，并通过其对几种肿瘤细胞系的体外细胞毒性活性和对某些肿瘤模型的体内抗肿瘤活性进行了评估，这些化合物既可以通过腹腔注射给药，也可以口服给药。具有3-氯吡啶-2-基团（9g）和3-氟-5-取代苯基哌嗪基团（29b、c和e）的化合物在体外测试中显示出显著的细胞毒性。其中，3-氰基-5-氟苯基衍生物（29b）表现出对包括人癌在内的几种肿瘤细胞的强效抗肿瘤活性，且在老鼠中没有引起不良反应。

  DOI：

  10.1248/cpb.53.153
• 作为产物：
  描述：

  2-肼基嘧啶 、 3-乙氧亚甲基-2,4-戊二酮 以 乙醇 为溶剂， 反应 1.0h， 生成 1-(5-methyl-1-pyrimidin-2-yl-1H-pyrazol-4-yl)-ethanone
  参考文献：
  名称：

  Synthesis and mechanism of action of novel pyrimidinyl pyrazole derivatives possessing antiproliferative activity

  摘要：

  Pyrimidinyl pyrazole derivatives 1-4, prepared as a new scaffold of an anti-tumor agent, showed antiproliferative activity against human lung cancer cell lines and inhibited tubulin polymerization. Furthermore, it was found that compound 2 bound at the colchicine site on tubulin, but the tubulin binding pattern was different from that of colchicine. Here, we describe the synthesis of the derivatives and the differences of the action mechanism on tubulin polymerization inhibition between compound 2 and colchicine. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00568-1

文献信息

• Synthesis and Antitumor Activity of Novel Pyrimidinyl Pyrazole Derivatives. II. Optimization of the Phenylpiperazine Moiety of 1-[5-Methyl-1-(2-pyrimidinyl)-4-pyrazolyl]-3-phenylpiperazinyl-1-trans-propenes.
  作者：Hiroyuki Naito、Satoru Ohsuki、Masamichi Sugimori、Ryo Atsumi、Megumi Minami、Yoshihide Nakamura、Mineko Ishii、Kenji Hirotani、Eiji Kumazawa、Akio Ejima

  DOI：10.1248/cpb.50.453

  日期：——

  A series of novel 3-substituted-1-[5-methyl-1-(2-pyrimidinyl)-4-pyrazolyl]-1-trans-propenes in order to improve the in vitro and in vivo activity of our prototype 3-[4-(3-chlorophenyl)-1-piperazinyl]-1-[5-methyl-1-(2-pyrimidinyl)-4-pyrazolyl]-1-trans-propene (2) were synthesized and evaluated by assays of growth inhibition against several tumor cell lines in vitro and antitumor activity against some tumor models when dosed both intraperitoneally and orally in vivo. Compounds 7a and 7e, the 3,5-difluorophenyl and 3,5-dichlorophenyl analogues of 2, respectively, showed significantly more potent cytotoxicity than 2 in vitro and potent antitumor activities without causing decrease of body temperature related to side effects.

  为提高原型化合物3-[4-(3-氯苯基)-1-哌嗪基]-1-[5-甲基-1-(2-嘧啶基)-4-吡唑基]-1-反式-丙烯（2）的体外和体内活性，合成了一系列新型的3-取代-1-[5-甲基-1-(2-嘧啶基)-4-吡唑基]-1-反式-丙烯，并通过体外对几种肿瘤细胞系的生长抑制试验和体内对某些肿瘤模型的抗肿瘤活性试验（经腹腔和口服给药）进行了评估。化合物7a和7e，分别是2的3,5-二氟苯基和3,5-二氯苯基类似物，其体外细胞毒性显著强于2，并有较强的抗肿瘤活性，且不会因副作用导致体温下降。
• Pyrimidinylpyrazole derivatives
  申请人：Daiichi Pharmaceutical Co., Ltd.

  公开号：US05852019A1

  公开（公告）日：1998-12-22

  The present invention provides a novel compound which is represented by formula (I): ##STR1## wherein preferable examples of R.sup.1 to R.sup.6 are as follows; R.sup.1 and R.sup.2 are each an alkyl group optionally substituted by a halogen atom, an amino group, a hydroxyl group, an alkoxyl group or a thiol group, a hydrogen atom, a halogen atom or an alkoxyl group; R.sup.3 is a hydrogen atom; R.sup.4 is a methyl group; R.sup.5 is a hydrogen atom or an alkyl group; and R.sup.6 is a group of the formula: ##STR2## wherein Z is a phenyl group; and has an antitumor effect.

  本发明提供了一种新型化合物，其由式(I)表示：##STR1##其中R.sup.1至R.sup.6的优选示例如下；R.sup.1和R.sup.2分别是可选择地由卤原子、氨基、羟基、烷氧基或硫醇基取代的烷基基团，氢原子，卤原子或烷氧基；R.sup.3是氢原子；R.sup.4是甲基基团；R.sup.5是氢原子或烷基基团；R.sup.6是下式的基团：##STR2##其中Z是苯基；并具有抗肿瘤作用。
• Synthesis and Antitumor Activity of Novel Pyrimidinyl Pyrazole Derivatives.
  作者：Hiroyuki NAITO、Masamichi SUGIMORI、Ikuo MITSUI、Yoshihide NAKAMURA、Michio IWAHANA、Mineko ISHII、Kenji HIROTANI、Eiji KUMAZAWA、Akio EJIMA

  DOI：10.1248/cpb.47.1679

  日期：——

  Novel pyrimidinyl pyrazole derivatives were synthesized and examined for cytotoxic and antitumor activity. Mannich reaction was employed to construct this scaffold. Among the compounds synthesized, a series of propene derivatives exhibited a potent cytotoxic activity against some tumor cell lines including multidrug resistant cell lines due to the overexpression of P-glycoprotein. The vinyl bond moiety in the scaffold was believed to be required for the cytotoxic activity. Among them, compound 14g, when administered intraperitoneally, showed potent antitumor activity against the malignant ascites caused by intraperitoneal inoculation of P388 cells in mice. This compound also showed high activity against a solid tumor Meth A mouse fibrosarcoma when administered both intraperitoneally and orally.

  新型的嘧啶基吡唑衍生物被合成并检测了其细胞毒性和抗肿瘤活性。通过Mannich反应构建了这一骨架。在合成的化合物中，一系列丙烯衍生物对某些肿瘤细胞系（包括由于P-糖蛋白过度表达而产生多药耐药性的细胞系）表现出强大的细胞毒活性。骨架中的乙烯键部分被认为是产生细胞毒活性的必要条件。其中，化合物14g通过腹腔给药，对小鼠因腹腔接种P388细胞引起的恶性腹水显示出强大的抗肿瘤活性。此化合物无论是腹腔注射还是口服，对Meth A小鼠纤维肉瘤这一实体瘤也显示出高活性。
• PYRIMIDINYLPYRAZOLE DERIVATIVE
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP0784055A1

  公开（公告）日：1997-07-16

  The present invention provides a novel compound which is represented by formula (I): wherein preferable examples of R1 to R6 are as follows; R1 and R2 are each an alkyl group optionally substituted by a halogen atom, an amino group, a hydroxyl group, an alkoxyl group or a thiol group, a hydrogen atom, a halogen atom or an alkoxyl group; R3 is a hydrogen atom; R4 is a methyl group; R5 is a hydrogen atom or an alkyl group; and R6 is a group of the formula: wherein Z is a phenyl group; and has an antitumor effect.

  本发明提供了一种由式（I）表示的新型化合物： 其中 R1 至 R6 的优选实例如下；R1 和 R2 各为可选被卤原子、氨基、羟基、烷氧基或硫醇基、氢原子、卤原子或烷氧基取代的烷基；R3 为氢原子；R4 为甲基；R5 为氢原子或烷基；R6 为式中的基团： 其中 Z 是苯基； 并具有抗肿瘤作用。
• US5852019A
  申请人：——

  公开号：US5852019A

  公开（公告）日：1998-12-22