7-chloro-3-isopropyl-1(2)H-pyrazolo[4,3-d]pyridine | 611211-02-0

• 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: 7-chloro-3-isopropyl-1(2)H-pyrazolo[4,3-d]pyridine
• 英文别名: 7-chloro-3-isopropyl-1H-pyrazolo[4,3-d]pyrimidine；7-chloro-3-isopropylpyrazolo[4,3-d]pyrimidine；7-chloro-3-(propan-2-yl)-1H-pyrazolo[4,3-d]pyrimidine；7-chloro-3-propan-2-yl-2H-pyrazolo[4,3-d]pyrimidine
• CAS: 611211-02-0
• 化学式: C₈H₉ClN₄
• 分子量: 196.639
• InChiKey: WDAPYYNLDHXLTJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  54.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-chloro-3-isopropyl-1(2)H-pyrazolo[4,3-d]pyridine 、 3-甲基-2-丁烯-1-胺盐酸盐(1:1) 在 N,N-二异丙基乙胺 作用下， 以 甲醇 、 乙醇 、 氯仿 为溶剂， 反应 12.0h， 以48%的产率得到7-(isopent-2-en-(1-yl)amino)-3-isopropylpyrazolo[4,3-d]pyrimidine
  参考文献：
  名称：

  Pyrazolo[4,3-D]pyrimidines, process for their preparation and methods of use

  摘要：

  公开号：

  EP1475094B8
• 作为产物：
  描述：

  5-异丙基-4-硝基-1H-吡唑-3-羧酸 在 RaNi 盐酸 、 氯化亚砜 、 氢气 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 乙二醇乙醚 、 乙醇 、 氯仿 、 水 为溶剂， 60.0~90.0 ℃ 、101.33 kPa 条件下， 反应 24.0h， 生成 7-chloro-3-isopropyl-1(2)H-pyrazolo[4,3-d]pyridine
  参考文献：
  名称：

  吡唑并[4,3-d]嘧啶为新一代细胞周期蛋白依赖性激酶抑制剂。

  摘要：

  在抗CDK嘌呤类似物中进行的研究导致鉴定出取代的吡唑并[4,3-d]嘧啶为CDK1 / cyclin B的新型抑制剂。这些衍生物中的某些还对癌细胞系K-562具有抗增殖活性。可能会找到抗癌药的应用。

  DOI：

  10.1016/s0960-894x(03)00631-0

文献信息

• [EN] 5-SUBSTITUTED 7-[4-(2-PYRIDYL)PHENYLMETHYLAMINO]-3-ISOPROPYLPYRAZOLO4,3-D]PYRIMIDINE DERIVATIVES, USE THEREOF AS MEDICAMENTS, AND PHARMACEUTICAL COMPOSITIONS<br/>[FR] DÉRIVÉS DE 7-[4-(2-PYRIDYL)PHÉNYLMÉTHYLAMINO]-3-ISOPROPYLPYRAZOLO-4,3-D]PYRIMIDINE 5-SUBSTITUÉS, LEUR UTILISATION À TITRE DE MÉDICAMENTS, ET COMPOSITIONS PHARMACEUTIQUES
  申请人：USTAV EXPERIMENTALNI BOTANIKY AV CR V V I

  公开号：WO2016180380A1

  公开（公告）日：2016-11-17

  The present invention relates to novel 5-substituted-7-[4-(2-pyridyl) phenylmethylamino]-3-isopropylpyrazolo[4,3-d]pyrimidines of formula I which are potent inhibitors of protein kinases, especially cyclin- dependerit kinases such as CDK2 and CDK5, and display antileukemic, pro-apoptotic, antiangiogenic and anticancer activities. The invention also relates to processes for their preparation, to pharmaceutical compositions comprising them and to their use as medicaments, particularly in the treatment of disorders involving cell proliferation, apoptosis, angiogenesis and inflammation, such as leukemia and metastatic solid cancer.

  本发明涉及一种新型的5-取代-7-[4-(2-吡啶基)苯甲基氨基]-3-异丙基吡唑[4,3-d]嘧啶的化合物，其化学式为I，该化合物是蛋白激酶的有效抑制剂，特别是细胞周期依赖性激酶如CDK2和CDK5，并具有抗白血病、促凋亡、抗血管生成和抗癌活性。本发明还涉及它们的制备方法、包含它们的药物组合物以及它们作为药物的用途，特别是在治疗涉及细胞增殖、凋亡、血管生成和炎症的疾病，如白血病和转移性实体癌。
• 5-Substituted 3-isopropyl-7-[4-(2-pyridyl)benzyl]amino-1(2)H-pyrazolo[4,3-d]pyrimidines with anti-proliferative activity as potent and selective inhibitors of cyclin-dependent kinases
  作者：Ladislava Vymětalová、Libor Havlíček、Antonín Šturc、Zuzana Skrášková、Radek Jorda、Tomáš Pospíšil、Miroslav Strnad、Vladimír Kryštof

  DOI：10.1016/j.ejmech.2016.01.011

  日期：2016.3

  kinase (FAK), well-established substrates of CDKs, has been found in treated cells. Cleavage of PARP-1, down-regulation of Mcl-1 and activation of caspases correlated well with CDK inhibition and confirmed apoptosis as the primary type of cell death induced in cancer cells treated with the compounds in vitro. A comparison of known purine-based CDK inhibitor CR8 with its pyrazolo[4,3-d]pyrimidine bioisosteres

  合成了一系列5-取代的3-异丙基-7- [4-（2-吡啶基）苄基]氨基-1（2）H-吡唑并[4,3- d ]嘧啶衍生物，并评估了它们的细胞周期蛋白依赖性激酶（CDK）抑制活性。最有效的化合物在5位上含有各种羟烷基胺，并具有低纳摩尔IC 50CDK2和CDK5的值。对50种蛋白激酶中活性最高的化合物之一的初步分析表明，它对CDK具有很高的选择性。这些化合物将细胞停在S和G2 / M期，并诱导了各种癌细胞系的凋亡。已经在处理过的细胞中发现了RNA聚合酶II和粘着斑激酶（FAK）的显着去磷酸化作用，这是CDKs公认的底物。PARP-1的切割，Mcl-1的下调和胱天蛋白酶的激活与CDK抑制密切相关，并证实凋亡是在体外用该化合物处理的癌细胞中诱导的主要细胞死亡类型。已知基于嘌呤的CDK抑制剂CR8与吡唑并[4,3- d]嘧啶生物等排体证实，新化合物在细胞分析中比嘌呤更有效。因此，吡唑并[4，3- d
• "Pyrazolo [4,3-d]pyrimidines, processes for their preparation and methods of use"
  申请人：Moravcova Daniela

  公开号：US20070167466A1

  公开（公告）日：2007-07-19

  The invention relates to 3-,7-disubstituted pyrazolo[4,3-d]pyrimidines represented by the general formula I (I), and pharmaceutically acceptable salts thereof, wherein R3 is selected from the group consisting of alkyl, cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl alkyl, cycloheteroalkyl, aryl, heterocycle, heteroaryl, arylalkyl, heteroarylalkyl, and heteroalkyl, wherein each of the groups may optionally be substituted, R7 is selected from the group consisting of halogen, hydroxyl, hydroxylamino, amino, carboxyl, cyano, nitro, amido, sulfo, sulfamido, carbamino, unsubstituted or substituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted cycloalkyl alkyl, substituted or unsubstituted cycloheteroalkyl alkyl; R7′-X— wherein X is an —NH—, —N(alkyl)-, -0- or —S— moiety and R7′ is selected from the group consisting of H, alkyl, cycloalkyl, aryl, alkylcycloalkyl, arylalkyl, heterocycle, heterocyclealkyl, substituted alkyl, substituted cycloalkyl, substituted aryl, substituted arylalkyl, substituted heterocycle, substituted heteroaryl, substituted heteroarylalkyl, substituted heteroalkyl, substituted cycloalkyl alkyl and substituted cycloheteroalkyl alkyl, wherein the groups are preferably substituted by more than one halogen, hydroxyl, amino, mercapto, carboxyl, cyano, nitro, amido, sulfo, sulfamido, carbamino, alkyl, alkoxy, and substituted alkyl group.

  本发明涉及由通式I (I) 表示的3-, 7-二取代吡唑并[4,3-d]嘧啶化合物，以及其药学上可接受的盐。其中，R3选自烷基、环烷基、环烷基烷基、环杂烷基烷基、环杂烷基、芳基、杂环、杂芳基、芳基烷基、杂芳基烷基和杂基，其中每个基团可以选择性地被取代；R7选自卤素、羟基、羟胺基、氨基、羧基、氰基、硝基、酰胺基、磺酰基、磺酰胺基、氨基甲酰基、未取代或取代烷基、取代或未取代环烷基、取代或未取代芳基烷基、取代或未取代杂基、取代或未取代杂芳基烷基、取代或未取代环烷基烷基、取代或未取代环杂烷基烷基；R7'-X-其中X是- NH-，-N（烷基）-，-O-或-S-基团，R7'选自氢、烷基、环烷基、芳基、烷基环烷基、芳基烷基、杂环、杂环烷基、取代烷基、取代环烷基、取代芳基、取代芳基烷基、取代杂环、取代杂芳基、取代杂芳基烷基、取代杂基、取代环烷基烷基和取代环杂烷基烷基，其中这些基团最好被多个卤素、羟基、氨基、巯基、羧基、氰基、硝基、酰胺基、磺酰基、磺酰胺基、氨基甲酰基、烷基、烷氧基和取代烷基基团取代。
• 5-SUBSTITUTED 7-[4-(2-PYRIDYL)PHENYLMETHYLAMINO]-3-ISO PROPYLPYRAZOLO[4,3-D]PYRIMIDINE DERIVATIVES, USE THEREOF AS MEDICAMENTS AND PHARMACEUTICAL COMPOSITIONS
  申请人：Ustav Experimentalni Botaniky Av CR, V.V.I.

  公开号：EP3294741B1

  公开（公告）日：2019-05-01
• 5-SUBSTITUTED 7-[4-(2-PYRIDYL)PHENYLMETHYLAMINO]-3-ISOPROPYLPYRAZOLO4,3-D]PYRIMIDINE DERIVATIVES, USE THEREOF AS MEDICAMENTS, AND PHARMACEUTICAL COMPOSITIONS
  申请人：USTAV EXPERIMENTALNI BOTANIKY AV CR, V.V.I.

  公开号：US20180072736A1

  公开（公告）日：2018-03-15

  5-substituted-7-[4-(2-pyridyl)phenylmethylamino]-3-isopropylpyrazolo[4,3-d]pyrimidines are potent inhibitors of protein kinases, especially cyclin-dependent kinases such as CDK2 and CDK5, and display antileukemic, pro-apoptotic, antiangiogenic and anticancer activities. The invention also relates to processes for their preparation, to pharmaceutical compositions and to their use as medicaments, particularly in the treatment of disorders involving cell proliferation, apoptosis, angiogenesis and inflammation, such as leukemia and metastatic solid cancer.