4-propylamino-2-(methylsulfanyl)pyrimidine-5-carboxylic acid ethyl ester | 774133-54-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4-propylamino-2-(methylsulfanyl)pyrimidine-5-carboxylic acid ethyl ester
• 英文别名: 2-methylsulfanyl-4-propylamino-pyrimidine-5-carboxylic acid ethyl ester；2-(methylthio)-4-(propylamino)pyrimidine-5-carboxylic acid ethyl ester；2-methylthio-4-propylamino-5-pyrimidine carboxylic acid ethyl ester；ethyl 2-methylthio-4-n-propylaminopyrimidine-5-carboxylate；ethyl 2-methylsulfanyl-4-(propylamino)pyrimidine-5-carboxylate
• CAS: 774133-54-9
• 化学式: C₁₁H₁₇N₃O₂S
• 分子量: 255.341
• InChiKey: TUEPAOXQYKBBBN-UHFFFAOYSA-N

物化性质

• 沸点：
  393.1±22.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  89.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-propylamino-2-(methylsulfanyl)pyrimidine-5-carboxylic acid ethyl ester 在 manganese(IV) oxide 、 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 氯仿 为溶剂， 反应 25.0h， 生成 2-methylsulfanyl-4-propylmino-pyrimidine-5-carbaldehyde
  参考文献：
  名称：

  Discovery of 8-Cyclopentyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-carbonitrile (7x) as a Potent Inhibitor of Cyclin-Dependent Kinase 4 (CDK4) and AMPK-Related Kinase 5 (ARK5)

  摘要：

  The success of imatinib, a BCR-ABL inhibitor for the treatment of chronic myelogenous leukemia, has created a great impetus for the development of additional kinase inhibitors as therapeutic agents. However, the complexity of cancer has led to recent interest in polypharmacological approaches for developing multikinase inhibitors with low toxicity profiles. With this goal in mind, we analyzed more than 150 novel cyano pyridopyrimidine compounds and identified structure-activity relationship trends that can be exploited in the design of potent kinase inhibitors. One compound, 8-cyclopentyl-2[-4-(4-methyl-piperazin-l-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-carbonitrile (7x), was found to be the most active, inducing apoptosis of tumor cells at a concentration of approximately 30-100 nM. In vitro kinase profiling revealed that 7x is a multikinase inhibitor with potent inhibitory activity against the CDK4/CYCLIN D1 and ARKS kinases. Here, we report the synthesis, structure-activity relationship, kinase inhibitory profile, in vitro cytotoxicity, and in vivo tumor regression studies by this lead compound.

  DOI：

  10.1021/jm401073p
• 作为产物：
  描述：

  正丙胺 、 4-氯-2-甲硫基嘧啶-5-羧酸乙酯 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 4-propylamino-2-(methylsulfanyl)pyrimidine-5-carboxylic acid ethyl ester
  参考文献：
  名称：

  新型和口服活性5-（1,3,4-恶二唑-2-基）嘧啶衍生物作为选择性FLT3抑制剂。

  摘要：

  5-（1,3,4-Oxadiazol-2-yl）嘧啶衍生物1从我们的化合物库中被鉴定为一类新的FLT3抑制剂。为了增强通过对1进行少量修饰而制备的2的抗肿瘤活性，进行了对嘧啶环2的2-，4-和5-位侧链的结构优化，以改善代谢稳定性。在1,3,4-恶二唑基上引入极性取代基有助于代谢稳定性的显着提高。结果，通过口服给药，一系列化合物在小鼠中显示出针对MOLM-13异种移植模型的增强的功效。

  DOI：

  10.1016/j.bmcl.2008.09.031

文献信息

• [EN] PYRIMIDINE COMPOUNDS AS KINASE INHIBITORS<br/>[FR] COMPOSÉS PYRIMIDINES EN TANT QU'INHIBITEURS DE KINASE
  申请人：ICAHN SCHOOL MED MOUNT SINAI

  公开号：WO2014151682A1

  公开（公告）日：2014-09-25

  This disclosure relates to compounds, methods for their preparation, pharmaceutical compositions including these compounds and methods for the treatment of cellular proliferative disorders, including, but not limited to, cancer.

  这份披露涉及化合物、它们的制备方法、包括这些化合物的药物组合物以及治疗细胞增殖障碍的方法，包括但不限于癌症。
• NITROGEN-CONTAINING HETEROCYCLIC COMPOUND OR SALT THEREOF
  申请人：FUJIFILM Corporation

  公开号：US20150045339A1

  公开（公告）日：2015-02-12

  The object is to provide an Fms-like tyrosine kinase 3 (FLT3) inhibitor useful as a therapeutic agent for acute myeloid leukemia (AML). A novel nitrogen-containing heterocyclic compound represented by the general formula [1] or a salt thereof is provided. The compound or a salt thereof of the present invention can be used as an active ingredient of a pharmaceutical composition for a treatment of a disease or condition relating to FLT3, such as acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL).

  该目的是提供一种类似于Fms酪氨酸激酶3（FLT3）的抑制剂，可用作急性髓系白血病（AML）的治疗药物。提供了一种由通式[1]表示的新型含氮杂环化合物或其盐。本发明的该化合物或其盐可用作与FLT3相关的疾病或病况的药物组合物的活性成分，如急性髓系白血病（AML）和急性早幼粒细胞白血病（APL）的治疗。
• 7,8-Dihydro-2,5,8-
  申请人：American Home Products Corporation

  公开号：US04215216A1

  公开（公告）日：1980-07-29

  7,8-Dihydro-2,5,8-trisubstituted-7-oxo-pyrido[2,3-d]pyrimidine-6-carboxylic acid derivatives are gastric anti-secretory agents for treatment of peptic ulcer disease and generally anti-allergic agents useful in the treatment of atopic immediate hypersensitivity reactions.

  7,8-二氢-2,5,8-三取代-7-氧代吡啶[2,3-d]嘧啶-6-羧酸衍生物是治疗消化性溃疡疾病的胃抗分泌剂，通常也是抗过敏剂，可用于治疗特应性即时型超敏反应。
• 5-Chloro-7,8-dihydro-7-oxo-pyrido[2,3-d]pyrimidine-6-carboxylic acid
  申请人：American Home Products Corporation

  公开号：US04233446A1

  公开（公告）日：1980-11-11

  7-Chloro-7,8-dihydro-7-oxo-pyrido[2,3]-d]pyrimidine-6-carboxylic acid derivatives are intermediates useful for the production of 7,8-dihydro-2,5,8-trisubstituted-7-oxo-pyrido[2,3-d]-pyrimidine-6-carboxyl ic acid derivatives which in turn are gastric anti-secretory agents for treatment of peptic ulcer disease and generally anti-allergic agents useful in the treatment of atopic immediate hypersensitivity reactions.

  7-氯-7,8-二氢-7-氧基-吡啶[2,3-d]嘧啶-6-羧酸衍生物是用于生产7,8-二氢-2,5,8-三取代-7-氧基-吡啶[2,3-d]嘧啶-6-羧酸衍生物的中间体，而这些衍生物则是治疗消化性溃疡疾病的胃抗分泌药物，通常也是治疗过敏反应的抗过敏药物，对于特应性即时过敏反应尤其有用。
• 2
  申请人：American Home Products Corporation

  公开号：US04236004A1

  公开（公告）日：1980-11-25

  2-Alkylsulfonyl-7,8-dihydro-5-hydroxy-7-oxo-pyrido[2,3-d]pyrimidine-6-carbo xylic acid derivatives are intermediates useful in the production of 7,8-dihydro-2-amino or alkoxy-7-oxo-pyrido[2,3-d]pyrimidine-6-carboxylic acid derivatives which are gastric anti-secretory agents for treatment of peptic ulcer disease and generally anti-allergic agents useful in the treatment of atopic immediate hypersensitivity reactions.

  2-烷基磺酰基-7,8-二氢-5-羟基-7-氧代-吡啶[2,3-d]嘧啶-6-羧酸衍生物是中间体，用于生产7,8-二氢-2-氨基或烷氧基-7-氧代-吡啶[2,3-d]嘧啶-6-羧酸衍生物，这些衍生物是治疗消化性溃疡疾病的胃抑酸剂，通常是治疗变态反应性疾病的抗过敏剂，有助于治疗过敏性疾病的即刻型超敏反应。