2-methylsulfanyl-4-propylmino-pyrimidine-5-carbaldehyde | 1537216-26-4

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2-methylsulfanyl-4-propylmino-pyrimidine-5-carbaldehyde
• 英文别名: 4-propylamino-2-(methylsulfanyl)pyrimidine-5-carboxaldehyde；2-Methylsulfanyl-4-(propylamino)pyrimidine-5-carbaldehyde
• CAS: 1537216-26-4
• 化学式: C₉H₁₃N₃OS
• 分子量: 211.288
• InChiKey: QUCQUHGGDNCHOC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  80.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-methylsulfanyl-4-propylmino-pyrimidine-5-carbaldehyde 在 溶剂黄146 、 间氯过氧苯甲酸 、 苄胺 作用下， 以 二氯甲烷 为溶剂， 反应 10.0h， 生成 2-methylsulfinyl-7-oxo-8-propyl-7,8-dihydropyrido[2,3-d]pyrimidine-6-carbonitrile
  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：

  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

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。
• PYRIMIDINE COMPOUNDS AS KINASE INHIBITORS
  申请人：ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

  公开号：US20160122361A1

  公开（公告）日：2016-05-05

  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.

  本公开涉及化合物、其制备方法、包括这些化合物的制药组合物以及治疗细胞增殖性疾病的方法，包括但不限于癌症。
• [EN] COVALENT CDK2-BINDING COMPOUNDS FOR THERAPEUTIC PURPOSES<br/>[FR] COMPOSÉS DE LIAISON À CDK2 COVALENTS UTILISÉS À DES FINS THÉRAPEUTIQUES
  申请人：UMBRA THERAPEUTICS INC

  公开号：WO2022187693A1

  公开（公告）日：2022-09-09

  Heteroaryl sulfonyl compounds and compositions that have a CDK2 Recognition Moiety bound to an electrophile for the selective covalent modification of CDK2 to treat CDK2-mediated disorders are described.

  本文描述了具有CDK2识别基团结合到亲电体的杂环磺酰化合物和组合物，用于选择性共价修饰CDK2以治疗CDK2介导的疾病。
• PYRIMIDINE COMPOUNDS FOR USE IN THE TREATMENT OF CANCER
  申请人：Icahn School of Medicine at Mount Sinai

  公开号：EP3733184A1

  公开（公告）日：2020-11-04

  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.

  本公开涉及化合物、其制备方法、包括这些化合物的药物组合物以及治疗细胞增殖性疾病（包括但不限于癌症）的方法。
• US9815847B2
  申请人：——

  公开号：US9815847B2

  公开（公告）日：2017-11-14