2-(methylthio)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-6-carbonitrile | 1537216-36-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: 2-(methylthio)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-6-carbonitrile
• 英文别名: 2-methylsulfanyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidine-6-carbonitrile；2-(Methylthio)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidine-6-carbonitrile；2-methylsulfanyl-7-oxo-8H-pyrido[2,3-d]pyrimidine-6-carbonitrile
• CAS: 1537216-36-6
• 化学式: C₉H₆N₄OS
• 分子量: 218.239
• InChiKey: YWHWECJZDGWDNJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.91
• 重原子数：
  15.0
• 可旋转键数：
  1.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  82.43
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  2-(methylthio)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-6-carbonitrile 在 sodium hydride 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 5.08h， 生成 2-benzylamino-8-cyclopentyl-7-oxo-7,8-dihydro-pyrido[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：

  2-甲基巯基-4-氨基嘧啶-5-甲酸乙酯 在 manganese(IV) oxide 、 lithium aluminium tetrahydride 、 溶剂黄146 、 苄胺 作用下， 以 四氢呋喃 、 氯仿 为溶剂， 反应 31.0h， 生成 2-(methylthio)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-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

文献信息

• 신규 피리도-피리미딘 유도체, 이의 제조방법 및 이를 유효성분으로 함유하는 단백질 키나아제 관련 질환의 예방 또는 치료용 약학적 조성물
  申请人：Daegu-Gyeongbuk Medical Innovation Foundation 재단법인 대구경북첨단의료산업진흥재단(120110319805) Corp. No ▼ 170122-0006899BRN ▼502-82-19772

  公开号：KR20200029946A

  公开（公告）日：2020-03-19

  본 발명은 신규 피리도-피리미딘 유도체, 이의 제조방법 및 이를 유효성분으로 함유하는 단백질 키나아제 관련 질환의 예방 또는 치료용 약학적 조성물에 관한 것으로, 본 발명에 따른 화학식 1로 표시되는 화합물, 이의 입체 이성질체, 또는 이의 약학적으로 허용 가능한 염은 JAK 키나아제(야누스 키나아제)에 대한 저해 활성이 우수할 뿐 아니라, 특히 JAK 3 키나아제에 대한 저해 활성이 우수한 바, 이를 유효성분으로 함유하는 JAK 키나아제(야누스 키나아제) 관련 질환, 특히 JAK 3 키나아제 관련 질환, 예를 들어, 복합 면역결핍(SCID), 류마티스 관절염, 골수섬유증, 건선, 크론병, 전신 홍반성 루프스, 다발성 경화증, 1형 당뇨병, 알레르기 질환, 만성 폐쇄성 폐 질환, 천식, 백혈병 또는 림프종의 예방 또는 치료용 약학적 조성물, 또는 예방 또는 개선용 건강기능성 식품 조성물이 제공될 수 있는, 유용한 효과가 있다.

  本发明涉及一种新型的吡咯烷-吡咯咪唑衍生物，其制备方法及包含该化合物的蛋白质激酶抑制剂，用于预防或治疗相关疾病。根据本发明的化学式1所示的化合物，其立体异构体或其药理学上可接受的盐对JAK激酶（雅努斯激酶）的抑制活性不仅优良，尤其是对JAK 3激酶的抑制活性更佳。包含该化合物的JAK激酶（雅努斯激酶）相关疾病，特别是JAK 3激酶相关疾病，例如，复合免疫缺陷(SCID)、类风湿性关节炎、骨髓纤维化、银屑病、克罗恩病、全身性红斑狼疮、多发性硬化症、1型糖尿病、过敏性疾病、慢性阻塞性肺病、哮喘、白血病或淋巴瘤的预防或治疗用药物组合物，或用于预防或改善的健康功能食品组合物，具有有益的效果。
• [EN] HETEROCYCLIC COMPOUNDS AS KINASE INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES EN TANT QU'INHIBITEURS DE KINASE
  申请人：NUVATION BIO INC

  公开号：WO2021003314A1

  公开（公告）日：2021-01-07

  Heterocyclic compounds as CDK4 or CDK6 or other CDK inhibitors are provided. The compounds may find use as therapeutic agents for the treatment of diseases and may find particular use in oncology.

  提供异环化合物作为CDK4或CDK6或其他CDK抑制剂。这些化合物可能作为治疗疾病的治疗剂，特别是在肿瘤学方面可能具有特殊用途。
• 2-SUBSTITUTED-8-ALKYL-7-OXO-7,8-DIHYDROPYRIDO[2,3-D]PYRIMIDINE-6-CARBONITRILES AND USES THEREOF
  申请人：Temple University - Of The Commonwealth System of Higher Education

  公开号：EP2600719B1

  公开（公告）日：2014-10-08
• Discovery of 8-Cyclopentyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido[2,3-<i>d</i>]pyrimidine-6-carbonitrile (<b>7x</b>) as a Potent Inhibitor of Cyclin-Dependent Kinase 4 (CDK4) and AMPK-Related Kinase 5 (ARK5)
  作者：M. V. Ramana Reddy、Balireddy Akula、Stephen C. Cosenza、Saikrishna Athuluridivakar、Muralidhar R. Mallireddigari、Venkat R. Pallela、Vinay K. Billa、D. R. C. Venkata Subbaiah、E. Vijaya Bharathi、Rodrigo Vasquez-Del Carpio、Amol Padgaonkar、Stacey J. Baker、E. Premkumar Reddy

  DOI：10.1021/jm401073p

  日期：2014.2.13

  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.