1-(4-chloro-2-(methylthio)pyrimidin-5-yl)ethanone | 66116-82-3

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 1-(4-chloro-2-(methylthio)pyrimidin-5-yl)ethanone
• 英文别名: 1-(4-chloro-2-(methylthio)pyrimidin-5-yl)ethan-1-one；1-(4-Chloro-2-(methylthio)pyrimidin-5-yl)ethanone；1-(4-chloro-2-methylsulfanylpyrimidin-5-yl)ethanone
• CAS: 66116-82-3
• 化学式: C₇H₇ClN₂OS
• 分子量: 202.664
• InChiKey: QHVLBWJEWVZLQX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  68.2
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302

反应信息

• 作为反应物：
  描述：

  1-(4-chloro-2-(methylthio)pyrimidin-5-yl)ethanone 在 氨 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 13.0h， 生成 1-(2-amino-4-chloropyrimidin-5-yl)ethan-1-one
  参考文献：
  名称：

  高效，高选择性PI3Kγ-PI3Kδ双重抑制剂的发现，优化和评估。

  摘要：

  开发了电子密度模型，并用于鉴定喹唑啉酮的新型吡咯烷酮替代物，喹唑啉酮是赋予PI3Kγ和PI3Kδ抑制剂选择性的常用部分。在分子对接的指导下，使用新的环状部分将这一新的特异性片段连接至抑制剂的铰链结合区。围绕铰链区域的进一步的结构-活性关系优化导致了候选化合物26的发现，该候选药物是一种在临床前物种中具有良好药物代谢和药代动力学特性的高效PI3Kγ-PI3Kδ双重抑制剂。

  DOI：

  10.1021/acs.jmedchem.8b02014
• 作为产物：
  描述：

  5-acetyl-2-(methylthio)pyrimidin-4(3H)-one 在 三氯氧磷 作用下， 反应 2.0h， 以72%的产率得到1-(4-chloro-2-(methylthio)pyrimidin-5-yl)ethanone
  参考文献：
  名称：

  Reaction of ethyl 3,3-diaminoacrylate with pyrimidine series o-chloro ketones. Synthesis of pyrido[4,3-d]pyrimidines and 6H-1,3,6,7-tetra-azaphenalenes

  摘要：

  Cyclocondensation of ethyl 3,3-diaminoacrylate with 5-acetyl-4-chloropyrimidines gave ortho- and peri-condensed heterocycles formed through substitution of the chlorine atom by the alpha-carbon atom of the enediamine and condensation of the amino group with the carbonyl or by addition of the amino group to the pyridine ring.

  DOI：

  10.1007/s10593-013-1269-2

文献信息

• [EN] ANTI-PROLIFERATIVE AGENTS FOR TREATING PAH<br/>[FR] AGENTS ANTIPROLIFÉRATIFS POUR LE TRAITEMENT DE L'HTAP
  申请人：PFIZER

  公开号：WO2020212865A1

  公开（公告）日：2020-10-22

  This invention relates to compounds of general Formula I in which A, R1, R2, R3 and R4 are as defined herein, and the pharmaceutically acceptable salts thereof; to pharmaceutical compositions comprising such compounds and salts; to methods of using such compounds, salts and compositions for treating pulmonary hypertension and related diseases, like pulmonary arterial hypertension; to methods of using such compounds, salts and compositions for treating abnormal cell growth, such as cancer; and to processes to make such compounds, salts and compositions.

  这项发明涉及一般式I中的化合物，其中A、R1、R2、R3和R4如本文所定义，以及其药用可接受的盐；涉及包含这种化合物和盐的药物组合物；涉及使用这种化合物、盐和组合物治疗肺动脉高压和相关疾病，如肺动脉高压；涉及使用这种化合物、盐和组合物治疗异常细胞生长，如癌症；以及制备这种化合物、盐和组合物的方法。
• C5-substituted pyrido[2,3-d]pyrimidin-7-ones as highly specific kinase inhibitors targeting the clinical resistance-related EGFR^T790M mutant
  作者：Tianfeng Xu、Ting Peng、Xiaomei Ren、Lianwen Zhang、Lei Yu、Jinfeng Luo、Zhang Zhang、Zhengchao Tu、Linjiang Tong、Zhaoru Huang、Xiaoyun Lu、Meiyu Geng、Hua Xie、Jian Ding、Ke Ding

  DOI：10.1039/c5md00208g

  日期：——

  C5-substituted pyrido[2,3-d]pyrimidin-7-ones were discovered as highly potent and specific inhibitors targeting the clinical resistance-related EGFR^L858R/T790M mutant.

  C5-取代的吡啶并[2,3-d]嘧啶-7-酮被发现为高效且特异的抑制剂，针对临床耐药相关的EGFR L858R/T790M突变体。
• NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS
  申请人：Merck Sharp & Dohme Corp.

  公开号：US20160145255A1

  公开（公告）日：2016-05-26

  Compounds of Formula I: are HIV reverse transcriptase inhibitors, wherein R 1 , R 2 , R E , L, M and Z are defined herein. The compounds of Formula I and their pharmaceutically acceptable salts are useful in the inhibition of HIV reverse transcriptase, the prophylaxis and treatment of infection by HIV and in the prophylaxis, delay in the onset or progression, and treatment of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.

  公式I的化合物：是HIV逆转录酶抑制剂，其中R1、R2、RE、L、M和Z在此定义。公式I的化合物及其药学上可接受的盐对于抑制HIV逆转录酶、预防和治疗HIV感染以及预防、延迟发病或进展和治疗AIDS非常有用。这些化合物及其盐可作为药物组成部分，可选地与其他抗病毒药物、免疫调节剂、抗生素或疫苗组合使用。
• Tricyclic lactams for use in HSPC-sparing treatments for Rb-positive abnormal cellular proliferation
  申请人：G1 Therapeutics, Inc.

  公开号：US10376519B2

  公开（公告）日：2019-08-13

  This invention is in the area of tricyclic lactam compounds for and methods of treating selected Rb-positive cancers and other Rb-positive abnormal cellular proliferative disorders while minimizing the deleterious effects on healthy cells, for example healthy Hematopoietic Stem Cells and Progenitor Cells (HSPCs), associated with current treatment modalities. In one aspect, treatment of select Rb-positive cancers is disclosed using specific compounds disclosed herein. In certain embodiments, the compounds described herein act as selective cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors when administered to subjects.

  本发明属于三环内酰胺化合物领域，用于治疗特定的 Rb 阳性癌症和其它 Rb 阳性异常细胞增殖性疾病，同时最大限度地减少当前治疗方法对健康细胞（例如健康的造血干细胞和祖细胞（HSPC））的有害影响。在一个方面，公开了使用本文公开的特定化合物治疗选择性 Rb 阳性癌症的方法。在某些实施方案中，本文所述化合物在给受试者用药时可作为选择性细胞周期蛋白依赖性激酶4/6（CDK 4/6）抑制剂。
• Chiral heterocyclic compound with hedgehog pathway antagonist activity, method and use thereof
  申请人：SUZHOU KINTOR PHARMACEUTICALS, INC.

  公开号：US10919889B2

  公开（公告）日：2021-02-16

  A chiral heterocyclic compound with hedgehog pathway antagonist activity, method and use thereof are provided. The chiral heterocyclic compound with hedgehog pathway antagonist activity has the structure represented by formula I. A pharmaceutical composition and combined application composition are also provided. Novel molecules of formula II that inhibit hedgehog pathway signaling and therapeutic applications for the treatment of malignancies, prevention of tumor regrowth, sensitization of radio-chemo therapies, and other diseases related to hedgehog signaling are also provided.

  本发明提供了一种具有刺猬蛋白通路拮抗剂活性的手性杂环化合物及其方法和用途。具有刺猬通路拮抗剂活性的手性杂环化合物具有式 I 所代表的结构。还提供了一种药物组合物和组合应用组合物。还提供了抑制刺猬蛋白通路信号转导的式 II 新型分子，以及用于治疗恶性肿瘤、防止肿瘤再生、放射化疗增敏和其他与刺猬蛋白信号转导相关疾病的治疗应用。