2-methylsulfanyl-4-(tetrahydro-2H-pyran-4-ylamino)pyrimidine-5-carbaldehyde | 933795-01-8

• 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-(tetrahydro-2H-pyran-4-ylamino)pyrimidine-5-carbaldehyde
• 英文别名: 2-Methylsulfanyl-4-(tetrahydro-2h-pyran-4-ylamino)pyrimidine-5-carbaldehyde；2-methylsulfanyl-4-(oxan-4-ylamino)pyrimidine-5-carbaldehyde
• CAS: 933795-01-8
• 化学式: C₁₁H₁₅N₃O₂S
• 分子量: 253.325
• InChiKey: ZGOGUWORGKHQKL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• 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：

  2-methylsulfanyl-4-(tetrahydro-2H-pyran-4-ylamino)pyrimidine-5-carbaldehyde 在 N-氯代丁二酰亚胺 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 二氯甲烷 、 水 为溶剂， 反应 21.25h， 生成
  参考文献：
  名称：

  Pyridopyrimidinone Derivatives as Potent and Selective c-Jun N-Terminal Kinase (JNK) Inhibitors

  摘要：

  A novel series of 2-aminopyridopyrimidinone based JNK (c-jun N-terminal kinase) inhibitors were discovered and developed. Structure activity relationships (SARs) were systematically developed utilizing biochemical and cell based assays and in vitro and in vivo drug metabolism and pharmacokinetic (DMPK) studies. Through the optimization of lead compound 1, several potent and selective JNK inhibitors with high oral bioavailability were developed. Inhibitor 13 was a potent JNK3 inhibitor (IC50 = 15 nM), had high selectivity against p38 (IC50 > 10 mu M), had high potency in functional cell based assays, and had high stability in human liver microsome (t(1/2) = 76 min), a clean CYP-450 inhibition profile, and excellent oral bioavailability (%F = 87). Moreover, cocrystal structures of compounds 13 and 22 in JNK3 were solved at 2.0 angstrom. These structures elucidated the binding mode (Type-1 binding) and can pave the way for further inhibitor design of this pyridopyrimidinone scaffold for JNK inhibition.

  DOI：

  10.1021/ml500474d
• 作为产物：
  描述：

  4-氯-2-甲硫基嘧啶-5-羧酸乙酯 在 manganese(IV) oxide 、 lithium aluminium tetrahydride 、 三乙胺 作用下， 以 四氢呋喃 、 氯仿 为溶剂， 反应 17.0h， 生成 2-methylsulfanyl-4-(tetrahydro-2H-pyran-4-ylamino)pyrimidine-5-carbaldehyde
  参考文献：
  名称：

  Pyridopyrimidinone Derivatives as Potent and Selective c-Jun N-Terminal Kinase (JNK) Inhibitors

  摘要：

  A novel series of 2-aminopyridopyrimidinone based JNK (c-jun N-terminal kinase) inhibitors were discovered and developed. Structure activity relationships (SARs) were systematically developed utilizing biochemical and cell based assays and in vitro and in vivo drug metabolism and pharmacokinetic (DMPK) studies. Through the optimization of lead compound 1, several potent and selective JNK inhibitors with high oral bioavailability were developed. Inhibitor 13 was a potent JNK3 inhibitor (IC50 = 15 nM), had high selectivity against p38 (IC50 > 10 mu M), had high potency in functional cell based assays, and had high stability in human liver microsome (t(1/2) = 76 min), a clean CYP-450 inhibition profile, and excellent oral bioavailability (%F = 87). Moreover, cocrystal structures of compounds 13 and 22 in JNK3 were solved at 2.0 angstrom. These structures elucidated the binding mode (Type-1 binding) and can pave the way for further inhibitor design of this pyridopyrimidinone scaffold for JNK inhibition.

  DOI：

  10.1021/ml500474d

文献信息

• PYRIDO-PYRIDIMIDINE DERIVATIVES USEFUL AS ANTIINFLAMMATORY AGENTS
  申请人：Verma Ashwani Kumar

  公开号：US20090221600A1

  公开（公告）日：2009-09-03

  Provided are novel pyrido-pyrimidine derivatives, having the structure of Formula (I): which can be used as anti-inflammatory agents. Also provided are pharmaceutical compositions comprising one or more pyrido-pyrimidine derivatives, as well as methods of treating autoimmune diseases, inflammation or associated pathologies, including for example, sepsis, rheumatoid arthritis, inflammatory bowel disease, type-1 diabetes, asthma, chronic obstructive pulmonary disorder, organ transplant rejection and psoriasis, comprising administering such compounds or pharmaceutical compositions comprising them.

  提供了新型的吡啶并嘧啶衍生物，其结构式为公式（I），可用作抗炎剂。还提供了包含一种或多种吡啶并嘧啶衍生物的药物组合物，以及治疗自身免疫性疾病、炎症或相关病理的方法，例如败血症、类风湿性关节炎、炎症性肠病、1型糖尿病、哮喘、慢性阻塞性肺疾病、器官移植排斥反应和银屑病，包括给予这种化合物或包含它们的药物组合物的方法。
• WO2007/36791
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] PYRIDO-PYRIDIMIDINE DERIVATIVES USEFUL AS ANTIINFLAMMATORY AGENTS<br/>[FR] DÉRIVÉS DE PYRIDO-PYRIMIDINE POUVANT ÊTRE EMPLOYÉS EN TANT QU'AGENTS ANTI-INFLAMMATOIRES
  申请人：RANBAXY LAB LTD

  公开号：WO2007036791A1

  公开（公告）日：2007-04-05

  [EN] Provided are novel pyrido-pyrimidine derivatives, having the structure of Formula (I): which can be used as anti-inflammatory agents. Also provided are pharmaceutical compositions comprising one or more pyrido-pyrimidine derivatives, as well as methods of treating autoimmune diseases, inflammation or associated pathologies, including for example, sepsis, rheumatoid arthritis, inflammatory bowel disease, type-1 diabetes, asthma, chronic obstructive pulmonary disorder, organ transplant rejection and psoriasis, comprising administering such compounds or pharmaceutical compositions comprising them.
  [FR] La présente invention a pour objet de nouveaux dérivés de pyrido-pyrimidine dont la structure est représentée par la Formule (I) : et pouvant être employés en tant qu'agents anti-inflammatoires. La présente invention a également pour objet des préparations pharmaceutiques comprenant un ou plusieurs dérivés de pyrido-pyrimidine, de même que des méthodes de traitement de maladies auto-immunes, de l'inflammation ou de pathologies associées, incluant, par exemple, sepsie, polyarthrite rhumatoïde, affection abdominale inflammatoire, diabète de type 1, asthme, bronchopneumopathie chronique obstructive, rejet de greffe d'organe et psoriasis, lesdites méthodes comprenant l'administration de tels composés ou de telles préparations pharmaceutiques les incluant.
• [EN] DISCOVERY OF COVALENT EGFR INHIBITOR THROUGH CYSTEINE 775<br/>[FR] DÉCOUVERTE D'UN INHIBITEUR COVALENT DE L'EGFR PAR LE BIAIS DE LA CYSTÉINE 775
  申请人：[en]DANA-FARBER CANCER INSTITUTE, INC.

  公开号：WO2023196409A1

  公开（公告）日：2023-10-12

  The disclosure relates to compounds that act as inhibitors of epidermal growth factor receptor (EGFR); pharmaceutical compositions comprising the compounds; and methods of treating or preventing kinase-mediated disorders, including cancer and other proliferation diseases.