4-(6-bromopyridin-2-ylmethyl)thiomorpholine 1,1-dioxide | 1206630-16-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-(6-bromopyridin-2-ylmethyl)thiomorpholine 1,1-dioxide
• 英文别名: 4-((6-Bromopyridin-2-yl)methyl)thiomorpholine 1,1-dioxide；4-[(6-bromopyridin-2-yl)methyl]thiomorpholine 1,1-dioxide；4-[(6-bromopyridin-2-yl)methyl]-1,4-thiazinane 1,1-dioxide
• CAS: 1206630-16-1
• 化学式: C₁₀H₁₃BrN₂O₂S
• 分子量: 305.195
• InChiKey: BIRIODPLODUCPW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  58.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(6-bromopyridin-2-ylmethyl)thiomorpholine 1,1-dioxide 、 3-isobutyl-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)imidazolidine-2,4-dione 在 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 反应 17.0h， 以29%的产率得到1-(4-(6-((1,1-dioxo-1λ6-thiomorpholin-4-yl)methyl)pyridin-2-yl)benzyl)-3-isobutylimidazolidine-2,4-dione
  参考文献：
  名称：

  Discovery and Optimization of 1-(4-(Pyridin-2-yl)benzyl)imidazolidine-2,4-dione Derivatives As a Novel Class of Selective Cannabinoid CB2 Receptor Agonists

  摘要：

  Here, we report the identification and optimization of 1-(4-(pyridin-2-yl)benzyl)imidazolidine-2,4-dione derivatives as a novel chemotype with selective cannabinoid CB2 receptor agonist activity. 1 is a potent and selective cannabinoid CB2 receptor agonist (hCB2 pEC(50) = 8.6). The compound was found to be metabolically unstable, which resulted in low oral bioavailability in rat (F-po = 4%) and possessed off-target activity at the hERG ion channel (pK(i), = 5.5). Systematic modification of physicochemical properties, such as lipophilicity and basicity, was used to optimize the pharmacokinetic profile and hERG affinity of this novel class of cannabinoid CB2 receptor agonists. This led to the identification of 44 as a potent, selective, and orally bioavailable cannabinoid CB2 receptor agonist (hCB2 pEC(50) = 8.0; hERG pK(i) < 4; F-po = 100%), which was active in a rat spinal nerve ligation model of neuropathic pain.

  DOI：

  10.1021/jm200916p
• 作为产物：
  描述：

  硫代吗啉-1,1-二氧化物 、 6-溴吡啶-2-甲醛 在 sodium triacetoxyborohydride 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 反应 2.25h， 以90%的产率得到4-(6-bromopyridin-2-ylmethyl)thiomorpholine 1,1-dioxide
  参考文献：
  名称：

  Discovery and Optimization of 1-(4-(Pyridin-2-yl)benzyl)imidazolidine-2,4-dione Derivatives As a Novel Class of Selective Cannabinoid CB2 Receptor Agonists

  摘要：

  Here, we report the identification and optimization of 1-(4-(pyridin-2-yl)benzyl)imidazolidine-2,4-dione derivatives as a novel chemotype with selective cannabinoid CB2 receptor agonist activity. 1 is a potent and selective cannabinoid CB2 receptor agonist (hCB2 pEC(50) = 8.6). The compound was found to be metabolically unstable, which resulted in low oral bioavailability in rat (F-po = 4%) and possessed off-target activity at the hERG ion channel (pK(i), = 5.5). Systematic modification of physicochemical properties, such as lipophilicity and basicity, was used to optimize the pharmacokinetic profile and hERG affinity of this novel class of cannabinoid CB2 receptor agonists. This led to the identification of 44 as a potent, selective, and orally bioavailable cannabinoid CB2 receptor agonist (hCB2 pEC(50) = 8.0; hERG pK(i) < 4; F-po = 100%), which was active in a rat spinal nerve ligation model of neuropathic pain.

  DOI：

  10.1021/jm200916p

文献信息

• 1-(4-(PYRIDIN-2-YL)BENZYL)IMIDAZOLIDINE-2,4-DIONE DERIVATIVES
  申请人：van der Stelt Marcelis

  公开号：US20100144724A1

  公开（公告）日：2010-06-10

  The invention relates to 1-(4-(pyridin-2-yl)benzyl)imidazolidine-2,4-dione derivative having the general Formula I wherein R 1 is H, (C 1-6 )alkyl (optionally substituted with oxo, (C 1-3 )alkyloxy, (C 1-3 )alkyloxycarbonyl, halogen or CN), (C 3-6 )cycloalkyl or (C 3-6 )cycloalkyl(C 1-3 )alkyl, each cycloalkyl ring optionally comprising a heteroatom selected from O and S; R 2 and R 3 are independently H or (C 1-3 )alkyl; or R 2 and R 3 form together with the carbon atom to which they are bound a (C 3-5 )cycloalkyl group; R 4 is H or 1 to 3 F substituents; R 5 is H or 1 to 4 F substituents; R 6 and R 7 are independently H or F; X represents R 8 , OR 8 , NR 8 R 9 , R 8 is (C 5-7 )cycloalkyl optionally comprising a heteroatom selected from O, S, SO and SO 2 ; R 9 is H or (C 1-4 )alkyl; R 10 represents 1-3 substituents independently selected from H, (C 1-3 )alkyl, halogen, oxo, CN and CF 3 ; Y is CF 2 , O, S, SO or SO 2 ; or a pharmaceutically acceptable salt thereof, to pharmaceutical compositions comprising the same, as well as to the use of said 1-(4-(pyridin-2-yl)benzyl)imidazolidine-2,4-dione derivatives in the treatment of pain such as for example peri-operative pain, chronic pain, neuropathic pain, cancer pain and pain and spasticity associated with multiple sclerosis.

  该发明涉及具有一般式I的1-(4-(吡啶-2-基)苄基)咪唑啉二酮衍生物，其中R1为H，(C1-6)烷基（可选择地取代为氧代、(C1-3)烷氧基、(C1-3)烷氧羰基、卤素或CN），(C3-6)环烷基或(C3-6)环烷基(C1-3)烷基，每个环烷基环可选择包含从O和S中选择的杂原子; R2和R3分别为H或(C1-3)烷基; 或R2和R3与它们连接的碳原子一起形成(C3-5)环烷基基团; R4为H或1至3个F取代基; R5为H或1至4个F取代基; R6和R7分别为H或F; X代表R8，OR8，NR8R9，R8为(C5-7)环烷基，可选择包含从O、S、SO和SO2中选择的杂原子; R9为H或(C1-4)烷基; R10代表1-3个取代基，独立选择自H、(C1-3)烷基、卤素、氧代、CN和CF3; Y为CF2、O、S、SO或SO2;或其药学上可接受的盐，以及包含该类化合物的药物组合物，以及所述1-(4-(吡啶-2-基)苄基)咪唑啉二酮衍生物在治疗疼痛中的用途，例如围手术期疼痛、慢性疼痛、神经性疼痛、癌症疼痛以及与多发性硬化相关的疼痛和痉挛。
• INHIBITORS OF JANUS KINASES
  申请人：Machacek Michelle R.

  公开号：US20110166129A1

  公开（公告）日：2011-07-07

  The instant invention provides for compounds that inhibit the four known mammalian JAK kinases (JAK1, JAK2, JAK3 and TYK2) and PDK1. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting the activity of JAK1, JAK2, JAK3, TYK2 and PDK1 by administering the compound to a patient in need of treatment for myeloproliferative disorders or cancer.

  本发明提供了一种抑制四种已知哺乳动物JAK激酶（JAK1、JAK2、JAK3和TYK2）和PDK1的化合物。本发明还提供了包含这些抑制剂化合物的组合物以及通过将该化合物向需要治疗骨髓增生性疾病或癌症的患者进行给药来抑制JAK1、JAK2、JAK3、TYK2和PDK1活性的方法。
• Inhibitors of Janus kinases
  申请人：Merck Sharp & Dohme Corp.

  公开号：US08278335B2

  公开（公告）日：2012-10-02

  The instant invention provides for compounds that inhibit the four known mammalian JAK kinases (JAK1, JAK2, JAK3 and TYK2) and PDK1. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting the activity of JAK1, JAK2, JAK3, TYK2 and PDK1 by administering the compound to a patient in need of treatment for myeloproliferative disorders or cancer.

  本发明提供了抑制四种已知哺乳动物JAK激酶（JAK1、JAK2、JAK3和TYK2）和PDK1的化合物。该发明还提供了包含这些抑制剂化合物的组合物以及通过向需要治疗骨髓增生性疾病或癌症的患者给予该化合物来抑制JAK1、JAK2、JAK3、TYK2和PDK1活性的方法。
• US8143246B2
  申请人：——

  公开号：US8143246B2

  公开（公告）日：2012-03-27
• US8278335B2
  申请人：——

  公开号：US8278335B2

  公开（公告）日：2012-10-02