(6-bromopyridin-2-yl) (cyclohexyl)methanone | 1228660-76-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (6-bromopyridin-2-yl) (cyclohexyl)methanone
• 英文别名: (6-Bromopyridin-2-yl)-cyclohexylmethanone
• CAS: 1228660-76-1
• 化学式: C₁₂H₁₄BrNO
• 分子量: 268.153
• InChiKey: JLVHBABYTMYWQU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  15
• 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：
  30
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (6-bromopyridin-2-yl) (cyclohexyl)methanone 在 二异丁基氢化铝 作用下， 以 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 17.25h， 生成 2-bromo-6-cyclohexylmethylpyridine
  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：

  环己甲腈 在 正丁基锂 、 硫酸 、 水 作用下， 以 四氢呋喃 、 乙醚 、 正己烷 、 水 为溶剂， 反应 6.17h， 生成 (6-bromopyridin-2-yl) (cyclohexyl)methanone
  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

• Visible Light-Driven Decarboxylative Alkylation of Aldehydes via Electron Donor–Acceptor Complexes of Active Esters
  作者：Fang-Yuan Nie、Yi-Ping Cai、Qin-Hua Song

  DOI：10.1021/acs.joc.1c02586

  日期：2022.1.21

  this paper, we have developed photocatalyst-free and visible light-driven decarboxylative alkylation of pyridinaldehydes. The photochemical reactions are initiated via photoinduced single electron transfer from triethylamine to N-hydroxyphthalimide esters in electron donor–acceptor complexes. This photochemical method can achieve to translate 15 pyridinaldehydes and 11 2-quinolinaldehydes to the corresponding

  有一些从广泛使用的醛到相应的酮的合成方法，但是它们涉及与格氏试剂或过渡金属催化剂的多步反应。在本文中，我们开发了无光催化剂和可见光驱动的吡啶醛脱羧烷基化。光化学反应是通过在电子供体-受体复合物中从三乙胺到N-羟基邻苯二甲酰亚胺酯的光诱导单电子转移引发的。这种光化学方法可以实现将15个吡啶醛和11个2-喹啉醛转化为相应的酮。此外，该策略还可以实现另外两种转化，二硫烷转化为芳基硫化物，苯乙烯砜转化为烷基取代的烯烃。
• 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。
• US8143246B2
  申请人：——

  公开号：US8143246B2

  公开（公告）日：2012-03-27
• [EN] 1-(4-(PYRIDIN-2-YL)BENZYL)IMIDAZOLIDINE-2,4-DIONE DERIVATIVES<br/>[FR] DÉRIVÉS DE 1-(4-(PYRIDIN-2-YL)BENZYL)IMIDAZOLIDINE-2,4-DIONE
  申请人：ORGANON NV

  公开号：WO2010063666A1

  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 R1 is H, (C1-6)alkyl (optionally substituted with oxo, (C1-3)alkyloxy, (C1-3)-alkyl- oxycarbonyl, halogen or CN), (C3-6)cycloalkyl or (C3-6)cycloalkyl(C1-3)alkyl, each cycloalkyl ring optionally comprising a heteroatom selected from O and S; R2 and R3 are independently H or (C1-3)alkyl; or R2 and R3 form together with the carbon atom to which they are bound a (C3-5)cycloalkyl group; R4 is H or 1 to 3 F substituents; R5 is H or 1 to 4 F substituents; R6 and R7 are independently H or F; X represents R8, OR8, NR8R9, Formulae (Ia) or (Ib); R8 is (C5-7)cycloalkyl optionally comprising a heteroatom selected from O, S, SO and SO2; R9 is H or (C1-4)alkyl; R10 represents 1-3 substituents independently selected from H, (C1-3)alkyl, halogen, oxo, CN and CF3; Y is CF2, O, S, SO or SO2; 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.
• 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
  作者：Mario van der Stelt、Jos Cals、Silvia Broeders-Josten、Jean Cottney、Antoon A. van der Doelen、Marcel Hermkens、Vera de Kimpe、Angela King、Jan Klomp、Julia Oosterom、Ilse Pols-de Rooij、Jeroen de Roos、Martin van Tilborg、Susan Boyce、James Baker

  DOI：10.1021/jm200916p

  日期：2011.10.27

  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.