N-(3-methoxybenzyl)-4-(pyridin-4-yl)benzamide | 862722-95-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(3-methoxybenzyl)-4-(pyridin-4-yl)benzamide
• 英文别名: N-(3-methoxybenzyl)-4-(4-pyridinyl)benzamide；N-(3-methoxybenzyl)-4-(4-pyridyl)benzamide；N-[(3-methoxyphenyl)methyl]-4-pyridin-4-ylbenzamide
• CAS: 862722-95-0
• 化学式: C₂₀H₁₈N₂O₂
• 分子量: 318.375
• InChiKey: JBLPUDJLELBRHC-UHFFFAOYSA-N

物化性质

• 沸点：
  545.4±45.0 °C(Predicted)
• 密度：
  1.166±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-bromo-N-(3-methoxybenzyl)benzamide 、 吡啶-4-硼酸 在 bis-triphenylphosphine-palladium(II) chloride sodium carbonate 作用下， 以 乙二醇二甲醚 、 乙醇 、 水 为溶剂， 反应 0.17h， 生成 N-(3-methoxybenzyl)-4-(pyridin-4-yl)benzamide
  参考文献：
  名称：

  Chemical Compounds

  摘要：

  提供了化合物的结构式（I）及其盐、溶剂合物和生理功能衍生物：其中R1为氢或C1-6烷基；n为1、2、3或4；R2为芳基，可选择地由卤素、羟基、氰基、C1-4烷基、C1-4烷氧基、C1-4烷酰、卤代C1-4烷基、卤代C1-4烷氧基、芳基、芳氧基、C1-4烷氧羰基、C1-4烷基磺酰和一个R3R4NSO2（其中R3和R4独立地为氢或C1-4烷基）和一个5-或6-成员杂芳基团；或n为0且R1和R2与它们连接的氮原子一起形成5-或6-成员单环杂环或9-或10-成员双环杂环，其中至少包含R1和R2连接的氮原子的环不是芳香的，5-或6-成员单环杂环或9-或10-成员双环杂环可选择地由卤素、羟基、氰基、氧、C1-4烷基、C1-4烷酰、C1-4烷氧基、卤代C1-4烷基、卤代C1-4烷氧基、芳基、芳氧基和C1-4烷氧羰基的一个或两个基团取代；X为吲唑基、吡唑基或一个基团：其中G为CH或N；Y1和Y2独立地为氢、卤素和一个NR5R6（其中R5和R6独立地为氢、C1-6烷基或C2-6烯基）的基团。

  公开号：

  US20080275062A1

文献信息

• [EN] SUBSTITUTED HETEROCYCLIC DERIVATIVES<br/>[FR] DÉRIVÉS HÉTÉROCYCLIQUES SUBSTITUÉS
  申请人：HOFFMANN LA ROCHE

  公开号：WO2014079850A1

  公开（公告）日：2014-05-30

  The present invention relates to compounds of general formula (I-1) or (I-2) wherein R1 is hydrogen, lower alkyl, lower alkoxy, halogen, O(CH2)2-lower akoxy, O(CH2)2N(CH3)2, or O(CH2)-morpholinyl; R1' is hydrogen, lower alkyl, lower alkoxy, halogen, O(CH2)2-lower akoxy, O(CH2)2N(CH3)2, or O(CH2)-morpholinyl; with the proviso that both R1 and R1' may be simultaneously hydrogen, but only one of R1 and R1' is lower alkyl, lower alkoxy, halogen, O(CH2)2-lower akoxy, O(CH2)2N(CH3)2, or O(CH2)-morpholinyl; Het is a 5-or 6 membered heteroaryl group, wherein the heteroatom is selected from N, O or S; X is -CRR'-, -CRR'-NR'-, -C(O)-, -CH2-S-, -CH2-S(O)2-, CH2-O- or -CH2-CRR'-; R/R' are independently from each other hydrogen, lower alkyl, hydroxy or phenyl, or R and R' may form together with the carbon atom to which they are attached a cyclopropyl ring; R2 is lower alkyl, -C(O)O-lower alkyl, C3-6-cycloalkyl optionally substituted by lower alkyl or =O, bridged cyclohexyl or C3-6-cycloalkenyl, or is a 5-membered heteroaryl group, wherein the heteroatom is selected from N, O or S and which is optionally substituted by one or more lower alkyl, or is pyridinyl, optionally substituted by halogen or lower alkoxy; or is phenyl, optionally substituted by one or more R2', selected from halogen, cyano, S(O)2-lower alkyl, lower alkyl, lower alkyl substituted by halogen, lower alkoxy, lower alkoxy substituted by halogen or amino, or is benzo[1,3]dioxolyl, naphthyl, indolyl, benzo-isoxazolyl, 2,3-dihydro-1H-indenyl, optionally substituted by lower alkoxy or by an oxo group, or is 3,4-dihydro-2H- [1,4]oxazinyl, optionally substituted by an oxo group, or is a five or six membered heterocycloalkyl group; or to a pharmaceutically acceptable acid addition salt, to a racemic mixture or to its corresponding enantiomer and/or optical isomers thereof. The compounds may be used for the treatment or prophylaxis of schizophrenia, obsessive-compulsive personality disorder, major depression, bipolar disorders, anxiety disorders, normal aging, epilepsy, retinal degeneration, traumatic brain injury, spinal cord injury, post-traumatic stress disorder, panic disorder, Parkinson's disease, dementia, Alzheimer's disease, mild cognitive impairment, chemotherapy-induced cognitive dysfunction, Down syndrome, autism spectrum disorders, hearing loss, tinnitus, spinocerebellar ataxia, amyotrophic lateral sclerosis, multiple sclerosis, Huntington's disease, stroke, radiation therapy, chronic stress, abuse of neuro-active drugs, such as alcohol, opiates, methamphetamine, phencyclidine and cocaine.

  本发明涉及通式（I-1）或（I-2）的化合物，其中R1为氢、较低烷基、较低烷氧基、卤素、O(CH2)2-较低烷氧基、O(CH2)2N(CH3)2或O(CH2)-吗啡啉基；R1'为氢、较低烷基、较低烷氧基、卤素、O(CH2)2-较低烷氧基、O(CH2)2N(CH3)2或O(CH2)-吗啡啉基；但要注意，R1和R1'中两者同时为氢，但只有一个为较低烷基、较低烷氧基、卤素、O(CH2)2-较低烷氧基、O(CH2)2N(CH3)2或O(CH2)-吗啡啉基；Het为5或6元杂芳基团，其中杂原子选自N、O或S；X为-CRR'-、-CRR'-NR'-、-C(O)-、-CH2-S-、-CH2-S(O)2-、CH2-O-或-CH2-CRR'-；R/R'独立地为氢、较低烷基、羟基或苯基，或R和R'可与它们连接的碳原子共同形成环丙基环；R2为较低烷基、-C(O)O-较低烷基、C3-6-环烷基（可选择地被较低烷基或=O取代）、桥环己基或C3-6-环烯基，或为5元杂芳基团，其中杂原子选自N、O或S，可选择地被一个或多个较低烷基取代，或为吡啶基，可选择地被卤素或较低烷氧基取代；或为苯基，可选择地被一个或多个来自卤素、氰基、S(O)2-较低烷基、较低烷基、被卤素取代的较低烷基、较低烷氧基、被卤素取代的较低烷氧基或氨基的R2'取代基，或为苯并[1,3]二氧杂环己基、萘基、吲哚基、苯并异噁唑基、2,3-二氢-1H-茚基，可选择地被较低烷氧基或氧羟基取代，或为3,4-二氢-2H-[1,4]噁唑基，可选择地被氧羟基取代，或为五元或六元杂环烷基团；或为药学上可接受的酸盐，或为外消旋混合物，或为其相应的对映体和/或光学异构体。这些化合物可用于治疗或预防精神分裂症、强迫性人格障碍、重性抑郁症、双相障碍、焦虑障碍、正常衰老、癫痫、视网膜退化、创伤性脑损伤、脊髓损伤、创伤后应激障碍、恐慌障碍、帕金森病、痴呆症、阿尔茨海默病、轻度认知障碍、化疗诱导的认知功能障碍、唐氏综合征、自闭症谱系障碍、听力损失、耳鸣、脊髓小脑性共济失调、肌萎缩侧索硬化、多发性硬化、亨廷顿病、中风、放射治疗、慢性压力、滥用神经活性药物，如酒精、阿片类药物、甲基苯丙胺、芬太尼和可卡因。
• INDUCTION OF PLURIPOTENT CELLS
  申请人：Lin Tongxiang

  公开号：US20120264218A1

  公开（公告）日：2012-10-18

  The slow kinetics and low efficiency of reprogramming methods to generate human induced pluripotent stem cells (iPSCs) impose major limitations on their utility in biomedical applications. Here we describe a chemical approach that dramatically improves (>200 fold) the efficiency of iPSC generation from human fibroblasts, within seven days of treatment. This will provide a basis for developing safer, more efficient, non-viral methods for reprogramming human somatic cells.

  人类诱导多能干细胞（iPSCs）生成的方法动力学缓慢且效率低，限制了它们在生物医学应用中的实用性。在这里，我们描述了一种化学方法，可显著提高从人类成纤维细胞生成iPSC的效率（提高了200倍以上），并在治疗后七天内完成。这将为开发更安全、更高效、非病毒方法重新编程人类体细胞奠定基础。
• Identification of Selective Dual ROCK1 and ROCK2 Inhibitors Using Structure-Based Drug Design
  作者：Adrian D. Hobson、Russell A. Judge、Ana L. Aguirre、Brian S. Brown、Yifang Cui、Ping Ding、Eric Dominguez、Enrico DiGiammarino、David A. Egan、Gail M. Freiberg、Sujatha M. Gopalakrishnan、Christopher M. Harris、Marie P. Honore、Karen L. Kage、Nicolas J. Kapecki、Christopher Ling、Junli Ma、Helmut Mack、Mulugeta Mamo、Stefan Maurus、Bradford McRae、Nigel S. Moore、Bernhard K. Mueller、Reinhold Mueller、Marian T. Namovic、Kaushal Patel、Steve D. Pratt、C. Brent Putman、Kara L. Queeney、Kathy K. Sarris、Lisa M. Schaffter、Vincent Stoll、Anil Vasudevan、Lei Wang、Lu Wang、William Wirthl、Kimberly Yach

  DOI：10.1021/acs.jmedchem.8b01098

  日期：2018.12.27

  structural data indicated the preferred configuration at the central benzylic carbon would be (R), and application of this information to compound design resulted in compound 16. This compound was shown to be a potent and selective dual ROCK inhibitor in both enzyme and cell assays and efficacious in the retinal nerve fiber layer model after oral dosing. This tool compound has been made available through the

  一项HTS运动确定了化合物1，这是一种出色的命中分子，可启动药物化学工作以优化ROCK1和ROCK2双重抑制剂。取代吡啶铰链结合基序的（2-Cl，2-NH 2，2 -F，3-F）或用嘧啶替代，提供了具有干净CYP抑制谱的化合物。在PKA，ROCK1和ROCK2中获得了早期铅化合物的共晶体结构。这为药物化学驱动化合物设计提供了关键的结构信息。结构数据表明，中心苄基碳原子的优选构型为（R），并且将该信息应用于化合物设计可得到化合物16。该化合物在酶和细胞分析中均显示为有效且选择性的双重ROCK抑制剂，口服给药后在视网膜神经纤维层模型中有效。该工具化合物可通过AbbVie Compound Toolbox获得。最后，共晶结构还确定了ROCK2中的天冬氨酸残基176和218（它们是PKA中的谷氨酸）可以作为残基来靶向，以同时驱动效价和激酶组选择性。在化合物系列中引入哌啶-3-氨基甲胺基团产生了化合
• PAIN REMEDY CONTAINING ROCK INHIBITOR
  申请人：Astellas Pharma Inc.

  公开号：EP1854484A1

  公开（公告）日：2007-11-14

  Since a ROCK inhibitor exerts a potent analgesic effect by a single dose after the onset of a cartilage-related disease such as osteoarthritis, and can regenerate or suppress destruction of cartilage tissue and alleviate pain associated with cartilage diseases by multiple doses, administration of an therapeutically effective amount of the ROCK inhibitor to a patient with cartilage-related disease such as osteoarthritis or rheumatoid arthritis can treat the patient with cartilage-related disease and the ROCK inhibitor is thus useful.

  由于 ROCK 抑制剂在软骨相关疾病（如骨关节炎）发病后单次给药可发挥强效镇痛作用，多次给药可再生或抑制软骨组织的破坏，减轻与软骨疾病相关的疼痛，因此，对软骨相关疾病（如骨关节炎或类风湿性关节炎）患者施用治疗有效量的 ROCK 抑制剂可治疗软骨相关疾病患者，因此 ROCK 抑制剂是有用的。
• Rho kinase inhiitors for use in the treatment of neuroblastoma
  申请人：Academisch Medisch Centrum

  公开号：EP2628482A1

  公开（公告）日：2013-08-21

  The invention therefore provides a Rho kinase inhibitor for the treatment of neuroblastoma. Preferably, said Rho kinase inhibitor causes differentiation of neuroblastoma cells. In a preferred embodiment, said Rho kinase inhibitor is selected from the group consisting of (+)-(R)-trans-4-(1-aminoethyl)-N-(4-piridyl)cyclohexanecarboxamide, 4[(1R)-1-aminoethyl]-N-(4-piridyl)benzamide (Fasudil), 1-(1-Hydroxy-5-isoquinolinesulfonyl)homopiperazine] (Hydroxyfasudil), 2-[4-(1H-indazol-5-yl)phenyl]-2-propanamine, N-(3-methoxybenzyl)-4-(4-piridyl)benzamide, 4-[(trans-4-aminocyclohexyl)amino]-2,5-difluorobenzamide, 4-[(trans-4-aminocyclohexyl)amino]-5-chloro-2-fluorobenzamide, 5-(hexahydro-1H-1,4-diazepin-1-ylsulfonyl)isoquinoline, Isoquinolinesulfonamide (K-115), (S)-(+)-2-methyl-1-[(4-methyl-5-isoquinoline)sulfonyl]-homopiperazine (H-1152P), N-(4-Pyridyl)-N'-(2,4,6-trichlorophenyl)urea, Y-27632, Y-39983, and ROCK siRNA or a pharmaceutically acceptable salt thereof.

  因此，本发明提供了一种用于治疗神经母细胞瘤的 Rho 激酶抑制剂。优选地，所述 Rho 激酶抑制剂可导致神经母细胞瘤细胞分化。在一个优选的实施方案中，所述Rho激酶抑制剂选自由(+)-(R)-反式-4-(1-氨基乙基)-N-(4-iridyl)环己甲酰胺、4[(1R)-1-氨基乙基]-N-(4-iridyl)苯甲酰胺（Fasudil）组成的组、1-(1-羟基-5-异喹啉磺酰基)均哌嗪]（羟基法舒地尔），2-[4-(1H-吲唑-5-基)苯基]-2-丙胺，N-(3-甲氧基苄基)-4-(4-嘧啶基)苯甲酰胺，4-[(反式-4-氨基环己基)氨基]-2、4-[(反式-4-氨基环己基)氨基]-2, 5-二氟苯甲酰胺，4-[(反式-4-氨基环己基)氨基]-5-氯-2-氟苯甲酰胺，5-(六氢-1H-1,4-二氮杂卓-1-基磺酰基)异喹啉，异喹啉磺酰胺 (K-115)、(S)-(+)-2-甲基-1-[(4-甲基-5-异喹啉)磺酰基]-高哌嗪 (H-1152P)、N-(4-吡啶基)-N'-(2,4,6-三氯苯基)脲、Y-27632、Y-39983 和 ROCK siRNA 或其药学上可接受的盐。