4-甲基-N-(4-吡啶基)苯甲酰胺 | 14547-74-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-甲基-N-(4-吡啶基)苯甲酰胺
• 英文名称: 4-methyl-N-(pyridin-4-yl)benzamide
• 英文别名: 4-(p-Tolamido)-pyridin；Pyridine, 4-(p-methylbenzamido)-；4-methyl-N-pyridin-4-ylbenzamide
• CAS: 14547-74-1
• 化学式: C₁₃H₁₂N₂O
• mdl: MFCD00744272
• 分子量: 212.251
• InChiKey: GCFLVEVTCIKTNM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.076
• 拓扑面积：
  42
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  溴甲苯 、 4-甲基-N-(4-吡啶基)苯甲酰胺 以 乙腈 为溶剂， 反应 1.0h， 以91%的产率得到1-benzyl-4-(4-methylbenzamido)pyridin-1-ium bromide
  参考文献：
  名称：

  Discovery of methoxy-naphthyl linked N-(1-benzylpiperidine) benzamide as a blood-brain permeable dual inhibitor of acetylcholinesterase and butyrylcholinesterase

  摘要：

  The cholinesterase enzymes play a vital role in maintaining balanced levels of the neurotransmitter acetylcholine in the central nervous system. However, the overexpression of these enzymes results in hampered neurotransmission. Both the major forms of cholinesterase enzymes viz. acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) play a crucial role in blocking neurotransmission; therefore, in recent years, a strategy of dual cholinesterase inhibition is being explored. Herein, we developed an energy-optimized e-pharmacophore hypothesis AHHPRR from AChE-donepezil complex and screened a set of 15 scaffolds that were designed imaginarily. The ligand with N-(1-benzylpyridinium) benzamide framework has shown the highest fitness and volume score, which was chosen for synthesis and validation. A series of pyridinium benzamides were synthesized and screened for cholinesterase inhibition that led to the identification of 7b, a naphthalene containing N-(1-benzylpiperidine) benzamide as a potent dual AChE and BChE inhibitor with IC₅₀ values of 0.176, and 0.47 μM, respectively. The kinetic study indicated that 7b inhibits AChE in a non-competitive manner with Ki value of 0.21 μM, and BChE in a mixed-fashion with Ki of 0.15 μM. The observed mode of inhibition was corroborated with molecular docking studies. The MD simulation studies pointed out that both AChE and BChE undergo low conformational changes in complex with 7b. The benzamide 7b displayed high BBB permeability in PAMPA assay, which indicates its potential for further exploration in preclinical studies for Alzheimer's disease.

  DOI：

  10.1016/j.ejmech.2020.112761
• 作为产物：
  描述：

  对甲基苯甲酸 在 草酰氯 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 4-甲基-N-(4-吡啶基)苯甲酰胺
  参考文献：
  名称：

  Discovery of methoxy-naphthyl linked N-(1-benzylpiperidine) benzamide as a blood-brain permeable dual inhibitor of acetylcholinesterase and butyrylcholinesterase

  摘要：

  The cholinesterase enzymes play a vital role in maintaining balanced levels of the neurotransmitter acetylcholine in the central nervous system. However, the overexpression of these enzymes results in hampered neurotransmission. Both the major forms of cholinesterase enzymes viz. acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) play a crucial role in blocking neurotransmission; therefore, in recent years, a strategy of dual cholinesterase inhibition is being explored. Herein, we developed an energy-optimized e-pharmacophore hypothesis AHHPRR from AChE-donepezil complex and screened a set of 15 scaffolds that were designed imaginarily. The ligand with N-(1-benzylpyridinium) benzamide framework has shown the highest fitness and volume score, which was chosen for synthesis and validation. A series of pyridinium benzamides were synthesized and screened for cholinesterase inhibition that led to the identification of 7b, a naphthalene containing N-(1-benzylpiperidine) benzamide as a potent dual AChE and BChE inhibitor with IC₅₀ values of 0.176, and 0.47 μM, respectively. The kinetic study indicated that 7b inhibits AChE in a non-competitive manner with Ki value of 0.21 μM, and BChE in a mixed-fashion with Ki of 0.15 μM. The observed mode of inhibition was corroborated with molecular docking studies. The MD simulation studies pointed out that both AChE and BChE undergo low conformational changes in complex with 7b. The benzamide 7b displayed high BBB permeability in PAMPA assay, which indicates its potential for further exploration in preclinical studies for Alzheimer's disease.

  DOI：

  10.1016/j.ejmech.2020.112761

文献信息

• [EN] INHIBITORS OF BRUTON'S TYROSINE KINASE<br/>[FR] INHIBITEURS DE TYROSINE KINASE DE BRUTON
  申请人：BIOCAD JOINT STOCK CO

  公开号：WO2018092047A1

  公开（公告）日：2018-05-24

  The present invention relates to a new compound of formula I: or pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: V1 is C or N, V2 is C(R2) or N, whereby if V1 is C then V2 is N, if V1 is C then V2 is C(R2), or if V1 is N then V2 is C(R2); each n, k is independently 0, 1; each R2, R11 is independently H, D, Hal, CN, NR'R", C(O)NR'R", C1-C6 alkoxy; R3 is H, D, hydroxy, C(O)C1-C6 alkyl, C(O)C2-C6 alkenyl, C(O)C2-C6 alkynyl, C1-C6 alkyl; R4 is H, Hal, CN, CONR'R", hydroxy, C1-C6 alkyl, C1-C6 alkoxy; L is CH2, NH, O or chemical bond; R1 is selected from the group of the fragments, comprising: Fragment 1, Fragment 2, Fragment 3 each A1, A2, A3, A4 is independently CH, N, CHal; each A5, A6, A7, A8, A9 is independently C, CH or N; R5 is H, CN, Hal, CONR'R", C1-C6 alkyl, non-substituted or substituted by one or more halogens; each R' and R" is independently selected from the group, comprising H, C1-C6 alkyl, C1-C6 cycloalkyl, aryl; R6 is selected from the group: [formula II] each R7, R8, R9, R10 is independently vinyl, methylacetylenyl; Hal is CI, Br, I, F, which have properties of inhibitor of Bruton's tyrosine kinase (Btk), to pharmaceutical compositions containing such compounds, and their use as pharmaceuticals for treatment of diseases and disorder.

  本发明涉及一种新的化合物，其化学式为I：或其药学上可接受的盐、溶剂化合物或立体异构体，其中：V1为C或N，V2为C(R2)或N，如果V1为C，则V2为N，如果V1为C，则V2为C(R2)，或者如果V1为N，则V2为C(R2)；每个n，k独立地为0或1；每个R2，R11独立地为H，D，Hal，CN，NR'R"，C(O)NR'R"，C1-C6烷氧基；R3为H，D，羟基，C(O)C1-C6烷基，C(O)C2-C6烯基，C(O)C2-C6炔基，C1-C6烷基；R4为H，Hal，CN，CONR'R"，羟基，C1-C6烷基，C1-C6烷氧基；L为CH2，NH，O或化学键；R1从包括的片段组中选择：片段1，片段2，片段3，每个A1，A2，A3，A4独立地为CH，N，CHal；每个A5，A6，A7，A8，A9独立地为C，CH或N；R5为H，CN，Hal，CONR'R"，C1-C6烷基，未取代或被一个或多个卤素取代；每个R'和R"独立地从包括H，C1-C6烷基，C1-C6环烷基，芳基的组中选择；R6从组中选择：[化学式II]每个R7，R8，R9，R10独立地为乙烯基，甲基乙炔基；Hal为CI，Br，I，F，具有布鲁顿酪氨酸激酶（Btk）抑制剂的性质，以及含有这种化合物的药物组合物，以及它们作为治疗疾病和紊乱的药物的用途。
• Rhodium-Catalyzed Synthesis of Amides from Functionalized Blocked Isocyanates
  作者：Joshua S. Derasp、André M. Beauchemin

  DOI：10.1021/acscatal.9b02641

  日期：2019.9.6

  Isocyanates are useful building blocks for the synthesis of amides, although their widespread use has been limited by their high reactivity, which often results in poor functional group tolerance and a propensity to oligomerize. Herein, a rhodium-catalyzed synthesis of amides is described coupling boroxines with blocked (masked) isocyanates. The success of the reaction hinges on the ability to form

  异氰酸酯是酰胺合成的有用组成部分，尽管它们的广泛使用受到其高反应性的限制，这通常导致较差的官能团耐受性和低聚倾向。在本文中，描述了铑催化的酰胺的合成，其将环硼氧烷与封闭的（被掩蔽的）异氰酸酯偶联。反应的成功取决于原位形成异氰酸酯和有机铑中间体的能力。依赖于掩蔽的异氰酸酯前体和有机铑中间体的高反应性，可实现宽泛的官能团耐受性，包括质子亲核基团（如胺，苯胺和醇）。
• 6-AMINOISOQUINOLINE COMPOUNDS
  申请人：Aerie Pharmaceuticals, Inc.

  公开号：US20130137721A1

  公开（公告）日：2013-05-30

  6-Amino isoquinoline compounds are provided that influence, inhibit or reduce the action of a kinase. Pharmaceutical compositions including therapeutically effective amounts of the 6-aminoisoquinoline compounds and pharmaceutically acceptable carriers are also provided. Various methods using the compounds and/or compositions to affect disease states or conditions such as cancer, obesity and glaucoma are also provided.

  提供了影响、抑制或减少激酶作用的6-氨基异喹啉化合物。还提供了包括治疗有效量的6-氨基异喹啉化合物和药学上可接受的载体的制药组合物。还提供了使用这些化合物和/或组合物影响癌症、肥胖症和青光眼等疾病状态或病情的各种方法。
• Dihydropteridinones in the treatment of respiratory diseases
  申请人：Maier Udo

  公开号：US20070043055A1

  公开（公告）日：2007-02-22

  The present invention relates to the use of dihydropteridinones of formula 1 wherein the groups X, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 have the meanings given in the claims and specification, for the preparation of a medicament for the treatment of respiratory diseases.
• INHIBITORS OF BRUTON'S TYROSINE KINASE
  申请人：Joint Stock Company "Biocad"

  公开号：US20190352276A1

  公开（公告）日：2019-11-21

  The present invention relates to a new compound of formula I: or pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: V 1 is C or N, V 2 is C(R 2 ) or N, whereby if V 1 is C then V 2 is N, if V 1 is C then V 2 is C(R 2 ), or if V 1 is N then V 2 is C(R 2 ); each n, k is independently 0, 1; each R 2 , R 11 is independently H, D, Hal, CN, NR′R″, C(O)NR′R″, C 1 -C 6 alkoxy; R 3 is H, D, hydroxy, C(O)C 1 -C 6 alkyl, C(O)C 2 -C 6 alkenyl, C(O)C 2 -C 6 alkynyl, C 1 -C 6 alkyl; R 4 is H, Hal, CN, CONR′R″, hydroxy, C 1 -C 6 alkyl, C 1 -C 6 alkoxy; L is CH 2 , NH, O or chemical bond; R 1 is selected from the group of the fragments, comprising: Fragment 1, Fragment 2, Fragment 3 each A 1 , A 2 , A 3 , A 4 is independently CH, N, CHal; each A 5 , A 6 , A 7 , A 8 , A 9 is independently C, CH or N; R 5 is H, CN, Hal, CONR′R″, C 1 -C 6 alkyl, non-substituted or substituted by one or more halogens; each R′ and R″ is independently selected from the group, comprising H, C 1 -C 6 alkyl, C 1 -C 6 cycloalkyl, aryl; R 6 is selected from the group: [formula II] each R 7 , R 8 , R 9 , R 10 is independently vinyl, methylacetylenyl; Hal is CI, Br, I, F, which have properties of inhibitor of Bruton's tyrosine kinase (Btk), to pharmaceutical compositions containing such compounds, and their use as pharmaceuticals for treatment of diseases and disorder.