N-methyl-4-(4-methyl-piperazin-1-ylmethyl)-aniline | 29608-12-6

• 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-methyl-4-(4-methyl-piperazin-1-ylmethyl)-aniline
• 英文别名: N-methyl-4-[(4-methylpiperazin-1-yl)methyl]aniline
• CAS: 29608-12-6
• 化学式: C₁₃H₂₁N₃
• mdl: MFCD09035990
• 分子量: 219.33
• InChiKey: AKZZXUVPISXUFF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.538
• 拓扑面积：
  18.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-溴-2-羟基烟酸甲酯 、 3.4-(亚甲基二氧基)苯硼酸 、 N-methyl-4-(4-methyl-piperazin-1-ylmethyl)-aniline 生成 5-(1,3-benzodioxol-5-yl)-N-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-2-oxo-1H-pyridine-3-carboxamide
  参考文献：
  名称：

  设计和合成5-间变性吡啶酮-羧酰胺作为间变性淋巴瘤激酶抑制剂。

  摘要：

  间变性淋巴瘤激酶（ALK）是治疗某些疾病的新希望靶标，例如间变性大细胞淋巴瘤（ALCL）和炎性肌成纤维细胞瘤（IMT）。我们已通过应用逐步过程确定了一系列新型吡啶酮作为ALK的激酶抑制剂，该过程涉及体外筛选新型靶向库，然后基于药物化学见解和虚拟库的计算排名对模板进行迭代修饰。使用此过程，我们发现了具有增强的效能和选择性的ALK选择性抑制剂。本文讨论了这些新颖的吡啶酮的设计过程和合成细节，以及它们的酶促活性和基于细胞的活性。

  DOI：

  10.1021/jm050824x

文献信息

• [EN] COMPOUNDS<br/>[FR] COMPOSÉS
  申请人：MEDICAL RES COUNCIL TECHNOLOGY

  公开号：WO2010106333A1

  公开（公告）日：2010-09-23

  A compound of formula (I), or a pharmaceutically acceptable salt or ester thereof, wherein R1 is selected from: aryl; heteroaryl; -NHR3; fused aryl-C4-7-heterocycloalkyI; -CONR4R5; -NHCOR6; -C3-7-cycloalkyl; -O-C3-7-cycloalkyl; -NR3R6; and optionally substituted -C1-6 alkyl; wherein said aryl, heteroaryl, fused aryl-C4-7-heterocycloalkyl and C4-7-heterocycloalkyl are each optionally substituted; R2 is selected from hydrogen, aryl, C1-6-alkyl, C2-6-alkenyl, C3-7-cycloalkyl, heteroaryl, C4-7 heterocycloalkyl and halogen, wherein said C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl and C4-7-heterocycloalkyl are each optionally substituted. Further aspects relate to pharmaceutical compositions, therapeutic uses and process for preparing compounds of formula (I).

  一种具有式（I）的化合物，或其药学上可接受的盐或酯，其中R1选自：芳基；杂环芳基；-NHR3；融合芳基-C4-7-杂环烷基；-CONR4R5；-NHCOR6；-C3-7-环烷基；-O-C3-7-环烷基；-NR3R6；和可选择地取代的-C1-6烷基；其中所述的芳基、杂环芳基、融合芳基-C4-7-杂环烷基和C4-7-杂环烷基均可选择地取代；R2选自氢、芳基、C1-6-烷基、C2-6-烯基、C3-7-环烷基、杂环芳基、C4-7-杂环烷基和卤素，其中所述的C1-6-烷基、C2-6-烯基、芳基、杂环芳基和C4-7-杂环烷基均可选择地取代。进一步涉及制备具有式（I）的化合物的药物组合物、治疗用途和制备方法的其他方面。
• 4,6-DI- AND 2,4,6-TRISUBSTITUTED QUINAZOLINE DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS USEFUL FOR TREATING VIRAL INFECTIONS
  申请人：Gao Ling-Jie

  公开号：US20100143299A1

  公开（公告）日：2010-06-10

  This invention provides the treatment of viral infections with a 4,6-disubstituted or 2,4,6-trisubstituted quinazoline derivative represented by the structural formula [(I)] wherein: R 2 is selected from the group consisting of hydrogen, NR′R″ and C 1-7 alkyl; —A is selected from the group consisting of a bond, O, S(O) n , C 1-7 alkylene, C 2-7 alkenylene and C 2-7 alkynylene; R 4 is selected from the group consisting of C 1-7 alkyl, C 2-7 alkenyl, C 3-10 cycloalkyl, C 3-10 cycloalkenyl, aryl, heterocyclic, arylalkyl, heterocyclic-substituted alkyl and cycloalkyl-alkyl; —Y is selected from the group consisting of a single bond, C 1-7 alkylene, C 2-7 alkenylene, and C 2-7 alkynylene; n is 0, 1 or 2; and R 6 is selected from the group consisting of halogen, heteroaryl and aryl; a pharmaceutically acceptable addition salt, a stereoisomer, a mono- or a di-Λ/-oxide, a solvate or a pro-drug thereof.

  本发明提供了一种使用4,6-二取代或2,4,6-三取代喹唑啉衍生物的治疗病毒感染的方法，其结构式表示为[(I)]，其中：R2选自氢、NR′R″和C1-7烷基的组；—A选自键、O、S(O)n、C1-7烷基、C2-7烯基和C2-7炔基的组；R4选自C1-7烷基、C2-7烯基、C3-10环烷基、C3-10环烯基、芳基、杂环、芳基烷基、杂环取代烷基和环烷基-烷基的组；—Y选自单键、C1-7烷基、C2-7烯基和C2-7炔基的组；n为0、1或2；R6选自卤素、杂芳基和芳基的组；以及其药学上可接受的加合物盐、立体异构体、单-或双-Λ/-氧化物、溶剂化合物或前药。
• COMPOUNDS
  申请人：Mciver Edward Giles

  公开号：US20100317646A1

  公开（公告）日：2010-12-16

  A compound of formula I, or a pharmaceutically acceptable salt or ester thereof, wherein R 1 is selected from: aryl; heteroaryl; —NHR 3 ; fused aryl-C 4-7 -heterocycloalkyl; —CONR 4 R 5 ; —NHCOR 6 ; —C 3-7 -cycloalkyl; —O—C 3-7 -cycloalkyl; —NR 3 R 6 ; and optionally substituted —C 1-6 alkyl; wherein said aryl, heteroaryl, fused aryl-C 4-7 -heterocycloalkyl and C 4-7 -heterocycloalkyl are each optionally substituted; R 2 is selected from hydrogen, aryl, C 1-6 -alkyl, C 2-6 -alkenyl, C 3-7 -cycloalkyl, heteroaryl, C 4-7 heterocycloalkyl and halogen, wherein said C 1-6 -alkyl, C 2-6 -alkenyl, aryl, heteroaryl and C 4-7 -heterocycloalkyl are each optionally substituted; R 3 is selected from aryl, heteroaryl, C 4-7 -heterocycloalkyl, C 3-7 -cycloalkyl, fused aryl-C 4-7 -heterocycloalkyl and C 1-6 -alkyl, each of which is optionally substituted; R 4 and R 5 are each independently hydrogen, or optionally substituted C 3-7 -cycloalkyl, aryl, heteroaryl, C 1-6 -alkyl or C 3-6 -heterocycloalkyl; or R 4 and R 5 together with the N to which they are attached form a C 3-6 -heterocycloalkyl ring; each R 6 is independently selected from C 1-6 -alkyl, C 3-7 cycloalkyl, C 4-7 -heterocycloalkyl, aryl and heteroaryl, each of which is optionally substituted each R 7 is selected from hydrogen, optionally substituted C 1-6 -alkyl and C 3-7 -cycloalkyl; each of R 8 and R 9 is independently hydrogen or optionally substituted C 1-6 -alkyl; or R 8 and R 9 together with the N to which they are attached form a C 4-6 -heterocycloalkyl; each R 10 is selected from C 3-7 -cycloalkyl and optionally substituted C 1-6 -alkyl; each R 11 is independently selected from C 1-6 -alkyl, C 3-7 -cycloalkyl, C 1-6 alkyl-C 3-7 -cycloalkyl, C 4-7 -heterocycloalkyl, aryl and heteroaryl, each of which is optionally substituted; A is selected from halogen, —NR 4 SO 2 R 5 , —CN, —OR 6 , —NR 4 R 5 , —NR 7 R 11 , hydroxyl, —CF 3 , —CONR 4 R 5 , —NR 4 COR 5 , —NR 7 (CO)NR 4 R 5 , —NO 2 , —CO 2 H, —CO 2 R 6 , —SO 2 R 6 , —SO 2 NR 4 R 5 , —NR 4 COR 5 , —NR 4 COOR 5 , C 1-6 -alkyl and —COR 6 . Further aspects relate to pharmaceutical compositions, therapeutic uses and process for preparing compounds of formula I.

  化合物I的公式，或其药学上可接受的盐或酯，其中R1选自：芳基；杂环芳基；—NHR3；融合的芳基-C4-7-杂环烷基；—CONR4R5；—NHCOR6；—C3-7-环烷基；—O—C3-7-环烷基；—NR3R6；和可选择取代的—C1-6烷基；其中所述的芳基，杂环芳基，融合的芳基-C4-7-杂环烷基和C4-7-杂环烷基均可选择取代；R2选自氢，芳基，C1-6-烷基，C2-6-烯基，C3-7-环烷基，杂环芳基，C4-7-杂环烷基和卤素，其中所述的C1-6-烷基，C2-6-烯基，芳基，杂环芳基和C4-7-杂环烷基均可选择取代；R3选自芳基，杂环芳基，C4-7-杂环烷基，C3-7-环烷基，融合的芳基-C4-7-杂环烷基和C1-6-烷基，每种均可选择取代；R4和R5各自独立地选自氢，或可选择取代的C3-7-环烷基，芳基，杂环芳基，C1-6-烷基或C3-6-杂环烷基；或R4和R5与它们连接的N一起形成C3-6-杂环烷基环；每个R6各自独立地选自C1-6-烷基，C3-7-环烷基，C4-7-杂环烷基，芳基和杂环芳基，每种均可选择取代；每个R7选自氢，可选择取代的C1-6-烷基和C3-7-环烷基；每个R8和R9各自独立地选自氢或可选择取代的C1-6-烷基；或R8和R9与它们连接的N一起形成C4-6-杂环烷基；每个R10选自C3-7-环烷基和可选择取代的C1-6-烷基；每个R11各自独立地选自C1-6-烷基，C3-7-环烷基，C1-6-烷基-C3-7-环烷基，C4-7-杂环烷基，芳基和杂环芳基，每种均可选择取代；A选自卤素，—NR4SO2R5，—CN，—OR6，—NR4R5，—NR7R11，羟基，—CF3，—CONR4R5，—NR4COR5，—NR7（CO）NR4R5，—NO2，—CO2H，—CO2R6，—SO2R6，—SO2NR4R5，—NR4COR5，—NR4COOR5，C1-6-烷基和—COR6。进一步方面涉及公式I化合物的制药组合物，治疗用途和制备过程。
• [EN] SUBSTITUTED BIS-ARYL AMIDE COMPOUND AND PREPARATION METHOD AND APPLICATION THEREFOR<br/>[FR] COMPOSÉ BIS-ARYLAMIDE SUBSTITUÉ, PROCÉDÉ DE PRÉPARATION ET UTILISATION ASSOCIÉS<br/>[ZH] 一种取代的双芳香基酰胺化合物及其制备方法和应用
  申请人：INST OF MEDICINAL BIOTECHNOLOGY CHINESE ACADEMY OF MEDICAL SCIENCES & PEKING UNION MEDICAL COLLEGE

  公开号：WO2020098710A1

  公开（公告）日：2020-05-22

  本申请提供一种取代的双芳香基酰胺化合物及其制备方法和应用，该取代的双芳香基酰胺化合物或其药用可接受的盐，其具有式[1]的结构，R 1独立地选自氢、取代或未取代的C1－12直链烷基、C 3－12支链烷基或C3－12环烷基；R2独立地选自-NO 2、-NH2、-NHCOR 5、-CF3、-NHSO 2NH2；R 3独立地选自氢、- 、-F、-CN、-NH2；R 4独立地选自氢、取代或未取代的杂环基；X独立地选自氢原子或氮原子。本申请提供的取代的双芳香基酰胺化合物或其药用可接受的盐具有抗丙肝病毒的活性。
• [EN] MEDICINE FOR TREATING OR PREVENTING DISEASES RELATED TO ACTIVITY OF LRRK2 KINASE OR ABNORMAL LRRK2 MUTANT KINASE<br/>[FR] MÉDICAMENT POUR LE TRAITEMENT OU LA PRÉVENTION DE MALADIES LIÉES À L'ACTIVITÉ DE LA KINASE LRRK2 OU DE LA KINASE MUTANTE LRRK2 ANORMALE<br/>[ZH] 一种治疗或预防与LRRK2激酶或异常LRRK2突变激酶活性相关疾病的药物
  申请人：[en]DM INTELLIGENCE LTD.;[zh]广州智睿医药科技有限公司

  公开号：WO2022062357A1

  公开（公告）日：2022-03-31

  一种治疗或预防与LRRK2激酶或异常LRRK2突变激酶活性相关疾病的药物，属于医药领域。所述药物包括化学式1表示的化合物、其光学异构体、其前体药物、其盐、其水合物、其溶剂化物、其N-氧化物、其氘化类似物中的至少一种，对LRRK2激酶或异常LRRK2突变激酶具有很好的抑制作用，能用于治疗或预防与LRRK2激酶或异常LRRK2突变激酶活性相关疾病，例如阿兹海默氏症、L多巴诱发性运动障碍、帕金森氏病、痴呆症、肾癌、乳腺癌、前列腺癌、血癌、乳头状瘤、肺癌、急性骨髓性白血病、多发性骨髓瘤、麻风病、克罗恩氏病、炎症性肠病、溃疡性结肠炎、肌肉萎缩性侧索硬化、类风湿性关节炎或强直性脊椎炎。