罗喹美克 | 84088-42-6

• 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: 罗喹美克
• 中文别名: 1,2-二氢-4-羟基-N,N-二甲基-2-氧代-N-苯基-3-喹啉甲酰胺
• 英文名称: roquinimex
• 英文别名: linomide；N-phenyl-N-methyl-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-quinoline-3-carboxamide；4-hydroxy-N,1-dimethyl-2-oxo-N-phenylquinoline-3-carboxamide
• CAS: 84088-42-6
• 化学式: C₁₈H₁₆N₂O₃
• mdl: MFCD00866331
• 分子量: 308.337
• InChiKey: SGOOQMRIPALTEL-UHFFFAOYSA-N

物化性质

• 熔点：
  200-204°
• 沸点：
  436.2±45.0 °C(Predicted)
• 密度：
  1.357±0.06 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：11 毫克/毫升

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.111
• 拓扑面积：
  60.8
• 氢给体数：
  1
• 氢受体数：
  3

ADMET

代谢

林索米德已知的人类代谢物包括：4,6-二羟基-N,1-二甲基-2-氧代-N-苯基-1,2-二氢喹啉-3-甲酰胺、4,7-二羟基-N,1-二甲基-2-氧代-N-苯基-1,2-二氢喹啉-3-甲酰胺、4,8-二羟基-N,1-二甲基-2-氧代-N-苯基-1,2-二氢喹啉-3-甲酰胺、4-羟基-1-甲基-2-氧代-N-苯基-1,2-二氢喹啉-3-甲酰胺、4-羟基-N-(4-羟基苯基)-N,1-二甲基-2-氧代-1,2-二氢喹啉-3-甲酰胺和4-羟基-N-甲基-2-氧代-N-苯基-1,2-二氢喹啉-3-甲酰胺。

Linomide has known human metabolites that include 4,6-dihydroxy-N,1-dimethyl-2-oxo-N-phenyl-1,2-dihydroquinoline-3-carboxamide, 4,7-dihydroxy-N,1-dimethyl-2-oxo-N-phenyl-1,2-dihydroquinoline-3-carboxamide, 4,8-dihydroxy-N,1-dimethyl-2-oxo-N-phenyl-1,2-dihydroquinoline-3-carboxamide, 4-hydroxy-1-methyl-2-oxo-N-phenyl-1,2-dihydroquinoline-3-carboxamide, 4-hydroxy-N-(4-hydroxyphenyl)-N,1-dimethyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, and 4-hydroxy-N-methyl-2-oxo-N-phenyl-1,2-dihydroquinoline-3-carboxamide.

来源:NORMAN Suspect List Exchange

安全信息

• 危险品标志：
  Xn
• 危险类别码：
  R22
• 危险品运输编号：
  UN 2811
• 海关编码：
  2933790090
• 安全说明：
  S36/37
• 包装等级：
  III
• 危险类别：
  6.1
• 危险性防范说明：
  P301+P310
• 危险性描述：
  H301
• 储存条件：
  室温

制备方法与用途

生物活性

Roquinimex（FCF 89、林莫德、LS 2616）可抑制TNF-α的分泌。这是一种新型免疫调节剂，能增强自然杀伤细胞(NK)活性和T淋巴细胞相关效应功能，并且是一种有效的口服抗肿瘤血管生成剂。

靶点

Target	Value
TNF-α

反应信息

• 作为反应物：
  描述：

  4-氟苯胺 、 罗喹美克 以 甲苯 为溶剂， 反应 1.0h， 以79%的产率得到N-(4-fluorophenyl)-4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide
  参考文献：
  名称：

  [EN] 1,2-DIHYDRO-4-HYDROXY-2-OXO-QUINOLINE-3-CARBOXANILIDES AS AHR ACTIVATORS.
  [FR] 1,2-DIHYDRO-4-HYDROXY-2-OXO-QUINOLÉINE-3-CARBOXANILIDES EN TANT QU'ACTIVATEURS D'AHR

  摘要：

  本发明涉及化合物，其为1,2-二氢-4-羟基-2-氧基喹啉-3-羧酰苯胺，其噻吩-吡啶酮类似物及其前药。本发明具体涉及含有羧酰苯胺基团中N-氢的衍生物，具有对芳香烃受体（AhR）的调节活性，特别是还涉及其前药。本发明还涉及将所述化合物用作药物，用于治疗癌症、自身免疫性疾病和其他具有免疫成分的疾病，以及包含一种或多种所述化合物的药物组合物和治疗方法。

  公开号：

  WO2012050500A1
• 作为产物：
  描述：

  靛红酸酐 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 16.0h， 生成 罗喹美克
  参考文献：
  名称：

  Synthesis and Biological Evaluation of New 1,2-Dihydro-4-hydroxy-2-oxo-3-quinolinecarboxamides for Treatment of Autoimmune Disorders:  Structure−Activity Relationship

  摘要：

  Roquinimex-related 3-quinolinecarboxamide derivatives were prepared and evaluated for treatment of autoimmune disorders. The compounds were tested in mice for their inhibitory effects on disease development in the acute experimental autoimmune encephalomyelitis model and selected compounds in the beagle dog for induction of proinflammatory reaction. Structure-activity relationships are discussed. Compound 8c, laquinimod, showed improved potency and superior toxicological profile compared to the lead compound roquinimex (1b, Linomide) and was selected for clinical studies (currently in phase II).

  DOI：

  10.1021/jm031044w

文献信息

• [EN] COMPOUNDS AND COMPOSITIONS COMPRISING CDK INHIBITORS AND METHODS FOR THE TREATMENT OF CANCER<br/>[FR] COMPOSÉS ET COMPOSITIONS COMPRENANT DES INHIBITEURS DES CDK ET MÉTHODES DE TRAITEMENT DU CANCER
  申请人：UNIV GEORGIA STATE RES FOUND

  公开号：WO2010129858A1

  公开（公告）日：2010-11-11

  Disclosed herein are compounds suitable for use as antitumor agents, methods for treating cancer wherein the disclosed compounds are used in making a medicament for the treatment of cancer, methods for treating a tumor comprising, administering to a subject a composition comprising one or more of the disclosed cytotoxic agents, and methods for preparing the disclosed antitumor agents.

  本文披露了适用作抗肿瘤药剂的化合物，用于治疗癌症的方法，其中所披露的化合物用于制备治疗癌症的药物，治疗肿瘤的方法包括向受试者施用包含一种或多种所披露的细胞毒性药剂的组合物，以及制备所披露的抗肿瘤药剂的方法。
• [EN] 2-QUINOLONE DERIVED INHIBITORS OF BCL6<br/>[FR] INHIBITEURS DE BCL6 DÉRIVÉS DE 2-QUINOLONE
  申请人：CANCER RESEARCH TECH LTD

  公开号：WO2018215798A1

  公开（公告）日：2018-11-29

  The present invention relates to compounds of formula I that function as inhibitors of BCL6(B- cell lymphoma 6) activity: Formula I wherein X1, X2, X3, R1, R2, R3, R4 and R5 are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer,as well as other diseases or conditions in which BCL6 activity is implicated.

  本发明涉及作为BCL6（B细胞淋巴瘤6）活性抑制剂的I式化合物：式中X1、X2、X3、R1、R2、R3、R4和R5分别如本文所定义。本发明还涉及制备这些化合物的方法，包括含有它们的药物组合物，以及它们在治疗增生性疾病（如癌症）以及其他BCL6活性所涉及的疾病或病况中的用途。
• [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。
• [EN] BRUTON'S TYROSINE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE LA TYROSINE KINASE DE BRUTON
  申请人：PFIZER

  公开号：WO2014068527A1

  公开（公告）日：2014-05-08

  Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (BTK). Methods for the preparation of the compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the BTK inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions. (Formula I)

  本文披露了一种与Bruton's酪氨酸激酶（BTK）形成共价键的化合物。公开了制备这些化合物的方法。还披露了包括这些化合物的药物组合物。公开了使用BTK抑制剂的方法，单独或与其他治疗剂联合治疗自身免疫疾病或症状、异源免疫疾病或症状、癌症，包括淋巴瘤，以及炎症性疾病或症状的方法。 (化学式I)
• CHROMENONE DERIVATIVES
  申请人：BARLAAM Bernard Christophe

  公开号：US20110098271A1

  公开（公告）日：2011-04-28

  The invention concerns chromenone derivatives of Formula I or a pharmaceutically-acceptable salts thereof, wherein each of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , n and R 9 has any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the treatment of cell proliferative disorders.

  这项发明涉及公式I的香豆素衍生物或其药用盐，其中R1、R2、R3、R4、R5、R6、R7、R8、n和R9中的每一个具有在描述中定义的任何含义；它们的制备方法，含有它们的药物组合物以及它们在制造用于治疗细胞增殖紊乱的药物的药物中的使用。