4-甲氧基-n-(2-(三氟甲基)联苯-4-基氨基甲酰)烟酰胺 | 1324003-64-6

• 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: 4-甲氧基-n-(2-(三氟甲基)联苯-4-基氨基甲酰)烟酰胺
• 中文别名: 4-甲氧基-N-[[[[2-三氟甲基][1,1'-联苯]-4-基]氨基]羰基]-3-吡啶甲酰胺
• 英文名称: TC-G1006
• 英文别名: 4-methoxy-N-(2-(trifluoromethyl)biphenyl-4-ylcarbamoyl)nicotinamide；S1P1 Agonist III；4-methoxy-N-[[4-phenyl-3-(trifluoromethyl)phenyl]carbamoyl]pyridine-3-carboxamide
• CAS: 1324003-64-6
• 化学式: C₂₁H₁₆F₃N₃O₃
• 分子量: 415.372
• InChiKey: MLDQTQOMWDNTNN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  80.3
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-(trifluoromethyl)biphenyl-4-amine 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 、 mineral oil 为溶剂， 反应 4.17h， 生成 4-甲氧基-n-(2-(三氟甲基)联苯-4-基氨基甲酰)烟酰胺
  参考文献：
  名称：

  4-Methoxy-N-[2-(trifluoromethyl)biphenyl-4-ylcarbamoyl]nicotinamide: A Potent and Selective Agonist of S1P₁

  摘要：

  The sphingosine-1-phosphate-1 receptor (S1P(1)) and its endogenous ligand sphingosine-1-phosphate (S1P) cooperatively regulate lymphocyte trafficking from the lymphatic system. Herein, we disclose 4-methoxy-N[2-(trifluoromethyl)biphenyl-4-ylcarbamoyl]nicotinamide (8), an uncommon example of a synthetic S1P(1) agonist lacking a polar headgroup, which is shown to effect dramatic reduction of circulating lymphocytes (POC = -78%) in rat 24 h after a single oral dose (1 mg/kg). The excellent potency that 8 exhibits toward S1P(1) (EC50 = 0.035 mu M, 96% efficacy) and the >100-fold selectivity that it displays against receptor subtypes S1P(2-5) suggest that it may serve as a valuable tool to understand the clinical relevance of selective S1P(1) agonism.

  DOI：

  10.1021/ml2001399

文献信息

• Generation of muscle lineage cells and therapeutic uses thereof
  申请人：Genea IP Holdings Pty Ltd

  公开号：US10258628B2

  公开（公告）日：2019-04-16

  Methods and compositions for producing mature myotubes are provided herein. In some instances, the method involves contacting a myoblast in an in vitro culture with a compound, wherein the contacting the myoblast in the in vitro culture with the compound results in generation of mature myotubes or myotube-like cells. In some cases, methods of treatment are provided involving treating a subject with a compound such as a Chk1 inhibitor in order to treat muscle deficiency. The compound may be administered as a stand-alone therapy or in combination with a cell therapy, such as introduction of muscle precursor cells such as satellite cells or myoblasts. Methods for identifying compounds that induce formation of mature myotubes or myotube-like cells from myoblasts are also provided herein, as well as methods of using the identified compounds to treat subjects.

  本文提供了生产成熟肌细胞的方法和组合物。在某些情况下，该方法涉及将体外培养中的肌母细胞与化合物接触，其中将体外培养中的肌母细胞与化合物接触导致产生成熟的肌管或肌管样细胞。在某些情况下，提供的治疗方法涉及用化合物（如 Chk1 抑制剂）治疗受试者，以治疗肌肉缺乏症。该化合物可作为独立疗法给药，也可与细胞疗法结合使用，如引入卫星细胞或肌母细胞等肌肉前体细胞。本文还提供了鉴定诱导从肌母细胞形成成熟肌管或肌管样细胞的化合物的方法，以及使用鉴定出的化合物治疗受试者的方法。
• GENERATION OF MUSCLE LINEAGE CELLS AND THERAPEUTIC USES THEREOF
  申请人：GENEA BIOCELLS USA (HOLDINGS), INC.

  公开号：US20210060024A1

  公开（公告）日：2021-03-04

  Methods and compositions for producing mature myotubes are provided herein. In some instances, the method involves contacting a myoblast in an in vitro culture with a compound, wherein the contacting the myoblast in the in vitro culture with the compound results in generation of mature myotubes or myotube-like cells. In some cases, methods of treatment are provided involving treating a subject with a compound such as a Chk1 inhibitor in order to treat muscle deficiency. The compound may be administered as a stand-alone therapy or in combination with a cell therapy, such as introduction of muscle precursor cells such as satellite cells or myoblasts. Methods for identifying compounds that induce formation of mature myotubes or myotube-like cells from myoblasts are also provided herein, as well as methods of using the identified compounds to treat subjects.
• [EN] IMPROVED GENERATION OF MUSCLE LINEAGE CELLS AND THERAPEUTIC USES THEREOF<br/>[FR] GÉNÉRATION AMÉLIORÉE DE CELLULES DE LIGNÉE MUSCULAIRE ET LEURS UTILISATIONS THÉRAPEUTIQUES
  申请人：GENEA BIOCELLS USA HOLDINGS INC

  公开号：WO2018076060A9

  公开（公告）日：2019-12-19

  [EN] Methods and compositions for producing mature myotubes are provided herein. In some instances, the method involves contacting a myoblast in an in vitro culture with a compound, wherein the contacting the myoblast in the in vitro culture with the compound results in generation of mature myotubes or myotube-like cells. In some cases, methods of treatment are provided involving treating a subject with a compound such as a Chk1 inhibitor in order to treat muscle deficiency. The compound may be administered as a stand-alone therapy or in combination with a cell therapy, such as introduction of muscle precursor cells such as satellite cells or myoblasts. Methods for identifying compounds that induce formation of mature myotubes or myotube-like cells from myoblasts are also provided herein, as well as methods of using the identified compounds to treat subjects.
  [FR] L'invention concerne des procédés et compositions pour produire des myotubes matures. Dans certains exemples, le procédé implique la mise en contact d'un myoblaste dans une culture in vitro avec un composé, la mise en contact du myoblaste dans la culture in vitro avec le composé permettant la génération de cellules de type myotubes ou de myotubes matures. Dans certains cas, l'invention concerne des procédés de traitement impliquant le traitement d'un sujet avec un composé tel qu'un inhibiteur de Chk1 afin de traiter une déficience musculaire. Le composé peut être administré en tant que thérapie autonome ou en combinaison avec une thérapie cellulaire, telle que l'introduction de cellules précurseurs musculaires telles que des cellules satellites ou des myoblastes. L'invention concerne des procédés d'identification de composés qui induisent la formation de cellules de type myotubes ou de myotubes matures à partir de myoblastes, ainsi que des procédés d'utilisation des composés identifiés pour traiter des sujets.
• 4-Methoxy-<i>N</i>-[2-(trifluoromethyl)biphenyl-4-ylcarbamoyl]nicotinamide: A Potent and Selective Agonist of S1P₁
  作者：Lewis D. Pennington、Kelvin K. C. Sham、Alexander J. Pickrell、Paul E. Harrington、Michael J. Frohn、Brian A. Lanman、Anthony B. Reed、Michael D. Croghan、Matthew R. Lee、Han Xu、Michele McElvain、Yang Xu、Xuxia Zhang、Michael Fiorino、Michelle Horner、Henry G. Morrison、Heather A. Arnett、Christopher Fotsch、Min Wong、Victor J. Cee

  DOI：10.1021/ml2001399

  日期：2011.10.13

  The sphingosine-1-phosphate-1 receptor (S1P(1)) and its endogenous ligand sphingosine-1-phosphate (S1P) cooperatively regulate lymphocyte trafficking from the lymphatic system. Herein, we disclose 4-methoxy-N[2-(trifluoromethyl)biphenyl-4-ylcarbamoyl]nicotinamide (8), an uncommon example of a synthetic S1P(1) agonist lacking a polar headgroup, which is shown to effect dramatic reduction of circulating lymphocytes (POC = -78%) in rat 24 h after a single oral dose (1 mg/kg). The excellent potency that 8 exhibits toward S1P(1) (EC50 = 0.035 mu M, 96% efficacy) and the >100-fold selectivity that it displays against receptor subtypes S1P(2-5) suggest that it may serve as a valuable tool to understand the clinical relevance of selective S1P(1) agonism.