[1,1'-biphenyl]-2-carboxamide, N-[(2S)-2-amino-2,3-dihydro-1H-inden-5-yl]-6-methyl-4'-(trifluoromethyl)- | 351415-08-2

• 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: [1,1'-biphenyl]-2-carboxamide, N-[(2S)-2-amino-2,3-dihydro-1H-inden-5-yl]-6-methyl-4'-(trifluoromethyl)-
• 英文别名: 6-methyl-4'-trifluoromethyl-biphenyl-2-carboxylic acid ((S)-2-amino-indan-5-yl)-amide；N-[(2S)-2-amino-2,3-dihydro-1H-inden-5-yl]-3-methyl-2-[4-(trifluoromethyl)phenyl]benzamide
• CAS: 351415-08-2
• 化学式: C₂₄H₂₁F₃N₂O
• 分子量: 410.439
• InChiKey: RNNQNFVSJBMSFH-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [1,1'-biphenyl]-2-carboxamide, N-[(2S)-2-amino-2,3-dihydro-1H-inden-5-yl]-6-methyl-4'-(trifluoromethyl)- 在 titanium(IV) isopropylate 、 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 2.5h， 生成 3-methyl-N-[(2S)-2-(1-phenylethylamino)-2,3-dihydro-1H-inden-5-yl]-2-[4-(trifluoromethyl)phenyl]benzamide
  参考文献：
  名称：

  鉴定和邻-联苯羧酰胺作为有效的平滑化拮抗剂抑制刺猬信号通路的结构与活性的关系

  摘要：

  最初作为微粒体甘油三酸酯转移蛋白（MTP）抑制剂制备的邻-联苯羧酰胺已被鉴定为Hedgehog信号通路的新型抑制剂。这类化合物的结构-活性关系研究降低了MTP抑制活性，并导致了低纳摩尔的刺猬抑制剂。结合测定显示该化合物充当平滑剂的拮抗剂，并显示出对人和小鼠受体的交叉反应性。

  DOI：

  10.1016/j.bmcl.2008.11.096
• 作为产物：
  描述：

  [1,1'-biphenyl]-2-carboxylic acid, 6-methyl-4'-(trifluoromethyl)-, methyl ester 在 吡啶 、 sodium hydroxide 、 草酰氯 、 碘代三甲硅烷 、 N,N-二甲基甲酰胺 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 21.25h， 生成 [1,1'-biphenyl]-2-carboxamide, N-[(2S)-2-amino-2,3-dihydro-1H-inden-5-yl]-6-methyl-4'-(trifluoromethyl)-
  参考文献：
  名称：

  Diaminoindanes as Microsomal Triglyceride Transfer Protein Inhibitors

  摘要：

  The synthesis and biological activities of biarylamide-substituted diaminoindanes as microsomal triglyceride transfer protein (MTP) inhibitors are described. One of the more potent compounds, 8aR, inhibited both the secretion of apoB from Hep G2 cells and the MTP-mediated transfer of triglycerides between synthetic acceptor and donor liposomes with IC50 values of 0.7 and 70 nM, respectively. In normolipidemic rats and dogs, oral administration of 8aR dose-dependently reduced both plasma triglycerides and total cholesterol. Moreover, in rats and dogs, 8aR also prevented the postprandial rise in plasma triglycerides following a bolus administration of a fat load. Because MTP inhibitors decrease very low density lipoprotein assembly in the liver, the potential for hepatic lipid accumulation was evaluated. In normolipidemic rats, hepatic cholesterol and triglyceride contents were dose-dependently increased by 8aR. However, hepatic lipid accumulation resulted in negligible change in total liver weight and was reversible after withdrawal of the compound.

  DOI：

  10.1021/jm010294e

文献信息

• Carboxamides useful as inhinitors of microsomal triglyceride transfer protein and of apolipoprotein b secretion
  申请人：——

  公开号：US20030109700A1

  公开（公告）日：2003-06-12

  1 Compounds of formula (1) wherein R 2 —C, R 3 —C, R 4 —C or R 5 —C may be replaced by N; and wherein n is 1, 2 or 3; R 1 is aryl, heteroaryl or (aryl or heteroaryl)-lower alkoxy; R 2 , R 3 , R 4 and R 5 are independently hydrogen, lower alkyl, lower alkoxy, halo, trifluoromethyl or cyano; R 6 is (i) or (ii) m is 1, 2 or 3; R 7 is hydrogen, lower alkyl (aryl or heteroaryl)-lower alkyl, lower alkoxy, (aryl or heteroaryl)-lower alkoxy, hydroxy, oxo, lower alkylenedioxy or lower alkanoyloxy; W is O, S or NR 8 ; R 8 is —COR a , (iii), —COOR d , —SO 2 R e , hydrogen, optionally substituted lower alkyl, aryl, heteroaryl or (aryl or heteroaryl)-lower alkyl; R a , R d and R e , are independently optionally substituted lower alkyl, cycloalkyl, adamantyl, aryl, heteroaryl or (aryl or heteroaryl)-lower alkyl; R b and R c are independently hydrogen, cycloalkyl, optionally substituted lower alkyl, aryl, heteroaryl or (aryl or heteroaryl) lower alkyl; or R b and R c together represent lower alkylene; and pharmaceutically acceptable salts thereof; and enantiomers thereof; which are useful as inhibitors of microsomal triglyceride transfer protein (MTP) and of apolipoprotein B (apoB) secretion.

  式（1）的化合物中，其中R2—C，R3—C，R4—C或R5—C可以被N取代；其中n为1、2或3；R1为芳基，杂环芳基或（芳基或杂环芳基）-较低烷氧基；R2、R3、R4和R5独立地为氢、较低烷基、较低烷氧基、卤素、三氟甲基或氰基；R6为（i）或（ii）m为1、2或3；R7为氢、较低烷基（芳基或杂环芳基）-较低烷基、较低烷氧基、（芳基或杂环芳基）-较低烷氧基、羟基、氧代、较低烷二氧基或较低烷酰氧基；W为O、S或NR8；R8为—CORa、（iii）、—COORd、—SO2Re、氢、可选择取代的较低烷基、芳基、杂环芳基或（芳基或杂环芳基）-较低烷基；Ra、Rd和Re独立地为可选择取代的较低烷基、环烷基、脱氢脂肪基、芳基、杂环芳基或（芳基或杂环芳基）-较低烷基；Rb和Rc独立地为氢、环烷基、可选择取代的较低烷基、芳基、杂环芳基或（芳基或杂环芳基）较低烷基；或Rb和Rc一起代表较低烷基；以及其药学上可接受的盐；以及其对映体；它们可用作微粒体三酰甘油转移蛋白（MTP）和载脂蛋白B（apoB）分泌的抑制剂。
• USE OF BIARYLCARBOXAMIES IN THE TREATMENT OF HEDGEHOG PATHWAY-RELATED DISORDERS
  申请人：Jain Rishi Kumar

  公开号：US20090306149A1

  公开（公告）日：2009-12-10

  The invention provides methods for modulating, e.g., antagonizing, the activity of the Hedgehog signaling pathway. In particular, the invention provides methods for inhibiting aberrant growth states resulting from phenotypes such as Ptc loss-of-function, Hedgehog gain-of-function, smoothened gain-of-function or Gli gain-of-function, comprising contacting a cell with a sufficient amount of a compound of the invention (e.g., a compound of Formula I).

  本发明提供了调节Hedgehog信号通路活性的方法，例如拮抗其活性。特别地，本发明提供了一种方法，用于抑制由Ptc功能丧失、Hedgehog功能增强、smoothened功能增强或Gli功能增强等表型导致的异常生长状态，包括将细胞与本发明的化合物（例如，公式I的化合物）接触，接触量足够即可。
• WO2007/120827
  申请人：——

  公开号：——

  公开（公告）日：——
• CARBOXAMIDES USEFUL AS INHIBITORS OF MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN AND OF APOLIPOPROTEIN B SECRETION
  申请人：Novartis AG

  公开号：EP1259484B1

  公开（公告）日：2005-05-18
• US6878707B2
  申请人：——

  公开号：US6878707B2

  公开（公告）日：2005-04-12