(S)-(5-amino-2,3-dihydro-1H-inden-2-yl)carbamic acid methyl ester | 256397-59-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: (S)-(5-amino-2,3-dihydro-1H-inden-2-yl)carbamic acid methyl ester
• 英文别名: (S)-(+)-5-amino-2-[(methoxycarbonyl)amino]-1-indane；(S)-(5-amino-indan-2-yl)-carbamic acid methyl ester；(S)-2-N-carbomethoxy-5-aminoindane；(S)-Methyl 5-amino-2,3-dihydro-1H-inden-2-ylcarbamate；methyl N-[(2S)-5-amino-2,3-dihydro-1H-inden-2-yl]carbamate
• CAS: 256397-59-8
• 化学式: C₁₁H₁₄N₂O₂
• 分子量: 206.244
• InChiKey: OKQRQQGVLMVAKQ-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  64.4
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2924299090

反应信息

• 作为反应物：
  描述：

  (S)-(5-amino-2,3-dihydro-1H-inden-2-yl)carbamic acid methyl ester 在 吡啶 、 碘代三甲硅烷 、 三乙酰氧基硼氢化钠 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 33.0h， 生成 (S)-6-methyl-N-(2-(thiazol-2-ylmethylamino)-2,3-dihydro-1H-inden-5-yl)-4''-(trifluoromethyl)biphenyl-2-carboxamide
  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：

  2-氨基茚 在 palladium on activated charcoal 硫酸 、 氢气 、 硝酸 、 sodium carbonate 作用下， 以 甲醇 、 乙酸甲酯 、 水 、 乙酸酐 、 溶剂黄146 为溶剂， -5.0~25.0 ℃ 、500.0 kPa 条件下， 反应 9.0h， 生成 (S)-(5-amino-2,3-dihydro-1H-inden-2-yl)carbamic acid methyl ester
  参考文献：
  名称：

  Efficient and Practical Syntheses of ( R )‐(5‐Amino‐2,3‐dihydro‐1 H ‐inden‐2‐yl)‐carbamic Acid Methyl Ester

  摘要：

  DOI：

  10.1002/1615-4169(200107)343:5<461::aid-adsc461>3.0.co;2-#

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。
• Amino Acids as a Chiral Pool: Synthesis of (<i>S</i>)‐and (<i>R</i>)‐2‐<i>N</i>‐Carbomethoxy‐5‐aminoindane from (<i>S</i>)‐ and (<i>R</i>)‐Phenylalanines
  作者：Liladhar M. Waykole、Joseph J. McKenna、Andrew Bach、Mahavir Prashad、Oljan Repič、Thomas J. Blacklock

  DOI：10.1080/00397910701226905

  日期：2007.5

  Abstract Enantioselective syntheses of (R)‐and (S)‐2‐N‐carbomethoxy‐5‐aminoindanes from (R)‐ and (S)‐phenylalanines, respectively, are described. A Friedel–Crafts reaction employing N‐carbomethoxy phenylalanine leads to chiral 2‐N‐carbomethoxy‐1‐indanone, which is diastereoselectively reduced to 1‐hydroxy‐2‐N‐carbomethoxyindane. After protection of the hydroxyl group, a regioselective nitration gives

  摘要描述了分别由 (R)- 和 (S)-苯丙氨酸对映选择性合成 (R)- 和 (S)-2-N-carbomethoxy-5-aminoindanes。使用 N-碳甲氧基苯丙氨酸的 Friedel-Crafts 反应生成手性 2-N-碳甲氧基-1-茚满酮，其被非对映选择性还原为 1-羟基-2-N-碳甲氧基茚满。羟基保护后，区域选择性硝化得到 6-硝基茚满中间体，加氢后得到 (R)-或 (S)-2-N-碳甲氧基-5-氨基茚满。
• [EN] N-BENZOCYCLOALKYL-AMIDE DERIVATIVES AND THEIR USE AS MEDICAMENTS<br/>[FR] DERIVES N-BENZOCYCLOALKYL-AMIDE ET LEUR UTILISATION COMME MEDICAMENTS
  申请人：NOVARTIS AG

  公开号：WO2000005201A1

  公开（公告）日：2000-02-03

  A compound of formula (I) or a pharmaceutically acceptable salt thereof; or an enantiomer thereof. Compounds of formula (I) are useful as inhibitors or microsomal triglyceride transfer protein (MTP) and apolipoprotein B (ApoB) secretion and accordingly for the prevention and treatment of MTP and Apo B dependent conditions.

  公式（I）的化合物或其药学上可接受的盐；或其对映体。公式（I）的化合物可用作微粒体甘油三酯转移蛋白（MTP）和载脂蛋白B（ApoB）分泌的抑制剂，因此可用于预防和治疗MTP和ApoB依赖性疾病。
• Diaminoindanes as Microsomal Triglyceride Transfer Protein Inhibitors
  作者：Gary M. Ksander、Reynalda deJesus、Andrew Yuan、Cynthia Fink、Michael Moskal、Eric Carlson、Paivi Kukkola、Natalie Bilci、Eli Wallace、Alan Neubert、David Feldman、Therese Mogelesky、Kevin Poirier、Michael Jeune、Ronald Steele、Jong Wasvery、Zouhair Stephan、Edna Cahill、Randy Webb、Aida Navarrete、Warren Lee、Joyce Gibson、Natalya Alexander、Haamid Sharif、Ashok Hospattankar

  DOI：10.1021/jm010294e

  日期：2001.12.1

  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.
• N-BENZOCYCLOALKYL-AMIDE DERIVATIVES AND THEIR USE AS MEDICAMENTS
  申请人：Novartis AG

  公开号：EP1097129A1

  公开（公告）日：2001-05-09