bis-(2-chloro-ethyl)-carbamic acid methyl ester | 35875-89-9

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: bis-(2-chloro-ethyl)-carbamic acid methyl ester
• 英文别名: Bis-(2-chlor-aethyl)-carbamidsaeure-methylester；N,N-bis-(2-chloroethyl)-carbamic acid methyl ester；Bis-<2-chlor-ethyl>-carbamidsaeure-methylester；methyl N,N-bis(2-chloroethyl)carbamate
• CAS: 35875-89-9
• 化学式: C₆H₁₁Cl₂NO₂
• 分子量: 200.065
• InChiKey: BCQUWJXVBOGPCJ-UHFFFAOYSA-N

物化性质

• 沸点：
  87 °C(Press: 0.2 Torr)
• 密度：
  1.266 g/cm3(Temp: 24 °C)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  11
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  bis-(2-chloro-ethyl)-carbamic acid methyl ester 、 [1,1'-biphenyl]-2-carboxamide, N-[(2S)-2-amino-2,3-dihydro-1H-inden-5-yl]-6-methyl-4'-(trifluoromethyl)- 在 N,N-二异丙基乙胺 作用下， 反应 3.0h， 生成 methyl 4-[(2S)-5-[[3-methyl-2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-2,3-dihydro-1H-inden-2-yl]piperazine-1-carboxylate
  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
• 作为产物：
  描述：

  二(2-氯乙基)胺盐酸盐 、 氯甲酸甲酯 以 二氯甲烷 为溶剂， 生成 bis-(2-chloro-ethyl)-carbamic acid methyl ester
  参考文献：
  名称：

  Carboxamides useful as inhinitors of microsomal triglyceride transfer protein and of apolipoprotein b secretion

  摘要：

  式（1）的化合物，其中R2-C，R3-C，R4-C或R5-C可被N替换;其中n为1，2或3; R1为芳基，杂环芳基或（芳基或杂环芳基）-低烷氧基; R2，R3，R4和R5独立地为氢，低烷基，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，低烷基（芳基或杂环芳基）-低烷基，低烷氧基，（芳基或杂环芳基）-低烷氧基，羟基，氧代，低烷基二氧基或低烷酰氧基; W为O，S或NR8; R8为—CORa，（iii），—COORd，—SO2Re，氢，可选地取代的低烷基，芳基，杂环芳基或（芳基或杂环芳基）-低烷基; Ra，Rd和Re独立地为可选地取代的低烷基，环烷基，金刚烷基，芳基，杂环芳基或（芳基或杂环芳基）-低烷基; Rb和Rc独立地为氢，环烷基，可选地取代的低烷基，芳基，杂环芳基或（芳基或杂环芳基）低烷基; 或Rb和Rc一起表示低烷基;以及其药学上可接受的盐;和对映体;它们是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。

  公开号：

  US20030109700A1

文献信息

• Carboxamides useful as inhibitors of microsomal triglyceride transfer protein and of apolipoprotein b secretion
  申请人：Ksander Gary Michael

  公开号：US06878707B2

  公开（公告）日：2005-04-12

  Compounds of formula (I) 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.

  化合物的公式（I），其中R2-C，R3-C，R4-C或R5-C可以被N替换;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、可选择性取代的较低烷基、芳基、杂环芳基或（芳基或杂环芳基）-较低烷基; Ra、Rd和Re独立地为可选择性取代的较低烷基、环烷基、金刚烷基、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、可选择性取代的较低烷基、芳基、杂环芳基或（芳基或杂环芳基）较低烷基;或Rb和Rc共同代表较低烷基;以及其药学上可接受的盐;和其对映异构体;这些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。
• Childs et al., Journal of the Chemical Society, 1948, p. 2175
  作者：Childs et al.

  DOI：——

  日期：——
• Bercot,P., Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1964, vol. 258, p. 224 - 226
  作者：Bercot,P.

  DOI：——

  日期：——
• ANGELINI, G.;SPERANZA, M.;WOLF, A. P.;SHIUE, C. -Y., J. LABELL. COMPOUNDS AND RADIOPHARM., 28,(1990) N2, C. 1441-1448
  作者：ANGELINI, G.、SPERANZA, M.、WOLF, A. P.、SHIUE, C. -Y.

  DOI：——

  日期：——
• 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