N-(2,2,2-trifluoroethyl)dodecylamine | 70655-36-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-(2,2,2-trifluoroethyl)dodecylamine
• 英文别名: N-dodecyl-2,2,2-trifluoroethylamine；N-(2,2,2-Trifluoroethyl)dodecan-1-amine
• CAS: 70655-36-6
• 化学式: C₁₄H₂₈F₃N
• mdl: MFCD18965163
• 分子量: 267.378
• InChiKey: WCZMBHFMWJVHFE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  18
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (Z)-十八碳-9-烯基氯甲酸酯 、 N-(2,2,2-trifluoroethyl)dodecylamine 在 4-二甲氨基吡啶 作用下， 以 乙醚 为溶剂， 反应 24.0h， 以17%的产率得到N-<(oleyloxy)carbonyl>-N-(2,2,2-trifluoroethyl)dodecylamine
  参考文献：
  名称：

  Selective delivery of cytotoxic compounds to cells by the LDL pathway

  摘要：

  Cancer cells need cholesterol to make new membrane. They get it either by de novo synthesis or from low-density lipoprotein (LDL), or both. Some types of cancer have very high LDL requirements. LDL particles, which circulate in the blood, contain a cholesteryl ester core surrounded by a phospholipid coat containing apoproteins that are recognized by LDL receptors on cell surfaces. After attachment to cells, LDL is endocytosed into lysosomes, where the core is exposed and hydrolyzed. A technique is known whereby LDL can be isolated, its core removed and replaced by a compatible lipophilic substance, and then reconstituted into intact LDL particles that are recognized and internalized by cells in the normal manner. A series of cytotoxic compounds has been synthesized, designed to be compatible with reconstituted LDL, and directed against cancers that copiously internalize LDL. They were evaluated by measuring the toxicity of reconstituted LDL toward test cells bearing LDL receptors. Selectivity was determined by comparison, either with mutant cells with few LDL receptors or with reconstituted methylated LDL (which is not recognized by LDL receptors) on normal cells. Two compounds, 19 and 25, were found that reconstitute well, kill or arrest the test cells at reasonably low concentrations, and are completely selective, suggesting that they are delivered to cells exclusively via the LDL pathway.

  DOI：

  10.1021/jm00374a017
• 作为产物：
  描述：

  N-dodecyl-2,2,2-trifluoroacetamide 在 硼烷 作用下， 以 四氢呋喃 为溶剂， 生成 N-(2,2,2-trifluoroethyl)dodecylamine
  参考文献：
  名称：

  Lysosomotropic agents. 1. Synthesis and cytotoxic action of lysosomotropic detergents

  摘要：

  Amines whose pK values lie between about 5 and 9 are lysosomotropic because lysosomes are acidic intracellular compartments. If such amines bear long hydrophobic chains, they become detergents upon protonation inside the lysosomes, rupturing the lysosomal membrane and killing the cell. Six types of lysosomotropic amines have been prepared that all behave in the expected manner. They are cytotoxic to all lysosome-bearing cells but not red blood cells, which lack lysosomes. Their mode of action, the effect of alkyl chain length on activity, and the fact that their cytotoxic action appears only above a threshhold intracellular concentration support the belief that they behave as lysosomotropic detergents. Among the potential applications is cancer chemotherapy.

  DOI：

  10.1021/jm00195a026

文献信息

• Lysosometropic detergent therapeutic agents
  申请人：Merck & Co., Inc.

  公开号：US04719312A1

  公开（公告）日：1988-01-12

  The present invention is concerned with the preparation of lysosomotropic detergent agents and pharmaceutical composition useful in the treatment of cancer. These compounds are amine derivatives having a pK of 3.5 of the general structure ##STR1## in which R.sub.1 is C.sub.8-30 alkyl, C.sub.8-30 -alkenyl, substituted C.sub.4-30 alkyl or substituted C.sub.4-30 -alkenyl; R.sub.2 is hydrogen or C.sub.1-4 alkyl and Y is an electron withdrawing group, to control the pK, selected from trifluoroethyl, and difluoroethyl.

  本发明涉及制备溶酶体靶向性清洁剂剂和用于癌症治疗的药物组合物。这些化合物是具有pK值为3.5的胺衍生物，其一般结构为##STR1##其中R.sub.1为C.sub.8-30烷基，C.sub.8-30烯基，取代的C.sub.4-30烷基或取代的C.sub.4-30烯基；R.sub.2为氢或C.sub.1-4烷基，Y为电子吸引基，以控制pK值，所选自三氟乙基和二氟乙基。
• Lysosomotropic fluorinated amine therapeutic agents and compositions containing them
  申请人：Merck & Co., Inc.

  公开号：EP0009944A2

  公开（公告）日：1980-04-16

  Compositions useful in the control of fertility, the inhibition of malignant cell growth, and the control of other diseases which accumulate macrophages at the disease site, comprising a pharmaceutical carrier and lysosomotropic substance comprising a weakly basic amine of pK 4.5 to 9 containing at least one hydrophobic substituent or a peptide conjugate hydrolyzable by lysosomal enzymes to a biologically active substance. Certain of the amines, viz. those of formula : in which R is an alkyl substituent of from 8-30 carbon atoms, R is hydrogen or alkyl, and R2 is fluoroloweralkyl of 2-3 carbons, are novel and constitute another embodiment of the present invention. The compositions of the present invention are used to inhibit or alter the function of lysosome-bearing cells.

  可用于控制生育、抑制恶性细胞生长和控制在疾病部位聚集巨噬细胞的其他疾病的组合物，包括药物载体和溶酶体促进物质，溶酶体促进物质包括pK 4.5至9的弱碱性胺，其中含有至少一个疏水取代基，或可被溶酶体酶水解为生物活性物质的肽轭合物。 某些胺，即式中：R为8-30个碳原子的烷基取代基，R为氢或烷基，R2为2-3个碳原子的氟代烷基的胺，是新颖的，构成本发明的另一个实施方案。 本发明的组合物用于抑制或改变含溶酶体细胞的功能。
• Lysosomotropic detergent therapeutic agents, compositions containing them and their uses
  申请人：Merck & Co., Inc.

  公开号：EP0055991A2

  公开（公告）日：1982-07-14

  Compositions useful in the control of fertility, the inhibition of malignant cell growth, and the control of other diseases which accumulate macrophages at the disease site, comprising a pharmaceutical carrier and lysosomotropic substance comprising certain heterocyclic amines having at least one hydrophilic substituent and a pK in the range 4.9 to 9. The compositions of the present invention are used to inhibit or alter the functions of lysosome-bearing cells.

  用于控制生育、抑制恶性细胞生长和控制在疾病部位聚集巨噬细胞的其他疾病的组合物，包括药物载体和溶酶体物质，溶酶体物质包括某些杂环胺，这些杂环胺至少具有一个亲水取代基，pK 在 4.9 至 9 之间。 本发明的组合物用于抑制或改变溶酶体细胞的功能。
• Lysosomotropic agents. 4. Carbobenzoxyglycylphenylalanyl, a new protease-sensitive masking group for introduction into cells
  作者：Raymond A. Firestone、Judith M. Pisano、Philip J. Bailey、Anita Sturm、Robert J. Bonney、Paul Wightman、Richard Devlin、C. Shirley Lin、Doris L. Keller、Patricia C. Tway

  DOI：10.1021/jm00347a012

  日期：1982.5

  Bioactive primary and secondary amines, when acylated with the Z-Gly-Phe group, are transported into pinocytic cells, such as macrophages, P-815 mastocytoma, SV-40 3T3, and leukemia 1210, much faster than the parent compounds. Amines such as lysosomotropic detergents [R. A. Firestone, J. M. Pisano, and R. J. Bonney, J. Med. Chem., 22, 1130 (1979) and nitrogen mustard, which are deactivated by acylation, are unmasked by enzymic action intracellularly, probably in lysosomes because an acidic pH maximum in activity exists which acts only on the L isomer. The added polarity and molecular weight brought about by acylation prevents the amines' normally facile entry into cells by simple diffusion, restricting it to an active-transport mechanism.
• US4719312A
  申请人：——

  公开号：US4719312A

  公开（公告）日：1988-01-12