methyl 2-acetamido-3-(9H-fluoren-2-yl)propanoate | 76932-46-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: methyl 2-acetamido-3-(9H-fluoren-2-yl)propanoate
• CAS: 76932-46-2
• 化学式: C₁₉H₁₉NO₃
• 分子量: 309.365
• InChiKey: QNQABEFVKSQDLM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 2-acetamido-3-(9H-fluoren-2-yl)propanoate 生成 (R)-2-Acetylamino-3-(9H-fluoren-2-yl)-propionic acid methyl ester
  参考文献：
  名称：

  Synthesis and biological activity of some very hydrophobic superagonist analogs of luteinizing hormone-releasing hormone

  摘要：

  The effect of increased hydrophobicity at position 6 of luteinizing hormone-releasing hormone (LH-RH) has been investigated by the incorporation of a series of 15 very hydrophobic, unnatural D-amino acids at this position. The unnatural amino acids studied can be considered analogues of phenylalanine with carbocyclic aromatic side chains consisting of substituted phenyl (e.g., 2,4,6-trimethylphenyl, p-biphenyl) or polycyclic aromatic (e.g., naphthalene, anthracene) units. When enzymatic resolution (subtilisin Carlsberg) of the most hydrophobic amino acids failed, the racemic amino acids were incorporated, and the diastereomeric LH-RH analogues were resolved by preparative high-performance liquid chromatography. The analogues were synthesized by the solid-phase technique. All of the synthetic compounds were very potent LH-RH superagonists, but [6-(3-(2-naphthyl)-D-alanine)]LH-RH, [6-(3-(2-naphthyl)-D-alanine), 7-(N alpha-methylleucine)]LH-RH and [6-(3-(2,4,6-trimethylphenyl)-D-alanine)]LH-RH appear to be among the most potent LH-RH agonist analogues yet reported when tested in a rat estrus cyclicity suppression assay designed to show the paradoxical antifertility effects of these compounds [ED50 approximately 7 x 10(-8) g; twice daily in saline]. These analogues are twice as potent as [D-Trp6,ProNHEt9]LH-RH in this assay system (i.e., approximately 200 times the potency of LH-RH).

  DOI：

  10.1021/jm00349a006
• 作为产物：
  描述：

  acetylamino-fluoren-2-ylmethyl-malonic acid diethyl ester 在 sodium hydroxide 、 三氟化硼乙醚 作用下， 反应 1.0h， 生成 methyl 2-acetamido-3-(9H-fluoren-2-yl)propanoate
  参考文献：
  名称：

  Synthesis and biological activity of some very hydrophobic superagonist analogs of luteinizing hormone-releasing hormone

  摘要：

  The effect of increased hydrophobicity at position 6 of luteinizing hormone-releasing hormone (LH-RH) has been investigated by the incorporation of a series of 15 very hydrophobic, unnatural D-amino acids at this position. The unnatural amino acids studied can be considered analogues of phenylalanine with carbocyclic aromatic side chains consisting of substituted phenyl (e.g., 2,4,6-trimethylphenyl, p-biphenyl) or polycyclic aromatic (e.g., naphthalene, anthracene) units. When enzymatic resolution (subtilisin Carlsberg) of the most hydrophobic amino acids failed, the racemic amino acids were incorporated, and the diastereomeric LH-RH analogues were resolved by preparative high-performance liquid chromatography. The analogues were synthesized by the solid-phase technique. All of the synthetic compounds were very potent LH-RH superagonists, but [6-(3-(2-naphthyl)-D-alanine)]LH-RH, [6-(3-(2-naphthyl)-D-alanine), 7-(N alpha-methylleucine)]LH-RH and [6-(3-(2,4,6-trimethylphenyl)-D-alanine)]LH-RH appear to be among the most potent LH-RH agonist analogues yet reported when tested in a rat estrus cyclicity suppression assay designed to show the paradoxical antifertility effects of these compounds [ED50 approximately 7 x 10(-8) g; twice daily in saline]. These analogues are twice as potent as [D-Trp6,ProNHEt9]LH-RH in this assay system (i.e., approximately 200 times the potency of LH-RH).

  DOI：

  10.1021/jm00349a006

文献信息

• Nonapeptide and decapeptide derivatives of luteinizing hormone releasing hormone, their preparation and pharmaceutical compositions containing them
  申请人：SYNTEX (U.S.A.) INC.

  公开号：EP0021234A1

  公开（公告）日：1981-01-07

  Nonapeptide and decapeptide analogs of LH-RH of the formula (pyro)Glu-His-V-Ser-W-X-Y-Arg-Pro-Z (I) and the pharmaceutically acceptable salt thereof wherein: V is tryptophyl, phenylalanyl or 3-(1-naphthyl)-L-alanyl; W is tyrosyl, phenylalanyl or 3-(1-pentafluorophenyl)-L-alanyl; X is a D-amino acid residue wherein R is (a) a carbocyclic aryl-containing radical selected from the group consisting of naphthyl, anthryl, fluorenyl, phenanthryl, biphenylyl, benzhydryl and phenyl substituted with three or more straight chain lower alkyl groups; or (b) a saturated carbocyclic radical selected from the group consisting of cyclohexyl substituted with three or more straight chain lower alkyl groups, perhydronaphthyl, perhydrobiphenylyl, perhydro-2,2-diphenylmethyl and adamantyl; Y is leucyl, isoleucyl, nor-leucyl or N-methyl-leucyl; Z is glycinamide or-NH-R1, wherein R' is lower alkyl, cycloalkyl, fluoro lower alkyl or wherein R2 is hydrogen or lower alkyl, are disclosed. These compounds exhibit potent LH-RH agonist properties.

  式中的 LH-RH 的非肽和十肽类似物 (焦)Glu-His-V-Ser-W-X-Y-Arg-Pro-Z (I)及其药学上可接受的盐 其中： V 是色氨酰、苯丙氨酰或 3-(1-萘基)-L-丙氨酰； W 是酪氨酰基、苯丙氨酰基或 3-(1-五氟苯基)-L-丙氨酰； X 是 D-氨基酸残基，其中 R 是 (a) 一个含碳环芳基，选自由萘基、蒽基、芴基、菲基、联苯基、苯hydryl 和被三个或三个以上直链低级烷基取代的苯基组成的组；或 (b) 饱和碳环基，选自由三个或三个以上直链低级烷基取代的环己基、全氢萘 基、全氢联苯基、全氢-2,2-二苯基甲基和金刚烷基组成的组； Y 是亮氨酰、异亮氨酰、去亮氨酰或 N-甲基亮氨酰； Z 是甘氨酰胺或-NH-R1，其中 R' 是低级烷基、环烷基、氟低级烷基或 其中 R2 是氢或低级烷基。这些化合物具有强效的 LH-RH 激动剂特性。
• Nonapeptide and decapeptide analogs of LHRH, useful as LHRH antagonists, methods of making them, and their pharmaceutical uses
  申请人：SYNTEX (U.S.A.) INC.

  公开号：EP0049628A2

  公开（公告）日：1982-04-14

  Nonapeptide and decapeptide analogs of LHRH which have the formula and the pharmaceutically acceptable salts thereof, wherein: X is a D-alanyl residue wherein one hydrogen on C-3 is replaced by: a) a carbocyclic aryl-containing radical selected from the group consisting of phenyl substituted with three or more straight chain lower alkyl groups, naphthyl, anthryl, fluorenyl, phenanthryl, biphenylyl and benzhydryl; or b) a saturated carbocyclic radical selected from the group consisting of cyclohexyl substituted with three or more straight chain lower alkyl groups, perhydronaphthyl, perhydrobiphenylyl, perhydro-2,2-diphenylmethyl, and adamantyl; or c) a heterocyclic aryl containing radical selected from the group consisting of radicals represented by the following structural formulas: wherein A" and A' are independently selected from the group consisting of hydrogen, lower alkyl, chlorine, and bromine, and G is selected from the group consisting of oxygen, nitrogen, and sulfur; A is an aminoacyl residue selected from the group consisting of L-pyroglutamyl, D-pyroglutamyl, N-acyl-L-prolyl, N-acyl-D-prolyl, N-acyl-D-tryptophanyl, N-acyl-D-phenylalanyl, N-acyl-D-p-halophenylalanyl, and N-acyl-X wherein X is as defined previously; B is an amino acyl residue selected from the group consisting of D-phenylalanyl, D-p-halophenylalanyl, 2,2-diphenylglycyl, and X wherein X is as defined previously; C is an amino acyl residue selected from the group consisting of L-tryptophanyl, D-tryptophanyl, D-phenylalanyl and X wherein X is as defined above; E is glycinamide or -NH-R1, wherein R1 is lower alkyl, cycloalkyl, fluoro lower alkyl or R2 is hydrogen or lower alkyl; are disclosed. These compounds are LHRH antagonists.

  LHRH 的非肽和十肽类似物，其分子式为 及其药学上可接受的盐类，其中 X是D-丙氨酰残基，其中C-3上的一个氢被下列物质取代 a) 一个含碳环芳基，选自由三个或三个以上直链低级烷基取代的苯基、萘基、蒽基、芴基、菲基、联苯基和二苯基组成的组；或 b) 饱和碳环基，选自由三个或三个以上直链低级烷基取代的环己基、过氢萘基、过氢联苯基、过氢-2,2-二苯基甲基和金刚烷基组成的组；或 c) 杂环芳基，选自由下列结构式所代表的基团组成的组： 其中 A "和 A'独立地选自氢、低级烷基、氯和溴组成的组，G 选自氧、氮和硫组成的组； A 是氨基酰基残基，选自由 L-焦谷氨酰、D-焦谷氨酰、N-酰基-L-脯氨酰、N-酰基-D-脯氨酰、N-酰基-D-色氨酰、N-酰基-D-苯丙氨酰、N-酰基-D-对卤苯丙氨酰和 N-酰基-X 所组成的组，其中 X 如前定义； B 是选自 D-苯丙氨酰、D-对卤代苯丙氨酰、2,2-二苯基甘氨酰和 X 所组成的组的氨基酰基残基，其中 X 如前所定义； C 是氨基酰基残基，选自由 L-色氨酰、D-色氨酰、D-苯丙氨酰和 X 所组成的组，其中 X 如前所定义； E 是甘氨酰胺或-NH-R1，其中 R1 是低级烷基、环烷基、氟低级烷基或-NH-R1。 R2 是氢或低级烷基； 这些化合物是 LHRH 拮抗剂。这些化合物是 LHRH 拮抗剂。
• US4234571A
  申请人：——

  公开号：US4234571A

  公开（公告）日：1980-11-18
• US4341767A
  申请人：——

  公开号：US4341767A

  公开（公告）日：1982-07-27
• US4419347A
  申请人：——

  公开号：US4419347A

  公开（公告）日：1983-12-06