N,N'-bis(2,2,2-trifluoroethyl)thiourea | 79652-02-1

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫脲类
• 英文名称: N,N'-bis(2,2,2-trifluoroethyl)thiourea
• 英文别名: 1,3-Di(2,2,2-trifluoroethyl)thiourea；1,3-bis(2,2,2-trifluoroethyl)thiourea
• CAS: 79652-02-1
• 化学式: C₅H₆F₆N₂S
• 分子量: 240.172
• InChiKey: UVIZATYHKDOPRJ-UHFFFAOYSA-N

物化性质

• 沸点：
  146.7±50.0 °C(Predicted)
• 密度：
  1.442±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  56.2
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N,N'-bis(2,2,2-trifluoroethyl)thiourea 在 palladium on activated charcoal 氢气 、 三乙胺 、 mercury dichloride 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 15.0h， 生成 N^G,N^G'-bis-(2,2,2-trifluoroethyl-)D-homoarginine toluenesulfonate
  参考文献：
  名称：

  Potent gonadotropin releasing hormone antagonists with low histamine-releasing activity

  摘要：

  The incorporation of Arg residues into position 6 of gonadotropin releasing hormone antagonists had resulted in compounds with increased in vivo potency but also made these analogues potent mast cell degranulators. We have focused on the substitution of position 8 by hArg(R)2 (N(G),N(G)'-dialkylhomoarginine) substitutions, based on the hypotheses that the Arg-Pro sequence is of major importance for this side effect and that shielding of the charge may be an effective way to block degranulation. Analogues in four series were evaluated: (A) [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal-(3)3,6,Arg5,hArg(R)2(8),D-Ala10]GnRH, (B) [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,6,hArg(R)2(5,8),D-Ala10]-GnRH, (C) [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,6,hArg(R)28,D-Ala10]GnRH, (D) [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,D-hArg(R)2(6),hArg(R)2(8),D-Ala10]GnRH. Although substitution by hArg(Et)2, hArg(Bu), hArg(CH2)3, and hArg(CH2CF3)2 was tested, in each series the hArg(Et)2 residue was superior. Two compounds were considered for clinical evaluation: [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,6,hArg(Et)2(8),D-Ala10]GnRH and [N-AC-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,D-hArg(Et)26,hArg-(Et)28,D-Ala10]GnRH (ganirelix acetate). These compounds had high potency for ovulation suppression and low histamine-releasing potency in vitro (ED50 = 0.6,0.29 mug/rat and EC50 = 196, 13 mug/mL, respectively). Ganirelix is currently in Phase II clinical trials and appears to be the most potent GnRH antagonist tested in humans (based upon ED50 for 24-h suppression of testosterone levels).

  DOI：

  10.1021/jm00099a023
• 作为产物：
  描述：

  硫光气 、 2,2,2-三氟乙胺盐酸盐 在 碳酸氢钠 作用下， 以 二氯甲烷 、 水 为溶剂， 以78%的产率得到N,N'-bis(2,2,2-trifluoroethyl)thiourea
  参考文献：
  名称：

  Potent gonadotropin releasing hormone antagonists with low histamine-releasing activity

  摘要：

  The incorporation of Arg residues into position 6 of gonadotropin releasing hormone antagonists had resulted in compounds with increased in vivo potency but also made these analogues potent mast cell degranulators. We have focused on the substitution of position 8 by hArg(R)2 (N(G),N(G)'-dialkylhomoarginine) substitutions, based on the hypotheses that the Arg-Pro sequence is of major importance for this side effect and that shielding of the charge may be an effective way to block degranulation. Analogues in four series were evaluated: (A) [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal-(3)3,6,Arg5,hArg(R)2(8),D-Ala10]GnRH, (B) [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,6,hArg(R)2(5,8),D-Ala10]-GnRH, (C) [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,6,hArg(R)28,D-Ala10]GnRH, (D) [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,D-hArg(R)2(6),hArg(R)2(8),D-Ala10]GnRH. Although substitution by hArg(Et)2, hArg(Bu), hArg(CH2)3, and hArg(CH2CF3)2 was tested, in each series the hArg(Et)2 residue was superior. Two compounds were considered for clinical evaluation: [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,6,hArg(Et)2(8),D-Ala10]GnRH and [N-AC-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,D-hArg(Et)26,hArg-(Et)28,D-Ala10]GnRH (ganirelix acetate). These compounds had high potency for ovulation suppression and low histamine-releasing potency in vitro (ED50 = 0.6,0.29 mug/rat and EC50 = 196, 13 mug/mL, respectively). Ganirelix is currently in Phase II clinical trials and appears to be the most potent GnRH antagonist tested in humans (based upon ED50 for 24-h suppression of testosterone levels).

  DOI：

  10.1021/jm00099a023

文献信息

• Haloguanidine compounds, pharmaceutical compositions and methods of use
  申请人：ICI Americas Inc.

  公开号：US04362728A1

  公开（公告）日：1982-12-07

  Compounds useful for inhibiting gastric acid secretion and for the treatment of peptic ulcers caused or exacerbated by gastric acidity having the following formula (I): ##STR1## in which R.sup.1 and R.sup.2, are H, C.sub.1-10 alkyl, C.sub.3-8 cycloalkyl or cycloalkylalkyl in which the alkyl part is C.sub.1-6 and the cycloalkyl part is C.sub.3-8, each of the alkyl, cycloalkyl and cycloalkylalkyls being optionally substituted by one or more halogens selected from F, Cl and Br, provided that at least one of R.sup.1 and R.sup.2 is a halogen substituted alkyl, cycloalkyl or cycloalkylalkyl and provided that there is no halogen substituent on the carbon directly attached to the nitrogen; and X, m, Y, n and R.sup.3 are as described in the specification; and the pharmaceutically-acceptable acid-addition salts thereof. Processes for producing compounds of formula (I), pharmaceutical compositions containing them, methods of utilizing such compositions and intermediates useful for synthesizing compounds of formula (I) are also described.

  用于抑制胃酸分泌和治疗由胃酸引起或加重的消化性溃疡的化合物具有以下结构式（I）：##STR1##其中R.sup.1和R.sup.2为H，C.sub.1-10烷基，C.sub.3-8环烷基或环烷基烷基，其中烷基部分为C.sub.1-6，环烷基部分为C.sub.3-8，每个烷基，环烷基和环烷基烷基可选择地被来自F、Cl和Br的一个或多个卤素取代，前提是R.sup.1和R.sup.2中至少有一个是卤素取代的烷基，环烷基或环烷基烷基，并且直接连接到氮的碳上没有卤素取代物；X，m，Y，n和R.sup.3如规范中所述；以及其药用可接受的酸加盐。还描述了制备结构式（I）化合物的方法，含有它们的药物组合物，利用这种组合物的方法以及用于合成结构式（I）化合物的中间体。
• Haloguanidine intermediates
  申请人：Imperial Chemical Industries, Ltd.

  公开号：US04762932A1

  公开（公告）日：1988-08-09

  Compounds useful for inhibiting gastric acid secretion and for the treatment of peptic ulcers caused or exacerbated by gastric acidity having the following formula (I): ##STR1## in which R.sup.1 and R.sup.2, are H, C.sub.1-10 alkyl, C.sub.3-8 cycloalkyl or cycloalkylalkyl in which the alkyl part is C.sub.1-6 and the cycloalkyl part is C.sub.3-8, each of the alkyl, cycloalkyl and cycloalkylalkyls being optionally substituted by one or more halogens selected from F, Cl and Br, provided that at least one of R.sup.1 and R.sup.2 is a halogen substituted alkyl, cycloalkyl or cycloalkylalkyl and provided that there is no halogen substituent on the carbon directly attached to the nitrogen; and X, m, Y, n and R.sup.3 are as described in the specification; and the pharmaceutically-acceptable acid-addition salts thereof. Processes for producing compounds of formula (I), pharmaceutical compositions containing them, methods of utilizing such compositions and intermediates useful for synthesizing compounds of formula (I) are also described.

  用于抑制胃酸分泌和治疗由胃酸引起或加重的消化性溃疡的化合物具有以下式(I)的结构：##STR1## 其中R.sup.1和R.sup.2是H、C.sub.1-10烷基、C.sub.3-8环烷基或环烷基烷基，其中烷基部分为C.sub.1-6，环烷基部分为C.sub.3-8，每个烷基、环烷基和环烷基烷基可选择地被一种或多种来自F、Cl和Br的卤素取代，前提是R.sup.1和R.sup.2中至少有一个是卤素取代的烷基、环烷基或环烷基烷基，并且直接连接到氮的碳上没有卤素取代基；而X、m、Y、n和R.sup.3如说明书所述；以及其药学上可接受的酸加成盐。还描述了制备式(I)化合物的方法、含有它们的药物组合物、利用这样的组合物的方法和合成式(I)化合物的有用中间体。
• Intramolecular van der Waals attraction. Conformational analysis of di(primary alkyl) derivatives of five- and six-membered heterocyclic systems
  作者：Ulf Berg、Ingrid Pettersson

  DOI：10.1021/jo00232a022

  日期：1987.11
• BERG, ULF;PETTERSSON, INGRID, J. ORG. CHEM., 52,(1987) N 23, 5177-5184
  作者：BERG, ULF、PETTERSSON, INGRID

  DOI：——

  日期：——
• Potent gonadotropin releasing hormone antagonists with low histamine-releasing activity
  作者：John J. Nestor、Ram Tahilramani、Teresa L. Ho、Jessie C. Goodpasture、Brian H. Vickery、Pierre Ferrandon

  DOI：10.1021/jm00099a023

  日期：1992.10

  The incorporation of Arg residues into position 6 of gonadotropin releasing hormone antagonists had resulted in compounds with increased in vivo potency but also made these analogues potent mast cell degranulators. We have focused on the substitution of position 8 by hArg(R)2 (N(G),N(G)'-dialkylhomoarginine) substitutions, based on the hypotheses that the Arg-Pro sequence is of major importance for this side effect and that shielding of the charge may be an effective way to block degranulation. Analogues in four series were evaluated: (A) [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal-(3)3,6,Arg5,hArg(R)2(8),D-Ala10]GnRH, (B) [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,6,hArg(R)2(5,8),D-Ala10]-GnRH, (C) [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,6,hArg(R)28,D-Ala10]GnRH, (D) [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,D-hArg(R)2(6),hArg(R)2(8),D-Ala10]GnRH. Although substitution by hArg(Et)2, hArg(Bu), hArg(CH2)3, and hArg(CH2CF3)2 was tested, in each series the hArg(Et)2 residue was superior. Two compounds were considered for clinical evaluation: [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,6,hArg(Et)2(8),D-Ala10]GnRH and [N-AC-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,D-hArg(Et)26,hArg-(Et)28,D-Ala10]GnRH (ganirelix acetate). These compounds had high potency for ovulation suppression and low histamine-releasing potency in vitro (ED50 = 0.6,0.29 mug/rat and EC50 = 196, 13 mug/mL, respectively). Ganirelix is currently in Phase II clinical trials and appears to be the most potent GnRH antagonist tested in humans (based upon ED50 for 24-h suppression of testosterone levels).