4-((2-methylphenyl)thio)-3-(trifluoromethyl)nitrobenzene | 21726-41-0

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 4-((2-methylphenyl)thio)-3-(trifluoromethyl)nitrobenzene
• 英文别名: 4-[(2-methylphenyl)thio]-3-(trifluoromethyl)nitrobenzene；1-(2-Methylphenyl)sulfanyl-4-nitro-2-(trifluoromethyl)benzene
• CAS: 21726-41-0
• 化学式: C₁₄H₁₀F₃NO₂S
• 分子量: 313.3
• InChiKey: LNLJAEUMRDSCSV-UHFFFAOYSA-N

物化性质

• 沸点：
  134-138 °C(Press: 0.05 Torr)
• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-((2-methylphenyl)thio)-3-(trifluoromethyl)nitrobenzene 在 盐酸 、 tin(ll) chloride 作用下， 以 乙醇 为溶剂， 以96%的产率得到4-(2-Methylphenyl)sulfanyl-3-(trifluoromethyl)aniline
  参考文献：
  名称：

  Structure-Based Design of Substituted Diphenyl Sulfones and Sulfoxides as Lipophilic Inhibitors of Thymidylate Synthase

  摘要：

  Six new diphenyl sulfoxide and five new diphenyl sulfones were designed, synthesized, and tested for their inhibition of human and Escherichia coli thymidylate synthase (TS) and of the growth of cells in tissue culture. The best sulfoxide inhibitor of human TS was 3-chloro-N-((3,4-dihydro-2-methyl-4-oxo-6-quinazolinyl)methyl)-4-(phenylsulfinyl)-N-(prop-2-ynyl)-aniline (7c) that had a K-i of 27 nM. No sulfone improved on TS inhibition by the previously reported 4-(N-((3,4-dihydro-2-methyl-6-quinazolinyl)methyl)-N-prop-2-ynylamino)phenyl phenyl sulfone (K-i = 12 nM). Nevertheless, one sulfone, 4-((2-chlorophenyl)sulfonyl)-N-((3,4-dihydro-2-methyl-4-oxo-6-quinazolinyl)methyl)-N-(prop-2-ynyl)analine, was selected, on the basis of its inhibition of both TS and cell growth, for antitumor testing; it gave a 61% increase in life span to mice bearing the thymidine kinase-deficient L5178Y (TK-) lymphoma. A crystal structure of N-((3,4-dihydro-2-methyl-4-oxo-6-quinazolinyl)methyl)-4-((2-methylphenyl)sulfinyl)-N-(prop-2-ynyl)aniline complexed with E. coli TS was solved and revealed selective binding of one sulfoxide enantiomer. AMBER calculations showed that the enantioselection was due to asymmetric electrostatic effects at the mouth of the active site. In contrast, a similar crystal structure of the sulfoxide 7c, along with AMBER calculations, indicated that both enantiomers bound, but with different affinities. The side chain of Phe176 shifted in order to structurally accommodate the chlorine of the more weakly bound enantiomer.

  DOI：

  10.1021/jm960613f
• 作为产物：
  描述：

  2-氟-5-硝基三氟甲苯 、 2-巯基甲苯 在 sodium hydride 作用下， 生成 4-((2-methylphenyl)thio)-3-(trifluoromethyl)nitrobenzene
  参考文献：
  名称：

  Structure-Based Design of Substituted Diphenyl Sulfones and Sulfoxides as Lipophilic Inhibitors of Thymidylate Synthase

  摘要：

  Six new diphenyl sulfoxide and five new diphenyl sulfones were designed, synthesized, and tested for their inhibition of human and Escherichia coli thymidylate synthase (TS) and of the growth of cells in tissue culture. The best sulfoxide inhibitor of human TS was 3-chloro-N-((3,4-dihydro-2-methyl-4-oxo-6-quinazolinyl)methyl)-4-(phenylsulfinyl)-N-(prop-2-ynyl)-aniline (7c) that had a K-i of 27 nM. No sulfone improved on TS inhibition by the previously reported 4-(N-((3,4-dihydro-2-methyl-6-quinazolinyl)methyl)-N-prop-2-ynylamino)phenyl phenyl sulfone (K-i = 12 nM). Nevertheless, one sulfone, 4-((2-chlorophenyl)sulfonyl)-N-((3,4-dihydro-2-methyl-4-oxo-6-quinazolinyl)methyl)-N-(prop-2-ynyl)analine, was selected, on the basis of its inhibition of both TS and cell growth, for antitumor testing; it gave a 61% increase in life span to mice bearing the thymidine kinase-deficient L5178Y (TK-) lymphoma. A crystal structure of N-((3,4-dihydro-2-methyl-4-oxo-6-quinazolinyl)methyl)-4-((2-methylphenyl)sulfinyl)-N-(prop-2-ynyl)aniline complexed with E. coli TS was solved and revealed selective binding of one sulfoxide enantiomer. AMBER calculations showed that the enantioselection was due to asymmetric electrostatic effects at the mouth of the active site. In contrast, a similar crystal structure of the sulfoxide 7c, along with AMBER calculations, indicated that both enantiomers bound, but with different affinities. The side chain of Phe176 shifted in order to structurally accommodate the chlorine of the more weakly bound enantiomer.

  DOI：

  10.1021/jm960613f

文献信息

• Structure-Based Design of Substituted Diphenyl Sulfones and Sulfoxides as Lipophilic Inhibitors of Thymidylate Synthase
  作者：Terence R. Jones、Stephen E. Webber、Michael D. Varney、M. Rami Reddy、Kathleen K. Lewis、Vinit Kathardekar、Hormoz Mazdiyasni、Judith Deal、Dzuy Nguyen、Katharine M. Welsh、Stephanie Webber、Amanda Johnston、David A. Matthews、Ward W. Smith、Cheryl A. Janson、Russell J. Bacquet、Eleanor F. Howland、Carol L. J. Booth、Steven M. Herrmann、Robert W. Ward、Jennifer White、Charlotte A. Bartlett、Cathy A. Morse

  DOI：10.1021/jm960613f

  日期：1997.2.1

  Six new diphenyl sulfoxide and five new diphenyl sulfones were designed, synthesized, and tested for their inhibition of human and Escherichia coli thymidylate synthase (TS) and of the growth of cells in tissue culture. The best sulfoxide inhibitor of human TS was 3-chloro-N-((3,4-dihydro-2-methyl-4-oxo-6-quinazolinyl)methyl)-4-(phenylsulfinyl)-N-(prop-2-ynyl)-aniline (7c) that had a K-i of 27 nM. No sulfone improved on TS inhibition by the previously reported 4-(N-((3,4-dihydro-2-methyl-6-quinazolinyl)methyl)-N-prop-2-ynylamino)phenyl phenyl sulfone (K-i = 12 nM). Nevertheless, one sulfone, 4-((2-chlorophenyl)sulfonyl)-N-((3,4-dihydro-2-methyl-4-oxo-6-quinazolinyl)methyl)-N-(prop-2-ynyl)analine, was selected, on the basis of its inhibition of both TS and cell growth, for antitumor testing; it gave a 61% increase in life span to mice bearing the thymidine kinase-deficient L5178Y (TK-) lymphoma. A crystal structure of N-((3,4-dihydro-2-methyl-4-oxo-6-quinazolinyl)methyl)-4-((2-methylphenyl)sulfinyl)-N-(prop-2-ynyl)aniline complexed with E. coli TS was solved and revealed selective binding of one sulfoxide enantiomer. AMBER calculations showed that the enantioselection was due to asymmetric electrostatic effects at the mouth of the active site. In contrast, a similar crystal structure of the sulfoxide 7c, along with AMBER calculations, indicated that both enantiomers bound, but with different affinities. The side chain of Phe176 shifted in order to structurally accommodate the chlorine of the more weakly bound enantiomer.