Etopside analogs

• US 5,332,811 A
• Filed: 05/01/1991
• Issued: 07/26/1994
• Est. Priority Date: 09/12/1989
• Status: Expired due to Term

• Current Assignee: University of South Carolina
• Original Assignee: University of North Carolina At Chapel Hill (University of North Carolina System)
• Inventors: Chang, Jang-Yang, Shen, Ya-Ching, Han, Fu-Shen, Wang, Zhe-Qing, Zhou, Xiao-Ming, Chen, Hong-Xing, Cheng, Yung-Chi, Lee, Kuo-Hsiung, Hu, Hong, Zhang, Yi-Lin
• Primary Examiner(s): Ivy, C. Warren
• Assistant Examiner(s): Trinh, Ba K.
• Application Number:
  US07/693,300
• Time in Patent Office: 1,182 Days
• Field of Search: 549/298, 514/232.5, 514/253, 514/338, 514/463, 514/468, 544/148, 544/378, 546/174, 546/197, 546/270
• US Class Current: 544/148
• CPC Class Codes: C07D 493/04 Ortho-condensed systems

Abstract

Compounds which are analogs of etoposide and which exhibit anti-tumor activity are disclosed. These compounds having the following structure: ##STR1## wherein R is selected from ##STR2## wherein R₁, R₂, R₃, R₄ and R₅ are each independently selected from H, CH₃, C₂ H₅, C₃ H₇, i--C₃ H₇, C₄ H₉, CF₃, OCH₃, OC₂ H₅ , OC₃ H₇, OC₄ H₉, O--i--C₃ H₇, O--i--C₄ H₉, --OCH₂ O--, --OCH₂ CH₂ O--, CH₂ OH, C₂ H₄ OH, CH₂ Cl C₂ H₄ Cl, CH₂ F, C₂ H₄ F, CH₂ OCH₃, COCH₃, COC₂ H₅, CO₂ CH₃, CO₂ C₂ H₅, NO₂, NH₂, NH₂.HCl, NH₂.HAc, NH₂.1/2H₂ SO₄ , NH₂.1/3H₃ PO₄, N(CH₃)₂, N(C₂ H₅)₂, OH, CN, N₃, SO₂ H, SO₂ NH₂ , SO₂ Cl, phenyl, substituted phenyl, phenoxy, substituted phenoxy, anilinyl, substituted anilinyl, cyclohexyl, piperidine, ##STR3## wherein R₆ is selected from hydrogen, methyl, ethyl, n-propyl, i-propyl, butyl and bridged methylene;

wherein R₇ is selected from ##STR4##

Claims

1. A compound having the formula II:

wherein R is ##STR76## wherein R₁, R₂, R₃, R₄ and R₅ are each independently selected from H, CH₃, C₂ H₅, C₃ H₇, i--C₃ H₇, C₄ H₉, CF₃, OCH₃, OC₂ H₅, OC₃ H₇, OC₄ H₉, O--i--C₃ H₇, O--i--C₄ H₉, --OCH₂ O--, --OCH₂ CH₂ O--, CH₂ OH, C₂ H₄ OH, CH₂ Cl C₂ H₄ Cl, CH₂ F, C₂ H₄ F, CH₂ OCH₃, COCH₃, COC₂ H₅, CO₂ CH₃, CO₂ C₂ H₅, NO₂, NH₂, NH₂.HCl, NH₂.HAc, NH₂.1/2H₂ SO₄, NH₂.1/3H₃ PO₄, N(CH₃)₂, N(C₂ H₅)₂, OH, CN, N₃, SO₂ H, SO₂ NH₂, SO₂ Cl, phenyl, phenoxy, anilinyl, cyclohexyl, piperidine, ##STR77##

2. A compound according to claim 1, wherein R is selected from benzylamino, 4"-nitrobenzylamino, 3"-nitrobenzylamino, 2"-nitrobenzylamino, 2"-fluorobenzylamino, 3"-fluorobenzylamino, 4"-fluorobenzylamino, 3"-cyanobenzylamino, 4"-cyanobenzylamino, 3",5"-dimethoxybenzylamino, 3"-aminobenzylamino, and 2"-aminobenzylamino.

3. A compound according to claim 1, wherein R is selected from 3"-fluorobenzylamino, 3"-cyanobenzylamino and 4"-cyanobenzylamino.

4. A pharmaceutical composition comprising a compound as claimed in claim 1 and a pharmaceutically acceptable carrier.