Design, synthesis, antineoplastic activity, and chemical properties of bis(carbamate) derivatives of 4,5-bis(hydroxymethyl)imidazole.

Abstract

A series of bis(carbamate) derivatives of 1,2-substituted 4,5-bis(hydroxymethyl)imidazoles were prepared and evaluated against murine P388 lymphocytic leukemia. Electron-withdrawing substituents at either N-1 or C-2 gave rise to inactive compounds. However, electron-donating substituents gave active compounds and the 2-(methylthio)-1-methyl derivative 2i (carmethizole), as the bis(N-methylcarbamate), was found to be very active. The derivative 2i, referred to by the name carmethizole, was also shown to be active against the MX-1 mammary xenograft, the human amelanotic melanoma cell line (LOX) xenograft, the M5076 sarcoma, and L1210 lymphocytic leukemia. The solution stability, water solubility, pKa, and log P of carmethizole are also reported.

• Authors: W K Anderson, D Bhattacharjee, D M Houston
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 32 Issue 1 Pg. 119-27 (Jan 1989) ISSN: 0022-2623 [Print] United States
• PMID: 2909723 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Carbamates
• Imidazoles
• carmethizole

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, therapeutic use)
• Carbamates (chemical synthesis, therapeutic use)
• Chemical Phenomena
• Chemistry
• Drug Evaluation, Preclinical
• Humans
• Imidazoles (chemical synthesis, therapeutic use)
• Leukemia, Experimental (drug therapy)
• Mammary Neoplasms, Experimental (drug therapy)
• Melanoma, Experimental (drug therapy)
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Structure-Activity Relationship