256934-83-5

Upstream product

• 91634-11-6 N-methyl-5-cyanoindole 
• 256935-68-9 (1S)-2-amino-1-(3,4,5-trimethoxyphenyl)ethanol 
• 128742-76-7 methyl 1-methyl-1H-indole-5-carboxylate 
• 256935-67-8 (1S)-2-azido-1-(3,4,5-trimethoxyphenyl)ethanol 
• 177329-70-3 (S)-1-(3,4,5-trimethoxyphenyl)-2-(p-toluenesulfonyloxy)ethanol 
• 177329-69-0 (S)-1-(3,4,5-trimethoxyphenyl)-1,2-ethanediol 
• 13400-02-7 3,4,5-trimethoxy styrene 
• 186129-25-9 1-methyl-1H-indole-5-carboxylic acid 

Relevant academic research and scientific papers

Synthesis and biological evaluation of 2-Indolyloxazolines as a new class of tubulin polymerization inhibitors. Discovery of A-289099 as an orally active antitumor agent

A series of indole containing oxazolines has been discovered as a result of structural modifications of the lead compound A-105972. The compounds exert their anticancer activity through inhibition of tubulin polymerization by binding at the colchicine site. A-289099 was identified as an orally active antimitotic agent active against various cancer cell lines including those that express the MDR phenotype. The anticancer activity, pharmacokinetics, and an efficient and enantioselective synthesis of A-289099 are described.

New antimitotic agents with activity in multi-drug-resistant cell lines and in vivo efficacy in murine tumor models

During a screen for compounds that could inhibit cell proliferation, a series of new tubulin-binding compounds was identified with the discovery of oxadiazoline 1 (A-105972). This compound showed good cytotoxic activity against non-multi-drug-resistant and multi-drug-resistant cancer cell lines, but its utility in vivo was limited by a short half-life. Medicinal chemistry efforts led to the discovery of indolyloxazoline 22g (A-259745), which maintained all of the in vitro activity seen with oxadiazoline 1, but also demonstrated a better pharmacokinetic profile, and dose-dependent in vivo activity. Over a 28 day study, indolyloxazoline 22g increased the life span of tumor-implanted mice by up to a factor of 3 upon oral dosing. This compound, and others of its structural class, may prove to be useful in the development of new chemotherapeutic agents to treat human cancers.