Process for Preparing Functionalized Oxazole Based Pharmaceutical Agents...

Title: Process for Preparing Functionalized Oxazole Based Pharmaceutical Agents Having Anti-Cancer Activities

Tech ID: 08-007

Inventors: Marvin Miller, Garrett Moraski

Date Added: August 7, 2020

Overview

Anti-cancer agents that prevent cell proliferation for select cancer cell lines.

Technology Summary

Microtubules, composed of ⍺-tubulin and ß-tubulin heterodimers, are among the most successful molecular targets in the design of anticancer drugs. Even the slightest disturbance of the microtubule dynamics can arrest the cell cycle at mitosis and lead to cell death, therefore preventing uncontrolled cell division. Many antimitotic drugs have proven to be successful but are less effective due to neurotoxicity and drug resistance. Some compounds have been synthesized in an attempt to limit these side effects, but few have shown promising results during clinical trials and have a narrow therapeutic window. A successful antimicrotubule agent that has a larger therapeutic window and reduces toxic side effects could provide more effective treatment options for patients.

Researchers at the University of Notre Dame and Montana State University have developed a new class of novel, low molecular weight anticancer agents which are potent inhibitors against select cancer cell lines particularly leukemia, breast, and colon cancer cell lines. The agents are composed of heterocyclic compounds and functionalized oxazoles which have shown to halt the proliferation of cancer cells arresting cell division in the G2 phase which has been used to improve the cytotoxicity of known agents. Notre Dame and Montana State University researchers have identified and synthesized two compounds in particular that have anti-proliferative activity. Compound 13e (which was the result of the discovery of 4e) not only provides strong antimicrotubule activity, but also antitumor activity which reduces proliferation. These compounds are simple to prepare which would allow for rapid structure-activity-relationship (SAR) determination and identification of potential lead molecules. In addition, these compounds have shown reduced toxicity in normal cell lines, and have shown anti-mitotic ability in leukemia, cervical, and breast cancer cell lines. These compounds work by an anti-cancer mechanism of action different from Taxol and more like Nocodazole. These compounds are successful antimitotic agents and eliminate the neurotoxic and drug resistant side effects due to their novel ability to inhibit proliferation of cancer cells.

Market Advantages

• Reduced side effects, lower toxicity
• Easy and cost effective to synthesize and manufacture
• Lead compound inhibited 63% tumor growth of human colorectal cancer in in vitro studies

Applications

3 oncology applications:

• Breast cancer
• Colon Cancer
• Leukemia

Technology Readiness Level

TRL 4 – Lab Validation

Intellectual Property Status

US Patent 8,268,874

Publications

N-((1-Benzyl-1H-1,2,3-triazol-4-yl)methyl)arylamide as a New Scaffold that Provides Rapid Access to Antimicrotubule Agents: Synthesis and Evaluation of Antiproliferative Activity Against Select Cancer Cell Lines. doi: 10.1021/jm1000979

Contact

Richard Cox

rcox4@nd.edu

574.631.5158