The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.

The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.

Date of Patent:
Feb. 25, 2025

Filed:

Dec. 16, 2022
Applicant:

The Board of Trustees of the University of Illinois, Urbana, IL (US);

Inventors:

Paul J. Hergenrother, Champaign, IL (US);

Timothy M. Fan, Mahomet, IL (US);

Riley L. Svec, Urbana, IL (US);

Attorneys:
Primary Examiner:
Int. Cl.
CPC ...
A61K 31/519 (2006.01); A61K 9/20 (2006.01); A61K 9/48 (2006.01); A61K 31/495 (2006.01); A61K 47/02 (2006.01); A61K 47/24 (2006.01); A61K 47/26 (2006.01); A61K 47/34 (2017.01); A61K 47/36 (2006.01); C07D 487/04 (2006.01);
U.S. Cl.
CPC ...
C07D 487/04 (2013.01); A61K 9/2009 (2013.01); A61K 9/2013 (2013.01); A61K 9/2018 (2013.01); A61K 9/2027 (2013.01); A61K 9/2054 (2013.01); A61K 9/2059 (2013.01); A61K 9/485 (2013.01); A61K 9/4858 (2013.01); A61K 9/4866 (2013.01); A61K 31/495 (2013.01); A61K 47/02 (2013.01); A61K 47/24 (2013.01); A61K 47/26 (2013.01); A61K 47/34 (2013.01); A61K 47/36 (2013.01);
Abstract

New synthetic methods to provide access to previously unexplored functionality at the C8 position of substituted imidazo[5,1-d][1,2,3,5]tetrazines of Formula I. Through synthesis and evaluation of a suite of compounds with a range of aqueous stabilities (from 0.5 to 40 hours), a predictive model for imidazotetrazine hydrolytic stability based on the Hammett constant of the C8 substituent was derived. Promising compounds were identified that possess activity against a panel of GBM cell lines, appropriate hydrolytic and metabolic stability, and brain-to-serum ratios dramatically elevated relative to TMZ, leading to lower hematological toxicity profiles and superior activity to TMZ in a mouse model of GBM.


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