IP Library Granted Patent US 10,973,835
Granted Patent B2
US 10,973,835 · App. 15/910,677 · Granted Apr 13, 2021

Boron-containing small molecules for inhibiting activity of a receptor-like protein tyrosine phosphatase

Inventors: Stephen J. Benkovic (State College, PA); Nicholas K. Tonks (Huntington, NY); Chun Yu Liu (Cary, NC); Navasona Krishnan (Cold Spring Harbor, NY); Chunliang Liu (Bellefonte, PA)
Assignees: The Penn State Research Foundation; Cold Spring Harbor Laboratory
A61K31/69C07F5/025C07F5/027
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Quick Facts
Patent No.
US 10,973,835
App. No.
15/910,677
Granted
Apr 13, 2021
Kind
B2
Abstract

A method is disclosed for altering the redox equilibrium of a transmembrane receptor-like protein tyrosine phosphatase (RPTP), particularly a type IIa RPTP, by chemically modulating the activity through contact of such an enzyme with a diaryl boron compound that preferentially reacts with an RPTP in an oxidized state (CyS-OH). This redox modulation is most readily observed and put to use by assaying the inhibition of the phosphatase activity of the RPTP. Such an assay can be carried out on an enzyme in vitro or by contacting the enzyme in a living organism (in vivo). A useful diaryl boron compound corresponds in structure to Formula I in which Ar-1, Ar-2, R 1 , R 2 , R 3 and R 4 are defined within. A pharmaceutical composition containing a useful diaryl boron compound is also disclosed, as are particularly preferred diaryl boron compounds.

Claims (7)

1. A compound of Formula IIIb, wherein R 1 is phenyl and R 2 is a substituent selected from

one or more of the group consisting of halogen, C 1 -C 6 -hydrocarbyl, trifluoromethyl, and nitro, and

wherein the sum of Hammett sigma function values for para and/or meta substituents of the R 1 and R 2 substituents as appropriate is greater than about zero.

2. The compound according to claim 1 , wherein R 2 is halogen.

3. The compound according to claim 1 , wherein said compound has a structural formula shown below

4. A compound of the structural Formula below

5. A compound of the structural Formula below

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 18, 2018
From: TONKS, NICHOLAS K.; KRISHNAN, NAVASONA
To: COLD SPRING HARBOR LABORATORY
Reel/Frame 047220/0373 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 25, 2018
From: BENKOVIC, STEPHEN; LIU, CHUNYU; LIU, CHUNLIANG
To: THE PENN STATE RESEARCH FOUNDATION
Reel/Frame 045632/0530 →
CONFIRMATORY LICENSE Recorded Apr 13, 2018
From: PENNSYLVANIA STATE UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 045587/0793 →
Continuity (2)
Provisional Application 62469081 · Mar 9, 2017
Related Publication 20180258106A1 · Sep 13, 2018