Thomas Richard Ioerger

US Patent:

20100113477, May 6, 2010

Filed:

Oct 20, 2009

Appl. No.:

12/589192

Inventors:

Joel S. Freundlich - Princeton NJ, US
James C. Sacchettini - College Station TX, US
Inna V. Kriger - College Station TX, US
Thomas R. Ioerger - College Station TX, US
Vijay Gawandi - College Station TX, US

International Classification:

A61K 31/192
C07C 59/90
C07C 69/738
C07D 409/04
C07D 233/64
C07D 207/444
C07D 333/24
C07D 213/55
C07D 239/26
C12N 1/20
A61K 31/235
A61K 31/381
A61K 31/4164
A61K 31/40
A61K 31/4402
A61K 31/4409
A61K 31/505
A61P 31/06
A61K 31/496
A61K 31/4965
A61P 31/04
C12Q 1/25
C12N 9/00

US Classification:

51425411, 562463, 560 53, 549 59, 560 11, 5483435, 548549, 549 72, 546314, 544335, 4352521, 514570, 514545, 514444, 514399, 514425, 514448, 514354, 514256, 51425506, 435 4, 435 29, 435183

Abstract:

The present invention provides aryl- or heteroaryl-diketo acid compounds effective to inhibit an activity of a Mycobacterial malate synthase enzyme or to inhibit a malate synthase activity in other bacteria having the enzyme. The compounds may be phenyl-naphthyl-, or thienyl-substituted diketo acids and carboxylate derivatives thereof. Also provided are methods of treating tuberculosis or other pathophysiological conditions associated with a malate synthase enzyme with the inhibitory compounds and methods of in silico design of the inhibitory compounds. In addition, the present invention provides the inhibitory compounds designed by this method. Furthermore, three-dimensional X-ray crystal structures of the Mycobacterial malate synthase complexed with the inhibitory compounds are provided. Further still a method for stabilizing an aromatic or heteroaromatic diketo acid or its prodrug or close analog in solution by derivatizing at least the ortho position on the aromatic ring is provided.

US Patent:

20140171444, Jun 19, 2014

Filed:

Mar 3, 2014

Appl. No.:

14/195146

Inventors:

Joel S. Freundlich - Princeton NJ, US
James C. Sacchettini - College Station TX, US
Inna V. Kriger - College Station TX, US
Thomas R. Ioerger - College Station TX, US
Vijay Gawandi - College Station TX, US

Assignee:

THE TEXAS A&M UNIVERSITY SYSTEM - College Station TX

International Classification:

C07C 59/90
C07C 69/738
A61K 31/235
C07D 333/06
A61K 31/381
C07C 317/46
C07D 233/64
A61K 31/4164
C07D 207/404
A61K 31/4015
C07D 333/22
C07D 333/56
C07D 307/46
A61K 31/341
C07D 307/80
A61K 31/343
C07D 213/50
A61K 31/4402
C07D 239/20
A61K 31/505
A61K 45/06
C12Q 1/527
A61K 31/19

US Classification:

51425411, 562470, 514570, 560 60, 514545, 549 59, 514444, 560 11, 5483415, 514399, 548549, 514425, 549 72, 514448, 549 57, 514443, 549488, 514461, 549468, 514469, 546314, 514354, 544335, 514256, 51425506, 4352531, 435 31

Abstract:

The present invention provides aryl- or heteroaryl-diketo acid compounds effective to inhibit an activity of a Mycobacterial malate synthase enzyme or to inhibit a malate synthase activity in other bacteria having the enzyme. The compounds may be phenyl- naphthyl-, or thienyl-substituted diketo acids and carboxylate derivatives thereof. Also provided are methods of treating tuberculosis or other pathophysiological conditions associated with a malate synthase enzyme with the inhibitory compounds and methods of in silico design of the inhibitory compounds. In addition, the present invention provides the inhibitory compounds designed by this method. Furthermore, three-dimensional X-ray crystal structures of the Mycobacterial malate synthase complexed with the inhibitory compounds are provided. Further still a method for stabilizing an aromatic or heteroaromatic diketo acid or its prodrug or close analog in solution by derivatizing at least the ortho position on the aromatic ring is provided.