Reata Pharmaceuticals, Inc.

Washington University

The University of Texas System

Reata Pharmaceuticals Holdings, LLC

Abbvie Inc.

Xin Jiang

Melean Visnick

Eric Anderson

Christopher F Bender

Gary Louis Bolton

Bradley W Caprathe

Chitase Lee

Xiaofeng Liu

William Howard Roark

Stephen S Szucs

Jack Greiner

Patrick Michael O'Brien

Douglas F Covey

Martha R Hotema

Robert M Kral, Jr

Deborah A Ferguson

Lester L Maravetz

Melanie Janelle Bevill

Jared Peters Smit

Christopher Scott Seadeek

John Allen Walling

Zachary S Sheldon

Haizhou Sun

Rolf Wagner

Allan C Krueger

Jef K De Brabander

Pamela L Donner

David J Grampovnik

Hui-Ju J Chen

Howard Robin Heyman

Jason P Shanley

Brian Edward Kornberg

Michael J Rozema

Jef De Brabander

Bo Liu

Christopher Bender

Ha Do

Brian Kornberg

David Grampovnik

Howard Heyman

Jason Shanley

Bradley William Caprathe

Jared P Smit

Melanie J Bevill

Christopher S Seadeek

Michael Rozema

Pamela Donner

Patrick M O'brien

Allan Krueger

William Roark

This invention provides, but is not limited to, novel oleanolic acid derivatives having the formula: wherein the variables are defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such compounds, methods and intermediates useful for making the compounds, and methods of using the compounds and compositions.

Antioxidant inflammation modulators: oleanolic acid derivatives with amino and other modifications at C-17

Disclosed herein are compounds of the formula: wherein the variables are defined herein. Also provided are pharmaceutical compositions thereof. In some aspects, the compounds and compositions provided herein may be used as antioxidant inflammation modulators. In some aspects, the present disclosure provides methods wherein the compounds and composition described herein are used for the treatment of diseases and disorders, including those associated with inflammation and cancer.

C17 polar-substituted heteroaromatic synthetic triterpenoids and methods of use thereof

Disclosed herein are compounds of the formulas: as well as analogs thereof, wherein the variables are defined herein. Also provided are pharmaceutical compositions thereof. In some aspects, the compounds and compositions provided herein may be used to inhibit RORγ and/or reduce the expression of IL-17. Also provided are methods of administering compounds and composition provided herein to a patient in need thereof, for example, for the treatment or prevention of diseases or disorders associated with inflammation or autoimmune disorders.

Pyrimidine tricyclic enone derivatives for inhibition of ROR-gamma and other uses

Provided herein are compounds, compositions and methods for treating and preventing diseases and disorders, comprising administering to patients therapeutically effective amounts of cysteine-dependent inverse agonists of the nuclear receptor RORγ/RORγt. In some such embodiments, the inverse agonists bind to cysteine 476 of a nuclear receptor RORγ in the patient. Also provided are methods, as well as compounds and compositions, for modulating the activity of RORγ and RORγt by binding to the allosteric binding site through a covalent bond. In some aspects, the present disclosure relates to using compounds containing Michael acceptor groups which bind to a cysteine residue in the allosteric binding site such as cysteine 476 in RORγ.

Cysteine-dependent inverse agonists of nuclear receptors ROR-gamma/ROR-gamma-t and methods of treating diseases or disorders therewith

Disclosed herein are compounds of the formula: as well as analogs thereof, wherein the variables are defined herein. Also provided are pharmaceutical compositions thereof. In some aspects, the compounds and compositions provided herein may be used to modulate the activity of IL-17 and RORγ. Also provided are methods of administering compounds and composition provided herein to a patient in need thereof, for example, for the treatment or prevention of diseases or disorders associated with inflammation or for autoimmune disorders.

Pyrazole and imidazole compounds for inhibition of IL-17 and RORgamma

Provided are biaryl amides and coumarin-based compounds with modified sugar groups for treatment of diseases associated with heat shock protein pathway. The compounds having the following formulas, wherein variables are as defined herein. Formulae (I), (II), (III), (IV), and (V), Pharmaceutical compositions of the compounds are also provided. These biaryl amides and coumarin-based derivatives with modified sugar groups are useful for treatment and prevention of diseases and disorders, including neurological disorders, such as neurodegenerative diseases and nerve damaging disorders, for example, diabetic peripheral neuropathy.

Biaryl amides with modified sugar groups for treatment of diseases associated with heat shock protein pathway

Disclosed herein are novel antioxidant inflammation modulators, including those of the formula: wherein the variables are defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such compounds. Methods and intermediates useful for making the compounds, and methods of using the compounds and compositions thereof are also provided.

Pyrazolyl and pyrimidinyl tricyclic enones as antioxidant inflammation modulators

Disclosed herein are C4 modified oleanolic acid derivatives of the formula: Formula (X) or Formula (XII), as well as analogs thereof, wherein the variables are defined herein. In addition, disclosed herein are pharmaceutical compositions of these derivatives or analogs, methods for their manufacture, and methods for their use, including for the prevention and treatment of diseases or disorders associated with overproduction of IL-17. 

C4-modified oleanolic acid derivatives for inhibition of IL-17 and other uses

Disclosed herein are novel C17-heteroaryl derivatives of oleanolic acid, including those of the formula: wherein the variables are defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such compounds. Methods and intermediates useful for making the compounds, and methods of using the compounds, for example, as antioxidant inflammation modulators, and compositions thereof are also provided.

C17-heteroaryl derivatives of oleanolic acid and methods of use thereof

Disclosed are co-crystal forms of N-(2-(5-(((2R,3R,4S,5R)-3,4-dihydroxy-5-methoxy-6,6-dimethyltetra-hydro-2H-pyran-2-yl)oxy)-3'-fluoro-[1,1&#x2032;-biphenyl]-2-yl)ethyl)-acetamide and L-proline or D-proline, their pharmaceutical compositions, processes of manufacture, and methods of use for treating neurodegenerative disorders such as diabetic peripheral neuropathy.

Co-crystal forms of a novobiocin analog and proline

Disclosed herein are compounds of the formulas: as well as analogs thereof, wherein the variables are defined herein. Also provided are pharmaceutical compositions thereof. In some aspects, the compounds and compositions provided herein may be used to inhibit ROR&#x3b3; and/or reduce the expression of IL-17. Also provided are methods of administering compounds and composition provided herein to a patient in need thereof, for example, for the treatment or prevention of diseases or disorders associated with inflammation or autoimmune disorders. 

Antioxidant inflammation modulators: oleanolic acid derivatives with amino and other modifications at c-17

Disclosed herein are compounds of the formula: (I), wherein the variables are defined herein. Also provided are pharmaceutical compositions thereof. In some aspects, the compounds and compositions provided herein may be used as antioxidant inflammation modulators. In some aspects, the present disclosure provides methods wherein the compounds and composition described herein are used for the treatment of diseases and disorders associated with inflammation and cancer. 

Imidazolyl tricyclic enones as antioxidant inflammation modulators

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Coppell, TX, United States of America

Xin Jiang