Vanderbilt University

James M Salovich

Craig William Lindsley

P Jeffrey Conn

Corey R Hopkins

Rocco D Gogliotti

Darren W Engers

Michael R Wood

Stephen W Fesik

Colleen M Niswender

James C Tarr

Yiu-Yin Cheung

Edward T Olejniczak

Bruce J Melancon

KyuOk Jeon

Shaun R Stauffer

Kwangho Kim

Michael Steven Poslusney

Plamen P Christov

Zhiguo Bian

Jason Phan

Bin Zhao

Subrata Shaw

Nagarathanam Veerasamy

Alex Gregory Waterson

Charles David Weaver

Michael C Burns

Changho Han

Joseph R Alvarado

Qi Sun

Jason R Abbott

Andrew Little

Kenneth M Meyers

William P Tansey

Jonathan D Macdonald

Feng Wang

Jonathan J Mills

Steve W Fesik

Jeffrey P Conn

Patrick R Gentry

Kyuok Jeon

Michael S Poslusney

The present disclosure provides for compounds that inhibit the activity of an anti-apoptotic Bcl-2 family member Myeloid cell leukemia-1 (Mcl-1) protein. The present disclosure also provides for pharmaceutical compositions as well as methods for using compounds for treatment of diseases and conditions (e.g., cancer) characterized by the over-expression or dysregulation of Mcl-1 protein.

Substituted indole Mcl-1 inhibitors

Benzamides and picolinamides that are meta-substituted with imino-, guanidino-, or heterocycle-containing groups disrupt the WDR5-MLL1 protein-protein interaction, and have use in pharmaceutical compositions and in treating proliferative disorders and conditions in a subject, such as cancer.

WDR5-MLL1 inhibitors and modulators

Benzimidazole compounds that increase the rate of SOS-mediated nucleotide exchange on Ras by binding to a functionally relevant, chemically tractable pocket on the SOS protein, as part of the Ras:SOS:Ras complex.

Substituted benzimidazoles as modulators of Ras signaling

Described are N-(6-(6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-2-yl)-2,3-dihydro-1H-inden-1-yl)benzamide and acetamide-containing compounds that inhibit WDR5 and associated protein-protein interactions, pharmaceutical compositions including the compounds, and methods of using the compounds and compositions for treating disorders and conditions in a subject.

WDR5 inhibitors and modulators

In one aspect, the invention relates to substituted 5-aminothieno[2,3-c]pyridazine-6-carboxamide analogs, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor M(mAChR M); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Substituted 5-aminothieno[2,3-C]pyridazine-6-carboxamide analogs as positive allosteric modulators of the muscarinic acetylcholine receptor M4

In one aspect, the invention relates to substituted 5-aminothieno[2,3-c]pyridazine-6 -carboxamide analogs, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor M(mAChR M); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Substituted 5-aminothieno[2,3&#x2014;C]pyridazine-6-carboxamide analogs as positive allosteric modulators of the muscarinic acetylcholine receptor M4

Heterocyclic sulfone compounds which are useful as allosteric potentiators/positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4); and methods of using the compounds, for example, in treating neurological and psychiatric disorders or other disease state associated with glutamate dysfunction.

Heterocyclic sulfone mGluR4 allosteric potentiators, compositions, and methods of treating neurological dysfunction

Pyrazolopyridine, pyrazolopyrazine, pyrazolopyrimidine, pyrazolothiophene and pyrazolothiazole compounds which are useful as allosteric potentiators/positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of using the compounds, for example, in treating neurological and psychiatric disorders or other disease state associated with glutamate dysfunction.

Pyrazolopyridine, pyrarolopyrazine, pyrazolopyrimidine, pyrazolothiophene and pyrazolothiazole compounds as MGLUR4 allosteric potentiators, compositions, and methods of treating neurological dysfunction

Pyrazolopyridine, pyrazolopyrazine, pyrazolopyrimidine, pyrazolothiophene and pyrazolothiazole compounds as MGLUR4 allosteric potentiators, compositions, and methods of treating neurological dysfunction

In one aspect, the invention relates to substituted 1H-pyrazolo[3',4&#x2032;:4,5]thieno[2,3-b]pyridin-3-amine analogs, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor M(mAChR M); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Substituted 1H-pyrazolo[3',4&#x2032;,4,5]thieno[2,3-b]pyridin-3-amine analogs as positive allosteric modulators of the muscarinic acetylcholine receptor M4

In one aspect, the invention relates to substituted pyrazolo[3',4&#x2032;:4,5]thieno[2,3-c]pyridazine-3-amine analogs, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor M(mAChR M); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Substituted pyrazolo[3',4&#x2032;:4,5]thieno[2,3-C]pyridazin-3-amine analogs as positive allosteric modulators of the muscarinic acetylcholine receptor M4

Compounds useful as allosteric potentiators/positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4) and use thereof.

MGLUR4 allosteric potentiators, compositions, and methods of treating neurological dysfunction

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Nashville, TN, United States of America

James M Salovich