Vanderbilt University

James C Tarr

Craig William Lindsley

P Jeffrey Conn

Michael R Wood

Stephen W Fesik

Kwangho Kim

Plamen P Christov

Edward T Olejniczak

Zhiguo Bian

Subrata Shaw

Bin Zhao

Michael Steven Poslusney

James M Salovich

Bruce J Melancon

Johannes Belmar

Nicholas F Pelz

Thomas M Bridges

Darren W Engers

Julie L Engers

Madeline Long

Sean R Bollinger

Paul K Spearing

KyuOk Jeon

Nagarathanam Veerasamy

Kyuok Jeon

Taekyu Lee

Michael S Poslusney

The present invention provides for compounds that inhibit the activity of an anti-apoptotic Bcl-2 family member Myeloid cell leukemia-1 (Mcl-1) protein. The present invention 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

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.

Disclosed herein are tricyclic compounds, including pyrimido[4',5&#x2032;:4,5]thieno[2,3-c]pyridazine-8-amine, pyrido[3&#x2032;,2&#x2032;:4,5]thieno[3,2-d]pyrimidine-4-amine, pyrazino[2&#x2032;,3&#x2032;:4,5]thieno[3,2-d]pyrimidin-4-amine, pyrido[3&#x2032;,2&#x2032;:4,5]furo[3,2-d]pyrimidin-4-amine, and pyrimido[4&#x2032;,5&#x2032;:4,5]furo[2,3-c]pyridazin-8-amine compounds, which may be useful as positive allosteric modulators of the muscarinic acetylcholine receptor M(mAChR M). Also disclosed herein are methods of 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.

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-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 M4 (mAChR M4); 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 thieno[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

In one aspect, the invention relates to substituted 4-(1H-pyrazol-4-yl)benzyl analogs compounds, 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.

[object Object]

In one aspect, the invention relates to indole compounds, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor M(mAChR M); synthetic 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.

Indole compounds as positive allosteric modulators of the muscarinic receptor

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Franklin, TN, United States of America

James C Tarr