Tufts College

Paratek Pharmaceuticals, Inc.

Darrell J Koza

Mark L Nelson

Glen Robert Rennie

Roger Frechette

David Messersmith

Mohamed Y Ismail

Beena Bhatia

Todd Bowser

Tadeusz Warchol

Peter Viski

Laura McIntyre

Atul K Verma

Paul Hawkins

Paul Sheahan

Upul Keerthi Bandarage

Karen Stapleton

Jimmy Dumornay

Gui Liu

Tad Warchol

Laura Mcintyre

Ted Warchol

The present invention pertains, at least in part, to novel 7-substituted tetracycline compounds. These tetracycline compounds can be used to treat numerous tetracycline compound-responsive states, such as bacterial infections and neoplasms, as well as other known applications for minocycline and tetracycline compounds in general, such as blocking tetracycline efflux and modulation of gene expression.

7-substituted tetracycline compounds

7-substituted tetracycline compounds, methods of treating tetracycline responsive states, and pharmaceutical compositions containing the 7-substituted tetracycline compounds are described.

7-N-substituted phenyl tetracycline compounds

7, 8 and 9-substituted tetracycline compounds, methods of treating tetracycline responsive states, and pharmaceutical compositions containing the 7, 8 and 9-substituted tetracycline compounds are described.

7, 8 and 9-substituted tetracycline compounds

7-phenyl-substituted tetracycline compounds, methods of treating tetracycline responsive states, and pharmaceutical compositions containing the 7-phenyl-substituted tetracycline compounds are described.

7-phenyl-substituted tetracycline compounds

The present invention relates to novel chemistries which allow for heretofore unobtainable substituted tetracycline compounds which exhibit significant activity in tetracycline responsive states. The methods disclosed herein utilize reactive tetracycline-based precursor compounds, reactive organic substituent precursors and transition metal catalysts under conditions such that a tetracycline compound substituted with the desired organic substituent is formed. In one embodiment of the invention, a substituted tetracycline compound may be prepared by combining a reactive tetracycline-based precursor compound such as an arene tetracycline diazonium salt, and a reactive organic substituent precursor, e.g., alkenes, substituted alkenes, vinyl monomers, aromatics and heteroaromatics, in the presence of a transition metal catalyst, such as palladium chloride, under conditions such that a tetracycline compound substituted with the organic substituent is formed. Such compounds may optionally act as intermediates for making other compounds, e.g., hydrogenation of unsaturated groups on the substituent.

Methods of preparing substituted tetracyclines with transition metal-based chemistries

The present invention pertains, at least in part, to novel 9-substituted minocycline compounds. These minocycline compounds can be used to treat numerous tetracycline compound-responsive states, such as bacterial infections and neoplasms, as well as other known applications for minocycline and tetracycline compounds in general, such as blocking tetracycline efflux and modulation of gene expression.

9-substituted minocycline compounds

7,8 and 9-substituted tetracycline compounds

The present invention relates to 9-substituted tetracycline derivatives as well as compositions and use thereof.

Growing community of inventors

Willimantic, CT, United States of America

Darrell J Koza