Cumbre Pharmaceuticals Inc.

University of Michigan

Cumbre IP Ventures, L.p.

Yafei Jin

Yong He

Charles Z Ding

In Ho Kim

Zhenkun Ma

Susan Harran

Jing Li

Keith P Minor

Jamie C Longgood

Keith D Combrink

Roderick J Sorenson

Genliang Lu

Hollis Showalter

Roger K Sunahara

Henry Mosberg

Richard Neubig

Christiane Wobus

Jiancheng Wang

Nicholas J Donato

Moshe Talpaz

Hauiling Zhong

Timothy W Morris

A Simon Lynch

Mary X O'Riordan

Jeffrey W Perry

Jeffrey William Perry

Roderick Joseph Sorenson

Jamie Carol Longgood

H D Hollis Showalter

Disclosed herein are methods of inhibiting a deubiquitinase (DUB), methods of treating pathogenic infections (e.g., viral, bacterial, and/or parasitic), methods of inhibiting cell proliferation, methods of treating a neurodegenerative disease, methods of treating one or more symptoms of a neurodegenerative disease or a genetic disorder, and compounds, wherein the compound can have a structure of formula (III): 

Deubiquitinase inhibitors and methods for use of the same

The compounds include substituted rifamycin derivatives in which a quinolone carboxylic acid pharmacophore is covalently bonded to a benzoxazinorifamycin or a spiropiperidinorifamycin. The rifamycin derivatives are useful as antimicrobial agents and are effective against a number of human and veterinary Gram positive and Gram negative pathogens. The advantage of the inventive compounds is that both the rifamycin and quinolone antibacterial pharmacophores are co-delivered with matched pharmacokinetics to the targeted pathogens of interests. Delivery of multiple antibacterial pharmacophores simultaneously to the targeted pathogens has the maximum chance of achieving synergy and minimizing the development of resistance to the antibiotics given.

Quinolone carboxylic acid-substituted rifamycin derivatives

Substituted rifamycin derivatives in which a nitroimidazole, nitrothiazole or nitrofuran pharmacophore is covalently bonded to a rifamycin, methods of using the rifamycin derivatives, and pharmaceutical compositions containing the rifamycin derivatives are disclosed. Methods of synthesizing these substituted rifamycin derivatives are also disclosed. The rifamycin derivatives possess antibacterial activity, and are effective against a number of human and veterinary pathogens in the treatment of bacterial diseases.

Nitroheteroaryl-containing rifamycin derivatives

The present invention relates to novel inhibitors of G-protein signaling. In particular, the present invention provides peptide inhibitors of G protein signaling proteins and methods of using such inhibitors to modulate physiological effects of G protein signaling. The present invention thus provides novel drug targets for a variety of pathologies mediated by defects in G-protein signaling.

Inhibitors of RGS proteins

Rifamycin derivatives having antimicrobial activities, including activities against drug-resistant microorganisms are claimed in this invention. The inventive rifamycin derivatives are uniquely designed in that they have a rifamycin moiety covalently linked to a linker group through the C-3 carbon of the rifamycin moiety and the linker is, in turn covalently linked to a therapeutic moiety or antibacterial agent/pharmacophore. The therapeutic moiety can be a quinolone, an oxazolidinone, a macrolide, an aminoglycoside, a tetracycline core or a structure/pharmacophore associated with an antibacterial agent.

Rifamycin derivatives effective against drug-resistant microbes

The present invention relates to rifamycin 3-iminomethylenyl (&#x2014;CH&#x2550;N&#x2014;) derivatives having antimicrobial activities, including activities against drug-resistant microorganisms. The claimed rifamycin derivative has a rifamycin moiety covalently linked to a linker through an iminomethylenyl (&#x2014;CH&#x2550;N&#x2014;) group at the C-3 carbon of the rifamycin moiety and the linker is, in turn, covalently linked to a quinolone structure or its pharmacophore within the DNA gyrase and topoisomerase IV inhibitor family. The inventive rifamycins are novel and exhibit activity against both rifampin and ciprofloxacin-resistant microorganisms.

Rifamycin imino derivatives effective against drug-resistant microbes

Novel rifamycin derivatives of formula I (both hydroquinone and corresponding quinone (C-C) forms): or their salts, hydrates or prodrugs thereof,wherein: a preferred R comprises hydrogen, acetyl; L is a linker, a preferred linker group elements selected from any combination of 1 to 5 groups shown FIG., provided L is not wherein Ris H, methyl or alkyl. The inventive compounds exhibit valuable antibiotic properties. Formulations having these compounds can be used in the control or prevention of infectious diseases in mammals, both humans and non-humans. In particular, the compounds exhibit a pronounced antibacterial activity, even against multiresistant strains of microbes.

Rifamycin derivatives

Rifamycin derivatives having the following structure of general formula I (both hydroquinone and corresponding quinone (C-C) forms): or its salts, hydrates or prodrugs thereof; wherein a preferred Rcomprises hydrogen or acetyl and a prefered Rcomprises hydrogen, methyl or other lower alkyls; wherein asterik (*) denotes the carbon bearing the chiral center, wherein absolute configuration is assigned as R or S. Methods of preparation of the aforementioned rifamycin derivatives are also described. The compounds exhibit antimicrobial activities, including activities against drug-resistant microorganisms.

(R/S) rifamycin derivatives, their preparations and pharmaceutical compositions

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Dallas, TX, United States of America

Yafei Jin