Oregon Health & Science University

The United States Government As Represented by the Department of Veterans Affairs

University of South Florida

Interlab Inc.

Medicines for Malaria Venture

The United States of America

Avi Biopharma, Inc.

David J Hinrichs

Rolf W Winter

Michael Kevin Riscoe

Jane Xu Kelly

Martin J Smilkstein

Aaron Nilsen

Dennis Edward Kyle

Roman Manetsch

Sovitj Pou

David Lawrence Flanigan

Richard Matthew Cross

Yuexin Li

Jeremy Burrows

Andrii Monastyrskyi

Patrick L Iversen

Dan V Mourich

Hong M Moulton

Compounds, compositions and methods useful for treating infectious diseases are provided. In particular, 3-aryl quinoline compounds, their synthesis, pharmaceutical compositions thereof and methods of treating infectious diseases such as malaria, are disclosed.

Compounds, compositions and associated methods comprising 3-aryl quinolines

(A1) A class of acridone compounds has been discovered that exhibits chemosensitizing and antiparasitic activity. Described herein are pharmaceutical compositions and methods for their use to treat parasitic infections, such as malaria and toxoplasmosis, and to sensitize resistant cells, such as multidrug resistant cells to other therapeutic agents. The pharmaceutical compositions and methods may also be used to treat and/or prevent psychotic diseases such as schizophrenia.

Acridone compounds

Compounds having antiparasitic or anti-infectious activity

A class of acridone compounds has been discovered that exhibits chemosensitizing and antiparasitic activity. Described herein are pharmaceutical compositions and methods for their use to treat parasitic infections, such as malaria and toxoplasmosis, and to sensitize resistant cells, such as multidrug resistant cells to other therapeutic agents. The pharmaceutical compositions and methods may also be used to treat and/or prevent psychotic diseases such as schizophrenia.

A compound, particularly an antimalarial compound, according to formula I: 

Compounds for treating parasitic disease

A method and conjugate for selectively killing antigen-activated T cells are disclosed. The conjugate is composed of a substantially uncharged antisense compound targeted against the human cFLIP protein, and a reverse TAT (rTAT) polypeptide coupled covalently to the antisense compound. The rTAT polypeptide is effective to produce selective uptake of the conjugate into antigen-activated T cells, relative to the uptake of the conjugate into non-activated T cells. The cFLIP antisense compound causes activation induced cell death (AICD) of activated lymphocytes. The method is useful in treating transplantation rejection and autoimmune conditions.

Antisense compound for inducing immunological tolerance

Aromatic ketones having an extended fluoro-alkyl or fluoro-alkoxy moiety are disclosed. In particular aspects, the compounds comprise substituted 9-acridone, 9-xanthone, 4(1H)-quinolone, 4(1H) pyridone, 1,4-naphthoquinone, 9,10-anthraquinone derivatives. These preparations possess potent pharmacological activity for inhibiting malaria and mosquito-borne () diseases. The haloalkyl/alkoxy aromatic compounds possess significant pharmacological activity, with ICvalues in the nanomolar and sub-nanomolar range, and reduced toxicity against host derived cells and tissues. Methods of using the fluoro-alkyl/alkoxy aromatic compounds in the treatment of malaria and other human and animal diseases are also disclosed. Agricultural uses of the fluoro-alkyl/alkoxy aromatic compounds, such as in control of fungal diseases and in the production of important commercial crops (apples, etc.), are also presented.

Aromatic ketones and uses thereof

Therapeutic compounds and compositions for the treatment of infectious diseases are disclosed. The compounds are xanthones and xanthone derivatives, such as 3,5-bis-&egr;-(N,N-diethylamino)amyloxyxanthone. The described compositions include such compounds and a pharmaceutical carrier. These compositions also can include additional materials conventionally used to form therapeutic compositions. 3,5-bis-&egr;-(N,N-diethylamino)amyloxyxanthone has an IC for of about 0.15 &mgr;M, and an IC for of <<0.5 &mgr;M. These compositions are additionally useful for forming soluble complexes with heme and porphyrins.

Xanthone analogs for treating infectious diseases and complexation of heme and porphyrins

Therapeutic compositions for the treatment of infectious diseases are disclosed. These compositions comprise xanthones and xanthone derivatives, such as 2,3,4,5,6-pentahydroxyxanthone. Also disclosed are methods for the treatment of infectious diseases using such compounds.

Xanthone analogs for the treatment of infectious diseases

Growing community of inventors

Lake Oswego, OR, United States of America

David J Hinrichs