The United States of America, As Represented by the Secretary, Department of Health and Human Services

Purdue Research Foundation

Other

The United States of America As Represented by the Department of Health

University of Minnesota

University of Kentucky Research Foundation

Sun Yat-senuniversity

Aronex Pharmaceuticals, Inc.

Provid Pharmaceuticals Inc.

Second Military Medical University, Pla

Dana-farber-cancer Institute Inc.

Genome Research Limited

An, Linkun

Yves Pommier

Mark Stanley Cushman

Christophe Marchand

Andrew E Morrell

Keli K Agama

Muthukaman Nagarajan

Smitha Antony

Timothy L MacDonald

Robert H Shoemaker

Daniel Edward Beck

Michael Currens

Jose S Madalengoitia

Trung X Nguyen

Martin M Conda-Sheridan

John Cardellina

Dominic Scudiero

Christopher Self

Terrence R Burke, Jr

Stephen H Hughes

Guangtao Zhang

Barry Johnson

David Waugh

Andrew Jobson

George Lountos

Mathieu Metifiot

Steven Smith

Xue Zhi Zhao

Linkun An

Arun K Ghosh

Mansukh C Wani

Tie-Lin Wang

Monroe E Wall

Michael E Hogan

Robert F Rando

Govindarajan Manikumar

Charles Michael Cook

Thomas G Burke

Nouri Neamati

Joshua O Ojwang

Marino Artico

Susan Fennewald

Joseph G Zendegui

David J Adams

Thomas S Dexheimer

Vito Nacci

Zhengqiang Wang

Mohamed S A Elsayed

Michael P Gamcsik

Evgeny A Kiselev

Antonio Garofalo

Andrew Vargha Colasanti

Ashok J Chavan

Ayhan S Demir

Roberto Di Santo

Roberta Costi

Yunlong Song

Ping Wang

Xiaodan Fu

Abhijit Mazumder

Cihangir Tanyeli

Jayakanth Kankanala

Muthusamy Jayaraman

Yunpeng Qi

Laurent Thibaut

Sudhir Kondapaka

Andy Jobson

Periyasamy Selvam

Yongwei Zhang

Alexandra S Ioanoviciu

Peng-Cheng Lu

O Michael Colvin

Pamela M Nagafuji

Kasthuraiah Maddali

Andrew Colasanti

Charles M Cook

John Cardelina

Robert Shoemaker

Christopher R Self

William Curtis Reinhold

Vinodh Nalin Rajapakse

Augustin Luna

Compounds of Formula I and the pharmaceutically acceptable salts thereof are disclosed The variables X, X, and Rare disclosed herein. The compounds are useful for treating cancer and related proliferative diseases. Pharmaceutical compositions containing compounds of Formula I and methods of treatment comprising administering compounds of Formula I are also disclosed.

Furoquinolinediones as inhibitors of TDP2

Compounds of Formula I and the pharmaceutically acceptable salts thereof are disclosed Formula I. The variables X, X, and Rare disclosed herein. The compounds are useful for treating cancer and related proliferative diseases. Pharmaceutical compositions containing compounds of Formula I and methods of treatment comprising administering compounds of Formula I are also disclosed. 

Tyrosyl-DNA Phosphodiesterases 1 and 2 (Tdp1 and Tdp2) can repair damaged DNA resulting from topoisomerase inhibitors (e.g. Top1) and a variety of other DNA-damaging agents. 7-Azaindenoisoquinolines that are inhibitors of each of Top1, Tdp1 and Tdp2 are disclosed. Also described are methods for preparing azaindenoisoquinoline and methods for treating patients of a cancer using the disclosed azaindenoisoquinoline compounds or a pharmaceutical formulation thereof.

Azaindenoisoquinoline compounds and uses thereof

The invention described herein pertains to four series of aza-A-ring indenoisoquinolines, which are inhibitors of topoisomerase IB (Top1), and the processes for preparing said aza-A-ring indenoisoquinolines. Also described are methods for treating cancer in mammals using the described aza-A-ring indenoisoquinoline compounds or pharmaceutical formulations thereof.

Aza-A-ring indenoisoquinoline topoisomerase I poisons

The invention provides a compound of formula (I), (II) or (III): wherein R, R, R, Rand Rhave any of the values described in the specification, as well as compositions comprising a compound of formula (I), (II) or (III). The compounds and compositions are useful as chemotherapeutic sensitizing agents.

Compounds for cancer chemotherapeutic sensitization

A method of inhibiting drug-resistant HIV-1 integrase in a subject comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt or ester thereof, having a structure of: wherein X is N, C(OH), or CH;Y is H or OH;each of Z-Zis independently H or halogen;Ris H, OH, NH, NHR, NRRor R;R, R, and Ris each independently H, halogen, OR, R, NHR, NRR, COR, CONRR, SONRR, or Rand Rtogether with the carbon atoms to which Rand Rare attached form an optionally-substituted carbocycle or optionally-substituted heterocycle; andRand Ris each independently H, optionally-substituted alkyl, optionally-substituted alkenyl, optionally-substituted alkynyl, optionally-substituted aryl, optionally-substituted cycloalkyl, optionally-substituted cycloalkylene, optionally-substituted heterocycle, optionally-substituted amide, optionally-substituted ester, or Rand Rtogether with the nitrogen to which Rand Rare attached form an optionally-substituted heterocycle.

Compounds for inhibiting drug-resistant strains of HIV-1 integrase

The invention described herein pertains to the synthesis and use of certain N-substituted indenoisoquinoline compounds which inhibit the activity Tyrosyl-DNA Phosphodiesterase I (Tdp1) or Topoisomerase I (Top1) or both, or otherwise demonstrate anticancer activity. Also disclosed are novel N-substituted indenoisoquinoline compounds and pharmaceutical compositions comprising the novel N-substituted indenoisoquinoline compounds.

Synthesis and use of dual tyrosyl-DNA phosphodiesterase I (Tdp1)&#x2014;topoisomerase I (Top1) inhibitors

N-Substituted indenoisoquinoline compounds, and pharmaceutical formulations of N-substituted indenoisoquinoline compounds are described. Also described are processes for preparing N-substituted indenoisoquinoline compounds. Also described are methods for treating cancer in mammals using the described N-substituted indenoisoquinoline compounds or pharmaceutical formulations thereof.

N-substituted indenoisoquinolines and syntheses thereof

The invention described herein pertains to substituted indenoisoquinoline compounds as described herein, wherein R, R, W, X and Y are defined herein, pharmaceutical compositions and formulations comprising the indenoisoquinoline compounds, their synthesis, and methods for their use in the treatment and/or prevention of cancer.

Alcohol-, diol-, and carbohydrate-substituted indenoisoquinolines as topoisomerase I inhibitors

A method of treating an Hepatitis C Virus infection in a patient, comprising providing a therapeutically effective amount, to a patient in need thereof, of a compound of Formula (I) or a pharmaceutically acceptable salt thereof, wherein: Gis a group of the formula or where n is 0, 1, 2, 3, or 4 and Het is a 5- or 6-membered heteroaryl group containing 1 to 4 heteroatoms independently chosen from N, O, and S, which Het is optionally substituted. 

Method of treating HCV infection with a small molecule CHK2 inhibitor

An indenoquinolone compounds of Formula (A) is disclosed, wherein the definition of each group is described in the description. These compounds may specifically inhibit topoisomerase I, and they have good activities against many kinds of human tumor cells, such as lung cancer, colon cancer, breast cancer, liver cancer and the like. They can be used in the manufacture of antitumor drugs. The method for preparing the compound of formula (A), and pharmaceutical compositions containing such compounds and the use in the manufacture of antitumor drugs are also disclosed. 

Indenoquinolone compound, preparation method and use thereof

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Bethesda, MD, United States of America

Yves Pommier