Auckland Uniservices Limited

Leland Stanford Junior University

Ruga Corporation

Mewburn Ellis

Michael Patrick Hay

William Alexander Denny

William Robert Wilson

Amato J Giaccia

Connie L Sun

Muriel Bonnet

Denise Chan

Edwin Lai

Olga Razorenova

Po-wai Yuen

Ho Huat Lee

Frederik Bastiaan Pruijn

Karin Pchalek

Kevin Owen Hicks

Ray Tabibiazar

Jeffrey Bruce Smaill

Adam Vorn Patterson

Amir Ashoorzadeh

Raymond Tabibiazar

Bronwyn Gae Siim

Guo-Liang Lu

Shangjin Yang

Adrian Blaser

Robert Forbes Anderson

John Irwin

Sandra Turcotte

Patrick Sutphin

Anna Claire Giddens

Provided herein are Substituted Benzamides, compositions, and method of their manufacture and use.

Substituted benzamides and their uses

The present invention provides methods for inhibiting growth and proliferation of HIF pathway proficient cells by administering GLUT1 inhibitors of the invention to HIF pathway proficient cells.

Synthetic lethal targeting of glucose transport

The invention provides novel prodrug compounds comprising a kinase inhibitor and a reductively-activated fragmenting aromatic nitroheterocycle or aromatic nitrocarbocycle trigger, where the compound carries a positive charge. In preferred embodiments, the compounds are of Formula I: where: X is any negatively charged counterion; Ris a group of the formula &#x2014;(CH)Tr, where Tr is an aromatic nitroheterocycle or aromatic nitrocarbocycle and &#x2014;(CH)Tr acts as a reductively-activated fragmenting trigger; and n is an integer from 0 to 6; R, Rand Rmay each independently be selected from aliphatic or aromatic groups of a tertiary amine kinase inhibitor (R)(R)(R)N, or two of R, R, and Rmay form an aliphatic or aromatic heterocyclic amine ring of a kinase inhibitor, or one of R, Rand Rmay be absent and two of R, Rand Rform an aromatic heterocyclic amine ring of a kinase inhibitor. The compounds of the invention are useful in treating proliferative diseases such as cancer.

Prodrug forms of kinase inhibitors and their use in therapy

The invention relates to novel tricyclic 1,2,4-triazine-1-oxides and novel tricyclic 1,2,4-triazine-1,4-dioxides of formula I and to related analogues, to their preparation, and to their use as hypoxia-selective drugs and radiosensitizers for cancer therapy, both alone or in combination with radiation and/or other anticancer drugs.

Tricyclic 1,2,4-triazine oxides and compositions for therapeutic use in cancer treatments

The compound 3-ethyl-6-[3-(4-morpholinyl)propoxy]-1,2,4-benzotriazine 1,4-dioxide and pharmacologically acceptable salts thereof. A method of treating cancer in a subject is also described in which 3-ethyl-6-[3-(4-morpholinyl)propoxy]-1,2,4-benzotriazine 1,4-dioxide or a pharmacologically acceptable salt thereof is administered to tumor cells in a hypoxic environment. Also described is a method of radiosensitising in a subject tumor cells of solid tumors in hypoxic conditions by administering to the subject a pharmaceutical composition containing 3-ethyl-6-[3-(4-morpholinyl)propoxy]-1,2,4-benzotriazine 1,4-dioxide or a pharmacologically acceptable salt thereof in an amount sufficient to produce radiosensitivity in the tumor cells, and subjecting the tumor cells to radiation. A pharmaceutical composition is additionally provided containing a therapeutically effective amount of 3-ethyl-6-[3-(4-morpholinyl)propoxy]-1,2,4-benzotriazine 1,4-dioxide or a pharmacologically acceptable salt thereof and a pharmaceutically acceptable excipient, adjuvant, carrier, buffer or stabiliser.

1,2,4-benzotriazine-1,4-dioxides

Enediyne compounds

Growing community of inventors

Auckland, New Zealand

Michael Patrick Hay