Max-planck-gesellschaft Zur F&#xf6;rderung Der Wissenschaften E. V.

The Provost Fellows and Scholars of the College of the Holy and Undivided Trinity of Queen Elizabeth, Near Dublin

Technische Universitat Darmstadt

The Provost, Fellows, Foundation Scholars & the Other Members of Board, of the College of the Holy & Undiv. Trinity of Queen Elizabeth, Near Dublin

David George Lloyd

Gregor Larbig

Eckhard Mandelkow

Eva-Maria Mandelkow

Jacek Biernat

Darren Fayne

Boris Schmidt

Billy Egan

Miriam Carr

Fernando Blanco

Gemma Karena Kinsella

D Clive Williams

Laura Caboni

Mary Jane Meegan

Wiliam Nicholas Jagoe

Markus Pickhardt

Non ligand binding pocket antagonists for the human androgen receptor. The androgen receptor (AR) is a member of the Nuclear Receptor (NR) family and its role is to modulate the biological effects of the endogenous androgens, testosterone (tes) and dihydrotestosterone (DHT). Synthetic androgens and anti-androgens have therapeutic value in the treatment of various androgen dependent conditions, from regulation of male fertility to prostate cancer. Current treatment of prostate cancer (PCa) typically involves administration of 'classical' antiandrogens, competitive inhibitors of natural AR ligands, DHT and tes, for the ligand binding pocket (LBP) in the C-terminal ligand binding domain (LBD) of the AR. However, prolonged LBP-targeting can often lead to androgen resistance and alternative therapies and therapeutic strategies are urgently required. Disclosed herein are a class of non-steroidal, small molecule AR antagonists which inhibit the transcriptional activity of the AR by non LBP-mediated modulation. The novel class reported demonstrates full ('true') antagonism in AR with low micromolar potency, high selectivity over both the Estrogen Receptors alpha and beta (ER&#x3b1; and ER&#x3b2;) and the Glucocorticoid Receptor (GR) and only micromolar partial antagonism in the Progesterone Receptor (PR). Data provide compelling evidence for such non-LBP intervention as an alternative approach to classical PCa therapy. (Formula I). 

Androgen receptor ligands

Described are compounds having a thiazolhydrazide scaffold, pharmaceutically acceptable salts of these compounds and pharmaceutical compositions containing at least one of these compounds together with pharmaceutically acceptable carrier, excipient and/or diluents. Said thiazolhydrazide compounds can be used for prophylaxis and/or treatment of neurodegenerative diseases and conditions.

Thiazolhydrazides for treatment of neurodegenerative diseases

Growing community of inventors

Malahide, Ireland

David George Lloyd