Tandem optimization of target activity and elimination of mutagenic potential in a potent series of N-aryl bicyclic hydantoin-based selective androgen receptor modulators
摘要:
Pharmacokinctic studies in cynomolgus monkeys with a novel prototype selective androgen receptor modulator revealed trace amounts of an aniline fragment released through hydrolytic metabolism. This aniline fragment was determined to be mutagenic in an Ames assay. subsequent concurrent optimization for target activity and avoidance of mutagenicity led to the identification of a pharmacologically superior clinical candidate without mutagenic potential. (c) 2007 Elsevier Ltd. All rights reserved.
Arylaminoaryl-alkyl-substituted imidazolidine-2,4-diones, process for preparing them, medicaments comprising these compounds, and their use
申请人:JAEHNE Gerhard
公开号:US20090215728A1
公开(公告)日:2009-08-27
This invention relates to arylaminoaryl-alkyl-substituted imidazolidone-2,4-diones of formula (I) and also to their physiologically tolerated salts:
Wherein R, R′, R1 to R10, A, D, E, G, L and p are as defined herein. The invention also relates to processes for preparing them, pharmaceutical compositions comprising them and their therapeutic use. The compounds are suitable, for example, as anti-obesity drugs and for treating cardiometabolic syndrome.
[EN] SELECTIVE ANDROGEN RECEPTOR DEGRADER (SARD) LIGANDS AND METHODS OF USE THEREOF<br/>[FR] LIGANDS DE COMPOSÉS DÉGRADANT DES RÉCEPTEURS D'ANDROGÈNES SÉLECTIFS (SARD) ET LEURS MÉTHODES D'UTILISATION
申请人:GTX INC
公开号:WO2016172330A1
公开(公告)日:2016-10-27
This invention provides novel 3-amino propanamide selective androgen receptor degrader (SARD) compounds, pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, androgenic alopecia or other hyperandrogenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.