53012-35-4Relevant articles and documents
MODULATORS OF ESTROGEN RECEPTOR PROTEOLYSIS AND ASSOCIATED METHODS OF USE
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Paragraph 00410; 00486; 000490, (2018/08/20)
The present disclosure relates to bifunctional compounds, which find utility as modulators of estrogen receptor (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a cereblon, Von Hippel-Lindau ligase-binding moiety, Inhibitors of Apotosis Proteins, or mouse double-minute homolog 2 ligand, which binds to the respective E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.
Derivatives related to betaxolol with α- and β-adrenergic activities
Leclerc,Decker,Schwartz
, p. 1357 - 1367 (2007/10/02)
The paper describes the synthesis and the pharmacological evaluation of some derivatives of betaxolol, all with an N-aralkylamine instead of the tertiobutylamine. These compounds have been tested for β1-adrenergic receptor antagonism on guinea pig atria, β2-adrenergic receptor antagonism on guinea pig trachea and α-adrenergic blocking activity on rat aorta. Compound U12 with a marked α-blocking activity and compound R8 with a β1/α ratio = 1 were selected for a haemodynamic study in the dog. The decrease in cardiac work and the diminution of total peripheral resistance exhibited by U12 are consistent with a dual α/β-blocking agent. Finally, structure-activity relationships are discussed.
