150544-79-9Relevant articles and documents
TARGETED PLASMA PROTEIN DEGRADATION
-
Page/Page column 127-129, (2021/08/14)
The present invention is directed to the bifunctional compounds and the use of such bifunctional compounds to lower plasma levels of extracellular target molecules by lysosomal degradation. Such bifunctional compounds have a cell surface receptor ligand covalently linked to a ligand that is capable of binding to an extracellular target molecule (such as a ligand for a growth factor, a cytokine, a chemokine, a hormone, a neurotransmitter, a capsid, a soluble receptor, an extracellular secreted protein, an antibody, a lipoprotein, an exosome, a virus, a cell, or a plasma membrane protein), where the cell surface receptor is associated with receptor mediated endocytosis, including asialoglycoprotein receptor (ASGPR) mediated lysosomal degradation and mannose-6-phosphate (M6PR) mediated lysosomal degradation. Pharmaceutical compositions comprising such bifunctional compounds and methods of treating a disease or disorder mediated by an extracellular molecule using such bifunctional compounds are also provided herein.
Synthesis and SAR of succinamide peptidomimetic inhibitors of cathepsin S
Chatterjee, Arnab K.,Liu, Hong,Tully, David C.,Guo, Jianhua,Epple, Robert,Russo, Ross,Williams, Jennifer,Roberts, Michael,Tuntland, Tove,Chang, Jonathan,Gordon, Perry,Hollenbeck, Thomas,Tumanut, Christine,Li, Jun,Harris, Jennifer L.
, p. 2899 - 2903 (2008/12/22)
Peptidic, non-covalent inhibitors of lysosomal cysteine protease cathepsin S (1 and 2) were investigated due to low oral bioavailability, leading to an improved series of peptidomimetic inhibitors. Utilizing phenyl succinamides as the P2 residue increased the oral exposure of this lead series of compounds, while retaining selective inhibition of the cathepsin S isoform. Concurrent investigation of the P1 and P2 subsites resulted in the discovery of several potent and selective inhibitors of cathepsin S with good pharmacokinetic properties due to the elimination of saturated aliphatic P2 residues.
Renin inhibitors containing a pyridyl amino diol derived C-terminus
Heitsch,Henning,Kleemann,Linz,Nickel,Ruppert,Urbach,Wagner
, p. 2788 - 2800 (2007/10/02)
Based on the concept of transition-state analogs, a series of nonpeptide renin inhibitors with the new (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy- 6-(2-pyridyl)hexane moiety at the C-terminal functionality were synthesized and evaluated for inhibition
