247035-06-9Relevant academic research and scientific papers
Tricyclic pharmacophore-based molecules as novel integrin αvβ3 antagonists. Part 2: Synthesis of potent αvβ3/αIIbβ3 dual antagonists
Ishikawa, Minoru,Kubota, Dai,Yamamoto, Mikio,Kuroda, Chizuko,Iguchi, Maki,Koyanagi, Akihiro,Murakami, Shoichi,Ajito, Keiichi
, p. 2109 - 2130 (2007/10/03)
We synthesized 4-aminopiperidine derivatives of our prototype integrin αvβ3 antagonist 1 in an attempt to increase the activity and water solubility. Introduction of one or two hydrophilic moieties into the central aromatic ring and/or the benzene ring at the C-terminus of 1 increased water solubility and enhanced inhibition of cell adhesion. The results of a structure-activity relationships (SAR) study indicated that the torsion angle between the central aromatic ring and the piperidine ring, and the acidity at the sulfonamide moiety, might be important for αvβ 3 receptor binding activity. Some of these compounds are novel and potent αvβ3/αIIbβ 3 dual antagonists with acceptable water solubility and a satisfactory early absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile.
