7 research outputs found
Synthesis and Pharmacological Evaluation of Isoindolo[1,2-b]quinazolinone and Isoindolo[2,1-a]benzimidazole Derivatives Related to the Antitumor Agent Batracylin
[ 99m Tc]TRODAT-1: a novel technetium-99m complex as a dopamine transporter imaging agent
Synthesis and Characterization of Technetium-99m-Labeled Tropanes as Dopamine Transporter-Imaging Agents
Optimization of a Potent Class of Arylamide Colony-Stimulating Factor-1 Receptor Inhibitors Leading to Anti-inflammatory Clinical Candidate 4-Cyano-<i>N</i>-[2-(1-cyclohexen-1-yl)-4-[1-[(dimethylamino)acetyl]-4-piperidinyl]phenyl]-1<i>H</i>-imidazole-2-carboxamide (JNJ-28312141)
A class of potent inhibitors of colony-stimulating factor-1
receptor
(CSF-1R or FMS), as exemplified by <b>8</b> and <b>21</b>, was optimized to improve pharmacokinetic and pharmacodynamic properties
and potential toxicological liabilities. Early stage absorption, distribution,
metabolism, and excretion assays were employed to ensure the incorporation
of druglike properties resulting in the selection of several compounds
with good activity in a pharmacodynamic screening assay in mice. Further
investigation, utilizing the type II collagen-induced arthritis model
in mice, culminated in the selection of anti-inflammatory development
candidate JNJ-28312141 (<b>23</b>, FMS IC<sub>50</sub> = 0.69
nM, cell assay IC<sub>50</sub> = 2.6 nM). Compound <b>23</b> also demonstrated efficacy in rat adjuvant and streptococcal cell
wall-induced models of arthritis and has entered phase I clinical
trials