1 research outputs found
Synthesis of Novel Tetrahydroisoquinoline CXCR4 Antagonists with Rigidified Side-Chains
A structure–activity
relationship study of potent TIQ15-derived
CXCR4 antagonists is reported. In this investigation, the TIQ15 side-chain
was constrained to improve its drug properties. The cyclohexylamino
congener <b>15a</b> was found to be a potent CXCR4 inhibitor
(IC<sub>50</sub> = 33 nM in CXCL12-mediated Ca<sup>2+</sup> flux)
with enhanced stability in liver microsomes and reduced inhibition
of CYP450 (2D6). The improved CXCR4 antagonist <b>15a</b> has
potential therapeutic application as a single agent or combinatory
anticancer therapy