780800-65-9Relevant academic research and scientific papers
Synthesis and SAR of 1,2,3,4-Tetrahydroisoquinoline-Based CXCR4 Antagonists
Wilson, Robert J.,Jecs, Edgars,Miller, Eric J.,Nguyen, Huy H.,Tahirovic, Yesim A.,Truax, Valarie M.,Kim, Michelle B.,Kuo, Katie M.,Wang, Tao,Sum, Chi Shing,Cvijic, Mary E.,Paiva, Anthony A.,Schroeder, Gretchen M.,Wilson, Lawrence J.,Liotta, Dennis C.
, p. 17 - 22 (2018)
CXCR4 is the most common chemokine receptor expressed on the surface of many cancer cell types. In comparison to normal cells, cancer cells overexpress CXCR4, which correlates with cancer cell metastasis, angiogenesis, and tumor growth. CXCR4 antagonists can potentially diminish the viability of cancer cells by interfering with CXCL12-mediated pro-survival signaling and by inhibiting chemotaxis. Herein, we describe a series of CXCR4 antagonists that are derived from (S)-5,6,7,8-tetrahydroquinolin-8-amine that has prevailed in the literature. This series removes the rigidity and chirality of the tetrahydroquinoline providing 2-(aminomethyl)pyridine analogs, which are more readily accessible and exhibit improved liver microsomal stability. The medicinal chemistry strategy and biological properties are described.
Synthesis and anti-hiv activity of a novel series of isoquinoline-based cxcr4 antagonists
Claes, Sandra,De Jonghe, Steven,Dehaen, Wim,Goffin, Eline,Schols, Dominique,Shad, Mastaneh Safarnejad,Van Loy, Tom
, (2021/10/29)
An expansion of the structure–activity relationship study of CXCR4 antagonists led to the synthesis of a series of isoquinolines, bearing a tetrahydroquinoline or a 3-methylpyridinyl moiety as head group. All compounds were investigated for CXCR4 affinity and antagonism in competition binding and calcium mobilization assays, respectively. In addition, the anti-HIV activity of all analogues was determined. All compounds showed excellent activity, with compound 24c being the most promising one, since it displayed consistently low nanomolar activity in the various assays.
