Synthesis and SAR of 1,2,3,4-Tetrahydroisoquinoline-Based CXCR4 Antagonists.
ACS Med Chem Lett
; 9(1): 17-22, 2018 Jan 11.
Article
in En
| MEDLINE
| ID: mdl-29348805
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
ACS Med Chem Lett
Year:
2018
Document type:
Article
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