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Synthesis, cytotoxic characterization, and SAR study of imidazo[1,2‐ b ]pyrazole‐7‐carboxamides
Author(s) -
Demjén András,
Alföldi Róbert,
Angyal Anikó,
Gyuris Márió,
Hackler László,
Szebeni Gábor J.,
Wölfling János,
Puskás László G.,
Kanizsai Iván
Publication year - 2018
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201800062
Subject(s) - pyrazole , chemistry , in vitro , cytotoxic t cell , potency , stereochemistry , human breast , cytotoxicity , structure–activity relationship , ic50 , cell culture , combinatorial chemistry , cancer cell , cancer , biochemistry , medicine , biology , genetics
The synthesis and in vitro cytotoxic characteristics of new imidazo[1,2‐ b ]pyrazole‐7‐carboxamides were investigated. Following a hit‐to‐lead optimization exploiting 2D and 3D cultures of MCF‐7 human breast, 4T1 mammary gland, and HL‐60 human promyelocytic leukemia cancer cell lines, a 67‐membered library was constructed and the structure–activity relationship (SAR) was determined. Seven synthesized analogues exhibited sub‐micromolar activities, from which compound 63 exerted the most significant potency with a remarkable HL‐60 sensitivity (IC 50 = 0.183 μM).