Literature review revealed that quinoline, benzothiazole, pyrazolo-pyrimidine, etc. possess potent anti proliferative activity. Thus, we design and synthesize N-(6-(4-amino-1-((2-4-methylpiperazin-1-yl)quinolin-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)benzo[d]thizol-2-yl)acetamide(10 ) using various name reactions like Vilsmeier-Haack, Appel & Suzuki reactions. 2-chloroquinoline-3-carbaldehyde(2 ) was synthesized by heating acetanilide(1 )/POCl3/DMF at 80�C for 12 h. It further stirred with methanol/NaBH4 at 0�C for 4 h to yield (2-chloroquinolin-3-yl)methanol(3 ). Suspension of 3  in DCM, triphenylphosphine and CBr4 stirred at 0�C for 12 h to yield 3-(bromomethyl)-2-chloroquiniline(4 ). 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine(5 ) in DMF was stirred with KOtBu for 10 min and compound 4  dissolved in DMF was added with stirring to yield 1-((2-chloroquinolin-3yl)methyl)-3-iodo-1H-pyrazolo[3,4-d]pyridine-4-amine(6 ). A mixture of 6  & 1-methyl piperazine(7 ) were mixed in 1,4-dioxan and refluxed for 18 h at 110�C to yield 3-iodo-1(2-(4-methylpiperazin-1-yl)quinolin-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine(8 ). A mixture of 8  & N-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]thiazol-2-yl)acetamide(9 ) were mixed in 1,4-dioxan and refluxed with K2CO3, Pd(PPh3)4 and deionized water for 6 h at 100-115�C to yield desired product 10  . Structure elucidation was done by FTIR, Mass, and 1H-NMR. It was evaluated for cytotoxicity on U937, ARH7 and RPMI 8226 by MTT assay with doxorubicin as standard showing EC50 value of 6.8�m, 795nm and 3.98�m, respectively. Designed compound can further exploit to develop novel anticancer agents.

Design, synthesis, and antiproliferative activity of N-(6-(4-amino-1-((2-4-methyl piperazin-1-yl)quinolin-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)benzo[d]thizol-2-yl)acetamide

245th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.