Novel 6- N-arylcarboxamidopyrazolo[4,3- d]pyrimidin-7-one derivatives as potential anti-cancer agents

• Published in: Bioorganic & medicinal chemistry letters 2010-03, Vol.20 (5), p.1630-1633
• Main Authors: Devegowda, Vani N., Kim, Jung Hyun, Han, Ki-Cheol, Yang, Eun Gyeong, Choo, Hyunah, Pae, Ae Nim, Nam, Ghilsoo, Choi, Kyung Il
• Format: Article
• Language: English
• Subjects: 6- N-Arylcarboxamidopyrazolo[4,3- d]pyrimidin-7-one; Anticancer activity; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - toxicity; Biological and medical sciences; Cell Line, Tumor; Drug Screening Assays, Antitumor; General aspects; Humans; Medical sciences; Pharmacology. Drug treatments; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Protein-Serine-Threonine Kinases - metabolism; Pyrazoles - chemical synthesis; Pyrazoles - chemistry; Pyrazoles - toxicity; Pyrimidines - chemical synthesis; Pyrimidines - chemistry; Pyrimidines - toxicity; Pyrimidinones - chemical synthesis; Pyrimidinones - chemistry; Pyrimidinones - toxicity; Structure-Activity Relationship
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2010.01.029

A library of 6- N-arylcarboxamidopyrazolo[4,3- d]pyrimidin-7-one derivatives ( I) was synthesized and structure-anticancer activity relationships have been established for R 1, R 2 and R 3. The most active compound 12b showed GI 50 value of 0.44 μM and 1.07 μM against cancer cell lines HT-29 and DU-145, respectively. A novel series of 3,5,6-trisubstituted pyrazolo[4,3- d]pyrimidin-7-one derivatives, especially 6- N-arylcarboxamidopyrazolo[4,3- d]pyrimidin-7-ones were synthesized and evaluated for their in vitro anticancer activities against various human cancer cell lines. The inhibitory activities for several kinases have also been tested. The prepared compounds library exhibited significant anticancer activity towards HT-29 colon and DU-145 prostate cancer cell lines. The structure–activity relationships of the 6- N-arylcarboxamidopyrazolo[4,3- d]pyrimidin-7-one scaffold at R 1, R 2 and R 3 have been elucidated. Among the synthesized compounds, 12b was the most active compound with GI 50 value of 0.44 μM and 1.07 μM against HT-29 and DU-145 cell lines, respectively, and 13a was the most selective compound towards colon cancer cell line.