Synthesis of novel spiro[pyrazolo[4,3-d]pyrimidinones and spiro[benzo[4,5]thieno[2,3-d]pyrimidine-2,3′-indoline]-2′,4(3H)-diones and their evaluation for anticancer activity

• Published in: Bioorganic & medicinal chemistry letters Vol. 27; no. 6; pp. 1446 - 1450
• Main Authors: Ismail, Kuthati, Bhaskar, Thalari, Gangadhar, Bommarapu, Venkatesham, Mulakayala, Chaitanya, Chitta, Suresh Kumar, Mulakayala, Naveen
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 15.03.2017; Elsevier
• Subjects: 4-Amino-1-methyl-3-propylpyrazole-5-carboxamide; Anticancer agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Carbon-13 Magnetic Resonance Spectroscopy; Cell Line, Tumor; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Drug Screening Assays, Antitumor; Humans; InCl3; Life Sciences & Biomedicine; Mass Spectrometry; Pharmacology & Pharmacy; Physical Sciences; Proton Magnetic Resonance Spectroscopy; Pyrimidines - chemical synthesis; Pyrimidines - chemistry; Pyrimidines - pharmacology; Science & Technology; Spiro[benzo[4,5]thieno[2,3-d]pyrimidine-2,3′-indoline]-2′,4(3H)-dione; Spiro[pyrazolo[4,3-d]pyrimidin]-7′(1′H)-ones; Spiro[pyrazolo[4,3-d]pyrimidin]-7′(1′H)-ones; InCl3; Spiro[benzo[4,5]thieno[2,3-d]pyrimidine-2,3′-indoline]-2′,4(3H)-dione; Anticancer agents; 4-Amino-1-methyl-3-propylpyrazole-5-carboxamide; Spiro[pyrazolo[4,3-d]pyrimidin]-7 '(I ' H)-ones; Spiro[benzo[4,5]thieno[2,3-d]pyrimidine-2,3 '-indoline]-2 ',4(3H)-dione; SIRTUINS; DERIVATIVES; CANCER; SIRT1; InCl
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2017.01.088

[Display omitted] An efficient and novel method for the preparation of spiro[pyrazolo[4,3-d]pyrimidin]-7′(1′H)-ones by the condensation of 4-amino-1-methyl-3-propylpyrazole-5-carboxamide with ketones under mild conditions using catalytic InCl3 was reported. This method has been extended for the synthesis of novel spiro[benzo[4,5]thieno[2,3-d]pyrimidine-2,3′-indoline]-2′,4(3H)-dione which are having potential applications in medicinal chemistry. All the synthesized compounds were evaluated for their anti-proliferative properties in vitro against cancer cell lines and several compounds were found to be active. Further in vitro studies revealed that inhibition of sirtuins could be the possible mechanism of action of these molecules.