Synthesis of novel 8-(het)ary1-6H-pyrano[4 ',3 ':4,5]thieno[3,2-b] pyridines by 6-endo-dig cyclization of Sonogashira products and halolactonizations with Cu salts/NXS. Preliminary antitumor evaluation

• Type: Article in International Scientific Journal
• Date: 2019

Authors

Rodrigues, JM (Author) Other; Buisson, P (Author) Other; Pereira, JM (Author) Other; Pinheiro, IM (Author) Other; Fernandez Marcelo, T (Author) Other; Helena Vasconcelos, MH (Author) FFUP; Berteina Raboin, S (Author) Other; Queiroz, MJRP (Author) Other

Journal

Title: Tetrahedron

Vol. 75

Pages: 1387-1397

ISSN: 0040-4020

Publisher: Elsevier

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Other information

Authenticus ID: P-00Q-9N2

DOI: 10.1016/j.tet.2019.01.054

Abstract (EN): Novel 8-(het)aryl-6H-pyrano[4',3':4,5]thieno[3,2-b]pyridines were prepared in good to high yields by a tandem one-pot procedure of Sonogashira coupling and 6-endo-dig lactonization from 3-bromothieno [3,2-bipyridine-2-carboxylic acid and (het)arylalkynes. Sonogashira coupling products were also prepared from the corresponding methyl ester giving in the same reaction the corresponding 6-endo-dig compounds as minor products. The Sonogashira phenyl ester product gave cyclization with electrophiles only in low to moderate yields. Nevertheless, halolactonizations using Cu(I) or (II) salts/N-halosuccinimides (NXS) from either the phenyl ester or the carboxylic acid derivatives occurred in good to high yields. The growth inhibition potential of the compounds was evaluated using human tumor cell lines, HCT-15 (colorectal adenocarcinoma) and NCI-H460 (non-small cell lung cancer) and studies of apoptosis induction were performed for the three most promising compounds in HCT-15 cells. Two of them caused almost 40% of cell death by apoptosis when tested at their 1.5 x GI(50) concentrations. The tricyclic lactone with a F atom in the meta position showed to be the most promising one.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11