Original scientific paper

https://doi.org/10.1515/acph-2016-0029

Simple approach to thieno[3,2-d]pyrimidines as new scaffolds of antimicrobial activities

HEND N. HAFEZ orcid.org/0000-0003-1541-8744 ; Al-Imam Mohammad Ibn Saud Islamic University (IMSIU), College of Science, Department of Chemistry, P. O. Box 90950, Riyadh 11623, Kingdom of Saudi Arabia, Photochemistry Department, (Heterocyclic & Nucleosides Unit), National Research Centre, Cairo, Egypt
ABDEL-RHMAN B. A. EL-GAZZAR ; Al-Imam Mohammad Ibn Saud Islamic University (IMSIU), College of Science, Department of Chemistry, P. O. Box 90950, Riyadh 11623, Kingdom of Saudi Arabia, Photochemistry Department, (Heterocyclic & Nucleosides Unit), National Research Centre, Cairo, Egypt
MAGDI E. A. ZAKI ; Al-Imam Mohammad Ibn Saud Islamic University (IMSIU), College of Science, Department of Chemistry, P. O. Box 90950, Riyadh 11623, Kingdom of Saudi Arabia, Photochemistry Department, (Heterocyclic & Nucleosides Unit), National Research Centre, Cairo, Egypt

Abstract

6-(4-Chlorophenyl)-spiro[cyclohexane-1,2-thieno[3,2-d][1,3]oxazin]-4(1H)-one (1) was synthesized and used as a starting material for the synthesis of a novel series of spiro compounds having biologically active sulfonamide (2a-e) and 3-(4-acetylphenyl)-6-(4-chlorophenyl)-1H-spiro[cyclohexane-1,2-thieno[3,2-d]pyrimidine-4(3H)-one (3). Compound 2a was used as a key intermediate for the synthesis of sulfonyl carbothioamide derivatives (4a-c). Also, compound 3 was used as an intermediate for the synthesis of 3H-spiro[cyclohexane-1,2-thieno[3,2-d]pyrimidin]-3-yl]phenyl}-2-imino-4-(substituted phenyl and/or thienyl)-1,2-dihydropyridine-3-carbonitrile derivatives (5a-e), 3H-spiro[cyclohexane-1,2-thieno[3,2-d]pyrimidin]-3-yl]phenyl}-2-oxo-4-(substituted phenyl and/or thienyl)-1,2-dihydropyridine-3-carbonitrile derivatives (6a-e), and 4-[(2Z)-3-substituted-arylprop-2-enoyl]phenyl-1H-spiro[cyclohexane-1,2-thieno[3,2-d]pyrimidine derivatives (7a-e). Cyclocondensation of 7a-e with hydrazine hydrate produced 6-(4-chlorophenyl)-3-[4-(5-substituted aryl-4,5-dihydro-1H-pyrazol-3-yl)phenyl]-1H-spiro[cyclohexane-1,2-thieno-[3,2-d]pyrimidin]-4(3H)-ones (8a-e), but with hydroxylamine hydrochloride afforded the corresponding isoxazoline derivatives (9a-e). Also, cyclocondensation by thiourea afforded 2-thioxo-1,2-dihydropyrimidin-4-yl)-phenyl-spiro-{cyclohexanethieno[3,2-d]pyrimidin}-4-one derivatives (10a-e). The new compounds were investigated for antimicrobial activity. Compounds 2c, 8b, c, 9b and 10b were the most potent ones against both Gram-negative and Gram-positive bacteria. Compound 8c exhibited higher antifungal activity towards the examined fungi with MIC of 1–2 µmol mL–1 compared to ketoconazole (MIC 2–3 µmol mL–1).

Keywords

thieno[3,2-d][1,3]oxazin]-4-one; thieno[3,2-d]pyrimidines; N-nucleophiles; spiro-thieno[3,2-d]pyrimidine; ring transformation; antimicrobial

Hrčak ID:

154044

URI

https://hrcak.srce.hr/154044

Publication date:

30.9.2016.

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