Simple approach to thieno[3,2-d]pyrimidines as new scaffolds of antimicrobial activities
6ʹ-(4-Chlorophenyl)-spiro[cyclohexane-1,2ʹ-thieno[3,2-d][1,3] oxazin]-4ʹ(1ʹH)-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 3ʹ-(4-acetylphenyl)-6ʹ- (4-chlorophenyl)-1ʹH-spiro[cyclohexane-...
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| Language: | English |
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2016-09-01
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| Series: | Acta Pharmaceutica |
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| Online Access: | https://doi.org/10.1515/acph-2016-0029 |
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| author | Hafez Hend N. El-Gazzar Abdel-Rhman B. A. Zaki Magdi E. A. |
| author_facet | Hafez Hend N. El-Gazzar Abdel-Rhman B. A. Zaki Magdi E. A. |
| author_sort | Hafez Hend N. |
| collection | DOAJ |
| description | 6ʹ-(4-Chlorophenyl)-spiro[cyclohexane-1,2ʹ-thieno[3,2-d][1,3] oxazin]-4ʹ(1ʹH)-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 3ʹ-(4-acetylphenyl)-6ʹ- (4-chlorophenyl)-1ʹH-spiro[cyclohexane-1,2ʹ-thieno[3,2-d] pyrimidine-4ʹ(3ʹH)-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 3ʹH-spiro[cyclohexane-1,2ʹ-thieno[3,2-d]pyrimidin]-3ʹ-yl] phenyl}-2-imino-4-(substituted phenyl and/or thienyl)-1,2-dihydropyridine- 3-carbonitrile derivatives 5a-e, 3ʹH-spiro[cyclohexane- 1,2ʹ- thieno[3,2-d]pyrimidin]-3ʹ-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-1ʹH-spiro[cyclohexane-1,2ʹ-thieno[3,2-d]pyrimidine derivatives 7a-e. Cyclocondensation of 7a-e with hydrazine hydrate produced 6ʹ-(4-chlorophenyl)-3ʹ-[4-(5-substituted aryl-4,5-dihydro- 1H-pyrazol-3-yl)phenyl]-1ʹH-spiro[cyclohexane-1,2ʹ-thieno- [3,2-d]pyrimidin]-4ʹ(3ʹH)-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 ). |
| format | Article |
| id | doaj-art-11ea79951210434c930b40154d83ed3d |
| institution | Kabale University |
| issn | 1846-9558 |
| language | English |
| publishDate | 2016-09-01 |
| publisher | Sciendo |
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| series | Acta Pharmaceutica |
| spelling | doaj-art-11ea79951210434c930b40154d83ed3d2025-02-02T09:44:22ZengSciendoActa Pharmaceutica1846-95582016-09-0166333135110.1515/acph-2016-0029acph-2016-0029Simple approach to thieno[3,2-d]pyrimidines as new scaffolds of antimicrobial activitiesHafez Hend N.0El-Gazzar Abdel-Rhman B. A.1Zaki Magdi E. A.2Al-Imam Mohammad Ibn Saud Islamic University (IMSIU) College of Science, Department of Chemistry, P. O. Box 90950 Riyadh 11623 Kingdom of Saudi ArabiaAl-Imam Mohammad Ibn Saud Islamic University (IMSIU) College of Science, Department of Chemistry, P. O. Box 90950 Riyadh 11623 Kingdom of Saudi ArabiaAl-Imam Mohammad Ibn Saud Islamic University (IMSIU) College of Science, Department of Chemistry, P. O. Box 90950 Riyadh 11623 Kingdom of Saudi Arabia6ʹ-(4-Chlorophenyl)-spiro[cyclohexane-1,2ʹ-thieno[3,2-d][1,3] oxazin]-4ʹ(1ʹH)-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 3ʹ-(4-acetylphenyl)-6ʹ- (4-chlorophenyl)-1ʹH-spiro[cyclohexane-1,2ʹ-thieno[3,2-d] pyrimidine-4ʹ(3ʹH)-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 3ʹH-spiro[cyclohexane-1,2ʹ-thieno[3,2-d]pyrimidin]-3ʹ-yl] phenyl}-2-imino-4-(substituted phenyl and/or thienyl)-1,2-dihydropyridine- 3-carbonitrile derivatives 5a-e, 3ʹH-spiro[cyclohexane- 1,2ʹ- thieno[3,2-d]pyrimidin]-3ʹ-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-1ʹH-spiro[cyclohexane-1,2ʹ-thieno[3,2-d]pyrimidine derivatives 7a-e. Cyclocondensation of 7a-e with hydrazine hydrate produced 6ʹ-(4-chlorophenyl)-3ʹ-[4-(5-substituted aryl-4,5-dihydro- 1H-pyrazol-3-yl)phenyl]-1ʹH-spiro[cyclohexane-1,2ʹ-thieno- [3,2-d]pyrimidin]-4ʹ(3ʹH)-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 ).https://doi.org/10.1515/acph-2016-0029thieno[3,2-d][1,3]oxazin]-4ʹ-onethieno[3,2-d]pyrimidinesn-nucleophilesspiro-thieno[3,2-d]pyrimidinering transformationantimicrobial |
| spellingShingle | Hafez Hend N. El-Gazzar Abdel-Rhman B. A. Zaki Magdi E. A. Simple approach to thieno[3,2-d]pyrimidines as new scaffolds of antimicrobial activities Acta Pharmaceutica thieno[3,2-d][1,3]oxazin]-4ʹ-one thieno[3,2-d]pyrimidines n-nucleophiles spiro-thieno[3,2-d]pyrimidine ring transformation antimicrobial |
| title | Simple approach to thieno[3,2-d]pyrimidines as new scaffolds of antimicrobial activities |
| title_full | Simple approach to thieno[3,2-d]pyrimidines as new scaffolds of antimicrobial activities |
| title_fullStr | Simple approach to thieno[3,2-d]pyrimidines as new scaffolds of antimicrobial activities |
| title_full_unstemmed | Simple approach to thieno[3,2-d]pyrimidines as new scaffolds of antimicrobial activities |
| title_short | Simple approach to thieno[3,2-d]pyrimidines as new scaffolds of antimicrobial activities |
| title_sort | simple approach to thieno 3 2 d pyrimidines as new scaffolds of antimicrobial activities |
| topic | thieno[3,2-d][1,3]oxazin]-4ʹ-one thieno[3,2-d]pyrimidines n-nucleophiles spiro-thieno[3,2-d]pyrimidine ring transformation antimicrobial |
| url | https://doi.org/10.1515/acph-2016-0029 |
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