title: Simple approach to thieno[3,2-d]pyrimidines as new scaffolds of antimicrobial activities.
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 ).
authors.forename: Hend N
authors.initials: HN
authors.lastname: Hafez
authors.forename: Abdel-Rhman B A
authors.initials: AR
authors.lastname: El-Gazzar
authors.forename: Magdi E A
authors.initials: ME
authors.lastname: Zaki
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001231:Aspergillus flavus / Q000187:drug effects / Q000254:growth & development; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development; D015195:Drug Design; D032902:Ganoderma / Q000187:drug effects / Q000254:growth & development; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000254:growth & development; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D044366:Transition Temperature
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D011743:Pyrimidines; D011744:Pyrimidinones; D013141:Spiro Compounds; D013876:Thiophenes