Synthesis of pyrimido[4,5-b]quinolindiones and formylation: ultrasonically assisted reactions
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ABSTRACT:
SUBMITTER: Trilleras J
PROVIDER: S-EPMC10915537 | biostudies-literature | 2024 Mar
REPOSITORIES: biostudies-literature
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Project description:BackgroundPoly-substituted xanthine derivatives are an important class of compounds in medicinal chemistry. Substitution at the 8-position of the purine ring is generally accessible by ring closure of a carboxamido-substituted uracil precursor. Although several procedures to accomplish this synthetic step have been suggested, it still remains difficult in many cases.ResultsRing closure reaction with hexamethyldisilazane was studied under microwave conditions. Reaction times were dramatically reduced by the application of microwaves in the syntheses of the 8-styrylxanthine derivative istradefylline, and in the preparation of 2-substituted pyrimido [1,2,3-cd]purines. Furthermore, the new procedure allowed the preparation of a previously unaccessible diazepino [1,2,3-cd]purine. Yields were generally improved by the new method. The addition of THF as a co-solvent proved to be crucial.ConclusionA new, fast, and efficient ring closure method for the imidazole ring of xanthine derivatives and related tricyclic compounds has been developed. Apart from improving the syntheses of known compounds, some of which are important pharmacological tools or in development as novel drugs, it allows the preparation of 2-substituted diazepino [1,2,3-cd]purines--a new class of tricyclic purine derivatives.
| S-EPMC1698928 | biostudies-literature
Project description:Trityl chloride (TrCl) was efficiently used as a neutral catalyst for the multicomponent cyclization reaction of an aldehyde with dimedone and 6-amino-1,3-dimethyluracil for the preparation of pyrimido[4,5-b] quinolines in chloroform under reflux condition.
| S-EPMC10543543 | biostudies-literature
Project description:Three types of sugar modified pyrimido[4,5-b]indole nucleosides (2'-deoxy-2'-fluororibo-, 2'-deoxy-2'-fluoroarabino- and arabinonucleosides) were synthesized by glycosylation of 4,6-dichloropyrimido[4,5-b]indole followed by modification of sugar moiety and introduction of substituents into position 4 by cross-coupling reactions or nucleophilic substitutions. Some 2'-fluororibo- and 2'-fluoroarabinonucleosides displayed interesting anti-HCV activities (IC50 = 1.6-20 μM) and the latter compounds also some anti-dengue activities (IC50 = 10.8-40 μM).
| S-EPMC6084004 | biostudies-literature
Project description:In order to expand the application of Fe3O4@SiO2-SnCl4 in the synthesis of heterocyclic compounds, in this study, we wish to report the use of one-pot three component synthesis of pyrimido [4,5-b]quinolone derivatives ( D1-D16 ) through reaction of 6-amino-2-(methylthio)pyrimidin-4 (3H)-one, dimedone, or 1,3-cyclohexadione and aldehydes in the presence of Fe3O4@SiO2-SnCl4 as an efficient eco-friendly catalyst under ultrasound irradiation. The final aim of this study is evaluation of antifungal activity of resulted products. Synthesis of pyrimido [4,5-b]quinolin derivatives were done via three components coupling reaction of aldehyde, dimedone or 1,3-cyclohexadione and 6-amino-2-(methylthio)pyrimidin-4 (3H)-one in the presence of Fe3O4@SiO2-SnCl4 under ultrasonic irradiation in water at 60 °C. The products structure were studied by FT-IRI, 1H NMR,II and 13C NMRII. All the compounds were screened for antimicrobial activity by broth microdilution methods as recommended by CLSIIII. Considering our results showed that compound ( D13 ) had the most antifungal activity against C. dubliniensis, C. Albicans, C. Tropicalis, and C. Neoformance at concentrations ranging (MIC90) from 1-4 μg/mL. Compounds ( D9 ), ( D10 ), ( D14 ), and ( D15 ) had significant inhibitory activities against C. dubliniensis at concentrations ranging (MIC90) from 4-8 μg/mL, respectively. 5-(3,4-dihydroxyphenyl)-8,8-dimethyl-2-(methylthio)-5,8,9,10-tetrahydropyrimido[4,5-b]quinoline-4,6(3H,7H)-dione ( D13 ) exhibited inhibitory and fungicidal activities against the tested yeasts. The specific binding mode or the binding orientation of more efficient compounds to CYP51 active site, have been also performed by molecular modeling investigations and showed that there is a good correlation with biological test.
| S-EPMC7462489 | biostudies-literature
Project description:An improved synthesis of 3-(substituted)pyrimido[4,5-c]pyridazine-5,7(1H,6H)-diones, a known subclass of 4-deazatoxoflavins, is reported. The approach involves treatment of 3-methyl-6-(1-methylhydrazinyl) uracil with representative phenyl and alkyl glyoxal monohydrates, which in turn are obtained by selenium dioxide oxidation of the corresponding phenyl and alkyl methyl ketones. The first entry into 4-monosubstituted isomers is also reported.
| S-EPMC2987637 | biostudies-literature
Project description:Novel 1H-pyrimido [4,5-c][1,2]diazepines 3 & 4 and pyrazolo [3,4-d]pyrimidines 6 were regioselectively synthesised by the reaction of 1,3-dimethyl-6-hydrazinouracils 1 with various alpha,beta-unsaturated compounds 2 and alpha-ketoalkynes 8 in excellent yields.
| S-EPMC1470455 | biostudies-literature
Project description:A series of 2,5,7-trisubstituted pyrimido[4,5-d]pyrimidine cyclin-dependent kinase (CDK2) inhibitors is designed and synthesized. 6-Amino-2-thiouracil is reacted with an aldehyde and thiourea to prepare the pyrimido[4,5-d]-pyrimidines. Alkylation and amination of the latter ones give different amino derivatives. These compounds show potent and selective CDK inhibitory activities and inhibit in vitro cellular proliferation in cultured human tumor cells.
| S-EPMC3163380 | biostudies-literature
Project description:A series of 2,5,7-trisubstituted pyrimido[4,5-d]pyrimidine cyclin-dependent kinase (CDK2) inhibitors is designed and synthesized. 6-Amino-2-thiouracil is reacted with an aldehyde and thiourea to prepare the pyrimido[4,5-d]-pyrimidines. Alkylation and amination of the latter ones give different amino derivatives. These compounds show potent and selective CDK inhibitory activities and inhibit in vitro cellular proliferation in cultured human tumor cells.
| S-EPMC3163380 | biostudies-literature
Project description:This study aimed to create an innovative acidic nano catalyst capable of producing pyrimido[4,5-b]quinolines under environmentally friendly conditions. To achieve this objective, 1,3-benzenedisulfonyl amide (BDSA) was immobilized onto the surface of magnetic graphene oxide (GO/Fe3O4@PTRMS@BDSA@SO3H), and its surface was acidified using chlorosulfonic acid. The synthesized catalyst's structure was thoroughly examined and verified through various analyses, including FTIR, EDX, elemental mapping, FESEM, XRD, TGA, and DSC. This novel nano catalyst exhibited exceptional activity and selectivity in synthesizing pyrimido[4,5-b]quinoline derivatives under solvent-free conditions, at low temperatures, and with high efficiency. Its catalytic effectiveness stemmed from features such as easy and eco-friendly synthesis methods, abundant accessible catalytic sites, a high surface area, remarkable selectivity, and facile separation from the reaction medium. Additionally, the catalyst proved to be cost-effective, safe, scalable, and reusable for up to four times.
| S-EPMC11402980 | biostudies-literature
Project description:The title compound, C(24)H(22)N(4)O(2)·H(2)O, was synthesized by the trimethyl-chloro-silane-catalysed reaction between urea, benzaldehyde and acetophenone. The organic mol-ecule comprises two fused tetra-hydro-pyrimidinone rings with phenyl substituents at the 4- and 5-positions on the tetra-hydro-pyrimidinone rings and a third phenyl substituent at the ring junction 8-position. The 4- and 5-substituted phenyl rings are inclined at a dihedral angle of 22.72 (11)° to one another and make angles of 47.95 (7) and 65.76 (7)° with the third phenyl substituent. In the crystal structure, inter-molecular N-H⋯O contacts link pyrimido[4,5-d]pyrimidine mol-ecules into centrosymmetric dimers. Additional N-H⋯O and O-H⋯O hydrogen bonds involving the water mol-ecule generate a three-dimensional network.
| S-EPMC2979643 | biostudies-literature