- Convenient One-Pot Four-Component Synthesis of 6,8-Disubstituted-5,6,7,8-tetrahydropyrimido[4,5-d]-pyrimidin-4(3H)-ones via a Triple Mannich Reaction
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An efficient and simple one-pot four-component protocol has been developed and performed for the synthesis of 6,8-disubstituted-5,6,7,8-tetrahydropyrimido[4,5-d]pyrimidin-4(3H)-ones, involving a triple Mannich reaction of 6-amino-2-(ethylthio)pyrimidin-4(3H)-one, formaldehyde, primary amines, and alcohols. Secondary amines were also utilised instead of alcohols as Mannich nucleophiles, and a variety of functional groups and electronically varied reaction partners were tolerated. This one-pot reaction facilitated the generation of a library of pyrimido[4,5-d]pyrimidin-4(3H)-ones in very good to excellent yields. The regioselectivity of this reaction was investigated using atomic charge calculations, and spectroscopic data confirmed that the triple Mannich products were 6,8-disubstituted-5,6,7,8-tetrahydropyrimido[4,5-d]pyrimidin-4(3H)-ones rather than the isomeric 3,6-disubstituted-5,6,7,8-tetrahydropyrimido[4,5-d]pyrimidin-4(3H)-ones. The structures of all compounds synthesised using the triple Mannich reaction were confirmed via spectroscopic and elemental analyses. The reaction mechanism was studied and confirmed by isolation of the intermediate.
- El-Mahdy, Ahmed F. M.,El-Sherief, Hassan A. H.,Hozien, Zainab A.
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- Synthesis of 2-ethylthio-6-(3-hydroxy-1,2-O- isopropylidenepropyl)pteridin-4(3H)-one
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A strategy has been described for the synthesis of 2-ethylthio-6-(3- hydroxy-1,2-O-isopropylidenepropyl)pteridin-4(3H)-one, which can be used as a useful intermediate for the conversion of neopterin to biopterin.
- Kang, Yonghan,Kim, Seungjin,Myoung, Youngchan,Baek, Daejin
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- Chemical synthesis of some novel 6-aminouracil-2-thiones and their glycoside analogues
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6-AMINOURACIL-2-THIONE (1) and its 5-bromo derivative 2 underwent alkylation yielding their respective S-alkyl products 4a-j. The reaction of compound 1 and aldehydes in the presence of chloroacetic acid afforded the respective thiazolopyrimidinyl acetamides 7a-d. The C-glycosides 8a, b and 9c-e were successfully prepared through condensing compound 1 and the appropriate sugar in the presence of chloroacetic acid. The behavior of certain S-alkyl derivative 4 towards amines and hydrazines was also studied. Structure elucidations for the new products were supported by compatible chemical and spectral measurements.
- Gaafar,Aly,Abu-Zied, Khadiga M.,Abdel-Rahman, Asmaa E.,Helmy
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p. 779 - 797
(2017/04/17)
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- Derivatives of 4-amino-6-hydroxy-2-mercaptopyrimidine as novel, potent, and selective A3 adenosine receptor antagonists
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A number of derivatives of 4-amino-6-hydroxy-2-mercaptopyrimidine (5) were synthesized and biologically evaluated as A3 adenosine receptor (A3 AR) antagonists. The new compounds were designed as open chain analogues of a triazolopyrimidinone derivative displaying submicromolar affinity for the A3 AR, which had been previously identified using a 3D database search. Substituents R, R′, and R″ attached to the parent compound 5 were chosen according to factorial design and stepwise lead optimization approaches, taking into account the essentially hydrophobic nature of the A3 AR binding site. As a result, 5m (R = n-C3H 7, R′ = 4-ClC6H4CH2, R″ = CH3) was identified among the pyrimidine derivatives as the ligand featuring the best combination of potency and selectivity for the target receptor. This compound binds to the A3 AR with a Ki of 3.5 nM and is devoid of appreciable affinity for the A1, A 2A, and A2B ARs.
- Cosimelli, Barbara,Greco, Giovanni,Ehlardo, Marina,Novellino, Ettore,Da Settimo, Federico,Taliani, Sabrina,La Motta, Concettina,Bellandi, Marusca,Tuccinardi, Tiziano,Martinelli, Adriano,Ciampi, Osele,Trincavelli, Maria Letizia,Martini, Claudia
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p. 1764 - 1770
(2008/12/22)
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- Hit-to-Lead studies: The discovery of potent, orally bioavailable thiazolopyrimidine CXCR2 receptor antagonists
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A Hit-to-Lead optimisation programme was carried out on a high throughput screening hit, the thiazolopyrimidine 1, resulting in the discovery of the potent, orally bioavailable CXCR2 antagonist 29.
- Baxter, Andrew,Cooper, Anne,Kinchin, Elizabeth,Moakes, Kerry,Unitt, John,Wallace, Alan
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p. 960 - 963
(2007/10/03)
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