Discovery of 7-<i>N</i>-Piperazinylthiazolo[5,4-<i>d</i>]pyrimidine Analogues as a Novel Class of Immunosuppressive Agents with in Vivo Biological Activity

Jang, Miyeon; Lin, Yuan; Jonghe, Steven De; Gao, Ling‐Jie; Vanderhoydonck, Bart; Froeyen, Mathy; Rozenski, Jef; Herman, Jean; Louat, Thierry; Belle, Kristien Van; Waer, Mark; Herdewijn, Piet

doi:10.1021/jm101254z

Cited by 35 publications

(23 citation statements)

References 32 publications

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“…For abacavir ( 6.37 ) the guanosine analogue comes via a stepwise process (Scheme 55) [130]. The key building block is diaminodichloropyrimidine 6.40 which can be prepared by cyclocondensation of guanidine with diethyl malonate ( 6.39 ), followed by chlorination using phosphorous oxychloride [131]. Formylation of both amines with formic acid in cold acetic anhydride gives rise to the bis -formamide 6.41 , which is then treated with aminocyclopentene 6.42 to yield the required purine ring system 6.43 .…”

Section: Reviewmentioning

confidence: 99%

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

Baumann¹,

Baxendale²

2013

Beilstein J. Org. Chem.

700

336

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This review which is the second in this series summarises the most common synthetic routes as applied to the preparation of many modern pharmaceutical compounds categorised as containing a six-membered heterocyclic ring. The reported examples are based on the top retailing drug molecules combining synthetic information from both scientific journals and the wider patent literature. It is hoped that this compilation, in combination with the previously published review on five-membered rings, will form a comprehensive foundation and reference source for individuals interested in medicinal, synthetic and preparative chemistry. 2265

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Section: Reviewmentioning

confidence: 99%

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

Baumann¹,

Baxendale²

2013

Beilstein J. Org. Chem.

700

336

View full text Add to dashboard Cite

show abstract

“…The second step in the synthesis of the targeted 5-substituted 2-amino-4,6-dichloropyrimidines B2-B11 (Scheme 1) consists of the transformation of the 4,6-dihydroxypyrimidine moiety into the 4,6-dichloropyrimidine residue. For such reactions, chlorides of mineral acids such as POCl 3 , PCl 5 , SOCl 2 , or COCl 2 with diverse additives like DMF, pyridine, 2-methylpyridine, diphenylamine, or triethylamine are generally used (Altenbach et al, 2008;Jang et al, 2011). Nevertheless, these classical procedures turned out to be unsuitable for the preparation of the desired 5-substituted 2-amino-4,6-dichloropyrimidines B2-B11, owing to their complicated isolations and very low isolated yields (max.…”

Section: Chemistrymentioning

confidence: 99%

5-Substituted 2-amino-4,6-dihydroxypyrimidines and 2-amino-4,6-dichloropyrimidines: synthesis and inhibitory effects on immune-activated nitric oxide production

et al. 2014

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A series of 5-substituted 2-amino-4,6-dihydroxypyrimidines were prepared by a modified condensation of the corresponding monosubstituted malonic acid diesters with guanidine in an excess of sodium ethoxide. The optimized procedure using Vilsmeier-Haack-Arnold reagent, followed by immediate deprotection of the (dimethylamino)methylene protecting groups, has been developed to convert the 2-amino-4,6-dihydroxypyrimidine analogs to novel 5-substituted 2-amino-4,6-dichloropyrimidines in high yields. Pilot screening for biological properties of the prepared compounds was done in mouse peritoneal cells using the in vitro nitric oxide (NO) assay. Irrespective of the substituent at the 5 position, 2-amino-4,6-dichloropyrimidines inhibited immune-activated NO production. The most effective was 5-fluoro-2-amino-4,6dichloropyrimidine with an IC 50 of 2 lM (higher activity than the most potent reference compound) while the IC 50 s of other derivatives were within the range of 9-36 lM. The 2-amino-4,6-dihydroxypyrimidine counterparts were devoid of any NO-inhibitory activity. The compounds had no suppressive effects on the viability of cells. The Mechanism of action remains to be elucidated.

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“…They also inhibit the proliferation of E. coli K 12 cells with IC 50 values between 0.5 and 6 μM for the n-propyl and ethyl group respectively, while for methyl and the bulky substituents, IC 50 values higher than 100 μM were observed. [56] This type of structures also possesses antiviral activity against poliovirus and hepatitis C genotype 1a (HCV-1a). Activated NEDD8 is needed in two DNA repair pathways.…”

Section: Miscellaneous Biological Activitymentioning

confidence: 99%

Synthesis and Biological Activity of Oxazolopyrimidines

et al. 2018

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In this work, the synthesis of oxazolo[4,5‐d]pyrimidines and oxazolo[5,4‐d]pyrimidines is reviewed. The review is focused on the construction of the scaffold rather than on its further modification. Nevertheless, selected examples illustrate some of the most common modifications of these scaffolds. The synthetic part is complemented by an overview of their biological activity. This review covers literature and patents from 1967 until the present.

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Discovery of 7-N-Piperazinylthiazolo[5,4-d]pyrimidine Analogues as a Novel Class of Immunosuppressive Agents with in Vivo Biological Activity

Cited by 35 publications

References 32 publications

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

5-Substituted 2-amino-4,6-dihydroxypyrimidines and 2-amino-4,6-dichloropyrimidines: synthesis and inhibitory effects on immune-activated nitric oxide production

Synthesis and Biological Activity of Oxazolopyrimidines

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