Thiazolo[4,5-d]pyrimidines as a privileged scaffold in drug discovery

Kuppast, Bhimanna; Fahmy, Hesham

doi:10.1016/j.ejmech.2016.02.031

Cited by 44 publications

(15 citation statements)

References 57 publications

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“…To our knowledge, there are several studies showing thiazolo[4,5‐ d ]pyrimidines scaffold as anti‐inflammatory agents, but few have reported on the cytokine‐inhibitory effects of thiazolo[3,2‐ a ]pyrimidine derivatives and their structure–activity relationship (SAR) . As shown in Table , compounds with halogen substitution on the phenyl moiety at the R 1 position such as 4‐bromo ( 11 a ) or 4‐fluoro ( 11 b ) group, showed similar potency to the lead compound 6 (phenyl).…”

Section: Resultsmentioning

confidence: 99%

“…Hence, there is a pressing need to identify an effective strategy to prevent or mitigate ALI. Thiazolo and pyrimidine fused heterocyclic rings are viable templates for the development of anti‐inflammatory molecules . In this study, we designed and synthesized a novel series of thiazolo[3,2‐ a ]pyrimidine analogues and evaluated their anti‐inflammatory activity relative to the lead compound 6 .…”

Section: Discussionmentioning

confidence: 99%

“…Thiazolo‐ and pyrimidine‐fused heterocyclic ring‐systems were commonly found in novel therapeutics, including antimicrobial ( 1 , Figure ), antiviral ( 2 ), anticancer ( 3 , 4 ), anti‐Parkinson's ( 5 ), and anti‐inflammatory agents . In the past, our research group has designed, synthesized and evaluated a number of compounds targeting pro‐inflammatory cytokines for the treatment of sepsis and ALI .…”

Section: Introductionmentioning

confidence: 99%

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Design, Synthesis, and Structure–Activity Relationship Analysis of Thiazolo[3,2‐a]pyrimidine Derivatives with Anti‐inflammatory Activity in Acute Lung Injury

Chen

Jin

et al. 2017

ChemMedChem

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Acute lung injury (ALI) has a high lethality rate, and interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) contribute most to tissue deterioration in cases of ALI. In this study, we designed and synthesized a new series of thiazolo[3,2-a]pyrimidine derivatives based on a previously identified lead compound, and we evaluated their anti-inflammatory activities. Structure-activity relationship studies led to the discovery of two highly potent inhibitors. The two promising compounds were found to inhibit lipopolysaccharide (LPS)-induced IL-6 and TNF-α release in a dose-dependent manner in mouse primary peritoneal macrophages (MPMs). Furthermore, administration of these compounds resulted in lung histopathological improvements and attenuated LPS-induced ALI in vivo. Taken together, these data indicate that these novel thiazolo[3,2-a]pyrimidine derivatives could be developed as candidate drugs for the treatment of ALI.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Design, Synthesis, and Structure–Activity Relationship Analysis of Thiazolo[3,2‐a]pyrimidine Derivatives with Anti‐inflammatory Activity in Acute Lung Injury

Chen

Jin

et al. 2017

ChemMedChem

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“…They exhibited anticancer [1][2][3][4][5], antioxidant [6][7][8], antifungal [9,10], and antibacterial activities [11][12][13][14]. Furthermore, thiazolopyrimidine derivatives were considered as potent cytotoxic, analgesic, and antifungal agents [24][25][26]. Furthermore, thiazolopyrimidine derivatives were considered as potent cytotoxic, analgesic, and antifungal agents [24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Some Novel Thiazolo[3,2‐a]pyrimidine and Pyrimido[2,1‐b][1,3]thiazine Derivatives and their Antimicrobial Evaluation

Behalo

2018

Journal of Heterocyclic Chem

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A 2‐(2‐Mercapto‐4‐(4‐phenoxyphenyl)‐6‐(thiophen‐2‐yl)‐1,6‐dihydropyrimidin‐5‐yl) acetic acid was used as a reactive key precursor to design various pyrimidine derivatives such as thiazolo[3,2‐a]pyrimidines and pyrimido[2,1‐b][1,3]thiazines. The chemical structures of the newly synthesized products were confirmed by their elemental analyses and spectral data (IR, 1H NMR, 13C NMR, and mass spectra). The antibacterial and antifungal activities of some of the synthesized products were also evaluated, and it was found that compounds 3, 5, 9, and 11 exhibited potent activity against tested microorganisms in comparison with standard drugs.

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“…While DHPMs have emerged as potential backbones of several calcium channel blockers, antihypertensive agents and neuropeptide Y antagonists, thiazolopyrimidines and their analogues have raised considerable interest as purine isosteres [1][2][3][4][5][6] .…”

Section: Introductionmentioning

confidence: 99%

<strong>Synthesis and characterization of 2-arylidene derivatives of thiazolopyrimidines with potential biological activity</strong>

Mahgoub

El‐Maghraby

Harb

et al. 2016

Proceedings of the 20th International Electronic Conference on Synthetic Organic Chemistry

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Aryl-3,4-dihydropyrimidinones (DHPM), thiazolopyrimidines and related heteroaromatic compounds are important classes of N-containing fused heterocycles widely used as key building blocks for pharmaceutical agents due to a wide range of biological activities that include antimicrobial and antitumor properties. As part of a program aimed at preparing new bioactive heterocycles, we designed and synthesized a series of thiazolopyrimidines and their 2-arylidene derivatives. The compounds were fully characterized by 1D-and 2D-NMR, high resolution ESI-MS/MS and single crystal X-ray diffraction analysis, which indicated a consistent Z configuration at the arylidene double bond. In addition, the ESI-MS fragmentation mechanisms for representatives of the DHPM, thiazolopyrimidine, and 2-arylidene-thiazolopyrimidine classes were elucidated. Studies are underway to assess the biological activities of the new compounds.

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Thiazolo[4,5-d]pyrimidines as a privileged scaffold in drug discovery

Cited by 44 publications

References 57 publications

Design, Synthesis, and Structure–Activity Relationship Analysis of Thiazolo[3,2‐a]pyrimidine Derivatives with Anti‐inflammatory Activity in Acute Lung Injury

Design, Synthesis, and Structure–Activity Relationship Analysis of Thiazolo[3,2‐a]pyrimidine Derivatives with Anti‐inflammatory Activity in Acute Lung Injury

Synthesis of Some Novel Thiazolo[3,2‐a]pyrimidine and Pyrimido[2,1‐b][1,3]thiazine Derivatives and their Antimicrobial Evaluation

<strong>Synthesis and characterization of 2-arylidene derivatives of thiazolopyrimidines with potential biological activity</strong>

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