Synthesis of thiophenecarboxamides, thieno[3,4- c ]pyridin-4(5 H )-ones and thieno[3,4- d ]pyrimidin-4(3 H )-ones and preliminary evaluation as inhibitors of poly(ADP-ribose)polymerase (PARP)

Shinkwin, Anne E.; Whish, William J. D.; Threadgill, Michael D.

doi:10.1016/s0968-0896(98)00210-7

Cited by 31 publications

(20 citation statements)

References 42 publications

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“…As has been reported, thiophenecarboxamide-type compounds have effects on many pharmacological events, such as anti-inflammation (Baxter et al 2004), cell cycle regulation (Janetka et al 2008), antifungal actions, DNA damage inhibition (Shinkwin et al 1999), and inhibition of Ca 2C -release-activated calcium channels (Yonetoku et al 2006), and no reports have been published on their anti-diabetic effects. Therefore, our current report that the thiophenecarboxamide derivative BBT efficiently improved b-cell dysfunction is expected to have expanded the pharmacological understanding of thiophenecarboxamide compounds.…”

Section: Discussionmentioning

confidence: 99%

BBT improves glucose homeostasis by ameliorating β-cell dysfunction in type 2 diabetic mice

Yao

Wang

et al. 2015

Journal of Endocrinology

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Impaired glucose-stimulated insulin secretion (GSIS) and increasing b-cell death are two typical dysfunctions of pancreatic b-cells in individuals that are destined to develop type 2 diabetes, and improvement of b-cell function through GSIS enhancement and/or inhibition of b-cell death is a promising strategy for anti-diabetic therapy. In this study, we discovered that the small molecule, N-(2-benzoylphenyl)-5-bromo-2-thiophenecarboxamide (BBT), was effective in both potentiating GSIS and protecting b-cells from cytokine-or streptozotocin (STZ)-induced cell death. Results of further studies revealed that cAMP/PKA and long-lasting (L-type) voltage-dependent Ca 2C channel/CaMK2 pathways were involved in the action of BBT against GSIS, and that the cAMP/PKA pathway was essential for the protective action of BBT on b-cells. An assay using the model of type 2 diabetic mice induced by high-fat diet combined with STZ (STZ/HFD) demonstrated that BBT administration efficiently restored b-cell functions as indicated by the increased plasma insulin level and decrease in the b-cell loss induced by STZ/HFD. Moreover, the results indicated that BBT treatment decreased fasting blood glucose and HbA1c and improved oral glucose tolerance further highlighting the potential of BBT in anti-hyperglycemia research.

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Section: Discussionmentioning

confidence: 99%

BBT improves glucose homeostasis by ameliorating β-cell dysfunction in type 2 diabetic mice

Yao

Wang

et al. 2015

Journal of Endocrinology

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“…[12][13][14][15][16][17][18][19][20] In particular, they are currently an important group of compounds that have anticancer activity especially against solid tumors (e.g., breast and ovarian). [21][22][23][24] Several mechanisms have been reported for the cytotoxic activity of thienopyrimidines including: inhibition of protein kinases (PKs) either as competitive or noncompetitive inhibitors. It was reported that they exerted their action by inhibiting tyrosine kinases (TKs) that represents a major advance in the treatment of solid tumors.…”

Section: -7)mentioning

confidence: 99%

Synthesis of Some Novel Thieno[3,2-<i>d</i>]pyrimidines as Potential Cytotoxic Small Molecules against Breast Cancer

Kandeel

Abdelhameid

Eman

et al. 2013

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…4a), the thieno [3,4-d]pyrimidine derivative ( Fig. 4b) expressed 93% inhibition of PARP at a dose of 10 μM [18]. Additionally, many PARP-1 inhibitors were declared to be used in clinical trials as: MK4827 [19] (Fig.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of Some Cyclohepta[b]Thiophene and Substituted Pentahydrocycloheptathieno[2,3‐d]Pyrimidine Derivatives

Elmongy

Khedr

Taleb

et al. 2016

Journal of Heterocyclic Chem

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This investigation describes the design of a series of cycloheptathieno [2,3-d]pyrimidines along with their synthetic strategy. The target compounds were screened for their PARP-1 inhibitory activity. The modeling study declared that most of the docked compounds showed the same interactions as 3-aminobenzamide, where Gly 894, His 862, Tyr 896, Arg 878, and Ser 864 were the main residues involved in hydrogen bond formation. Compounds eliciting the top ranked docking results were screened for their PARP-1 inhibitory activity giving promising results, and three representative compounds were tested for their cytotoxic activity using Doxorubicin as a reference standard. The target compounds 1-17 including cyclohepta [b]thiophene and pentahydrocycloheptathieno [2,3-d]pyrimidine cores were designed, prepared, and tested for their PARP-1 inhibitory activity. Compounds 16 (R: -NHC(S)NH2) and 11 (R: -C¼S) were the most potent ones.

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Synthesis of thiophenecarboxamides, thieno[3,4- c ]pyridin-4(5 H )-ones and thieno[3,4- d ]pyrimidin-4(3 H )-ones and preliminary evaluation as inhibitors of poly(ADP-ribose)polymerase (PARP)

Cited by 31 publications

References 42 publications

BBT improves glucose homeostasis by ameliorating β-cell dysfunction in type 2 diabetic mice

BBT improves glucose homeostasis by ameliorating β-cell dysfunction in type 2 diabetic mice

Synthesis of Some Novel Thieno[3,2-<i>d</i>]pyrimidines as Potential Cytotoxic Small Molecules against Breast Cancer

Design, Synthesis, and Biological Evaluation of Some Cyclohepta[b]Thiophene and Substituted Pentahydrocycloheptathieno[2,3‐d]Pyrimidine Derivatives

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