18678-30-3

Upstream product

• 120-92-3 cyclopentanone 
• 4815-29-6 ethyl 2-amino-4H,5H,6H-cyclopentenothiophene-3-carboxylate 
• 100-47-0 benzonitrile 
• 825-60-5 benzimidic acid ethyl ester 

Downstream Products

• 87752-96-3 4-Chloro-2-phenyl-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidine 
• 1225504-98-2 2-phenyl-4-(prop-2-yn-1-yloxy)-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidine 
• 1225504-99-3 2-phenyl-3-prop-2-yn-1-yl-3,5,6,7-tetrahydro-4H-cyclopenta[4,5]thieno[2,3-d]pyrimidine-4-one 
• 487024-78-2 2-phenyl-4-hydrazino-5,6,7-trihydrocyclopenta[b]thieno[2,3-d]pyrimidine 

Relevant academic research and scientific papers

Discovery of Thieno[2,3- d]pyrimidine-Based Hydroxamic Acid Derivatives as Bromodomain-Containing Protein 4/Histone Deacetylase Dual Inhibitors Induce Autophagic Cell Death in Colorectal Carcinoma Cells

Bromodomain-containing protein 4 (BRD4) and histone deacetylases (HDAC) are both attractive epigenetic targets in cancer and other chronic diseases. Based on the integrated fragment-based drug design, synthesis, and in vitro and in vivo evaluations, a series of novel thieno[2,3-d]pyrimidine-based hydroxamic acid derivatives are discovered as selective BRD4-HDAC dual inhibitors. Compound 17c is the most potent inhibitor for BRD4 and HDAC with IC50 values at nanomolar levels, as well as the expression level of c-Myc, and increases the acetylation of histone H3. Moreover, 17c presents inhibitory effects on the proliferation of colorectal carcinoma (CRC) cells via inducing autophagic cell death. It also has a good pharmacokinetic profile in rats and oral bioavailability of 40.5%. In the HCT-116 xenograft in vivo models, 17c displays potent inhibitory efficiency on tumor growth by inducing autophagic cell death and suppressing IL6-JAK-STAT signaling pathways. Our results suggest that the BRD4-HDAC dual inhibition might be an attractive therapeutic strategy for CRC.

Discovery of a Small-Molecule Bromodomain-Containing Protein 4 (BRD4) Inhibitor That Induces AMP-Activated Protein Kinase-Modulated Autophagy-Associated Cell Death in Breast Cancer

Upon the basis of The Cancer Genome Atlas (TCGA) data set, we identified that several autophagy-related proteins such as AMP-activated protein kinase (AMPK) were remarkably downregulated in breast cancer. Combined with coimmunoprecipitation assay, we demonstrated that BRD4 might interact with AMPK. After analyses of the pharmacophore and WPF interaction optimization, we designed a small-molecule inhibitor of BRD4, 9f (FL-411) which was validated by cocrystal structure with BD1 of BRD4. Subsequently, 9f was discovered to induce ATG5-dependent autophagy-associated cell death (ACD) by blocking BRD4-AMPK interaction and thus activating AMPK-mTOR-ULK1-modulated autophagic pathway in breast cancer cells. Interestingly, the iTRAQ-based proteomics analyses revealed that 9f induced ACD pathways involved in HMGB1, VDAC1/2, and eEF2. Moreover, 9f displayed a therapeutic potential on both breast cancer xenograft mouse and zebrafish models. Together, these results demonstrate that a novel small-molecule inhibitor of BRD4 induces BRD4-AMPK-modulated ACD in breast cancer, which may provide a candidate drug for future cancer therapy.

BRD4 inhibitors and applications thereof in tumor treating medicines

The invention relates to BRD4 targeting inhibitors and applications thereof in tumor treating medicines, and belongs to the technical field of antitumor pharmacy. A technical problem to be overcome is to provide compounds adopted as the BRD4 inhibitors. The compounds include compounds shown as follows, or pharmaceutically acceptable salts thereof. The compounds or the pharmaceutically acceptable salts thereof can be adopted as the BRD4 inhibitors and have obvious breast cancer treating effects.

Synthesis and theoretical studies on energetics of novel N- and O- perfluoroalkyl triazole tagged thienopyrimidines - Their potential as adenosine receptor ligands

A series of novel N- and O- perfluoroalkyl triazole tagged thienopyrimidines 6a-c and 7a-d was synthesized in two steps from thienopyrimidin-4-ones 2 through O- and N-propargylated regioisomers 3a-i and 4a-i respectively. Compound 2 was reacted with propargyl bromide to form O- and N-propargylated regioisomers 3 and 4 in definite proportions. Each regioisomer was separated and independently subjected to [3?+?2] cycloaddition using perfluoroalkyl azides through Click reaction under Sharpless conditions and obtained exclusively anti product in each case. The formation of two regioisomers in the first step and single anti addition product in the next step could be explained based on computational studies carried out at B3LYP/6-31G(d) level of theory. Results of Fukui function indices at the reactive centers are in accordance with the observations. On evaluation of the synthesized molecules for their binding affinities towards adenosine receptors, 4d and 4f were found to be selective to A1 over A2A receptors.

Synthesis and antibacterial activity of some novel triazolothienopyrimidines

A novel series of some novel 5-substituted-1,2,4-triazolo[4,3-c]8,9,10- trihydrocyclopenta/8,9,10,11,12-pentahydrocyclohepta[ b]thieno[3,2-e]pyrimidin- 3-thiones has been synthesized. The intermediates 4-chloro-2-substituted-5,6,7- trihydrocyclopenta/5,6,

Thieno[2.3-d]-4-pyrimidones: Synthesis, structure and pharmacological properties

The cyclization of 2-amino-3-carbethoxy or -carboxamido thophenes yields substituted or unsubstituted 4-pyrimidones. Their structure and their 'lactam-lactam' tautomerism have been investigated by i.r. spectroscopy. The eighteen compounds synthesized were tested for a few pharmacological activities. They have no anti-edema activity except for two. Ten of them have shown an analgesic activity equal or superior to that of acetyl salicylic acid.