109532-65-2

Upstream product

• 98-03-3 thiophene-2-carbaldehyde 
• 17356-08-0 thiourea 
• 105-56-6 ethyl 2-cyanoacetate 
• 31330-51-5 ethyl 2-cyano-3-(2-thienyl)acrylate 

Downstream Products

• 791828-43-8 3-amino-5-oxo-7-(2-thienyl)-5H-thiazolo[3,2-a]pyrimidine-2,6-dicarbonitrile 
• 769168-07-2 2-[(5-cyano-2-ethylthio-6-(2-thienyl)pyrimidin-4-yl)amino]benzoic acid 
• 769167-96-6 2-ethylsulfanyl-4-mercapto-6-thiophen-2-yl-pyrimidine-5-carbonitrile 

Relevant academic research and scientific papers

Synthesis, molecular modeling, and biological evaluation of novel benzimidazole derivatives as inhibitors of hepatitis C virus RNA replication

In this study, synthesis and docking studies of a series of new benzimidazole derivatives linked to substituted pyrimidines either through the methylenethio linkage or its bioisosteric methylene amino bridge were carried out. All the synthesized compounds were evaluated for their hepatitis C virus (HCV) RNA replication-inhibitory activity. Compounds 4d, 4f, and 4h were found to be more potent than VX-950 (IC50/90of 4d=0.123/0.321, 4f=0.145/0.345, 4h=0.129/0.432, VX-950=0.20/0.45μM, respectively) and 6d (IC50/90=0.116/0.452μM) displayed activity very similar to that of the standard. Compounds 4d, 4f, 4h, and 6d were potent HCV RNA replication inhibitors and are good drug candidates for further investigations.

α-Amino-β-carboxymuconate-?-semialdehyde Decarboxylase (ACMSD) Inhibitors as Novel Modulators of de Novo Nicotinamide Adenine Dinucleotide (NAD+) Biosynthesis

NAD+ has a central function in linking cellular metabolism to major cell-signaling and gene-regulation pathways. Defects in NAD+ homeostasis underpin a wide range of diseases, including cancer, metabolic disorders, and aging. Although the beneficial effects of boosting NAD+ on mitochondrial fitness, metabolism, and lifespan are well established, to date, no therapeutic enhancers of de novo NAD+ biosynthesis have been reported. Herein we report the discovery of 3-[[[5-cyano-1,6-dihydro-6-oxo-4-(2-thienyl)-2-pyrimidinyl]thio]methyl]phenylacetic acid (TES-1025, 22), the first potent and selective inhibitor of human ACMSD (IC50 = 0.013 μM) that increases NAD+ levels in cellular systems. The results of physicochemical-property, ADME, and safety profiling, coupled with in vivo target-engagement studies, support the hypothesis that ACMSD inhibition increases de novo NAD+ biosynthesis and position 22 as a first-class molecule for the evaluation of the therapeutic potential of ACMSD inhibition in treating disorders with perturbed NAD+ supply or homeostasis.

Green synthesis and 3D pharmacophore study of pyrimidine and glucoside derivatives with in vitro potential anticancer and antioxidant activities

A facile and an efficient one-pot green synthesis of pyrimidine derivatives using the environmentally friendly Cerium(IV) ammonium nitrate (CAN) as catalyst and water as a solvent has been described. Some of the synthesized pyrimidines react with 2,3,4,6-

Quantitative analysis of hydrogen and chalcogen bonds in two pyrimidine-5-carbonitrile derivatives, potential DHFR inhibitors: An integrated crystallographic and theoretical study

Two potential bioactive pyrimidine-5-carbonitrile derivatives have been synthesized and characterized by spectroscopic techniques (1H and 13C-NMR) and the three dimensional structures were elucidated by single crystal X-ray diffraction at low temperature (160 K). In both structures, the molecular conformation is locked by an intramolecular C-H?C interaction involving the cyano and CH of the thiophene and phenyl rings. The intermolecular interactions were analyzed in a qualitative manner based on the Hirshfeld surface and 2D-fingerprint plots. The results suggest that the phenyl and thiophene moieties have an effect on the crystal packing. For instance, the chalcogen bonds are only preferred in the thiophene derivative. However, both structures uses a common N-H?O hydrogen bond motif. Moreover, the structures of 1 and 2 display 1D isostructurality and molecular chains stabilize by intermolecular N-H?O and N-H?N hydrogen bonds. The nature and extent of different non-covalent interactions were further characterized by the topological parameters derived from the quantum theory of atoms-in-molecules approach. This analysis indicates that apart from N-H?O hydrogen bonds, other non-covalent interactions are closed-shell in nature. A strong and linear N-H?O hydrogen bond shows intermediate bonding character between shared and closed-shell interactions. The molecular docking analysis suggests that both compounds display potential inhibitory effect against the dihydrofolate reductase (DHFR) enzyme from humans and Staphylococcus aureus.

Synthesis and in vitro investigation of novel cytotoxic pyrimidine and pyrazolopyrimidne derivatives showing apoptotic effect

A series of novel derivatives of hydrazinylpyrimidines, pyrazolylpyrimidines and 3-amino[3,4-d]pyrazolopyrimidines have been synthesized and tested for their in vitro cytotoxic activity against 60 tumor cell lines by NCI. The in vitro cytotoxic IC50 values for the most active compounds were determined against the colon-KM12 cell line (5d, 7c and 7d), breast-MCF-7 (6a) and melanoma-MDA-MB-435 (6h) using 5-fluorouracil (5-FU) as a positive control. Derivatives 5d and 7c were found to be the most potent derivatives against KM12 cell line (IC50 = 1.73 and 1.21 μM, respectively) with a high selectivity index (SI) (18.82 and 35.49, respectively) compared to 5-FU (IC50 = 12.26 μM, SI = 1.93). Compounds 5d and 7c were further investigated for their apoptotic behavior in KM12 cell line. The investigations showed the up-regulation of caspase 3/9 and the pro-apoptotic factor Bax. On the other hand, the expression of the anti-apoptotic factor Bcl-2, was down-regulated, as well as its inhibition at a nanomolar concentration. Furthermore, the apoptotic effect for derivatives 5d and 7c in KM12 cells was detected using annexin V-FITC staining method.

Discovery of Potent and Selective 2-(Benzylthio)pyrimidine-based DCN1-UBC12 Inhibitors for Anticardiac Fibrotic Effects

DCN1, a co-E3 ligase, interacts with UBC12 and activates cullin-RING ligases (CRLs) by catalyzing cullin neddylation. Although DCN1 has been recognized as an important therapeutic target for human diseases, its role in the cardiovascular area remains unknown. Here, we first found that DCN1 was upregulated in isolated cardiac fibroblasts (CFs) treated by angiotensin (Ang) II and in mouse hearts after pressure overload. Then, structure-based optimizations for DCN1-UBC12 inhibitors were performed based on our previous work, yielding compound DN-2. DN-2 specifically targeted DCN1 at molecular and cellular levels as shown by molecular modeling studies, HTRF, cellular thermal shift and co-immunoprecipitation assays. Importantly, DN-2 effectively reversed Ang II-induced cardiac fibroblast activation, which was associated with the inhibition of cullin 3 neddylation. Our findings indicate a potentially unrecognized role of DCN1 inhibition for anticardiac fibrotic effects. DN-2 may be used as a lead compound for further development.

Design, Synthesis and Antibacterial Activity of Novel Pyrimidine-Containing 4H-Chromen-4-One Derivatives**

A series of pyrimidine-containing 4H-chromen-4-one derivatives were designed and synthesized by combining bioactive substructures. Preliminary biological activity results showed that most of the compounds displayed significant inhibitory activities in vit

INHIBITORS OF α-AMINO-β-CARBOXYMUCONIC ACID SEMIALDEHYDE DECARBOXYLASE

The present disclosure discloses compounds capable of modulating the activity of α-amino-β-carboxymuconic acid semialdehyde decarboxylase (ACMSD), which are useful for the prevention and/or the treatment of diseases and disorders associated with defects in NAD+ biosynthesis, e.g., metabolic disorders, neurodegenerative diseases, chronic inflammatory diseases, kidney diseases, and diseases associated with ageing. The present application also discloses pharmaceutical compositions comprising said compounds and the use of such compounds as a medicament.

Substituted pyrimidine-containing myricetin derivative as well as preparation method and application thereof

The invention discloses a substituted pyrimidine-containing myricetin derivative as well as a preparation method and application thereof. The general structural formula of the myricetin derivative isshown in the specification, R represents a substituted phenyl group or a substituted aromatic heterocyclic group; n is the number of carbon in a carbon chain and is 2-6; wherein the substituted phenylgroup is on the ortho-, meta-and para- position of a benzene ring and contains C1-6 alkyl groups, C1-6 alkoxyl groups, nitro groups, halogen atoms and hydrogen atoms; the aromatic heterocyclic groupis thienyl, furyl, pyrrolyl or pyridyl; and substituent groups on substituted aromatic heterocycle are ortho-, meta-and para- positions and contain C1-6 alkyl groups, C1-6 alkoxyl groups, nitro groups, halogen atoms and hydrogen atoms. The derivative can well inhibit the activity of pathogenic bacteria of plants.

INHIBITORS OF α-AMINO-β-CARBOXYMUCONIC ACID SEMIALDEHYDE DECARBOXYLASE

The present disclosure discloses compounds capable of modulating the activity of α-amino-β-carboxymuconic acid semialdehyde decarboxylase (ACMSD), which are useful for the prevention and/or the treatment of diseases and disorders associated with defects in NAD+ biosynthesis, e.g., metabolic disorders, neurodegenerative diseases, chronic inflammatory diseases, kidney diseases, and diseases associated with ageing. The present application also discloses pharmaceutical compositions comprising said compounds and the use of such compounds as a medicament.