14103-22-1

Upstream product

• 4852-81-7 2-benzoyl-3H-benzo[f]chromen-3-one 
• 94-02-0 ethyl 3-oxo-3-phenylpropionate 
• 708-06-5 2-hydroxynaphthalene-1-carbaldehyde 
• 135-19-3 β-naphthol 

Downstream Products

• 1148118-58-4 6-phenyl-5-[2''-hydroxynaphthyl-(1'')-methyl]-1-allyl-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one 
• 1148118-57-3 6-phenyl-5-[2''-hydroxynaphthyl-(1'')-methyl]-1-ethyl-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one 
• 1148118-59-5 6-phenyl-5-[2''-hydroxynaphthyl-(1'')-methyl]-1-propyl-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one 
• 1148118-60-8 6-phenyl-5-[2''-hydroxynaphthyl-(1'')-methyl]-1-butyl-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one 
• 1148118-56-2 6-phenyl-5-[2''-hydroxynaphthyl-(1'')-methyl]-1-methyl-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one 
• 1148118-41-5 6-phenyl-5-[2''-hydroxynaphthyl-(1'')-methyl]-1H-pyrimidine-2,4-dione 
• 1597709-79-9 4-[(2-hydroxynaphthalen-1-yl)methyl]-5-phenyl-2,3-dihydro-1H-pyrazol-3-one 

Relevant academic research and scientific papers

Selective reduction of the endocyclic double bond of 3-substituted coumarins by hantzsch 1,4-dihydropyridine

Hantzsch 1,4-dihydropyridine is a valuable reagent to effect the chemoselective reduction of the 3,4-double bond of 3-substituted coumarins. Georg Thieme Verlag Stuttgart.

COMPOSITIONS AND METHODS FOR INHIBITING N-SMASE2

Provided herein are compounds of Formula (I) and (II) and their salts, and compositions comprising such compounds that are useful for useful for modulating neutral sphingomyelinase 2 (n-SMase2) in cells. Also disclosed herein are methods of using the disc

Development of pyrazolone and isoxazol-5-one cambinol analogues as sirtuin inhibitors

Sirtuins are a family of NAD+-dependent protein deacetylases that play critical roles in epigenetic regulation, stress responses, and cellular aging in eukaryotic cells. In an effort to identify small molecule inhibitors of sirtuins for potential use as chemotherapeutics as well as tools to modulate sirtuin activity, we previously identified a nonselective sirtuin inhibitor called cambinol (IC50 ≈ 50 μM for SIRT1 and SIRT2) with in vitro and in vivo antilymphoma activity. In the current study, we used saturation transfer difference (STD) NMR experiments with recombinant SIRT1 and 20 to map parts of the inhibitor that interacted with the protein. Our ongoing efforts to optimize cambinol analogues for potency and selectivity have resulted in the identification of isoform selective analogues: 17 with >7.8-fold selectivity for SIRT1, 24 with >15.4-fold selectivity for SIRT2, and 8 with 6.8- and 5.3-fold selectivity for SIRT3 versus SIRT1 and SIRT2, respectively. In vitro cytotoxicity studies with these compounds as well as EX527, a potent and selective SIRT1 inhibitor, suggest that antilymphoma activity of this compound class may be predominantly due to SIRT2 inhibition.

Simplification of the tetracyclic SIRT1-selective inhibitor MC2141: Coumarin- and pyrimidine-based SIRT1/2 inhibitors with different selectivity profile

In this report we describe the synthesis and biological characterization of two series of sirtuins' inhibitors (SIRTi), designed as simplification products of the previously reported SIRT1-selective inhibitor MC2141 (4). In the first series (5a-t) we report a number of 2-substituted-1,2-dihydrobenzo[f]chromen-3- ones with a marked selectivity for the inhibition of SIRT2 over SIRT1. Some of such derivatives showed also high pro-apoptotic (5i and 5l) and/or cytodifferentiating (5d, 5i, and 5o) properties in a human leukemia cell line (U937). The second group of SIRTi (6a-q) is characterized by some analogues of cambinol (3), a well known SIRTi active against the Burkitt lymphoma. Such compounds, differently from the unselective prototype, are endowed with a selective inhibition of SIRT1 over SIRT2, and, in some cases (6j, 6k, and 6q), are more efficient than 3 to induce apoptosis in U937 cells.

PYRIMIDE DERIVATIVES AND THEIR PHARMACEUTICAL USE

The invention provides a compound according to formula (I): wherein: X is O or S; Y is O or S; each Ar and Ar' is independently a mono-, bi- or tricyclic aryl or heteroaryl group optionally substituted with one or more substituents selected from halo, alk

Novel cambinol analogs as sirtuin inhibitors: Synthesis, biological evaluation, and rationalization of activity

The tenovins and cambinol are two classes of sirtuin inhibitor that exhibit antitumor activity in preclinical models. This report describes modifications to the core structure of cambinol, in particular by incorporation of substitutents at the N1-position, which lead to increased potency and modified selectivity. These improvements have been rationalized using molecular modeling techniques. The expected functional selectivity in cells was also observed for both a SIRT1 and a SIRT2 selective analog.

Methods for inhibiting deacetylase activity

A method for identifying a compound that inhibits the NAD+-dependent deacetylase activity of a SIR2 protein is disclosed. These compounds are useful for the treatment of cancers and other diseases, through the activation of silenced genes, through the promotion of apoptosis in cancerous cells, and through the inhibition of transcriptional repressor activity in oncogenes.