122850-52-6

Upstream product

• 1111-97-3 3-chloro-3-methylbut-1-yne 
• 121-33-5 vanillin 

Downstream Products

• 1442415-87-3 5′,5″-diisoamyltetrahydrocurcumin 
• 18423-13-7 4-hydroxy-3-methoxy-5-(3-methylbut-2-en-1-yl)benzaldehyde 
• 1442415-88-4 C₁₇H₂₄O₅ 
• 1258290-39-9 2'.4'-dihydroxy-3-methoxy-2,2-dimethylpyrano(5,6:5,4)chalcone 

Relevant academic research and scientific papers

Synthesis, characterization and biological evaluation of novel dihydropyranoindoles improving the anticancer effects of HDAC inhibitors

The dihydropyranoindole scaffold was identified as a promising target for improving the anti-cancer activity of HDAC inhibitors from the preliminary screening of a library of compounds. A suitable methodology has been developed for the preparation of novel dihydropyranoindoles via the Hemetsberger indole synthesis using azido-phenylacrylates, derived from the reaction of corresponding alkynyl-benzaldehydes with methyl azidoacetate, followed by thermal cyclization in high boiling solvents. Anti-cancer activity of all the newly synthesized compounds was evaluated against the SH-SY5Y and Kelly neuroblastoma cells as well as the MDA-MB-231 and MCF-7 breast adenocarcinoma cell lines. Biological studies showed that the tetracyclic systems had significant cytotoxic activity at higher concentration against the neuroblastoma cancer cells. More importantly, these systems, at the lower concentration, considerably enhanced the SAHA toxicity. In addition to that, the toxicity of designated systems on the healthy human cells was found to be significantly less than the cancer cells.

Synthetic methods for prenylated chalcones and pyranochalcones

The inventors of the present invention invented a simple and effective way to synthesize compounds 1-9 of natural prenylated chalcones and pyrano chalcones by using Claisen-Schmidt condensation as a main step. In addition, an anti-inflammatory effect of synthetic compounds was evaluated in RAW 264.7 macrophages which were stimulated with a lipopolysaccharide. As a result, chalcone compounds having prenyl groups in a ring A (an acetophenone part) show weak inhibition or no inhibition on the generation of nitrogen oxide while chalcones (5, 6, 8, and 9) having no prenyl groups in the ring A show normal or good activity, and have no cytotoxicity.COPYRIGHT KIPO 2017

Synthesis and pharmacological properties of naturally occurring prenylated and pyranochalcones as potent anti-inflammatory agents

An efficient approach has been developed for the synthesis of naturally occurring prenylated chalcones viz. kanzonol C (1), stipulin (2), crotaorixin (3), medicagenin (4), licoagrochalcone A (5) and abyssinone D (6) along with the pyranochalcones paratocarpin C (7), anthyllisone (8) and 3-O-methylabyssinone A (9). The key step of the synthesis is a Claisen-Schmidt condensation. Subsequently, their anti-inflammatory effects were investigated in lipopolysaccharides (LPSs)-induced RAW-264.7 macrophages. Of the synthesized chalcones, compounds 5 (IC50 = 10.41 μmol/L), 6 (IC50 = 9.65 μmol/L) and 8 (IC50 = 15.34 μmol/L) show remarkable activity with no cytotoxicity. Compound 9 (IC50 = 4.5 μmol/L) exhibits maximum (83.6%) nitric oxide (NO) inhibition, but shows slight cytotoxicity. The results reveal that the chalcones bearing the prenyl group at 3- and/or 5-position on ring A (acetophenone moiety), i.e., 1-4 and 7 show weak, or no inhibition activity, whereas chalcones having the prenyl group only on ring B (aldehyde part), i.e., 5, 6 and 8 show significant activity on the production of inflammatory mediated NO with no cytotoxicity.

The synthesis and evaluation of new benzophenone derivatives as tubulin polymerization inhibitors

Inspired by the potent inhibition activity of phenstatin and millepachine against cancer cell growth, a series of new benzophenone derivatives were synthesized and evaluated as tubulin polymerization inhibitors. Among them, compound 10a exhibited 0.029-0.062 μM of IC50 for five human cancer cell lines, which is much better than that of the two leading compounds. Flow cytometric analysis showed that 10a induces G2/M phase arrest and apoptosis in A549 cells. Cellular studies revealed that the induction of apoptosis by 10a was associated with the collapse of the mitochondrial membrane potential (MMP). Overall, the current study demonstrates that the benzophenone derivatives are promising anticancer agents by targeting tubulin.

Dissecting the pharmacophore of curcumin. Which structural element is critical for which action?

The dietary phenolic curcumin (1a) is the archetypal network pharmacological agent, but is characterized by an ill-defined pharmacophore. Nevertheless, structure-activity studies of 1a have mainly focused on a single biological end-point and on a single structural element, the aliphatic bis-enoyl moiety. The comparative investigation of more than one end-point of curcumin and the modification of its aromatic region have been largely overlooked. To address these issues, we have investigated the effect of aromatic C-prenylation in the three archetypal structural types of curcuminoids, namely, curcumin itself (1a), its truncated analogue 2a (C5-curcumin), and (as the reduced isoamyl version) the tetrahydro derivative 3a, comparatively evaluating reactivity with thiols and activity in biochemical (inhibition of NF-κB, HIV-1-Tat transactivation, Nrf2 activation) and phenotypic (anti-HIV action) assays sensitive, to a various extent, to thia-Michael addition. Prenylation, a validated maneuver for bioactivity modulation in plant phenolics, had no effect on Michael reactivity, but was detrimental for all biological end-points investigated, dissecting thiol trapping from activity, while hydrogenation attenuated, but did not completely abrogate, the activity of 1a. The C 5-curcuminoid 2a outperformed the natural product in all end-points investigated and was identified as a novel high-potency anti-HIV lead in a cellular model of HIV infection. Taken together, these observations show that Michael reactivity is a critical element of the curcumin pharmacophore, but also reveal a surprising sensitivity of bioactivity to C-prenylation of the vanillyl moiety.

HYPOXIA INDUCIBLE FACTOR-1 PATHWAY INHIBITORS AND USES AS ANTICANCER AND IMAGING AGENTS

This disclosure relates to Hypoxia Inducible Factor-1 pathway inhibitors and uses as anticancer and imaging agents. In certain embodiments, the disclosure contemplates compounds and pharmaceutical compositions disclosed herein.

Design and in vitro activities of N -alkyl- N -[(8- R -2,2-dimethyl-2 H -chromen-6-yl)methyl]heteroarylsulfonamides, novel, small-molecule hypoxia inducible factor-1 pathway inhibitors and anticancer agents

The hypoxia inducible factor (HIF) pathway is an attractive target for cancer, as it controls tumor adaptation to growth under hypoxia and mediates chemotherapy and radiation resistance. We previously discovered 3,4-dimethoxy-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N- phenylbenzenesulfonamide as a novel, small-molecule HIF-1 pathway inhibitor in a high-throughput cell-based assay, but its in vivo delivery is hampered by poor aqueous solubility (0.009 μM in water; log P7.4 = 3.7). Here we describe the synthesis of 12 N-alkyl-N-[(8-R-2,2-dimethyl-2H-chromen-6-yl) methyl]heteroarylsulfonamides, which were designed to possess optimal lipophilicities and aqueous solubilities by in silico calculations. Experimental log P7.4 values of 8 of the 12 new analogs ranged from 1.2-3.1. Aqueous solubilities of three analogs were measured, among which the most soluble N-[(8-methoxy-2,2-dimethyl-2H-chromen-6-yl)methyl]-N-(propan-2-yl) pyridine-2-sulfonamide had an aqueous solubility of 80 μM, e.g., a solubility improvement of ～9000-fold. The pharmacological optimization had limited impact on drug efficacy as the compounds retained IC50 values at or below 5 μM in our HIF-dependent reporter assay.

Synthesis of Naturally Occurring Chromenes

Naturally occurring chromenes (3a), E- and Z-werneriachromenes (3d and 3e), E- and Z-lonchocarpenes (3f and 3g) and chromene (3b) have been conveniently synthesised either in one or two steps.