1246964-08-8

Upstream product

• 41979-39-9 4-piperidone hydrochloride 
• 89-98-5 2-chloro-benzaldehyde 
• 41661-47-6 piperidin-4-one 

Downstream Products

• 1547101-57-4 (E)-9-(2-chlorobenzylidene)-5-(2-chlorophenyl)-3-phenyl-6,7,8,9-tetrahydro-5H-pyrido[4,3-d]thiazolo[3,2-a]pyrimidine 
• 1547101-78-9 (E)-9-(2-chlorobenzylidene)-5-(2-chlorophenyl)-3-(4-fluorophenyl)-6,7,8,9-tetrahydro-5H-pyrido[4,3-d]thiazolo[3,2-a]pyrimidine 
• 1547101-99-4 (E)-9-(2-chlorobenzylidene)-5-(2-chlorophenyl)-3-(4-chlorophenyl)-6,7,8,9-tetrahydro-5H-pyrido[4,3-d]thiazolo[3,2-a]pyrimidine 
• 1547102-20-4 (E)-9-(2-chlorobenzylidene)-5-(2-chlorophenyl)-3-(4-methoxyphenyl)-6,7,8,9-tetrahydro-5H-pyrido[4,3-d]thiazolo[3,2-a]pyrimidine 
• 1636872-39-3 2-((3E,5E)-3,5-bis(2-chlorobenzylidene)-4-oxopiperidin-1-yl)-2-oxoethyl morpholine-4-carbodithioate 
• 1636871-95-8 C₂₁H₁₆Cl₃NO₂ 

Relevant academic research and scientific papers

Highly functionalized 2-amino-4H-pyrans as potent cholinesterase inhibitors

Novel highly functionalized 2-amino-4H-pyrans were achieved in excellent yields under simple grinding at ambient temperature and were assessed for their potential for treating Alzheimer's disease (AD). The 2-amino-4H-pyran bearing nitro groups on both the aryl rings showed the highest activity, with an IC50 of 1.98 ± 0.09 μM against acetylcholinesterase (AChE) and 10.62 ± 0.21 μM against butyrylcholinesterase (BChE), the inhibition mechanisms on AChE and BChE receptors were revealed by means of molecular docking simulations.

Synthesis and anti-tumor activity of EF24 analogues as IKKβ inhibitors

EF24 is an IKKβ inhibitor (IC50: 72 μM) containing various anti-tumor activities. In this study, a series of EF24 analogs targeting IKKβ were designed and synthesized. Several IKKβ inhibitors with better activities than EF24 were screened out and B3 showed best IKKβ inhibitory (IC50: 6.6 μM). Molecular docking and dynamic simulation experiments further confirmed this inhibitory effect. B3 obviously suppressed the viability of Hela229, A549, SGC-7901 and MGC-803 cells. Then, in SGC-7901 and MGC-803 cells, B3 blocked the NF-κB signal pathway by inhibiting IKKβ phosphorylation, and followed arrested the cell cycle at G2/M phase by suppressing the Cyclin B1 and Cdc2 p34 expression, induced the cell apoptosis by down-regulating Bcl-2 protein and up-regulating cleaved-caspase3. Moreover, B3 significantly reduced tumor growth and suppressed the IKKβ-NF-κB signal pathway in SGC-7901 xenograft model. In total, this study present a potential IKKβ inhibitor as anti-tumor precursor.

An expedient synthesis, acetylcholinesterase inhibitory activity, and molecular modeling study of highly functionalized hexahydro-1,6-naphthyridines

A series of hexahydro-1,6-naphthyridines were synthesized in good yields by the reaction of 3,5-bis[(E)-arylmethylidene] tetrahydro-4(1H)-pyridinones with cyanoacetamide in the presence of sodium ethoxide under simple mixing at ambient temperature for 6-10 minutes and were assayed for their acetylcholinesterase (AChE) inhibitory activity using colorimetric Ellman's method. Compound 4e with methoxy substituent at ortho-position of the phenyl rings displayed the maximum inhibitory activity with IC50 value of 2.12 μM. Molecular modeling simulation of 4e was performed using three-dimensional structure of Torpedo californica AChE (TcAChE) enzyme to disclose binding interaction and orientation of this molecule into the active site gorge of the receptor.

Ionic liquid mediated synthesis of mono- and bis-spirooxindole- hexahydropyrrolidines as cholinesterase inhibitors and their molecular docking studies

One pot, three-component reaction of 1-acryloyl-3,5- bisarylmethylidenepiperidin-4-ones with isatin and sarcosine in molar ratios of 1:1:1 and 1:2:2 furnished to mono- and bis-spiropyrrolidine heterocyclic hybrids comprising functionalized piperidine, pyrrolidine and oxindole structural motifs. Both mono and bis-spiropyrrolidines displayed good inhibitory activity against acetylcholinesterase (AChE) with IC50 values of 2.36-9.43 μM. For butyrylcholinesterase (BChE), mono-cycloadducts in series 8 with IC50 values of lower than 10 μM displayed better inhibitory activities than their bis-cycloadduct analogs in series 9 with IC50 values of 7.44-19.12 μM. The cycloadducts 9j and 8e were found to be the most potent AChE and BChE inhibitors with IC50 values of 2.35 and 3.21 μM, respectively. Compound 9j was found to be competitive inhibitor of AChE while compound 8e was a mixed-mode inhibitor of BChE with calculated K i values of 2.01 and 6.76 μM, respectively. Molecular docking on Torpedo californica AChE and human BChE showed good correlation between IC 50 values and free binding energy values of the synthesized compounds docked into the active site of the enzymes.

Cholinesterase inhibitory activity versus aromatic core multiplicity: A facile green synthesis and molecular docking study of novel piperidone embedded thiazolopyrimidines

Novel thiazolopyrimidine derivatives have been synthesized via microwave assisted, domino cascade methodology in ionic liquid and evaluated in vitro for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. Among the newly synthesized compounds 6d, 6a, 6e and 6b displayed higher AChE inhibitory activity than standard drug, galanthamine, with IC 50 values of 0.53, 1.47, 1.62 and 2.05 μM, respectively. Interestingly, all the compounds except for 6m-r and 6x displayed higher BChE inhibitory potentials than galanthamine with IC50 values ranging from 1.09 to 18.56 μM. Molecular docking simulations for 6d possessing the most potent AChE and BChE inhibitory activities, disclosed its binding interactions at the active site gorge of AChE and BChE enzymes.

An efficient ionic liquid mediated synthesis, cholinesterase inhibitory activity and molecular modeling study of novel piperidone embedded α,β-unsaturated ketones

A series of hitherto unreported piperidone embedded α,β- unsaturated ketones were synthesized efficiently in ionic solvent and evaluated for cholinesterase inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Most of the synthesized compounds displayed good enzyme inhibition; therein compounds 7i and 7f displayed significant activity against AChE with IC50 values of 1.47 and 1.74 μM, respectively. Compound 6g showed the highest BChE inhibitory potency with IC50 value of 3.41 μM, being 5 times more potent than galanthamine. Molecular modeling simulation was performed using AChE and BChE receptors extracted from crystal structure of human AChE and human BChE to determine the amino acid residues involved in the binding interaction of synthesized compounds and their relevant receptors.

C5-curcuminoid-dithiocarbamate based molecular hybrids: Synthesis and anti-inflammatory and anti-cancer activity evaluation

A series of C5-curcumin bearing morpholine based dithiocarbamates was synthesized. Molinspiration and Osiris software were used for theoretical prediction of physico-chemical properties of these molecules and the majority of the hybrids showed theoretical physico-chemical properties similar or better than curcumin. These hybrids (4a-4v) were evaluated for in vitro cytotoxicity on chronic myeloid leukemia (KBM5) and colon cancer (HCT116) cell lines, and down modulation of TNF-α-induced NF-κB activation at 5 μM. Most of the hybrids exhibit higher cytotoxicity against KBM5 cells compared to HCT116 cell lines. Further, all the hybrids showed potential to suppress the TNF-α-induced NF-κB activation at 5 μM KBM5 cells and seventeen hybrids have shown higher potential to inhibit NF-κB activation in comparison to curcumin.

Facile, regio- And diastereoselective synthesis of spiro-pyrrolidine and pyrrolizine derivatives and evaluation of their antiproliferative activities

A number of novel spiro-pyrrolidines/pyrrolizines derivatives were synthesized through [3+2]-cycloaddition of azomethine ylides with 3,5-bis[(E)- Arylmethylidene]tetrahydro-4(1H)-pyridinones 2a-n. Azomethine ylides were generated in situ from the reaction of 1H-indole-2,3-dione (isatin, 3) with N-methylglycine (sarcosine), phenylglycine, or proline. All compounds (50 μM) were evaluated for their antiproliferative activity against human breast carcinoma (MDA-MB-231), leukemia lymphoblastic (CCRF-CEM), and ovarian carcinoma (SK-OV-3) cells. N-α-Phenyl substituted spiro-pyrrolidine derivatives (5a-n) showed higher antiproliferative activity in MDA-MB-231 than other cancer cell lines. Among spiro-pyrrolizines 6a-n, a number of derivatives including 6a-c and 6i-m showed a comparable activity with doxorubicin in all three cell lines. Among all compounds in three classes, 6a, 6b, and 6m, were found to be the most potent derivatives showing 64%, 87%, and 74% antiproliferative activity in MDA-MB-231, SK-OV-3, and CCRF-CEM cells, respectively. Compound 6b showed an IC50 value of 3.6 μM in CCRF-CEM cells. These data suggest the potential antiproliferative activity of spiro-pyrrolidines/pyrrolizines.

Synthesis and discovery of novel piperidone-grafted mono- and bis-spirooxindole-hexahydropyrrolizines as potent cholinesterase inhibitors

Three-component reaction of a series of 1-acryloyl-3,5- bisbenzylidenepiperidin-4-ones with isatin and l-proline in 1:1:1 and 1:2:2 molar ratios in methanol afforded, respectively the piperidone-grafted novel mono- and bisspiro heterocyclic hybrids comprising functionalized piperidine, pyrrolizine and oxindole ring systems in good yields. The in vitro evaluation of cholinesterase enzymes inhibitory activity of these cycloadducts disclosed that monospiripyrrolizines (8a-k), are more active with IC50 ranging from 3.36 to 20.07 μM than either the dipolarophiles (5a-k) or bisspiropyrrolizines (9a-k). The compounds, 8i and 8e with IC50 values of 3.36 and 3.50 μM, respectively showed the maximum inhibition of acethylcholinesterase (AChE) and butrylylcholinestrase (BuChE). Molecular modeling simulation, disclosed the binding interactions of the most active compounds to the active site residues of their respective enzymes. The docking results were in accordance with the IC50 values obtained from in vitro cholinesterase assay.

A facile chemo-, regio- and stereoselective synthesis and cholinesterase inhibitory activity of spirooxindole-pyrrolizine-piperidine hybrids

A series of novel hybrid spiro heterocycles comprising pyrrolizine, spiroxindole and piperidine moieties was synthesized chemo-, regio- and stereoselectively in good yields from 1,3-dipolar cycloaddition reaction of a series of 1-acryloyl-3,5-bisarylmethylidenepiperidin-4-ones with azomethine ylides generated in situ from 5-choloroisatin and l-proline in methanol. These cycloadducts displayed significant cholinesterase inhibitory activity. Among the compounds screened, 8g and 8e, showed maximum inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinestrase (BChE) with IC50 values of 3.33 and 3.13 μM, respectively.