4553-20-2

Upstream product

• 2759-28-6 1-phenylmethylpiperazine 
• 574-98-1 2-(2-bromoethyl)isoindoline-1,3-dione 
• 100-44-7 benzyl chloride 
• 1074-82-4 potassium phtalimide 
• 6820-93-5 2-(2-(piperazin-1-yl)ethyl)isoindoline-1,3-dione 
• 85-44-9 phthalic anhydride 
• 140-31-8 aminoethylpiperazine 
• 100-39-0 benzyl bromide 

Downstream Products

• 4553-21-3 2-(4-benzylpiperazin-1-yl)-ethylamine 
• 1325456-08-3 N-(2-(4-benzylpiperazin-1-yl)ethyl)cyclohexanecarboxamide 
• 883810-86-4 N-(2-(piperaz-1-yl)ethyl)cyclohexanecarboxamide 
• 1351412-00-4 N-(2-(4-(6-nitropyridin-2-yl)piperazin-1-yl)ethyl)cyclohexanecarboxamide 
• 1351411-05-6 ⁽¹⁸⁾F-N-(2-(4-(6-fluoropyridin-2-yl)piperazin-1-yl)ethyl)cyclohexanecarboxamide 

Relevant academic research and scientific papers

Novel donepezil?arylsulfonamide hybrids as multitarget-directed ligands for potential treatment of Alzheimer?s disease

Alzheimer’s disease (AD) is one of the most devastating neurodegenerative disorders, characterized by multiple pathological features. Therefore, multi-target drug discovery has been one of the most active fields searching for new effective anti-AD therapies. Herein, a series of hybrid compounds are reported which were designed and developed by combining an aryl-sulfonamide function with a benzyl-piperidine moiety, the pharmacophore of donepezil (a current anti-AD acetylcholinesterase AChE inhibitor drug) or its benzyl-piperazine analogue. The in vitro results indicate that some of these hybrids achieve optimized activity towards two main AD targets, by displaying excellent AChE inhibitory potencies, as well as the capability to prevent amyloid-β (Aβ) aggregation. Some of these hybrids also prevented Aβ-induced cell toxicity. Significantly, drug-like properties were predicted, including for blood-brain permeability. Compound 9 emerged as a promising multi-target lead compound (AChE inhibition (IC50 1.6 μM); Aβ aggregation inhibition 60.7%). Overall, this family of hybrids is worthy of further exploration, due to the wide biological activity of sulfonamides.

Derivatives of tenuazonic acid as potential new multi‐target anti‐alzheimer’s disease agents

Alzheimer’s disease (AD) is generally recognized as a multifactorial neurodegenerative pathology with an increasing impact on society. Tenuazonic acid (TA) is a natural compound that was recently identified as a potential multitarget ligand with anti‐cholinesterase, anti-amyloidogenic and antioxidant activities. Using its structure as a chemical scaffold, we synthesized and evaluated new derivatives (1–5), including tenuazonic‐donepezil (TA‐DNP) hybrids (4 and 5) due to the clinical importance of the anti‐AD drug donepezil. These novel compounds all achieved activity in the micromolar range towards all selected targets and demonstrated to be potentially orally absorbed. Moreover, a selected compound (1) was further investigated as a chelating agent towards copper (II), zinc (II) and iron (III) and showed good chelating ability (pFe = 16.6, pCu = 11.6, pZn = 6.0 at pH 7.4). Therefore, the TA motif can be considered an interesting building block in the search for innovative multi‐functional anti‐neurodegenerative drugs, as exemplified by hybrid 5, a promising non‐cytotoxic lead compound adequate for the early stages of AD, and capable of ameliorating the oxidative status of SH‐SY5Y human neuroblastoma cells.

Design, synthesis, and in vitro evaluation of hydroxybenzimidazole-donepezil analogues as multitarget-directed ligands for the treatment of Alzheimer's disease

A series of multi-target-directed ligands (MTDLs), obtained by attachment of a hydroxyphenylbenzimidazole (BIM) unit to donepezil (DNP) active mimetic moiety (benzylpiperidine /-piperazine) was designed, synthesized, and evaluated as potential anti-Alzheimer's disease (AD) drugs in terms of biological activity (inhibition of acetylcholinesterase (AChE) and β-amyloid (Aβ) aggregation), metal chelation, and neuroprotection capacity. Among the DNP-BIM hybrids studied herein, the structural isomerization did not significantly improve the biological properties, while some substitutions, namely fluorine atom in each moiety or the methoxy group in the benzyl ring, evidenced higher cholinergic AChE activity. All the compounds are able to chelate Cu and Zn metal ions through their bidentate BIM moieties, but compound 5, containing a three-dentate chelating unit, is the strongest Cu(II) chelator. Concerning the viability on neuroblastoma cells, compounds 9 and 10 displayed the highest reduction of Aβ-induced cell toxicity. In silico calculations of some pharmacokinetic descriptors indicate that all the compounds but the nitro derivatives have good potential oral-bioavailability. Overall, it can be concluded that most of the studied DNP-BIM conjugates showed quite good anti-AD properties, therefore deserving to be considered in further studies with the aim of understanding and treating AD.

Piperazine-and piperidine-containing thiazolo[5,4-d]pyrimidine derivatives as new potent and selective adenosine a2a receptor inverse agonists

The therapeutic use of A2A adenosine receptor (AR) antagonists for the treatment of neurodegenerative disorders, such as Parkinson and Alzheimer diseases, is a very promising approach. Moreover, the potential therapeutic role of A2A AR antagonists to avoid both immunoescaping of tumor cells and tumor development is well documented. Herein, we report on the synthesis and biological evaluation of a new set of piperazine-and piperidine-containing 7-amino-2-(furan-2-yl)thiazolo[5,4-d]pyrimidine derivatives designed as human A2A AR antagonists/inverse agonists. Binding and potency data indicated that a good number of potent and selective hA2A AR inverse agonists were found. Amongst them, the 2-(furan-2-yl)-N5-(2-(4-phenylpiperazin-1-yl)ethyl)thiazolo[5,4-d]pyrimidine-5,7-diamine 11 exhibited the highest A2A AR binding affinity (Ki = 8.62 nM) as well as inverse agonist potency (IC50 = 7.42 nM). In addition, bioinformatics prediction using the web tool SwissADME revealed that 8, 11, and 19 possessed good drug-likeness profiles.

Deep Eutectic Solvents as Effective Reaction Media for the Synthesis of 2‐Hydroxyphenylbenzimidazole-based Scaffolds en Route to Donepezil‐Like Compounds

An unsubstituted 2‐hydroxyphenylbenzimidazole has recently been included as a scaffold in a series of hybrids (including the hit compound PZ1) based on the framework of the acetylcholinesterase (AChE) inhibitor Donepezil, which is a new promising multi‐target ligand in Alzheimer’s disease (AD) treatment. Building upon these findings, we have now designed and completed the whole synthesis of PZ1 in the so‐called deep eutectic solvents (DESs), which have emerged as an unconventional class of bio‐renewable reaction media in green synthesis. Under optimized reaction conditions, the preparation of a series of 2‐hydroxyphenylbenzimidazole‐based nuclei has also been perfected in DESs, and comparison with other routes which employ toxic and volatile organic solvents (VOCs) provided. The functionalization of the aromatic ring can have implications on some important biological properties of the described derivatives and will be the subject of future studies of structure‐activity relationships (SARs).

Donepezil structure-based hybrids as potential multifunctional anti-Alzheimer’s drug candidates

A new series of multifunctional hybrids, based on the structure of the donepezil (DNP) drug, have been developed and evaluated as potential anti Alzheimer’s disease (AD) agents. The rationale of this study was the conjugation of a benzylpiperidine/benzylpiperazine moiety with derivatives of bioactive heterocyclics (benzimidazole or benzofuran), to mimic the main structure of DNP and to endow the hybrids with additional relevant properties such as inhibition of amyloid beta (Aβ) peptide aggregation, antioxidant activity and metal chelation. Overall, they showed good activity for AChE inhibition (IC50=4.0–30.0?μΜ) and moderate ability for inhibition of Aβ1–42 self-mediated aggregation. The hybrids containing chelating groups showed improvement in the inhibition of Cu-induced Aβ42 aggregation and the antioxidant capacity. Moreover, neuroprotective effects of these compounds were evidenced in neuroblastoma cells after Aβ1–42 induced toxicity. Structure–activity relationship allowed the identification of some promising compounds and the main determinant structural features for the targeted properties.

Design, synthesis and bioactivity of novel phthalimide derivatives as acetylcholinesterase inhibitors

A series of novel phthalimide derivatives related to benzylpiperazine were synthesized and evaluated as cholinesterase inhibitors. The results showed that all compounds were able to inhibit acetylcholinesterase (AChE), with two of them dramatically inhibiting butyrylcholinesterase (BuChE). Most compounds exhibited potent anti-AChE activity in the range of nM concentrations. In particular, compounds 7aIII and 10a showed the most potent activity with the IC50 values of 18.44 nM and 13.58 nM, respectively. To understand the excellent activity of these compounds, the structure-activity relationship was further examined. The protein-ligand docking study demonstrated that the target compounds have special binding modes and these results are in agreement with the kinetic study.

NOVEL IMIDAZOLYLALKYLCARBONYL DERIVATIVES AS CALCIUM CHANNEL MODULATORS AND PREPARATION METHOD THEREOF

Disclosed are novel imidazolylalkylcarbonyl derivatives useful as calcium channel modulators and a preparation method of the same. Also disclosed is a method for the treatment of diseases by administering the above compounds based on their inhibitory acti

Indazole derivatives having monocyclic amine

An indazole compound having the formula (I): wherein: R1 is hydrogen, C1 -C6 alkyl, C3 -C6 alkenyl or C3 -C6 cycloalkyl; Q is carbonyl, thiocarbonyl or methylene; and R2 is a group of the formula (II) or (IV); STR1 wherein R1 is C1 -C6 alkyl, C3 -C6 alkenyl or benzyl, of which a phenyl group thereof is optionally mono- or di-substituted by the same or different halogen or methoxy; m is 0 to 2; n and o is 1 or 2. The compound exhibits 5-HT4 receptor agonist activity.