39244-79-6

Usage

Chemical structure

A piperazine ring with a thiophene and a methyl group attached to it

Use in pharmaceutical research

As a building block for the synthesis of various bioactive compounds, including potential drug candidates

Potential properties

Antipsychotic and antidepressant

Reactivity

Unique structure and reactivity that makes it a valuable tool for the development of new therapeutic agents for the treatment of neurological disorders

Mechanism of action

Modulation of serotonin and dopamine receptors in the central nervous system.

Upstream product

• 415959-63-6 ethyl 4-[(thien-2-yl)methyl]piperazine-1-carboxylate 
• 636-72-6 2-thiophenemethanol 
• 110-85-0 piperazine 
• 765-50-4 2-Chloromethylthiophene 
• 77278-68-3 tert-butyl 4-(thiophen-2-ylmethyl)piperazine-1-carboxylate 
• 98-03-3 thiophene-2-carbaldehyde 

Downstream Products

• 1226860-24-7 6-methylbenzo[b]thiophene-2-carboxylic acid {1-[(S)-1-benzyl-4-(4-thiophen-2-ylmethylpiperazin-1-yl)butylcarbamoyl]cyclopentyl}amide 
• 1354972-22-7 2-(2,4-difluorophenyl)-1-(4-(thiophen-2-ylmethyl)piperazin-1-yl)-3-(1H-1,2,4-triazol-1-yl)propan-2-ol 

Relevant academic research and scientific papers

Design, synthesis and SAR of antitubercular benzylpiperazine ureas

Abstract: N-furfuryl piperazine ureas disclosed by scientists at GSK Tres Cantos were chosen as antimycobacterial hits from a phenotypic whole-cell screen. Bioisosteric replacement of the furan ring in the GSK Tres Cantos molecules with a phenyl ring led to molecule (I) with an MIC of 1?μM against Mtb H37Rv, low cellular toxicity (HepG2 IC50 ~ 80?μM), good DMPK properties and specificity for Mtb. With the aim of delineating the SAR associated with (I), fifty-five analogs were synthesized and screened against Mtb. The SAR suggests that the piperazine ring, benzyl urea and piperonyl moieties are essential signatures of this series. Active compounds in this series are metabolically stable, have low cellular toxicity and are valuable leads for optimization. Molecular docking suggests these molecules occupy the Q0 site of QcrB like Q203. Graphic Abstract: Bioisosteric replacement of N-furfuryl piperazine-1-carboxamides yielded molecule (I) a novel lead with satisfactory PD, metabolism, and toxicity profiles.[Figure not available: see fulltext.]

Discovery of Novel Apigenin-Piperazine Hybrids as Potent and Selective Poly (ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors for the Treatment of Cancer

Poly (ADP-ribose) polymerase-1 (PARP-1) is a potential target for the discovery of chemosensitizers and anticancer drugs. Amentoflavone (AMF) is reported to be a selective PARP-1 inhibitor. Here, structural modifications and trimming of AMF have led to a series of AMF derivatives (9a-h) and apigenin-piperazine/piperidine hybrids (14a-p, 15a-p, 17a-h, and 19a-f), respectively. Among these compounds, 15l exhibited a potent PARP-1 inhibitory effect (IC50 = 14.7 nM) and possessed high selectivity to PARP-1 over PARP-2 (61.2-fold). Molecular dynamics simulation and the cellular thermal shift assay revealed that 15l directly bound to the PARP-1 structure. In in vitro and in vivo studies, 15l showed a potent chemotherapy sensitizing effect against A549 cells and a selective cytotoxic effect toward SK-OV-3 cells through PARP-1 inhibition. 15l·2HCl also displayed good ADME characteristics, pharmacokinetic parameters, and a desirable safety margin. These findings demonstrated that 15l·2HCl may serve as a lead compound for chemosensitizers and the (BRCA-1)-deficient cancer therapy.

Discovery of highly potent triazole antifungal derivatives by heterocycle-benzene bioisosteric replacement

On the basis of our previously discovered triazole antifungal lead compounds, heterocycle-benzene bioisosteric replacement was used to improve their pharmacokinetic profile. The designed new triazole derivatives have good antifungal activity toward a wide range of pathogenic fungi. Their binding mode with the target enzyme was clarified by molecular docking. The MIC value of the highly potent compound 8f against Candida albicans, Candida tropicalis, and Cryptococcus neoformans is 0.016 μg/mL, 0.004 μg/mL, and 0.016 μg/mL, respectively. Moreover, preliminary pharmacokinetic studies revealed that it showed improved oral absorption as compared to the lead compound iodiconazole and deserved for further evaluations.

TRIAZOLE DERIVATIVES HAVING ANTIFUNGAL ACTIVITY, METHOD FOR THE PREPARATION THEREOF, AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME

A triazole derivative of formula 1 or a pharmaceutically acceptable salt, hydrate, solvate or isomer thereof is superior to the conventional antifungal drugs in antifungal activity against a wide spectrum of pathogenic fungi, and has advantageously low toxicity.

A convenient synthesis by microwave heating and pharmacological evaluation of novel benzoyltriazole and saccharine derivatives as 5-HT1A receptor ligands

A series of novel 1,2,3-4-benzoyltriazole and saccharine derivatives were designed and synthesized by microwave heating. They were evaluated on a battery of receptors, including serotonin 5-HT1A, 5-HT2A and 5-HT2C, and the most interesting compounds were further evaluated on dopaminergic D1, D2 and adrenergic α1, α2 receptors. Conventional and microwave heating of the reactions were compared. Synthesis by microwave heating gave the desired compounds in better yields than those obtained by conventional heating. The overall times for the syntheses were considerably reduced. All compounds displayed moderate affinity for 5-HT1A receptor. The most interesting compound 33 showed a high affinity (Ki=93 nM) which was combined with no affinity on the other receptors considered.

Synthesis by microwave irradiation and binding properties of novel 5-HT1A receptor ligands

This work reports the synthesis by microwave irradiation and the binding tests on the 5-HT1A, 5-HT2A and 5-HT2C receptors of new substituted piperazines in order to identify selective ligands for 5-HT1A subtype receptor. Conventional heating and microwave irradiation of the reactions was compared. Synthesis by microwave irradiation gave the desired compounds in better yields than those obtained by conventional heating. The overall times for the syntheses were considerably reduced. Some resulting active compounds (29 and 39) were characterised by a good selectivity profile for the 5-HT1A subtype receptor. The more active compounds were selected and further evaluated for their binding affinities on D1, D2 dopaminergic and α1, α2 adrenergic receptors. The compound with higher affinity and selectivity for the 5-HT1A over all the considered receptors was the 3-{4-[4-(1,2,3,4-tetrahydronaphthyl)-1-piperazinyl]butan}-benzotriazinone (-)29 (5-HT1A Ki=36 nM, other receptors not active).