81514-10-5

Upstream product

• 109-70-6 1.3-chlorobromopropane 
• 2252-63-3 1-(4-Fluorophenyl)piperazine 
• 105173-87-3 3-(4-(4-fluorophenyl)piperazin-1-yl)propan-1-ol 
• 16141-90-5 p-Fluorophenylpiperazine hydrochloride 

Downstream Products

• 81514-03-6 3-{3-[4-(4-Fluoro-phenyl)-piperazin-1-yl]-propyl}-3H-benzooxazol-2-one 
• 148101-72-8 3<3<4(4-Fluorophenyl)piperazinyl>propyl>-6-butanoyl-2(3H)benzoxazolone 
• 170631-60-4 2-[3-[4-(4-fluorophenyl)piperazin-1-yl]propyl]-3,4-dihydro-2H-1,2-benzothiazin-4-one 1,1-dioxide ethylene acetal 
• 150159-37-8 7-[3-[4-(4-fluorophenyl)piperazin-1-yl]propyl]-1-methyl-1,4,5,6,7,8-hexahydropyrrolo[2,3-c]azepine-4,8-dione 
• 136481-44-2 1-[3-(4-(4-fluorophenyl)piperazinyl)propyl]-5,6-dihydro(1H,4H)-1,2,5-thiadiazolo[4,3,2-ij]quinoline 2,2-dioxide 

Relevant academic research and scientific papers

Discovery of phenylselenoether-hydantoin hybrids as ABCB1 efflux pump modulating agents with cytotoxic and antiproliferative actions in resistant T-lymphoma

Multidrug resistance (MDR) in cancer cells is a crucial aspect to consider for a successful cancer therapy. P-gp/ABCB1, a member of ABC transporters, is involved in the main tumour MDR mechanism, responsible for the efflux of drugs and cytotoxic substances. Herein, we describe a discovery of potent selenium-containing ABCB1 MDR efflux pump modulators with promising anticancer activity. On three groups of selenoethers comprehensive studies in terms of design, synthesis, and biological assays, including an insight into cellular mechanisms of anticancer action as well as an ADMET-screening in vitro were performed, followed by in-depth SAR analysis. Among the investigated new phenylselenoether hybrids, four compounds showed significant cytotoxic and anti-proliferative effects, in particular, in resistant cancer cells. Hydantoin derivatives (5–7) were significantly more effective than the reference inhibitor verapamil (up to 2.6-fold at a 10-fold lower concentration) modulating ABCB1-efflux pump, also possessing a good drug-drug interaction profile. The best compound (6) was further evaluated in human JURKAT T-lymphocytic cancer cells for its impact on cell proliferation rate. Mechanistically, the expression of cyclin D1, an enhancer of the cell cycle, decreases, while p53, an inhibitor of cell proliferation, was up-regulated upon the treatment with compound 6 alone or in combination with the chemotherapeutic agent doxorubicin. In summary, a new chemical space of highly active selenium-containing anticancer agents has been discovered, with a new lead compound 6 that warrants more in-depth biological evaluation and further pharmacomodulation.

Design, synthesis, and biological evaluation of arylpiperazine-benzylpiperidines with dual serotonin and norepinephrine reuptake inhibitory activities

The limitations of established serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE) reuptake inhibitors necessitate the development of safer and more effective therapeutic agents. Based on the structures of 4-benzylpiperidine carboxamides and trazodone, arylpiperazine-benzylpiperidines with chemical scaffolds different from those of marketed drugs were designed, synthesized, and evaluated for their neurotransmitter reuptake inhibitory activities. The majority of the synthesized compounds showed greater NE than 5-HT reuptake inhibition. The activities were even greater than those of the standard drug, venlafaxine hydrochloride were. The derivatives with a three-carbon linker showed better activities than the derivatives with a two-carbon linker. Among the newly synthesized compounds, 2d exhibited the strongest reuptake inhibition of the neurotransmitters (IC50 = 0.38 μM for NE and 1.18 μM for 5-HT). The biological activity data demonstrate that arylpiperazine-benzylpiperidines have the potential to be developed as a new class of therapeutic agents to treat neuropsychiatric and neurodegenerative disorders.

Synthesis and in vitro evaluation of novel indole-based sigma receptors ligands

To investigate the molecular features involved in sigma (σ) receptors binding, a series of compounds based on indole scaffolds were synthesized and their chemical structures were confirmed by 1H-NMR, IR, and elemental analysis. Their affinity t

Preparation of piperazine derivatives as 5-HT7 receptor antagonists

Twenty-four compounds of 4-methoxy-N-[3-(4-substituted phenyl-piperazine-1-yl)propyl] benzene sulfonamides and N-[3-(4-substituted phenyl-piperazine-1-yl)propyl] naphthyl sulfonamides were prepared and evaluated as 5-HT7 receptor antagonists. Most of the compounds showed the IC50 values of 12-580 nM. Four methyl branched analogues were also obtained, but the activity for methyl branched analogues was almost same as its straight chain congeners. Among the synthesized compounds, 3c showed a good activity on 5-HT7 receptors and a good selectivity on 5-HT1a, 5-HT2a, 5-HT2c, and 5-HT6 receptors.

Synthesis of new 1,2,3-benzotriazin-4-one-arylpiperazine derivatives as 5-HT(1A) serotonin receptor ligands

A series of novel 1,2,3-benzotriazin-4-one derivatives was prepared and evaluated as ligands for 5-HT receptors. Radioligand binding assays proved that the majority of the novel compounds behaved as good to excellent ligands at the 5-HT(1A) receptor, some of which were selective with respect 5-HT(2A) and 5-HT(2C) receptors. Six analogues (1a, 2a, 2b, 2c, 2e and 2i) were selected and further evaluated for their binding affinities on D1, D2 dopaminergic and α1-, α2-adrenergic receptors. A o-OCH3 derivative (2e) bound at 5-HT(1A) sites with subnanomolar affinity (IC50=0.059 nM) and shows high selectivity over all considered receptors and may offer a new lead for the development of therapeutically efficacious agents. Copyright (C) 2000 Elsevier Science Ltd.

3-[2-[4-(4-Fluorobenzoyl)piperidin-1-yl]ethyl]- 5,6,7,8-tetrahydro-4(3H)-quinazolinones: Serotonin 5-HT(2A) receptor antagonists endowed with potent central action

A series of 5,6,7,8-tetrahydro-4(3H)-quinazolinones substituted at the 3-position with 4-benzoyl-1-ethylpiperidine, 4-(4-fluorobenzoyl)-1-ethylpiperidine, 4-[bis-(4-fluorophenyl)methylene]-1-ethylpiperidine, or 4-(4-fluorophenyl)-1-propylpiperazine have been prepared and evaluated in binding assays to determine their affinity at serotonin 5-HT(2A) receptors as well as in a functional test, ie, wet dog shakes (WDS) induced by L-5-hydroxytryptophan (L-5-HTP), a behavioural response which is mediated by stimulation of 5-HT(2A) receptors. Among the compounds prepared, 3-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-5,6,7,8-tetrahydro-4(3H) -quinazolinone (10a) and 2-methyl-3-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-5,6,7,8-tetrahydro -4(3H)-quinazolinone (10b) proved to be the most potent 5-HT(2A) receptor antagonists. In binding assays, the two compounds displayed similar affinity for 5-HT(2A) receptors in the nanomolar range to ketanserin and ritanserin. In the WDS test, they were even more potent than ketanserin and ritanserin. Compound 10b, which was found to possess the highest potency and duration of action in the WDS test, was chosen for a preliminary evaluation of its ability to inhibit ethanol intake in rats, a response linked to blockade of the central 5-HT(2A) receptors. This compound significantly reduced ethanol intake in rats from the first day of treatment. The results of the present study indicate that 10b is a potent centrally acting antagonist at 5-HT(2A), receptors.

SEROTONIN ANTAGONISTS, THEIR PREPARATION AND MEDICATIONS CONTAINING THEM

This invention relates to compounds of formula: STR1 in which R. sub.1 denotesa 1,2,3,6-tetrahydro-1-pyridyl radical substituted in the 4-position by an optionally substituted phenyl, optionally substituted 3-indolyl or 3-(5-hydroxyindolyl) radical, a 1-piperazinyl radical substituted in the 4-position by an optionally substituted phenyl, 1,2-benzisothiazol-3-yl, 1,2-benzisoxazol-3-yl or 2-pyridyl radical,a piperidino radical substituted in the 4-position by an optionally substituted phenyl, bis(4-fluorophenyl)methylene, 4-fluorobenzoyl, optionally substituted 2-oxo-1-benzimidazolinyl, optionally substituted 3-indolyl or 3-(5-hydroxyindolyl) radical, by two phenyl radicals or a hydroxyl radical and an optionally substituted phenyl radicalR 2 denotes a radical SO. sub.2 R 4 in which R 4 denotes an alkyl or phenyl radical,R 3 denotes a phenyl or naphthyl radical, or else R 2 and R 3 together with the nitrogen atom to which they are attached form a ring,n is equal to 2, 3 or 4, processes for their preparation and medications containing them. The invention relates to treating a disease ameliorated by serotonin.

Derivatives of (AZA)naphthalenesultam, their preparation and compositions containing them

This invention relates to a compound STR1 in which R 1 representsa 1,2,3,6-tetrahydro-1-pyridyl radical substituted in the 4-position by (a) a phenyl radical, (b) a phenyl radical substituted by a halogen atom or an alkyl, hydroxy or alkoxy radical, (c) a 3-indolyl radical, (d) a 3-indolyl radical substituted on the nitrogen atom by an alkyl or alkylcarbonyl radical and/or in the 5-position by a halogen atom or (e) a 3-(5-hydroxyindolyl) radical.a 1-piperazinyl radical substituted in the 4-position by (a) a phenyl radical, (b) a phenyl radical substituted by an alkoxy, alkyl, hydroxy, nitro or amino radical or a halogen atom, (c) a 1,2-benzisothiazol-3-yl radical, (d) a 1,2-benzisoxazol-3-yl radical or (e) a 2-pyridyl radical.a piperidino radical substituted in the 4-position by (a) a phenyl radical, (b) a phenyl radical substituted by a halogen atom or a hydroxy, alkyl or alkoxy radical, (c) two phenyl radicals, (d) a bis(4-fluorophenyl)methylene radical, (e) a 4-fluorobenzoyl radical, (f) a 2-oxo-1-benzimidazolinyl radical, (g) a 2-oxo-1-benzimidazolinyl radical substituted in the 3-position by an alkylcarbonyl or benzoyl radical, (b) a hydroxy radical and a phenyl radical optionally substituted with an alkyl, alkoxy or hydroxy radical or a halogen atom, (i) a 3-indolyl radical, (j) a 3-indolyl radical substituted on the nitrogen atom by an alkyl or alkylcarbonyl radical and/or in the 5-position by a halogen atom or (k) a 3-(5-hydroxyindolyl) radical.either:R 2 and R 3, which are identical, represent a hydrogen or halogen atom and R 4 represents a hydrogen atom orR 2 and R 4 represent a hydrogen atom and R 3 represents a halogen atom or an acetylamino radical orR 2 and R 3 represent a hydrogen atom and R 4 represents a halogen atom and R 5 represents a --CH group.or R 2, R 3 and R 4 represent a hydrogen atom and R 5 represents a nitrogen atom.R 6 represents an alkylene chain containing 2 to 4 carbon atoms or a propylene chain substituted in the 1- or 3-position by an alkyl radical or in the 2-position by an alkyl, alkoxy, hydroxy, dialkylamino, piperidino, morpholino or thiomorpholino radical,with the reservation that when R 6 represents a propylene radical substituted in the 2-position by a dialkylamino, piperidino, morpholino or thiomorpholino radical, R 1 cannot be a radical containing a hydroxy radical, and their salts, are useful in therapy for their ability to block serotonin receptors.

Phenylpiperazine derivatives of hetarylphenols and hetarylanilines, their preparation, and therapeutic agents containing these compounds

Novel phenylpiperazinylpropane and -butane derivatives of hetarylphenols and hetarylanilines of the formula STR1 where R1 is hydrogen or alkyl of 1 to 4 carbon atoms, R2 is hydrogen, halogen, alkyl of 1 to 4 carbon atoms or alkoxy wh