40255-41-2

Upstream product

• 115338-24-4 2-[4-(4-phenylpiperazin-1-yl)butyl]-1H-isoindole-1,3(2H)-dione 
• 92-54-6 4-phenyl-1-piperazine 
• 5394-18-3 2-(4-bromobutyl)isoindoline-1,3-dione 
• 25220-31-9 4-(4-phenylpiperazin-1-yl)butanenitrile 
• 4004-95-9 1-phenylpiperazine hydrochloride 

Downstream Products

• 115338-26-6 1-phenyl-4-(N-acetyl-4-aminobutyl)piperazine 
• 115338-27-7 1-phenyl-4-(N-benzoyl-4-aminobutyl)piperazine 
• 138753-06-7 (1S,2R,6S,7R)-4-[4-(4-Phenyl-piperazin-1-yl)-butyl]-4-aza-tricyclo[5.2.1.0^2,6]decane-3,5-dione 
• 444145-81-7 (7-methoxy-1,2,3,4-tetrahydro-naphthalen-2-yl)-[4-(4-phenyl-piperazin-1-yl)-butyl]-amine 
• 1003565-57-8 6,7-dimethoxy-N-[4-(4-phenylpiperazin-1-yl)butyl]-1,2,3,4-tetrahydronaphthalen-2-amine 
• 1026083-80-6 N-(4-(4-phenylpiperazin-1-yl)butyl)-1,4-dioxaspiro[4.5]decan-8-amine 
• 1596369-53-7 4-phenyl-N-(4-(4-phenylpiperazin-1-yl)butyl)piperazine-1-carboxamide 

Relevant academic research and scientific papers

Design and synthesis of new potent 5-HT7 receptor ligands as a candidate for the treatment of central nervous system diseases

Owing to their multifunctional pharmacological profiles (including dual 5-HT1A/5-HT7 action), arylpiperazine derivatives are widely used for treating central nervous system diseases including the depression or neuropathic pain. Herein we describe the design, synthesis and evaluation of biological activity of novel 5-HT7 ligands derived of 2,4,6-triamino-1,3,5-triazine. The studied compounds showed affinity and high selectively towards 5-HT7 receptor with the two most active compounds 34 (Ki = 61 nM), 22 (Ki = 109 nM) showing good metabolic stability and moderate affinity to CYP3A4 isoenzyme. Compound 22 had high hepatotoxicity at a concentration below 50 μM, while compound 34 showed low hepatotoxicity even at a concentration above 50 μM.

Design, synthesis, and evaluation of N-(4-(4-phenyl piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamides as selective dopamine D3 receptor ligands

As part of our on-going effort to explore the role of dopamine receptors in drug addiction and identify potential novel therapies for this condition, we have a identified a series of N-(4-(4-phenyl piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide D3 ligands. Members of this class are highly selective for D3 versus D2, and we have identified two compounds (13g and 13r) whose rat in vivo IV pharmacokinetic properties that indicate that they are suitable for assessment in in vivo efficacy models of substance use disorders.

Design, Synthesis, Structure-Activity Relationship Studies, and Three-Dimensional Quantitative Structure-Activity Relationship (3D-QSAR) Modeling of a Series of O-Biphenyl Carbamates as Dual Modulators of Dopamine D3 Receptor and Fatty Acid Amide Hydrolase

We recently reported molecules designed according to the multitarget-directed ligand paradigm to exert combined activity at human fatty acid amide hydrolase (FAAH) and dopamine receptor subtype D3 (D3R). Both targets are relevant for tackling several types of addiction (most notably nicotine addiction) and other compulsive behaviors. Here, we report an SAR exploration of a series of biphenyl-N-[4-[4-(2,3-substituted-phenyl)piperazine-1-yl]alkyl]carbamates, a novel class of molecules that had shown promising activities at the FAAH-D3R target combination in preliminary studies. We have rationalized the structural features conducive to activities at the main targets and investigated activities at two off-targets: dopamine receptor subtype D2 and endocannabinoid receptor CB1. To understand the unexpected affinity for the CB1 receptor, we devised a 3D-QSAR model, which we then prospectively validated. Compound 33 was selected for PK studies because it displayed balanced affinities for the main targets and clear selectivity over the two off-targets. 33 has good stability and oral bioavailability and can cross the blood-brain barrier.

An interactive SAR approach to discover novel hybrid thieno probes as ligands for D2-like receptors with affinities in the subnanomolar range

A series of [(phenylpiperazinyl)alkyl]-isoindole-1,3-dione derivatives was synthesized to serve as probes for dopaminergic receptors. Among this series, compound 6a showed the highest affinity towards D4 and D3 receptors with K i values in the low nanomolar range, and D2/D4- and D2/D3-selectivity indices of 72 and 20, respectively. Optimization rounds were adopted and led to the D4-selective ligand thiophene-2-carboxamide 9a with a Ki(D4) value of 0.62 nM, and to its butyl analog, 10a, with Ki(D4) and Ki(D3) values of 0.03 and 0.26 nM, respectively. Docking experiments revealed the importance of the unique D4 residue Arg186 in manipulating the ligands' D4-subtype-receptor selectivity. Copyright

Synthesis and pharmacological evaluation of [(4-Arylpiperazin-1-yl)-alkyl]- carbamic acid ethyl ester derivatives as potential anxiolytic agents

On the basis of our earlier studies, a series of N-{4-[4-(aryl) piperazin-1-yl]-phenyl}-amine derivatives containing terminal carbamoyl fragment with alkyl spacer of different lengths (15-20) were synthesized as ligands, for 5-hydroxytryptamine-1A (5-HT1A

Further structure-activity relationships study of hybrid 7-{[2-(4-phenylpiperazin-1-yl)ethyl]propylamino}-5,6,7,8-tetrahydronaphthalen-2- ol analogues: identification of a high-affinity D3-preferring agonist with potent in vivo activity with long duration

This paper describes an extended structure-activity relationships study of aminotetralin-piperazine-based hybrid molecules developed earlier for dopamine D2/D3 receptors. Various analogues as positional isomers have been developed where location of the ph

Synthesis and biological characterization of novel hybrid 7-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro- naphthalen-2-ol and their heterocyclic bioisosteric analogues for dopamine D2 and D3 receptors

In a recent preliminary communication we described the development of a series of hybrid molecules for the dopamine D2 and D3 receptor subtypes. The design of these compounds was based on combining pharmacophoric elements of aminotetralin and piperazine m

Hybrid 2-aminotetralin and aryl-substituted piperazine compounds and their use in altering cns activity

Hybrid compounds containing in aminotetralin moiety or a heterocyclic and/or open chain analog thereof linked through an alkylene group to an aryl ring system-substituted piperidiene moiety exhibit high levels of CNS activity, in some cases exhibiting especially high relative binding efficiencies between D3 and D2 dopaminergic receptor subtypes.

A novel series of hybrid compounds derived by combining 2-aminotetralin and piperazine fragments: Binding activity at D2 and D3 receptors

A series of 7-hydroxy-2-[N-alkyl-(N-(4-phenylpiperazine)-alkyl)amino]tetralins was developed based on a novel hybrid approach that combined 2-aminotetralin and arylpiperazine pharmacophoric moieties. Our preliminary study revealed that a four-methylene bu

A new series of selective dopamine D4 ligands: 3-([4-arylpiperazin-1-yl]alkylamino)-2H-1,4-benzoxazines

A series of 3-([4-arylpiperaz-1-yl)alkylamino]-2H-1,4-benzoxazines were prepared and their affinities for cloned human D2, D3, and D4 dopamine receptor subtypes were measured. This led to the identification of 1a, 1f, and 1g as high affinity selective antagonists at the D4 receptor.