367275-36-3

Usage

Structure

Contains a piperazine ring connected to a butyl chain, which is attached to an isoindole-1,3(2H)-dione moiety.

Functional Groups

Contains 2,3-dichlorophenyl and piperazine groups, suggesting potential pharmacological activity.

Potential Applications

May have applications in medicinal chemistry and drug development, particularly in drugs with psychoactive and neurological effects.

Further Research

Additional research is needed to fully understand its properties and potential uses.

Upstream product

• 5394-18-3 2-(4-bromobutyl)isoindoline-1,3-dione 
• 119532-26-2 1-(2,3-dichlorophenyl)-piperazine hydrochloride 
• 1074-82-4 potassium phtalimide 
• 136918-14-4 phthalimide 
• 608-27-5 2,3-dichloroaniline 

Downstream Products

• 189061-44-7 4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butylamine 
• 1301179-07-6 N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)propionamide 
• 1301179-09-8 4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-N-propylbutan-1-amine 
• 1301179-13-4 N-((9H-fluoren-2-yl)methyl)-4-(4-(2,3-dichlorophenyl)-piperazin-1-yl)-N-propylbutan-1-amine 
• 1301179-15-6 4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-N-(naphthalen-2-ylmethyl)-N-propylbutan-1-amine 

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.

Multitarget Compounds for Bipolar Disorder: From Rational Design to Preliminary Pharmacokinetic Evaluation

Due to the complex and multifactorial nature of bipolar disorder (BD), single-target drugs have traditionally provided limited relief with no disease-modifying effects. In line with the polypharmacology paradigm, we attempted to overcome these limitations by devising two series of multitarget-directed ligands endowed with both a partial agonist profile at dopamine receptor D3 (D3R) and inhibitory activity against glycogen synthase kinase 3 beta (GSK-3β). These are two structurally unrelated targets that play independent, yet connected, roles in cognition and mood regulation. Two compounds (7 and 10) emerged as promising D3R/GSK-3β multitarget-directed ligands with nanomolar activity at D3R and low-micromolar inhibition of GSK-3β, thereby confirming, albeit preliminarily, the feasibility of our strategy. Furthermore, 7 showed promising drug-like properties in stability and pharmacokinetic studies.

Compound with dopamine D3 receptor adjusting activity, and applications thereof

The invention relates to a compound with dopamine D3 receptor adjusting activity, and applications thereof, and more specifically discloses dopamine receptor D3R as a novel target of post-traumatic stress disorder (PTSD) in prevention, treatment/or auxiliary treatment of PTSD, and screening of anti-PTSD medicines, and relates to applications of a compound with dopamine receptor D3R adjusting activity in preparation of medicines used for preventing, treatment and/or auxiliary treatment of PTSD.

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, and evaluation of bitopic arylpiperazine-phthalimides as selective dopamine D3 receptor agonists

The dopamine D3 receptor (D3R) is a proven therapeutic target for the treatment of neurological and neuropsychiatric disorders. In particular, D3R-selective ligands that can eliminate side effects associated with dopamine D2 receptor (D2R) therapeutics have been validated. However, the high homology in signaling pathways and the sequence similarity between D2R and D3R have rendered the development of D3R-selective ligands challenging. Herein, we designed and synthesized a series of piperazine-phthalimide bitopic ligands based on a fragment-based and molecular docking inspired design. Compound 9i was identified as the most selective D3R ligand among these bitopic ligands. Its selectivity was improved compared to reference compounds 1 and 2 by 9- and 2-fold, respectively, and it was 21-fold more potent than compound 2. Molecular docking demonstrated that the orientation of Leu2.64 and Phe7.39 and the packing at the junction of helices may affect the specificity for D3R over D2R. Functional evaluation revealed that D3R-selective ligand 9i displayed a subpicomolar agonist activity at D3R with a 199-fold increase in potency compared to quinpirole. These results may be useful for the fragment-based design of bitopic compounds as selective D3R ligands.

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.

Design, synthesis and evaluation of bitopic arylpiperazinephenyl-1,2,4-oxadiazoles as preferential dopamine D3 receptor ligands

The dopamine D3 receptor (D3R) was proposed as a therapeutic target for drug development to treat drug abuse and addiction and neuropsychiatric disorders. Several D3R-selective modulators over the dopamine D2 receptor (D2R) can avoid extrapyramidal sympto

High Affinity Dopamine D3 Receptor (D3R)-Selective Antagonists Attenuate Heroin Self-Administration in Wild-Type but not D3R Knockout Mice

The dopamine D3 receptor (D3R) is a promising target for the development of pharmacotherapeutics to treat substance use disorders. Several D3R-selective antagonists are effective in animal models of drug abuse, especially

PHENYL CARBAMATES AND THEIR USE AS INHIBITORS OF THE FATTY ACID AMIDE HYDROLASE (FAAH) ENZYME AND MODULATORS OF THE D3 DOPAMINE RECEPTOR (D3DR)

The invention provides compounds of Formula (I) or pharmaceutically acceptable salts thereof wherein Ar', R1, R2, R3, R4, X, Y are as defined in the description of invention, as multi-target directed ligands (MT

Applying a multitarget rational drug design strategy: The first set of modulators with potent and balanced activity toward dopamine D3 receptor and fatty acid amide hydrolase

Combining computer-assisted drug design and synthetic efforts, we generated compounds with potent and balanced activities toward both D3 dopamine receptor and fatty acid amide hydrolase (FAAH) enzyme. By concurrently modulating these targets, our compounds hold great potential toward exerting a disease-modifying effect on nicotine addiction and other forms of compulsive behavior.