- Synthesis, preclinical evaluation and molecular modelling of macrocyclic appended 1-(2-methoxyphenyl)piperazine for 5-HT1A neuroreceptor imaging
-
5-HT1A receptors are known to be implicit in a number of neuropsychiatric fluctuations related to mood and anxiety. Their visualization in the human brain using PET, SPECT or MRI is of great importance in the management and treatment of neurolo
- Hazari, Puja Panwar,Prakash, Surbhi,Meena, Virendra Kumar,Singh, Niraj,Chuttani, Krishna,Chadha, Nidhi,Singh, Pooja,Kukreti, Shrikant,Mishra, Anil Kumar
-
-
Read Online
- 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
- Boateng, Comfort A.,Bakare, Oluyomi M.,Zhan, Jia,Banala, Ashwini K.,Burzynski, Caitlin,Pommier, Elie,Keck, Thomas M.,Donthamsetti, Prashant,Javitch, Jonathan A.,Rais, Rana,Slusher, Barbara S.,Xi, Zheng-Xiong,Newman, Amy Hauck
-
-
Read Online
- Synthesis and radiolabelling of [123I]-4-iodo-N-(4-(4-(2-methoxyphenyl)-piperazin-1-yl) butyl)-benzamide, a potential dopamine D3 antagonist for SPECT studies
-
Schizophrenia is a devastating mental disorder characterized by relapsing psychotic episodes accompanied with emotional, professional and social decline. The classical dopamine hypothesis of schizophrenia postulates that hyperactivity of dopaminergic neur
- Staelens,Dumont,De Vos,Oltenfreiter,Vandecapelle,Dierckx,Slegers
-
-
Read Online
- Synthesis and radiolabelling of [123I]-4-iodo-N-(4-(4-(2-methoxyphenyl)-piperazin-1-yl) butyl)-benzamide, a potential dopamine D3 antagonist for SPECT studies
-
Schizophrenia is a devastating mental disorder characterized by relapsing psychotic episodes accompanied with emotional, professional and social decline. The classical dopamine hypothesis of schizophrenia postulates that hyperactivity of dopaminergic neur
- Staelens,Dumont,De Vos,Oltenfreiter,Vandecapelle,Dierckx,Slegers
-
-
Read Online
- Photochromic Dopamine Receptor Ligands Based on Dithienylethenes and Fulgides
-
We describe the incorporation of the well-investigated class of photochromic dithienylethenes (DTEs) and fulgides into known dopamine receptor ligands such as 1,4-disubstituted aromatic and hydroxybenzoxazinone piperazines as well as aminoindanes. Subtype
- Lachmann, Daniel,Studte, Carolin,M?nnel, Barbara,Hübner, Harald,Gmeiner, Peter,K?nig, Burkhard
-
-
Read Online
- 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.
- Drabczyk, Anna K.,Latacz, Gniewomir,Ja?kowska, Jolanta,Ku?aga, Damian,Pla?uk, Damian,Rózga, Karolina,Sata?a, Grzegorz
-
-
- Synthesis, in silico, and in vitro studies of novel dopamine D2 and D3 receptor ligands
-
Dopamine is an important neurotransmitter in the human brain and its altered concentrations can lead to various neurological diseases. We studied the binding of novel compounds at the dopamine D2 (D2R) and D3 (D3/sub
- Elek, Milica,Djokovic, Nemanja,Frank, Annika,Oljacic, Slavica,Zivkovic, Aleksandra,Nikolic, Katarina,Stark, Holger
-
-
- The one-pot synthesis of butyl-1H-indol-3-alkylcarboxylic acid derivatives in ionic liquid as potent dual-acting agent for management of BPH
-
Based on the SAR of both α1-AR antagonists and 5α-reductase (5AR) inhibitors, the dual-acting agent 4-(1-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-1H-indol-3-yl)butanoic acid 4aaa was designed against BPH and synthesized by two steps of N-alkylation. One-pot protocol towards 4aaa was newly developed. With IL [C6min]Br as solvent, the yield of 4aaa was increased to 75.1% from 16.0% and the reaction time was shortened in 1.5 h from 48 h. 25 derivatives structurally based on arylpiperazine and indolyl butyric acid with alkyl linker were prepared. The protocol was futher extended to get another 14 derivatives wherein O-alkylation was involved, and applied to the synthesis of biologically efficient molecules DPQ and Aripiprazole. Expectedly, compound 4aaa exhibited dual inhibition of α1-AR and 5α-reductase, and exhibited no obvious cytotoxicity against human cells. The pharmacokinetic properties of 4aaa was also determined.
- Chen, Kaixuan,Jiang, Zhenzhou,Liu, Shuwen,Xi, Baomin,Yang, Fubiao,Zeng, Li-Yan,Zeng, Yunong
-
-
- 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.
- Chen, Peng-Jen,Taylor, Michelle,Griffin, Suzy A.,Amani, Armaghan,Hayatshahi, Hamed,Korzekwa, Kenneth,Ye, Min,Mach, Robert H.,Liu, Jin,Luedtke, Robert R.,Gordon, John C.,Blass, Benjamin E.
-
p. 2690 - 2694
(2019/08/07)
-
- Benzyl Phenylsemicarbazides: A Chemistry-Driven Approach Leading to G Protein-Biased Dopamine D4 Receptor Agonists with High Subtype Selectivity
-
Many subtype-selective dopamine receptor ligands developed for the D2-D4 family incorporate a 1-arylpiperazine-derived primary recognition motif, which is connected to a lipophilic moiety occupying an extended binding pocket (EBP) of the receptor via an aliphatic linker of variable lengths. The evaluation of a novel group of dopamine receptor ligands now showed that highly subtype-selective ligands [up to Ki(D4.4) = 0.25 nM, D2L/D4.4 = 320, D3/D4.4 = 710 for APH199 (17)] can be obtained by choosing a relatively large and conformationally flexible 1-benzyl-1-phenylsemicarbazide substructure to fill the EBP. The novel chemotype APH199 (17) was found to act as a full agonist at the D4 receptor showing significant bias toward G protein activation over β-arrestin recruitment in comparison to quinpirole.
- Pirzer, Anna S.,Lasch, Roman,Friedrich, Heike,Hübner, Harald,Gmeiner, Peter,Heinrich, Markus R.
-
p. 9658 - 9679
(2019/11/13)
-
- 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.
- De Simone, Alessio,Russo, Debora,Ruda, Gian Filippo,Micoli, Alessandra,Ferraro, Mariarosaria,Di Martino, Rita Maria Concetta,Ottonello, Giuliana,Summa, Maria,Armirotti, Andrea,Bandiera, Tiziano,Cavalli, Andrea,Bottegoni, Giovanni
-
supporting information
p. 2287 - 2304
(2017/04/03)
-
- Discovery of naphthalimide conjugates as fluorescent probes for α1-adrenoceptors
-
α1-Adrenoceptors (α1-ARs), including at least three subtypes, α1A, α1B and α1D, which play essential roles in G protein-coupled receptors (GPCRs), can convey multiple pivotal extracellular signals in varied tissues and organs. In this research, a series of napthalimide-based small-molecule fluorescent probes (1a–1f) for α1-ARs, including two parts, a pharmacophore (quinazoline and phenylpiperazine) for α1-AR recognition and a fluorophore (naphthalimide) for visualization, were designed and synthesized successfully. These compounds display excellent fluorescence property and high affinity to receptors, which were used successfully for in vitro visualization of α1-adrenoceptors.
- Zhang, Wei,Zhou, Xin-Yang,Yu, Qin-Ying,Du, Lu-Pei,Li, Min-Yong
-
p. 185 - 189
(2018/03/22)
-
- 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
- -
-
Page/Page column 33; 35; 36
(2015/02/02)
-
- Synthesis of several MPP derivatives for 99mTc-labelling and evaluated as potential 5-HT1A receptor imaging agents
-
The (2-methoxyphenyl) piperazine (MPP) was selected as the functional group and conjugated to dithiocarbamate through different spacers. A series of new MPP derivatives (MPPnDTC, n = 2-6) were synthesized and radiolabelled with 99mTc-nitrido core or 99mTc-tricarboxyl core as potential 5-HT1A receptor imaging agents. All the six 99mTc-labelled complexes were lipophilic and neutral. Biodistribution results showed that those radiotracers had moderate initial brain and hippocampus uptake. There have no significant relation was observed between the biological properties of these tracers with the length of its carbon chain. The radioactivity concentrations of hippocampus of 99mTcN-MPP2DTC, 99mTcN-MPP3DTC, 99mTcN-MPP4DTC, 99mTcN-MPP5DTC, 99mTcN-MPP6DTC and 99mTc(CO)3-MPP3DTC at 2 min post-injection time (p.i.) were 0.43, 1.15, 0.99, 1.04, 1.13 and 0.83 %ID/g, respectively.
- Yang, Wenjiang,Lin, Yan,Zhang, Xianzhong,Zhang, Junbo,Wang, Xuebin
-
p. 1148 - 1154
(2012/04/04)
-
- NOVEL DOPAMINE D3 RECEPTOR LIGANDS, THE PREPARATION AND USE THEREOF
-
The invention discloses novel piperazine derivatives represented by formula I having activity for modulating dopamine D3 receptor, their stereoisomers, pharmaceutical salts, solvates, and the pharmaceutical compositions containing such compounds, their preparation and the use of such compounds for preventing or treating the diseases correlated with central nervous system disorder, such as Parkinson's disease, schizophrenia, drug addiction and relapse and the like, as well as the use of such compounds for kidney protection and immune modulation, or as implemental medicine for researching the function of D3R and the diseases correlated with disorder of D3R function.
- -
-
Page/Page column 14
(2011/09/12)
-
- NOVEL DOPAMINE D3 RECEPTOR LIGANDS AND PREPARATION AND MEDICAL USES OF THE SAME
-
The present invention relates to a novel piperazine derivative represented by Formula I having an activity for regulating dopamine D3 receptor, stereoisomers thereof, pharmaceutically acceptable salts or solvates, and a pharmaceutical composition comprising the compound, a process for preparing the same, and use thereof in the prevention or treatment of a disease associated with central nervous system dysfunction, such as Parkinson''s disease, schizophrenia, drug addiction and relapse, as well as kidney protection and immunoregulation, or as a tool for researching D3R function or diseases associated with D3R dysfunction.
- -
-
Page/Page column 8-9
(2012/01/13)
-
- Synthesis and pharmacological evaluation of fluorine-containing D 3 dopamine receptor ligands
-
A series of fluorine-containing N-(2-methoxyphenyl)piperazine and N-(2-fluoroethoxy)piperazine analogues were synthesized, and their affinities for human dopamine D2, D3, and D4 receptors were determined. Radioligand binding studies identified five compounds, 18a, 20a, 20c, 20e, and 21e, which bind with high affinity at D3 (K i = 0.17-5 nM) and moderate to high selectivity for D3 vs D2 receptors (ranging from ~25- to 163-fold). These compounds were also evaluated for intrinsic activity at D2 and D3 receptors using a forskolin-dependent adenylyl cyclase assay. This panel of compounds exhibits varying receptor subtype binding selectivity and intrinsic activity at D2 vs D3 receptors. These compounds may be useful for behavioral pharmacology studies on the role of D2-like dopamine receptors in neuropsychiatric and neurological disorders. Furthermore, compound 20e, which has the highest binding affinity and selectivity for the D3 receptor (Ki = 0.17 nM for D3, 163-fold selectivity for D3 vs D2 receptors), represents a candidate fluorine-18 radiotracer for in vivo PET imaging studies on the regulation of D3 receptor expression.
- Tu, Zhude,Li, Shihong,Cui, Jinquan,Xu, Jinbin,Taylor, Michelle,Ho, David,Luedtke, Robert R.,MacH, Robert H.
-
supporting information; experimental part
p. 1555 - 1564
(2011/06/19)
-
- RADIOLABELED COMPOUNDS AND METHODS THEREOF
-
The present invention relates to radiodiagnostic compounds, methods of making those compounds, and methods of use thereof as imaging agents for preferably a HA serotonin 5-HT1A receptor for use in PET or SPECT, preferably PET. Compositions comprising an imaging-effective amount of radiolabeled compounds are also disclosed. The present invention also relates to non-radiolabeled compounds, methods of making those compounds, and methods of use thereof to treat various neurological and/or psychiatric disorders.
- -
-
Page/Page column 162
(2011/12/14)
-
- Synthesis and in vitro binding studies of piperazine-alkyl-naphthamides: Impact of homology and sulphonamide/carboxamide bioisosteric replacement on the affinity for 5-HT1A, α2A, D4.2, D3 and D2L receptors
-
A series of carboxamide and sulphonamide alkyl(ethyl to hexyl)piperazine analogues were prepared and tested for their affinity to bind to a range of receptors potentially involved in psychiatric disorders. These chemical modifications led us to explore th
- Résimont, Mélissa,Liégeois, Jean-Fran?ois
-
scheme or table
p. 5199 - 5202
(2010/10/03)
-
- NOVEL CHROMENE AND THIOCHROMENE CARBOXAMIDE DERIVATIVES, METHODS FOR PREPARING SAME AND THERAPEUTIC APPLICATIONS OF SAME
-
The present invention relates to novel chromene or thiochromene carboxamide derivatives, the preparation of same, pharmaceutical compositions of same and the use of same as dopamine D3 ligands as a medicament for central nervous system disorders.
- -
-
Page/Page column 25-26
(2008/06/13)
-
- MODULATORS OF ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTORS AND THERAPEUTIC USES THEREOF
-
The present invention relates to compounds with α7 nAChR agonistic activity, processes for their preparation, pharmaceutical compositions containing the same and the use thereof for the treatment of neurological, psychiatric, cognitive, immunological and inflammatory disorders.
- -
-
Page/Page column 15; 37
(2010/02/15)
-
- Synthesis and initial PET imaging of new potential dopamine D3 receptor radioligands (E)-4,3,2-[11C]methoxy-N-4-(4-(2-methoxyphenyl) piperazin-1-yl)butyl-cinnamoylamides
-
D3 receptor radioligands (E)-4,3,2-[11C]methoxy-N-4- (4-(2-methoxyphenyl)piperazin-1-yl)butyl-cinnamoylamides (4-[11C]MMC, [11C]1a; 3-[11C]MMC, [11C]1b; and 2-[ 11C]MMC, [11
- Gao, Mingzhang,Mock, Bruce H.,Hutchins, Gary D.,Zheng, Qi-Huang
-
p. 6233 - 6243
(2007/10/03)
-
- N-(ω)-(4-(2-methoxyphenyl)piperazin-1-yl)alkyl)carboxamides as dopamine D2 and D3 receptor ligands
-
The dopamine D3 receptor is recognized as a potential therapeutic target for the treatment of various neurological and psychiatric disorders. Targetting high affinity and D3 versus D2 receptor-preferring ligands, the parti
- Hackling, Anneke,Ghosh, Robin,Perachon, Sylvie,Mann, André,H?ltje, Hans-Dieter,Wermuth, Camille G.,Schwartz, Jean-Charles,Sippl, Wolfgang,Sokoloff, Pierre,Stark, Holger
-
p. 3883 - 3899
(2007/10/03)
-
- Analogues of the 5-HT(1A) serotonin antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine with reduced α1-adrenergic affinity
-
1-(2-Methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine (NAN-190; 1a) is a putative postsynaptic 5-HT(1A) serotonin antagonist. This high affinity ligand (K(i) = 0.6 nM), although selective for 5-HT(1A) versus other 5-HT receptors, binds with nearly equa
- Raghupathi,Rydelek-Fitzgerald,Teitler,Glennon
-
p. 2633 - 2638
(2007/10/02)
-
- Thiophene Systems. 11. The Synthesis of Novel Thieno Tricyclic Ring Systems
-
The synthesis of thieno tricyclic compounds is described.The N-1 alkylation of I produced the alkanoic ester precursors.After hydrolysis, the corresponding carboxylic acids were cyclized to the title compounds II.This cyclization step was accomp
- Russell, Roland K.,Rampulla, Richard A.,Nievelt, Caroline E. van,Klaubert, Dieter H.
-
p. 1761 - 1770
(2007/10/02)
-
- Arylpiperazine Derivatives as High-Affinity 5-HT1A Serotonin Ligands
-
Although simple arylpiperazines are commonly considered to be moderately selective for 5-HT1B serotonin binding sites, N4-substitution of such compounds can enhance their affinity for 5-HT1A sites and/or decrease their affinity for 5
- Glennon, Richard A.,Naiman, Noreen A.,Lyon, Robert A.,Titeler, Milt
-
p. 1968 - 1971
(2007/10/02)
-
- ISOINDOLINYL-ALKYL-PIPERAZINES
-
The invention is generally concerned with isoindolinyl-alkylpiperazine compounds generally characterized by the formula STR1 wherein X is halogen or trifluoromethyl; n is an integer ranging from 2 to 5; Y is STR2 in which R 1 is hydrogen, halogen, lower alkyl, lower alkoxy, trifluoromethyl, cyano; R 2 is hydrogen, halogen, lower alkyl, lower alkoxy; and R 3 is hydrogen, cyano. These compounds are useful as diuretic and/or antihypertensive agents.
- -
-
-