20529-23-1Relevant academic research and scientific papers
Synthesis, in silico, and in vitro studies of novel dopamine D2 and D3 receptor ligands
Elek, Milica,Djokovic, Nemanja,Frank, Annika,Oljacic, Slavica,Zivkovic, Aleksandra,Nikolic, Katarina,Stark, Holger
, (2021/02/26)
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
Benzyl Phenylsemicarbazides: A Chemistry-Driven Approach Leading to G Protein-Biased Dopamine D4 Receptor Agonists with High Subtype Selectivity
Pirzer, Anna S.,Lasch, Roman,Friedrich, Heike,Hübner, Harald,Gmeiner, Peter,Heinrich, Markus R.
, p. 9658 - 9679 (2019/11/13)
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.
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
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
, p. 2287 - 2304 (2017/04/03)
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.
Discovery of naphthalimide conjugates as fluorescent probes for α1-adrenoceptors
Zhang, Wei,Zhou, Xin-Yang,Yu, Qin-Ying,Du, Lu-Pei,Li, Min-Yong
supporting information, p. 185 - 189 (2018/03/22)
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.
Synthesis and evaluation of antiproliferative activity of novel quinazolin-4(3H)-one derivatives
Venkatesh, Ramineni,Kasaboina, Suresh,Janardhan, Sridhara,Jain, Nishant,Bantu, Rajashaker,Nagarapu, Lingaiah
, p. 2070 - 2081 (2016/10/03)
Two series of novel quinazolin-4(3H)-one derivatives (10a–g and 11a–g) have been synthesized and evaluated for their in vitro antiproliferative activity against human HeLa, MIAPACA, MDA-MB-231, and IMR-31 cancer cell lines. The synthesized compounds were characterized by spectral (Fourier transform infrared, 1H nuclear magnetic resonance, 13C nuclear magnetic resonance, high-resolution mass spectra) methods. Among them, compounds 11e and 11g exhibited potent in vitro antiproliferative activity with GI50 values 0.02, less than 0.01 μM against MIAPACA human cancer cell line. Significantly, compounds 10a, 10b, 10c, 10g, 11b, 11c, 11d, 11e, 11f showed activity with GI50 values ranging from 0.1 to 0.87 μM against human cancer cell lines MIAPACA, MDA-MB-231, and IMR-31. We have explored the probable binding mode and key active site interactions in HDAC8 and EHMT2 proteins. The docking results are complementary to the experimental results.
Novel naftopidil-related derivatives and their biological effects as alpha1-adrenoceptors antagonists and antiproliferative agents
Huang, Junjun,He, Fei,Huang, Minyi,Liu, Xiawen,Xiong, Yan,Huang, Yajian,Zhu, Liu,Yang, Ya,Xu, Xingjie,Yuan, Mu
supporting information, p. 83 - 91 (2015/04/22)
Eleven novel naftopidil-related compounds that contain amide and indole groups were designed and synthesized. The biological effects of these compounds on three ±1-adrenoceptor subtypes and cancerous human prostate cell lines (PC-3, DU-145, and LNCaP) were determined. Compounds 2, 3, 5, 11, and 12 exhibited an 1-adrenoceptor antagonistic activity, whereas compounds 9, 10, and 12 displayed moderate antiproliferative activities. Compound 3 exhibited a significant ±1D/1A blocking activity in isolated rat tissues (97.7-and 64.6-fold selective for ±1D and ±1A compared with 1B) but not a relevant cytotoxic activity. Compound 12 demonstrated a potent and selective 1D/1A antagonistic activity (47.9-and 19.1-fold for 1D and ±1A compared with ±1B) and a potent antiproliferative activity in PC-3 cells (IC50 = 15.70 μM). Further testing confirmed that compound 12 inhibited the growth of PC-3 cells by inducing apoptosis and G0/G1 cell cycle arrest, which was mediated by ±1-adrenoceptor. Therefore, compound 12 is a potential multipotent agent that can act as an effective ±1-adrenoceptor subtype antagonist for treating benign prostatic hyperplasia and a preventive medication against human prostate cancer.
PHENYL CARBAMATES AND THEIR USE AS INHIBITORS OF THE FATTY ACID AMIDE HYDROLASE (FAAH) ENZYME AND MODULATORS OF THE D3 DOPAMINE RECEPTOR (D3DR)
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Page/Page column 33; 37; 38; 41, (2015/02/02)
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
Synthesis and pharmacological evaluation of [(4-Arylpiperazin-1-yl)-alkyl]- carbamic acid ethyl ester derivatives as potential anxiolytic agents
Khatri, Manisha,Rai, Santosh K.,Ranbhor, Ranjit,Kishore, Krishna,Tiwari, Manisha
, p. 1143 - 1152 (2012/11/07)
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
Synthesis of several MPP derivatives for 99mTc-labelling and evaluated as potential 5-HT1A receptor imaging agents
Yang, Wenjiang,Lin, Yan,Zhang, Xianzhong,Zhang, Junbo,Wang, Xuebin
experimental part, p. 1148 - 1154 (2012/04/04)
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.
Synthesis and biological evaluation of (phenylpiperazinyl-propyl)arylsulfonamides as selective 5-HT2A receptor antagonists
Yoo, Euna,Yoon, Juhee,Pae, Ae Nim,Rhim, Hyewhon,Park, Woo-Kyu,Kong, Jae Yang,Park Choo, Hea-Young
experimental part, p. 1665 - 1675 (2010/05/02)
A novel series of 5-HT2A ligands that contain a (phenylpiperazinyl-propyl)arylsulfonamides skeleton was synthesized. Thirty-seven N-(cycloalkylmethyl)-4-methoxy-N-(3-(4-arylpiperazin-1-yl)propyl)-arylsulfonamide and N-(4-(4-arylpiperazin-1-yl)b
