- Identification of bivalent ligands with melatonin receptor agonist and fatty acid amide hydrolase (FAAH) inhibitory activity that exhibit ocular hypotensive effect in the rabbit
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Activation of melatonin receptors and inhibition of fatty acid amide hydrolase (FAAH) have both shown potential benefits for the treatment of glaucoma. To exploit the combination of these biological activities in single therapeutic agents, we designed dua
- Spadoni, Gilberto,Bedini, Annalida,Furiassi, Lucia,Mari, Michele,Mor, Marco,Scalvini, Laura,Lodola, Alessio,Ghidini, Andrea,Lucini, Valeria,Dugnani, Silvana,Scaglione, Francesco,Piomelli, Daniele,Jung, Kwang-Mook,Supuran, Claudiu T.,Lucarini, Laura,Durante, Mariaconcetta,Sgambellone, Silvia,Masini, Emanuela,Rivara, Silvia
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p. 7902 - 7916
(2018/09/18)
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- 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
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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
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p. 2287 - 2304
(2017/04/03)
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- As opioid receptor antagonists or inverse agonists of the novel compounds
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Novel compounds which are antagonists or inverse agonists at one or more of the opioid receptors, pharmaceutical compositions containing them, to processes for their preparation.
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Paragraph 0146-0149; 0151
(2016/10/08)
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- 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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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
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Page/Page column 33; 34; 39
(2015/02/02)
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- 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
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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.
- De Simone, Alessio,Ruda, Gian Filippo,Albani, Clara,Tarozzo, Glauco,Bandiera, Tiziano,Piomelli, Daniele,Cavalli, Andrea,Bottegoni, Giovanni
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supporting information
p. 4904 - 4907
(2014/05/06)
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- Aerobic oxidative heck/dehydrogenation reactions of cyclohexenones: Efficient access to meta-substituted phenols
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Jockeying for the (meta)position: A new dicationic palladium(II) catalyst, employing a 6,6′-dimethyl-2,2′-bipyridine ligand, promotes both the aerobic oxidative Heck coupling and dehydrogenation reactions of cyclohexenones. These reactions may be combined in a one-pot sequence to enable the straightforward synthesis of meta-substituted phenols (see scheme). Copyright
- Izawa, Yusuke,Zheng, Changwu,Stahl, Shannon S.
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supporting information
p. 3672 - 3675
(2013/04/23)
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- PYRIDYL NON-AROMATIC NITROGENATED HETEROCYCLIC-1-CARBOXYLATE ESTER DERIVATIVE
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[Problem] To provide a compound usable for treatment of diseases associated with fatty acid amide hydrolase (FAAH), especially for treatment of urinary frequency and urinary incontinence, overactive bladder and/or pain. [Means for Solution] We have found that a novel pyridyl non-aromatic nitrogen-containing heterocyclic-1-carboxylate derivative and its pharmaceutically acceptable salt has a potent FAAH-inhibitory activity. Further, the pyridyl non-aromatic nitrogen-containing heterocyclic-1-carboxylate derivative of the present invention has an excellent effect for increasing an effective bladder capacity, an excellent effect for relieving urinary frequency and an excellent anti-allodynia effect, and is therefore usable for treatment of urinary frequency and urinary incontinence, overactive bladder and/or pain.
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Page/Page column 28
(2008/06/13)
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- Cyclohexylcarbamic acid 3′- or 4′-substituted biphenyl-3-yl esters as fatty acid amide hydrolase inhibitors: Synthesis, quantitative structure-activity relationships, and molecular modeling studies
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Fatty acid amide hydrolase (FAAH) is a promising target for modulating endocannabinoid and fatty acid ethanolamide signaling, which may have important therapeutic potential. We recently described a new class of O-arylcarbamate inhibitors of FAAH, includin
- Mor, Marco,Rivara, Silvia,Lodola, Alessio,Plazzi, Pier Vincenzo,Tarzia, Giorgio,Duranti, Andrea,Tontini, Andrea,Piersanti, Giovanni,Kathuria, Satish,Piomelli, Daniele
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p. 4998 - 5008
(2007/10/03)
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- MODULATION OF ANXIETY THROUGH BLOCKADE OF ANANDAMIDE HYDROLYSIS
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Fatty acid amide hydrolase inhibitors of the Formula (I) are provided, wherein X is NH, CH2, O, or S; Q is O or S; Z is O or N; R is an aromatic moiety selected from the group consisting of substituted or unsubstituted aryl; substituted or unsubstituted b
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