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Page 1 de 22 résultats
Novel pyridine derivatives as potent and selective CB2 cannabinoid receptor agonists.
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Replacement of the phenyl ring in our previous (morpholinomethyl)aniline carboxamide cannabinoid receptor ligands with a pyridine ring led to the discovery of a novel chemical series of CB2 ligands. Compound 3, that is, 2,2-dimethyl-N-(5-methyl-4-(morpholinomethyl)pyridin-2-yl)butanamide was
Furo[2,3-b]pyridine-based cannabinoid-1 receptor inverse agonists: synthesis and biological evaluation. Part 1.
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The synthesis, SAR and binding affinities of cannabinoid-1 receptor (CB1R) inverse agonists based on furo[2,3-b]pyridine scaffolds are described. Food intake, mechanism specific efficacy, pharmacokinetic, and metabolic evaluation of several of these compounds indicate that they are effective orally
Tetrahydropyrazolo[4,3-c]pyridine derivatives as potent and peripherally selective cannabinoid-1 (CB1) receptor inverse agonists.
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Peripherally restricted CB1 receptor inverse agonists hold potential as useful therapeutics to treat obesity and related metabolic diseases without causing undesired CNS-mediated adverse effects. We identified a series of tetrahydropyrazolo[4,3-c]pyridine derivatives as potent and highly
Discovery of a high affinity and selective pyridine analog as a potential positron emission tomography imaging agent for cannabinoid type 2 receptor.
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As part of our efforts to develop CB2 PET imaging agents, we investigated 2,5,6-substituted pyridines as a novel class of potential CB2 PET ligands. A total of 21 novel compounds were designed, synthesized, and evaluated for their potency and binding properties toward human and rodent CB1 and CB2.
Identification and Preclinical Development of a 2,5,6-Trisubstituted Fluorinated Pyridine Derivative as a Radioligand for the Positron Emission Tomography Imaging of Cannabinoid Type 2 Receptors
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Despite the broad implications of the cannabinoid type 2 receptor (CB2) in neuroinflammatory processes, a suitable CB2-targeted probe is currently lacking in clinical routine. As part of our medicinal chemistry program, we have recently identified the pyridine-based CB2 PET radioligand
Cannabinoids. Synthesis and central nervous system activity of 8-substituted 10-hydroxy-5,5-dimethyl-5H-[1]benzopyrano[4,3-c]pyridine and derivatives.
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Structure-Activity Relationship Studies of Pyridine-Based Ligands and Identification of a Fluorinated Derivative for the Positron Emission Tomography Imaging of Cannabinoid Type 2 Receptors.
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The cannabinoid type 2 receptor has emerged as valuable target for therapy and imaging of immune- mediated pathologies. With the aim to find a suitable radiofluorinated analogue of the previously reported CB2 PET radioligand [11C]RSR-056, 38 fluorinated derivatives were synthesized and
Design, synthesis, and pharmacological properties of new heteroarylpyridine/heteroarylpyrimidine derivatives as CB(2) cannabinoid receptor partial agonists.
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Recent developments indicate that CB(2) receptor ligands have the potential to become therapeutically important. To explore this potential, it is necessary to develop compounds with high affinity for the CB(2) receptor. Very recently, we have identified the oxazinoquinoline carboxamides as a novel
Evaluation of the role of nicotinic acetylcholine receptor subtypes and cannabinoid system in the discriminative stimulus effects of nicotine in rats.
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Male Wistar rats were trained to discriminate (-)-nicotine (0.4 mg/kg) from saline under a two-lever, fixed-ratio 10 schedule of water reinforcement. During test sessions the following drugs were coadministered with saline (substitution studies) or nicotine (0.025-0.4 mg/kg; combination studies):
Identification and analytical characterization of four synthetic cannabinoids ADB-BICA, NNL-1, NNL-2, and PPA(N)-2201.
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Since the first appearance as psychotropic drugs in illegal markets in 2008, the spread of synthetic cannabinoids is becoming a serious problem in many countries. This paper reports on the analytical properties and structure elucidation of four cannabimimetic derivatives in seized material:
Periaqueductal grey CB1 cannabinoid and metabotropic glutamate subtype 5 receptors modulate changes in rostral ventromedial medulla neuronal activities induced by subcutaneous formalin in the rat.
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This study was undertaken to analyze the involvement of periaqueductal gray (PAG) cannabinoid or group I metabotropic glutamate receptors in the formalin-induced changes on the rostral ventromedial medulla (RVM) ON- and OFF-cells activities. S.c. injection of formalin into the hind paw produced a
Prospective therapeutic agents for obesity: molecular modification approaches of centrally and peripherally acting selective cannabinoid 1 receptor antagonists.
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Presently, obesity is one of the major health problems in the developed as well as developing countries due to lack of physical work and increasing sedentary life style. Endocannabinoid system (ECS) and especially cannabinoid 1 (CB1) receptor play a key role in energy homeostasis. Food intake and
Can A Recently Developed Pig Model Be Used for In Vivo Metabolism Studies of 7-Azaindole Derived Synthetic Cannabinoids? A Study Using 5F-MDMB-P7AICA
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New psychoactive substances (NPS), especially synthetic cannabinoids (SC) remain a public health concern. Due to ethical reasons, systematic controlled human studies to elucidate their toxicodynamics and/or toxicokinetics are usually not possible. However, such knowledge is necessary, for example,
In vitro and in vivo metabolism of a novel cannabinoid-1 receptor inverse agonist, taranabant, in rats and monkeys.
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The metabolism and excretion of taranabant (MK-0364, N-[(1S,2S)-3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl]-2-methyl-2{[5-(trifluoromethyl)pyridine-2-yl]oxy}propanamide), a potent cannabinoid-1 receptor inverse agonist, were evaluated in rats and rhesus monkeys. Following administration of
Drugs derived from cannabinoids. 5. delta6a,10a-Tetrahydrocannabinol and heterocyclic analogs containing aromatic side chains.
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Ten new delta6a,10a-THC analogs with arylalkyl side chains, one with a dimethylaminoalkyl side chain, and six heterocyclic delta6a,10a-THC analogs [8-substituted 5,5-dimethyl-10-hydroxy-2-(2-propynyl)-1,2,3,4-tetrahydro-5H-[1]benzo-pyrano[4,3-c]pyridines] were prepared. They showed pharmacological
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