56469-10-4Relevant articles and documents
METHODS AND COMPOSITIONS RELATING TO ULTRAPURE 5-(1,1-DIMETHYLHEPTYL)-RESORCINOL
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Page/Page column 30; 34, (2019/05/10)
The invention provides methods and compositions relating to an ultrapure formulation of 5-(1,1-dimethylheptyl)-resorcinol (ultrapure DMHR). The invention features methods for making ultrapure DMHR, including methods that minimize the production of unwanted side products (e.g., the production of homologous alkyl-chain impurities). The invention also features methods of making cannabinoids, such as (6aR,10aR)-1-hydroxy-6,6-dimethyl-3-(2-methyl-2-octanyl)-6a,7,10,10a-tetrahydro-6H-benzo[c]chromene-9-carboxylic acid (ajulemic acid), using ultrapure DMHR, including methods that minimize the production of unwanted side products (e.g., the production of homologous alkyl-chain impurities) in the resulting cannabinoid preparation.
Chromenopyrazole, a Versatile Cannabinoid Scaffold with in Vivo Activity in a Model of Multiple Sclerosis
Morales, Paula,Gómez-Ca?as, María,Navarro, Gemma,Hurst, Dow P.,Carrillo-Salinas, Francisco J.,Lagartera, Laura,Pazos, Ruth,Goya, Pilar,Reggio, Patricia H.,Guaza, Carmen,Franco, Rafael,Fernández-Ruiz, Javier,Jagerovic, Nadine
, p. 6753 - 6771 (2016/08/06)
A combination of molecular modeling and structure-activity relationship studies has been used to fine-tune CB2 selectivity in the chromenopyrazole ring, a versatile CB1/CB2 cannabinoid scaffold. Thus, a series of 36 new derivatives covering a wide range of structural diversity has been synthesized, and docking studies have been performed for some of them. Biological evaluation of the new compounds includes, among others, cannabinoid binding assays, functional studies, and surface plasmon resonance measurements. The most promising compound [43 (PM226)], a selective and potent CB2 agonist isoxazole derivative, was tested in the acute phase of Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD), a well-established animal model of primary progressive multiple sclerosis. Compound 43 dampened neuroinflammation by reducing microglial activation in the TMEV.
Structure-affinity relationships and pharmacological characterization of new alkyl-resorcinol cannabinoid receptor ligands: Identification of a dual cannabinoid receptor/TRPA1 channel agonist
Brizzi, Antonella,Aiello, Francesca,Marini, Pietro,Cascio, Maria Grazia,Corelli, Federico,Brizzi, Vittorio,De Petrocellis, Luciano,Ligresti, Alessia,Luongo, Livio,Lamponi, Stefania,Maione, Sabatino,Pertwee, Roger G.,Di Marzo, Vincenzo
, p. 4770 - 4783 (2014/10/15)
In our ongoing program aimed at deeply investigating the endocannabinoid system (ES), a set of new alkyl-resorcinol derivatives was prepared focusing on the nature and the importance of the carboxamide functionality. Binding studies on CB1 and CB2 receptors, monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH) showed that some of the newly developed compounds behaved as very potent cannabinoid receptor ligands (Ki in the nanomolar range) while, however, none of them was able to inhibit MAGL and/or FAAH. Derivative 11 was a potent CB1 and CB2 ligand, with Ki values similar to WIN 55,212, exhibiting a CB 1 and CB2 agonist profile in vitro. In the formalin test of peripheral acute and inflammatory pain in mice, this compound showed a weak and delayed antinociceptive effect against the second phase of the nocifensive response, exhibiting, interestingly, a quite potent transient receptor potential ankyrin type-1 (TRPA1) channel agonist activity. Moreover, derivative 14, characterized by lower affinity but higher CB2 selectivity than 11, proved to behave as a weak CB2 competitive inverse agonist.
Chromenopyrazoles: Non-psychoactive and Selective CB1 Cannabinoid Agonists with Peripheral Antinociceptive Properties
Cumella, Jose,Hernandez-Folgado, Laura,Giron, Rocio,Sanchez, Eva,Morales, Paula,Hurst, Dow P.,Gomez-Canas, Maria,Gomez-Ruiz, Maria,Pinto, Diana C.G.A.,Goya, Pilar,Reggio, Patricia H.,Martin, Maria Isabel,Fernandez-Ruiz, Javier,Silva, Artur M.S.,Jagerovic, Nadine
experimental part, p. 452 - 463 (2012/06/18)
The unwanted psychoactive effects of cannabinoid receptor agonists have limited their development as medicines. These CB1-mediated side effects are due to the fact that CB1 receptors are largely expressed in the central nervous system (CNS). As it is known that CB1 receptors are also located peripherally, there is growing interest in targeting cannabinoid receptors located outside the brain. A library of chromenopyrazoles designed analogously to the classical cannabinoid cannabinol were synthesized, characterized, and tested for cannabinoid activity. Radioligand binding assays were used to determine their affinities at CB1 and CB2 receptors. Structural features required for CB1/CB2 affinity and selectivity were explored by molecular modeling. Some compounds in the chromenopyrazole series were observed to be selective CB1 ligands. These modeling studies suggest that full CB1 selectivity over CB2 can be explained by the presence of a pyrazole ring in the structure. The functional activities of selected chromenopyrazoles were evaluated in isolated tissues. Invivo behavioral tests were then carried out on the most effective CB1 cannabinoid agonist, 13a. Chromenopyrazole 13a did not induce modifications in any of the tested parameters on the mouse cannabinoid tetrad, thus discounting CNS-mediated effects. This lack of agonistic activity in the CNS suggests that this compound does not readily cross the blood-brain barrier. Moreover, 13a can induce antinociception in a rat peripheral model of orofacial pain. Taking into account the negative results obtained with the hot-plate test, the antinociception induced by 13a in the orofacial test could be mediated through peripheral mechanisms.
Resorcinol-sn-glycerol derivatives: Novel 2-Arachidonoylglycerol mimetics endowed with high affinity and selectivity for cannabinoid type 1 receptor
Brizzi, Antonella,Cascio, Maria Grazia,Frosini, Maria,Ligresti, Alessia,Aiello, Francesca,Biotti, Irene,Brizzi, Vittorio,Pertwee, Roger Guy,Corelli, Federico,Di Marzo, Vincenzo
body text, p. 8278 - 8288 (2012/02/04)
Since the discovery of the endocannabinoid system, evidence has been progressively accumulating to suggest that 2-arachidonoylglycerol (2-AG) rather than anandamide (AEA) is the endogenous ligand for both cannabinoid (CB) receptors. Moreover, other studies have shown that another lipid molecule, 2-arachidonyl-glycerol ether (2-AGE, noladin ether), which acts as a full agonist at cannabinoid receptors, might occur in tissues. Having previously designed a resorcinol-AEA hybrid model, in this paper we have explored the cannabinoid receptor binding properties, the CB1 functional activity, and the stability to plasma esterases of a novel series of compounds characterized by the conversion of the amide head into the glycerol-ester or glycerol-ether head, typical of 2-AG or the "putative" endocannabinoid 2-AGE, respectively. Glyceryl esters 39 and 41 displayed greater potency for CB1 (Ki in the nanomolar range) than for CB2 receptors plus the potential to be exploited as useful hits for the development of novel 2-AG mimetics. (Figure presented)
New resorcinol-anandamide "hybrids" as potent cannabinoid receptor ligands endowed with antinociceptive activity in vivo
Brizzi, Antonella,Brizzi, Vittorio,Cascio, Maria Grazia,Corelli, Federico,Guida, Francesca,Ligresti, Alessia,Maione, Sabatino,Martinelli, Adriano,Pasquini, Serena,Tuccinardi, Tiziano,Di Marzo, Vincenzo
experimental part, p. 2506 - 2514 (2010/03/26)
Bearing in mind the pharmacophoric requirements of both (-)-trans-Δ9-tetrahydrocannabinol (THC) and anandamide (AEA), we designed a novel pharmacophore consisting of both a rigid aromatic backbone and a flexible chain with the aim to develop a series of stable and potent ligands of cannabinoid receptors. In this paper we report the synthesis, docking studies, and structure-activity relationships of new resorcinol-anandamide "hybrids" differing in the side chain group. Compounds bearing a 2-methyloctan-2-yl group at position 5 showed a significantly higher affinity for cannabinoid (CB) receptors, in particular when an alkyloxy chain of 7 or 10 carbon atoms was also present at position 1. Derivative 32 was a potent CB 1 and CB2 ligand, with Ki values similar to that of WIN 55-212 and potent antinociceptive activity in vivo. Moreover, derivative 38, although less potent, proved to be the most selective ligand for CB2 receptor (Ki(CB1)) 1 μM, K i(CB2)) 35 nM).
High enantiomeric purity dexanabinol for pharmaceutical compositions
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Page/Page column 9, (2010/02/07)
The present invention relates to a synthetic cannabinoid, dexanabinol, of enantiomeric purity in excess of 99.90%, or to a pharmaceutically acceptable salt, ester or solvate of said compound. The present invention also relates to pharmaceutical grade compositions comprising said compound of high enantiomeric purity, and uses thereof for prevention and treatment of neurological disorders, chronic degenerative diseases, CNS poisoning, cognitive impairment, inflammatory diseases or disorders, autoimmune diseases or disorders, pain, emesis, glaucoma and wasting syndromes.
Pharmaceutical compositions comprising cannabidiol derivatives
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, (2008/06/13)
The present invention relates to cannabidiol derivatives and to pharmaceutical compositions comprising cannabidiol derivatives being antiinflammatory agents having analgesic, antianxiety, anticonvulsive, neuroprotective, antipsychotic and anticancer activity. The present invention also relates to a process for the preparation of cannabidiol derivatives. It also relates to the use of cannabidiol derivatives and of pharmaceutical compositions comprising same in the preparation of a medicament, in a method of the treatment of human beings with cannabidiol derivatives or with a pharmaceutical preparations comprising same.
Novel tetrahydrocannabinol type compounds
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, (2008/06/13)
A pharmaceutical composition of matter substantially devoid of "cannabis-e" CNS activity containing as active ingredient a compound of the formula STR1 wherein A-----B designates a 1(2) or a 6(1) double bond and wherein R' designates --H or --CO--R where R is lower alkyl, and R" designates alkyl and novel compounds of the 3S,4S configuration of the formula STR2 wherein A----B designates a 1(2) or a 6(1) double bond, R' designates hydrogen or --CO--R where --R is lower alkyl, and R" designates alkyl of at least 6 carbon atoms.
