Some Analogs of Synthetic Tetrahydrocannabinol

Alles, Gordon A.; Icke, Roland N.; Feigen, George A.

doi:10.1021/ja01261a010

Cited by 11 publications

(7 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A stirred solution of 3-pentylphenol ( 9 ) (1.376 g, 8.4 mmol) and 2,6-di- tert -butyl-4-methylpyridine (2.414 g, 11.8 mmol) in dry CH 2 Cl 2 (42 mL) was treated with triflic anhydride (1.65 mL, 10.1 mmol) at 0 °C, and the mixture was stirred at room temperature for 3.5 h. The resulting suspension was filtered, and the filtrate was diluted with AcOEt, washed with 2 N HCl solution, saturated NaHCO 3 and brine, dried (Na 2 SO 4 ), and evaporated under vacuum. The residue (3.10 g) was chromatographed on silica gel (100 g) using hexane as eluent to give 2.205 g (89%) of 10 as an oil.…”

Section: Methodsmentioning

confidence: 99%

“…[1,1′-Biphenyl]-3-acetic acid ( 4m ) was prepared by Suzuki cross-coupling of 7 with phenylboronic acid followed by alkaline hydrolysis (Scheme ). The synthesis of [3′-pentyl-1,1′-biphenyl]-4-butanoic acid ( 4n ) was carried out in six steps from 3-pentylphenol ( 9 ) . After triflation of 9 , the triflate 10 was subjected to a Suzuki cross-coupling with 3-hydroxyphenylboronic acid to give [3′-pentyl-1,1′-biphenyl]-3-ol ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

New N-Arachidonoylserotonin Analogues with Potential “Dual” Mechanism of Action against Pain

et al. 2007

View full text Add to dashboard Cite

N-arachidonoylserotonin (AA-5-HT, 1a) is an inhibitor of fatty acid amide hydrolase (FAAH) that acts also as an antagonist of transient receptor potential vanilloid-type 1 (TRPV1) channels and is analgesic in rodents. We modified the chemical structure of 1a with the aim of developing "hybrid" FAAH/TRPV1 blockers more potent than the parent compound or obtaining analogues with single activity at either of the two targets to study the mechanism of the analgesic action of 1a. Thirty-eight AA-5-HT analogues, containing a serotonin "head" bound to a variety of lipophilic moieties via amide, urea, or carbamate functionalities, were synthesized. Unlike 1a, most of the new compounds possessed activity at only one of the two considered targets. The amides 1b and 1c of alpha- and gamma-linolenic acid, however, showed "hybrid" activity similar to 1a. The carbamate 3f (OMDM106), although unable to antagonize TRPV1 receptors, was the most potent FAAH inhibitor in this study (IC50=0.5 microM). Compounds 3f and 1m (OMDM129), which exhibited activity at only FAAH or TRPV1, respectively, were 10-fold less potent than 1a at preventing formalin-induced hyperalgesia in mice.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

New N-Arachidonoylserotonin Analogues with Potential “Dual” Mechanism of Action against Pain

et al. 2007

View full text Add to dashboard Cite

show abstract

“…(a) Chemicals, Materials, and Methods. All reagents and compounds 7 and 19 − 27 were purchased from Sigma-Aldrich with the exception of 8c , 8d , 8e , 8h , and biphenyl-3-ylamine, whose preparation is reported in the literature. Solvents were RP grade unless otherwise indicated.…”

Section: Methodsmentioning

confidence: 99%

Design, Synthesis, and Structure−Activity Relationships of Alkylcarbamic Acid Aryl Esters, a New Class of Fatty Acid Amide Hydrolase Inhibitors

et al. 2003

View full text Add to dashboard Cite

Fatty acid amide hydrolase (FAAH), an intracellular serine hydrolase enzyme, participates in the deactivation of fatty acid ethanolamides such as the endogenous cannabinoid anandamide, the intestinal satiety factor oleoylethanolamide, and the peripheral analgesic and anti-inflammatory factor palmitoylethanolamide. In the present study, we report on the design, synthesis, and structure−activity relationships (SAR) of a novel class of potent, selective, and systemically active inhibitors of FAAH activity, which we have recently shown to exert potent anxiolytic-like effects in rats. These compounds are characterized by a carbamic template substituted with alkyl or aryl groups at their O- and N-termini. Most compounds inhibit FAAH, but not several other serine hydrolases, with potencies that depend on the size and shape of the substituents. Initial SAR investigations suggested that the requirements for optimal potency are a lipophilic N-alkyl substituent (such as n-butyl or cyclohexyl) and a bent O-aryl substituent. Furthermore, the carbamic group is essential for activity. A 3D-QSAR analysis on the alkylcarbamic acid aryl esters showed that the size and shape of the O-aryl moiety are correlated with FAAH inhibitory potency. A CoMSIA model was constructed, indicating that whereas the steric occupation of an area corresponding to the meta position of an O-phenyl ring improves potency, a region of low steric tolerance on the enzyme active site exists corresponding to the para position of the same ring. The bent shape of the O-aryl moieties that best fit the enzyme surface closely resembles the folded conformations observed in the complexes of unsaturated fatty acids with different proteins. URB524 (N-cyclohexylcarbamic acid biphenyl-3-yl ester, 9g) is the most potent compound of the series (IC50 = 63 nM) and was therefore selected for further optimization.

show abstract

“…Toluenesulfonic ester 6 was prepared from the reaction of hydroxy ester 5 with p-toluenesulfonyl chloride in pyridine. Inversion of the C-10' position was accomplished by reaction of 6 with tetraethylammonium acetate in refluxing methyl ethyl ketone to give 7. The conversion of 7 to 8…”

mentioning

confidence: 99%

Hashish. Importance of the phenolic hydroxyl group in tetrahydrocannabinols

Uliss¹,

Dalzell²,

Handrick³

et al. 1975

J. Med. Chem.

View full text Add to dashboard Cite

Optically active delta-3- and delta-8-tetrahydrocannabinols (THC's), cannabidiol and racemic delta-9-cis-THC, and their corresponding analogs (1b yields 4b) in which the positions of the phenolic hydroxyl group and the n-C5 side chain have been interchanged are compared in selected pharmacological tests in mice. the results indicate that the phenolic hydroxyl group in the 1 position in THC's is very important for eliciting activity and that cannabidiol and delta-9-cis-THC possess weak CNS depressant properties.

show abstract

Some Analogs of Synthetic Tetrahydrocannabinol

Cited by 11 publications

References 4 publications

New N-Arachidonoylserotonin Analogues with Potential “Dual” Mechanism of Action against Pain

New N-Arachidonoylserotonin Analogues with Potential “Dual” Mechanism of Action against Pain

Design, Synthesis, and Structure−Activity Relationships of Alkylcarbamic Acid Aryl Esters, a New Class of Fatty Acid Amide Hydrolase Inhibitors

Hashish. Importance of the phenolic hydroxyl group in tetrahydrocannabinols

Contact Info

Product

Resources

About