Evaluation of agonistic activity of fluorinated and nonfluorinated fentanyl analogs on μ-opioid receptor using a cell-based assay system

The agonistic activity of fluorinated and nonfluorinated fentanyl analogs on μ-opioid receptor was investigated using a cell-based assay system. Based on the activity, fentanyl analogs were ranked as follows: fentanyl>isobutyrylfentanyl≈butyrylfentanyl≈methoxyacetylfentanyl>acetylfentanyl. However, among the fentanyl analogs fluorinated on the Nphenyl ring, 2-fluoro analogs and 3-fluoro analogs showed the strongest and weakest activities, respectively. These results suggest that the 2-fluorinated isomers of fentanyl analogs are more likely to cause poisoning.

ADJUVANTED CONJUGATE OPIOID VACCINE

The adjuvanted conjugate opioid vaccine described herein is a conjugate of a protein carrier and at least one opioid backbone component or hapten conjugated thereto, admixed with at least one adjuvant. Anti-opioid effects are demonstrated after administration of a vaccine made up of the CRM197 protein carrier linked to a FEN backbone, combined with adjuvants such as dmLT or LTA1.

Chemoselective Reductive Aminations in Aqueous Nanoreactors Using Parts per Million Level Pd/C Catalysis

Casotti, Gianluca,Gao, Eugene S.,Jin, Henry S.,Lipshutz, Bruce H.,Takale, Balaram S.,Thakore, Ruchita R.

supporting information,

Condensation in recyclable water between aldehydes or ketones and amines occurs smoothly within the hydrophobic cores of nanomicelles, resulting in imine formation that is subject to subsequent reduction leading, overall, to reductive amination. This micellar technology enables the synthesis of several types of pharmaceuticals, a new procedure that relies on only 2000 ppm (0.20 mol %) palladium from commercially available Pd/C. A broad range of substrates can be used under mild conditions, leading to high chemical yields of the desired secondary and tertiary amines.

Fentanyl family at the mu-opioid receptor: Uniform assessment of binding and computational analysis

Interactions of 21 fentanyl derivatives with μ-opioid receptor (μOR) were studied using experimental and theoretical methods. Their binding to μOR was assessed with radioligand competitive binding assay. A uniform set of binding affinity data contains val

Metabolism of butyrylfentanyl in fresh human hepatocytes: Chemical synthesis of authentic metabolite standards for definitive identification

The metabolism of butyrylfentanyl, a new designer drug, was investigated using fresh human hepatocytes isolated from a liver-humanized mouse model. In the culture medium of hepatocytes incubated with butyrylfentanyl, the desphenethylated metabolite (nor-butyrylfentanyl), w-hydroxy-butyrylfentanyl, (w-1)-hydroxy-butyrylfentanyl, 4′-hydroxy-butyrylfentanyl, β-hydroxy-butyrylfentanyl, 4′-hydroxy-3′- methoxy-butyrylfentanyl, and w-carboxy-fentanyl were identified as the metabolites of butyrylfentanyl. Each metabolite was definitively identified by comparing the analytical data with those of authentic standards. The amount of the main metabolite, nor-butyrylfentanyl, reached 37% of the initial amount of butyrylfentanyl at 48 h. W-Hydroxy-butyrylfentanyl and (w-1)-hydroxy-butyrylfentanyl, formed by hydroxylation at the Nbutyryl group of butyrylfentanyl, were the second and third largest metabolites, respectively. The majority of 4′-hydroxy-butyrylfentanyl and 4′-hydroxy-3′-methoxy-butyrylfentanyl was considered to be conjugated. CYP reaction phenotyping for butyrylfentanyl using human liver microsomes and various anti-CYP antibodies revealed that CYP3A4 was involved in the formation of nor-butyrylfentanyl, (w-1)-hydroxybutyrylfentanyl, and β-hydroxy-butyrylfentanyl. In contrast, CYP2D6 was involved in the formation of w-hydroxy-butyrylfentanyl.

Fentanyl, also known as ‘jackpot’, is a synthetic opiate that is 50–100 times more potent than morphine. Clandestine laboratories produce analogues of fentanyl, known as fentalogues to circumvent legislation regarding its production. Three pyridyl fentalogues were synthesized and then hyperpolarized by signal amplification by reversible exchange (SABRE) to appraise the forensic potential of the technique. A maximum enhancement of -168-fold at 1.4 T was recorded for the ortho pyridyl 1H nuclei. Studies of the activation parameters for the three fentalogues revealed that the ratio of ligand loss trans to hydride and hydride loss in the complex [Ir(IMes)(L)3(H)2]+ (IMes=1,3-bis(2,4,6-trimethylphenyl)imidazole-2-ylidene) ranged from 0.52 to 1.83. The fentalogue possessing the ratio closest to unity produced the largest enhancement subsequent to performing SABRE at earth’s magnetic field. It was possible to hyperpolarize a pyridyl fentalogue selectively from a matrix that consisted largely of heroin (97 : 3 heroin:fentalogue) to validate the use of SABRE as a forensic tool.

A 4 – anilino – N – phenethyl piperidine simple synthesis of process

The invention discloses a 4 – anilino – N – phenethyl piperidine simple synthesis process, comprising the following steps: the reaction bottle, adding raw material N – phenethyl – 4 – piperidone and organic solvent dichloromethane, opening stirring, after

Metabolism of fentanyl and acetylfentanyl in human-induced pluripotent stem cell-derived hepatocytes

To evaluate the capability of human-induced pluripotent stem cell-derived hepatocytes (h-iPS-HEP) in drug metabolism, the profiles of the metabolites of fentanyl, a powerful synthetic opioid, and acetylfentanyl, an N-acetyl analog of fentanyl, in the cells were determined and analyzed. Commercially available h-iPSHEP were incubated with fentanyl or acetylfentanyl for 24 or 48 h. After enzymatic hydrolysis, the medium was deproteinized with acetonitrile, then analyzed by LC/MS. Desphenethylated metabolites and some hydroxylated metabolites, including 4′-hydroxy-fentanyl and β-hydroxy-fentanyl, were detected as metabolites of fentanyl and acetylfentanyl in the medium. The main metabolite of fentanyl with h-iPS-HEP was the desphenethylated metabolite, which was in agreement with in vivo results. These results suggest that h-iPSHEP may be useful as a tool for investigating drug metabolism.

N-phenethyl-4-aniline-based process for preparation of piperidines

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The invention relates to a method for preparing N-phenethyl-4-phenylaminopiperidine. The method comprises the main steps of carrying out hydrogenation and amination on N-phenethyl-4-piperidone (structural formula as shown in a formula (II)) and aniline (structural formula as shown in a formula (III)) in ethanol in the presence of Raney Ni at the temperature of 50-100 DEG C so as to obtain the target product. The method for preparing N-phenethyl-4-phenylaminopiperidine has the advantages of cheap and available raw material, less byproduct, good product purity, high yield, low cost and the like.

Palladium-catalyzed hydroaminocarbonylation of alkenes with amines promoted by weak acid

The weak acid has been identified as an efficient basicity-mask to overcome the basicity barrier imparted by aliphatic amines in the Pd-catalyzed hydroaminocarbonylation, which enables both aromatic and aliphatic amines to be applicable in the palladium-catalyzed hydroaminocarbonylation reaction. Notably, by using this protocol, the marketed herbicide of Propanil and drug of Fentanyl could be easily obtained in a one-pot manner. Buy Fentanyl Precursor 4-ANPP online