Cocaine: Pharmacokinetics and biotransformation in man

1989 ◽  
Vol 67 (9) ◽  
pp. 1154-1157 ◽  
Author(s):  
T. Inaba
Keyword(s):  
Methyl Ester ◽  
Ester Group ◽  
Oral Route ◽  
Plasma Cholinesterase ◽  
Pharmacokinetic Studies ◽  
Hydrolytic Cleavage ◽  
Bicyclic Structure ◽  
Anesthetic Action ◽  
Pharmacologically Active ◽  
Cytochrome P 450

Pharmacokinetic studies of cocaine have been carried out only in the last decade, although its local anesthetic action and addictive properties have been known for almost 100 years. Elimination half-lives of cocaine in man estimated from serial plasma concentration are relatively short and range from 0.5 to 1.1 h after i.v. and 0.9–1.5 h after administration by the nasal or oral route. The bioavailability after nasal inhalation is about 60%. The bicyclic structure of cocaine is characterized by functional groups including N-methyl, carboxyl methyl ester, and benzoyl ester, which are susceptible to biotransformation. Hydrolysis of the benzoyl group to ecgonine methyl ester is catalyzed by plasma cholinesterase and is thus under monogenic control. The hydrolytic cleavage of the other ester group, methyl ester, to benzoyl ecgonine occurs spontaneously at body temperature. In contrast, N-demethylation of cocaine mediated by microsomal cytochrome P-450 produces norcocaine and this metabolite was shown to be pharmacologically active, the action being similar to cocaine.Key words: cocaine, hydrolysis, plasma cholinesterase, cytochrome P-450.

Synthetic Approaches to the Bifunctional Chelators for Radio­nuclides Based On Pyridine-Containing Azacrown Compounds

Synthesis ◽  
2019 ◽  
Vol 52 (07) ◽  
pp. 1087-1095
Author(s):  
Anastasia D. Zubenko ◽  
Anna A. Shchukina ◽  
Olga A. Fedorova
Keyword(s):  
Drug Delivery ◽  
Methyl Ester ◽  
Targeted Drug Delivery ◽  
Pyridine Ring ◽  
Ester Group ◽  
Metal Chelation ◽  
Carboxylate Groups ◽  
Pyridine Fragment ◽  
Targeted Drug ◽  
Synthetic Approaches

Synthetic ways to introduce functional groups (CO2Me, CO2H, OCH2CO2H, OCH2C≡CH, CH2OH, CH2Cl, CH2N3) into the pyridine ring of pyridine-containing azacrown compounds are described. These groups were introduced at position-4 of the pyridine ring, while keeping the macrocyclic carboxylate groups available for metal chelation. The derivatives were obtained by macrocyclization reaction of 4-substituted, trimethyl pyridine-2,4,6-tricarboxylate or by modification of methyl ester group in pyridine fragment of macrocycles. Obtained derivatives can be applied for preparing radiotherapeutic agents by conjugation to different vector biomolecules for targeted drug delivery to cancer cells without damaging healthy tissue.

New sesquiterpenoids bearing 11-methyl ester group of agarwood

Fitoterapia ◽  
2020 ◽  
Vol 143 ◽  
pp. 104557
Author(s):  
Wei Li ◽  
Yi-Ling Yang ◽  
Li Yang ◽  
Hao Wang ◽  
Wen-Hua Dong ◽  
...  
Keyword(s):  
Methyl Ester ◽  
Ester Group

scholarly journals Methyl 3,5-bis(cyclohexylmethoxy)benzoate

2014 ◽  
Vol 70 (4) ◽  
pp. o400-o401 ◽  
Author(s):  
Peter W. R. Corfield ◽  
Michele L. Paccagnini ◽  
Amy M. Balija
Keyword(s):  
Methyl Ester ◽  
Hydrogen Bonds ◽  
Aromatic Ring ◽  
Title Compound ◽  
Ester Group ◽  
Interplanar Distance ◽  
Compound C ◽  
The Mean

In the title compound, C22H32O4, the atoms of the methyl ester group and the alkoxy O atoms are all coplanar with the central aromatic ring, with an r.m.s. deviation of 0.008 Å. Bonds to the methylene and cyclohexyl groups are also very close to this plane, so that the molecule is essentially flat, apart from the cyclohexyl groups. The mean planes through the cyclohexyl groups are tilted by 30.08 (9) and 36.14 (7)° with respect to the central aromatic ring. In the crystal, pairs of molecules linked by C—H...O hydrogen bonds form planar units which are stacked along theaaxis, with an average interplanar distance of 3.549 (2) Å. Stacking appears to be stabilized by further weak C—H...O hydrogen bonds.

Determination of Aspartame in Beverages Using an Alcohol Oxidase Enzyme Electrode

1989 ◽  
Vol 72 (1) ◽  
pp. 30-33
Author(s):  
Vicki J Smith ◽  
Richard A Green ◽  
Thomas R Hopkins
Keyword(s):  
Liquid Chromatography ◽  
Standard Deviation ◽  
Methyl Ester ◽  
Alcohol Oxidase ◽  
Ester Group ◽  
Oxygen Electrode ◽  
Artificial Sweetener ◽  
Relative Standard ◽  
Oxidase Enzyme

Abstract A new method for the determination of the artificial sweetener aspartame is described. α-Chymotrypsin is used to cleave the methyl ester group of aspartame, producing methanol hydrolytically. The methanol is detected using an electrode which is constructed by physically trapping yeast alcohol oxidase enzyme at the tip of a dissolved oxygen electrode. The decrease in oxygen concentration, which occurs as methanol is enzymatically oxidized to formaldehyde, is measured amperometrically. Aspartame levels in diet soft drinks as determined by the proposed method and by liquid chromatography are in excellent agreement. The relative standard deviation of the measurements is 0.83%. The methanol present in diet cola as a result of aspartame degradation can also be measured by using the electrode without α-chymotrypsin.

Isohexide hydroxy esters: synthesis and application of a new class of biobased AB-type building blocks

RSC Advances ◽  
2014 ◽  
Vol 4 (89) ◽  
pp. 47937-47950 ◽  
Author(s):  
Shanmugam Thiyagarajan ◽  
Jing Wu ◽  
Rutger J. I. Knoop ◽  
Jacco van Haveren ◽  
Martin Lutz ◽  
...  
Keyword(s):  
Methyl Ester ◽  
Building Blocks ◽  
Ester Group ◽  
Hydroxyl Group ◽  
Secondary Hydroxyl ◽  
New Class ◽  
New Family ◽  
Hydroxy Esters

Here we present the synthesis of a new family of sugar derived 1,4:3,6-dianhydrohexitol based AB-type monomers, containing one methyl ester group and a secondary hydroxyl group in all four possible stereo isomers (RR, RS, SR, SS).

scholarly journals Studies on Medicago lupulina saponins. 1. Isolation and identification of sapogenins from M. lupulina tops

2014 ◽  
Vol 53 (4) ◽  
pp. 515-525 ◽  
Author(s):  
Piotr M. Górski ◽  
Marian Jurzysta ◽  
Stanisław Burda ◽  
Wiesław A. Oleszek ◽  
Michał Płoszyński
Keyword(s):  
Mass Spectrometry ◽  
Methyl Ester ◽  
Ester Group ◽  
Infrared Spectrometry ◽  
Isolation And Identification ◽  
Medicago Lupulina ◽  
Chromatography Mass Spectrometry ◽  
Medicagenic Acid ◽  
First Time

Saponins from <em>M. lupulina</em> tops were investigated for the first time. Eight aglycones were found in the acid hydrolysates of saponins. All of the aglycones were isolated. On the basis of chromatography, mass spectrometry and infrared spectrometry the aglycanes were identified as soyasapogenols B, C, D, E, F and medicagenic acid. Two new aglycones were also isolated and identified as pentacyclic triterpens of β-amyrin structure. Both possess a methyl ester group which is rarely present in nature.

ANESTHETIC ACTION OF ETOMIDATE IS ENHANCED BY THE NO-SYNTHASE INHIBITOR NITRO-L-ARGININE-METHYL-ESTER (L-NAME)

1998 ◽  
Vol 89 (Supplement) ◽  
pp. 180A
Author(s):  
T. Krause ◽  
P. H. Tonner ◽  
J. Scholz ◽  
E. Suppe ◽  
J. Schulte Esch
Keyword(s):  
Methyl Ester ◽  
No Synthase ◽  
No Synthase Inhibitor ◽  
Anesthetic Action ◽  
Synthase Inhibitor

Practical Early Development Synthesis of Nav1.7 Inhibitor GDC-0310

Synthesis ◽  
2020 ◽  
Vol 52 (22) ◽  
pp. 3406-3414 ◽  
Author(s):  
Andreas Stumpf ◽  
Frédéric St-Jean ◽  
David Lao ◽  
Zhigang Ken Cheng ◽  
Remy Angelaud ◽  
...  
Keyword(s):  
Methyl Ester ◽  
Early Development ◽  
Enantiomeric Excess ◽  
Coupling Reaction ◽  
Active Pharmaceutical Ingredient ◽  
Ester Group ◽  
Cross Coupling Reaction ◽  
Palladium Catalyzed ◽  
Aromatic Bromination ◽  
Displacement Approach

The concise early development route to the Nav1.7 inhibitor GDC-0310 is described. The active pharmaceutical ingredient (API) contains one stereocenter, which was obtained with high enantiomeric excess (>99:1) by using an SN2 displacement approach to connect two intermediates: a chiral benzyl alcohol and a piperidine. The synthesis of the piperidine building block proceeded via a regioselective SNAr reaction on 1-chloro-2,4-difluorobenzene by N-Boc-4-piperidinemethanol, followed by installation of the methyl ester group by electrophilic aromatic bromination and a palladium-catalyzed alkoxycarbonylation. A subsequent Suzuki–Miyaura cross-coupling reaction was then telescoped directly into cleavage of the Boc group to provide the advanced piperidine intermediate. The key feature of the synthesis is the highly selective SN2 displacement of the chiral mesylate of (R)-1-(3,5-dichlorophenyl)ethan-1-ol with the piperidine intermediate, followed by a chiral purity upgrade via the corresponding (1S)-(+)-camphorsulfonic acid salt. After standard hydrolysis of the methyl ester and CDI mediated amidation to couple the resulting acid with methanesulfonamide, enantiomerically pure GDC-0310 was obtained in high overall yield (37%) on a 6.5 kilogram scale.

scholarly journals PHARMACOKINETIC STUDY OF MATRIX MEMBRANE MODERATED TRANSDERMAL SYSTEM OF BOSENTAN MONOHYDRATE

2017 ◽  
Vol 10 (9) ◽  
pp. 255
Author(s):  
Revathi Mannam ◽  
Indira Muzib Yallamalli
Keyword(s):  
Controlled Release ◽  
High Performance ◽  
Release Kinetics ◽  
Research Work ◽  
Fold Increase ◽  
Oral Route ◽  
Fickian Diffusion ◽  
Pharmacokinetic Studies ◽  
The Matrix

Objective: The objective of the present research work is to carry out the pharmacokinetic studies of optimized matrix membrane moderatedtransdermal patch of bosentan monohydrate.Materials and Methods: The matrix membrane moderated transdermal system was formulated using HPMC, HPMC K4M and E RLPO. In vitrodiffusion studies were carried out using modified Franz diffusion cell and for the optimized transdermal patch, pharmacokinetic studies were carriedout using New Zealand male rabbits. Plasma samples were quantified using high-performance liquid chromatography.Results: The in vitro diffusion studies revealed that formulation F3 with HPMC K4M and E RLPO had controlled release up to 28 hrs, and a maximumof 95.02±2.68% drug was released. The release kinetics followed mixed order non-Fickian diffusion. The pharmacokinetic studies of the optimizedpatch revealed controlled release up to 45 hrs where a 2.2-fold increase in area under curve (AUC) and 3.8 times increase in mean residence time(MRT) were observed compared to oral route. The results were appeared to be significant at p≤0.05. The variation in half-life was found to be notstatistically significant when compared between oral and transdermal routes.Conclusion: The pharmacokinetic results concluded that the matrix membrane moderated transdermal system with extended AUC and MRT canenhance the bioavailability of bosentan monohydrate by minimizing the drug-related side effects in oral route.

Synthesis of carbocycles from ω-substituted α,β-unsaturated esters via radical-induced cyclizations

1987 ◽  
Vol 65 (8) ◽  
pp. 1859-1866 ◽  
Author(s):  
Stephen Hanessian ◽  
Daljit S. Dhanoa ◽  
Pierre L. Beaulieu
Keyword(s):  
Ester Group ◽  
Carbon Chain ◽  
Radical Cyclization ◽  
Unsaturated Esters ◽  
Carbocyclic Compounds ◽  
Bicyclic Structure

The intramolecular radical cyclization of ω-bromo α,β-unsaturated esters for the synthesis of carbocyclic compounds is described. The effect of carbon chain substituents, the bulk of the ester group, and the olefin geometry were examined. The highest level of stereoselectivity (trans/cis: 9/1) was achieved with the Z ester via an exo cyclization. The sequential radical cyclization of a dihalodienoate to give a cis-fused bicyclic structure is also described.

Sign in / Sign up

Export Citation Format

Share Document