Acid Alkylamides Research Articles

4-Hydroxy-2-quinolones 121. Synthesis and biological properties of 1-hydroxy-3-oxo-5,6-dihydro-3h-pyrrolo[3,2,1-ij]quino-line-2-carboxylic acid alkylamides

A simple method is proposed for preparing 1-hydroxy-3-oxo-5,6-dihydro-3H-pyrrolo[3,2,1-ij]-quinoline-2-carboxylic acid alkylamides. For the case of the secondary butylamide features of the steric structure of the synthesized compounds is discussed. The results of a study of their anti-inflammatory and diuretic activities are presented.

Liver Enzyme-Mediated Oxidation of Echinacea purpurea Alkylamides: Production of Novel Metabolites and Changes in Immunomodulatory Activity

The medicinal plant Echinacea is widely used to treat upper respiratory infections and is reported to stimulate the human immune system. A major constituent class of Echinacea, the alkylamides, has immunomodulatory effects. Recent studies show that alkylamides are oxidized by cytochrome P450 enzymes, but the immunomodulatory activity of these products is unknown. The objectives of this study were to characterize the products formed by incubation of an Echinacea extract and an isolated alkylamide with human liver microsomes, and to evaluate the influence of Echinacea alkylamides and metabolites on cytokine production by Jurkat human T cells. A novel class of carboxylic acid alkylamide metabolites was identified and shown to be the major constituents present after 2-h incubation of alkylamides with human liver microsomes. Echinacea alkylamides suppressed IL-2 secretion by stimulated T cells, and this effect was significantly lessened upon oxidation of the alkylamides to carboxylic acids and hydroxylated metabolites. These findings highlight the importance of considering the influence of liver enzyme metabolism when evaluating the immunomodulatory effects of alkylamides.

Effect of multivalency on the performance of enantioselective separation media for chiral HPLC prepared by linking multiple selectors to a porous polymer support via aliphatic dendrons.

Chiral stationary phases (CSPs) containing L-proline indananilide chiral selectors attached through a multivalent dendritic linker to monodisperse macroporous poly(2-hydroxyethyl methacrylate-co-ethylene dimethacrylate) beads have been prepared using two different approaches. The convergent method involves the preparation of ligands in solution and their subsequent attachment to the support. The divergent approach is based on the stepwise "on-bead" formation of the linker using methods that are typical of solid-phase synthesis. While the convergent CSPs feature well-defined ligands, their loading is relatively low. In contrast, the divergent technique affords CSPs with higher loading but with more limited control over precise ligand architecture. Excellent enantioselectivities characterized by separation factors of up to 31 were achieved for the separation of racemic N-(3,5-dinitrobenzoyl)-alpha-amino acid alkyl amides with these new CSPs under normal-phase HPLC conditions.

Preparation of highly selective stationary phases for high-performance liquid chromatographic separation of enantiomers by direct copolymerization of monomers with single or twin chiral ligands

Uniformly sized macroporous polymer beads, which can be used as chiral stationary phase (CSP), have been prepared by the staged templated suspension polymerization process using chiral monomer as one of the copolymerization components. This approach enables the preparation of CSPs for which properties such as pore size, pore volume, surface area, chemistry, and chiral ligands can be tuned over a broad range. Several types of well-defined chiral monomers were prepared and allowed to assess synergistic effect of multiple selectors attached to a branched linker as well as the effect of the length and chemistry of the linker. Microscale batch screening was used for simple and rapid evaluation of selectivity. The most promising candidate CSPs were prepared on a larger scale and packed into HPLC columns. Their performance was demonstrated on the separation of racemic N-(3,5-dinitrobenzoyl)-α-amino acid alkylamides. The highest separation factors α of up to 27 were observed for CSPs prepared from monomers containing the branched spacer. These highly selective CSPs also enabled the separation of larger amounts of the target racemates upon column overload conditions.

Azacycloalkanes. XXXIII. Synthesis and Antialcohol Activity of α-Alkylamino-γ-hydroxybutyric Acid Alkylamides

Azacycloalkanes. XXXIII. Synthesis and Antialcohol Activity of α-Alkylamino-γ-hydroxybutyric Acid Alkylamides

ChemInform Abstract: Synthesis, in vitro anti-Breast Cancer Activity, and Intracellular Decomposition of Amino Acid Methyl Ester and Alkyl Amide Phosphoramidate Monoesters of 3′-Azido-3′-deoxythymidine (AZT).

We report the synthesis and anticancer activity of a series of AZT phosphoramidate monoesters containing amino acid methyl ester (3a−11a) and N-alkyl amide (3b−11b, 9c−9f) moieties. The aromatic amino acid methyl esters were found to be more cytotoxic than the aliphatic analogues toward MCF-7 cells (human pleural effusion breast adenocarcinoma cell line). A marked stereochemical preference for the l-amino acid stereochemistry was also observed in MCF-7 cells. There was no consistent enhancement of cytotoxicity of the methyl amides over the corresponding methyl esters. AZT and the two AZT aromatic amino acid methyl ester phosphoramidates 8a and 9a were found to be more cytotoxic toward MCF-7 cells than to CEM cells (human T-cell lymphoblastic leukemia). The selective cytotoxicity toward MCF-7 cells may be associated with greater intracellular levels of phosphoramidate monoester and/or phosphorylated AZT.

Synthesis, in vitro anti-breast cancer activity, and intracellular decomposition of amino acid methyl ester and alkyl amide phosphoramidate monoesters of 3'-azido-3'-deoxythymidine (AZT).

We report the synthesis and anticancer activity of a series of AZT phosphoramidate monoesters containing amino acid methyl ester (3a-11a) and N-alkyl amide (3b-11b, 9c-9f) moieties. The aromatic amino acid methyl esters were found to be more cytotoxic than the aliphatic analogues toward MCF-7 cells (human pleural effusion breast adenocarcinoma cell line). A marked stereochemical preference for the L-amino acid stereochemistry was also observed in MCF-7 cells. There was no consistent enhancement of cytotoxicity of the methyl amides over the corresponding methyl esters. AZT and the two AZT aromatic amino acid methyl ester phosphoramidates 8a and 9a were found to be more cytotoxic toward MCF-7 cells than to CEM cells (human T-cell lymphoblastic leukemia). The selective cytotoxicity toward MCF-7 cells may be associated with greater intracellular levels of phosphoramidate monoester and/or phosphorylated AZT.

On-bead combinatorial approach to the design of chiral stationary phases for HPLC.

A library of 36 L-amino acid anilides, which are potential selectors for chiral HPLC, was synthesized in solution and attached to functionalized macroporous polymer beads. The best selector from the library was identified by a deconvolution process using the HPLC separation of several racemic N-(3,5-dinitrobenzoyl)-alpha-amino acid alkylamides as a probe. In each deconvolution step, a series of chiral stationary phases (CSPs) containing a subset of the amino acid anilide selector library was screened for enantioselectivity. After the best CSP was chosen, the library was further deconvoluted until the single best selector was found. The highest selectivity was obtained with a L-proline-1-indananilide that exhibited alpha values up to 23 under normal-phase HPLC conditions. In addition, six CSPs were prepared using individual selectors from the library, and screening results indicate that the deconvolution process indeed led to the most selective receptor.

Synthesis and antiinflammatory activity of 2-arylamino-6,7-dihydro-5H-pyrindine-3-carboxylic acid alkylamides

Synthesis and antiinflammatory activity of 2-arylamino-6,7-dihydro-5H-pyrindine-3-carboxylic acid alkylamides

Synthesis and antispasmodic activity of 2-chloro- and 2-arylamino-4,6-dimethylnicotinic acid alkylamides

Synthesis and antispasmodic activity of 2-chloro- and 2-arylamino-4,6-dimethylnicotinic acid alkylamides

Synthetic inhibitors of human leukocyte elastase, Part 3. Peptides with alkyl groups at the N- or C-terminus. Non-toxic competitive inhibitors of human leukocyte elastase.

A series of carboxy-alkylamidated and N-acetylated amino acids and peptides were synthesized and examined for their ability to inhibit human leukocyte elastase. The Boc-amino acid alkylamides were found to be potent specific and competitive inhibitors of this enzyme. They were found not to or only poorly inhibit several other serine proteinases such as bovine trypsin, alpha-chymotrypsin, porcine pancreatic elastase and human leukocyte cathepsin G at concentrations less than 10(-4) M. Specificity and maximum inhibition of human leukocyte elastase were achieved when the N-terminus of the amino acid was protected by a t-butyloxy-carbonyl (Boc) group, the oligopeptide fragment consisted of valine residues and when the alkyl chain was between 10 and 12 carbon atoms in length and attached to the C-terminus of the peptide fragment. Highest inhibition was obtained with the compound Boc-[Val]3-NH[CH2]11--CH3 (Ki = 0.21 microM). These specific inhibitors were also found to be non-toxic after oral administration to mice and rats (LD50 greater than 3.0 g/kg body weight).

Peptide synthesis catalyzed by papain at alkaline pH values.

The synthesis of peptides in the presence of papain at pH 8-9.5 is described. Starting substances are acylamino acid alkyl esters (the carboxyl component) and amides or tert.-butylesters of amino acids, as well as peptide (the amino component). Under such conditions secondary hydrolysis is not essential, making the synthesis of peptides soluble in aqueous medium. The yield of peptides is 50-94%. The effect of different factors (temperature, solvents, reagent concentrations) on the result of the reaction has been studied. It has been found that an excess of the carboxyl component is expedient to increase the yield of peptides.

Research on naphthyridines. 10. Synthesis and ionization constants of 10-alkylaminobenzo[b]-1,8-naphthyridines

10-Alkylaminobenzo[b]-1,8-naphthyridines were synthesized by cyclization of 2-arylaminonicotinic acid alkylamides by means of phosphorus oxychloride. The pKal values of the 10-alkylaminobenzo[b]-1,8-naphthyridines, which range from 8.74 to 8.50, were determined by potentiometric titration in anhydrous ethanol.

Eien papierchromatographische trennung von fluor-thiono-diphosphorsäurealkylamiden

A procedure for the separation of fluoro-thiono-diphosphoric acid alkylamides by means of paper chromatography is reported. Chromatography is carried out on paper impregnated with petroleum and 50% acetic acid serves as solvent. The R F values depend only on the PS/PO ratio in the molecule.

局所麻醉剤の研究 (第4報)

In order to find out the influence of the S-alkyl group on the effect, 7 kinds of N, N′-disubstituted benzamidines, 4 kinds of N, N-disubstituted benzamidines, and 14 kinds of naphthoamidines, all possessing a thioalkyl group, were synthesized. Preparation of N, N′-disubstituted compounds was carried out by the halogenation and amination of the corresponding thioalkylbenzoic acid alkylamides, and the N, N-compounds by the Grignard reaction of the corresponding benzonitriles. The hydrochlorides of the former were of low hydrophilic properties when the alkyl in N and N′ were of aromatic nucleus and were assumed to be unsuitable as local anesthetics. On the other hand, the physical properties of the N, N-disubstituents were found to be more suitable for such application. Their pharmacological actions are shown in Report V.