Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “AMIDINES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 793 records · Page 44Linked to original sources
PubMed1987

Identification of the metabolites of a new hypoglycaemic agent, midaglizole, in dogs.

1. The metabolism of a new hypoglycaemic agent, midaglizole, was studied. Six major metabolites were isolated from the urine of dogs dosed with 14C-midaglizole. The structures of these metabolites were elucidated by n.m.r., i.r., u.v. and mass spectrometry, and confirmed by comparison with synthesized authentic samples. 2. For midaglizole, oxidation on the imidazoline ring and subsequent ring-opening were the major metabolic pathways in dogs. 3. Two metabolites, namely, the imidazole analogue (M-I) and amidine analogue (M-III), had hypoglycaemic activity.

Animals↗
PubMed1981

The X-ray structural investigation of 6-(n,n-1,6-hexyleneformamidine)-penicillanic acid (mecillinam).

A new type of 6-formamidinepenicillanic acid in which the omega-nitrogen atom is involved in the azaheptane ring (mecillinam) having a strong selective activity against Gram-negative bacteria strains has been investigated by the X-ray single-crystal diffraction methods using crystals in the solvated state. The conformation of penam part as well as of the amidine group is discussed. Two independent molecules of mecillinam found in the asymmetric unit of the crystal cell differ from each other in their detailed conformations. The problem of the stability of the compound has been discussed also.

Amdinocillin↗
PubMed1983

The antibiotic edeine. XII. Isolation and structure of edeine F.

The peptide antibiotic edeine F produced by Bacillus brevis Vm4, one of the components of edeine antibiotics complex, was isolated from a fermentation broth and was also obtained by amidination of edeine D. Edeine F is composed of amino acids: (S)-beta-phenyl-beta-alanine, (S)-isoserine, (S)-2,3-diaminopropionic acid, (2R,6S)-diamino-(7R)-hydroxyazelaic acid, glycine and a polyamine guanidylspermidine. Enzymatic degradation of antibiotic with carboxypeptidase B, dinitrophenylation of edeine and of its enzymatic degradation products and synthesis of edeine F from edeine D of known structure permitted to postulate the chemical structure for edeine F.

Anti-Bacterial Agents↗
PubMed1987

Modification of the cysteamine side chain of thienamycin. III.

Thienamycin derivatives (4) having a cyclic amidine moiety at the C-2 position were prepared. The susceptibility to renal dehydropeptidase-1 and the antimicrobial activity of these compounds were determined. Their structure-activity relationships are also discussed.

Chemical Phenomena↗
PubMed1991

Synthesis and biological activity of 1-N-[4-(substituted)amidino and guanidino-2-hydroxybutyryl]kanamycins A and B.

The synthesis and biological properties of 1-N-[4-(substituted)amidino and guanidino-2-hydroxybutyryl]kanamycins A and B are described. Reaction of 3,3",6'-tri-N-tert-butoxycarbonyl-amikacin with an appropriate amidinating or guanidinating reagent and subsequent deblocking gave a series of amikacin derivatives having an amidino or guanidino group on the 4"'-position. The corresponding kanamycin B analogs were also prepared by a similar procedure. Among these derivatives, 1-N-(4-formamidino- and guanidino-2-hydroxybutyryl)kanamycins A (7a and 7k) and B (11 and 14) exhibited antibacterial activity similar to the corresponding 4-amino analogs. The nephrotoxic potential of selected compounds is also briefly discussed.

Animals↗
PubMed1991

Synthesis and activity of butirosin derivatives with 5''-amidino and 5''-guanidino substituents.

The preparation and antibacterial activity of the 5''-guanidino (6) and 5''-amidino (7) derivatives of 4'-deoxybutirosin A (1) as well as the 5''-guanidino derivative (8) of butirosin A are described. The key intermediates, tetra-N-benzyloxycarbonyl-5''-azido derivatives were selectively reduced with NiCl2-NaBH4 to give the corresponding 5'-amino derivatives. Subsequent guanidination or amidination followed by deblocking afforded the final compounds 6, 7 and 8. The 5''-guanidino derivatives (6 and 8) were more active against Gram-positive and Gram-negative bacteria than the corresponding 5''-hydroxy derivatives (1 and butirosin A). Compound 6 was also active against a variety of methicillin-resistant Staphylococcus aureus (MRSA).

Animals↗
PubMed1993

Synthesis and antibacterial activity of new 2-substituted penems. I.

A new type of penem derivative (3-6) having a cyclic amidine moiety or a quaternary heterocycle moiety at the C-2 position was prepared. The susceptibility to renal dehydropeptidase-1 (DHP-1) and the antimicrobial activity of these compounds were determined. Some of these compounds (5,6) showed a broad spectrum of antibacterial activity, including activity against Pseudomonas aeruginosa.

Anti-Bacterial Agents↗
PubMed2002

Novel stachyflin derivatives from Stachybotrys sp. RF-7260. Fermentation, isolation, structure elucidation and biological activities.

Stachybotrys sp. RF-7260 was found to produce stachyflins, novel anti-influenza virus agents, under solid-state fermentation conditions. Feeding DL-lysine to a culture of Stachybotrys sp. RF-7260 induced the formation of the novel compounds, SQ-02-S-L2 and -L1, and feeding DL-valine the formation of SQ-02-S-VI and -V2. The structures of these metabolites were determined by detailed 2D NMR analyses in comparison with acetylstachyflin. SQ-02-S-L2 and -L1 have the lysine moiety and SQ-02-S-V1 has the valine moiety. SQ-02-S-V2 has an amidine moiety instead of the lactam moiety in acetylstachyflin. SQ-02-S-L2, -L1 and -V1, substituted on the lactam amide hydrogen, displayed only a low level of the antiviral activity. However, deacetyl SQ-02-S-V2 showed potent antiviral activity similar to stachyflin.

Animals↗
PubMed1976

Hapten-sandwich labeling. III. Bifunctional reagents for immunospecific labeling of cell surface antigens.

Bifunctional reagents have been prepared which permit extensive coupling of haptens to antibodies with retention of antibody-binding capacity. This modification procedure increases the sensitivity with which cell-surface antigens can be labeled for fluorescent or electron microscopy by the hapten-sandwich method to a level comparable to or greater than may usually be achieved by conventional indirect techniques. With two different haptens, and amplifying with anti-hapten antibodies bearing fluorescent or other markers, different antigens can be distinguished readily on a single cell or on separate cells. Mouse alloantigens detected only with difficulty by conventional fluorescence can be discerned clearly and with high specificity. The reagent, either methyl hydroxybenzimidate (HB) or methyl 3,5-dihydroxybenzimidate (DHB), is first reacted with a diazonium phenyl hapten. Since the resulting azo-derivative retains the imido ester function, the reaction solution can be used directly to amidinate antibodies. Both HB and DHB are easily prepared and may be stored for use as needed. With these reagents, the hapten-sandwich procedure may be applied to proteins other than immunoglobulins, e.g., hormones and mitogens. In addition to labeling antigens for fluorescent or electron microscopy, haptenamidinated antibodies or other ligands may be used in conjunction with appropriately modified antihapten amplifiers for a variety of purposes in cell biology, such as radioisotope studies, selective cell killing or suppression, and isolation of membrane antigens.

Animals↗
PubMed1999

Relationships between topoisomerase II inhibition, sequence-specificity and DNA binding mode of dicationic diphenylfuran derivatives.

Four diphenylfuran derivatives possessing different dicationic terminal side chains were used to investigate sequence-specific binding to DNA and poisoning of human topoisomerase II. Footprinting experiments with a range of DNA substrates attest that all four drugs bind selectively to AT-rich sequences in DNA. However, the quantitative analysis of the footprinting profiles reveals significant differences in terms of AT-selectivity according to the nature of the basic side chains. Furimidazoline (DB60) shows a reduced capacity to interact selectively with A.T tetrads compared with furamidine (DB75) and the 3-pentyl-substituted diamidine analogue DB226. DB244, for which the two amidine ends are substituted with a cyclopentyl group, exhibits the most pronounced AT specificity. It binds tightly to sites composed of at least four adjacent AT base pairs, such as 5'-TAAT, AATT and TTTT. At low concentrations (< 2 microM) DB60 is also capable of forming stable complexes with AT sites but at higher concentrations the binding becomes totally non-specific due to additional intercalation of drug molecules into GC-rich sequences. Nevertheless, DB60 is the only drug is the series which stabilizes DNA-topoisomerase II covalent complexes. This compound effectively promotes DNA cleavage by topoisomerase II whereas DB75, DB226 and DB244 have practically no effect. The topoisomerase II poisoning activity of DB60 correlates with its ability to intercalate into GC sites in DNA whereas the three other diphenylfurans essentially behave as typical AT-selective minor groove binders. The study suggests that the antimicrobial activity of the diphenylfurans, which are active against the Pneumocystis carinii pathogen (PCP), depends essentially on their capacity to recognize AT-rich DNA sequences rather than their ability to interfere with topoisomerase II. In contrast, the cytotoxicity of drugs like DB60 would be connected with the formation of intercalation complexes and the stimulation of DNA cleavage by human topoisomerase II.

Anti-Bacterial Agents↗
PubMed1999

[Five-ring analogs of nifedipine. 3. Synthesis and reactions of 1,4-dihydropyridines with 4-(4-nitro-5-imidazolyl)-substituents].

In the Hantzsch pyridine synthesis the 4-nitro-5-imidazolylcarbaldehydes 4 react with methyl 3-aminocrotonate or 3-aminocrotononitrile in acetic acid to yield the 1,4-dihydropyridines (DHP) 5 and 6. The corresponding pyridines 7 and 8 are obtained by oxidation with cerium(IV) or chromium(VI), respectively. Reduction of the nitro group in 7 with iron in acetic acid leads to the lactames 9, while from 8a the imidazolylamine 10 is isolated. Compound 8a reacts with dithionite to yield the cyclic amidine 11. Irradiation of the DHP 5 and 6b with UV-A light affords the 4-nitroso-5-imidazolyl-pyridines 12 and 13. The half wave potentials E1/2 of the DHP 5 were determined by anodic oxidation using difference pulse voltammetry (DPV); nifedipine was used as reference substance. The DHP 5 inhibit the growth of Staphylococcus aureus in the platelet diffusion test.

Blood Platelets↗
PubMed2000

Mechanism of an antibody-catalysed allylic isomerization.

The catalytic antibody 4B2, which was generated against a substituted amidine 1, catalyses the allylic isomerization of beta, gamma-unsaturated ketones with an acceleration factor (k(cat)/k(uncat)) of 1.5x10(3). On the basis of the 'bait and switch' strategy, it was reasoned that the positively charged hapten could elicit, by charge complementarity, an acidic residue (Asp or Glu) in the antibody-binding site in the right position to catalyse this proton transfer reaction. The pH dependence curve of k(cat)/K(m) shows a bell-shaped feature with an optimum at approx. pH 4.5. By cloning and sequencing the light and heavy chains of the 4B2 antibody, we confirmed the presence of several Asp and Glu residues in the complementarity-determining region loops. The antibody catalyses the alpha-proton exchange on the same substrates, demonstrating the involvement of a dienol intermediate in the reaction mechanism. Kinetic studies with (2)H-NMR provide evidence that alpha-proton abstraction is stereospecific. Whether the process involves one or two acid/base residues in this simple proton transfer or whether it is a concerted mechanism is discussed.

Amino Acid Sequence↗
PubMed1975

[Purification of an anionic trypsin from the gastric juice of the crayfish Cambarus affinis say by means of affinity chromatography].

Beside other digestion enzymes the crayfish Cambarus affinis SAY possess an anionic trypsin. This enzyme could be separated from all the other proteins of the crude gastric juice by a single affinity chromatographic step on immobilized natural inhibitor. The dissociation of the thus produced enzyme-inhibitor complex was achieved by specific elution with ben-amidine. The soluble benzamidine-trypsin-complex was dialyzed and separated by gelfiltration on Sephadex G-50. Of the ligands used Trasylol proved to be the most effective one. Trypsin isolated by this ligand was in a discelectrophoretic homogeneous state. On the other hand, trypsin purified by Soybean trypsin inhibitor and Contrykal contains impurities.

Animals↗
PubMed2000

Glycosidase inhibitors and their chemotherapeutic value, Part 3.

The various compounds that have been investigated as glycosidase inhibitors are reviewed. The last one of three parts of this review article covers the following classes of compounds: amidines, amidrazones, amidoximes, sugars with sulphur in the ring, carba sugars, pseudo oligosaccharides, cyclitols and trehazolamine analogues, fused heterocycles and trehazolin analogues, dioxane derivatives, open chain compounds, heterocyclic compounds with hydroxyalkyl residues, aromatic compounds, amino acids and other derivatives.

Animals↗
PubMed2000

Inhibitory effects of pentamidine analogues on protein biosynthesis in vitro.

Pentamidine despite its rather high toxicity, is currently in clinical use. For development of new drugs of this type it is important to know the mechanism of their action. Two new amidines (I and II) and 4',6-diamidino-2-phenylindole (DAPI) were found in preliminary experiments to inhibit protein synthesis in vitro in the cell-free rat liver system. The three compounds differed in the precise mode of action. The inhibitory effect of I on the activity of the eukaryotic elongation factor eEF-2 and ribosomes seems to suggest that the binding site of eEF-2 on the ribosome was blocked by this compound. eEF-2 has been identified as the primary target of II and eEF-1 as the primary target of DAPI in the system studied.

Animals↗
PubMedDate not supplied

Determination of insecticides in honey by matrix solid-phase dispersion and gas chromatography with nitrogen-phosphorus detection and mass spectrometric confirmation.

A multiresidue method was developed for the determination of 12 organophosphorus insecticides (diazinon, parathion methyl, fenitrothion, pirimiphosmethyl, malathion, fenthion, chlorpyrifos, quinalphos, methidathion, ethion, azinphosmethyl, coumaphos), one carbamate (pirimicarb), and one amidine (amitraz) in unifloral and multifloral honeys. The analytical procedure was based on the matrix solid-phase dispersion of honey on a mixture of Florisil and anhydrous sodium sulfate in small glass columns and subsequent extraction with a low volume of hexane-ethyl acetate (90 + 10, v/v), assisted by sonication. The insecticide residues were determined by capillary chromatography with nitrogen-phosphorus detection and confirmed by mass spectrometry. Average recoveries at the 0.05-0.5 microg/g levels were >80% for organophosphorus insecticides and about 60% for the other insecticides, pirimicarb and amitraz, with relative standard deviations <10%. The detection limit for the different insecticides ranged between 6 and 15 microg/kg. The main advantages of the proposed method are that extraction and cleanup are performed in a single step with a low volume of organic solvent. The method is simple, rapid, and less laborious than conventional methods. Several Spanish honeys were analyzed with the proposed method and no residues of the studied insecticides were found.

Gas Chromatography-Mass Spectrometry↗
PubMed2003

[Advances in the development of antitubercular agents containing no heterocyclics in the pharmacophore. Part 1. Derivatives of carboxylic acid].

The present paper is the twentieth communication in a series of review papers on the development of antituberculotics and the ninth communication summarizing the work in the development of antituberculotics within recent 15 years. The first seven communications were devoted to heterocyclic compounds, the eighth to substances containing an alkylsulfanyl group in the pharmacophore. The present paper summarizes information about cyrboxylic acids, their amides, anilides, hydrazides, thioamides, thioanilides, thiohydrazides, and amidines. The communication includes papers published after 1980 in order to link up with a review paper devoted to the same topic published in the present series in 1982.

Antitubercular Agents↗
PubMed1992

Metabolic N-hydroxylation of diminazene in vitro.

The two N-hydroxylated derivatives (amide oximes) and the corresponding amides of the trypanocidal diamidine diminazene (Berenil, CAS 536-71-0) have been synthesized. These reference compounds made it possible to investigate the in vitro metabolism of the amidine functionalities of diminazene. Diminazene metabolites were detected for the first time, in the form of the corresponding mono- and di(amide oxime), after incubation with 12000 g supernatants from rabbit liver homogenates and careful workup (freeze drying). The identification was based on the behavior in thin-layer chromatography and on comparison of the mass spectral data for the metabolites with those for synthetic material. The N-hydroxylation of diminazene showed the properties typical of a reaction catalyzed by a microsomal monoxygenase. Diminazene amides did not occur as metabolites. The di(amide oxime) of diminazene was tested for its trypanocidal and leishmanicidal activity on various laboratory strains of trypanosomes in mice and on Leishmania donovani in hamsters. The studies showed that the di(amide oxime) has a trypanocidal effect on various strains of trypanosomes (T. brucei, T. vivax, T. congolense and T. evansi), but this is distinctly weaker than that of diminazene. A diminazene-resistant strain of T. rhodesiense is also unaffected by the di(amide oxime). The di(amide oxime) also has a leishmanicidal effect, but this again is distinctly less than that of diminazene.

Animals↗