benzofurans and coumaran

Covering: 2000 to 2018 Natural products containing the 2,3-dihydrobenzofuran (2,3-DHB) skeleton have been the focus of a substantial number of synthetic studies since 2000. Herein, we review the total syntheses of decursivine, serotobenine, lithospermic acid, linderol A, bisabosqual A, pterocarpans, conocarpan, heliannuols, and some resveratrol oligomers, with emphasis on the synthetic strategies employed.

Topics: Benzofurans; Biological Products; Depsides; Heterocyclic Compounds, 4 or More Rings; Indole Alkaloids; Indoles; Molecular Structure

Topics: Benzofurans; Catalysis; Indolequinones

Herein, a series of 2,3-dihydrobenzofurans have been developed as highly potent bromo and extra-terminal domain (BET) inhibitors with 1000-fold selectivity for the second bromodomain (BD2) over the first bromodomain (BD1). Investment in the development of two orthogonal synthetic routes delivered inhibitors that were potent and selective but had raised

Topics: Benzofurans; Dose-Response Relationship, Drug; Humans; Molecular Structure; Proteins; Solubility; Structure-Activity Relationship

Development of a visible light-induced and singlet oxygen-mediated green protocol has been accomplished for the first time for the photochemical transformation of 4-hydroxy-α-benzopyrones to a new series of biorelevant 2-hydroxy-3-oxo-2,3-dihydrobenzofuran-2-carboxamides and 2-hydroxy-3-oxo-2,3-dihydrobenzofuran-2-carboxylates using rose bengal as a triplet photosensitizer at ambient temperature. Metal-free one-pot synthesis, broader substrate scope, good-to-excellent yields, use of cost-effective and eco-friendly starting materials and photosensitizer, and energy efficiency are the salient features of this newly developed method.

Topics: Benzofurans; Light; Photosensitizing Agents; Rose Bengal; Singlet Oxygen

2,3-Dihydrobenzofurans are key pharmacophores in many natural and synthetic bioactive molecules. A biocatalytic strategy is reported here for the highly diastereo- and enantioselective construction of stereochemically rich 2,3-dihydrobenzofurans in high enantiopurity (>99.9% de and ee), high yields, and on a preparative scale via benzofuran cyclopropanation with engineered myoglobins. Computational and structure-reactivity studies provide insights into the mechanism of this reaction, enabling the elaboration of a stereochemical model that can rationalize the high stereoselectivity of the biocatalyst. This information was leveraged to implement a highly stereoselective route to a drug molecule and a tricyclic scaffold featuring five stereogenic centers via a single-enzyme transformation. This work expands the biocatalytic toolbox for asymmetric C-C bond transformations and should prove useful for further development of metalloprotein catalysts for abiotic carbene transfer reactions.

Topics: Benzofurans; Biocatalysis; Models, Molecular; Molecular Structure; Myoglobin; Protein Conformation; Thermodynamics

A route to access 3-amino-2,3-dihydrobenzofurans that utilizes microwave-assisted organic synthesis to rapidly generate analogues has been developed. The route begins with an acid-catalyzed, microwave-assisted aldol condensation to generate chalcone intermediates, followed by a Corey-Bakshi-Shibata reduction and subsequent Sharpless asymmetric epoxidation to access stereoisomeric epoxyalcohols. The final step is a one-pot, microwave-assisted, regioselective, acid-catalyzed epoxide opening with various amines followed by an intramolecular nucleophilic aromatic substitution reaction to generate the 3-amino-2,3-dihydrobenzofurans. This route provides ready access to stereochemically and structurally diverse analogues of these flavonoid scaffolds. Additionally, a pilot library was synthesized, and the biological activity diversity of the chalcones and dihydrobenzofurans was explored in human carcinoma cell lines.

Topics: Benzofurans; Catalysis; Chalcones; Flavonoids; Humans; Microwaves; Molecular Structure

Stilbenoids, in particular, resveratrol and its dimers are abundantly present in Vitis vinifera and proved to be quenchers with selective singlet oxygen. However, only a few mechanisms are reported for their complex molecular architectures. Hence, UHPLC combined with accurate MS is employed to investigate the photo-radiation mechanism of resveratrol dimers systematically. Ⅰ: Resorcinol ring exists in Scirpusin A 1, Trans-ε-viniferin 2 and Trans-σ-viniferin 3. The photochemical products were 14Da or 16Da higher than reagents and underwent an endoperoxide intermediate to quinones; Ⅱ: [2+2] cyclization of intra-molecular trans-double bond. The products were 18Da greater than substrates thereby cycloaddited to oxygen heterocyclic; Ⅲ : [4+1], [4+2] cyclization of oxetane formed products were 28Da and 44Da higher than 3, 2 and 1. Ⅳ : 5-phenol-2,3-dihydrobenzofuran ring exists in 2 been oxidized, causing the products at 16Da, 32Da higher than 2. This is the first to reveal the generally regular mechanism of stilbenoids quenching singlet oxygen.

Topics: Benzofurans; Isomerism; Resveratrol; Singlet Oxygen; Stilbenes

Benzofuran and 2,3-dihydrobenzofuran scaffolds are core components in a large number of biologically active natural and synthetic compounds including approved drugs. Herein, we report efficient synthetic protocols for preparation of libraries based on 3-carboxy 2-aryl benzofuran and 3-carboxy 2-aryl trans-2,3-dihydrobenzofuran scaffolds using commercially available salicylaldehydes, aryl boronic acids or halides and primary or secondary amines. The building blocks were selected to achieve variation in physicochemical properties and statistical molecular design and subsequent synthesis resulted in 54 lead-like compounds with molecular weights of 299-421 and calculated octanol/water partition coefficients of 1.9-4.7.

Topics: Aldehydes; Amination; Benzofurans; Boronic Acids; Combinatorial Chemistry Techniques; Small Molecule Libraries; Stereoisomerism

The diastereo- and enantioselective synthesis of 2,3-disubstituted trans-2,3-dihydrobenzofuran derivatives (15 examples, up to 96 : 4 dr, 95 : 5 er) via intramolecular Michael addition has been developed using keto-enone substrates and a bifunctional tertiary amine-thiourea catalyst. This methodology was extended to include non-activated ketone pro-nucleophiles for the synthesis of 2,3-disubstituted indane and 3,4-disubstituted tetrahydrofuran derivatives.

Topics: Amines; Benzofurans; Catalysis; Chemistry Techniques, Synthetic; Furans; Ketones; Molecular Structure; Solvents; Stereoisomerism; Temperature; Thiourea

O-Heterocyclic structures such as 2,3-dihydrobenzofurans are key motifs in many natural compounds and pharmaceuticals. Enantioselective formation of chiral dihydrobenzofurans and analogues was achieved through a copper-catalyzed desymmetrization strategy with a chiral cyclic 1,2-diamine. A broad range of substrates are compatible with this Cu(I)-diamine catalytic system and afford the desired coupling products with chiral tertiary or quaternary carbon centers in high yields and good to excellent enantioselectivities under mild conditions.

Topics: Benzofurans; Catalysis; Chromans; Copper; Stereoisomerism

As part of our ongoing effort to expand the scope of cross-coupling reactions of alkyl electrophiles, we have pursued a strategy wherein the nucleophilic coupling partner includes a pendant olefin; after transmetalation by such a substrate, if β-migratory insertion proceeds faster than direct cross-coupling, an additional carbon-carbon bond and stereocenter can be formed. With the aid of a nickel/diamine catalyst (both components are commercially available), we have established the viability of this approach for the catalytic asymmetric synthesis of 2,3-dihydrobenzofurans and indanes. Furthermore, we have applied this new method to the construction of the dihydrobenzofuran core of fasiglifam, as well as to a cross-coupling with a racemic alkyl electrophile; in the latter process, the chiral catalyst controls two stereocenters, one that is newly generated in a β-migratory insertion and one that begins as a mixture of enantiomers.

Topics: Alkenes; Benzofurans; Catalysis; Cyclization; Indans; Nickel; Stereoisomerism

Novel substituted 2,3-dihydrobenzofuran-7-carboxamide (DHBF-7-carboxamide) and 2,3-dihydrobenzofuran-3(2H)-one-7-carboxamide (DHBF-3-one-7-carboxamide) derivatives were synthesized and evaluated as inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1). A structure-based design strategy resulted in lead compound 3 (DHBF-7-carboxamide; IC50 = 9.45 μM). To facilitate synthetically feasible derivatives, an alternative core was designed, DHBF-3-one-7-carboxamide (36, IC50 = 16.2 μM). The electrophilic 2-position of this scaffold was accessible for extended modifications. Substituted benzylidene derivatives at the 2-position were found to be the most potent, with 3',4'-dihydroxybenzylidene 58 (IC50 = 0.531 μM) showing a 30-fold improvement in potency. Various heterocycles attached at the 4'-hydroxyl/4'-amino of the benzylidene moiety resulted in significant improvement in inhibition of PARP-1 activity (e.g., compounds 66-68, 70, 72, and 73; IC50 values from 0.718 to 0.079 μM). Compound 66 showed selective cytotoxicity in BRCA2-deficient DT40 cells. Crystal structures of three inhibitors (compounds (-)-13c, 59, and 65) bound to a multidomain PARP-1 structure were obtained, providing insights into further development of these inhibitors.

Topics: Amides; Animals; Benzofurans; Cell Line; Chickens; Drug Discovery; Enzyme Inhibitors; Poly(ADP-ribose) Polymerase Inhibitors; Structure-Activity Relationship

Recent studies proved that the biofumigants could be an alternative to chemical fumigants against stored grain insect pests. For this reason, it is necessary to understand the mode of action of biofumigants. In the present study the prospectus of utilising Lantana camara as a potent fumigant insecticide is being discussed. Inhibition of acetylcholinesterase (AChE) by Coumaran, an active ingredient extracted from the plant L. camara, was studied. The biofumigant was used as an enzyme inhibitor and acetylthiocholine iodide as a substrate along with Ellman's reagent to carry out the reactions. The in vivo inhibition was observed in both dose dependent and time dependent in case of housefly, and the nervous tissue (ganglion) and the whole insect homogenate of stored grain insect exposed to Coumaran. The possible mode of action of Coumaran as an acetylcholinesterase inhibitor is discussed.

Topics: Acetylcholinesterase; Animals; Benzofurans; Edible Grain; Insecta; Insecticides; Lantana; Pesticides; Plant Extracts; Plant Leaves

Cesium-exchanged Cs(x)H(3.0-x)PW12O40 (X = 2.0, 2.3, 2.5, 2.8, and 3.0) heteropolyacid nanocatalysts were prepared, and they were applied to the catalytic decomposition of lignin model compound to aromatics. Successful formation of cesium-exchanged Cs(x)H(3.0-x)PW12O40 (X = 2.0-3.0) catalysts was confirmed by FT-IR, ICP-AES, and XRD measurements. 2,3-Dihydrobenzofuran was employed as a lignin model compound for representing β-5 bond in lignin. Phenol, ethylbenzene, and 2-ethylphenol were mainly produced by the catalytic decomposition of 2,3-dihydrobenzofuran. Conversion of 2,3-dihydrobenzofuran and total yield for main products (phenol, ethylbenzene, and 2-ethylphenol) were closely related to the surface acidity of Cs(x)H(3.0-x)PW12O40 (X = 2.0-3.0) catalysts. Conversion of 2,3-dihydrobenzofuran and total yield for main products increased with increasing surface acidity of the catalysts. Among the catalysts tested, Cs2.5H0.5PW12O40 with the largest surface acidity showed the highest conversion of 2,3-dihydrobenzofuran and the highest total yield for main products. These results indicate that surface acidity of Cs(x)H(3.0-x)PW12O40 (X = 2.0-3.0) catalysts served as an important factor determining the catalytic performance in the decomposition of 2,3-dihydrobenzofuran to aromatics.

Topics: Acids; Benzene Derivatives; Benzofurans; Cesium; Lignin; Nanostructures; Surface Properties

The enantioselective synthesis of 2,3-dihydrobenzofurans was achieved by using two sequential C-H functionalization reactions, a rhodium-catalyzed enantioselective intermolecular C-H insertion followed by a palladium-catalyzed C-H activation/C-O cyclization. Further diversification of the 2,3-dihydrobenzofuran structures was possible by a subsequent palladium-catalyzed intermolecular Heck-type sp(2) C-H functionalization.

Topics: Benzofurans; Molecular Structure; Stereoisomerism

A simple, general route to the 1,2-dihydronaphtho[2,1-b]furans and 2,3-dihydrobenzofurans substituted at C-2 by an acyl or aryl group, starting from phenolic Mannich bases and pyridinium ylides, has been developed. The mechanism of the reaction is believed to involve the formation of the o-quinone methide intermediate, Michael-type addition of the ylide to the o-quinone methide, followed by intramolecular nucleophilic substitution.

Topics: Benzofurans; Furans; Molecular Structure; Naphthalenes; Pyridinium Compounds; Quinones; Stereoisomerism

Fine-tuning: Three types of optically active trans-2,3-disubstituted-2,3-dihydrobenzofurans having three contiguous stereogenic centers can be efficiently accessed by one-pot reaction cascades (see scheme; TMS = trimethylsilyl). High substitution diversity of the final products can be achieved from the same common precursors by fine-tuning of their reactivity through simple structural modifications.

Topics: Benzofurans; Catalysis; Molecular Structure; Stereoisomerism

A new bifunctional phosphine catalyst, (2'-hydroxy-biphenyl-2-yl)-diethylphosphane (LBBA-1), was developed for the highly stereoselective synthesis of cis-2,3-dihydrobenzofurans via an aza-Morita-Baylis-Hillman/umpolung addition domino reaction of salicyl N-thiophosphinyl imines with electron-deficient allenes. Dual activation of both nucleophile and electrophile by the bifunctional catalyst accounts for the observed high reactivity and stereoselectivity.

Topics: Alkadienes; Benzofurans; Biphenyl Compounds; Catalysis; Crystallography, X-Ray; Imines; Models, Molecular; Molecular Structure; Phosphines; Stereoisomerism

We recently discovered and reported a series of N-alkyl-isatin acylhydrazone derivatives that are potent cannabinoid receptor 2 (CB(2)) agonists. In an effort to improve the druglike properties of these compounds and to better understand and improve the treatment of neuropathic pain, we designed and synthesized a new series of 2,3-dihydro-1-benzofuran derivatives bearing an asymmetric carbon atom that behave as potent selective CB(2) agonists. We used a multidisciplinary medicinal chemistry approach with binding mode prediction through ligand-steered modeling. Enantiomer separation and configuration assignment were carried out for the racemic mixture for the most selective compound, MDA7 (compound 18). It appeared that the S enantiomer, compound MDA104 (compound 33), was the active enantiomer. Compounds MDA42 (compound 19) and MDA39 (compound 30) were the most potent at CB(2). MDA42 was tested in a model of neuropathic pain and exhibited activity in the same range as that of MDA7. Preliminary ADMET studies for MDA7 were performed and did not reveal any problems.

Topics: Analgesics, Non-Narcotic; Animals; Benzofurans; CHO Cells; Cricetinae; Cricetulus; Drug Design; Humans; Hyperalgesia; Ligands; Male; Models, Molecular; Molecular Structure; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB2; Structure-Activity Relationship

Microbial hydroxylation of o-bromophenylacetic acid provided 2-bromo-5-hydroxyphenylacetic acid. This enabled a route to the key intermediate 4-bromo-2,3-dihydrobenzofuran for synthesizing a melatonin receptor agonist and sodium hydrogen exchange compounds. Pd-mediated coupling reactions of 4-bromo-2,3-dihydrobenzofuran provided easy access to the 4-substituted-2,3-dihydrobenzofurans.

Topics: Aspergillus; Benzofurans; Biotransformation; Hydroxylation; Molecular Structure; Phenylacetates

(-)-Conocarpan (1) was synthesized by a method based on radical cyclization, and the absolute configuration was established by chemical degradation; the original 2R,3R-assignment to (+)-conocarpan should be reversed, as suggested by a later chiroptical study of model 2,3-dihydrobenzofurans.

Topics: Benzofurans; Cyclization; Furans; Molecular Conformation; Stereoisomerism

2,3-Dihydrobenzofurans can be diastereoselectively prepared by condensation of aromatic aldehydes with 2,3-dihydrobenzoxasilepines under the catalysis of Ag(I) complexes, and in the presence of a source of fluoride ion. The application of this strategy by using chiral catalysts leads to a new enantioselective total synthesis of natural cis-pterocarpans and their trans isomers. Through this method, the first enantioselective total synthesis of the antifungal agent (-)-pterocarpin was achieved. In addition, a new entry into the heteroaromatic system of 2,5-dihydrobenzoxepine is also presented.

Topics: Benzofurans; Catalysis; Models, Chemical; Pterocarpans; Silver; Stereoisomerism

Compounds (2R*,3S*)-1-(3,4-dimethoxyphenyl)-3-{3-methoxy-2-[(2R*)-tetrahydropyran-2-yloxy]phenyl}-2,3-epoxy-1-propanone, C23H26O7, (I), and trans-1-(3,4-dimethoxyphenyl)-3-[3-methoxy-2-(methoxymethoxy)phenyl]-2,3-epoxy-1-propanone, C20H22O7, (II), were obtained on epoxidation of chalcones. The stereochemistries of (I) and (II) were elucidated. In both compounds, the substituents on the oxirane ring are trans-oriented. Compound (I) was obtained together with a diastereometric form that differs from (I) with respect to the configuration of the asymmetric C atom in the tetrahydropyran group. The geometries of the substituted oxirane rings of (I) and (II) are very similar. The hydrogen-bonding patterns, mediated via weak C-H...O interactions, differ considerably. The crystal structures of (I) and (II) are compared with those of related chalcone epoxides. The conversion of (I) and (II) into lignin-related phenylcoumarans is discussed.

Topics: Benzofurans; Chalcones; Crystallography, X-Ray; Hydrogen Bonding; Lignin; Models, Molecular; Molecular Structure

Two novel chemical classes of kappa opioid receptor agonists, chroman-2-carboxamide derivatives and 2,3-dihydrobenzofuran-2-carboxamide derivatives, were synthesized. These agents exhibited high and selective affinity for the kappa opioid receptor.

Topics: Amides; Analgesics, Opioid; Animals; Benzofurans; Chromans; Humans; Receptors, Opioid, kappa

The correlation between the helicity (absolute conformation) of the O-heterocyclic ring of chiral 2,3-dihydrobenzo[b]furan (1) and chromane (2) derivatives and their (1)L(b) band CD was investigated. The same helicity rule was found for both unsubstituted chromophores: P/M helicity of the heterocyclic ring leads to a negative/positive CD within the (1)L(b) band. While the substitution of the fused benzene ring by achiral substituents does not change this helicity rule for the chromane chromophore, it leads to its inversion for the 2,3-dihydrobenzo[b]furan chromophores. On the basis of these observations, the published absolute configurations of natural flavonol and pterocarpan derivatives were confirmed and the configurational assignments of several natural neolignans revised.

Topics: Benzofurans; Chromans; Circular Dichroism; Molecular Conformation; Stereoisomerism; Thermodynamics

A novel synthesis of 2,3-dihydrobenzo[b]thiophene-5-ol based on intramolecular homolytic substitution on sulfur was reported. The "antioxidant profile" of the series of 2,3-dihydrobenzo[b]furan-5-ol (2a) its 1-thio (2b), 1-seleno (2c) and 1-telluro (2d) analogues was determined by studies of redox properties, the capacity to inhibit stimulated lipid peroxidation, the reactivity toward tert-butoxyl radicals, the ability to catalyze decomposition of hydrogen peroxide in the presence of glutathione, and the inhibiting effect on stimulated peroxidation in liver microsomes. The one-electron reduction potentials of the aroxyl radicals corresponding to compounds 2a-2d, E degrees (ArO(*)/ArO(-)) were 0.49, 0.49, 0.49, and 0.52 V vs NHE, respectively, as determined by pulse radiolysis. With increasing chalcogen substitution the compounds become slightly more acidic (pK(a) = 10.6, 10.0, 9.9, and 9.5, respectively, for compounds 2a-2d). By using Hess' law, the homolytic O-H bond dissociation enthalpies of compounds 2a-2d (340, 337, 336, and 337 kJ mol(-)(1), respectively) were calculated. The reduction potentials for the proton coupled oxidation of compounds 2a-2d (ArOH --> ArO(*) + H(+)) as determined by cyclic voltammetry in acetonitrile were 1.35 (irreversible), 1.35 (quasireversible) 1.13 (reversible), and 0.74 (reversible) V vs NHE, respectively. As judged by the inhibited rates of peroxidation, R(inh), in a water/chlorobenzene two-phase lipid peroxidation system containing N-acetylcysteine as a thiol-reducing agent in the aqueous phase, the antioxidant capacity increases (2d > 2c = 2b > 2a) as one traverses the group of chalcogens. Whereas the times of inhibition, T(inh), were slightly reduced for the oxygen (2a) and sulfur (2b) derivatives in the absence of the thiol-reducing agent, they were drastically reduced for the selenium (2c) and tellurium (2d) derivatives. This seems to indicate that the organochalcogen compounds are continuously regenerated at the lipid aqueous interphase and that regeneration is much more efficient for the selenium and tellurium compounds. The absolute rate constants for the oxidation of compounds 2a-2b by the tert-butoxyl radical in acetonitrile/di-tert-butyl peroxide (10/1) were the same-2 x 10(8) M(-)(1) s(-)(1). Whereas the oxygen, sulfur, and selenium derivatives 2a-2c were essentially void of any glutathione peroxidase-like activity, the organotellurium compound 2d accelerated the initial reduction of hydrogen peroxide, tert-

Topics: Animals; Antioxidants; Benzofurans; Free Radicals; Hydrogen Peroxide; Lipid Peroxidation; Male; Microsomes; Oxidation-Reduction; Rats; Rats, Sprague-Dawley

A series of 2,3-dihydro-5-benzofuranamines (5-aminocoumarans) were developed for the treatment of traumatic and ischemic central nervous system (CNS) injury. Compounds within this class were extremely effective inhibitors of lipid peroxidation in vitro and antagonized excitatory behavior coupled with peroxidative injury induced by spinal intrathecal injection of FeCl2 (mouse-FeCl2-it assay) in vivo. Selected compounds were tested for antagonistic activity on methamphetamine (MAP)-induced hypermotility resulting from dopamine release in the mouse brain. Among the compounds synthesized, compound 26n (2,3-dihydro-2,4,6,7-tetramethyl-2-[(4-phenyl-1-piperidinyl) methyl]-5-benzofuranamine) exhibited potent effects in these assays (inhibition of lipid peroxidation, IC50 = 0.07 microM; mouse-FeCl2-it assay, ID50 = 10.4 mg/ kg, po; MAP-induced hypermotility, 98% inhibition, 10 mg/kg, ip). The S-(+)-form of compound 26n dihydrochloride (TAK-218), which has 30 times more potent antagonistic activity on MAP-induced hypermotility than the R-(-)-form, improved more significantly the survival rate in the cerebral ischemia model (rat, 1-3 mg/kg, ip) during the period of 1-14 days after ischemia and decreased functional disorders in the traumatic brain injury model (rat, 0.1-1 mg/kg, ip) 3-14 days after injury. These results imply a role for dopamine in deterioration of CNS function after ischemic and traumatic injury. TAK-218 is a promising compound for the treatment of stroke and CNS trauma and is now under clinical investigation.

Topics: Animals; Benzofurans; Brain Ischemia; Central Nervous System; Dopamine; Ferrous Compounds; Isomerism; Lipid Peroxides; Male; Mice; Microsomes, Liver; Rats; Rats, Wistar

The stereospecific oxidation of indan and indene was examined with mutant and recombinant strains expressing naphthalene dioxygenase of Pseudomonas sp. strain 9816-4. Pseudomonas sp. strain 9816/11 and Escherichia coli JM109(DE3)[pDTG141] oxidized indan to (+)-(1S)-indanol, (+)-cis-(1R,2S)-indandiol, (+)-(1S)-indenol, and 1-indanone. The same strains oxidized indene to (+)-cis-(1R,2S)-indandiol and (+)-(1S)-indenol. Purified naphthalene dioxygenase oxidized indan to the same four products formed by strains 9816/11 and JM109(DE3)[pDTG141]. In addition, indene was identified as an intermediate in indan oxidation. The major products formed from indene by purified naphthalene dioxygenase were (+)-(1S)-indenol and (+)-(1R,2S)-indandiol. The results show that naphthalene dioxygenase catalyzes the enantiospecific monooxygenation of indan to (+)-(1S)-indanol and the desaturation of indan to indene, which then serves as a substrate for the formation of (+)-(1R,2S)-indandiol and (+)-(1S)-indenol. The relationship of the desaturase, monooxygenase, and dioxygenase activities of naphthalene dioxygenase is discussed with reference to reactions catalyzed by toluene dioxygenase, plant desaturases, cytochrome P-450, methane monooxygenase, and other bacterial monooxygenases.

Topics: Benzofurans; Biodegradation, Environmental; Dioxygenases; Electron Transport; Hydroxylation; Indans; Indenes; Indoles; Multienzyme Complexes; Oxygenases; Pseudomonas; Recombinant Proteins; Stereoisomerism; Substrate Specificity

The effects of dietary administration of equimolar doses (5 mmol/kg body wt per day) of trimethylene oxide, trimethylene sulfide, coumaran, benzofuran, indole, and indole-3-carbinol on the activities of microsomal epoxide hydrolase and several other xenobiotic metabolizing enzymes were measured in the liver of female CD-1 mouse. Every compound, with the exception of indole, caused a significant increase (P less than 0.01) of the styrene oxide epoxide hydrolase activity over controls in hepatic microsomes. These results indicate that the enzyme activity is elevated in vivo by several heterocyclic compounds with strained bond angles to a nucleophilic hetero-atom. In addition, the ability of sulfur-containing trimethylene sulfide and nitrogen-containing indole-3-carbinol to elevate the enzyme activity indicates that the heterocyclic oxygen atom is not an absolute requirement for this effect. Data from the other xenobiotic metabolizing enzymes indicate that trimethylene oxide and trimethylene sulfide enhance the epoxide hydrolase activity rather specifically, while not affecting the activities of the other enzymes measured. While the oxygen-containing coumaran and benzofuran both increased the NADH: quinone reductase activity in hepatic cytosol, the nitrogen-containing indole and indole-3-carbinol did not. This indicated a specific requirement for the oxygen atom in elevating the quinone reductase activity, which was not the case for the elevation of microsomal epoxide hydrolase activity.

Topics: Animals; Benzofurans; Butylated Hydroxyanisole; Butylated Hydroxytoluene; Epoxide Hydrolases; Ethers, Cyclic; Female; Glutathione Transferase; Heterocyclic Compounds; Indoles; Mice; Mice, Inbred Strains; Microsomes, Liver; Quinone Reductases; Structure-Activity Relationship

Topics: Animals; Benzofurans; Mice; Schistosomiasis; Schistosomicides

Ethyldimethyl(7-methylcoumaran-3-yl)ammonium iodide (SK&F 90,109) and its guanidine analogue [N-(7-methylcoumaran-3-yl)guanidine nitrate] (SK&F 90,238) abolish the effects of adrenergic nerve stimulation in cats, as do xylocholine and bretylium. SK&F 90,109 has slight sympathomimetic actions; these are less marked than in SK&F 90,238. Large doses of SK&F 90,109 have an action, dependent on local noradrenaline stores, that delays the appearance of adrenergic-neurone blockade in conscious cats. Responses to adrenaline are, in general, enhanced by each drug, but SK&F 90,238 transiently antagonizes tachycardia induced by adrenaline and isoprenaline. Both drugs inhibit the release of noradrenaline from the spleen during splenic nerve stimulation, but the release of catechol amines from the adrenal glands, in response to electrical or chemical stimulation, is unimpaired. In contrast to the prolonged adrenergic-neurone blocking action, any inhibition of the effects of cholinergic nerve stimulation is transient. Large intravenous doses produce neuromuscular blockade. The compounds have a slight central depressant action. In contrast to reserpine and guanethidine the noradrenaline content of rat hearts is not appreciably lowered 24 hr after a single dose of either drug. Unlike xylocholine they are not local anaesthetics. Related compounds also block the effects of adrenergic-nerve stimulation. The possible modes of action of these drugs are discussed.

Topics: Adrenergic Agents; Adrenergic Neurons; Animals; Autonomic Nerve Block; Benzofurans; Blood Flow Velocity; Catecholamines; Cats; Coumarins; Electric Stimulation; Epinephrine; Female; Gastrointestinal Motility; Guanethidine; Guanidines; Heart Rate; Humans; Isoproterenol; Myocardium; Neurophysiology; Nictitating Membrane; Norepinephrine; Pharmacology; Rats; Research; Salivation; Splanchnic Nerves; Spleen; Stomach; Sympathetic Nervous System; Sympatholytics; Sympathomimetics; Tachycardia; Uterus

Topics: alpha-Tocopherol; Benzofurans; Isomerism; Vitamin E; Vitamins

Topics: Benzofurans; Humans; Morphine; Morphine Derivatives