Showing papers on "Benzopyran published in 2002"

Novel sigma receptor ligands. Part 2. SAR of spiro[[2]benzopyran-1,4'-piperidines] and spiro[[2]benzofuran-1,4'-piperidines] with carbon substituents in position 3.

Abstract: Several spiro[[2]benzopyran-1,4‘-piperidines] and spiro[[2]benzofuran-1,4‘-piperidines] were synthesized and evaluated for their binding properties for σ1 and σ2 receptors. The key step for the introduction of a one carbon residue is the reaction of the cyclic methyl acetals 2a and 3a with trimethylsilyl cyanide to yield the nitriles 5 and 20. The reaction of the lactols 2b and 3b with stabilized phosphoranes affords spiropiperidines with a two carbon residue in position 3. In agreement with previously reported σ1 and σ2 receptor binding data, the investigated spiro compounds display higher affinity for σ1 vs σ2 receptors. Compounds with a cyano group in position 3 of the spirocycle show high σ1 receptor affinity and selectivity. The spirobenzopyran nitrile 5 and the homologous spirobenzofuran nitriles 20 and 23 show almost identical σ1 affinities, whereas the spirobenzopyran nitrile 13 with a methylene spacer is 10-fold less potent. Among the reported compounds, 1‘-benzyl-3,4-dihydrospiro[[2]benzopyran-1...

Resorcinol Derivatives: A Novel Template for the Development of Cannabinoid CB1/CB2 and CB2-Selective Agonists

Abstract: The role of the oxygen of the benzopyran substituent of Δ9-tetrahydrocannabinol in defining affinity for brain cannabinoid (CB1) receptors is not well understood; however, it is known that opening the pyran ring can result in either increased potency and affinity, as in CP 55,940 [(−)- cis- 3-[2-hydroxy-4(1,1- dimethyl-heptyl)phenyl]- trans- 4-(3-hydroxy-propyl)cyclohexanol], or in an inactive cannabinoid, as in cannabidiol. In the present study, a series of bicyclic resorcinols that resemble cannabidiol were synthesized and tested in vitro and in vivo. Analysis of the structure-activity relationships of these analogs revealed several structural features that were important for maintaining CB1receptor recognition and in vivo activity, including the presence of a branched lipophilic side chain and free phenols as well as substitution of a cyclohexane as the second ring of these bicyclic cannabinoids. Many of these analogs exhibited CB2 selectivity, particularly the dimethoxyresorcinol analogs, and this selectivity was enhanced by longer side chain lengths. Hence, unlike cannabidiol, these resorcinol derivatives had good affinity for CB1 and/or CB2 receptors as well as potent in vivo activity. These results suggest that the resorcinol series represent a novel template for the development of CB2-selective cannabinoid agonists that have the potential to offer insights into similarities and differences between structural requirements for receptor recognition at CB1 and CB2 receptors.

Direct α-Fluorination of Ketones Using N-F Reagents

Abstract: The use of 1-fluoro-4-hydroxy-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Accufluor NFTh) as a fluorine atom transfer reagent and methanol as solvent enabled direct regiospecific fluorofunctionalization of the u-carbonyl position in ketones without prior activation of the target molecules. Methoxy or hydroxy substituted derivatives of 1-indanone, 1-tetralone and oxo derivatives of thiophene, benzo[b]thiophene, benzofuran and benzopyran were regiospecifically transformed to the corresponding α-fluoro derivatives in high yield, while 2α-fluoro-5α-cholestan-3-one (28) and 16α-fluoro-3β-hydroxy-5α-androstan-17-one (30) were regio- and stereospecifically obtained starting directly from the corresponding keto steroids.

Prevention of lipopolysaccharide-induced apoptosis by (2S, 3S, 4R)-N -cyano-N-(6-amino-3,4-dihydro-3-hydroxy-2-methyl-2-dimethoxymethyl- 2H-benzopyran-4-yl)-N'-benzylguanidine, a benzopyran analog, in endothelial cells

Abstract: This study describes the antiapoptotic action of (2 S ,3 S ,4 R )- N "-cyano- N -(6-amino-3,4-dihydro-3-hydroxy-2-methyl-2-dimethoxymethyl-2 H -benzopyran-4-yl)- N ′-benzylguanidine (KR-31378), a novel benzopyran analog, in human umbilical vein endothelial cells (HUVECs) in comparison with its acetylated metabolite, (2 S ,3 S ,4 R )- N "-cyano- N -(6-acetylamino-3,4-dihydro-3-hydroxy-2-methyl-2-dimethoxymethyl-2 H -benzopyran-4-yl)- N ′-benzylguanidine (KR-31612), and with α-tocopherol. Exposure of HUVECs to lipopolysaccharide (LPS) (1 μg/ml) induced time- and concentration-dependent cytotoxicity and oligonucleosomal DNA fragmentation. KR-31378, KR-31612, and α-tocopherol potently suppressed LPS-induced cell death in association with significant reduction in the intracellular reactive oxygen species (ROS) and tumor necrosis factor-α (TNF-α) that are stimulated by LPS. KR-31378 more effectively protected HUVECs from LPS-induced DNA fragmentation and was more effective in peroxyl radical scavenging than α-tocopherol. Incubation with LPS markedly decreased the Bcl-2 level, which was totally reversed by KR-31378 and to a lesser degree by KR-31612 and by α-tocopherol. In contrast, the greatly increased Bax protein and cytochrome c release stimulated by LPS were markedly suppressed by KR-31378 and by KR-31612, and to a lesser degree by α-tocopherol. Taken together, KR-31378 strongly inhibited cell death in HUVECs in association with antiapoptotic effects, which were accompanied by up-regulation of Bcl-2 protein expression and down-regulation of Bax protein and suppression of cytochrome c release. KR-31378 also showed the properties to scavenge the intracellular ROS and peroxyl radicals, and to reduce the TNF-α production induced by LPS.

Novel benzopyran compounds and process for their preparation and use

Abstract: Novel benzopyran compounds that are useful as beta 3-adrenergic receptor agonists, pharmaceutical compositions containing these compounds, and processes for their preparation and use.

2H-1-benzopyran derivatives processes for their preparation and pharmaceutical compositions thereof

Abstract: 2H-1-Benzopyran derivatives, processes for their preparation and use thereof for the preparation of pharmaceutical compositions for the prevention and treatment of postmenopausal pathologies.

A useful enantioselective synthesis of chroman-2-ylmethanol

Abstract: An enantioselective synthesis of chromanylmethanol is described An allylic alcohol moiety is, first, introduced on the aromatic ring through a Claisen transposition Chirality is then introduced through asymmetric Sharpless epoxidation on the allylic alcohol moiety Cyclization into the benzopyran ring is achieved by an intramolecular coupling between the tertiary alcoholic hydroxy and the hydroquinone moiety with an excellent retention of configuration

Synthesis of 2h-1-benzopyran derivatives with a strongly electron-withdrawing substituent at 6-position

Abstract: 5-Bromo- and 5-nitro-2-hydroxybenzaldehyde react with the acetylenic ester 1 (R = Me and Bu') in the presence of triphenylphosphine to give the corresponding 6-substituted 2H-1-benzopyran-2,3-dicarboxylic esters 4. Isolated yields in the one-pot preparation of compounds 4 are excellent. Reaction mechanism for the formation of compouds 4 is proposed. The structures of compounds 4a-c have been confirmed by IR, MS and 1 H and 1 3 C NMR spectroscopy and elemental analyses.

Benzopyrans. Part 43.1 Reactions of Some Simple Condensates of 4-oxo-4H-1-Benzopyran-3-Carboxaldehyde with Ethyl β-Aminocrotonate:

Abstract: With ethyl (3-aminocrotonate, the chromone 2A (X = H(A), Me(B), Cl(C)) gives a mixture of the dihydropyridine 4A and pyranopyridine 15A, 2B gives 4B, and 2C gives varying amounts of the substituted enamine 3C, pyridone 4Cand benzophenone 8. 5-Hydroxy-5H-[1]benzopyrano-[4,3-b]pyridine 11 (< 3%) was obtained in each case. Palladised charcoal dehydrogenates dihydropyridines 4A and 4B to respectively 12A and 12B and ammonia converts 12A into the diazanaphthalene 13.

Substituted benzopyran anti-fungus compound

Abstract: The present invention relates to a novel substituted benzopyran antifungal compound. Said invention also provides its chemical structural formula, and said compound possesses strong antifungal activity, and its toxicity is low.

Zinc-induced reduction of ethyl 2-cyano-3-(4-oxo-4H-1-benzopyran-3-yl)propenoates: a medium-dependent reaction

Abstract: Reduction of acrylates 1 1 with Zn in THF containing aqueous NH 4 Cl produces the cyclopentadienones 4, whereas with Zn in acetic acid reduction produces the cyanopropanoates 5.

[Synthesis and vasorelaxant activities of benzopyran-4-one hydrazone derivatives].

Abstract: Aim In search of more potent, less toxic and selective potassium channel openers. Methods According to the structure-activity relationships of benzopyran compounds and the features of structures of aprikalim, dofetilide and nifekalant, twenty benzopyran-4-one hydrazone derivatives have been designed and synthesized from 4-cyanophenos through acetylation, Fries rearrangment, cyclization, hydrazone, substitution reaction and so on. The compounds were tested for their vasorelaxant activity in low (30 mmol.L-1) and high (80 mmol.L-1) KCl-induced contraction of rat aorta to identify potential potassium channel openers in vitro. Results Three series of twenty benzopyran-4-one hydrazone derivatives, nominated N-aminoacetyl-(6-cyano-3,4-dihydrospiro [2H-1-benzopyran-2,1'-cyclohexane]-4)-one hydrazone (I), 2-(6-cyano-3, 4-dihydro-2H-1-benzopyran-4-ylene) hydrazinethiocarboxamide derivatives (II) and N-(2-arylethyl) aminoacetyl-(6-cyano-3,4-dihydro-2H-1-benzopyran)-4-one hydrazone (III), have been synthesized. They (I1-9, II1-4 and III1-7) are new compounds. Their chemical structures were determined by IR, 1HNMR, MS and elemental analysis. The vasorelaxant effects of those novel compounds indicated that some of the compounds have vasorelaxant activities at 1 x 10(-6) mol.L-1. Conclusion The vasorelaxant activities of compounds I9, III2 and III5 in inhibiting low KCl-induced vasocontraction at 1 x 10(-6) mol.L-1 are less potent than the reference compound emakalim. However they are more potent than emakalim to inhibition high concentration KCl-induced vasocontraction at 1 x 10(-5) mol.L-1. It is worthy of further study.

Synthesis of 2H‐1‐Benzopyran Derivatives with a Strongly Electron‐Withdrawing Substituent at 6‐Position

Abstract: 5-Bromo- and 5-nitro-2-hydroxybenzaldehyde react with the acetylenic ester 1 (R = Me and Bu') in the presence of triphenylphosphine to give the corresponding 6-substituted 2H-1-benzopyran-2,3-dicarboxylic esters 4. Isolated yields in the one-pot preparation of compounds 4 are excellent. Reaction mechanism for the formation of compouds 4 is proposed. The structures of compounds 4a-c have been confirmed by IR, MS and 1 H and 1 3 C NMR spectroscopy and elemental analyses.

Novel crystal form of (3s-trans)-2-[3,4-dihydro-4- hydroxy-3-(phenylmethyl)-2h-1-benzopyran-7- yl]-4-(trifluoromethyl)-benzoic acid

Abstract: PROBLEM TO BE SOLVED: To obtain a novel polymorphic crystal and a novel salt of anhydrous crystalline (3S-trans)-2-[3,4-dihydro-4-hydroxy-3-(phenylmethyl)-2H-1-benzopyran-7- yl]-4-(trifluoromethyl)-benzoic acid [hereafter, abbreviated as the compound (I)] and a hydrate of the aforesaid compound. SOLUTION: Each novel composition has specific characteristics for contributing to be used in pharmaceutical preparations. A novel monohydrate of the compound (I) is described, advantageously isolated from a water-containing solvent and capable of being formulated by wet granulation. Novel ethylenediamine (mono)salts are described and express excellent solubilities and abilities to be biologically used. Further, a polymorphic compound A of the anhydrous crystal compound (I) has excellent heat stability and a polymorphic compound B of (I) has an excellent solubility. Further, a medicinal composition comprising the compound and a method for curing inflammatory diseases and the likes using thereof are described.

Benzopyran derivative and antiallergic agent

Abstract: The present invention provides a compound which is highly safe in terms of toxicity and has a stronger antiallergic action, and particularly has an action of inhibiting both immediate and delayed type allergic reactions. A benzopyran derivative represented by the general formula (I): wherein R1 is an alkyl group having 1-10 carbon atoms or an alkenyl group having 2-10 carbon atoms, and one of R2, R3, R4, and R5 is an alkoxy group substituted with a hydroxygroup or an alkoxy group substituted with a carboxy group, and the others are hydrogen atoms or physiologically acceptable salts thereof are superior as the active ingredient of an antiallergic agent.

Crystalline forms of (3S-trans)-2-&lsqb 3,4-dihydro-4-hydroxy-3-(phenylmethyl)-2H-1-benzopyran-7-yl&rsqb -4-(trifluoromethyl)-benzoic acid

Abstract: The present invention provides novel polymorphic forms of anhydrous crystalline (3S-trans)-2-[3,4-dihydro-4-hydroxy-3-(phenylmethyl)-2H-1-benzopyran-7-yl]-4-(trifluoromethyl)-benzoic acid, hereinafter compound (I), and a novel salt, and a hydrate of said compound, wherein each novel composition has particular characteristics that contribute to its use in pharmaceutical formulations. The novel monohydrate of compound (I) is described, which can be advantageously isolated from water wet solvents and formulated via wet granulation techniques. The novel ethylene diamine (mono) salt is also described, and demonstrates superior solubility and bioavailability. Additionally, polymorphic forms A and B of anhydrous crystalline compound (I) are described, wherein form A has superior thermal stability, and form B has superior solubility. Additionally, there are described pharmaceutical compositions that comprise these substances, and methods for the treatment of disease states therewith, in particular, the treatment of inflammatory diseases.

Aminobenzopyran derivatives and compositions

Abstract: Benzopyran derivatives including aminobenzopyran derivatives are described. Compositions that include the aminobenzopyran derivatives are also provided.

Process for producing benzopyran carboxamide

Abstract: A first process for producing a benzopyran carboxamide represented by the general formula [1] includes reacting 3-aminopropionitrile.½ sulfate, N≡CCH 2 CH 2 NH 2 .½(H 2 SO 4 ), with a benzopyran carboxylic halide represented by the general formula [2], in the presence of a base. A second process for producing the benzopyran carboxamide includes the steps of (a) reacting 3-aminopropionitrile.½ sulfate with a base, thereby forming 3-aminopropionitrile; and (b) reacting the 3-aminopropionitrile with the benzopyran carboxylic halide [2], thereby producing the benzopyran carboxamide. A process for stabilizing 3-aminopropionitrile includes turning the 3-aminopropionitrile into a sulfate of the 3-aminopropionitrile. where R is a straight-chain or non-straight-chain perfluoroalkyl group represented by C n F 2n+1 where n is an integer of 1-10; and X is fluorine, chlorine, bromine or iodine.

A Useful Enantioselective Synthesis of Chroman-2-ylmethanol.

Abstract: An enantioselective synthesis of chromanylmethanol is described. An allylic alcohol moiety is, first, introduced on the aromatic ring through a Claisen transposition. Chirality is then introduced through asymmetric Sharpless epoxidation on the allylic alcohol moiety. Cyclization into the benzopyran ring is achieved by an intramolecular coupling between the tertiary alcoholic hydroxy and the hydroquinone moiety with an excellent retention of configuration.