Showing papers on "Pyran published in 1991"

Inhibitors of cholesterol biosynthesis. 3. Tetrahydro-4-hydroxy-6-[2-(1H-pyrrol-1-yl)ethyl]-2H-pyran-2-one inhibitors of HMG-CoA reductase. 2. Effects of introducing substituents at positions three and four of the pyrrole nucleus.

Abstract: A series of trans-tetrahydro-4-hydroxy-6-[2-(2,3,4,5-substituted-1H-pyrrol-1-yl) ethyl]-2H-pyran-2-ones and their dihydroxy acids were prepared and tested for their ability to inhibit the enzyme HMG-CoA reductase in vitro. Inhibitory potency was found to increase substantially when substituents were introduced into positions three and four of the pyrrole ring. A systematic exploration of structure-activity relationships at these two positions led to the identification of a compound ((+)-33,(+)-(4R)-trans-2-(4-fluororphenyl)-5-(1-methylethyl)-N,3- diphenyl-1- [(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrole-4- carboxamide) with five times the inhibitory potency of the fungal metabolite compactin.

Sequential directed ortho metalation-boronic acid cross-coupling reactions. A general regiospecific route to oxygenated dibenzo[b,d]pyran-6-ones related to ellagic acid

Abstract: A general regiospecific synthesis of dibenzo[b,d]pyran-6-one derivatives 1a,c and 8a-i related to ellagic acid is described (Scheme I, Table I). The sequence involves directed ortho metalation-boronation of benzamides 4 to give the arylboronic acids 5, which, upon palladium-catalyzed cross-coupling with alkoxybromobenzenes 6 leads to the biphenylamides 7. BBr 3 demethylation followed by acid-catalyzed cyclization affords pyranone 8. In this manner, the naturally occurring dibenzopyranones 1a, autumnariol (1c), and the heterocyclic analogue 13 (Scheme III) were efficiently prepared

Inhibitors of cholesterol biosynthesis. 4. trans-6-[2-(substituted-quinolinyl)ethenyl/ethyl]tetrahydro-4-hydroxy-2 H-pyran-2-ones, a novel series of HMG-CoA reductase inhibitors.

Abstract: A series of substituted quinoline mevalonolactones were prepared and evaluated for their ability to inhibit the enzyme HMG-CoA reductase both in vitro and (cholesterol biosynthesis) in vivo. Since previous studies suggested that the 4-(4-fluorophenyl) and 2-(1-methylethyl) substituents afforded optimum potency, attention was focused on variations at position 6 of the quinoline ring. Biological evaluation of a small number of analogues bearing a variety of 6-substituents showed that modification at this position had little effect on potency. Several compounds (8b, 8e, and 11) were identified that showed comparable potency to compactin and mevinolin in both the in vitro and in vivo assays.

Photochromic chromene compounds

Abstract: Described are a series of novel photochromic benzopyran and naphthopyran compounds substituted with (1) a cyclopropyl group and (2) a phenyl, substituted phenyl, or 5-member aromatic heterocyclic group at the 2-position of the benzopyran or naphthopyran ring. Also described are organic host materials that contain or that are coated with such compounds. Articles such as ophthalmic or plano lenses that incorporate the novel pyran compounds or combinations of the novel pyran compounds with other complementary photochromic compounds are described.

Restricticin, a novel glycine-containing antifungal agent.

Abstract: Restricticin (1) is a naturally-occurring antifungal agent which contains triene, pyran and glycine ester functionalities and is unrelated to any previously known family of natural products. This unstable compound, as well as its corresponding N,N-dimethyl derivative (2), have been produced and isolated from both solid and liquid fermentations of Penicillium restrictum. The desglycyl hydrolysis product, restrictinol (3), was produced via the hydrolysis of pure restricticin and as an artifact of the isolation of restricticin.

Cinnamoylnitrile-, pyran-, and pyranopyrazole-derivatives containing the salicylanilide moiety with anticipated molluscicidal activity.

Abstract: The reaction of new cinnamonitriles containing the salicylyl moiety with active methylene reagents leads to the formation of the corresponding heterocycles. Their reaction with aniline yields the corresponding salicylanilide derivatives. The obtained pyrans and anilides were tested for molluscicidal activity.

A New General Synthesis of 2,2-Dialkyl-2,3-dihydro-4H-pyran-4-ones and Their Application for the in situ Preparation of Electron-Rich Dienes in Carbonyl-Alkyne Exchange Reactions with Acetylenes†

Abstract: The substituted 2,2-dialkyl-2,3-dihydro-4H-pyran-4-ones of type II and III have been prepared by acid-catalyzed cyclization of the corresponding substituted acetylenic ketones I in good to excellent yields (Scheme 1). These 2,2-dialkyl-2,3-dihydro-4H-pyran-4-ones II and III have been used for the in situ preparation of highly reactive dienes of type IV–VI (Scheme 2) in carbonyl-alkyne exchange reactions with electron-poor alkynes VII to yield the highly substituted aromatic compounds VIII and IX. These reactions proceed in good yields and with excellent degree of regioselectivity. Aryl-substituted 2,2-dialkyl-2,3-dihydro-4H-pyran-4-ones III (R1 = Ar) subsequently yield highly substituted biaryls. Reaction mechanisms are presented for the formation of the 2,2-dialkyl-2,3-dihydro-4H-pyran-4-ones as well as for the carbonyl-alkyne exchange reactions with electron-poor acetylenes.

Reactions of six-membered heterocyclic β-enaminonitriles with electrophilic reagents

Abstract: The nitriles I reacted with acetylacetone and with ethyl acetoacetate to afford 2-amino-3-cyano-4 H -pyran derivatives. They reacted further to yield pyranopyridine derivatives. The reaction of V with acetylacetone afforded the pyridinethione VIII . This afforded, reacting with aromatic aldehydes or with cinnamonitriles quinoline derivatives XVII .

Solid state photochromism of 2,4,4,6-tetraphenyl-4H-pyran and 1,4-dihydropyridine derivatives

Abstract: Results of a study on the photochromic behaviour of various 2,4,4,6-tetraphenyl-4 H -pyrans ( 1 ), 2,4,4,6-tetraphenyl-1,4-dihydropyridines ( 2 and 3 ) and 1,2,4,4,6-pentaphenyl-1,4-dihydropyridines ( 4 ) are reported. Most investigated materials undergo a photochromic change in the solid state after illumination with UV light. The maxima of the new absorption bands are located in the range 545–630 nm, depending on the chemical structure of the substituents. The non-exponential time dependence of photochromic decolouration of the model compound, 1-methyl-2,4,4,6-tetraphenyl-1,4-dihydropyridine ( 3a ), is analysed in terms of a dispersive first-order reaction, i.e. is described by the formula exp(− t α ), where α is the dispersion parameter.

Pyran derivatives as inhibitors of 5-lipoxygenase

Abstract: The invention concerns a heterocyclene derivative of the formula I wherein Ar 1 is optionally substituted phenyl, naphthyl or a 9- or 10-membered bicyclic heterocyclic moiety ; A 1 is a direct link to X 1 or (1-3C)alkylene ; X 1 is oxy, thio, sulphinyl, sulphonyl or imino; Ar 2 is optionally substituted 5-membered heterocydene moiety ; R 1 is (1-4C)alkyl, (3-4C)alkenyl or (3-4C)alkynyl ; and R 2 and R 3 together form a group of the formula -A2-X 2 -A 3- which, together with the carbon atom to which A 2 and A3 are attached, defines a ring having 5 to 7 ring atoms, wherein each of A 2 and A3 is (1-3C)alkylene and X 2 is oxy, thio, sulphinyl or sulphonyl ; or a pharmaceutically-acceptable salt thereof. The compounds of the invention are inhibitors of the enzyme 5-lipoxygenase.

Conformational and steric modifications of the pyran ring of the potassium-channel activator cromakalim

Abstract: The syntheses of analogues of the novel smooth muscle relaxant cromakalim, in which the C-2 methyl groups have been successively replaced by hydrogen, are described and the relative stereochemistry of the two corresponding, isomeric monomethyl compounds, unambiguously assigned by 1H NMR spectroscopic techniques. Single-crystal X-ray analysis of the 2α-monomethyl compound showed that it existed in a distorted half-chair conformation in the solid state and confirmed the relative orientation of the C-2, C-3 and C-4 substituents. The 2β-Me isomer appeared to exist in a single conformation in solution, with the pyran ring adopting a half-chair conformation and with all the substituents in this ring occupying a pseudoequatorial position. The solution behaviour of the 2α-Me isomer is more complex, however, although it seems likely to exist as a distorted half-chair conformer similar to that found in the solid state. The syntheses of two related benzoxepines are also described. All compounds were less potent than cromakalim itself, which is consistent with the view that dimethyl substitution at C-2 is essential for optimal activity.

Bicyclic pyran derivatives and their use as inhibitors of 5-lipoxygenase

Abstract: The invention concerns a bicyclic heterocyclic compound of the formula I, or a pharmaceutically-acceptable salt thereof. The invention concerns also processes for the manufacture of a bibyclic heterocyclic compound of the formula I, or a pharmaceutically-acceptable salt thereof, and pharmaceutical compositions containing said compound. Also included in the invention is a method of treating various inflammatory or allergic diseases using a bibyclic heterocyclic compound of the formula I, or a pharmaceutically-acceptable salt thereof, and the use of such a compound in the production of a new medicament for such use.

3-¬4-(1-substituted-4-piperazinyl)butyl|-4-thiazolidinone and related compounds

Abstract: There are disclosed compounds of the formula, ##STR1## where n is 0, 1 or 2; A is ##STR2## where X in each occurrence is independently hydrogen, halogen, loweralkyl, hydroxy, nitro, loweralkoxy, amino, cyano, trifluoromethyl or methylthio; Y in each occurrence is independently hydrogen, halogen, loweralkyl, hydroxy, nitro, loweralkoxy, amino, cyano, trifluoromethyl or methylthio; m is 1 or 2; k is 1 or 2; R1 and R2 are independently hydrogen, loweralkyl, ##STR3## or aryl except that when R1 is ##STR4## or aryl, R2 is hydrogen, or alternatively R1 +R2 taken together with the carbon atom to which they are attached form a cyclopentane, cyclohexane, cycloheptane, pyran, thiopyran, indan or piperidine ring; R3 and R4 are independently hydrogen or loweralkyl, or alternatively R3 +R4 taken together with the carbon atom to which they are attached form a cyclopentane, cyclohexane, cycloheptane, pyran, thiopyran, pyrrolidine or piperidine ring, the term aryl signifying an unsubstituted phenyl group or a phenyl group substituted with 1, 2 or 3 substituents each of which being independently loweralkyl, loweralkoxy, hydroxy, halogen, loweralkylthio, cyano, amino or trifluoromethyl, which are useful as antipsychotic, analgesic, anticonvulsant and anxiolytic agents.

A convenient synthesis of 5-substituted 2-pyrrolidinones via 2h-pyran-3(6h)-ones

Abstract: Jones oxidation of 6-hydroxy-2H-pyran-3(6H)-ones, subsequent hydrogenation, oxime formation and catalytic hydrogenation constitute and efficient route for the synthesis of various 5-substituted 2-pyrrolidinone derivatives starting from aldehydes or ketones

Benzo[6,7]cyclohepta[1,2-b]pyran derivatives with platelet antiaggregating and other activities.

Abstract: The synthesis of some N,N-disubstituted 4-amino-6,7-dihydro-3-phenylbenzo[6,7]cyclohepta[1,2-b]pyran-2(5H) -ones by reaction of phenylchloroketene with a series of N,N-disubstituted 6-aminomethylene-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ones, followed by dehydrochlorination of the primary adducts with DBN, is described. Some compounds showed a platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid, as well as a weak local anesthetic activity in mice and antiinflammatory activity in rats.