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The synthesis of 5-hydroxy-2,3-dihydrobenzo(B)thiophene (1) via an efficient one step preparation of 5-nitro-benzo(B) thiophene-2-carboxylate (3A)

The preparation of 5-hydroxy-2,3-dihydrobenzothiophene 1 from 5-nitro-benzothiophene-2-carboxylate 3a is described along with an efficient one pot synthesis of 3a.

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Structural Evolution and Pharmacology of a Novel Series of Triacid Angiotensin II Receptor Antagonists

cis-4-(4-Phenoxy)-1-<1-oxo-2(R)-<4-<(2-sulfobenzoyl)amino>-1H-imidazol-1-yl>octyl>-L-proline derivatives represent a novel class of potent nonpeptide angiotensin II (Ang II) receptor antagonists.These compounds evolved from directed structure-activity relationship (SAR)studies on a lead identified by random screening.Further SAR studies revealed that acidic modification of the 4-phenoxy ring system produced a series of triacid derivatives possessing oral activity in pithed rats.The most potent compound, cis-4-<4-(phosphonomethyl)phenoxy>-1-<1-oxo-2(R)-<4-<(2-sulfobenzoyl)amino>-1H-imidazol-1-yl>octyl>-L-proline (1e), inhibited the pressor response to exogenously administered Ang II for periods up to 8 h following oral dosing.The antihypertensive activity of 1e was evaluated in the Lasix-pretreated conscious spontaneously hypertensive rat (SHR) where it produced a dose-dependent fall in blood pressure following oral dosing lasting > 12 h.Antagonists such as 1e may serve as useful therapeutic agents for the treatment of hypertension as well as for studying the role of Ang II in various disease states.

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Copper-Catalyzed Hydroxylation of (Hetero)aryl Halides under Mild Conditions

The combination of Cu(acac)2 and N,N?-bis(4-hydroxyl-2,6-dimethylphenyl)oxalamide (BHMPO) provides a powerful catalytic system for hydroxylation of (hetero)aryl halides. A wide range of (hetero)aryl chlorides bearing either electron-donating or -withdrawing groups proceeded well at 130 C, delivering the corresponding phenols and hydroxylated heteroarenes in good to excellent yields. When more reactive (hetero)aryl bromides and iodides were employed, the hydroxylation reactions completed at relatively low temperatures (80 and 60 C, respectively) at low catalytic loadings (0.5 mol % Cu).

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NOVEL INHIBITORS OF BETA-LACTAMASE

This invention provides novel beta-lactamase inhibitors of the aryl- and heteroarylsulfonamidomethylphosphonate monoester class having nitrogen-based cations or quarternary ammonium groups. The compounds inhibit three classes of beta-lactamases and synergize the antibacterial effects of beta-lactam antibiotics (e.g., imipenem and ceftazidime) against those micro-organisms normally resistant to the beta-lactam antibiotics as a result of the presence of the Beta-lactamases. Formula (I) or pharmaceutically acceptable salt thereof.

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Synthesis and biological evaluation of 3-heteroaryloxy-4-phenyl-2(5H)-furanones as selective COX-2 inhibitors

A series of 3-heteroaryloxy-4-phenyl-2-(5H)-furanones were prepared and evaluated for their potency and selectivity as COX-2 inhibitors. This led to the identification of L-778,736 as a potent, orally active and selective inhibitor of the COX-2 enzyme.

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Bacterial dioxygenase- and monooxygenase-catalysed sulfoxidation of benzo[b]thiophenes

Asymmetric heteroatom oxidation of benzo[b]thiophenes to yield the corresponding sulfoxides was catalysed by toluene dioxygenase (TDO), naphthalene dioxygenase (NDO) and styrene monooxygenase (SMO) enzymes present in P. putida mutant and E. coli recombinant whole cells. TDO-catalysed oxidation yielded the relatively unstable benzo[b]thiophene sulfoxide; its dimerization, followed by dehydrogenation, resulted in the isolation of stable tetracyclic sulfoxides as minor products with cis-dihydrodiols being the dominant metabolites. SMO mainly catalysed the formation of enantioenriched benzo[b]thiophene sulfoxide and 2-methyl benzo[b]thiophene sulfoxides which racemized at ambient temperature. The barriers to pyramidal sulfur inversion of 2- and 3-methyl benzo[b]thiophene sulfoxide metabolites, obtained using TDO and NDO as biocatalysts, were found to be ca.: 25-27 kcal mol-1. The absolute configurations of the benzo[b]thiophene sulfoxides were determined by ECD spectroscopy, X-ray crystallography and stereochemical correlation. A site-directed mutant E. coli strain containing an engineered form of NDO, was found to change the regioselectivity toward preferential oxidation of the thiophene ring rather than the benzene ring.

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IN VIVO IMAGING OF SULFOTRANSFERASES

Radiolabeled tracers for sulfotransferases (SULTs), their synthesis, and their use are provided. Included are substituted phenols, naphthols, coumarins, and flavones radiolabeled with 18F, 123I, 124I, 125I, or 11C. Also provided are in vivo techniques for using these and other tracers as analytical and diagnostic tools to study sulfotransferase distribution and activity, in health and disease, and to evaluate therapeutic interventions.

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Toluene dioxygenase-catalyzed cis-dihydroxylation of benzo[b]thiophenes and benzo[b]furans: Synthesis of benzo[b]thiophene 2,3-oxide

Enzymatic cis-dihydroxylation of benzo[b]thiophene, benzo[b]furan and several methyl substituted derivatives was found to occur in both the carbocyclic and heterocyclic rings. Relative and absolute configurations and enantiopurities of the resulting dihydrodiols were determined. Hydrogenation of the alkene bond in carbocyclic cis-dihydrodiols and ring-opening epimerization/reduction reactions of heterocyclic cis/trans-dihydrodiols were also studied. The relatively stable heterocyclic dihydrodiols of benzo[b]thiophene and benzo[b]furan showed a strong preference for the trans configuration in aqueous solutions. The 2,3-dihydrodiol metabolite of benzo[b]thiophene was utilized as a precursor in the chemoenzymatic synthesis of the unstable arene oxide, benzo[b]thiophene 2,3-oxide.

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Fused thiophone derivatives and drugs containing the same as the active ingredient

The present invention relates to a fused thiophene derivative of the formula (I) (wherein all the symbols are defined as described in the specification) and an inhibitor of producing interleukin-6 and/or interleukin-12 comprising the said derivative as an active ingredient.A fused thiophene derivative of the formula (I) is useful as an agent for the prevention and/or treatment of various inflammatory diseases, sepsis, multiple myeloma, plasma cell leukemia, osteoporosis, cachexia, psoriasis, nephritis, renal cell carcinoma, Kaposi’s sarcoma, rheumatoid arthritis, gammopathy, Castleman’s disease, atrial myxoma, diabetes mellitus, autoimmune diseases, hepatitis, multiple sclerosis, colitis, graft versus host immune diseases, infectious diseases.

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Bismuth(III)-catalyzed dehydrative etherification and thioetherification of phenolic hydroxy groups

Use of a bismuth catalyst allowed efficient dehydrative substitution of phenolic hydroxy groups with alcohols and thiols to form C-O and C-S bonds. The reaction required equimolar amounts of two readily available substrates that generated H2O as the only byproduct. The relatively mild reaction conditions were compatible with the functional groups selected, and provided excellent chemoselectivity.

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Benzothiophene – Wikipedia,
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