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Structural studies on cycloadducts of furan, 2-methoxyfuran, and 5-trimethylsilylcyclopentadiene with maleic anhydride and N-methylmaleimide

(Chemical Equation Presented) The early stages of the retro-Diels-Alder reaction are clearly apparent in the structures of the cycloadducts formed between furan or 5-trimethylsilylcyclopentadiene with maleic anhydride and N-methylmaleimide. The degree of lengthening of the C-C bonds that break in this reaction is clearly related to the known reactivity of these cycloadducts toward this reaction. In the structures of the cycloadducts 21 and 22 derived from 2-methoxyfuran, the early stages of an alternative fragmentation reaction are apparent, consistent with the reactivity of these compounds in solution.

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Benzofuran – Wikipedia,
Benzofuran | C8H2885O – PubChem

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Crystal structures of highly stabilized ylides: Methyl(3-methoxy,2-methoxycarbonylbenzoyl)triphenylphosphoranylideneacetate and methyl(2-methoxycarbonyl,6-nitrobenzoyl)triphenylphosphoranylideneacetate and the salt methyl(triphenylphosphoranylidene)acetate tetrafluoroborate

At lower temperatures stabilized ylides react with unsymmetrically substituted phthalic anhydrides to give two acyclic adducts. When the reactions are allowed to proceed at higher temperature enol lactones are formed. Identification of the acyclic intermediates was necessary to understand the mechanism of these Wittig reactions. The transient species trapped in the reaction with trimethyloxonium tetrafluoroborate were unambiguously identified by crystallographic methods. The crystal structures of the tetrafluoroborate salt of methyl(triphenylphosphoranylidene)-acetate (8), methyl(3-methoxy,2-methoxycarbonylbenzoyl)triphenylphosphoranylideneacetate (6beta), and methyl(2-methoxycarbonyl,6-nitrobenzoyl)triphenylphosphoranylideneacetate (7alpha) were studied by X-ray diffraction. The ionic salt (8) is monoclinic, P21/c, a = 12.640(5), b = 13.945(9), c = 14.825(6) A, beta = 125.32(3), Z = 4, and R = 0.065 (F > 5.4 sigma(F)). Crystal 6beta is monoclinic, P21/c, a = 16.391(16), b = 9.029(6), c = 19.835(19) A, beta = 116.60(6), Z = 4, and R = 0.070 (F > 4.6 sigma(F)), while crystal 7alpha is also monoclinic, P21/c, a = 9.513(5), b = 9.361(3), c = 30.908(13) A, beta = 98.42(3), Z = 4, and R = 0.057 (F > Ssigma(F)). In the BF4- salt (12), the four P – C distances are equal (1.791(5)-1.801(7) A) with identical tetrahedral angles. For the two triphenylphosphoranylideneacetate compounds, the fourth P-C(1) bond is shorter (1.762(6)-1.734(5) A) than the three P-C(Ph) bonds (avg. 1.809(5) A). The angles C(1)-P-C(Ph) are also larger (avg. 112.9(2) for 6beta and 111.9(2) for 7alpha) than the C(Ph)-P-C(Ph) angles (avg. 105.8(2) for 6beta and 106.9(2) for 7alpha). These values suggest a multiple nature for the P-C(1) bond. In the nitro derivative, the nitro and the ester groups are disordered equally in positions 2 and 6.

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Benzofuran – Wikipedia,
Benzofuran | C8H2880O – PubChem

Simple exploration of 4-Methoxyisobenzofuran-1,3-dione

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17O NUCLEAR MAGNETIC RESONANCE SPECTROSCOPIC STUDY OF SUBSTITUTED PHTHALIC ANHYDRIDES AND PHTHALIDES

17O chemical shift data (natural abundance) for 3-substituted phthalic anhydrides and 4- and 7-substituted phthalides in acetonitrile at 75 deg C are reported.Steric interactions of substituents ortho to the carbonyl groups result in deshielding effects (9-22 ppm) relative to parent compounds regardless of the electronic character of the substituents.Factors contributing to the deshielding effects are discussed.The relationship between 17O chemical shifts and regiochemistry of the phthalic anhydrides is discussed.

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Benzofuran – Wikipedia,
Benzofuran | C8H2863O – PubChem

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Trisubstituted benzene leukotriene B4 receptor antagonists: Synthesis and structure-activity relationships

A series of trisubstituted benzenes which demonstrate leukotriene B4 (LTB4, 1) receptor affinity was prepared. Previous trisubstituted benzenes from our laboratory showed high affinity to the LTB4 receptor but demonstrated agonist activity in functional assays. Compound 3a, the initial lead compound of this new series, showed only modest affinity (IC50 = 0.20 muM). However, 3a was a receptor antagonist with no demonstrable agonist activity up to 30 muM. Further modification of the lipid tail and aryl head groups region led to the discovery of 3b (ONO-4057). This compound, free of agonist activity, possesses high affinity to the LTB4 receptor (K(i) = 3.7¡À0.9 nM).

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Benzofuran – Wikipedia,
Benzofuran | C8H2875O – PubChem

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A VERSATILE SYNTHESIS OF HYDROXY-9,10-ANTHRAQUINONE-2-CARBOXYLIC ACIDS

Islandicin, a mould metabolite, can be synthesised in a few, robust, high yielding steps.This procedure can be further elaborated to give a variety of hydroxy-9,10-anthraquinone-2-carboxylic acids.

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Benzofuran – Wikipedia,
Benzofuran | C8H2882O – PubChem

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N-(pyridinylamino) isoindolines and related compounds

Novel N-(pyridinylamino)isoindolines and related compounds, intermediates and processes for the preparation thereof, and methods of relieving memory dysfunction and treating depression utilizing the N-(pyridinylamino)isoindolines and related compounds, the intermediates or compositions thereof are disclosed.

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Discovery of (S)-N-{2-[1-(3-ethoxy-4-methoxy-phenyl)-2- methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1 H-isoindol-4-yl}acetamide (Apremilast), a potent and orally active phosphodiesterase 4 and tumor necrosis factor-a inhibitor

In this communication, we report the discovery of 1S (apremilast), a novel potent and orally active phosphodiesterase 4 (PDE4) and tumor necrosis factor-alpha inhibitor. The optimization of previously reported 3-(1,3-dioxo-1,3-dihydroisoindol-2-yl)-3-(3,4-dimethoxyphenyl)propionic acid PDE4 inhibitors led to this series of sulfone analogues. Evaluation of the structure-activity relationship of substitutions on the phthalimide group led to the discovery of an acetylamino analogue 1S, which is currently in clinical trials.

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Benzofuran – Wikipedia,
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The Discovery of Potent Nonpeptide Angiotensin II Receptor Antagonists: A New Class of Potent Antihypertensives

A new class of potent antihypertensives has been discovered that exert their effect through blockade of the angiotensin II (AII) receptor.Most AII antagonists reported so far are peptide mimics of the endogenous vasoconstrictor octapeptide angiotensin II.The compounds of this paper are nonpeptides and therefore constitute a new class of potent AII receptor antagonists.Based on the overlap of a conformation of AII with literature lead 3, a hypothesis was developed suggesting the need for an additional acidic functionality to increase the lead’s potency.The substitution of an additional carboxylic acid resulted in a 10-fold increase in binding affinity observed for diacid 4.The binding affinities for subsequent compounds were eventually increased 1000-fold over that of the literature leads through a systematic SAR study.Thus the AII receptor binding affinity of 15 muM for literature lead 1, for example, was increased to 0.018 and 0.012 muM for compounds 33 and 53.A structure-affinity relationship has been found requiring the presence of four key elements for good activity: (1) an additional phenyl ring at the N-benzyl para position of the benzylimidazole nucleus, (2) an acidic functionality at the ortho position of the terminal aromatic ring, (3) a lipophilic side chain at the imidazole 2-position of three to five carbon atoms in length, and (4) a group at the imidazole 5-position capable of hydrogen bonding.The synthesis as well as the pharmacological activity of the compounds in this new series of AII receptor antagonists are presented.

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Benzofuran – Wikipedia,
Benzofuran | C8H2870O – PubChem