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Using computer-aided conformational analysis, based on molecular dynamics simulation, cluster analysis, and Monte Carlo techniques, we have designed and synthesized compounds in which a benzyloxy substituent has been incorporated into a series of pyrazoloquinoline benzodiazepine receptor (BZR) ligands.Earlier studies had shown that the benzyloxy group could act as part of the agonist pharmacophoric determinant in the beta-carboline ring system.Furthermore, the agonist beta-carboline had been correlated with a binding site orientation and volume fit for an agonist 6-phenylimidazobenzodiazepine carboxylate.The present study was undertaken to determine whether the benzyloxy substituent could be used as an agonist pharmacophoric descriptor for the phenylpyrazolo<4,3-c>quinolin-3-one BZR ligands.The results of a determination of GABA shift ratios for the synthetic ligands indicate that 8-(benzyloxy)-2-phenylpyrazolo<4,3-c>quinolin-3-one can be predicted to be an agonist at the BZR.

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Reference:
Phosphine ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate

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The dehalogenation of the 1-aryl-3-chloro-4-oxo-azetidine-2-carboxylic acid-ester (3a-d) and (4a-d), which may be obtained by the addition of chloroketene to the aniles (2a-d) leads to the title compounds in good yield. – Key words: Aryloximinoacetic acid-ethylester, 1-Aryl-3-chloro-4-oxo-azetidine-2-carboxylic acid-ethylester, Chloroketene, Tri-n-butyltinhydride

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Reference:
Phosphine ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate

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Though much progress has been made in the inhibition of HIV-1 integrase catalysis, clinical resistance mutations have limited the promise of long-term drug prescription. Consequently, allosteric inhibition of integrase activity has emerged as a promising approach to antiretroviral discovery and development. Specifically, inhibitors of the interaction between HIV-1 integrase and cellular cofactor LEDGF/p75 have been validated to diminish proviral integration in cells and deliver a potent reduction in viral replicative capacity. Here, we have contributed to the development of novel allosteric integrase inhibitors with a high-throughput AlphaScreen-based random screening approach, with which we have identified novel 5-carbonyl-1H-imidazole-4-carboxamides capable of inhibiting the HIV-1 integrase-LEDGF/p75 interaction in vitro. Following a structure-activity relationship analysis of the initial 1H-imidazole-4,5- dicarbonyl core, we optimized the compound’s structure through an industrial database search, and we went further to synthesize a selective and non-cytotoxic panel of inhibitors with enhanced potency.

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Reference:
Phosphine ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate

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Compounds that selectively inhibit the binding of ligands to alpha4beta1 integrin (VLA-4) and methods for their preparation are disclosed. In one embodiment, compounds of the invention are represented by Formula I: 1As selective inhibitors of VLA-4 mediated cell adhesion, compounds of the present invention are useful in the treatment of conditions associated with such adhesion, including, but not limited to, such conditions as inflammatory and autoimmune responses, diabetes, asthma, psoriasis, inflammatory bowel disease, transplantation rejection, and tumor metastasis. Also disclosed are pharmaceutical compositions, methods of inhibiting VLA-4 mediated cell adhesion and methods of treating conditions associated with LA-4 mediated cell adhesion, which involve compounds of Formula I.

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Reference:
Phosphine ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate

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In the course of our studies on non-peptide bradykinin (BK) B2 receptor ligands, it was suggested that the 4-substituent of the quinoline ring may play a critical role in determining binding affinities for human and guinea pig B2 receptors, as well as agonist/antagonist properties. We carried out an extensive investigation to elucidate the structure-activity relationships (SAR) for this key pharmacophore. Introduction of lower alkoxy groups to the 4-position of the quinoline ring of 3 led to the identification of 4-ethoxy derivative 22b as a unique partial agonist. This compound significantly stimulated inositol phosphates (IPs) formation in Chinese hamster ovary cells expressing the cloned human B2 receptor at concentrations greater than 10 nM and displayed one-tenth of the intrinsic activity of BK. The agonist activity of 22b was selective for the B2 receptor and was inhibited by selective peptide and non-peptide B2 antagonists. On the other hand, 22b strongly suppressed BK-induced IPs formation through the cloned human B2 receptor. Further studies on the key pharmacophore led to identification of a 2-picolyloxy moiety as a powerful agonist switch, leading to the discovery of a potent and efficacious non-peptide B2 agonist, 19a. Successive optimization of the acyl side chain afforded 38, which exhibited full agonist activity on stimulation of IPs formation. Furthermore, this strategy could be applied successfully to the benzimidazole series. The representative 1-(2-picolyl)benzimidazole derivative 47c increased PGE2 production at a 1 muM concentration to the same level as the maximum effect of BK. Thus, we have established the medicinal chemistry modifications required to convert our highly potent non-peptide B 2 antagonists to agonists with potent efficacy.

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Reference:
Phosphine ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate

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An expedient organic photoredox Pschorr reaction has been developed that opens up a synthetic route to 6 H-benzo[ c[chromenes. The process can be performed under mild conditions by using eosin Y as a photoredox catalyst and acetonitrile as the solvent. The diazonium salts can be either preformed or generated in situ from the corresponding amines with t-BuONO. The process is amenable to gram-sale synthesis of 6 H-benzo[ c[chromenes, which can be further transformed into both 6 H-benzo[ c[chromen-6-ones through oxidation or to 6 H-benzo[ c[chromen-6-amine through sp 3 C-H bond amination. The protocol provides an attractive route for the synthesis of a library of 6 H-benzo[ c[chromes.

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Reference:
Phosphine ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate

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The Pschorr cyclization of various arylamines with t-butyl thionitrate under nonaqueous conditions gave the corresponding cyclic products in moderate yields.The same reaction was also found to proceed readily with p-toluenesulfonyl nitrite at room tempoerature.Treatment of o-aminophenyl allyl ether or sulfide with t-butyl thionitrate resulted in the intramolecular Meerwein arylation to the olefinic bond affording 3-chlorochroman or – thiochroman, through the yield was low.The plausible mechanism of the Pschorr cyclization with t-butyl thionitrate is discussed.

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Reference:
Phosphine ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate

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Certain 1H-imidazo[4,5-c]quinolines, 6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolines, 1H-imidazo[4,5-c][1,5]naphthyridines, 6,7,8,9-tetrahydro-1H-imidazo[4,5-c][1,5]naphthyridines, and 1H-imidazo[4,5-c]pyridines substituted at the 1- and 2-positions, pharmaceutical compositions containing these compounds, methods of making the compounds, and methods of use of these compounds as immunomodulators, for inducing cytokine biosynthesis in animals and in the treatment of diseases including viral and neoplastic diseases, are disclosed.

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Reference:
Phosphine ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate

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In an article, published in an article, once mentioned the application of 1079-66-9, Name is Chlorodiphenylphosphine,molecular formula is C12H10ClP, is a conventional compound. this article was the specific content is as follows.category: chiral-phosphine-ligands

There is provided a process for producing an aromatic amine compound having an aralkyloxy or heteroaralkyloxy group, in which an aromatic nitro compound having an aralkyloxy or heteroaralkyloxy group is reacted with hydrogen under mild conditions in accordance with a simple procedure while preventing the removal of aralkyl or heteroaralkyl group and keeping stable the other substituents on the aryl group or heteroaryl group so that the substituent does not take part in the reaction, to selectively reduce only the nitro group. The present invention is directed to a process for producing an aromatic amine compound which comprises reacting an aromatic nitro compound represented by the general formula (1): wherein Ar represents an aryl group or heteroaryl group which may have a substituent, and Z represents a divalent aromatic group which may have a substituent, with hydrogen in the presence of a metal catalyst to obtain an aromatic amine compound represented by the general formula (2): wherein Ar and Z have the meaning as defined above.

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Reference:
Phosphine ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate

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We describe the first total synthesis of the cytotoxic carbazole alkaloid excavatine-A. The carbazole framework was constructed through double C?H bond activation of a diarylamine by using our palladium(II)-catalyzed oxidative cyclization. Treatment of the intermediate 8-hydroxycarbazoles with prenal and different additives led either to pyrano[2,3-a]carbazoles or to [1,4]oxazepino[2,3,4-jk]carbazoles. The pyran annulation was investigated to determine the influence of substitution pattern, additives, and reaction time on the selectivity.

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Reference:
Phosphine ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate