Some scientific research about 3-Phenyl-6-chloropyridazine

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2-(3,4-Dichlorophenyl)-N-methyl-N-<2-(1-pyrrolidinyl)-1-substituted-ethyl>acetamides: The Use of Conformational Analysis in the Development of a Novel Series of Potent Opioid kappa Agonists

This paper describes the synthesis of a series of N-<2-(1-pyrrolidinyl)ethyl>acetamides (1), methylated at C1 and/or C2 of the ethyl linking group, and their biological evaluation as opioid kappa agonists.Conformational analysis of corresponding desaryl analogues 2 suggested that only those compounds capable of occupying an energy minimum close to that of the known kappa agonist N-<2-(1-pyrrolidinyl)cyclohexyl>acetamide U-50488 might possess kappa agonist properties.Starting from chiral amino acids, other alkyl and aryl substituents were introduced at C1 of the ethyl-linking moiety, giving compounds capable of adopting the same conformation as U-50488.The most potent of these, 2-(3,4-dichlorophenyl)-N-methyl-N-<(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl>acetamide (8), was 146-fold more active than U-50488 in vitro in the mouse vas deferens model and exhibited potent naloxone-reversible analgesic effects (ED50 = 0.004 mg/kg sc) in an abdominal constriction model.

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POLYCYCLIC TLR7/8 ANTAGONISTS AND USE THEREOF IN THE TREATMENT OF IMMUNE DISORDERS

The present invention relates to compounds of Formula (I) and pharmaceutically acceptable compositions thereof, useful as toll-like receptor 7/8 (TLR7/8) antagonists. In Formula (I), Ring A is aryl or heteroaryl; Ring B is aryl or heteroary; and X is C(R4)2, O, NR4, S, S(R4), or S(R4)2.

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Syntheses of acyclic analogs of didemnin B

The syntheses of three modified peptide fragments of the cyclodepsipeptide didemnin B are reported. The HIP and isostatine (Ist) units of the didemnin B macrocycle were simplified to a Z-alanine residue and the ester linkage (through threonine of the tetrapeptide) was replaced with amide linkages through the amines of glycine. D-alanine and an ethylenediamine linker. The latter permitted the attachment of a N-Me-D-Leu-Pro-Lac moiety to afford analogs 2, 3 and 4 respectively.

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Relaxing substrate specificity in antibody-catalyzed reactions: Enantioselective hydrolysis of N-Cbz-amino acid esters

For a catalytic antibody to be generally useful for organic synthetic chemistry, it must be able to accept a broad range of substrates, yet retain high selectivity. In this work, we propose a hapten design to endow antibody catalysts with two opposing qualities, such as high enantioselectivity and broad substrate specificity. Racemic hapten 2 induced two separate classes of catalytic antibodies to hydrolyze either the L- or D-isomers of N-Cbz-amino acid esters 1. In the kinetic resolution of racemic ester 9, antibodies 7G12 and 3G2 gave 96% ee of L-10 and 94% ee of D-10, respectively. In addition, antibody 7G12 displayed broad substrate specificity, hydrolyzing the L-esters of Ala (1a), Leu (1b), Norleu (1c), Met (1d), Phe (1e), Val (1f), and phenylglycine (1g) with high enantioselectivity. Antibody 3G2 also hydrolyzed the D-isomers of these esters without sacrificing the enantioselectivity. This observation suggests that the use of haptens that fit snugly into the antigen-combining site, and leave the linker moiety outside, is an effective approach for the generation of catalytic antibodies with high selectivity and broad substrate applicability.

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Synthesis of N-urethane protected alpha-aminoalkyl-alpha-cyanomethyl ketones; Application to the synthesis of 3-substituted 5-amino-1H-pyrazole tethered peptidomimetics

The preparation of N-protected amino/peptide alpha-cyanomethyl ketones through cyanation of the corresponding alpha-bromomethyl ketones is described. The utility of the resulting alpha-cyanomethyl ketones in the synthesis of 3-substituted-5-amino-1H-pyrazoles has also been demonstrated. In both steps a wide range of N-protected amino/peptide acids has been employed and the products are obtained in good yield. The enantiomeric purity of both the alpha-cyanomethyl ketones and pyrazoles were confirmed by chiral HPLC analysis of the corresponding Z-protected d- and l-Ala-OH as model substrates. The synthesis of peptide pyrazolecarboxamides is also delineated. Georg Thieme Verlag Stuttgart ¡¤ New York.

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Total synthesis and determination of the absolute configuration of guadinomines B and C2

This article describes the determination of the absolute configurations of the guadinomines, which are novel cyclic guanidyl natural products that are inhibitors of the type III secretion system (TTSS) of bacteria. Any compound that interrupts the TTSS of bacteria is potentially an ideal anti-infectious drug. The reliable asymmetric synthesis of guadinomines has revealed their absolute configurations, which could not have been defined without this synthetic approach. Our report not only describes the asymmetric total synthesis of the title compounds, but also demonstrates the novel concise synthesis of tri-substituted piperazinone cores as optically pure forms. The novel feature of our method is an intramolecular SN2 cyclization that uses PPh 3 and I2 to construct the unique 5membered cyclic guanidine substructure.

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New synthetic routes to optically active alpha-quaternary alpha-aryl amino acid derivatives via the diastereoselective Stevens and Sommelet-Hauser rearrangements

The Stevens rearrangement of N-allylic alpha-aryl amino acid-derived ammonium salts and the Sommelet-Hauser rearrangement of N-benzylic alpha-alkyl amino acid-derived ammonium salts are shown to proceed with remarkably high levels of diastereoselectivity. The methods presented in this work provide new routes to optically active alpha-quaternary alpha-aryl amino acid derivatives. The Royal Society of Chemistry 2008.

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Awesome Chemistry Experiments For 3-Phenyl-6-chloropyridazine

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PS-IIDQ: a supported coupling reagent for efficient and general amide bond formation

Polystyrene-IIDQ, a polymer-supported coupling reagent, was synthesized in three steps from Merrifield resin in 86% overall conversion. This reagent efficiently coupled carboxylic acids to amines in good yields and high purities, required no pre-activation step, and was tolerant of the order of reagent addition. PS-IIDQ was observed to be more efficient than polymer-supported carbodiimides (PS-EDC and PS-DCC) and gave higher yields than HATU for general amide bond formation, including the coupling of anilines and hindered substrates. When evaluated with five carboxylic acids and nine amines (including anilines and secondary amines) PS-IIDQ gave an average isolated yield of 73%.

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Highly enantioselective fluorescent recognition of serine and other amino acid derivatives

The BINOL-amino alcohol compound (S)-4 was found to conduct enantioselective fluorescent recognition of a serine derivative with an unprecedented high ef [enantioselective fluorescent enhancement = (ID – I0)/(IL – I0)] of 12.5. Both (S)-4 and (S)-5 are also found to be highly enantioselective fluorescent sensors for a number of other amino acid derivatives.

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Synthesis and binding properties of peptide receptor

Macrocyclic receptor 2, with an amidopyridine unit as the binding site for carboxylic acid functionally and amide functionality to provide additional hydrogen bonding sites, has been synthesised. Preliminary binding studies with 2 and various peptidic guests are described.

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