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N-But-3-enyl-alpha- and beta-amino acids can be prepared by cleaving 1,3-oxazolidin-5-ones and 1,3-oxazinan-6-ones in the presence of allylsilanes and boron trifluoride etherate at room temperature in good to excellent yields. Georg Thieme Verlag Stuttgart.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N2762 – PubChem

 

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Crystal structures of two vancomycin complexes with phosphate and N-acetylD-Ala (AcDA) were determined. Each complex involves two crystallographically independent vancomycin molecules (V1 and V2) in the asymmetric unit, which form a usually observed back-to-back arranged vancomycin dimer V1V2 with two disaccharide chains packed in a head-to-head manner, but only one of the two ligand-binding sites is occupied. Comparison of the published crystal structures of low-affinity (small in molecular size) ligand complexes of vancomycin with high-affinity (large) ligand complexes reveals that when the high-affinity ligand binds, three structural factors (hydrogen-bonding interactions between the two peptide-backbones and hydrophobic intra-dimer sugarring and ring (face)ring (edge) interactions) work to enhance the stabilization of the back-to-back dimer-interface, an important factor that is believed to promote antibacterial activity. It has also been revealed, by examining the high-affinity ligand complexes (including N-acetylDAlaD-Ala), that sugarligand interaction could cause different affinities of the two halves of the dimer; this is a factor responsible for the failure of the ligand binding to V1 in the AcDA complex. Possible scenarios for the formation of vancomycin complexes with low-affinity as well as high-affinity ligands are presented.

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Pyridazine – Wikipedia,
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In this letter we report the design and synthesis of a series of plasmin inhibitors, which share the amino acid-based linker with limited free rotation between the hydantoin moiety and the benzimidazole scaffold. Our studies led to potent plasmin inhibitors and yielded important new insights into their structure-activity relationship for binding to the active site of plasmin.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N2757 – PubChem

 

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Disclosed herein, inter alia, are compounds and methods of use thereof for the modulation of CCR4 activity.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N2554 – PubChem

 

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Each amino acid in a peptide contributes three atom units to main-chains, hence natural cyclic peptides can be 9, 12, 15, …. i.e. 3n membered-rings, where n is the number of amino acids. Cyclic peptides that are 9 or 12-membered ring compounds tend to be hard to prepare because of strain, while their one amino acid homologs (15-membered cyclic pentapeptides) are not conformationally homogeneous unless constrained by strategically placed proline or d-amino acid residues. We hypothesized that replacing one genetically encoded amino acid in a cyclic tetrapeptide with a rigid beta-amino acid would render peptidomimetic designs that rest at a useful crossroads between synthetic accessibility and conformational rigidity. Thus this research explored non-proline containing 13-membered ring peptides 1 featuring one anthranilic acid (Anth) residue. Twelve cyclic peptides of this type were prepared, and in doing so the viability of both solution- and solid-phase methods was demonstrated. The library produced contained a complete set of four diastereoisomers of the sequence 1aaf (i.e. cyclo-AlaAlaPheAnth). Without exception, these four diastereoisomers each adopted one predominant conformation in solution; basically these conformations feature amide N-H vectors puckering above and below the equatorial plane, and approximately oriented their N-H atoms towards the polar axis. Moreover, the shapes of these conformers varied in a logical and predictable way (NOE, temperature coefficient, D/H exchange, circular dichroism). Comparisons were made of the side-chain orientations presented by compounds 1aaa in solution with ideal secondary structures and protein-protein interaction interfaces. Various 1aaa stereoisomers in solution present side-chains in similar orientations to regular and inverse gamma-turns, and to the most common beta-turns (types I and II). Consistent with this, compounds 1aaa have a tendency to mimic various turns and bends at protein-protein interfaces. Finally, proteolytic- and hydrolytic stabilities of the compounds at different pHs indicate they are robust relative to related linear peptides, and rates of permeability through an artificial membrane indicate their structures are conducive to cell permeability.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N2770 – PubChem

 

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Synthesis and pharmacological properties of hydrazide, methylamide, 2-aminoethylamide, dimethylamide and butylamide of 2-Leu-enkephalin are described.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N2633 – PubChem

 

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The first synthetic approach towards D-Phe-D-allo-Thr-D-Ala-L-Alanilol-O-(3,4-di-O-Me-Rhap), the glycolipid of C-mycoside is described.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N2635 – PubChem

 

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A novel efficient asymmetric hydrogenation (AH) process was developed for the preparation of (R)-1-(3,5-bis(trifluoromethyl)phenyl)ethanol (3), using a catalyst Ru/(4R,5R)-(+)-4,5-bis(diphenylphosphinomethyl)-2,2-dimethyl-1,3-dioxoane-(R,R-Diop)-2R-(alpha-methylmethanamine)-4,7-dimethyl-1H-benzo[d]imidazole (R-D-Me-BIMAH) in toluene in the presence of potassium t-butoxide. Various hydrogenation parameters, such as ligand, solvent, and substrate-to-catalyst (S/C) ratio, were investigated. The hydrogenation was carried out for four times on a 5 kg scale at 30 atm and 25 C with S/C of 20000 with an enantiomeric excess of >89%.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N2771 – PubChem

 

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Homochiral (alphaMe)Leu/Ala and Leu/Ala model peptides were synthesized by solution methods and fully characterized.A solution conformational analysis of the tripeptides was carried out using FT-IR absorbtion and 1H NMR.The crystal-state structure of Z-D-(alphaMe)Leu-(D-Ala)2-OMe monohydrate was resolved by X-ray diffraction.The results obtained support the conclusion that the tendency of the non-coded (alphaMe)Leu residue to fold into beta-bends and helical structures is markedly higher than that of its unmethylated protein counterpart (Leu).

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Pyridazine – Wikipedia,
Pyridazine | C4H4N2666 – PubChem

 

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N-Terminal tetrapeptide analogs of fibrin alpha-chain were synthesized by the solution method using a new active ester, the ester of the oxime of p-nitroacetophenone, and by the solid-phase method. Their inhibitory effects on fibrinogen/thrombin clotting were examined. Of the synthetic peptides, amide analogs of Gly-Pro-Arg-Pro exhibited a more potent inhibitory effect.

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Reference:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2669 – PubChem