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A series of amino acid ester prodrugs of the dual VEGFR-2/FGFR-1 kinase inhibitor 1 (BMS-540215) was prepared in an effort to improve the aqueous solubility and oral bioavailability of the parent compound. These prodrugs were evaluated for their ability to liberate parent drug 1 in in vitro and in vivo systems. The L-alanine prodrug 8 (also known as brivanib alaninate/BMS-582664) was selected as a development candidate and is presently in phase II clinical trials.

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In nonpolar solvents, the cyclic hexapeptide 2, which comprises alternating D-alpha-amino and D-alpha-aminoxy acids, adopts a C3-symmetric conformation with alternating eight (N-O turns)- and seven (gamma turns)-membered-ring hydrogen bonds. A series of anion-binding studies has suggested that 2 can function as an effective anion receptor that not only displays a high selectivity for chloride ions, but also the capability to extract chloride ions from aqueous solutions into organic phases.

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The synthesis and biological activity of four novel analogues of the cytostatic and antimitogenic agents chlamydocin and HC-toxin are reported in which the natural products’ reactive epoxy ketone side-chain moiety is replaced by a chloromethyl or a diazomethyl ketone functionality, but the respective 12-membered cyclic tetrapeptide ring systems are retained.Syntheses of the linear tetrapeptide sequences were, in each case, achieved by conventional methodology and designed such that cyclization would be onto proline.The use of suitably protected L-2-aminosuberic acid (Asu) enabled the ready assimilation of the desired chloromethyl and diazomethyl ketone functionalities after cyclization.Cyclization was accomplished by using bis(2-oxo-3-oxazolidinyl)phosphinic chloride (BOP-Cl).Yields of cyclic product were comparable to or, in the case of the HC-toxin ring system, better than those previously reported.Liberation of the Asu-side-chain acid and manipulation to the required functionalities via mixed anhydride to the diazomethyl ketone and quenching with HCl to yield the chloromethyl ketone was achieved in excellent yield for the HC-toxin analogues but in only moderate yield for the chlamydocin analogue.The antimitogenic activities of HC-toxin chloromethyl ketone (IC50 = 30-40 ng/mL) and chlamydocin chloromethyl ketone (IC50 = 3-10 ng/mL) were found to be 3-4-fold lower than those of the natural products themselves.The diazomethyl ketone analogue of HC-toxin was found to be inactive (IC50 > 2000 ng/mL).A modification of the HC-toxin peptide ring system, 3-HC-toxin chloromethyl ketone was found not to be a more active analogue (IC50 = 40-100 ng/mL).The nature of the putative target molecule, the binding interactions of the various analogues and the contribution of rate of inhibition toward activity are briefly discussed.The chloromethyl ketones herein reported constitute the most potent synthetic antimitogenic cyclic tetrapeptide analogues yet designed.

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Ten peptides of the general formula A-Phe-Lys-X where A = H, H-D-Val, H-L-Val, H-D-Ala, H-L-Ala and X = OH, NH2 were obtained and tested for their antiplasmin activity with the use of amidolytic test.

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The synthesis of the stereoisomeric esters of L- and D-N-benzoylalanine and L- and D-N-benzoylalaninol is described. – Keywords: N-Benzoylalaninyl-N’-benzoylalaninate, Stereoisomeric Esters, 1H NMR Data, 13C NMR Data, CD Data

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The modular synthesis of a novel pseudopeptide scaffold based on a bis(thiourea)hydrazide motif is reported. This compound class is designed to display “amphifinity”, i.e. association with a peptide strand on one but not the other face of the scaffold, and hence could potentially inhibit beta-sheet aggregation.

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Four isomers of the L-aspartyl-D-alanine fenchyl esters were prepared as potential peptide sweeteners. L-Aspartyl-D-alanine (+)-alpha-fenchyl ester and L-aspartyl-D-alanine (-)-beta-fenchyl ester showed sweetness with potencies 250 and 160 times higher than that of sucrose, respectively. In contrast, L-aspartyl-D-alanine (+)-beta-fenchyl ester and L-aspartyl-D-alanine (-)-alpha-fenchyl ester had the highest sweetness potencies at 5700 and 1100 times that of sucrose, respectively. In particular, L-aspartyl-D-alanine (-)-alpha-fenchyl ester had an excellent sweetness quality, but L-aspartyl-D-alanine (+)-beta-fenchyl ester did not have an excellent quality of sweetness because it displayed an aftertaste caused by the strong sweetness.

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In homogeneous catalysis, the catalyst is in the same phase as the reactant. The number of collisions between reactants and catalyst is at a maximum.In a patent, 20375-65-9, name is 3-Phenyl-6-chloropyridazine, introducing its new discovery. Recommanded Product: 3-Phenyl-6-chloropyridazine

The total synthesis of (-)-actinobolin 3, an antipode of the natural product, starting from d-glucose is described. A three-component coupling reaction of functionalized cyclohexenone (+)-6 derived from d-glucose by way of Ferrier’s carbocyclization reaction, with vinyl cuprate and 2-alkoxypropanal 7 effectively constructed the carbon framework of 3 in a highly stereoselective manner. In an aldol process of the three-component coupling reaction, stereochemical control (chelation and Felkin-Anh conditions) was achieved by the choice of the protecting groups of a hydroxy function in 2-hydroxypropanal and the reaction solvents. The formal synthesis of the natural enantiomer, (+)-actinobolin 1, starting from d-glucose was also accomplished.

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A library of iminolactones was prepared by esterification of several 2-hydroxyketones with a number of N-protected d- and l-alpha-amino acids. Some of the hydroxyketones were of terpenoid origin while others were obtained via synthesis. After N-deprotection of the intermediate esters, the free amines spontaneously underwent condensation with the ketone to form iminolactones. Esters of (1S,2S,5S)-2-hydroxypinan-3-one with both d- and l-alpha-amino acids were partially epimerized at the alpha-carbon atom to give a diastereomeric ester mixture. Only iminolactones of l-amino acids were formed after cyclization of (1S,2S,5S)-2-hydroxypinan-3-one, and correspondingly only d-amino acid iminolactones were formed after reaction with (1R,2R,5R)-2-hydroxypinan-3-one. The protocol thus enables inversion of the absolute configuration of amino acids. Some members of the prepared library of iminolactones displayed significant anti-proliferative effects toward three cancer cell lines (EL4, MCF7, PC3) with insignificant effect on non-malign cell lines (McCoy, MCF10A, NIH3T3). Thus, iminolactones appear to be potential lead structures for preparation of drugs selectively affecting proliferation of malign cell lines.

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The peptide compound represented by the formula: STR1 which is useful as a germicide or disinfectant, is produced by reducing a compound of the formula: STR2 wherein Y is amino group which may optionally be protected; R1 is hydrogen or protective group; and R2 is hydrogen or protective group; and subjecting the reduction product compound to deprotection reaction when required. A compound of the formula: STR3 wherein Z is amino group which may optionally be protected; R1 is hydrogen or protective group; and R2 is hydrogen or protective group, is a useful as intermediate for production of the first-mentioned compound.

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Pyridazine – Wikipedia,
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