- THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE
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Provided are methods of treating a cancer characterized by the presence of a mutant allele of IDH1/2 comprising administering to a subject in need thereof a compound described here.
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Page/Page column
(2015/02/19)
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- THERAPEUTICALLY ACTIVE COMPOUNDS AND USE THEREOF
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Provided are therapeutically active compounds and the use in manufacture of medicaments for treating a cancer characterized by the presence of a mutant allele of IDH1.
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Page/Page column 93
(2015/02/19)
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- THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE
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Provided are methods of treating a cancer characterized by the presence of a mutant allele of IDH1/2 comprising administering to a subject in need thereof a compound described here.
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Page/Page column 93
(2015/02/19)
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- HEPATITIS C VIRUS INHIBITORS
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The invention provides compounds of formulas (I) or (II): wherein the variables are defined in the specification, or a pharmaceutically-acceptable salt thereof, that are inhibitors of replication of the hepatitis C virus. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat hepatitis C viral infections, and processes and intermediates useful for preparing such compounds.
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Paragraph 0295; 0296
(2013/11/06)
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- THERAPEUTICALLY ACTIVE COMPOSITIONS AND THEIR METHODS OF USE
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Provided are methods of treating a cancer characterized by the presence of a mutant allele of IDH1/2 comprising administering to a subject in need thereof a compound described here.
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Page/Page column
(2013/07/31)
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- THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE
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Provided are methods of treating a cancer characterized by the presence of a mutant allele of IDH1/2 comprising administering to a subject in need thereof a compound described here.
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Page/Page column 92; 93
(2013/07/31)
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- Carboxymethylproline synthase catalysed syntheses of functionalised N-heterocycles
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The utility of wild-type and variant carboxymethylproline synthases for biocatalysis was demonstrated by preparing functionalised 5-, 6- and 7-membered N-heterocycles from amino acid aldehydes and (alkylated) malonyl-coenzyme A derivatives; the N-heterocycles produced were converted to the corresponding bicyclic β-lactams by a carbapenem synthetase. The Royal Society of Chemistry 2010.
- Hamed, Refaat B.,Mecinovic, Jasmin,Ducho, Christian,Claridge, Timothy D. W.,Schofield, Christopher J.
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supporting information; experimental part
p. 1413 - 1415
(2010/06/12)
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- Synthesis of a new dual metalloprotease inhibitor. I. Diastereoselective alkylation of protected 6-oxopipecolic acid esters
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Diastereoselective methylation of the enolate generated from various protected 6-oxopipecolic acid esters (3aa-3cd) was studied. The protecting groups on the carboxylic acid and amino groups significantly influenced the trans/cis selectivity in the methylation reaction. The optimal substrate (3ca), bearing benzhydryl ester and carbobenzyloxy moieties gave a trans/cis isomer ratio of ca. 4:1. Investigation of the reaction conditions revealed that the reaction solvent, alkylating reagent, and base employed to generate the enolate, were decisive factors for diastereoselectivity. Further optimization of reaction conditions, including the amounts of the reagents and their addition sequence enabled maximization of reaction conversion and minimization of by-products to produce the trans rich 5-methyl-6-oxopipecolic acid ester (4ca) on a large scale.
- Akasaka, Kozo,Akamatsu, Hiroshi,Kimoto, Yuichi,Komatsu, Yuki,Shimizu, Toshikazu,Shimomura, Naoyuki,Tagami, Katsuya,Negi, Shigeto
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p. 1525 - 1531
(2007/10/03)
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- Hydrolytic cleavage of pyroglutamyl-peptide bond. I. The susceptibility of pyroglutamyl-peptide bond to dilute hydrochloric acid
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The susceptibility of the pyroglutamyl-peptide bond in some biologically active peptides, dog neuromedin U-8 fragment (pGlu-Phe-Leu-Phe-Arg-Pro-Arg- OH), human big gastrin fragment (pGlu-Leu-Gly-Pro-OH) and thyrotropin releasing hormone (TRH) fragments (pGlu-His-Pro-OH, pGlu-His-OH), to 1 N HCl under mild conditions and/or at 60°C was studied. It was found that the N- terminal portion of pGlu-peptides is extremely labile to acid hydrolysis, giving not only the ring-opened product of the pyrrolidone moiety of the pGlu residue, but also the cleavage product of the pGlu-peptide linkage. The ring- opening reaction predominated over the cleavage reaction in hydrolysis of the four peptides in 1 N HCl at 60°C. The ring-opening reaction and the cleavage reaction of pGlu-peptide linkage proceeded faster than the cleavage of internal peptide bonds. The rate of hydrolysis was affected by the reaction temperature, and the ring-opening reaction was greatly diminished at 4°C in comparison with the cleavage reaction. Thus, the phenomenon that the pGlu- peptide bond is susceptible to dilute HCl as compared to the other peptide bonds appears to be a general one.
- Hashimoto,Ohki,Sakura
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p. 2068 - 2074
(2007/10/03)
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- Synthesis of Thyrotropin-Releasing Hormone Analogues. 2. Tripeptides Structurally Greatly Differing from TRH with High Central Nervous System Activity
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A new series of thyrotropin-releasing hormone (TRH) analogues, obtained by further modifications of our most potent central nervous system (CNS) stimulating neutral tripeptides at both termini, were synthesized by the pentafluorophenyl ester method and tested for CNS and thyrotropin (TSH) releasing activity.Replacement of pyroglutamic acid by pyro-2-aminoadipic acid, 2-oxoimidazolidine-4-carboxylic acid or γ-butyrolactone-γ-carboxylic acid and that of proline by pipecolic acid, thiazolidine-4-carboxylic acid, or homoproline in 2>- and 2>TRH led to tripeptides structurally widely different from TRH.In spite of this fact, 7 of the 17 analogues (1, 2, 8-10, 16, and 17) have stronger anticataleptic effect than TRH, with negligible or no hormonal potency.The highest CNS activity was achieved when pyroglutamic acid was replaced by pyro-2-aminoadipic acid at the N-terminus .A novel synthesis of L-2-aminoadipic acid suitable for large-scale preparation is also described.
- Szirtes, Tamas,Kisfaludy, Lajos,Palosi, Eva,Szporny, Laszlo
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p. 1654 - 1658
(2007/10/02)
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- Mild and Simple Biomimetic Conversion of Amines to Carbonyl Compounds
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4-Formyl-1-methylpyridinium benzenesulfonate is a convenient reagent for the chemical modification of primary amines to aldehydes and ketones.This method mimics the biological process for transamination reactions with pyridoxal (vitamin b6).As in that process, it involves imine formation, prototropic rearrangement, and hydrolysis.The conditions are extremely mild and are compatible with a large variety of sensitive functional groups.This process provides a simple and a efficient alternative to the somewhat harsher procedures generally employed for such transformations.
- Buckley, Thomas F.,Rapoport, Henry
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p. 4446 - 4450
(2007/10/02)
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- Dehydroabietylammonium salts of 6-oxo-2-piperidinecarboxylic acid
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6-Oxo-2-piperidinecarboxylic acid has been resolved via direct crystallization of pure S-6-oxo-2-piperidinecarboxylic acid dehydroabietylammonium salt from a solvent system consisting of dimethylformamide, cyclohexane and acetone. The S-enantiomer is a required component for making certain tripeptides related to thyrotropin releasing hormone (TRH) which are central nervous system stimulants.
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