- ASPARAGINE DERIVATIVES AND METHODS OF USE THEREOF
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The present invention relates to compounds of formulas (A) and (I), pharmaceutically acceptable salts thereof, and solvates of any of them, pharmaceutical compositions comprising them, methods of preparation thereof, intermediate compounds useful for the preparation thereof, and methods of treatment or prophylaxis of diseases, in particular cancer, such as colorectal cancer, using these. (A) (I)
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Paragraph 00150-00151
(2021/12/31)
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- COVALENT RAS INHIBITORS AND USES THEREOF
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The disclosure features compounds, or pharmaceutically acceptable salts thereof, alone and in combination with other therapeutic agents, pharmaceutical compositions, and protein conjugates thereof, capable of modulating biological processes including Ras, and their uses in the treatment of cancers.
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Page/Page column 172
(2021/06/04)
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- RAS INHIBITORS
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The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.
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Paragraph 1667-1668
(2021/05/07)
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- Method for preparing 2-methylserine
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The invention relates to a method for preparing 2-methylserine, and mainly solves the technical problem of being long in route, complicated in operation, and not conducive to mass production of the existing synthetic method. The method comprises the following steps: Cbz-chiral alanine and Benzaldehyde dimethyl acetal are reacted under the action of thionyl chloride and zinc chloride, a reaction product is crystallized to obtain an intermediate 1, the intermediate 1 is reacted under cooperation of an alkaline reagent to obtain an intermediate 2, an intermediate 3 is obtained from the intermediate 2 by the action of lithium hydroxide, and the final product 2-methylserine is obtained from the intermediate 3 by palladium carbon catalytic hydrogenolysis. High purity 2-methylserine can be obtained by the method.
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Paragraph 0036
(2019/01/24)
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- CYCLIZED SULFAMOYLARYLAMIDE DERIVATIVES AND THE USE THEREOF AS MEDICAMENTS FOR THE TREATMENT OF HEPATITIS B
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Inhibitors of HBV replication of Formula (I-A), including stereochemically isomeric forms, and salts, hydrates, solvates thereof, wherein Ra to Rd, and R1 to R8 have the meaning as defined herein. The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them and their use, alone or in combination with other HBV inhibitors, in HBV therapy.
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Page/Page column 162; 163
(2017/01/23)
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- Synthesis of 4-hydroxy-2-methylproline derivatives via pyrrolidine ring assembly: chromatographic resolution and diastereoselective synthesis approaches
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4-Hydroxy-2-methylproline diastereomers are successfully prepared without the use of an external chiral auxiliary. Dihydroxylation of the key intermediate 2 resulted in lactone 4 as a mixture of diastereomers in good yield. Mesylation, hydrogenation and c
- Tiwari, Vinay Shankar,Murugula, Raghavendra,Yadav, Shyam Raj,Haq, Wahajul
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p. 865 - 871
(2016/09/02)
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- PEPTIDOMIMETIC COMPOUNDS AND ANTIBODY-DRUG CONJUGATES THEREOF
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This invention relates to peptidomimetic linkers and anti-body drug conjugates thereof, to pharmaceutical compositions containing them, and to their use in therapy for the prevention or treatment of cancer.
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Page/Page column 110; 111
(2015/07/07)
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- Stereoselective Synthesis of (R)-3-Methylthalidomide by Piperidin-2-one Ring Assembly Approach
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A simple and stereoselective synthesis of 3-methylthalidomide, a configurationally stable thalidomide analog, is presented. Herein we describe the synthesis of (R)-3-methylthalidomide starting from (S)-alanine by piperidin-2-one ring assembly approach in high yield and enantiomeric purity without using a chiral auxiliary or reagent. Starting from (R)-alanine, the corresponding (S)-3-methylthalidomide can be prepared using the same methodology. Chirality 27:619-624, 2015.
- Yadav, Shyam Raj,Tiwari, Vinay Shankar,Haq, Wahajul
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p. 619 - 624
(2015/08/25)
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- Design and synthesis of a tetradentate '3-amine-1-carboxylate' ligand to mimic the metal binding environment at the non-heme iron(ii) oxidase active site
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Non-heme iron(ii) oxidases (NHIOs) catalyse a diverse array of oxidative chemistry in Nature. As part of ongoing efforts to realize biomimetic, iron-mediated C-H activation, we report the synthesis of a new 'three-amine-one-carboxylate' ligand designed to
- Dungan, Victoria J.,Ortin, Yannick,Mueller-Bunz, Helge,Rutledge, Peter J.
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scheme or table
p. 1666 - 1673
(2010/07/03)
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- Synthesis and utilization of chiral α-methylated α-amino acids with a carboxyalkyl side chain in the design of novel Grb2-SH2 peptide inhibitors free of phosphotyrosine
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The growth factor receptor-bound protein 2 (Grb2) is an SH2 domain-containing docking module that represents an attractive target for anticancer therapeutic intervention. To improve the potency and bioavailability of the Grb2-SH2 inhibitors, the chiral α-methyl-α-carboxyalkyl amino acid [(α-Me)Aa] was designed to cover dual structural and functional features separately contributed by 1-aminocyclohexanecarboxylic acid (Ac6c) and α-aminoadipic acid (Adi) in position Y + 1. The enantiopure L(or D)-(α-Me)Aa bearing various chain length carboxylalkyl side chain was conveniently synthesized by an optimized oxazolidinone methodology. The incorporation of (S)-(α-Me)Aa into the non-pTyr-containing peptide framework with a 5-amino acid sequence binding motif of X-2-Leu- (3′-substituted-Tyr)0-X+1-Asn really improved the inhibitory activity, affording potent (R)-sulfoxide-bridged cyclic and an open-chain series of pentapeptide inhibitors of Grb2-SH2 domain (IC50 = 1.1-5.8 μM). More significantly, these (α-Me)Aa incorporated peptide inhibitors showed excellent activities in inhibiting the growth of erbB2-dependent MDA-MB-453 tumor cell lines with low micromolar IC50 values, owing to the reduced peptidic nature and absence of pTyr or pTyr mimetics.
- Long, Ya-Qiu,Xue, Ting,Song, Yan-Li,Liu, Zu-Long,Huang, Shao-Xu,Yu, Qiang
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experimental part
p. 6371 - 6380
(2009/10/17)
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- Preparation of diazabicyclo[4.3.0]nonene-based peptidomimetics
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(Chemical Equation Presented) Several functionalized diazabicyclo[4.3.0] nonenes and other heterocycles have been prepared as potential peptidomimetic scaffolds. A novel and efficient method has been developed for the preparation of N-substituted γ-lactam
- Hutton, Craig A.,Bartlett, Paul A.
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p. 6865 - 6872
(2008/02/11)
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- The formation of a crystalline oxazolidin-5-one from (L)-alanine and its use as a chiral template in the practical synthesis of α-substituted alanine esters
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Three different protocols to synthesize oxazolidin-5-ones have been studied with the goal to develop a method to synthesize a diastereomerically pure oxazolidin-5-one. A novel method is reported that uses a dynamic crystallization-induced asymmetric transformation to isolate a single diastereomer of an oxazolidin-5-one in 92% yield on kilogram scale. Alkylation of the oxazolidin-5-one template leads to good-to-excellent yields of N-protected α-substituted alanine esters in >98-99% ee. Schweizerische Chemische Gesellschaft.
- Eriksson, Magnus,Napolitano, Elio,Xu, Jinghua,Kapadia, Suresh,Byrne, Denis,Nummy, Laurence,Grinberg, Nelu,Shen, Sherri,Lee, Heewon,Farina, Vittorio
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p. 566 - 573
(2007/10/03)
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- Potassium trimethylsilanolate induced cleavage of 1,3-oxazolidin-2- and 5-ones, and application to the synthesis of (R)-salmeterol.
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A convenient and efficient method for the cleavage of 1,3-oxazolidin-5-ones and 1,3-oxazolidin-2-ones utilising potassium trimethylsilanolate in tetrahydrofuran is described. The benzyloxycarbonyl-protecting group is readily removed under the reaction conditions, whereas the N-benzoyl group is stable. A synthesis of (R)-salmeterol exploiting the 2-oxazolidinone ring as a protecting group for the ethanolamine moiety is also described.
- Coe, Diane M,Perciaccante, Rossana,Procopiou, Panayiotis A
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p. 1106 - 1111
(2007/10/03)
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- Convergent synthesis of (-)-mirabazole C using a chloroimidazolidium coupling reagent, CIP
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Convergent synthesis of (-)-mirabazole C (1), a tetra thiazoline/thiazole alkaloid isolated from blue-green alga, has been described. The successive thiazoline rings of (-)-mirabazole C were formed by a single-step cyclization mediated by TiCl4 treatment of tripeptide amide 4. Convergent synthesis of the key intermediate 33 derived from three 2-methylcysteine residues was first achieved using a newly developed coupling reagent, 2-chloro-1,3-dimethylimidazolidium hexafluorophosphate (CIP). The effectiveness of CIP for the coupling of α,α-dialkyl amino acids and the reaction pathway of the activation were clarified by the syntheses of model peptides containing an α,α-dimethylamino acid. A practical method of asymmetric synthesis of 2-methylcysteine by alkylation of 2,4-cis-oxazolidinone 23 has also been described.
- Akaji, Kenichi,Kuriyama, Naohiro,Kiso, Yoshiaki
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p. 3350 - 3357
(2007/10/03)
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- Versatile Stereoselective Synthesis of Completely Protected Trifunctional α-Methylated α-Amino Acids Starting from Alanine
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A new route to completely protected α-methylated α-amino acids starting from alanine is described (see Scheme).These derivatives, which are obtained via base-catalyzed opening of the oxazolidinones (2S,4R)- and (2R,4S)-2, can be directly employed in pepti
- Altmann, Eva,Nebel, Kurt,Mutter, Manfred
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p. 800 - 806
(2007/10/02)
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