- QUINOLINONE DERIVATIVES AS METHIONINE ADENOSYLTRANSFERASE 2A INHIBITORS
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Disclosed herein are certain quinolinone derivatives of Formula (A) that are methionine adenosyltransferase 2A (MAT2A) inhibitors. Also disclosed are pharmaceutical compositions comprising such compounds and methods of treating diseases treatable by inhibition of MAT2A such as cancer, including cancers characterized by reduced or absence of methylthioadenosine phosphorylase (MTAP) activity.
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Paragraph 0242
(2021/12/31)
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- Diazepam hapten, diazepam artificial antigen, and preparation method and application thereof
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The invention discloses a diazepam hapten, a diazepam artificial antigen as well as a preparation method and application thereof. The diazepam artificial antigen provided by the invention is an antigen obtained by coupling the diazepam hapten shown as a formula I with a carrier protein. The diazepam artificial antigen provided by the invention is simple in synthesis method, high in purity and highin yield, and has important value in preparation of diazepam antibodies and detection of diazepam drug residues.
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Paragraph 0026; 0030
(2020/08/25)
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- Structure-Activity Relationship Studies of Retro-1 Analogues against Shiga Toxin
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High-throughput screening has shown that Retro-1 inhibits ricin and Shiga toxins by diminishing their intracellular trafficking via the retrograde route, from early endosomes to the Golgi apparatus. To improve the activity of Retro-1, a structure-activity relationship (SAR) study was undertaken and yielded an analogue with a roughly 70-fold better half-maximal effective concentration (EC50) against Shiga toxin cytotoxicity measured in a cell protein synthesis assay.
- Abdelkafi, Hajer,Michau, Aurélien,Pons, Valérie,Ngadjeua, Flora,Clerget, Alexandra,Ait Ouarab, Lilia,Buisson, David-Alexandre,Montoir, David,Caramelle, Lucie,Gillet, Daniel,Barbier, Julien,Cintrat, Jean-Christophe
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p. 8114 - 8133
(2020/09/21)
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- COMPOSITIONS AND METHODS FOR REDUCING TACTILE DYSFUNCTION, ANXIETY, AND SOCIAL IMPAIRMENT
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The present invention provides novel peripherally-restricted benzodiazepines with reduced blood brain barrier permeability and methods of use thereof for reducing tactile dysfunction, social impairment, and anxiety in a subject diagnosed with Autism Spectrum Disorder, Rett syndrome, Phelan McDermid syndrome, or Fragile X syndrome.
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Page/Page column 21; 43
(2020/10/20)
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- Improved and scalable methods for the synthesis of midazolam drug and its analogues using isocyanide reagents
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Abstract: In this research, two improved and scalable methods for the synthesis of midazolam and its analogues have been described. Midazolam has been synthesized using isocyanide reagents in satisfactory yield. In this methodology, imidazobenzodiazepine intermediates can be easily prepared via an improved process. One-pot condensation of benzodiazepines with mono-anion of tosylmethyl isocyanide or ethyl isocyanoacetate under mild condition led to formation of imidazobenzodiazepine. In the first method, tosylmethyl isocyanide (Tos-MIC) is used and the number of synthetic steps are decreased in comparison to previous report. In the second method, ethyl isocyanoacetate which is commonly used for the synthesis of some imidazobenzodiazepines, is consumed to generate midazolam. The latter, a relatively different method for the synthesis of midazolam analogues has been reported. Graphical abstract: [Figure not available: see fulltext.].
- Taghizadeh, Mohammad Javad,malakpouri, Gholam reza,Javidan, Abdollah
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p. 785 - 794
(2019/03/27)
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- Effect of substituents on the configurational stability of the stereogenic nitrogen in metal(II) complexes of α-amino acid Schiff bases
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Herein, we report a general method for quantitative measurement of the configurational stability of the stereogenic nitrogen coordinated to M (II) in the corresponding square planar complexes. This stereochemical approach is quite sensitive to steric and electronic effects of the substituents and shown to work well for Ni(II), Pd(II), and Cu(II) complexes. Structural simplicity of the compounds used, coupled with high sensitivity and reliability of experimental procedures, bodes well for application of this approach in evaluation of chemical stability and stereochemical properties of newly designed chiral ligands for general asymmetric synthesis of tailor-made amino acids.
- Mei, Haibo,Jean, Marion,Albalat, Muriel,Vanthuyne, Nicolas,Roussel, Christian,Moriwaki, Hiroki,Yin, Zizhen,Han, Jianlin,Soloshonok, Vadim A.
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supporting information
p. 401 - 409
(2019/04/01)
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- Second-order asymmetric transformation and its application for the practical synthesis of α-amino acids
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We report a discovery of a new rimantadine [1-(1-adamantyl)ethanamine]-derived chiral ligand and its application for the preparation of α-amino acids using the second-order asymmetric transformation approach. The operational ease of experimental procedures coupled with excellent chemical yields and stereochemical outcome suggests some potential synthetic generality of this approach.
- Takeda, Ryosuke,Kawamura, Akie,Kawashima, Aki,Sato, Tatsunori,Moriwaki, Hiroki,Izawa, Kunisuke,Abe, Hidenori,Soloshonok, Vadim A.
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p. 4968 - 4972
(2018/07/25)
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- METHOD FOR SYNTHESIZING OPTICALLY ACTIVE a-AMINO ACID USING CHIRAL METAL COMPLEX COMPRISING AXIALLY CHIRAL N-(2-ACYLARYL)-2-[5,7-DIHYDRO-6H-DIBENZO[c,e]AZEPIN-6-YL] ACETAMIDE COMPOUND AND AMINO ACID
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Objects of the present invention are to provide an industrially applicable method for producing an optically active α-amino acid in high yield and in a highly enantioselective manner, to provide a simple production method of an optically active α,α-disubstituted α-amino acid, and to provide an intermediate useful for the above production methods of an optically active α-amino acid and an optically active α,α-disubstituted α-amino acid. The present invention provides a production method of an optically active α-amino acid or a salt thereof, the production method comprising introducing a substituent into the α carbon in the α-amino acid moiety of a metal complex represented by the following Formula (1): by an alkylation reaction, an aldol reaction, the Michael reaction, or the Mannich reaction, and releasing an optically pure α-amino acid enantiomer or a salt thereof by acid decomposition of the metal complex.
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Paragraph 0271-0273
(2016/05/10)
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- Advanced asymmetric synthesis of (1R,2S)-1-amino-2-vinylcyclopropanecarboxylic acid by alkylation/cyclization of newly designed axially chiral Ni(II) complex of glycine Schiff base
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Asymmetric synthesis of (1R,2S)-1-amino-2-vinylcyclopropanecarboxylic acid (vinyl-ACCA) is in extremely high demand due to the pharmaceutical importance of this tailor-made, sterically constrained α-amino acid. Here we report the development of an advanced procedure for preparation of the target amino acid via two-step SN2 and SN2′ alkylation of novel axially chiral nucleophilic glycine equivalent. Excellent yields and diastereoselectivity coupled with reliable and easy scalability render this method of immediate use for practical synthesis of (1R,2S)-vinyl-ACCA.
- Kawashima, Aki,Shu, Shuangjie,Takeda, Ryosuke,Kawamura, Akie,Sato, Tatsunori,Moriwaki, Hiroki,Wang, Jiang,Izawa, Kunisuke,Acea, Jos Luis,Soloshonok, Vadim A.,Liu, Hong
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p. 973 - 986
(2016/04/04)
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- AXIAL-ASYMMETRIC N-(2-ACYLARYL)-2-[5, 7-DIHYDRO-6H-DIBENZO [C, E] AZEPINE-6-YL] ACETAMIDE COMPOUND AND CHIRALITY CONVERSION METHOD FOR A-AMINO ACID USING SAME
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An object of the present invention is to provide a method for producing an optically active amino acid in high yield and in a highly enantioselective manner, which method has fewer restrictions on the material that can be used as the substrate, and to provide, among others, a compound useful as a chiral auxiliary for the method. The present invention provides an N-(2-acylaryl)-2-[5,7-dihydro-6H-dibenzo[c,e]azepin-6-yl]ac etamide compound represented by Formula (1): or a salt thereof, or a metal complex represented by Formula (3) :
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Paragraph 0115; 0116
(2015/11/27)
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- METHOD FOR SYNTHESIZING OPTICALLY ACTIVE α-AMINO ACID USING CHIRAL METAL COMPLEX COMPRISING AXIALLY CHIRAL N-(2-ACYLARYL)-2-[5,7-DIHYDRO-6H-DIBENZO[c,e]AZEPIN-6-YL]ACETAMIDE COMPOUND AND AMINO ACID
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Objects of the present invention are to provide an industrially applicable method for producing an optically active ±-amino acid in high yield and in a highly enantioselective manner, to provide a simple production method of an optically active ±,±-disubstituted ±-amino acid, and to provide an intermediate useful for the above production methods of an optically active ±-amino acid and an optically active ±,±-disubstituted ±-amino acid. The present invention provides a production method of an optically active ±-amino acid or a salt thereof, the production method comprising introducing a substituent into the ± carbon in the ±-amino acid moiety of a metal complex represented by the following Formula (1): by an alkylation reaction, an aldol reaction, the Michael reaction, or the Mannich reaction, and releasing an optically pure ±-amino acid enantiomer or a salt thereof by acid decomposition of the metal complex.
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Paragraph 0436-0438
(2016/11/17)
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- Chemical Dynamic Thermodynamic Resolution and S/R Interconversion of Unprotected Unnatural Tailor-made α-Amino Acids
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Described here is an advanced, general method for purely chemical dynamic thermodynamic resolution and S/R interconversion of unprotected tailor-made α-amino acids (α-AAs) through intermediate formation of the corresponding nickel(II)-chelated Schiff bases. The method features virtually complete stereochemical outcome, broad substrate generality (35 examples), and operationally convenient conditions allowing for large-scale preparation of the target α-AAs in enantiomerically pure form. Furthermore, the new type of nonracemizable axially chiral ligands can be quantitatively recycled and reused, rendering the whole process economically and synthetically attractive.
- Wang, Shuni,Zhou, Shengbin,Wang, Jiang,Nian, Yong,Kawashima, Aki,Moriwaki, Hiroki,Ace?a, José L.,Soloshonok, Vadim A.,Liu, Hong
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p. 9817 - 9830
(2015/11/03)
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- NH-type of chiral Ni(ii) complexes of glycine Schiff base: Design, structural evaluation, reactivity and synthetic applications
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The work being reported here deals with the design of a new type of "N-H" Ni(ii) complexes of glycine Schiff bases and study general aspects of their reactivity. It was confirmed that the presence of NH function in these Ni(ii) complexes does not interfere with the homologation of the glycine residue, rendering these derivatives of high synthetic value for the general synthesis of α-amino acids. In particular, the practical application of these NH-type complexes was demonstrated by asymmetric synthesis of various-substituted pyroglutamic acids via Michael addition reactions with chiral Michael acceptors.
- Bergagnini, MacKenzie,Fukushi, Kazunobu,Han, Jianlin,Shibata, Norio,Roussel, Christian,Ellis, Trevor K.,Acena, Jose Luis,Soloshonok, Vadim A.
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p. 1278 - 1291
(2014/03/21)
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- Chemical dynamic kinetic resolution and S/R interconversion of unprotected α-amino acids
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Reported herein is the first purely chemical method for the dynamic kinetic resolution (DKR) of unprotected racemic α-amino acids (α-AAs), a method which can rival the economic efficiency of the enzymatic reactions. The DKR reaction principle can be readily applied for S/R interconversions of α-AAs, the methodological versatility of which is unmatched by biocatalytic approaches. The presented process features a virtually complete stereochemical outcome, fully recyclable source of chirality, and operationally simple and convenient reaction conditions, thus allowing its ready scalability. A quite unique and novel mode of the thermodynamic control over the stereochemical outcome, including an exciting interplay between axial, helical, and central elements of chirality is proposed. A new player for DKR: Dynamic kinetic resolution of α-amino acids has been achieved upon complexation with nickel(II) and a chiral ligand derived from optically active bis(naphthyl)amine under thermodynamic control, thus affording excellent diastereoselectivities and chemical yields. The S to R interconversion of α-amino acids is also described.
- Takeda, Ryosuke,Kawamura, Akie,Kawashima, Aki,Sato, Tatsunori,Moriwaki, Hiroki,Izawa, Kunisuke,Akaji, Kenichi,Wang, Shuni,Liu, Hong,Ace?a, José Luis,Soloshonok, Vadim A.
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supporting information
p. 12214 - 12217
(2016/02/18)
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- Design and synthesis of (S)- and (R)-α-(phenyl)ethylamine-derived NH-type ligands and their application for the chemical resolution of α-amino acids
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This work presents the first chemical approach for the resolution of α-amino acids offering the following advantages: (1) The specially designed resolving reagent is derived from α-(phenyl)ethylamine, the most inexpensive chiral auxiliary, which can be re
- Takeda, Ryosuke,Kawamura, Akie,Kawashima, Aki,Moriwaki, Hiroki,Sato, Tatsunori,Acena, Jose Luis,Soloshonok, Vadim A.
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p. 6239 - 6249
(2014/08/05)
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