- Synthesis of a Precursor of the Antiviral Agent A-315675
-
Ethyl 2-(acetylamino)-3-methoxy-3-methylhexanoate, a key precursor of the known pyrrolidine antiviral agent A-315675, was synthesized starting with the readily available acetoacetic ester.
- Egorov,Gimalova
-
p. 241 - 244
(2019/05/01)
-
- Rhodium-catalyzed asymmetric hydrogenation of tetrasubstituted β-acetoxy-α-enamido esters and efficient synthesis of droxidopa
-
A rhodium-catalyzed asymmetric hydrogenation of challenging tetrasubstituted β-acetoxy-α-enamido esters was developed, giving chiral β-acetoxy-α-amido esters in high yields with excellent enantioselectivities (up to >99% ee). The products could be easily transformed to β-hydroxy-α-amino acid derivatives which are valuable chiral building blocks and a novel route for the synthesis of droxidopa was also developed.
- Guan, Yu-Qing,Gao, Min,Deng, Xu,Lv, Hui,Zhang, Xumu
-
supporting information
p. 8136 - 8139
(2017/07/24)
-
- Hydrogenolysis of geminal diazides
-
The complete hydrogenolysis of compounds containing the geminal diazido functionality is described. Using hydrogen over palladium on charcoal, the diazides are reduced, and primary amines are obtained. For example, aminomalonates and glycines are generated in a straightforward manner. A protocol that provides direct access to acetylated amines derived from 2-amino-1,3-diketones in good to excellent yields, via hydrogenation in the presence of acetic anhydride, is also presented.
- Biallas, Phillip,Kirsch, Stefan F.
-
supporting information
p. 4209 - 4211
(2017/10/06)
-
- HETEROCYCLICALLY SUBSTITUTED TRIFLUOROMETHYLPYRIMIDINONES AND THEIR USE
-
The present application relates to novel heterocyclically substituted 6-(trifluoromethyl)pyrimidin-4(3H)-one derivatives, to processes for their preparation, to their use alone or in combinations for the treatment and/or prevention of diseases, and to their use for preparing medicaments for the treatment and/or prevention of diseases, in particular for treatment and/or prevention of cardiovascular, renal, inflammatory and fibrotic diseases.
- -
-
Paragraph 0212
(2017/02/24)
-
- Nonpeptidic Selective Inhibitors of the Chymotrypsin-Like (β5 i) Subunit of the Immunoproteasome
-
Elevated expression of the immunoproteasome has been associated with autoimmune diseases, inflammatory diseases, and various types of cancer. Selective inhibitors of the immunoproteasome are not only scarce, but also almost entirely restricted to peptide-based compounds. Herein, we describe nonpeptidic reversible inhibitors that selectively block the chymotrypsin-like (β5i) subunit of the human immunoproteasome in the low micromolar range. The most potent of the reversibly acting compounds were then converted into covalent, irreversible, nonpeptidic inhibitors that retained selectivity for the β5i subunit. In addition, these inhibitors discriminate between the immunoproteasome and the constitutive proteasome in cell-based assays. Along with their lack of cytotoxicity, these data point to these nonpeptidic compounds being suitable for further investigation as β5i-selective probes for possible application in noncancer diseases related to the immunoproteasome.
- Sosi?, Izidor,Gobec, Martina,Brus, Boris,Knez, Damijan,?ivec, Matej,Konc, Janez,Le?nik, Samo,Ogrizek, Mitja,Obreza, Ale?,?igon, Du?an,Jane?i?, Du?anka,Mlinari?-Ra??an, Irena,Gobec, Stanislav
-
supporting information
p. 5745 - 5748
(2016/05/09)
-
- PSORALEN DERIVATIVES AS NON-PEPTIDIC INHIBITORS OF CHYMOTRYPSIN-LIKE ACTIVITY OF THE IMMUNOPROTEASOME
-
This invention relates to new inhibitors of chymothrypsin-like activity of the immunoproteasome (inhibitors of β5? or LMP7 subunit) with the general formula (I), where substituents are described in patent description. Compounds can be in the form of pure enantiomers or as racemic mixtures, or in the form of pharmaceutically acceptable salts. The present invention relates to the use of these inhibitors for the treatment of diseases where immunoproteasome activity is increased.
- -
-
Paragraph 0165; 0166; 0167; 0168
(2016/10/11)
-
- HETEROCYCLIC SUBSTITUTED TRIFLUOROMETHYL PYRIMIDINONES AND THEIR USE
-
The present application relates to novel heterocyclically substituted 6-(trifluoromethyl)pyrimidin-4(3H)-one derivatives, to processes for their preparation, to their use alone or in combinations for the treatment and/or prevention of diseases, and to their use for preparing medicaments for the treatment and/or prevention of diseases, in particular for treatment and/or prevention of cardiovascular, renal, inflammatory and fibrotic diseases.
- -
-
Paragraph 0514
(2016/10/04)
-
- METHOD FOR PREPARING (2RS)-AMINO-(3S)-HYDROXY-BUTYRIC ACID AND ITS DERIVATIVES
-
The present invention relates to a method for easily preparing (2RS)-amino-(3S)-hydroxy-butyric acid, which is a chiral amino acid, in a high yield and a high purity using a chemical synthesis and enzymatic reduction reaction; an intermediate therefor; and a method for preparing the intermediate.
- -
-
-
- Site-selective solid phase synthesis of carbonylated peptides
-
Abstract The aim of our research was to design an efficient method for the solid phase synthesis of carbonylated peptides. For this purpose, we designed and synthesized a fully protected derivative Fmoc-amino(2,5,5-trimetyhyl-1,3-dioxolan-2-yl)acetic acid
- Waliczek, Mateusz,Kijewska, Monika,Stefanowicz, Piotr,Szewczuk, Zbigniew
-
p. 1353 - 1365
(2015/06/16)
-
- Ti(iv)-catalyzed cascade synthesis of tetrahydrofuro[3,2-d]oxazole from arene-1,4-diones
-
A tetrahydrofuro[3,2-d]oxazole scaffold was synthesized efficiently and stereoselectively. The tandem ionic hydrogenation, ketalization, and intramolecular cyclization of arene-1,4-diones with a combination of TiCl4/Et3SiH give facile access to tetrahydrofuro[3,2-d]oxazole derivatives in good yields at room temperature.
- Li, Gang,Li, Li,Huang, Haihong,Yin, Dali
-
p. 4418 - 4421
(2015/04/14)
-
- NOVEL ARYLPIPERAZINE-CONTAINING IMIDAZOLE 4-CARBOXAMIDE DERIVATIVES AND PHARMACEUTICAL COMPOSITION COMPRISING SAME
-
A novel arylpiperazine-containing imidazole 4-carboxamide derivative or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising the same as an active ingredient for preventing or treating a depressive disorder are provided.
- -
-
Page/Page column 31; 47
(2011/02/24)
-
- Design and synthesis of novel arylpiperazine derivatives containing the imidazole core targeting 5-HT2A receptor and 5-HT transporter
-
Serotonin antagonist reuptake inhibitor (SARI) drugs that block both 5-HT2 receptors and the serotonin transporters have been developed. The human 5-HT2A/2C receptor has been implicated in several neurological conditions, and potent
- Seo, Hee Jeong,Park, Eun-Jung,Kim, Min Ju,Kang, Suk Youn,Lee, Suk Ho,Kim, Hyun Jung,Lee, Ki Nam,Jung, Myung Eun,Lee, Minwoo,Kim, Mi-Soon,Son, Eun-Jung,Park, Woo-Kyu,Kim, Jeongmin,Lee, Jinhwa
-
experimental part
p. 6305 - 6318
(2011/11/06)
-
- Amino-Containing Compounds Which Inhibit Memapsin 2 Beta-Secretase Activity and Methods of Use Thereof
-
The present invention provides novel beta-secretase inhibitors and methods for their use, including methods of treating of Alzheimer's disease.
- -
-
Page/Page column 20
(2008/12/05)
-
- Pd-catalyzed enantioselective synthesis of quaternary α-amino acid derivatives using a phenylalanine-derived P-chirogenic diaminophosphine oxide
-
A Pd-catalyzed enantioselective synthesis of quaternary α-amino acid derivatives using a phenylalanine-derived P-chirogenic diaminophosphine oxide is described. Asymmetric allylic substitution using acyclic β-keto esters with a nitrogen functional group at the α-carbon as prochiral nucleophiles proceeded in the presence of 5 mol % of Pd catalyst, 10 mol % of chiral diaminophosphine oxide 1j, BSA, and appropriate additives, affording the corresponding quaternary α-amino acid derivatives in excellent yield and in up to 92% ee.
- Nemoto, Tetsuhiro,Harada, Teisuke,Matsumoto, Takayoshi,Hamada, Yasumasa
-
p. 6304 - 6307
(2008/02/10)
-
- Design, synthesis and X-ray structure of protein-ligand complexes: Important insight into selectivity of memapsin 2 (β-secretase) inhibitors
-
Structure-based design, synthesis, and X-ray structure of protein-ligand complexes of memapsin 2 are described. The inhibitors are designed specifically to interact with S2- and S3-active site residues to provide selectivity over mem
- Ghosti, Arun K.,Kumaragurubaran, Nagaswamy,Hong, Lin,Lei, Hui,Hussain, Khaja Azhar,Liu, Chun-Feng,Devasamudram, Thippeswamy,Weerasena, Vajira,Turner, Robert,Koelsch, Gerald,Bilcer, Geoffrey,Tang, Jordan
-
p. 5310 - 5311
(2007/10/03)
-
- BICYCLIC COMPOUNDS WHICH INHIBIT BETA-SECRETASE ACTIVITY AND METHODS OF USE THEREOF
-
The present invention provides bicyclic beta-secretase inhibitors and methods for their use, including methods of treating of Alzheimer’s disease.
- -
-
Page/Page column 61-62
(2010/10/20)
-
- Rhodium-catalyzed synthesis of α-amido- and α-carboxylic- β-ketoesters
-
The rhodium-catalyzed N-H and O-H insertion of amides and carboxylic acids with α-diazo-β-ketoesters to give different α-amido- and α-carboxylic-β-ketoesters is presented. Investigations were carried out to establish an efficient N-H and O-H insertion reaction using a range of different amides and carboxylic acids for the synthesis of intermediates e.g. for receptor antagonists. The reactions were performed under mild conditions with 1 mol% of catalyst and the products were formed in good yields. Georg Thieme Verlag Stuttgart.
- Bertelsen, Soren,Nielsen, Martin,Bachmann, Stephan,Jorgensen, Karl Anker
-
p. 2234 - 2238
(2007/10/03)
-
- Compounds and methods which modulate feeding behavior and related diseases
-
There are provided compounds, compositions and methods of use thereof in the modulation of feeding behavior, obesity, diabetes, cancer (tumor), inflammatory disorders, depression, stress related disorders, Alzheimer's disease and other disease conditions.
- -
-
-
- ASYMMETRIC SYNTHESIS. PRACTICAL PRODUCTION OF D AND L THREONINE. DYNAMIC KINETIC RESOLUTION IN RHODIUM AND RUTHENIUM CATALYZED HYDROGENATION OF 2-ACYLAMINO-3-OXOBUTYRATES.
-
Enantioselective syntheses of D and L threonine are described.Racemic methyl and ethyl 2-acylamino-3-oxobutyrate 1 were synthesized from the corresponding acetoacetates 6 and then hydrogenated stereoselectively via dynamic kinetic resolution with various chiral P * P Rh(I) 8 and Ru(II) 10 catalysts to give syn optically active alcohols which could be converted by hydrolysis and treatment with propylene oxide into threonine.The best results were obtained using (-) CHIRAPHOS Ru and (+) BINAP Ru as catalysts, in the hydrogenation step leading respectively to D threonine (ee : 99percent) and L threonine (ee : 94percent) in 26-34percent overall yields.
- Genet, J.P.,Pinel, C.,Mallart, S.,Juge, S.,Thorimbert, S.,Laffitte, J.A.
-
p. 555 - 567
(2007/10/02)
-
- Stereoselective synthesis of cis-4-(substituted) monobactams from ethyl acetoacetate
-
The stereoselective synthesis of cis-3-amino-4-methyl-2-oxoazetidine-1-sulphonic acid (25) from ethyl acetoacetate is described. Nitrosation of this compound and reduction of the resulting oxime gave the corresponding amine, which after treatment with different acyl halides, yielded the acylamino derivatives (6)-(8). Condensation with p-anisidine gave the enamines (12)-(14), which were then reduced to the β-amino acid esters (15)-(17). Stereoselective cyclization with Grignard reagents as base, and appropriate deprotection and sulphonation of the resulting β-lactams (18)-(20), led to the title compounds.
- Fernandez-Resa, Piedad,Herranz, Rosario,Conde, Santiago,Arribas, Enrique
-
-
- An Enantioselective Synthesis of L-Threonine
-
An enantioselective synthesis of L-threonine (1) is described.Racemic ethyl 2-acetamido-3-oxobutyrate (6) was synthesized from ethyl acetoacetate (2) (4) (5) and then transformed to the epimeric optically active alcohols 7a and 7b by microbiological reduction with Saccharomyces rouxii.The mixture 7a/7b could be converted to 1 by slightly modified, known methods in a yield of ca. 52percent with respect to 7a/7b.
- Soukup, Milan,Wipf, Beat,Hochuli, Erich,Leuenberger, Hans G. W.
-
p. 232 - 236
(2007/10/02)
-
- 2-amido-3-aminocarboxylic acid esters and process of preparation thereof
-
2,3-Diaminocarboxylic acid compounds are prepared by (A) nitrosating a β-keto ester to form a 3-keto-2-oximino ester, (B) converting the resultant oxime to a protected 2-amine, (C) reductively aminating the 3-position of the protected 2-amine to form a 2,
- -
-
-
- Amino Acids, 2. N-Acetyl α,β-Didehydro α-Amino Acid Esters from α-Azidocarboxylic Acid Esters and Acetic Anhydride by Nitrogen Elimination with Rhenium Catalysts
-
α-Azidocarboxylic acid esters 2 react with acetic anhydride in presence of catalytic amounts of rhenium heptasulfide and - if necessary - by addition of hydrochloric acid to give N-acetyl 3 or/and N,N-diacetyl-α,β-didehydro-α-amino acid esters 4 in very g
- Effenberger, Franz,Beisswenger, Thomas
-
p. 1497 - 1512
(2007/10/02)
-