- Structure-activity relationship studies of dipeptide-based hepsin inhibitors with Arg bioisosteres
-
Hepsin is a type II transmembrane serine protease (TTSP) associated with cell proliferation and overexpressed in several types of cancer including prostate cancer (PCa). Because of its significant role in cancer progression and metastasis, hepsin is an attractive protein as a potential therapeutic and diagnostic biomarker for PCa. Based on the reported Leu-Arg dipeptide-based hepsin inhibitors, we performed structural modification and determined in vitro hepsin- and matriptase-inhibitory activities. Comprehensive structure-activity relationship studies identified that the p-guanidinophenylalanine-based dipeptide analog 22a exhibited a strong hepsin-inhibitory activity (Ki = 50.5 nM) and 22-fold hepsin selectivity over matriptase. Compound 22a could be a prototype molecule for structural optimization of dipeptide-based hepsin inhibitors.
- Kwon, Hongmok,Ha, Hyunsoo,Jeon, Hayoung,Jang, Jaebong,Son, Sang-Hyun,Lee, Kiho,Park, Song-Kyu,Byun, Youngjoo
-
supporting information
(2020/12/25)
-
- Amidoearbonylation of aldehydes utilizing cobalt oxide-supported gold nanoparticles as a heterogeneous catalyst
-
Cobalt oxide-supported gold-nanoparticles-catalyzed transformation of aldehydes and their equivalents to N-acyl-α-arnino acids was achieved. The desired products were obtained in moderate to excellent yields under milder reaction conditions than previous reports employing octacarbonyldicobalt as a catalyst. Copyright
- Hamasaki, Akiyuki,Liu, Xiaohao,Tokunaga, Makoto
-
supporting information; experimental part
p. 1292 - 1293
(2009/12/03)
-
- Application of aminoacylase I to the enantioselective resolution of α-amino acid esters and amides
-
Aminoacylase I from Aspergillus melleus, a readily available and inexpensive enzyme mainly used in the industrial production of enantiopure L-amino acids from their N-acetyl derivatives, is shown to hydrolyze the esters and amides of natural and non-natural amino acids with high enantioselectivity (for the ester hydrolysis, E is up to 76, in case of amides E >300). The reaction rates of amide and ester hydrolysis are comparable, and in some cases these conversions proceeded even faster than 'traditional' aminoacylase- catalyzed hydrolysis of N-acetyl derivatives thus providing new possibilities for the resolution of the corresponding racemates. This novel approach provides an alternative route for the biocatalytic production of optically active amino acids and their derivatives.
- Youshko, Maxim I.,Van Langen, Luuk M.,Sheldon, Roger A.,Svedas, Vytas K.
-
p. 1933 - 1936
(2007/10/03)
-
- 7-AMINOIMIDAZOTRIAZONES
-
The invention relates to novel 7-amino-imidazotriazinones, processes for their preparation and their use in medicaments, esp. for the treatment and/or prophylaxis of inflammatory processes and/or immune diseases.
- -
-
Page/Page column 25
(2010/02/07)
-
- 5-ETHYL-IMIDAZO (5,1-F) (1,2,4,) TRIAZIN-4 (3H) -ONES AS PHOSPHODIESTERASE INHIBITORS
-
The invention relates to novel 5-ethyl-imidazotriazinones, processes for their preparation and their use in medicaments, esp. for the treatment and/or prophylaxis of inflammatory processes and/or immune diseases.
- -
-
Page/Page column 21
(2010/02/07)
-
- 5-ETHYLIMIDAROTRIAZONES
-
The invention relates to novel 5-ethyl-imidazotriazinones, processes for their preparation and their use in medicaments, esp. for the treatment and/or prophylaxis of inflammatory processes and/or immune diseases.
- -
-
Page/Page column 26
(2010/02/07)
-
- Novel heterocycles 3
-
The invention relates to 7-(4-tert butyl-cyclohexyl)-imidazotriazinones, processes for their preparation and their use in medicaments, esp. for the treatment and/or prophylaxis of inflammatory processes and/or immune diseases.
- -
-
-
- Synthesis of N-Acetyl-α-aminobutyric Acid via Amidocarbonylation: A Case Study
-
The synthesis of N-acetyl-α-aminobutyric acid by amidocarbonylation of propionaldehyde with acetamide in the presence of palladium catalysts is studied in detail. The influence of various reaction conditions and compositions (e.g., the co-catalysts acid and bromide) on the yield of N-acetyl-α-aminobutyric acid is shown. For the first time it is demonstrated that the palladium-catalyzed amidocarbonylations of aldehydes can be run with significantly lower halide concentrations (a major yield decrease. While phosphine-free catalyst systems give best yields at low CO pressure, phosphine-ligated palladium catalysts lead to better yields at higher CO pressure. At low palladium loadings (0.1 mol %), unwanted condensation reactions of propionaldehyde become increasingly competitive.
- Goerdes, Dirk,Neumann, Helfried,Von Wangelin, Axel Jacobi,Fischer, Christine,Drauz, Karlheinz,Krimmer, Hans-Peter,Beller, Matthias
-
p. 510 - 516
(2007/10/03)
-
- Substituted imidazotriazinones
-
The present invention relates to new substituted imidazotriazinones, processes for their preparation, and their use for the production of medicaments, in particular for improving perception, concentration power, learning power and/or memory power.
- -
-
-
- L-Methionine related 1-amino acids by acylase cleavage of their corresponding N-acetyl-DL-derivatives
-
Acylase I from Aspergillus oryzae is an even more useful enzyme than suggested so far. Besides standard amino acids such as L-Met, L-Val and L-Phe, a number of additional sulfur- and selenium-containing amino acids can be obtained at useful reaction rates and in very high enantiomeric purity by kinetic resolution of the respective N-acetyl-DL-amino acids.
- Bommarius, Andreas S.,Drauz, Karlheinz,Guenther, Kurt,Knaup, Guenter,Schwarm, Michael
-
p. 3197 - 3200
(2007/10/03)
-
- Synthesis and application of (3R,4R)-3,4-bis(diphenylphosphino)tetrahydrofuran as ligand for asymmetric hydrogenation of acrylic acids
-
A new, chiral bisphosphine, (3R,4R)-3,4-bis(diphenylphosphino)tetrahydrofuran (4), is synthesized in three steps from (R,R)-tartaric acid esters. With rhodium(I) complexes of 4 enantiomeric excesses of 54 to 97% are obtained on catalytic hydrogenation of 2-(acetylamino)acrylic acid, 2-(acetylamino)cinnamic acids and itaconic acid. The applied substrate/catalyst ratios were between 250:1 and 11,000:1.
- Terfort
-
p. 951 - 953
(2007/10/02)
-
- Kinetic Resolution of Unnatural and Rarely Occuring Amino Acids: Enantioselective Hydrolysis of N-Acyl Amino Acids Catalyzed by Acylase I
-
Acylase I (aminoacylase; N-acylamino-acid amidohydrolase, EC 3.5.1.14, from porcine kidney and the fungus Aspergillus) is broadly applicable enzymatic catalyst for the kinetic resolution of unnatural and rarely occuring α-amino acids.Its enantioselectivity for the hydrolysis of N-acyl L-α-amino acids is nearly absolute, yet it accepts substrates having a wide range of structure and functionality.This paper reports the initial rates of enzyme-catalyzed hydrolysis of over 50 N-acyl amino acids and analogues, the stabilities of the enzymes in aqueous and aqueous/organic solutions, and the effects of different acyl groups and metal ions on the rates of enzymatic hydrolysis.Eleven α-amino and α-methyl α-amino acids were resolved on a 2-29-g scale.Crude L- and D-amino acid products had generally >90percent ee.The utility of resolved amino acids as chiral synthons was illustrated by the preparation of (R)- and (S)-1-butene oxide and the diastereoselective (cis:trans, 7-8:1) iodolactonization of three 2-amino-4-alkenoic acid derivatives.
- Chenault, H. Keith,Dahmer, Juergen,Whitesides, George M.
-
p. 6354 - 6364
(2007/10/02)
-
- Racemic Structures of Organic Ammonium Salts of N-Acetyl-DL-2-aminobutyric Acid and N-Acetyl-DL-norvaline and Optical Resolution by Preferential Crystallization of DL-Ammonium Salts
-
The racemic structures of the ammonium salts (AM salts) and seven organic ammonium salts of N-acetyl-DL-2-aminobutyric acid (Dl-AcAbu) and N-acetyl-DL-norvaline (DL-AcNva) were studied on the basis of thermodynamic analyses to explore the possibility of optical resolution by preferential crystallization.An empirical equation has been derived from thermodynamic data and melting points of ammonium and organic ammonium salts of N-acyl-DL-amino acids to predict racemic structure around room temperature.The AM salts of DL-AcAbu and -AcNva exist in conglomerate around room temperature.It is possible to resolve optically these DL-AM salts by preferential crystallization in ethanol at 10 deg C, and the succesive preferential crystallization followed by purification gave D- and L-2-aminobutyric acids and -norvalines with optical purities close to 100percent.
- Shiraiwa, Tadashi,Yoshida, Hirokazu,Tsuda, Makoto,Kurokawa, Hidemoto
-
p. 947 - 952
(2007/10/02)
-
- ENANTIOSELECTIVE HYDROLYSIS BY BAKER'S YEAST - II. ESTERS OF N-ACETYL AMINO ACIDS
-
D-N-Acetyl amino acid esters were obtained via enantioselective hydrolysis of their racemates by use of fermenting yeast.Evidence is given that proteinases are the enzymes involved.
- Glaenzer, B. I.,Faber, K.,Griengl, H.
-
p. 771 - 778
(2007/10/02)
-
- STUDIES ON HYDROCARBOXYLATION OF N-ACETYLIMINES, ENAMINES AND ALLYLAMINES.
-
Treatment of an amide with an aldehyde in the presence of Co2(CO)8/CO/H2 results in N-acyl-α-amino acids. The scope and limitations of this reaction are explored
- Magnus, Philip,Slater, Martin
-
p. 2829 - 2832
(2007/10/02)
-
- ASYMMETRISCHE KATALYSEN. XXX. ENANTIOSELEKTIVE HYDRIERUNG VON CROTONSAEUREDERIVATEN MIT RHODIUM-PHOSPHIN-KATALYSATOREN
-
The Z- and E-isomers of the α-N-benzoylamino-2-butenoic acid methyl ester, the E/Z mixtures of α-N-benzoylamino-2-butenoic acid, and the Z-form of α-N-acetylamino-2-butenoic acid were hydrogenated enantioselectively.The hydrogenation products are derivatives of α-aminobutyric acid, which can be reduced to aminobutanol, the optically active component of the antituberculosis drug (+)-ethambutol.In situ catalysts consisting of 2 and the optically active phosphine ligands (+)- and (-)-Norphos, (+)-Prophos, (-)-Chiraphos, (-)-BPPFA, (-)-Diop, and (+)- and (-)-CpMn(CO)2diop were used.The best results were obtained with the substrate (Z)-α-acetylamino-2-butenoic acid and the catalyst 2/(-)-Norphos with 91.5percent e.e.
- Brunner, Henri,Knott, Alfons,Kunz, Manfred,Thalhammer, Elisabeth
-
-
- ENANTIOSELECTIVE HYDROLYSIS BY BAKER'S YEAST
-
Optically active N-acetylamino acid esters were obtained by enantioselective hydrolysis of their racemates using fermenting baker's yeast.
- Glaenzer, B.I.,Faber, K.,Griengl, H.
-
p. 4293 - 4294
(2007/10/02)
-
- Process for production of N-acyl-α-amino acids
-
A process for the production of an N-acyl-α-amino acid represented by the general formula STR1 wherein R1, R2, R3 and R4, independently from each other, represent a hydrogen atom, an alkyl or cycloalkyl group which may be substituted, or an aryl or heteroaromatic group selected from the group consisting of furyl, pyrrolyl, pyridinyl, thienyl and indolyl which may be substituted, which comprises reacting an oxirane represented by the general formula STR2 wherein R1 and R2 are as defined above, an amide compound represented by the general formula wherein R3 and R4 are as defined above, and carbon monoxide in the presence of hydrogen, a cobalt-containing catalyst, and a promoter composed of a compound containing a metal selected from Groups I, II, III and IV of the periodic table.
- -
-
-
- NEW SYNTHETIC ROUTE TO N-ACYL-α-AMINO ACIDS VIA AMIDOCARBONYLATION BY MEANS OF HOMOGENEOUS BINARY CATALYST SYSTEMS
-
New catalytic processes which lead to the formation of N-acyl-α-amino acids promoted by homogeneous binary systems are described: (a) the isomerization-amidocarbonylation of allylic alcohols catalyzed by transition metal binary systems, e.g., Co-Rh, Co-Pd, Co-Fe, giving various aliphatic N-acyl-α-amino acids; (b) the isomerization-amidocarbonylation of oxiranes catalyzed by cobalt-Lewis acid systems giving N-acyl-α-amino acids; The process is extremely effective for the synthesis of N-acetylphenylalanine from styrene oxide and (c) the hydroformylation-amidocarbonylation of trifluoropropene catalyzed by cobalt-rhodium binary system giving N-acetyltrifluorovaline in excellent regioselectivity and yield.Possible mechanisms for these new processes are discussed.
- Hirai, Kenji,Fujita, Makoto,Fuchikami, Takamasa
-
p. 203 - 214
(2007/10/02)
-
- Apparent Molal Volumes of Amino Acids, N-Acetylamino Acids, and Peptides in Aqueous Solutions
-
The apparent molal volumes of 24 α-amino acids, 6 N-acetylamino acids, and 9 peptides in aqueous solutions have been determined at 298.15 K from precise density measurements.Limiting partial molal volumes, , have been also evaluated from the apparent molal volumes at various solute concentrations.Group additivity relationships were examined from the data of these solutes as well as from those of several homologous series of compounds available in the literature.It has been shown that the presence of hydrophilic groups in close proximity in α-amino acids and N-acetylamino acids decreases the functional-group contribution as well as the contribution due to hydrophobic hydratoin toward relative to those observed in the monofunctional compounds.It is also found that the values of the peptides estimated from the values of the constituent amino acids, with a proper consideration of change in the electrostriction volume due to separation of the charged centers, agree with the experimental values.Concentration dependence of the apparent molal volumes of the solutes has been explained on the basis of combined effects of hydrophilic and hydrophobic solute-solute interactions mediated through the typical structure of water.
- Mishra, Awadhesh K.,Ahluwalia, Jagdish C.
-
-
- DIRECT CONVERSION OF ALLYLIC ALCOHOLS INTO N-ACYL-α-AMINO ACIDS BY CATALYTIC AMIDOCARBONYLATION BY MEANS OF HOMOGENEOUS BINARY SYSTEMS
-
N-Acyl-α-amino acids are synthesized by the amidocarbonylation of allylic alcohols catalyzed by homogeneous binary systems which consist of cobalt carbonyl and rhodium (or iron or palladium) complexes.
- Hirai, Kenji,Takahashi, Yoshitaka,Ojima, Iwao
-
p. 2491 - 2494
(2007/10/02)
-
