- Preparation method of N-[1-(S)-ethoxy carbonyl-3-phenyl propyl]-L-alanine
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The invention provides a preparation method of N-[1-(S)-ethoxy carbonyl-3-phenyl propyl]-L-alanine. The preparation method comprises the following steps: performing addition reaction on a compound I and a compound II under the action of a first catalyst to obtain an addition product, wherein the first catalyst is selected from a first thiourea compound and/or a urea compound; performing hydrogenation reaction on the addition product to obtain the N-[1-(S)-ethoxy carbonyl-3-phenyl propyl]-L-alanine. The first catalyst (the first thiourea compound and/or the urea compound) can be added to the reaction system, the selectivity of the addition reaction is improved and the separation efficiency of the required product in the addition reaction process is improved, so that the yield of the final product N-[1-(S)-ethoxy carbonyl-3-phenyl propyl]-L-alanine is increased. The method has the advantages of being short in synthesis route, simple in aftertreatment, capable of being applied to industrialized production and the like.
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Paragraph 0067; 0074; 0078; 0082; 0086; 0090; 0094; 0098
(2018/07/15)
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- Kinetic study of the alkaline degradation of imidapril hydrochloride using a validated stability indicating HPLC method
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An aqueous alkaline degradation study was performed for imidapril hydrochloride (IMD) drug in the presence of its degradation products and an isocratic stability indicating method was presented using a HPLC technique. The separations were performed using an ACE Generix 5C8, 150 × 4.6 mm column and a mobile phase consisting of buffer solution (0.1 M potassium dihydrogen phosphate and 0.02 M tetra-N-butyl ammonium hydrogen sulphate of pH = 4.5 with 1 N HCl) and acetonitrile 60:40 (v/v). The wavelength of the detector was adjusted at 210 nm. The method showed high sensitivity concerning accuracy, precision, linearity and specificity within the acceptable range from 0.1 to 100 μg mL-1 and the limit of quantification was found to be 0.0211 μg mL-1 for IMD. The proposed method was used to determine the drug in its pharmaceutical formulation and to investigate the degradation kinetics of the drug's alkaline-stressed sample. The reactions were found to follow a first-order reaction. The activation energy could also be estimated. The optimized stability indicating HPLC method was validated according to ICH guidelines.
- Abdulla, Shabaan A.,Frag, Eman Y.,Ahmed, Heba E.
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p. 69239 - 69250
(2016/08/05)
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- Impurity profiling of trandolapril under stress testing: Structure elucidation of by-products and development of degradation pathway
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Various regulatory authorities like International Conference on Harmonization (ICH), US Food and Drug Administration, Canadian Drug and Health Agency are emphasizing on the purity requirements and the identification of impurities in active pharmaceutical drugs. Qualification of the impurities is the process of acquiring and evaluating data that establishes biological safety of an individual impurity; thus, revealing the need and scope of impurity profiling of drugs in pharmaceutical research. As no stability-indicating method is available for identification of degradation products of trandolapril, a new angiotensin converting enzyme inhibitor (ACEI), under stress testing, the development of an accurate method is needed for quantification and qualification of degradation products. Ultra high performance liquid chromatography (UPLC) coupled to electrospray tandem mass spectrometry was used for the rapid and simultaneous analysis of trandolapril and its degradation products. Chromatographic separation was achieved in less than 4 min, with improved peak resolution and sensitivity. Thanks to this method, the kinetics of trandolapril degradation under various operating conditions and the characterization of the structure of the by-products formed during stress testing have been determined. Thereafter, a mechanism of trandolapril degradation in acid and neutral conditions, including all the identified products, was then proposed.
- Dendeni,Cimetiere,Amrane,Hamida, N. Ben
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- N-(4-oxo-butanoic acid) -L-amino acid-ester derivatives and methods of preparation thereof
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The present invention provides a compound of the following formula (I): wherein R1 is methyl or 4-aminobutyl, which may be acylated; X is phenyl or substituted phenyl; W is an esterified group removable by hydrogenolysis. Also disclosed is the preparation method and the application of formula (I) compound.
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Page/Page column 4
(2010/02/15)
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- Process for preparing pharmacologically acceptable salt of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl amino acids
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There is provided a process for preparing a pharmacologically acceptable salt of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-amino acid which comprises condensing an amino acid and N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanine.N-carboxyanhydride under basic condition, carrying out decarboxylation under between neutral and acidic condition to obtain N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-amino acid, and forming a pharmacologically acceptable salt thereof, wherein the production of a by-product (3): is suppressed by carrying out in an aqueous liquid a series of operations till formation of the pharmacologically acceptable salt or till isolation of the pharmacologically acceptable salt. The present invention enables to prepare the pharmacologically acceptable salt of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-amino acid having high quality, in a commercial scale with high yield and economical efficiency.
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- Conversion of a hydroxy group in certain alcohols into a fluorosulfonate ester or a trifluoromethylsulfonate ester
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The present invention provides a method of converting a hydroxy group in alcohols containing an electron withdrawing group into perfluoroalkane sulfonate and fluorosulfonate esters, which are good leaving groups, with inversion of configuration where the hydroxyl-bearing carbon is chiral. The method consists of converting an alcohol to an O—N,N-dialkylsulfamate ester and reacting it with a perfluoroalkansulfonic or fluorosulfonic acid. The method has applications in the synthesis of pharmaceutical and agrochemical compounds.
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Page column 13
(2010/02/05)
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- A process for preparing N-substituted amino acid esters
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A process for preparing N-substituted amino acid esters having the formula (I): , wherein R1 and R4, are the same or different, are an alkyl, aralkyl, cycloalkyl or aryl group; and R2 and R3, are the same or different, are an alkyl, aralkyl, aryl, hetero-cycle-alkyl, aminoalkyl or guanidylalkyl, by the reaction of α-amino acid esters with α-substituted carboxylic acid esters, under conditions substantially free from solvent.
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- Studies on Angiotensin Converting Enzyme Inhibitors. 4. Synthesis and Angiotensin Converting Enzyme Inhibitory Activities of 3-Acyl-1-alkyl-2-oxoimidazolidine-4-carboxylic Acid Derivatives
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(4S)-1-Alkyl-3-acyl>-2-oxoimidazolidine-4-carboxylic acid derivatives (3) were prepared by two methods.Their angiotensin converting enzyme (ACE) inhibitory activities and antihypertensive effects were evaluated, and the structure-activity relationships were discussed.The dicarboxylic acids 3a-n possessing S,S,S configuration showed potent in vitro ACE inhibitory activities with IC 50 values of 1.1x10-8-1.5x10-9 M.The most potent compound in this series, monoester 3p, had an ID 50 value of 0.24 mg/kg, po for inhibition of angiotensin I induced pressor response in normotensive rats and produced a dose-dependent decrease in systolic blood pressure of spontaneously hypertensive rats (SHRs) at doses of 1-10 mg/kg, po.
- Hayashi, Kimiaki,Nunami, Ken-ichi,Kato, Jyoji,Yoneda, Naoto,Kubo, Masami,et al.
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p. 289 - 297
(2007/10/02)
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- A Stereoselective Synthesis of N--L-alanine Derivatives by Means of Reductive Amination
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A stereoselective synthesis of N--L-alanine, a portion of the molecule of angiotensin converting-enzyme(ACE) inhibitors, by reductive amination utilizing catecholborane and further applications of the reaction to the synthesis of ACE inhibitors are described.
- Iwasaki, Genji,Kimura, Rieko,Numao, Naganori,Kondo, Kiyoshi
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p. 1691 - 1694
(2007/10/02)
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- Compounds for treating hypertension
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Compounds of the formula STR1 and their pharmaceutically acceptable salts, wherein the substituents are as defined herein, having antihypertensive activity.
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- COMPOUNDS FOR TREATING HYPERTENSION
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Compounds of the formula STR1 and their pharmaceutically acceptable salts, wherein the substituents are as defined herein, having antihypertensive activity.
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- ANTIHYPERTENSIVE 2-OXO-IMIDAZOLIDINE DERIVATIVES
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Novel 2-oxo-imidazolidine derivative of the formula: STR1 wherein R 1 is lower alkyl or phenyl-lower alkyl, R 2 is lower alkyl, R. sup.3 is alkyl of one to 12 carbon atoms or phenyl-lower alkyl and R 4 is hydrogen or lower alkyl, and a pharmaceutically acceptable salts thereof are disclsoed. Said compounds (I) and salts thereof are useful as hypotensive agents.
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- Process for the separation of (S,S) diastereoisomers
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The (S,S) optical isomer of a compound having the general formula STR1 wherein R and R1-5 are as defined herein, is recovered essentially free of the (R,S) and (S,R) isomers, by forming a solution of the esters of the (S,S) and the (R,S) and/or (S,R) isomers of said compound, selectively precipitating an acid salt (e.g. maleate) of the (S,S) ester from the solution, and treating the precipitate to form the desired free acid.
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- 7-Carboxyalkylaminoacyl-1,4-dithia-7-azaspiro[4.4]-nonane-8-carboxylic acids
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This invention relates to 7-carboxyalkyl-aminoacyl-1,4-adithia-7-azaspiro[4.4]nonane-8-carboxylic acids. The compounds of the invention are useful in the treatment of cardiovascular disorders and especially as antihypertensive agents.
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- A FAVOURABLE DIASTEREOSELECTIVE SYNTHESIS OF N-(1-S-ETHOXYCARBONYL-3-PHENYLPROPYL)-S-ALANINE
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N-(1-S-Ethoxycarbonyl-3-phenylpropyl)-S-alanine is prepared by Michael addition of S-alaninebenzylester to ethyl-4-oxo-4-phenyl-2-butenoate in a regio- and diastereoselective fashion and subsequent catalytic hydrogenolysis.
- Urbach, H.,Henning, R.
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p. 1143 - 1146
(2007/10/02)
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