- Synthesis, pharmacological evaluation and molecular docking of novel R-/S-2-(2-hydroxypropanamido)-5-trifluoromethyl benzoic acid as dual anti-inflammatory anti-platelet aggregation agents
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R-/S-2-(2-hydroxypropanamido) benzoic acid (R-/S-HPABA), marine-derived anti-inflammatory antiplatelet drugs, were initially synthesised in our group. However, preliminary research showed that R-/S-HPABA were eliminated rapidly because of extensive hydroxylation metabolism of phenyl ring in vivo. In order to reduce significant hydroxylation metabolism to improve pharmacological activity and bioavailability, trifluoromethyl group was incorporated into R-/S-HPABA to synthesise R-/S-2-(2-hydroxypropanamido)-5-trifluoromethyl benzoic acid (R-/S-HFBA), respectively. The purposes of this study were to report the synthesis of R-/S-HFBA and compare the anti-inflammatory antiplatelet effect and pharmacokinetic properties of R-/S-HFBA with those of R-/S-HPABA. Carrageenan-induced rat paw edema assay was used for the evaluation of the anti-inflammatory activity. R-/S-HFBA showed better results in inhibiting edema and were able to prolong the anti-inflammatory effect after carrageenan injection. The antiplatelet aggregation activity of R-/S-HFBA and R-/S-HPABA was studied on arachidonic acid-induced platelet aggregation of rabbit platelet-rich plasma. The aggregation inhibition rate of R-/S-HFBA was significantly (p max, larger AUC0-∞, and longer t1/2, which, as expected, are more metabolically stable.
- Rong, Rong,Zhang, Rui-zhen,Wang, Xin,Dan, Yu-han,Zhao, Yun-li,Yu, Zhi-guo
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p. 967 - 978
(2019/12/12)
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- 3-Aminoquinazoline–phosphine ligands and their ruthenium(II) complexes: application in catalytic hydrogenation and transfer hydrogenation reactions
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3-Aminoquinazolinone–phosphine proligands (5a–e) and their Ru(II) complexes (6a–e) were prepared and characterized by NMR (1H, 13C, 31P{1H}), FTIR and microanalysis. The 3-aminoquinazolinone–phosphine ligands were found to coordinate with the Ru(II) center via their phosphorus and nitrogen atoms. The Ru(II) complexes were applied as catalysts for the hydrogenation and transfer hydrogenation of prochiral ketones. The results showed that these complexes are efficient transfer hydrogenation catalysts.
- Y?lmaz, Mustafa Kemal,Kele?, Mustafa
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p. 285 - 292
(2018/02/19)
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- Preparation method and application of 2-lactoyl aminobenzoic acid
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The invention relates to a new medicinal application of a chiral compound. The chiral compound is chemically named as R-/S-2-lactoyl aminobenzoic acid and has a structural formula as follows: formula (shown in the description). The compound is initially extracted and separated from secondary metabolite of microorganisms and can be obtained by virtue of a chemical synthetic method. An initial pharmacology experiment shows that the compound has good pain-easing and anti-inflammation activities and relatively low stimulation to gastrointestinal tracts. Recent researches prove that the compound has relatively good anti-platelet aggregation and anti-thrombus activities and is expected to be a novel non-steroidal anti-platelet aggregation and anti-thrombus drug.
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Paragraph 0039; 0040
(2017/08/30)
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- CONTINUOUS PROCESS FOR THE PREPARATION OF (S)-2-ACETYLOXYPROPIONIC ACID CHLORIDE
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The present invention relates to a continuous method for the preparation of (S)-2-acetyloxypropionic acid from an aqueous solution of lactic acid and acetic anhydride, in acetic acid. (S)-2-acetyloxypropionic acid is used for the preparation of (S)-2-acetyloxypropionic acid chloride, an essential intermediate compound for the preparation of Iopamidol and has to be industrially produced with high purity and suitable quality for producing Iopamidol according to the Pharmacopoeia requirements. The continuous process according to the invention, comprises therefore also the chlorination steps of (S)-2-acetyloxypropionic acid with thionyl chloride to give the corresponding (S)-2-acetyloxypropionic acid chloride which is further distilled to give the suitable purity characteristics for its use for the preparation of non-ionic iodinated contrast agents as Iopamidol.
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Page/Page column 18
(2014/07/07)
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- 3-Aminoquinazolinones as chiral ligands in catalytic enantioselective diethylzinc and phenylacetylene addition to aldehydes
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A series of readily known enantiomerically pure 3-aminoquinazolinones 1a-d were synthesised from easily accessible chiral pool α-hydroxy acids and α-amino acids in only four steps without any requirement of chromatography. These quinazolinones were examined as chiral ligands for catalytic enantioselective diethylzinc and phenylacetylene additions to aldehydes. For enantioselective alkylations, the effects of temperature, solvent, diethylzinc and ligand criteria were analysed, and the desired chiral alcohols were obtained in up to 86% ee. 3-Aminoquinazolinones 1a-d were also shown to be very useful ligands in enantioselective alkynylations of aldehydes. Based upon the optimised conditions, the corresponding propargylic alcohols were obtained in up to 94% ee.
- Karabuga, Semistan,Karakaya, Idris,Ulukanli, Sabri
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p. 851 - 855
(2014/06/23)
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- PROCESS FOR MAKING THIENOPYRIMIDINE COMPOUNDS
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Process methods for making the dual mTOR/PI3K inhibitor GDC-0980, named as (S)-1-(4-((2-(2-aminopyrimidin-5-yl)-7-methyl-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)-2-hydroxypropan-1-one, having the structure: and stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof.
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Page/Page column
(2014/04/18)
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- An efficient synthesis of dichotomine a via cyclization of l-tryptophan derivative
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A new synthetic method for dichotomine A is reported. The key step of the synthetic process is the efficient cyclization of L-tryptophan derivative via a modified Bischler-Napieralski reaction which aluminium chloride is used as a mild catalyst. Dichotomine A is obtained in 5 steps and 63.9 % yield.
- Shi, Xiu Xiao,He, Dian,Li, Shao Bai,Lei, Xin,Yang, Huan
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p. 6387 - 6390
(2013/07/26)
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- Stereoregularity of poly(lactic acid) and their model compounds as studied by NMR and quantum chemical calculations
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In order to understand the origin of the tacticity splitting in the NMR spectra of poly(lactic acid), monomer and dimer model compounds were synthesized and their 1H and 13C NMR chemical shifts were observed. Two stable conformations were obtained from Ramachandran map calculated as a function of the internal rotation angles for the monomer model using Gaussian 09 calculations. Four preferred conformations were selected and optimized for each dimer model. The conformations of neighboring residues were energetically interdependent. The 1H and 13C chemical shifts for dimer model compounds were calculated by averaging the occurrence probabilities obtained from the optimized conformational energies and the calculated chemical shift of each conformation. It was confirmed that the solvent effect on the tacticity-dependent relative chemical shifts was small from the NMR experiments of the model compound observed in different solvents, dimethyl sulfoxide, chloroform, and chloroform/carbon tetrachloride (20/80 v/v) mixture. Good agreement between observed and calculated chemical shifts was obtained for the relative chemical shifts of isotactic and syndiotactic 1H and 13C NMR peaks of the dimer model compounds. The observed tacticity splitting of poly(lactic acid) at the diad level was rationalized on the basis of these chemical shift calculations.
- Suganuma, Koto,Horiuchi, Ken,Matsuda, Hironori,Cheng,Aoki, Akihiro,Asakura, Tetsuo
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experimental part
p. 9247 - 9253
(2012/04/18)
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- Synthesis of 4,4′-biquinazoline alcohols as chiral catalysts in enantioselective alkynylation of aldehydes with phenyl acetylene
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Optically active propargylic alcohols are important chiral-building blocks in asymmetric synthesis, while the asymmetric addition of a terminal alkyne to an aldehyde is one of the most important procedures to prepare these chiral-building blocks. In this work, a family of chiral 4,4′-biquinazoline alcohols has been conveniently prepared from the easily accessible (S)-2-acetoxycarboxylic acid chlorides by reaction sequences beginning with condensation and followed by key synthetic steps including chlorination, nickel(0)-mediated homocoupling, and deprotection in addition to being examined as potential ligands in the enantioselective addition of phenylacetylene to aldehydes. These chiral ligands can be combined with Ti(OiPr)4 and then used to catalyze the asymmetric addition of zinc acetylide, produced in situ by the reaction of phenylacetylene with diethylzinc, to aldehydes. The best enantiomeric excess obtained in this study was 75%.
- Catir, Mustafa,Cakici, Murat,Karabuga, Semistan,Ulukanli, Sabri,Sahin, Ertan,Kilic, Hamdullah
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experimental part
p. 2845 - 2853
(2010/04/02)
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- Quinazolinone-based fungal efflux pump inhibitors. Part 1: Discovery of an (N-methylpiperazine)-containing derivative with activity in clinically relevant Candida spp.
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The discovery of a series of quinazolinone-based fungal efflux pump inhibitors by high-throughput screening for potentiation of fluconazole in C. albicans is described. Attempts to improve the aqueous solubility of screening hits led to the discovery of an analog with greatly improved physical properties and activity against clinically-relevant Candida spp.
- Lemoine, Rémy C.,Glinka, Tomasz W.,Watkins, William J.,Cho, Aesop,Yang, Jessie,Iqbal, Nadeem,Singh, Rajeshwar,Madsen, Deidre,Lolans, Karen,Lomovskaya, Olga,Oza, Uma,Dudley, Michael N.
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p. 5127 - 5131
(2007/10/03)
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- Fungal efflux pump inhibitors
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This invention relates to compounds that are efflux pump inhibitors and therefore are useful as potentiators of anti-fungal agents for the treatment of infections caused by fungi that employ an efflux pump resistance mechanism.
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- PROCESS FOR THE PREPARATION OF A DICARBOXYLIC ACID DICHLORIDE
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The present invention refers to a Process for the preparation of S-(-)-5-[[2-(acetyloxy)-1-oxopropyl]amino]-2,4,6-triiodo-1,3-benzenedicarboxylic acid dichloride of formula (I) comprising the reaction between S-(-)-[2-(acetyloxy)]propionic acid chloride and 5-amino-2,4,6-triiodo-, 1,3-benzenedicarboxylic acid dichloride, in an aprotic dipolar solvent and in presence of a halogenhydric acid.
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- First synthesis and crystal structures of chiral 1,3-dienylborates
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We report on the synthesis of bicyclic 1,3-dienylborates (1a/1b and 2a/2b), wherein the boron and nitrogen atoms are chiral. The absolute configuration of these molecules was established by single X-Ray diffraction studies and qualitative homonuclear NOE difference spectroscopy. The conformational stability of these molecules is low at ambient or subambient temperature. The diastereomeric borates (2a/2b) were found to be very reactive toward dienophiles in the Diels-Alder reaction.
- Mortier, Jacques,Vaultier, Michel,Plunian, Barbara,Toupet, Loic
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p. 703 - 711
(2007/10/03)
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- Preparation and use of (S)-O-acetyllactyl chloride (Mosandl's reagent) as a chiral derivatizing agent
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(S)-O-Acetyllactyl chloride is used as a versatile chiral derivatizing agent for the chromatographic determination of the enantiomeric excesses of alcohols or amines. However, some precautions must be taken to avoid its racemization during preparation and use. In addition, the racemic counterpart of this reagent can be used to determine the best analytical separation conditions.
- Buisson, Didier,Azerad, Robert
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p. 2997 - 3002
(2007/10/03)
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- A simple procedure for the synthesis of enantiopure α-acetoxy ketones
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Cross-coupling reactions of α-acetoxy carboxylic acid chlorides with organocopper reagents, derived from Grignard reagents, cuprous bromide and lithium bromide, provide a simple and straightforward method for the synthesis of enantiopure α-acetoxy ketones.
- Babudri, Francesco,Fiandanese, Vito,Marchese, Giuseppe,Punzi, Angela
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p. 2431 - 2440
(2007/10/03)
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- Desilylative elimination of the quinazolinone ring from 1-(4-oxoquinazolin-3-yl)-2-silylaziridines; preparation of an N-H aziridine in high enantiomeric excess by in situ nucleophilic addition to the derived azirine
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Aziridination of vinylsilanes PhCH=CHSiR3 (R = Me, Et, Ph) with enantiopure 3-acetoxyaminoquinazolinone 11 gives the corresponding aziridines 12 [diastereoisomer ratio (dr) 10:1], 18 (dr 13:1) and 20 (dr 2:1). Desilylative elimination of the quinazolinone from these aziridines by caesium fluoride in the presence of cyanide gives aziridine 14 by cyanide addition to the 3-unsubstituted azirine 13, produced in situ. Acylation of aziridine 14 with (S)-acetoxypropionyl chloride gives N-acylaziridine 16; the good correlation between the diastereoisomer ratios of aziridines 12, 18 and 20 and those of the N-acylaziridine 16 produced in each case suggests that intermediate azirine 13 is configurationally stable.
- Atkinson, Robert S.,Coogan, Michael P.,Lochrie, Ian S. T.
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p. 897 - 900
(2007/10/03)
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- Process for the preparation of a dicarboxylic acid di-chloride
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The present invention refers to a Process for the preparation of S-(-)-5-??2-(acetyloxy)-1-oxopropyl!amino!-2,4,6-triiodo-1,3-benzenedicarboxylic acid dichloride of formula (I) comprising the reaction between S-(-)-?2-(acetyloxy)!propionic acid chloride and 5-amino-2,4,6-triiodo-, 1,3-benzenedicarboxylic acid dichloride, in an aprotic dipolar solvent and in presence of a halogenhydric acid.
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- First Asymmetric Synthesis of (S)-(-)-2-(1-Hydroxyethyl)-quinazolin-4(3H)-one (Chrysogenine), a Fungal Metabolite, and Confirmation of the Proposed Absolute Configuration
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Chiral (S)-(-)-2-(1-hydroxyethyl)quinazolin-4(3H)-one (chrysogenine; 7), a fungal metabolite, has been synthesised from anthranilamide and S-(+)-lactic acid, confirming the proposed absolute configuration.
- Maiti, Dilip K.,Ghoshdastidar, Partha Pratim,Bhattacharya, Pranab K.
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p. 306 - 307
(2007/10/03)
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- Enantioselective Preparation of α-Acyloxy Ketones from α-Hydroxy and α-Amino Acids
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Various chiral α-acyloxy ketones have been easily prepared, in high yields with an excellent enantiomeric purity, by acylation of organomanganese reagents with the corresponding α-acyloxy carboxylic acid chlorides prepared from α-hydroxy and α-amino acids.
- Cahiez, Gerard,Metais, Eric
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p. 6449 - 6452
(2007/10/02)
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- The Rational Design and Application of New Chiral Phosphonates for the Enantiomeric Excess Determination of Unprotected Amino Acids. Remarkable pH Dependency of the Diastereomeric Shift Differences.
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Diastereomeric amide derivatives of chiral phosphorinane 8 and unprotected amino acids are easily prepared in aqueous solutions, showing well separated signals in the 31P NMR spectra allowing accurate enentiomeric excess determination.Moreover, the obtained diastereomeric shift dispersion appears to be highly pH dependent, indicating the influence of intramolecular ion pair formation on the diastereomeric shift dispersion.
- Hulst, Ron,Vries, N. Koen de,Feringa, Ben L.
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p. 11721 - 11728
(2007/10/02)
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- Radical decarboxylative alkylation of tartaric acid
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New derivatives of L-(+)-tartaric acid have been synthesized from the monomethyl-2,3-O-isopropylidene (R,R)-(+)-tartrate by visible light photolysis of its N-hydroxy-2-thiopyridone ester derivative in presence of activate alkenes. The carbon radical generated at the dioxolane ring adds stereoselectively to olefins to give the addition products with retention of configuration.
- Barton,Gateau-Olesker,Gero,Lacher,Tachdjian,Zard
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p. 4589 - 4602
(2007/10/02)
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- Amination with 3-acetoxyaminoquinazolin-4-(3H)ones: Preparation of α-aminoacid esters by reaction with silyl ketene acetals followed by N-N bond cleavage
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Solutions of 3-acetoxyaminoquinazoline (5) react with enol ethers and silyl ketene acetals to give α-aminoaldehyde α-aminoketone or α-aminoacid derivatives. Acylation of the exocyclic nitrogen in these derivatives, as a preliminary to reductive N-N bond cleavage, could only be accomplished by indirect means. Samarium diiodide, however, effected the reduction of this N-N bond without the necessity for N-acylation. Solutions of the corresponding enantiopure 3-acetoxyaminoquinazolinone (34) brought about the disastereoselective amination of the prochiral silyl ketene acetal (15) and reductive N-N bond cleavage of the major disastereoisomer lead to enantiopure 2-phenylalanine methyl ester.
- Atkinson,Kelly,Williams
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p. 7713 - 7730
(2007/10/02)
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- Triazole antifungals. III. Stereocontrolled synthesis of an optically active triazolylmethyloxirane precursor to antifungal oxazolidine derivatives
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Stereocontrolled synthesis of an optically active triazolylmethyloxirane 2, an important intermediate for the preparation of antifungal oxazolidine compounds 1, was achieved by two methods using L-lactic acid as a starting material. The key intermediate ketone 6 used in the procedures also served for the synthesis of the enantiomer of 2 and the corresponding diastereomeric epoxide.
- Konosu,Miyaoka,Tajima,Oida
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p. 2241 - 2246
(2007/10/02)
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- Synthesis of chrysogine, a metabolite of Penicillium chrysogenum and some related 2-substituted 4-(3H)-quinazolinones
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Syntheses of both enantiomers of chrysogine, 2-(α-hydroxyethyl)-4(3H)-quinazolinone, 1 from 2-ammobenzamide are reported. Thus reaction of 2-aminobenzamide and optically active α-acetoxypropionyl chloride gave 9, which upon saponification and cyclization induced by aqueous sodium carbonate at room temperature gave chrysogine. The enantiomeric purity of 1 was determined by NMR. Inversion of (-)-(S)-1, using the Mitsunobo reaction, gave (+)-(R)-1. Reduction of 2-acetyl-4(3H)-qumazolinone 2 with baker's yeast gave the S-enantiomer of 1. The cyclization method used could be extended and a number of 2-(a-hydroxy)alkyl-4-(3H)-quinazolinones are also reported.
- Bergman, Jan,Brynolf, Anna
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p. 1295 - 1310
(2007/10/02)
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