- Multi odd-even effects on cell parameters, melting points, and optical properties of chiral crystal solids based on S-naproxen
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A set of chiral crystal solids with odd and even numbers of carbon atoms based on S-naproxen, ester S-naproxen-R1 (R1 = H, methyl, ethyl, n-propyl, n-butyl, and n-amyl), has been prepared, alternatively crystallizing in the space groups P21 and P212121, respectively, which shows the multi odd-even effects on cell parameters, melting points, and optical properties.
- Tang, Gui-Mei,Wang, Jin-Hua,Zhao, Chao,Wang, Yong-Tao,Cui, Yue-Zhi,Cheng, Fei-Yue,Ng, Seik Weng
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- Design and synthesis of novel (S)-Naproxen hydrazide-hydrazones as potent VEGFR-2 inhibitors and their evaluation in vitro/in vivo breast cancer models
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Naproxen is a common non-steroidal anti-inflammatory drug, which is the most usually used propionic acid derivative for the treatment of many types of diseases. In this study, a series of novel (S)-Naproxen derivatives bearing hydrazide-hydrazone moiety were designed, synthesized, and evaluated for anticancer activity. The structures of these compounds were characterized by spectral (1H–13C NMR, FT-IR, and HR-MS analyses) methods. All synthesized compounds were screened for anticancer activity against two different human breast cancer cell lines (MDA-MB-231 and MCF-7). Among them, (S)-2-(6-methoxynaphthalen-2-yl)-N'-{(E)-[2-(trifluoromethoxy)phenyl]methylidene} propanehydrazide (3a) showed the most potent anticancer activity against both cancer cell lines with a good selectivity (IC50 = 22.42 and 59.81 μM, respectively). Furthermore, the molecular modeling of these compounds was studied on Vascular Endothelial Growth Factor Receptor 2. Inhibition of VEGFR-2 and apoptotic protein Bcl-2 was investigated in MDA-MB-231 cells treated with compound 3a by using Western Blotting. Apoptosis was also detected by staining with DAPI in fluorescence microscopy. Flow Cytometry analyses related to cell cycle phases showed that a dramatic increase in S and M phases was established compared to untreated control cells indicating the cancer cell cycle arrest. The anticancer activity of compound 3a was investigated in the Ehrlich acid tumor model, a well-validated in vivo ectopic breast cancer model, in mice. Our results showed that compound 3a had anticancer activity and decreased the tumor volume in both low (60 mg/kg) and high (120 mg/kg) doses in mice.
- ünal, G?khan,Atalay, P?nar,Ayd?n, ?mer,Dayan, Serkan,Han, M. ?hsan,Kü?ükgüzel, ?. Güniz,Tun?, Cansu ümran
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- Synthesis and pharmacological evaluation of condensed heterocyclic 6-substituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives of naproxen
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Some 6-substituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives (4a-f and 5a-d) have been synthesized by cyclisation of 4-amino-5-[1-(6-methoxy-2-naphthyl)ethyl]-3-mercapto-(4H)-1,2,4-triazole (3) with various substituted aromatic acids and aryl/al
- Amir, Mohammad,Kumar, Harish,Javed, Sadique A.
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- 1,3,4-Oxadiazole-naphthalene hybrids as potential VEGFR-2 inhibitors: design, synthesis, antiproliferative activity, apoptotic effect, and in silico studies
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In the current work, some 1,3,4-oxadiazole-naphthalene hybrids were designed and synthesised as VEGFR-2 inhibitors. The synthesised compounds were evaluated in?vitro for their antiproliferative activity against two human cancer cell lines namely, HepG-2 and MCF-7. Compounds that exhibited promising cytotoxicity (5, 8, 15, 16, 17, and 18) were further evaluated for their VEGFR-2 inhibitory activities. Compound 5 showed good antiproliferative activity against both cell lines and inhibitory effect on VEGFR-2. Besides, it induced apoptosis by 22.86% compared to 0.51% in the control (HepG2) cells. This apoptotic effect was supported by a 5.61-fold increase in the level of caspase-3 compared to the control cells. Moreover, it arrested the HepG2 cell growth mostly at the Pre-G1 phase. Several in silico studies were performed including docking, ADMET, and toxicity studies to predict binding mode against VEGFR-2 and to anticipate pharmacokinetic, drug-likeness, and toxicity of the synthesised compounds.
- Hagras, Mohamed,Saleh, Marwa A.,Ezz Eldin, Rogy R.,Abuelkhir, Abdelrahman A.,Khidr, Emad Gamil,El-Husseiny, Ahmed A.,El-Mahdy, Hesham A.,Elkaeed, Eslam B.,Eissa, Ibrahim H.
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p. 380 - 396
(2021/12/24)
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- Synthesis, Antimicrobial Evaluation, and Molecular Modeling Studies of New Thiosemicarbazide-Triazole Hybrid Derivatives of (S)-Naproxen
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The discovery of new antimicrobial molecules is crucial for combating drug-resistant bacterial and fungal infections that pose a dangerous threat to human health. In the current research, we applied a molecular hybridization approach to synthesize original thiosemicarbazide-triazole derivatives starting from (S)-naproxen (7a–7k). After structural characterization using FT-IR, 1H-NMR, 13C-NMR, and HR-MS, the obtained compounds were screened for their antimicrobial activities against Staphylococcus aureus ATCC 29213, Escherichia coli ATCC 25922, Candida albicans ATCC 10231 and their isolates, as well. Although all compounds were found to be moderate antimicrobial agents, in general, their antibacterial activities were better than antifungal effects. Among the tested compounds, 7j carrying nitrophenyl group on the thiosemicarbazide functionality represented the best MIC value against S. aureus isolate. Finally, molecular docking studies were performed in the active pocket of S. aureus flavohemoglobin to rationalize the obtained biological data.
- Gündüz, Miyase G?zde,Han, M. ?hsan,Ince, Ufuk,Kü?ükgüzel, ?. Güniz
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- Green Esterification of Carboxylic Acids Promoted by tert-Butyl Nitrite
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In this work, the green esterification of carboxylic acids promoted by tert-butyl nitrite has been well developed. This transformation is compatible with a broad range of substrates and exhibits excellent functional group tolerance. Various drugs and substituted amino acids are applicable to this reaction under near neutral conditions, with good to excellent yields.
- Cheng, Xionglve,Jiang, Gangzhong,Li, Xingxing,Tao, Suyan,Wan, Xiaobing,Zhao, Yanwei,Zheng, Yonggao
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supporting information
p. 2713 - 2718
(2021/06/25)
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- Design of multifaceted antioxidants: Shifting towards anti-inflammatory and antihyperlipidemic activity
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Oxidative stress and inflammation are two conditions that coexist in many multifactorial diseases such as atherosclerosis and neurodegeneration. Thus, the design of multifunctional compounds that can concurrently tackle two or more therapeutic targets is an appealing approach. In this study, the basic NSAID structure was fused with the antioxidant moieties 3,5-di-tert-butyl-4-hydroxybenzoic acid (BHB), its reduced alcohol 3,5-di-tert-butyl- 4-hydroxybenzyl alcohol (BHBA), or 6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid (Trolox), a hydrophilic analogue of α-tocopherol. Machine learning algorithms were utilized to validate the potential dual effect (anti-inflammatory and antioxidant) of the designed analogues. Derivatives 1-17 were synthesized by known esterification methods, with good to excellent yields, and were pharmacologically evaluated both in vitro and in vivo for their antioxidant and anti-inflammatory activity, whereas selected compounds were also tested in an in vivo hyperlipidemia protocol. Furthermore, the activity/binding affinity of the new compounds for lipoxygenase-3 (LOX-3) was studied not only in vitro but also via molecular docking simulations. Experimental results demonstrated that the antioxidant and anti-inflammatory activities of the new fused molecules were increased compared to the parent molecules, while molecular docking simulations validated the improved activity and revealed the binding mode of the most potent inhibitors. The purpose of their design was justified by providing a potentially safer and more efficient therapeutic approach for multifactorial diseases.
- Kourounakis, Angeliki,Lambrinidis, George,Tzara, Ariadni
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- Reshaping the active pocket of esterase Est816 for resolution of economically important racemates
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Bacterial esterases are potential biocatalysts for the production of optically pure compounds. However, the substrate promiscuity and chiral selectivity of esterases usually have a negative correlation, which limits their commercial value. Herein, an efficient and versatile esterase (Est816) was identified as a promising catalyst for the hydrolysis of a wide range of economically important substrates with low enantioselectivity. We rationally designed several variants with up to 11-fold increased catalytic efficiency towards ethyl 2-arylpropionates, mostly retaining the initial substrate scope and enantioselectivity. These variants provided a dramatic increase in efficiency for biocatalytic applications. Based on the best variant Est816-M1, several variants with higher or inverted enantioselectivity were designed through careful analysis of the structural information and molecular docking. Two stereoselectively complementary mutants, Est816-M3 and Est816-M4, successfully overcame and even reversed the low enantioselectivity, and several 2-arylpropionic acid derivatives with highEvalues were obtained. Our results offer potential industrial biocatalysts for the preparation of structurally diverse chiral carboxylic acids and further lay the foundation for improving the catalytic efficiency and enantioselectivity of esterases.
- Liu, Xiaolong,Zhao, Meng,Fan, Xinjiong,Fu, Yao
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p. 6126 - 6133
(2021/09/28)
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- Manganese Catalyzed Hydrogenation of Enantiomerically Pure Esters
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A manganese-catalyzed hydrogenation of esters has been accomplished with TONs up to 1000, using cheap, environmentally benign, potassium carbonate and simple alcohols as activator and solvent, respectively. The weakly basic conditions lead to good functional group tolerance and enable the hydrogenation of enantiomerically enriched α-chiral esters with essentially no loss of stereochemical integrity.
- Widegren, Magnus B.,Clarke, Matthew L.
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supporting information
p. 2654 - 2658
(2018/05/17)
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- Efficient resolution of profen ethyl ester racemates by engineered Yarrowia lipolytica Lip2p lipase
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Enzyme-catalyzed enantiomer discrimination is still a great challenge for the development of industrial pharmaceutical processes. For the resolution of ibuprofen, naproxen and ketoprofen racemates, three major anti-inflammatory drugs, only lipases from Candida rugosa present a high selectivity if solvent and surfactant use is discarded. However, their catalytic activities are too low. In the present work, we demonstrate that the lipase Lip2p from the yeast Yarrowia lipolytica has a higher catalytic activity than C. rugosa lipases to hydrolyze the ethyl esters of ibuprofen, naproxen and ketoprofen, but its selectivity is not sufficient [E?=?52 (S); 11 (S) and 1.5 (R) respectively]. The enantioselectivity was further improved by site-directed mutagenesis, targeted at the substrate binding site and guided by molecular modelling studies. By investigating the binding modes of the (R)- and (S)-enantiomers in the active site, two amino acid residues located in the hydrophobic substrate binding site of the lipase, namely residues 232 and 235, were identified as crucial for enantiomer discrimination and enzyme activity. The (S) enantioselectivity of Lip2p towards ethyl ibuprofen esters was rendered infinite (E???300) by replacing V232 by an A or C residue. Substitution of V235 by C, M, S, or T amino acids led to a great increase in the (S)-enantioselectivity (E???300) towards naproxen ethyl ester. Finally, the variant V232F enabled the efficient kinetic resolution of ethyl ketoprofen ester enantiomers [(R)-enantiopreference; E???300]. In addition to the increase in selectivity, a remarkable increase in velocity by 2.6, 2.7 and 2.5?times, respectively, was found for ibuprofen, naproxen and ketoprofen ethyl esters.
- Gérard, Doriane,Guéroult, Marc,Casas-Godoy, Leticia,Condoret, Jean-Stéphane,André, Isabelle,Marty, Alain,Duquesne, Sophie
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p. 433 - 441
(2017/03/24)
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- Design, synthesis and QSAR studies on a series of 2, 5-disubstituted-1,3,4-oxadiazole derivatives of diclofenac and naproxen for analgesic and anti-inflammatory activity
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A series of twenty molecules belonging to 2, 5-disubstituted-1, 3, 4-oxadiazole derivatives of Diclofenac and Naproxen were designed, synthesized and their structures were confirmed by spectroscopy. The target compounds were evaluated for anti-inflammator
- Ilango, Kaliappan,Valentina, Parthiban,Kumar, Gajendra,Dixit, Dushyant,Nilewar, Shrikant,Kathiravan, Muthu K.
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p. 753 - 763
(2015/12/01)
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- Transformations of naproxen into pyrazolecarboxamides: Search for potent anti-inflammatory, analgesic and ulcerogenic agents
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Many derivatives of naproxen containing a variety of pyrazolecarboxamides were synthesized through the reaction of naproxenoyl hydrazide with formylpyrazole, acetylacetone, enaminone, Mannich base, and arylhydrazonomalononitrile derivatives. Also, many derivatives of naproxen were synthesized through the reaction of naprexenoyl chloride with amine derivatives containing pyrazole moiety. The synthesized compounds were screened for anti-inflammatory, analgesic, and ulcerogenic activities. Screening of anti-inflammatory revealed that compound 5 having a 1,3-diphenyl-pyrazol-4-yl moiety had the most promising activity. Compounds 8, 9, and 12, possessing 3,5-dimethyl-pyrazol-1-yl, 3-phenyl-pyrazol-1-yl, and 3,5-diamino-4-(4- methoxyphenylazo)-pyrazol-1-yl groups, respectively, showed moderate activity. Moreover, compounds 8 and 12 showed higher analgesic activity than the reference drug. In ulcerogenic effect, compound 22 which has methoxphenyl pyrazoline moiety devoid of ulcerogenic effect.
- El-Sehemi, Abdullah G.,Bondock, Samir,Ammar, Yousry A.
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p. 827 - 838
(2014/03/21)
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- PROCESS FOR SYNTHESIZING PHENYLACETIC ACID BY CARBONYLATION OF TOLUENE
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A production process for substituted phenylacetic acids or ester analogues thereof is disclosed. In this process toluene or toluene substituted with various substituents, an alcohol, an oxidant and carbon monoxide are used as raw materials to obtain compounds comprising structure of phenylacetic acid ester or analogues thereof by catalysis of the complex catalyst formed from transition metal and ligand, and such compounds are hydrolyzed to obtain various substituted phenylacetic acid based compounds. This type of compounds and their derivatives serve as important fine chemicals used widely in the industries of pharmaceuticals, pesticides, perfume and the like.
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Paragraph 0106; 0107
(2013/11/19)
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- Thermally driven asymmetric domino reaction catalyzed by a thermostable esterase and its variants
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We have developed a thermally driven domino reaction for the synthesis of (S)-a-arylpropionates (profens) using a thermostable esterase from Sulfolobus tokodaii strain 7. Stereoselectivity was improved considerably by engineering of the active site. Stereoselective decarboxylation at the active site of an esterase is a new reaction for the synthesis of optically active carboxylic acids. Crown Copyright.
- Wada, Reina,Kumon, Takashi,Kourist, Robert,Ohta, Hiromichi,Uemura, Daisuke,Yoshida, Shosuke,Miyamoto, Kenji
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p. 1921 - 1923
(2013/04/10)
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- One-pot synthesis of phthalazines and pyridazino-aromatics: A novel strategy for substituted naphthalenes
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A new one-pot strategy for the synthesis of phthalazines and pyridazino-aromatics starting from aromatic aldehydes has been developed. A variety of substituents ranging from electron withdrawing to donating is tolerated furnishing the desired 1,2-diazine in good to excellent yields. The products have been applied to the bidentate Lewis acid catalyzed inverse electron-demand Diels-Alder (IEDDA) reaction opening a novel two-step entry into substituted naphthalenes, such as Naproxen.
- Kessler, Simon N.,Wegner, Hermann A.
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p. 3268 - 3271
(2012/08/28)
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- METHOD FOR THE PREPARATION OF NAPROXEN CHLORIDE
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The invention relates to a method for the preparation of 2-(6'-methoxy-2'-naphthyl)propionic acid chloride(naproxen chloride) using phosgene, and a method for the preparation of esters and amides derived from the thus prepared naproxen chloride.
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Page/Page column 16-17
(2012/06/15)
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- Pd-catalyzed decarboxylative cross-couplings of potassium malonate monoesters with aryl halides
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An efficient catalytic protocol for Pd-catalyzed decarboxylative cross-coupling of potassium malonate monoesters and derivatives with aryl bromides and chlorides are described. Because of its broad applicability, this new catalytic system provides an alternative method for the preparation of diverse aryl acetic acids and derivatives.
- Feng, Yi-Si,Wu, Wei,Xu, Zhong-Qiu,Li, Yan,Li, Ming,Xu, Hua-Jian
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p. 2113 - 2120
(2012/03/26)
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- Chemoenzymatic synthesis of (2S)-2-arylpropanols through a dynamic kinetic resolution of 2-arylpropanals with alcohol dehydrogenases
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We applied Horse Liver Alcohol Dehydrogenase (HLADH) to the enantioselective synthesis of six (2S)-2-arylpropanols, useful intermediates in the synthesis of Profens. The influence of substrate structure and reaction conditions on yields and enantioselectivity were investigated. The high yields and high enantioselectivity towards the (S)-enantiomer obtained in the bioreduction of 2-arylpropionic aldehydes, clearly indicate the achievement of a DKR process through a combination of an enzyme-catalyzed kinetic reduction with a chemical base-catalyzed racemization of the unreacted aldehydes. The racemization step is represented by the keto-enol equilibrium of the aldehyde and can be controlled by modulating pH and reaction conditions.
- Galletti, Paola,Emer, Enrico,Gucciardo, Gabriele,Quintavalla, Arianna,Pori, Matteo,Giacomini, Daria
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supporting information; experimental part
p. 4117 - 4123
(2010/10/03)
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- METHOD FOR THE SYNTHESIS OF CHIRAL ALPHA-ARYL PROPIONIC ACID DERIVATIVES
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The present invention provides a method for the synthesis of optically pure α-aryl propionic acid derivatives comprising subjecting the corresponding racemic α-aryl propionic acid derivatives to high sheer or impact forces, such as grinding.
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Page/Page column 9
(2010/08/18)
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- On the scope of radical reactions in aqueous media utilizing quaternary ammonium salts of phosphinic acids as chiral and achiral hydrogen donors
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A broad range of fundamental free radical reactions such as hydrogen atom transfer, radical deoxygenations, and radical cyclizations utilizing quaternary ammonium salts of phosphinic acids as chiral and achiral hydrogen donors at room temperature are investigated. The reactions proceed in good to excellent yields with some degree of enantioselectivity.
- Perchyonok,Tuck, Kellie L.,Langford, Steven J.,Hearn, Milton W.
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p. 4777 - 4779
(2008/12/22)
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- Non-carboxylic analogues of naproxen: Design, synthesis, and pharmacological evaluation of some 1,3,4-oxadiazole/thiadiazole and 1,2,4-triazole derivatives
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A series of substituted 1,3,4-oxadiazole (2-7 and 14-19), 1,2,4-triazole (20-25), and 1,3,4-thiadiazole (26-31) derivatives of naproxen have been synthesized by cyclization of 2-(6-methoxy-2-naphthyl)propanoic acid hydrazide 1 and N1[2-(6-methoxy-2-naphthyl) propanoyl]-N4-alkyl/aryl- thiosemicarbazides (8-13) under various reaction conditions. All the compounds were screened for their anti-inflammatory activity by carrageenan-induced rat paw edema test method. Compounds showing high anti-inflammatory activity were also tested for their analgesic, ulcerogenic, and lipid peroxidation. Few of the synthesized compounds showed significant anti-inflammatory and analgesic activities along with reduced ulcerogenic effect and lipid peroxidation.
- Amir, Mohammad,Kumar, Harish,Javed, Sadique A.
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p. 577 - 585
(2008/12/21)
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- METHOD OF REMOVING ORGANOTIN RESIDUE
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The invention provides a method of separating soluble organotin residue from a reduced product of a reduction reaction that uses an organotin hydride as a reducing agent, the method comprising: (i) contacting a reaction medium comprising said reduced product and soluble organotin residue with a substrate which, (a) is substantially insoluble in the reaction medium, (b) binds at least a portion of said soluble organotin residue, and (c) does not substantially bind the reduced product; (ii) separating said substrate from the reaction medium, thereby removing said at least a portion of organotin residue from the reaction medium; andrecovering the reaction medium comprising the reduced product. The invention also provides a method of performing a reduction reaction using an organotin hydride as a reducing agent that incorporates the method of separating soluble organotin residue.
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- ENANTIOSELECTIVE REDUCTION METHOD
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The invention provides a method for enantioselectively reducing a prochiral carbon centred radical having one or more electron donor groups attached directly to the central prochiral carbon atom of the radical, and/or attached to a carbon atom within 1 to 4 atoms of the central prochiral carbon atom of the radical, said method comprising generating said radical from a radical precursor compound and reacting said radical with a chiral non-racemic organotin hydride in the presence of a Lewis acid and a co-reducing agent, wherein said co-reducing agent is capable of regenerating chiral non-racemic organotin hydride without substantially reducing said radical or said radical precursor compound.
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- ORGANOGERMANIUM COMPOUNDS AND METHODS FOR THEIR USE
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The invention provides a method for enantioselectively reducing a prochiral carbon centred radical having one or more electron donor groups attached directly to the central prochiral carbon atom of the radical, and/or attached to a carbon atom within 1 to 4 atoms of the central prochiral carbon atom, comprising treating said radical with a chiral non-racemic organogermanium hydride in the presence of a Lewis acid. The invention also provides a novel class of chiral non-racemic organogermanium hydrides and a method of preparing chiral non-racemic organogermanium compounds.
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Page/Page column 27-28
(2010/02/06)
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- CHIRAL ORGANOSILICON HYDRIDES
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The invention provides a method for enantioselectively reducing a prochiral carbon centred radical having one or more electron donor groups attached directly to the central prochiral carbon atom of the radical, and/or attached to a carbon atom within 1 to 4 atoms of the central prochiral carbon atom, comprising treating said radical with an activated chiral non-racemic organosilicon hydride in the presence of a Lewis acid. The invention also provides a novel class of activated chiral non-racemic organosilicon hydrides.
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- Synthesis, characterization and enantioselective free radical reductions of (1R,2S,5R)-menthyldiphenylgermane and its enantiomer
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a- a- a- (1R,2S,5R)-Menthyldiphenylgermane and its enantiomer have been prepared in a few steps from germanium tetrachloride. The initial step in this sequence, namely the reaction between germanium tetrachloride and menthylmagnesium chloride, produces menthylgermanium trichloride, which is the exclusive product of this Grignard reaction, presumably due to the bulk of the menthyl group. When used at a low temperature (-78°C) and in conjunction with Lewis acids, such as magnesium salts, these chiral germanes are capable of reducing ester functionalized radicals in high enantioselectivity, but in low-moderate yield. For example, (R)-naproxen ethyl ester was obtained in 15% yield and 99% ee by reaction in toluene of 2-bromonaproxen ethyl ester with (1R,2S,5R)-menthyldiphenylgermane in toluene at -78°C in the presence of magnesium bromide. At 80°C, (1R,2S,5R)-menthyldiphenylgermane reacted with primary alkyl radicals with a rate constant of 1.02×106 M-1 s-1. Kinetic studies reveal the Arrhenius expression for this reaction to be: log(k/M-1 s-1) = (11.1 ± 0.4) - (34.6±3.1)/θ where θ=2.3RT kJ mol-1.
- Zeng, Le,Dakternieks, Dainis,Duthie, Andrew,Perchyonok, Tamara,Schiesser, Carl
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p. 2547 - 2554
(2007/10/03)
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- Enzymatic resolution of naproxen
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Trichosporon sp. (TSL), a newly found strain isolated from a locally fermented cottage cheese has been found to be highly stereoselective in the resolution of (S)-(+)-naproxen (ee >99%, E~500) from the corresponding racemic methyl ester. The process of resolution using whole cells has been scaled up to multi-kg level. Optimization of experimental conditions including downstream processing at 80-100 g/L substrate concentration with >90% recovery has been achieved. Changes in the physical parameters such as the particle size of the substrate play an important role in the resolution kinetics. A new strain of Trichosporon sp. having high cell density in cultivation (>60 g dry cell mass L-1 in 14-16 h) is found to be sufficiently stable for two years in dry powder form at 5-8°C. The viability of the resolution process has been further improved by the development of a simple racemization process for the enriched (R)-(-)-ester.
- Koul, Surrinder,Parshad, Rajinder,Taneja, Subhash C.,Qazi, Ghulam N.
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p. 2459 - 2465
(2007/10/03)
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- Single enantiomer free-radical chemistry - Lewis acid-mediated reductions of racemic halides using chiral non-racemic stannanes
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Additions of one to two equivalents of Lewis acids that include magnesium salts to free-radical reduction reactions involving ester functionalized radicals and (1R,2S,5R)-menthyldiphenyltin hydride 4, bis((1R,2S,5R)-menthyl) phenyltin hydride 5, tris((1R,
- Dakternieks, Dainis,Perchyonok, V. Tamara,Schiesser, Carl H.
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p. 3057 - 3068
(2007/10/03)
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- Enantioselective hydrolysis of various racemic α-substituted arylacetonitriles using Rhodococcus sp. CGMCC 0497
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The enantioselective hydrolysis of 17 racemic α-substituted arylacetonitriles by Rhodococcus sp. CGMCC 0497 is described. The corresponding (R)-amides and (S)-acids were obtained with excellent enantiomeric excess in most cases. The effect of steric and electronic factors on the outcome of the reactions are discussed here. The results prove that nitrile-converting enzymes are efficient tools for the synthesis of sterically unencumbered chiral α-arylpropionic acids and amides.
- Wu, Zhong-Liu,Li, Zu-Yi
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p. 3305 - 3312
(2007/10/03)
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- Synthesis and antiinflammatory activity of some new 6-methoxy-α- methyl-2-naphthalene acetic acid derivatives
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A number of oxadiazole, thiadiazote and triazole derivatives have been synthesized and evaluated for their antiinflammatory activity. The tested compounds show 18.9 to 65.4% inhibition at 100mg/kg dose compared to naproxen which shows 60.8% inhibition at 50 mg/kg dose in carragenan induced paw edema in rats.
- Amir, Mohammad,Oberoi, Antu,Alam, Shah
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p. 237 - 239
(2007/10/03)
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- Synthesis and resolution of propionic acid derivatives
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A process for the production of disubstituted propionic acid derivatives which are intermediates in the synthesis of α-arylpropionic acids such as naproxen, involves the reaction of a naphthalene derivative such as 2-methoxynaphthalene, with an alkylating agent such as an alkyl pyruvate in the presence of a catalyst, and then dehydrating and hydrogenolising, or directly hydrogenolising, or derivatising and then hydrogenolising the product thereof, to produce the desired compound.
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- Production of racemic 2-(6-methoxy-2-naphthyl) propionic acid of precursors thereof
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In producing (±)-2-(6-methoxy-2-naphthyl)propionic acid or precursor thereof from 2-bromo-6-methoxynaphthalene, use is made of 2-bromo-6-methoxynaphthalene formed by (a) methylating 6-bromo-2-naphthol with methyl chloride in a solvent comprising one or more compounds, RZ, where R is a hydrogen atom or an alkyl group, and Z is --OH or --CN provided that if Z is --CN, R is alkyl, and in the presence of a strong base; and (b) recovering and purifying 2-bromo-6-methoxynaphthalene so formed. Preferably, the 6-bromo-2-naphthol is formed by (1) reacting 1,6-dibromo-2-naphthol with hydrogen, in a solvent comprising (a) organic halide in which the halogen has an atomic number of 35 or less or (b) a mixture of water and such organic halide, and in the presence of catalytically effective amounts of (i) a tungsten carbide-based catalyst, and (ii) phase transfer catalyst; and (2) separating 6-bromo-2-naphthol from the organic halide solvent so that the 6-bromo-2-naphthol is substantially free of halogen-containing impurities before use in the above methylation reaction. This technology makes possible reductions in quantities of co-products formed, eliminates need for use of excess iron and/or dimethyl sulfate as reaction components, and makes possible improvements in plant operating efficiency. Precursors of (±)-2-(6-methoxy-2-naphthyl)propionic acid formed from such 2-bromo-6-methoxynaphthalene are Grignard reagent of 2-bromo-6-methoxynaphthalene, bis(6-methoxy-2-naphthyl)zinc, 6-methoxy-2-naphthylzinc halide, 6-methoxy-2-naphthyllithium, 6-methoxy-2-naphthylcopper(I), bis(6-methoxy-2-naphthyl)cadmium, 6-methoxy-2-naphthylcadmium halide, and 6-methoxy-2-vinylnaphthalene.
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- Esters of naproxen as prodrugs for skin penetration, I: Synthesis and physico-chemical properties
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Several esters of the nonsteroidal antiinflammatory drug Naproxen [2-(6-methoxy-2-naphthyl)propionic acid] were synthesized by standard procedures. Melting points and enthalpies of melting were obtained by differential scanning calorimetry. Solubilities in water were measured using HPLC. The partition coefficients (octanol/water) were calculated according to Rekker and Mannhold and Rm-values were determined by RP-TLC. The two latter parameters were correlated with high significance.
- Weber,Meyer-Trumpener
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p. 337 - 345
(2007/10/02)
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- Comparison of the enzymatic activity of commercial and semipurified lipase of Candida cylindracea in the hydrolysis of the esters of (R,S) 2-aryl propionic acids
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A semipurified lipase of Candida cylindradea (LS) - easily obtained from commercial crude lipase (LC) - is used in the enantioselective hydrolysis of (R,S) 2-arylpropionates. The semipurification treatment diminishes the lipase activity more than the esterase activity. The addition of lactose (24 h) increases both activities. LS is more active than LC - at the same amount of protein - in the hydrolysis of (R,S) 2-aryl propionates. This semipurification showed a remarkable improvement in yield in the enantioespecific hydrolysis of these esters.
- Hernaiz, Maria J.,Sanchez-Montero, Jose M.,Sinisterra, Jose V.
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p. 10749 - 10760
(2007/10/02)
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- Enantiomer separation by transesterification
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Disclosed is a process for resolving enantiomeric mixtures of 2-substituted propanoic acids and related compounds by first derivatizing the compounds to produce water soluble ester forms of the acids, and using the ester forms in an enantiomerically selective enzyme catalyzed reaction. The water soluble substrates are disposed in an aqueous solution of a water soluble donor alcohol in the presence of a hydrolase enzyme and produce by transesterification a product ester rich in one of the two enantiomers having reduced water solubility. Separation of the enantiomers thereafter may be conducted using various conventional means. The process is versatile and efficient because it can be conducted in aqueous solution to produce an easily separated product which inherently is a relatively poor substrate for hydrolase enzyme catalyzed hydrolysis.
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- Method of preparing α-aromatic propionic acids and intermediates thereof
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A method for the preparation of an ester of α-thio-α-aromatic propionic acid derivatives of the formula: STR1 wherein R1 is alkyl, phenyl or benzothiazolyl, R2 is alkyl and Ar is an aromatic substituent. The method comprises reacting an ester of α-chloro-α-thiopropionic acid of the formula: STR2 with an aromatic compound of the formula ARH, in the presence of a Lewis acid. The method provides good reactivity and positional selectivity in the Friedel-Crafts reaction. Many esters of the formula (2) are useful as pharmaceuticals, agricultural chemicals, perfumes or their intermediates.
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- A NEW CONVENIENT SYNTHESIS OF α-ARYLPROPIONIC ACID ESTERS AND α-ARYLPROPIONITRILES
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Various types of α-arylpropionic acid esters were effectively obtained by the coupling reaction of aryl Grignard reagents and α-bromopropionic acid esters in the presence of nickel catalysts. α-Arylpropionitriles, precursors of α-arylpropionic acids, were also synthesized by the reaction of α-methanesulfonyloxypropionitrile and arylcopper reagents prepared from equimolar amount of arylmagnesium halides and copper(I) bromide.
- Amano, Takehiro,Yoshikawa, Kensei,Sano, Tatsuhiko,Ohuchi, Yutaka,Shiono, Manzo,et al.
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p. 499 - 508
(2007/10/02)
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- SHORT-STEP SYNTHESIS OF NAPROXENE. REGIOSELECTIVE FRIEDEL-CRAFTS REACTION OF 2-CHLORO-2-ALKYLTHIO-PROPIONATES
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2-(6-Methoxy-2-naphthyl)propionic acid (4), dl-naproxen, was conveniently prepared by the regioselective reaction of alkyl 2-chloro-2-alkylthio-propionate (2) and 2-methoxynaphtalene (1) in good yield.This Friedel-Crafts reaction was found to be applicable to the other electron-rich aromatics.
- Arai, Kazutaka,Ohara, Yoshio,Iizumi, Toyoko,Takaguwa, Yasuo
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p. 1531 - 1534
(2007/10/02)
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- Esters of α-Arylalkanoic Acids from 'Masked' α-Halogenoalkyl Aryl Ketones and Silver Salts: Synthetic, Kinetic, and Mechanistic Aspects
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A method for the synthesis of alkyl esters of α-arylalkanoic acids is given based on silver-ion-assisted (AgBF4, AgOSO2CF3, AgSbF6, AgNO3) solvolysis of alkyl acetals of primary and secondary α-halogenoalkyl aryl ketones (Hal = I, Br, Cl) in an alcoholic medium (methanol, ethanol).The reaction is quite selective and alkyl esters are the only reaction products; ethers, which are possible substitution products, are not found.The importance of masking the carbonyl as the acetal is emphasised.The reaction is found to be first-order in AgBF4 and in the primary α-halogeno acetal.A three-point Hammett correlation (ρ = -3.29) between ?+ and the rate constants suggests a large cationic contribution as well as strong aryl participation in the transition state.The role payed by the oxygen of the acetal group in the specificity of the reaction is discussed in comparison with the reactivity of analogous compounds with saturated skeletons and of α-halogenoalkyl aryl ketones.
- Giordano, Claudio,Castaldi, Graziano,Casagrande, Francesco,Belli, Aldo
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p. 2575 - 2582
(2007/10/02)
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- Process for preparing 2-(6-methoxy-2-naphthyl)propionic acid
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2-(6-Methoxy-2-naphthyl)propionic acid is prepared by reacting di(6-methoxy-2-naphthyl)-zinc or 6-methoxy-2-naphthylzinc halide with a lower alkyl 2-halopropionate in a suitable solvent to form a lower alkyl 2-(6-methoxy-2-naphthyl)propionate and hydrolyzing the ester group thereof. The product has anti-inflammatory, analgesic and anti-pyretic activities.
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