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Amide Derivatives (amide + derivative)
Selected AbstractsChemInform Abstract: Synthesis and Biological Evaluation of Amide Derivatives of (6-Chloro-2,3-dihydro-1H-inden-1-yl)acetic Acid as Potential Antiinflammatory Agents with Lower Gastrointestinal Toxicity.CHEMINFORM, Issue 43 2008Meenakshi Sharma Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] ChemInform Abstract: Ceric Ammonium Nitrate (CAN) Promoted Efficient Solid Phase Synthesis of Amide Derivatives: A Green Approach.CHEMINFORM, Issue 20 2008Ch. Sanjeeva Reddy Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Nickel-Catalyzed Coupling of Isocyanates with 1,3-Iodoesters and Halobenzenes: A Novel Method for the Synthesis of Imide and Amide Derivatives.CHEMINFORM, Issue 5 2006Jen-Chieh Hsieh Abstract For Abstract see ChemInform Abstract in Full Text. [source] Preparation of Enantiopure Butane-2,3-diacetals of Glycolic Acid and Alkylation Reactions Leading to ,-Hydroxyacid and Amide Derivatives.CHEMINFORM, Issue 15 2005Steven V. Ley Abstract For Abstract see ChemInform Abstract in Full Text. [source] Practical Asymmetric Synthesis of Vicinal Diamines Through the Catalytic Highly Enantioselective Alkylation of Glycine Amide Derivatives.CHEMINFORM, Issue 12 2004Takashi Ooi Abstract For Abstract see ChemInform Abstract in Full Text. [source] Improved 2,4-Diarylthiazole-Based Antiprion Agents: Switching the Sense of the Amide Group at C5 Leads to an Increase in PotencyCHEMMEDCHEM, Issue 9 2010Abstract Amide derivatives of 2,4-diarylthiazole-5-carboxylic acids were synthesised and tested for efficacy in a cell line model of prion disease. A number of compounds demonstrating antiprion activity were thereby identified from the screening libraries, showing improved potency and reproducibility of results relative to amide derivatives of the related 2,4-diphenyl-5-aminothiazole, which have been documented previously. Thus, 'switching' the sense of the amide bond at thiazole C5 revealed a more promising lead series of potential prion disease therapeutics. Furthermore, 3,5-diaryl-1,2,4-thiadiazoles isolated as by-products during library synthesis provided a handful of additional examples possessing an antiprion effect, thereby augmenting the set of newly identified active compounds. Evaluation of binding to cellular prion protein (PrPC) showed only weak affinities at best, suggesting that the newly identified antiprion agents do not mediate their biological effect through direct interaction with PrPC. [source] Synthesis and Anticonvulsant Activity of N -(2-Hydroxy-ethyl)amide DerivativesARCHIV DER PHARMAZIE, Issue 1 2009Li-Ping Guan Abstract A series novel of N -(2-hydroxyethyl)amide derivatives was synthesized and screened for their anticonvulsant activities by the maximal electroshock (MES) test, and their neurotoxicity was evaluated by the rotarod test (Tox). The maximal electroshock test showed that N -(2-hydroxyethyl)decanamide 1g, N -(2-hydroxyethyl)palmitamide 1l, and N -(2-hydroxyeth-yl)stearamide 1n were found to show a better anticonvulsant activity and also had lower toxicity than the marked anti-epileptic drug valproate. In the anti-MES potency test, these compounds exhibited median effective doses (ED50) of 22.0, 23.3, 20.5 mg/kg, respectively, and median toxicity doses (TD50) of 599.8, >1000, >1000 mg/kg, respectively, resulting in a protective index (PI) of 27.5, >42.9, >48.8, respectively. This is a much better protective index than that of the marked anti-epileptic drug valproate (PI = 1.6). To further investigate the effects of the anticonvulsant activity in several different models, compounds 1g, 1l, and 1n were tested having evoked convulsions with chemical substances, including pentylenetetrazloe, isoniazide, 3-mercaptopropionic acid, bicuculline, thiosemicarbazide, and strychnine. [source] Incorporation of a (Cyclopentadienyl)molybdenum Oxo Complex in MCM-41 and Its Use as a Catalyst for Olefin EpoxidationEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 24 2004Marta Abrantes Abstract The tricarbonyl complex [(,5 -C5H4 -COOMe)Mo(CO)3Cl] was prepared from the reaction of sodium (methoxycarbonyl)cyclopentadienide, (C5H4 -CO2Me)Na, with (Bu4N)[Mo(CO)5I]. Heating the ester with 3-(triethoxysilyl)propylamine gave the amide derivative {[,5 -C5H4 -CONH-C3H6Si(OEt)3]Mo(CO)3Cl}. The functionalised tricarbonyl complex was immobilised in the ordered mesoporous silica MCM-41 with a loading of 13 wt.-% Mo (1.4 mmol·g,1) by carrying out a grafting reaction in dichloromethane. Powder X-ray diffraction and nitrogen adsorption,desorption analysis indicated that the structural integrity of the support was preserved during the grafting and that the channels remained accessible, despite significant reductions in surface area, pore volume and pore size. The success of the coupling reaction was confirmed by 29Si and 13C (CP) MAS NMR spectroscopy. A supported dioxo complex of the type [(,5 -C5H4R)MoO2Cl] was subsequently prepared by oxidative decarbonylation of the tethered tricarbonyl complex using tert -butyl hydroperoxide (TBHP). The oxidised material is an active catalyst for the liquid phase epoxidation of cyclooctene with TBHP as the oxygen source. Similar catalytic results were obtained using the tethered tricarbonyl complex directly as a pre-catalyst since fast oxidative decarbonylation occurs under the reaction conditions used. For both systems, the desired epoxide was the only product and the initial activities were about 13 mol·molMo,1·h,1. The solid catalysts were recycled several times. Some activity was lost between the first and second runs but thereafter tended to stabilise. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004) [source] A New and Efficient Synthesis of the HMG-CoA Reductase Inhibitor PitavastatinHELVETICA CHIMICA ACTA, Issue 6 2007Murat Acemoglu Abstract A new synthetic method for the preparation of pitavastatin is described. The approach circumvents various synthetic problems associated with the buildup of the 3,5-dihydroxy-C7 acid side chain of HMG-CoA reductase inhibitors (statins). The use of the C6 -amide derivative 5 instead of ester derivatives in the coupling reaction with carboxaldehyde 8 (Scheme,3) prevents undesired side reactions, such as eliminations and retro -aldol reactions. The method provides synthetic statins, such as pitavastatin, in >99% ee and exceptionally high overall yield. The enantiomerically pure starting material, (3S)-3-{[(tert -butyl)dimethylsilyl]oxy}-5-oxo-5-{[(1S)-1-phenylethyl]amino}pentanoic acid (3c), is prepared by an improved procedure from 3-{[(tert -butyl)dimethylsilyl]oxy}glutaric anhydride (1) and (1S)-1-phenylethylamine (2c; Scheme,1). [source] Characterization of the anticonvulsant profile and enantioselective pharmacokinetics of the chiral valproylamide propylisopropyl acetamide in rodentsBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2003Nina Isoherranen Propylisopropyl acetamide (PID) is a new chiral amide derivative of valproic acid. The purpose of this study was to evaluate the anticonvulsant activity of PID in rodent models of partial, secondarily generalized and sound-induced generalized seizures which focus on different methods of seizure induction, both acute stimuli, and following short-term plastic changes as a result of kindling, and to assess enantioselectivity and enantiomer,enantiomer interactions in the pharmacokinetics and pharmacodynamics of racemic PID and its pure enantiomers in rodents. Anticonvulsant activity of (S)-PID, (R)-PID and racemic PID was evaluated in the 6 Hz psychomotor seizure model in mice, in the hippocampal kindled rat, and in the Frings audiogenic seizure susceptible mouse. The pharmacokinetics of (S)-PID and (R)-PID was studied in mice and rats. In mice (S)-PID, (R)-PID and racemic PID were effective in preventing the 6 Hz seizures with (R)-PID being significantly (P<0.05) more potent (ED50 values 11 mg kg,1, 46 mg kg,1 and 57 mg kg,1 at stimulation intensities of 22, 32 and 44 mA, respectively) than (S)-PID (ED50 values 20 mg kg,1, 73 mg kg,1 and 81 mg kg,1 at stimulation intensities of 22, 32 and 44 mA, respectively). (S)-PID, (R)-PID and racemic PID also blocked generalized seizures in the Frings mice (ED50 values 16 mg kg,1, 20 mg kg,1 and 19 mg kg,1 respectively). In the hippocampal kindled rat a dose of 40 mg kg,1 of (R)- and (S)-PID prevented the secondarily generalized seizure, whereas racemic PID also blocked the expression of partial seizures following an i.p. dose of 40 mg kg,1. Racemic PID also significantly increased the seizure threshold in this model. Mechanistic studies showed that PID did not affect voltage-sensitive sodium channels or kainate-, GABA- or NMDA- evoked currents. The pharmacokinetics of PID was enantioselective following i.p. administration of individual enantiomers to mice, with (R)-PID having lower clearance and longer half-life than (S)-PID. In rats and mice, no enantioselectivity in the pharmacokinetics of PID was observed following administration of the racemate, which may be due to enantiomer,enantiomer interaction. This study demonstrated that PID has both enantioselective pharmacokinetics and pharmacodynamics. The better anticonvulsant potency of (R)-PID in comparison to (S)-PID may be due to its more favorable pharmacokinetic profile. The enhanced efficacy of the racemate over the individual enantiomers in the kindled rat may be explained by a pharmacokinetic enantiomer,enantiomer interaction in rats. This study also showed the importance of studying the pharmacokinetics and pharmacodynamics of chiral drugs following administration of the individual enantiomers as well as the racemic mixture. British Journal of Pharmacology (2003) 138, 602,613. doi:10.1038/sj.bjp.0705076 [source] A Cyclam Core Dendrimer Containing Dansyl and Oligoethylene Glycol Chains in the Branches: Protonation and Metal CoordinationCHEMISTRY - A EUROPEAN JOURNAL, Issue 35 2006Barbara Branchi Dr. Abstract We have synthesized a dendrimer (1) consisting of a 1,4,8,11-tetraazacyclotetradecane (cyclam) core, appended with four benzyl substituents that carry, in the 3- and 5-positions, a dansyl amide derivative (of type 2), in which the amide hydrogen is replaced by a benzyl unit that carries an oligoethylene glycol chain in the 3- and 5-positions. All together, the dendrimer contains 16 potentially luminescent moieties (eight dansyl- and eight dimethoxybenzene-type units) and three distinct types of multivalent sites that, in principle, can be protonated or coordinated to metal ions (the cyclam nitrogen atoms, the amine moieties of the eight dansyl units, and the 16 oligoethylene glycol chains). We have studied the absorption and luminescence properties of 1, 2, and 3 in acetonitrile and the changes taking place upon titration with acid and a variety of divalent (Co2+, Ni2+, Cu2+, Zn2+), and trivalent (Nd3+, Eu3+, Gd3+) metal ions as triflate and/or nitrate salts. The results obtained show that: 1) double protonation of the cyclam ring takes place before protonation of the dansyl units; 2) the oligoethylene glycol chains do not interfere with protonation of the cyclam core and the dansyl units in the ground state, but affect the luminescence of the protonated dansyl units; 3) the first equivalent of metal ion is coordinated by the cyclam core; 4) the interaction of the resulting cyclam complex with the appended dansyl units depends on the nature of the metal ion; 5) coordination of metal ions by the dansyl units follows at high metal-ion concentrations; 6) the effect of the metal ion depends on the nature of the counterion. This example demonstrates that dendrimers may exhibit complete functionality resulting from the integration of the specific properties of their component units. [source] Synthesis and some reactions of 4-(ethoxycarbonyl)-1,5-diphenyl-1H -pyrazole-3-carboxylic acidJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 5 2007Ahmet, ener 1,5-Diphenyl-1H -pyrazole-3,4-dicarboxylic acid-4-ethyl ester 2, obtained from the 4-ethoxycarbonyl-5-phenyl-2,3-furandione 1 and N -benzylidene- N,-phenyl hydrazine, was converted via reactions of its acid chloride 3 with various alcohols or N-nucleophiles into the corresponding ester 5 or amide derivatives 6, respectively. In addition, 2 was decarboxylated to give ethyl 1,5-diphenylpyrazole-4-carboxylate 4. Nitrile 7 derivative of 2 was also obtained by dehydration of 6a in a mixture of SOCl2 and DMF. While cyclocondensation reaction of 2 with hydrazine hydrate leads to the formation of pyrazolo[3,4- d]pyridazine-4,7-dione 8, the reaction of 3 with anhydrous hydrazine provided a new bis pyrazole derivative 9. [source] Studies on the reactions of cyclic oxalyl compounds with hydrazines or hydrazones : Synthesis and reactions of 4-benzoyl-1-(3-nitrophenyl)-5-phenyl-1H -pyrazole-3-carboxylic acidJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 5 2002Ahmet, ener The 1H -pyrazole-3-carboxylic acid 2, obtained from the furan-2,3-dione 1 and N -Benzylidene- N'-(3-nitrophenyl) hydrazine, was converted via reactions of its acid chloride 3 with various alcohols or N-nucleo-philes into the corresponding ester or amide derivatives 4 or 5, respectively. Nitrile 6 and anilino-pyrazole acid 7 derivatives of 2 were also obtained by dehydration of 5a in a mixture of SOCl2 with DMF and reduction of 2 with sodium polysulphide, respectively. While cyclocondensation reactions of 2 or 7 with phenyl hydrazine or hydrazine hydrate and 6 with only anhydrous hydrazine lead to derivatives of pyrazolo[3,4- d]-pyridazinone 8 and pyrazolo[3,4- d]pyridazine amine 9, respectivel. The reaction of 2 with 2-hydrazinopyri-dine provided hydrazono-pyrazole acid derivative 10, which was decarboxylated to give hydrazono-pyra-zole derivative 11. Pyrazolo[4,3- d]oxazinone 12 and 2-quinolyl pyrazolo[3,4- d]pyridazine 13 derivatives were also prepared by cyclocondensation reactions of 2 with hydroxylamine hydrochloride and 7 with acetaldehyde, respectively. [source] Synthesis and Anticonvulsant Activity of N -(2-Hydroxy-ethyl)amide DerivativesARCHIV DER PHARMAZIE, Issue 1 2009Li-Ping Guan Abstract A series novel of N -(2-hydroxyethyl)amide derivatives was synthesized and screened for their anticonvulsant activities by the maximal electroshock (MES) test, and their neurotoxicity was evaluated by the rotarod test (Tox). The maximal electroshock test showed that N -(2-hydroxyethyl)decanamide 1g, N -(2-hydroxyethyl)palmitamide 1l, and N -(2-hydroxyeth-yl)stearamide 1n were found to show a better anticonvulsant activity and also had lower toxicity than the marked anti-epileptic drug valproate. In the anti-MES potency test, these compounds exhibited median effective doses (ED50) of 22.0, 23.3, 20.5 mg/kg, respectively, and median toxicity doses (TD50) of 599.8, >1000, >1000 mg/kg, respectively, resulting in a protective index (PI) of 27.5, >42.9, >48.8, respectively. This is a much better protective index than that of the marked anti-epileptic drug valproate (PI = 1.6). To further investigate the effects of the anticonvulsant activity in several different models, compounds 1g, 1l, and 1n were tested having evoked convulsions with chemical substances, including pentylenetetrazloe, isoniazide, 3-mercaptopropionic acid, bicuculline, thiosemicarbazide, and strychnine. [source] Tetramethylcyclopropyl analogue of the leading antiepileptic drug, valproic acid: Evaluation of the teratogenic effects of its amide derivatives in NMRI mice,BIRTH DEFECTS RESEARCH, Issue 9 2008Akinobu Okada Abstract BACKGROUND: Although valproic acid (VPA) is used extensively for treating various kinds of epilepsy, it causes hepatotoxicity and teratogenicity. In an attempt to develop a more potent and safer second generation to VPA drug, the amide derivatives of the tetramethylcyclopropyl VPA analogue, 2,2,3,3-tetramethylcyclopropanecarboxamide (TMCD), N -methyl-TMCD (MTMCD), 4-(2,2,3,3-tetramethylcyclopropanecarboxamide)-benzenesulfonamide (TMCD-benzenesulfonamide), and 5-(TMCD)-1,3,4-thiadiazole-2-sulfonamide (TMCD-thiadiazolesulfonamide) were synthesized and shown to have more potent anticonvulsant activity than VPA. Teratogenic effects of these CNS-active compounds were evaluated in Naval Medical Research Institute (NMRI) mice susceptible to VPA-induced teratogenicity by comparing them to those of VPA. METHODS: Pregnant NMRI mice were given a single sc injection of either VPA or TMC-amide derivatives on gestation day 8.5, and then the live fetuses were examined to detect any external malformations on gestation day 18. After double-staining for bone and cartilage, their skeletons were examined. RESULTS: In contrast to VPA, which induced NTDs in a high number of fetuses at 2.4,4.8 mmol/kg, TMCD, TMCD-benzenesulfonamide, and TMCD-thiadiazolesulfonamide at 4.8 mmol/kg and MTMCD at 3.6 mmol/kg did not induce a significant number of NTDs. TMCD-thiadiazolesulfonamide exhibited a potential to induce limb defects in fetuses. Skeletal examination also revealed that fetuses exposed to all four of the tetramethylcyclopropanecarboxamide derivatives developed vertebral and rib abnormalities less frequently than those exposed to VPA. Our results established that TMCD, MTMCD, and TMCD-benzenesulfonamide are distinctly less teratogenic than VPA in NMRI mice. CONCLUSIONS: The CNS-active amides containing a tetramethylcyclopropanecarbonyl moiety demonstrated better anticonvulsant potency compared to VPA and a lack of teratogenicity, which makes these compounds good second-generation VPA antiepileptic drug candidates. Birth Defects Research (Part A), 2008. © 2008 Wiley-Liss, Inc. [source] Asymmetric 1,4-Addition of Oxazolones to Nitroalkenes by Bifunctional Cinchona Alkaloid Thiourea Organocatalysts: Synthesis of ,,,-Disubstituted ,-Amino AcidsCHEMISTRY - A EUROPEAN JOURNAL, Issue 35 2008José Alemán Dr. Abstract An easy and simple synthetic approach to optically active ,,,-quaternary ,-amino acids using asymmetric organocatalysis is presented. The addition of oxazolones to nitroalkenes catalyzed by thiourea cinchona derivatives provides the corresponding ,,,-quaternary ,-amino acid derivatives with good yields, excellent diastereoselectivities (up to 98,% dr), and from moderate to good enantioselectivities (up to 92,% ee). The reaction can be performed on a large scale. The optically active oxazolone,nitroalkene addition products can be opened in a one-pot reaction to the corresponding ester,amide derivatives. Additional transformations are also presented, such as the synthesis of amino esters, amino acids, and transformation into 3,4-disubstituted pyrrolidin-2-ones. [source] Improved 2,4-Diarylthiazole-Based Antiprion Agents: Switching the Sense of the Amide Group at C5 Leads to an Increase in PotencyCHEMMEDCHEM, Issue 9 2010Abstract Amide derivatives of 2,4-diarylthiazole-5-carboxylic acids were synthesised and tested for efficacy in a cell line model of prion disease. A number of compounds demonstrating antiprion activity were thereby identified from the screening libraries, showing improved potency and reproducibility of results relative to amide derivatives of the related 2,4-diphenyl-5-aminothiazole, which have been documented previously. Thus, 'switching' the sense of the amide bond at thiazole C5 revealed a more promising lead series of potential prion disease therapeutics. Furthermore, 3,5-diaryl-1,2,4-thiadiazoles isolated as by-products during library synthesis provided a handful of additional examples possessing an antiprion effect, thereby augmenting the set of newly identified active compounds. Evaluation of binding to cellular prion protein (PrPC) showed only weak affinities at best, suggesting that the newly identified antiprion agents do not mediate their biological effect through direct interaction with PrPC. [source] Probing Novel 1-Aza-9-oxafluorenes as Selective GSK-3, InhibitorsCHEMMEDCHEM, Issue 1 2008Burkhardt Voigt Dr. Abstract Within the histopathology of Alzheimer's disease (AD) certain hallmarks are beeing observed. The occurance of protein deposits belong to such characteristic features. Such deposits can be found extracellular as ,-amyloid (A,) plaques and intracellular as neurofibrillary tangles (NFTs). In the search for novel AD therapeutics it became of great interest to investigate the formation of NFTs and their contribution to the AD symptomatic. NFTs consist of hyperphosphorylated tau protein. Within the phosphorylation process of tau protein two kinases are of great importance: cyclin dependent kinase 5 (cdk5) and its truncated regulatory subunit p25 and glycogen synthase kinase 3, (GSK-3,). The role of both kinases within the NFT formation process is still under debate. To better understand the pathophysiological process highly selective inhibitors of both kinases are of value. Known inhibitors lack the necessary selectivity. We developed novel 1-aza-9-oxafluo-renes as selective GSK-3, inhibitors. Structure,activity relationships of a series of 4-phenyl substituted derivatives are discussed. Variation of the 3-side chain led to selective carbonyl amide derivatives with selectivity factors of more than 100 at the tested ATP competitor concentrations. Such selectivities permit specific investigation of the role of GSK-3, within the NFT formation processes. [source] Synthesis and Microbial Studies of New Pyridine Derivatives-IIICHINESE JOURNAL OF CHEMISTRY, Issue 9 2007N. B. Patel Abstract 2-Amino substituted benzothiazole 4a,4l and p -acetamidobenzenesulfonyl chloride 2 were used to prepare 2-(p -aminophenylsulfonamido) substituted benzothiazole 6a,6l using mixture of pyridine and acetic anhydride which formed an electrophilic complex (N -acetyl pyridinium) to facilitate condensation to give desired product by removal of HCl. 2-{p -[(3-Carboxypyrid-2-yl)amino]phenylsulfonamido}benzothiazoles 8a,8l were synthesized from 2-chloropyridine-3-carboxylic acid 7 and 6a,6l in 2-ethoxy ethanol using Cu-powder and K2CO3. Acid chlorides 9a,9l were condensed with 2-hydroxyethyl piperazine 10 and 2,3-dichloropiperazine 11 for amide derivatives 2-(p -((3-(4-(2-hydroxyethyl)piperazin-1-ylcarbonyl)pyrid-2-yl)amino)phenylsulfonamido)benzothiazoles 12a,12l and 2-{p -[3-(2,3-dichloropiperazin-1-ylcarbonyl)pyrid-2-ylamino]phenylsulfonamido}benzothiazoles 13a,13l respectively. The structures of the new compounds have been established on the basis of their chemical analysis and spectral data (IR, 1H NMR and mass). All the compounds have been screened for their antibacterial and antifungal activities. [source] | |||||||||||||||||||||||||