- Synthesis and cytotoxicity of novel chromenone derivatives bearing 4-nitrophenoxy phenyl acryloyl moiety
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This work describes synthesis of novel chromenone derivatives bearing 4-nitrophenoxy phenyl acryloyl moiety through the reaction of 4-(4-nitrophenoxy)benzaldehydes and 3-acetyl-2H-chromen-2-ones in refluxing toluene. Cytotoxicity of all compounds was eval
- Mahdavi, Mohammad,Mohammadi-Izad, Samira,Saeedi, Mina,Safavi, Maliheh,Ebrahimi, Seyed Esmaeil Sadat,Foroumadi, Alireza,Shafiee, Abbas
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- Fe-MIL-101 modified by isatin-Schiff-base-Co: a heterogeneous catalyst for C-C, C-O, C-N, and C-P cross coupling reactions
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A metal-organic framework functionalized with a cobalt-complex is preparedviapost-synthetic modification of Fe-MIL-101-NH2. Initially, Fe-MIL-101-NH2reacted with isatin to produce Fe-MIL-101-isatin-Schiff-base, which can anchor the cobalt by the addition of cobalt acetate. The resulting MOF-Co catalyst is characterized by employing multiple techniques. This new modified MOF acts as a heterogeneous and recyclable catalyst for efficient Ullmann, Buchwald-Hartwig, Hirao, Hiyama and Mizoroki-Heck cross-coupling reactions of several aryl halides/phenylboronic acid/phenyltosylate with phenols, anilines/heterocyclic amines, triethyl phosphite, triethoxyphenylsilane and alkenes and generates the expected coupling products in good to high yields.
- Farrokhi, Alireza,Rouzifar, Majid,Sansano, José Miguel,Sobhani, Sara
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p. 19963 - 19976
(2021/11/12)
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- Computational study and synthesis of a new class of anticonvulsants with 6 Hz psychomotor seizure test activity: 2-(1,3-benzodioxol-5-yloxy)-N'-[substituted]-acetohydrazides
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Background: About 50 million epileptic cases worldwide and 12 million in India are re-ported. Currently, available drugs yield adequate control of seizure in 60-70% of patients and show many toxic effects. These actualities provoked the search for novel, more efficacious and safer anti-convulsants. Objective: The concatenation of 2-(1,3-benzodioxol-5-yloxy)-N'-[substituted]-acetohydrazides SA 1-10 was designed by molecular hybridization, optimized by computational study and synthesized with the objective of obtaining a prototype of potent anticonvulsant molecules especially active against partial seizures. Methods: Computational study was performed to calculate the pharmacophoric design, projection of the pharmacokinetic parameters and docking scores of the titled compounds with molecular targets of epilepsy. The anticonvulsant activity was ascertained by 6 Hz psychomotor seizure test. Minimal motor impairment showing neurotoxicity was assessed using the Rotarod test. Results: Titled compounds possessed the indispensable elements of pharmacophore and displayed good binding affinity with molecular targets of epilepsy, such as GABA (A) alpha-1 & delta receptor, glutamate receptor, Na+/H+ exchanger and GABA-aminotransferase in docking studies. The most potent compound of the concatenation was 2-(1,3-benzodioxol-5-yloxy)-N'-[4-(4-chlorophenoxy)benzylidene]-acetohydrazide SA 4, showing 100% protection at four different time points with ED50 value 146.8 mg/kg at a TPE of 1 h in mice. Conclusion: The protection shown in 6 Hz test is implicated as the compound's ability to control partial seizures. Thus, the titled compounds can be considered as potential prototype candidates for antiepileptic therapy against partial seizures.
- Kumar, Praveen,Tripathi, Laxmi
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p. 1175 - 1193
(2021/12/21)
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- Importance of the proximity and orientation of ligand-linkage to the design of cinnamate-GW9662 hybrid compounds as covalent PPAR agonists
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Covalent agonists of PPAR cause unique receptor conformational changes and behave as selective PPAR modulators, whereas there are few covalent agonists other than endogenous unsaturated fatty acids metabolites. Previously, we established a cell-based stra
- Utsugi, Yuki,Kobuchi, Hirona,Kawamura, Yukio,Atito, Ahmed Salahelden Aboelhamd,Nagao, Masaya,Isoda, Hiroko,Miyamae, Yusaku
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- Synthesis and evaluation of new diaryl ether and quinoline hybrids as potential antiplasmodial and antimicrobial agents
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Synthesis and bioevaluation of new diaryl ether hybridized quinoline derivatives as antiplasmodial, antibacterial and antifungal agents is reported. It was encouraging to discover that several compounds displayed 2-3 folds better efficacy than chloroquine in chloroquine-resistant K1 strain of Plasmodium falciparum. Further, a few members of the library displayed good antibacterial efficacy against gram positive strains of bacteria but none of the compounds displayed any significant antifungal activity.
- Mishra, Amita,Batchu, Harikrishna,Srivastava, Kumkum,Singh, Pratiksha,Shukla, Pravin K.,Batra, Sanjay
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supporting information
p. 1719 - 1723
(2014/04/17)
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- Room temperature Ullmann type C-O and C-S cross coupling of aryl halides with phenol/thiophenol catalyzed by CuO nanoparticles
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C-O/C-S cross coupling of aryl halides with phenol or thiophenol was studied under ligand-free condition at room temperature over CuO nanocatalyst. The scope of the reaction was extended to various aryl halides and substituted phenols under optimized condition. In general, efficient, selective, and reusable heterogeneous nano CuO catalytic system has been developed for room temperature C-O and C-S Ullmann type cross coupling reactions.
- Babu, S. Ganesh,Karvembu
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p. 1677 - 1680
(2013/03/28)
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- Augmentation of GABAergic neurotransmission by novel N-(substituted)-2-[4- (substituted)benzylidene]hydrazinecarbothioamides - A potential anticonvulsant approach
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New N-(substituted)-2-[4-(substituted)benzylidene]hydrazinecarbothioamides were designed, synthesized and evaluated for anticonvulsant activity and neurotoxicity. The anticonvulsant activity was established in three seizure models i.e. MES, scMET and 6 Hz model. The most active compound was N-(4-methoxyphenyl)-2-[4-(4-methylphenoxy) benzylidene]hydrazinecarbothioamide PT 30 which showed 100% protection in both MES and 6 Hz test. Compound PT 30 showed protection at three different time points in 6 Hz test at a dose of 100 mg/kg. Compound 2-[4-(4-Chlorophenoxy)benzylidene]-N-cyclohexylhydrazine carbothioamide PT 4 was also found to be active in both MES and 6 Hz test. Titled compounds exhibited good binding properties with epilepsy molecular targets GABA (A) delta and GABA (A) alpha-1 receptors, in LGA based flexible docking studies. Compounds PT 30 and PT 4 were found to elevate γ-aminobutyric acid (GABA) levels in the midbrain and medulla oblongata regions of rat brain. A computational study was carried out for calculation of pharmacophore pattern and prediction of pharmacokinetic properties.
- Tripathi, Laxmi,Kumar, Praveen
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p. 477 - 487
(2013/07/19)
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- Design, synthesis and anticonvulsant evaluation of novel N-(4-substituted phenyl)-2-[4-(substituted) benzylidene]-hydrazinecarbothio amides
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Thirty six new N-(4-substituted phenyl)-2-[4-(substituted) benzylidene]-hydrazinecarbothioamides were synthesized and evaluated for anticonvulsant activity and neurotoxicity. The anticonvulsant activity was established in three seizure models i.e. MES, scMET and 6 Hz model. The most active compound was 2-[4-(4-chlorophenoxy)benzylidene]-N-(4-fluorophenyl) hydrazinecarbothioamide PC 31 which showed 100% protection at 0.5 h in the 6 Hz test. Compound 2-[4-(4-bromophenoxy) benzylidene]-N-(4-bromophenyl) hydrazinecarbothioamide PC 23 was found to be active in both the MES and 6 Hz test. A computational study was carried out from calculation of a pharmacophore pattern and the prediction of pharmacokinetic properties. Titled compounds have also exhibited good binding properties with epilepsy molecular targets such as glutamate, GABA (A) delta and GABA (A) alpha-1 receptors, in the Lamarckian genetic algorithm based on flexible docking studies.
- Tripathi, Laxmi,Kumar, Praveen,Singh, Ranjit,Stables, James P.
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experimental part
p. 153 - 166
(2012/03/09)
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- A New class of anticonvulsants possessing 6 hz psychomotor seizure test activity: 2-(1H-benzotriazol-1-yl)-N'-[substituted] acetohydrazides
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A series of 2-(1H-Benzotriazol-1-yl)-N'-[substituted]acetohydrazides was designed and synthesized keeping in view the structural requirement of pharmacophore and evaluated for anticonvulsant activity and neurotoxicity. The new compounds were characterized using FT-IR, 1H NMR, mass spectral data and elemental analysis. The anticonvulsant activity of the titled compounds was assessed using the 6 Hz psychomotor seizure test. The neurotoxicity was assessed using the rotarod method. The most active compound of the series was N'-[4-(1,3-Benzodioxol-5-yloxy)benzylidene]-2-(1Hbenzotriazol-1-yl) acetohydrazide (BTA 9), which showed good activity with 75 % protection (3/4, 0.5 h) at a dose of 100 mg/kg in mice. None of the compounds exhibited neurotoxicity. A computational study was carried out for the calculation of pharmacophore pattern and prediction of pharmacokinetic properties. Titled compounds have also exhibited good binding properties with epilepsy molecular targets such as glutamate, GABA (A) delta, GABA (A) alpha-1 receptors and Na/H exchanger, in Lamarckian genetic algorithm based flexible docking studies.
- Kumar, Praveen,Tripathi, Laxmi
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experimental part
p. 337 - 348
(2012/08/28)
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- Design, synthesis, and anticonvulsant evaluation of some novel 1, 3 benzothiazol-2-yl hydrazones/acetohydrazones
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A series of 2-[2-(substituted)hydrazinyl]-1,3-benzothiazole and 2-(1,3-benzothiazol-2-ylsulfanyl)-N′-(substituted)acetohydrazide were designed and synthesized keeping in view the structural requirement of pharmacophore and evaluated for anticonvulsant activity and neurotoxicity. The anticonvulsant activity of the titled compounds was assessed using the 6 Hz psychomotor seizure test. The most active compound of the series was 2-(1,3-benzothiazol-2-ylsulfanyl)-N′-[4-(4-bromophenoxy)benzylidene] acetohydrazide BT 15, which showed 75% protection (3/4, 1.0 h) and 50% protection (2/4, 0.5 h) at a dose of 100 mg/kg in mice. A computational study was carried out for calculation of pharmacophore pattern and prediction of pharmacokinetic properties. Titled compounds have also exhibited good binding properties with epilepsy molecular targets such as GABA (A) alpha-1, glutamate, GABA (A) delta receptors and Na/H exchanger, in Lamarckian genetic algorithmbased flexible docking studies. Springer Science+Business Media, LLC 2011.
- Kumar, Praveen,Shrivastava, Birendra,Pandeya, Surendra N.,Tripathi, Laxmi,Stables, James P.
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p. 2428 - 2442
(2012/10/30)
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- Design & synthesis of N′-[substituted] pyridine-4-carbohydrazides as potential anticonvulsant agents
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A series of N′-[substituted] pyridine-4-carbohydrazides were designed and synthesized keeping in view the structural requirement of pharmacophore and evaluated for anticonvulsant activity and neurotoxicity. The anticonvulsant activity of the titled compounds was established after intraperitoneal administration in three seizure models, which include MES, scMET and 6 Hz model. The most active compound of the series was N′-[4-(4-fluorophenoxy) benzylidene]pyridine-4-carbohydrazide PCH 6, which showed a MES ED50 value of 128.3 mg/kg and 6 Hz ED50 value of 53.3 mg/kg in mice. The median toxic dose (TD50) was 343.6 mg/kg, providing compound PCH 6 with a protection index of 2.67 in the MES test and 6.44 in 6 Hz test. A computational study was also carried out, including calculation of pharmacophore pattern, prediction of pharmacokinetic properties and docking studies.
- Tripathi, Laxmi,Singh, Ranjit,Stables, James P.
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experimental part
p. 509 - 518
(2011/03/19)
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- Design, synthesis and potential 6 Hz psychomotor seizure test activity of some novel 2-(substituted)-3-{[substituted]amino}quinazolin-4(3H)-one
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Thirty new 2-(substituted)-3-{[substituted]amino}quinazolin-4(3H)-one were designed and synthesized keeping in view the structural requirement of pharmacophore and evaluated for anticonvulsant activity and neurotoxicity. The anticonvulsant activity of the titled compounds was assessed using the 6 Hz psychomotor seizure test. The most active compound of the series was 3-({(E)-[3-(4-chloro-3-methylphenoxy)phenyl]methylidene}amino) -2-phenylquinazolin-4(3H)-one PhQZ 7, which showed 100% protection (4/4, 0.5 h) and 75% protection (3/4, 0.25 h) at a dose of 100 mg/kg in mice. A computational study was carried out for calculation of pharmacophore pattern and prediction of pharmacokinetic properties. Titled compounds have also exhibited good binding properties with epilepsy molecular targets such as glutamate, GABA (A) delta and GABA (A) alpha-1 receptors, in Lamarckian genetic algorithm based flexible docking studies.
- Kumar, Praveen,Shrivastava, Birendra,Pandeya, Surendra N.,Stables, James P.
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scheme or table
p. 1006 - 1018
(2011/04/24)
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- Anticonvulsant and neurotoxicity evaluation of some novel cyclohexyl-[4-substituted benzylidene/2-oxo-1,2-dihydro-indol-3-ylidene] thiosemicarbazides
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A series of novel cyclohexyl-[4-substituted benzylidene/2-oxo-1,2-dihydro- indol-3-ylidene]thiosemicarbazides were synthesized and screened for anticonvulsant activity in maximal electroshock induced seizure (MES) and subcutaneous metrazol (scMET) induced seizure models in mice. The neurotoxicity was assessed using the rotorod method. The compounds cyclohexyl-[4-(4- chlorophenoxy)- benzylidene]thiosemicarbazide (7d) and cyclohexyl-[2-oxo-1,2- dihydro-indol-3-ylidene]thiosemicarbazide (7i) emerged as the most promising one with anti-MES activity in mice i.p. All the compounds exhibited no neurotoxicity in rotorod method.
- Tripathi, Laxmi,Singh, Ranjit
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experimental part
p. 447 - 450
(2011/11/04)
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- Preparation and study of new phenolic azomethine compounds
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New phenolic azomethine compounds having the general formula HO-M-X were prepared by the classical condensation reaction of aromatic amines with various para-substituted benzaldehydes. M represents a calamitic azomethine mesogen and X is -NO2; -N(CH3)2; -N(CH2CH 3)2 or -NH2. The thermal properties of these compounds were investigated using different techniques, such as differential scanning calorimetry (DSC), thermo-optical analysis (TOA), polarized light microscopy (PLM) and thermogravimetric analysis (TGA). The phenolic azomethines having aspect ratio (L/D) values greater than 3.7 exhibited thermotropic liquid crystalline (TLC) behavior. These compounds showed absorption bands in UV due to both the π - π* and π - π* electronic transitions which seemed to be influenced by the electrono-donor or electrono-acceptor character of the end groups, Some structural parameters, such as molecular polarizability (a), stress optical coefficient (SOC) and anisotropy of polarizability (b 1-b2), were calculated and proved to correlate with both the UV and TLC behavior of these phenolic azomethine compounds.
- Cozan, Vasile,Marin, Luminita,Brumǎ, Maria
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p. 641 - 648
(2007/10/03)
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- Synthesis and study of new symmetric azomethine trimers containing biphenyl units
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New symmetric azomethines containing 4,47prime;-biphenylyl central moiety were prepared by acid catalyzed condensation reaction of 4,4′-bis(p- aminophenoxy)biphenyl with various aromatic aldehydes. End functional groups having an electrono-acceptor character such as -NO2, or electrono-donor character, such as di-alkylamino were selected. The influence of the end functional groups nature on the thermal and optical properties was investigated.
- Marin, Luminita,Cozan, Vasile,Bruma, Maria
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p. 649 - 653
(2007/10/03)
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- Checkpoint kinase inhibitors: SAR and radioprotective properties of a series of 2-arylbenzimidazoles
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The discovery of a series of novel, potent, and highly selective inhibitors of the DNA damage control kinase chk2 is disclosed. Here we report the first SAR study around inhibitors of this kinase. High-throughput screening of purified human chk2 led to the identification of a novel series of 2-arylbenzimidazole inhibitors of the kinase. Optimization was facilitated using homology models of chk2 and docking of inhibitors, leading to the highly potent 2-arylbenz-imidazole 2h (IC50 15 nM). Compound 2h is an ATP-competitive inhibitor of chk2 that dose dependency protects human CD4 + and CD8+ T-cells from apoptosis due to ionizing radiation. This work suggests that a selective small molecule inhibitor of chk2 could be a useful adjuvant to radiotherapy, increasing the therapeutic window of such treatment.
- Arienti, Kristen L.,Brunmark, Anders,Axe, Frank U.,McClure, Kelly,Lee, Alice,Blevitt, Jon,Neff, Danielle K.,Huang, Liming,Crawford, Shelby,Pandit, Chennagiri R.,Karlsson, Lars,Breitenbucher, J. Guy
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p. 1873 - 1885
(2007/10/03)
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- MESO-SUBSTITUTED PORPHYRINS
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Meso-substituted porphyrins of general formula (I) suitable for the use as photosensitising agents, in particular in photodynamic therapy, are herein described.
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- Carbocyclic and heterocyclic substituted semicarbazones and thiosemicarbazones and the use thereof
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This invention is related to carbocyclic and heterocyclic substituted semicarbazones and thiosemicarbazones represented by Formula I: or a pharmaceutically acceptable salt or prodrug thereof, wherein: Y is oxygen or sulfur; R1, R21, R22 and R23 are independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl; or R22 and R23, together with the N, form a heterocycle; A1 and A2 are independently aryl, heteroaryl, saturated or partially unsaturated carbocycle or saturated or partially unsaturated heterocycle, any of which is optionally substituted; X is one or O, S, NR24, CR25R26, C(O), NR24C(O), C(O)NR24, SO, SO2 or a covalent bond; where R24, R25 and R26 are independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl. The invention also is directed to the use of carbocycle and heterocycle substituted semicarbazones and thiosemicarbazones for the treatment of neuronal damage following global and focal ischemia, for the treatment or prevention of neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS), for the treatment and prevention of otoneurotoxicity and eye diseases involving glutamate toxicity and for the treatment, prevention or amelioration of pain, as anticonvulsants, and as antimanic depressants, as local anesthetics, as antiarrhythmics and for the treatment or prevention of diabetic neuropathy and urinary incontinence.
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- 3-diphenyl substituted octahydroindolizine analgesic compounds
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Octahydroindolizine compounds of formula (I): STR1 wherein Q is --NR--, --(CH2)z --, --CH=CH--, --C C--, --OCH2 --, --SCH2 --, --SO2 --, --SO--, --CO--, or an oxygen or a sulfur atom and where R, R1 and R2 are substituents such as alkyl and x, y and z are independently the integers 0-3. Also, pharmaceutical compositions containing (I), intermediates and methods for treating pain.
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