cas 61343-99-5, 4-(4-CHLOROPHENOXY)BENZALDEHYDE

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Design, synthesis and structure-activity relationship study of novel urea compounds as FGFR1 inhibitors to treat metastatic triple-negative breast cancer
Triple-negative breast cancer (TNBC) is an aggressive type of cancer characterized by higher metastatic and reoccurrence rates, where approximately one-third of TNBC patients suffer from the metastasis in the brain. At the same time, TNBC shows good responses to chemotherapy, a feature that fuels the search for novel compounds with therapeutic potential in this area. Recently, we have identified novel urea-based compounds with cytotoxicity against selected cell lines and with the ability to cross the blood-brain barrier in vivo. We have synthesized and analyzed a library of more than 40 compounds to elucidate the key features responsible for the observed activity. We have also identified FGFR1 as a molecular target that is affected by the presence of these compounds, confirming our data using in silico model. Overall, we envision that these compounds can be further developed for the potential treatment of metastatic breast cancer.
Akwii, Racheal,Alvina, Karina,Ashraf-Uz-Zaman, Md,Farshbaf, Mohammad Jodeiri,German, Nadezhda A.,Kallem, Raja Reddy,Mikelis, Constantinos M.,Putnam, William,Sajib, Md Sanaullah,Shahi, Sadisna,Trippier, Paul C.,Wang, Wei,Zhang, Ruiwen
supporting information

(2020/10/12)

Design and synthesis of methoxyphenyl- and coumarin-based chalcone derivatives as anti-inflammatory agents by inhibition of NO production and down-regulation of NF-κB in LPS-induced RAW264.7 macrophage cells
Exaggerated inflammatory responses may cause serious and debilitating diseases such as acute lung injury and rheumatoid arthritis. Two series of chalcone derivatives were prepared as anti-inflammatory agents. Methoxylated phenyl-based chalcones 2a-l and c
Emam, Soha H.,Sonousi, Amr,Osman, Eman O.,Hwang, Dukhyun,Kim, Gun-Do,Hassan, Rasha A.
(2021/01/20)

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
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
p. 1175 - 1193
(2021/12/21)

Design, synthesis, and evaluation of compounds capable of reducing Pseudomonas aeruginosa virulence
Anti-virulence approaches in the treatment of Pseudomonas aeruginosa (PA)-induced infections have shown clinical potential in multiple in vitro and in vivo studies. However, development of these compounds is limited by several factors, including the lack of molecules capable of penetrating the membrane of gram-negative organisms. Here, we report the identification of novel structurally diverse compounds that inhibit PqsR and LasR-based signaling and diminish virulence factor production and biofilm growth in two clinically relevant strains of P. aeruginosa. It is the first report where potential anti-virulent agents were evaluated for inhibition of several virulence factors of PA. Finally, co-treatment with these inhibitors significantly reduced the production of virulence factors induced by the presence of sub-inhibitory levels of ciprofloxacin. Further, we have analyzed the drug-likeness profile of designed compounds using quantitative estimates of drug-likeness (QED) and confirmed their potential as hit molecules for further development.
Hossain, Mohammad Anwar,Sattenapally, Narsimha,Parikh, Hardik I.,Li, Wei,Rumbaugh, Kendra P.,German, Nadezhda A.
supporting information

(2019/11/26)

Chlorination of Conjugated Nitroalkenes with PhICl 2and so 2Cl 2for the Synthesis of α-Chloronitroalkenes
Chlorination of conjugated nitroalkenes with iodobenzene dichloride or sulfuryl chloride to give target α-chloronitroalkenes in good yields is described. Details of the procedure depend on the donating ability of the nitroalkene substituents. The activity of the described chlorinating agents increases in order 'PhICl 2/Py' 2Cl 2' 2Cl 2/HCl' with the former producing the best yields for highly donating substrates and the latter for non-activated groups. An autocatalytic role of hydrogen chloride and the chemoselectivity of chlorination were also demonstrated.
Fadeeva, Anastasia A.,Ioffe, Sema L.,Tabolin, Andrey A.
supporting information
p. 2679 - 2688
(2020/11/02)

CoII Immobilized on Aminated Magnetic-Based Metal–Organic Framework: An Efficient Heterogeneous Nanostructured Catalyst for the C–O Cross-Coupling Reaction in Solvent-Free Conditions
Abstract: In this paper, we report the synthesis of Fe3O4?AMCA-MIL53(Al)-NH2-CoII NPs based on the metal–organic framework structures as a magnetically separable and environmentally friendly heterogeneous nanocatalyst. The prepared nanostructured catalyst efficiently promotes the C–O cross-coupling reaction in solvent-free conditions without the need for using toxic solvents and/or expensive palladium catalyst. Graphic Abstract: [Figure not available: see fulltext.].
Mohammadinezhad, Arezou,Akhlaghinia, Batool
p. 332 - 352
(2020/01/11)

Pyrimidine onium compound and application thereof
The invention relates to a pyrimidine onium compound, nitride oxides, salt of the nitride oxides and a composition comprising the compound. The invention further relates to an application of the compound to plant pest control.
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Paragraph 0220-0223

(2019/10/23)

Cinnamonitrile adjuvants restore susceptibility to β-lactams against methicillin-resistant staphylococcus aureus
β-Lactams are used routinely to treat Staphylococcus aureus infections. However, the emergence of methicillin-resistant S. aureus (MRSA) renders them clinically precarious. We describe a class of cinnamonitrile adjuvants that restore the activity of oxacillin (a penicillin member of the β-lactams) against MRSA. The lead adjuvants were tested against six important strains of MRSA, one vancomycin-intermediate S. aureus (VISA) strain, and one linezolid-resistant S. aureus strain. Five compounds out of 84 total compounds showed broad potentiation. At 8 μM (E)-3-(5-(3,4-dichlorobenzyl)-2-(trifluoromethoxy)phenyl)-2-(methylsulfonyl)acrylonitrile (26) potentiated oxacillin with a >4000-fold reduction of its MIC (from 256 to 0.06 mg·L-1). This class of adjuvants holds promise for reversal of the resistance phenotype of MRSA.
Speri, Enrico,Kim, Choon,De Benedetti, Stefania,Qian, Yuanyuan,Lastochkin, Elena,Fishovitz, Jennifer,Fisher, Jed F.,Mobashery, Shahriar
p. 1148 - 1153
(2019/08/27)

Synthesis and biological evaluation of new thiosemicarbazone derivative schiff bases as monoamine oxidase inhibitory agents
Twenty-six novel thiosemicarbazone derivative B1–B26 were synthesized via condensation reactions between the corresponding thiosemicarbazides and aldehydes. The chemical characterization of the compounds was carried out by infrared (IR), mass (MS), proton and carbon nuclear magnetic resonance (1H- and 13C-NMR) spectroscopic analyses. The compounds were investigated for their monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) inhibitory activity and most of them were more potent against MAO-A enzyme when compared with MAO-B enzyme. N-Cyclohexyl-2-[4-[(4-chlorophenyl)thio]benzylidene]hydrazine-1-carbothioamide (B24) was the most active compound against MAO-A. The enzyme kinetics study revealed that compound B24 has a reversible and competitive mode of binding. Interaction modes between compound B24 and MAO-A were clarified by docking studies. In addition, the favourable absorption, distribution, metabolism, and excretion (ADME) properties and non-toxic nature of compound B24 make this compound a promising MAO-A inhibitor.
?avu?o?lu, Betül Kaya,Sa?l?k, Beg m Nurpelin,Sa?l?k, Begüm Nurpelin,Osmaniye, Derya,Levent, Serkan,Evik, Ulviye Acar,Karaduman, Abdullah Burak,Zkay, Yusuf,Kaplanc?kl?, Zafer As?m
(2018/01/26)

Derivatives of 1H-imidazole-4,5-dicarboxamide and Use Thereof in Preparation of Anticoccidial Drugs
Disclosed are derivatives of 1H-imidazole-4,5-dicarboxamide and use thereof in preparation of anticoccidial drugs. The derivatives have structural formulae as shown in formulae (I) to (VI). The derivatives of 1H-imidazole-4,5-dicarboxamide as disclosed in the present invention have significant anticoccidial effect, especially against coccidia that show a resistance to other anticoccidial drugs, and thus they can be used in preparation of anticoccidial drug.
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Paragraph 0141-0144

(2019/01/10)

Palladium-on-Carbon-Catalyzed Coupling of Nitroarenes with Phenol: Biaryl Ether Synthesis and Evidence of an Oxidative-Addition-Promoted Mechanism
Nucleophilic substitution in nitroarenes to form biaryl ethers is of fundamental importance in organic synthesis. Under non-catalytic conditions, this can occur if highly activated nitroarenes are used or if the nucleophile is activated by a strong stoichiometric base. We established a new method involving the use of a ligand-free palladium-on-carbon (Pd/C) catalyst for the cross-coupling of activated nitroarenes with relatively non-nucleophilic phenol derivatives, including naphthol, in the absence of harsh bases. Control experiments, hot filtration, the three-phase test, and inductively coupled plasma atomic emission spectroscopy analysis revealed that the catalysis proceeded through an usual oxidative addition step of the nitroarene to Pd/C, which resulted in the release of active palladium particles having extremely high catalytic activity. DFT calculations revealed the origin of the selectivity of the activated nitroarenes.
Begum, Tahshina,Mondal, Manoj,Borpuzari, Manash Protim,Kar, Rahul,Gogoi, Pradip K.,Bora, Utpal
supporting information
p. 3244 - 3248
(2017/06/21)

Highly efficient heterogeneous copper-catalysed O-arylation of phenols by nitroarenes leading to diaryl ethers
The heterogeneous O-arylation of phenols by nitroarenes was achieved in DMF at 100 °C by using an MCM-41-immobilised bidentate nitrogen copper(II) complex [MCM-41-2N-Cu(OAc)2] as catalyst, yielding a variety of unsymmetrical diaryl ethers in good to excellent yields. This heterogeneous copper catalyst can be easily prepared by a simple procedure from commercially readily available and inexpensive reagents, recovered by filtration of the reaction solution and recycled at least seven times without significant loss of activity.
Du, Yingying,Yao, Fang,Tuo, Yuxin,Cai, Mingzhong
p. 725 - 729
(2018/01/08)

Design, synthesis and insecticidal evaluation of aryloxy dihalopropene derivatives
Plutella xylostella (P. xylostella) is a highly migratory, cosmopolitan species and one of the most important pest of cruciferous crops worldwide. Pyridalyl as a novel class of insecticides has good efficacy against P. xylostella. On the basis of the commercial insecticide pyridalyl, a series of new aryloxy dihalopropene derivatives were designed and synthesized by using Intermediate Derivatization Methods. Their chemical structures were confirmed by 1H NMR, high-resolution mass spectrum (HRMS), and single-crystal X-ray diffraction analysis. The insecticidal activities of the new compounds against P. xylostella were evaluated. The results of bioassays indicated that most of the compounds showed moderate to high activities at the tested concentration, especially compounds 10e and 10g displayed more than 75% insecticidal activity against P. xylostella at 6.25 mg/L, while pyridalyl showed 50% insecticidal activity at the same concentration. The field trials result of the insecticidal activities showed that compound 10e as a 10% emulsifiable concentrate (EC) was effective in the control of P. xylostella at 75-150 g a.i./ha, and the mortality of P. xylostella for treatment with compound 10e at 75 g a.i./ha was equivalent to pyridalyl at 105 g a.i./ha.
Yang, Ji-Chun,Li, Miao,Wu, Qiao,Liu, Chang-Ling,Chang, Xiu-Hui
p. 383 - 390
(2016/01/25)

Probing the Azaaurone Scaffold against the Hepatic and Erythrocytic Stages of Malaria Parasites
The potential of azaaurones as dual-stage antimalarial agents was investigated by assessing the effect of a small library of azaaurones on the inhibition of liver and intraerythrocytic lifecycle stages of the malaria parasite. The whole series was screened against the blood stage of a chloroquine-resistant Plasmodium falciparum strain and the liver stage of P. berghei, yielding compounds with dual-stage activity and sub-micromolar potency against erythrocytic parasites. Studies with genetically modified parasites, using a phenotypic assay based on the P. falciparum Dd2-ScDHODH line, which expresses yeast dihydroorotate dehydrogenase (DHODH), showed that one of the azaaurone derivatives has the potential to inhibit the parasite mitochondrial electron-transport chain. The global urgency in finding new therapies for malaria, especially against the underexplored liver stage, associated with chemical tractability of azaaurones, warrants further development of this chemotype. Overall, these results emphasize the azaaurone chemotype as a promising scaffold for dual-stage antimalarials.
Carrasco, Marta P.,Machado, Marta,Gon?alves, Lídia,Sharma, Moni,Gut, Jiri,Lukens, Amanda K.,Wirth, Dyann F.,André, Vania,Duarte, Maria Teresa,Guedes, Rita C.,dos Santos, Daniel J. V. A.,Rosenthal, Philip J.,Mazitschek, Ralph,Prudêncio, Miguel,Moreira, Rui
p. 2194 - 2204
(2016/10/19)

5,5-HETEROAROMATIC ANTI-INFECTIVE COMPOUNDS
The invention provides a series of 5,5-heteroaromatic compounds, syntheses thereof, compositions thereof, and methods of using such compounds and compositions. Various embodiments provide methods of killing and/or inhibiting the growth of M. tuberculosis
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Paragraph 0181

(2015/08/04)

5,5-HETEROAROMATIC ANTI-INFECTIVE COMPOUNDS
The invention provides a series of 5,5-heteroaromatic compounds, syntheses thereof, compositions thereof, and methods of using such compounds and compositions. Various embodiments provide methods of killing and/or inhibiting the growth of M. tuberculosis
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Paragraph 0216; 0251; 0252

(2016/10/10)

Synthesis and biological evaluation of novel n' (4-Aryloxybenzylidene)- 1h-Benzimidazole-2 carbohydrazide derivatives as anti-Tubercular agents
A series of structurally novel, (E)-N'-(4-Aryloxybenzylidene)-1H- Benzimidazole-2-Carbohydrazide derivatives were synthesized by molecular hybridization technique. All these compounds were evaluated against Mycobacterium tuberculosis H37Rv strains using R
Ali Siddiki, Afsar,Bairwa, Vinod Kumar,Telvekar, Vikas N.
p. 630 - 638
(2014/10/15)

INHIBITORS OF LEUKOTRIENE A4 HYDROLASE
The present invention is directed to compounds encompassed by the Formula (I), pharmaceutical compositions thereof, methods for inhibiting LTA-4 hydrolase, and methods for the treatment of a disease and disorder which is ameliorated by the inhibition of L
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(2014/10/04)

Probing the aurone scaffold against Plasmodium falciparum: Design, synthesis and antimalarial activity
A library comprising 44 diversely substituted aurones derivatives was synthesized by straightforward aldol condensation reactions of benzofuranones and the appropriately substituted benzaldehydes. Microwave enhanced synthesis using palladium catalyzed protocols was introduced as a powerful strategy for extending the chemical space around the aurone scaffold. Additionally, Mannich-base derivatives, containing a 7-aminomethyl-6-hydroxy substitution pattern at ring A, were also prepared. Screening against the chloroquine resistant Plasmodium falciparum W2 strain identified novel aurones with IC 50 values in the low micromolar range. The most potent compounds contained a basic moiety, with the ability to accumulate in acidic digestive vacuole of the malaria parasite. However, none of those aurones revealed significant activity against hemozoin formation and falcipain-2, two validated targets expressed during the blood stage of P. falciparum infection and functional in digestive vacuole of the parasite. Overall, this study highlight (i) the usefulness of aurones as platforms for synthetic procedures using palladium catalyzed protocols to rapidly deliver lead compounds for further optimization and (ii) the potential of novel aurone derivatives as promising antimalarial compounds.
Carrasco, Marta P.,Newton, Ana S.,Gon?alves, Lídia,Góis, Ana,Machado, Marta,Gut, Jiri,Nogueira, Fátima,H?nscheid, Thomas,Guedes, Rita C.,Dos Santos, Daniel J.V.A.,Rosenthal, Philip J.,Moreira, Rui
p. 523 - 534
(2014/05/20)

Augmentation of GABAergic neurotransmission by novel N-(substituted)-2-[4- (substituted)benzylidene]hydrazinecarbothioamides - A potential anticonvulsant approach
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
p. 477 - 487
(2013/07/19)

First palladium-catalyzed denitrated coupling reaction of nitroarenes with phenols
The first palladium-catalyzed protocol for the denitrated coupling reaction of nitroarenes with phenols has been developed, achieving unsymmetrical diaryl ethers in moderate to excellent yields. The cyclopalladated ferrocenylimine (catalyst Ic) exhibited highly catalytic activity for this transformation with low catalyst loading (0.75 mol%) and short reaction time (2 h). The efficiency of this reaction was demonstrated by its compatibility with a range of groups. Moreover, the rigorous exclusion of air or moisture was not required in these transformations. Copyright
Wang, Hailei,Yu, Ajuan,Cao, Aijuan,Chang, Junbiao,Wu, Yangjie
p. 611 - 614
(2013/10/21)

Ligand-free copper-catalyzed coupling of phenols with nitroarenes by using a metal-organic framework as a robust and recoverable catalyst
A highly porous metal-organic framework Cu2(BDC)2(DABCO) (H2BDC=1,4-benzenedicarboxylic acid, DABCO=1,4-diazabicyclo[2.2.2]octane) was synthesized and used as an efficient recyclable heterogeneous catalyst for the coupling reaction of phenols with nitroarenes to form diaryl ethers without using a ligand. Physical characterization of the MOF was obtained by using XRD, SEM, TEM, thermogravimetric analysis (TGA), FTIR spectroscopy, atomic absorption spectrophotometry (AAS), H2 temperature-programmed reduction (H2-TPR), and N2 physisorption measurements. The Cu2(BDC)2(DABCO)-catalyzed coupling reaction offers several advantages compared to the conventional Ullmann reaction for the synthesis of unsymmetrical diaryl ethers. To the best of our knowledge, the ligand-free Cu-catalyzed O-arylation reaction of phenols with nitroarenes that uses a heterogeneous catalyst has not been mentioned previously in the literature.
Phan, Nam T. S.,Nguyen, Tung T.,Nguyen, Vu T.,Nguyen, Khoa D.
p. 2374 - 2381
(2013/08/23)

A 2,2′-bipyridine-palladacycle catalyzed the coupling of arylboronic acids with nitroarenes
A novel palladium-catalyzed protocol for the synthesis of diaryl ethers derivatives has been developed. In the presence of 2,2′-bipyridine- cyclopalladated ferrocenylimine complex (Cat. Ic), diaryl ethers were selectively generated by adjusting reaction parameters through the coupling of arylboronic acids and nitroarenes with yields ranging from poor to good. The efficiency of this reaction was demonstrated by its compatibility with a range of groups. Moreover, the rigorous exclusion of air or moisture was not required in these transformations.
Peng, Dongpo,Yu, Ajuan,Wang, Hailei,Wu, Yangjie,Chang, Junbiao
p. 6884 - 6889
(2013/07/26)

Benzimidazole inhibitors of the protein kinase CHK2: Clarification of the binding mode by flexible side chain docking and protein-ligand crystallography
Two closely related binding modes have previously been proposed for the ATP-competitive benzimidazole class of checkpoint kinase 2 (CHK2) inhibitors; however, neither binding mode is entirely consistent with the reported SAR. Unconstrained rigid docking o
Matijssen, Cornelis,Silva-Santisteban, M. Cris,Westwood, Isaac M.,Siddique, Samerene,Choi, Vanessa,Sheldrake, Peter,Van Montfort, Rob L.M.,Blagg, Julian
supporting information
p. 6630 - 6639
(2013/01/15)

Design, synthesis and anticonvulsant evaluation of novel N-(4-substituted phenyl)-2-[4-(substituted) benzylidene]-hydrazinecarbothio amides
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.
experimental part
p. 153 - 166
(2012/03/09)

A New class of anticonvulsants possessing 6 hz psychomotor seizure test activity: 2-(1H-benzotriazol-1-yl)-N'-[substituted] acetohydrazides
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
experimental part
p. 337 - 348
(2012/08/28)

Design, synthesis, and anticonvulsant evaluation of some novel 1, 3 benzothiazol-2-yl hydrazones/acetohydrazones
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.
p. 2428 - 2442
(2012/10/30)

Ligand-free copper-catalyzed O-arylation of nitroarenes with phenols
The first example of ligand-free copper-catalyzed O-arylation of nitroarenes with phenols was developed, achieving unsymmetrical diaryl ethers in moderate to excellent yields. This arylation proceeded smoothly without promotion of the ligands, and displayed great functional group compatibility. Thus, the method represents a new, facile, and cost-effective approach to access unsymmetrical diaryl ethers.
Chen, Jiuxi,Wang, Xingyong,Zheng, Xingwang,Ding, Jinchang,Liu, Miaochang,Wu, Huayue
supporting information
p. 8905 - 8907
(2012/10/29)

Design & synthesis of N′-[substituted] pyridine-4-carbohydrazides as potential anticonvulsant agents
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.
experimental part
p. 509 - 518
(2011/03/19)

Design, synthesis and potential 6 Hz psychomotor seizure test activity of some novel 2-(substituted)-3-{[substituted]amino}quinazolin-4(3H)-one
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.
scheme or table
p. 1006 - 1018
(2011/04/24)

Anticonvulsant and neurotoxicity evaluation of some novel cyclohexyl-[4-substituted benzylidene/2-oxo-1,2-dihydro-indol-3-ylidene] thiosemicarbazides
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
experimental part
p. 447 - 450
(2011/11/04)

The coupling of arylboronic acids with nitroarenes catalyzed by rhodium
The coupling of arylboronic acids with electron-deficient nitroarenes was realized for the first time by using a rhodium(I) catalyst under an air atmosphere, achieving unsymmetrical diaryl ethers with yields ranging from poor to good. From a deuterium labeling experiment, the oxygen atom is derived from ambient water. The efficiency of this reaction was demonstrated by its compatibility with fluoro, bromo, chloro, and trifluoromethyl groups.
Zheng, Xingwang,Ding, Jinchang,Chen, Jiuxi,Gao, Wenxiao,Liu, Miaochang,Wu, Huayue
supporting information; experimental part
p. 1726 - 1729
(2011/05/06)

THIAZOLE COMPOUNDS AS ACTIVATORS OF SOLUBLE GUANYLATE CYCLASE
Disclosed are compounds of formula (I) wherein R1 and R2 are independently selected from hydrogen, halo, C1-4alkyl, C1-4alkoxy, CF3 and OCF3; -Y- represents formula (IA) R3 represents hydrogen, fluoro, chloro or C1-4alkyl; R4a and R4b each independently represent hydrogen, C1-4alkyl, C1-4alkoxy, CF3 or halo; and R5 represents a group Z-X; wherein Z is absent or represents (CH2)2 or O; and X represents formula (IB) wherein: J and L both represent CH, or one of J and L represents CH and the other represents N; when both J and L represent CH, R6 represents hydrogen, halo, CF3, C1-4alkyl or C1-4alkoxy in a meta or ortho position relative to the R7 substituent and R7 represents hydrogen, halo, CF3, OCF3, C1-4alkyl, C1-4alkoxy, CH2OH, CN, CONR8R9 or CO2H; or when one of J or L represents N, R6 represents hydrogen or halo in a meta or ortho position relative to the R7 substituent and R7 represents hydrogen, halo, CF3, C1-4alkyl, C1-4alkoxy, CH2OH, CN, CONR8R9 or CO2H; and R8 and R9 are independently selected from hydrogen and C1-4alkyl; or salts thereof which activate soluble guanylate cyclase (sGC), pharmaceutical compositions containing them, their use in medicine, and processes for their preparation.
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Page/Page column 53

(2010/04/03)

Synthesis and antiparasitic and antifungal evaluation of 2′-arylsubstituted-1H,1′H-[2,5′]bisbenzimidazolyl-5-carboxamidines
A series of 2′-arylsubstituted-1H,1′H-[2,5′]-bisbenzimidazolyl-5-carboxamidines were prepared in a six-step process starting from 4-amino-3-nitrobenzonitrile. The antiparasitic activity against Trypanosoma brucei rhodesiense (T.b.r.), Plasmodium falciparu
Alp, Mehmet,Goeker, Hakan,Brun, Reto,Yildiz, Sulhiye
experimental part
p. 2002 - 2008
(2009/10/02)

Synthesis and structure-activity relationships of 4-pyridones as potential antimalarials
A series of diaryl ether substituted 4-pyridones have been identified as having potent antimalarial activity superior to that of chloroquine against Plasmodium falciparum in vitro and murine Plasmodium yoelii in vivo. These were derived from the anticoccidial drug clopidol through a systematic study of the effects of varying the side chain on activity. Relative to clopidol the most active compounds show > 500-fold improvement in IC50 for inhibition of P. falciparum in vitro and about 100-fold improvement with respect to ED50 against P. yoelii in mice. These compounds have been shown elsewhere to act selectively by inhibition of mitochondrial electron transport at the cytochrome bc1 complex.
Yeates, Clive L.,Batchelor, John F.,Capon, Edward C.,Cheesman, Neil J.,Fry, Mitch,Hudson, Alan T.,Pudney, Mary,Trimming, Helen,Woolven, James,Bueno, José M.,Chicharro, Jesús,Fernández, Esther,Fiandor, José M.,Gargallo-Viola, Domingo,De Las Heras, Federico Gómez,Herreros, Esperanza,León, María L.
p. 2845 - 2852
(2008/12/23)

ANTIDIABETIC OXAZOLIDINEDIONES AND THIAZOLIDINEDIONES
Phenoxyphenyl and phenoxybenzyl oxazolidine-2,4-diones and thiazolidine-2,4-diones are agonists or partial agonists of PPAR gamma and are useful in the treatment and control of hyperglycemia that is symptomatic of type II diabetes, as well as dyslipidemia
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Page/Page column 33

(2010/11/25)

FUSED AROMATIC COMPOUNDS HAVING ANTI-DIABETIC ACTIVITY
Fused aromatic compounds of Formula (I) are PPAR gamma agonists or partial agonists and are useful in the treatment or control of type II diabetes, including hyperglycemia, dyslipidemia, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, and obes
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Page/Page column 38

(2010/11/23)

Thio-substituted tricyclic and bicyclic aromatic methanesulfinyl derivatives
The present invention is related to chemical compositions, processes for the preparation thereof and uses of the composition. Particularly, the present invention relates to compositions of compounds of Formula (A): wherein Ar, Y, R1 and q are as defined herein; and their use in the treatment of diseases, including treatment of sleepiness, promotion of wakefulness, treatment of Parkinson's disease, cerebral ischemia, stroke, sleep apneas, eating disorders, stimulation of appetite and weight gain, treatment of attention deficit hyperactivity disorder ("ADHD"), enhancing function in disorders associated with hypofunctionality of the cerebral cortex, including, but not limited to, depression, schizophrenia, fatigue, in particular, fatigue associated with neurologic disease, such as multiple sclerosis, chronic fatigue syndrome, and improvement of cognitive dysfunction.
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Page/Page column 29

(2008/06/13)

ANTIDIABETIC OXAZOLIDINEDIONES AND THIAZOLIDINEDIONES
Phenoxyphenyl and phenoxybenzyl oxazolidine-2,4-diones and thiazolidine-2,4-diones of formula (I) are agonists or partial agonists of PPAR gamma and are useful in the treatment and control of hyperglycemia that is symptomatic of type II diabetes, as well
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Page/Page column 30

(2010/02/13)

5-Aryl thiazolidine-2,4-diones as selective PPARγ agonists
A series of 5-aryl thiazolidine-2,4-diones containing 4-phenoxyphenyl side chains was designed, synthesized, and evaluated for PPAR agonist activities. One such compound 28 exhibited comparable levels of glucose correction to rosiglitazone in the db/db mouse type 2 diabetes animal model.
Koyama, Hiroo,Boueres, Julia K.,Han, Wei,Metzger, Edward J.,Bergman, Jeffrey P.,Gratale, Dominick F.,Miller, Daniel J.,Tolman, Richard L.,MacNaul, Karen L.,Berger, Joel P.,Doebber, Thomas W.,Leung, Kwan,Moller, David E.,Heck, James V.,Sahoo, Soumya P.
p. 1801 - 1804
(2007/10/03)

5-Aryl thiazolidine-2,4-diones: Discovery of PPAR dual α/γ agonists as antidiabetic agents
A novel series of 5-aryl thiazolidine-2,4-diones based dual PPARα/γ agonists was identified. A number of highly potent and orally bioavailable analogues were synthesized. Efficacy study results of some of these analogues in the db/db mice model of type 2 diabetes showed them superior to rosiglitazone in correcting hyperglycemia and hypertriglyceridemia.
Desai, Ranjit C.,Han, Wei,Metzger, Edward J.,Bergman, Jeffrey P.,Gratale, Dominick F.,MacNaul, Karen L.,Berger, Joel P.,Doebber, Thomas W.,Leung, Kwan,Moller, David E.,Heck, James V.,Sahoo, Soumya P.
p. 2795 - 2798
(2007/10/03)

Substituted benzimidazoles and imidazo-[4,5]-pyridines
2-Aryl substituted benzimidazoles and imidazo[4,5]pyridines are disclosed as inhibitors of Cds1 and useful as adjuvants to chemotherapy or radiation therapy in the treatment of cancer.
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(2008/06/13)

Thiol compounds, their production and use
Compounds represented by general formula (1) or salts thereof which have a matrix metalloprotease inhibitory activity and are useful as drugs, wherein the rings A and B represent each an optionally substituted homocycle or heterocycle, etc.; R1s are the same or different and each represents hydrogen, optionally substituted hydrocarbyl, acyl, etc.; X1represents a bond, optionally substituted divalent aliphatic hydrocarbyl, etc.; X2represents a bond, optionally substituted divalent aliphatic hydrocarbyl, —O—, etc.; Ys are the same or different represents hydrogen, optionally substituted hydrocarbyl, oxo, etc.; m is 0 or 1; n is an integer of 1 to 3; q1is an integer of 1 to 2n+4; and q2is an integer of 0 to 2n+3, provided that q1+q2is 2n+4.
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(2008/06/13)

Inhibitors of acyl-CoA:cholesterol O-acetyltransferase (ACAT). Part 1: Identification and structure-activity relationships of a novel series of substituted N-alkyl-N-biphenylmethyl-N'-arylureas
A series of N-alkyl-N-biphenylylmethyl-N'-arylurea and related derivatives represented by 1 have been prepared and evaluated for their ability to inhibit acyl-CoA:cholesterol O-acyltransferase in vitro and to lower plasma cholesterol levels in cholesterol-fed rats in vivo. Linking of two phenyl groups via oxygen and introduction of fluorine at appropriate positions on the biphenyl moiety improved in vitro and in vivo activity. From this series of analogs, compound 40 (FR179254), which had potent in vitro potency (rabbit intestinal microsomes IC50 = 25 nM), showed excellent plasma cholesterol-lowering activity when administered via the diet (ED50 = 0.045 mg/kg). However, the hypocholesterolemic effect of this compound was moderate when dosed by oral gavage in PEG400 as a vehicle (ED50 = 5.3 mg/kg). Modification of the N'-aryl moiety led to the identification of compound 50 (FR182980) which was efficacious in both dosing models (ED50 = 0.034 mg/kg and 0.11 mg/kg, respectively).
Tanaka, Akira,Terasawa, Takeshi,Hagihara, Hiroyuki,Sakuma, Yuri,Ishibe, Noriko,Sawada, Masae,Takasugi, Hisashi,Tanaka, Hirokazu
p. 15 - 30
(2007/10/03)

(Aryloxy)aryl semicarbazones and related compounds: A novel class of anticonvulsant agents possessing high activity in the maximal electroshock screen
A number of (aryloxy)aryl semicarbazones and related compounds were synthesized and evaluated far anticonvulsant activities. After intraperitoneal injection to mice, the semicarbazones were examined in the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ), and neurotoxicity (NT) screens. The results indicated that greater protection was obtained in the MES test than the scPTZ screen. Quantitation of approximately one-third of the compounds revealed an average protection index (PI, i.e. TD50/ED50) of approximately 9. After oral administration to rats, a number of compounds displayed significant potencies in the MES screen (ED50 of 1-5 mg/kg) accompanied by very high protection indices. In fact over half the compounds had PI figures of greater than 100, and two were in excess of 300. The compounds were essentially inactive in the scPTZ and NT screens after oral administration to rats. Various compounds displayed greater potencies and PI figures in the mouse intraperitoneal and rat oral screens than three reference clinically used drugs. The data generated supported a binding site hypothesis. Quantitative structure-activity relationships indicated a number of physicochemical parameters which contributed to activity in the MES screen. X-ray crystallography of five compounds suggested the importance of certain interatomic distances and bond angles for activity in the mouse and rat MES screens.
Dimmock, Jonathan R.,Puthucode, Ramanan N.,Smith, Jennifer M.,Hetherington, Mark,Quail, J. Wilson,Pugazhenthi, Uma,Lechler, Terry,Stables, James P.
p. 3984 - 3997
(2007/10/03)

A convenient method for the preparation of 4-aryloxyphenols
A convenient method for the preparation of 4-aryloxyphenols via the homologation of preformed phenols is described. Condensation of various 4-substituted phenols with either 4-fluorobenzaldehyde (8) or 4-fluoroacetophenone (9) yielded the corresponding 4-aryl-oxybenzaldehydes, 10, and acetophenones, 11, in 70-93% yield. Baeyer-Villiger oxidation of these materials with 3-chloroperoxybenzoic acid (MCPBA) yielded the corresponding 4-formyloxy and 4-acetoxyphenyl ethers which were hydrolyzed without purification to the desired 4-aryloxyphenols 12 in 72-94% yield. Both 4-fluorobenzaldehyde (8) and 4-fluoroacetophenone (9) are synthetically equivalent to the a4 umpoled synthon 6. Extension of this methodology of the preparation of 4,4'-[arylbis(oxy)]bisphenols from aromatic diols is also described. Condensation of various aromatic diols with 8 or 9 yielded the corresponding 4,4'-[arylbis(oxy)]bisbenzaldehydes 15 and acetophenones 16 in 71-89% yield. Baeyer-Villiger oxidation of these compounds with MCPBA yielded the desired 4,4'-[arylbis(oxy)]bisphenyl bisformates 17 and bisacetates 18 in 67-84% yield. Hydrolysis of these compounds afforded the desired 4,4'-[arylbis(oxy)bisphenols 19 in 70-91% yield.
Yeager,Schissel
p. 63 - 68
(2007/10/02)