- Design and synthesis of novel chalcone derivatives and evaluation of their inhibitory activities against acetylcholinesterase
-
According to the cholinergic hypothesis, an increase in the acetylcholine level in Alzheimer's disease patients relatively slows down the symptoms of the disease. The most commonly used drug, donepezil, is a cholinesterase inhibitor. In this study, 12 new
- Levent, Serkan,Osmaniye, Derya,?zkay, Yusuf,Ceyhun, ?l?im,Kaplanc?kl?, Zafer A.,Karaca, ?evval,Sa?l?k, Begüm N.
-
-
- A novel and unusual method for C[sbnd]N bond formation between benzene ring and various amines
-
A new approach to form C[sbnd]N bond without metal catalysis was developed. 4-acetylbenzoyl isocyanate reacted with various amines through a mild method to form C[sbnd]N bond. This reaction was amenable to scale-up and it afforded the corresponding products with good to excellent yields and tolerates a wide range of functional groups.
- Wang, Peng,Wang, Chen,Zhu, Zhenzhen,Xu, Sicong,Hou, Yunlei,Zhao, Yanfang
-
-
- Design, Synthesis and Antitubercular Activity of Novel Isoniazid?Cyclic?Amine?Azachalcones Hybrids
-
In this work, it is described the design of twenty-four heterocyclic amine-azachalcones compounds through molecular hybridization of chalcone scaffold and fragments of isoniazid, fluoroquinolones, and linezolid with antituberculosis potential. The new compounds were synthesized via Claisen-Schmidt condensation, providing yields of 36-95%. Fifteen compounds showed antituberculosis activity against Mycobacterium tuberculosis H37Rv strain. Two amine-azachalcones 15 and 17 showed relevant biological activity with minimum inhibitory concentration (MIC) values of 6.62 and 4.85 μM, respectively. Compound 12 showed the best profile of antitubercular activity with MIC = 9.54 μM and selectivity index (SI) = 9.33. It was found that morpholine group is important to increase potency of antimycobacterial activity but also to add some toxicity to the chalcone molecular framework. The results described herein would be a guide in the designing of novel and optimized antitubercular derivatives based on the chalcone scaffold.
- Barbosa, Sandro L.,Baroni, Adriano C. M.,Croda, Júlio,Gomes, Giovana B.,Guerrero, Palimécio G.,Moreira, Flora M. F.,Oliveira, Jefferson R. S.,Perdomo, Renata T.,Shiguemoto, Cristiane Y. K.,das Neves, Amarith R.
-
p. 1284 - 1295
(2020/10/14)
-
- Aryl-Diadamantyl Phosphine Ligands in Palladium-Catalyzed Cross-Coupling Reactions: Synthesis, Structural Analysis, and Application
-
Synthesis, temperature-dependent NMR structure investigation and utilization of a new, stable and easily accessible aryl-diadamantylphosphine ligand family is reported. The bulky and electron-rich phosphorus center of the ligand enhances the catalytic activity of palladium in cross-coupling reactions of sterically demanding ortho-substituted aryl halides. In our study, we demonstrated the synthetic applicability of the new phosphine ligands in Buchwald-Hartwig and tosyl hydrazone coupling reactions.
- Sinai, ádám,Simkó, Dániel Cs.,Szabó, Fruzsina,Paczal, Attila,Gáti, Tamás,Bényei, Attila,Novák, Zoltán,Kotschy, András
-
supporting information
p. 1122 - 1128
(2020/03/03)
-
- Application of hydrazino and hydrazido linkers to connect benzenesulfonamides with hydrophilic/phobic tails for targeting the middle region of human carbonic anhydrases active site: Selective inhibitors of hCA IX
-
Herein we report the design and synthesis of three different sets of novel benzenesulfonamides (5a-e, 7a-e and 10a-d) incorporating hydrophilic/hydrophobic tails by hydrazido or hydrazino linkers. The newly synthesized benzenesulfonamides were examined in vitro for their inhibitory activity towards four human (h) carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, hCA I, II, IX and XII using a stopped-flow CO2 hydrase assay. All these isoforms were inhibited by the sulfonamides (5a-e, 7a-e and 10a-d) with variable degrees in the following KI ranges: 76.8–357.4 nM for hCA I, 8.2–94.6 nM for hCA II, 2.0–46.3 nM for hCA XI, and 8.3–88.3 nM for hCA XII. The sulfonamide 7d exhibited potent anti-proliferative activity against breast MCF-7 cancer cell line under both normoxic and hypoxic conditions with IC50 values equal 3.32 ± 0.06 and 8.53 ± 0.32 μM, respectively, which are comparable to the reference drug doxorubicin (IC50 = 2.36 ± 0.04 and 8.39 ± 0.25 μM, respectively). Furthermore, 7d was screened for cell cycle disturbance and apoptosis induction in MCF-7 cells. It was found to persuade cell cycle arrest at G2-M stage as well as to alter the Sub-G1 phase, also, 7d resulted in a significant increase in the percent of annexinV-FITC positive apoptotic cells from 1.03 to 18.54%. Molecular docking study was carried out for 7d within the hCA IX and hCA XII active sites to rationalize the obtained inhibition results.
- Allam, Heba Abdelrasheed,Fahim, Samar H.,F.Abo-Ashour, Mahmoud,Nocentini, Alessio,Elbakry, Mohamed E.,Abdelrahman, Mohamed A.,Eldehna, Wagdy M.,Ibrahim, Hany S.,Supuran, Claudiu T.
-
p. 547 - 556
(2019/07/04)
-
- PYRIMIDINONE DERIVATIVES AND USES THEREOF TO NEUTRALIZE THE BIOLOGICAL ACTIVITY OF CHEMOKINES
-
A subject of the present invention is a compound having the general formula (I) a pharmaceutically acceptable salt thereof or a tautomeric form thereof, wherein A, B3, B4, B5, Y, X, B1 and B2 are as defined in any one of claims 1 to 10. Another subject of the invention is the compound as defined above for use as a medicament, in particular for preventing and/or treating inflammation and inflammatory diseases, immune and auto-immune diseases, pain related diseases, genetic diseases and/or cancer.
- -
-
Page/Page column 48
(2018/02/28)
-
- Design, synthesis and biological evaluation of novel aryldiketo acids with enhanced antibacterial activity against multidrug resistant bacterial strains
-
Antimicrobial resistance (AMR) is a major health problem worldwide, because of ability of bacteria, fungi and viruses to evade known therapeutic agents used in treatment of infections. Aryldiketo acids (ADK) have shown antimicrobial activity against several resistant strains including Gram-positive Staphylococcus aureus bacteria. Our previous studies revealed that ADK analogues having bulky alkyl group in ortho position on a phenyl ring have up to ten times better activity than norfloxacin against the same strains. Rational modifications of analogues by introduction of hydrophobic substituents on the aromatic ring has led to more than tenfold increase in antibacterial activity against multidrug resistant Gram positive strains. To elucidate a potential mechanism of action for this potentially novel class of antimicrobials, several bacterial enzymes were identified as putative targets according to literature data and pharmacophoric similarity searches for potent ADK analogues. Among the seven bacterial targets chosen, the strongest favorable binding interactions were observed between most active analogue and S. aureus dehydrosqualene synthase and DNA gyrase. Furthermore, the docking results in combination with literature data suggest that these novel molecules could also target several other bacterial enzymes, including prenyl-transferases and methionine aminopeptidase. These results and our statistically significant 3D QSAR model could be used to guide the further design of more potent derivatives as well as in virtual screening for novel antibacterial agents.
- Cvijeti?, Ilija N.,Verbi?, Tatjana ?.,Ernesto de Resende, Pedro,Stapleton, Paul,Gibbons, Simon,Jurani?, Ivan O.,Drakuli?, Branko J.,Zloh, Mire
-
p. 1474 - 1488
(2017/11/17)
-
- Exploring Tandem Ruthenium-Catalyzed Hydrogen Transfer and SNAr Chemistry
-
A hydrogen-transfer strategy for the catalytic functionalization of benzylic alcohols via electronic arene activation, accessing a diverse range of bespoke diaryl ethers and aryl amines in excellent isolated yields (38 examples, 70% average yield), is reported. Taking advantage of the hydrogen-transfer approach, the oxidation level of the functionalized products can be selected by judicious choice of simple and inexpensive additives.
- Polidano, Kurt,Reed-Berendt, Benjamin G.,Basset, Ana?s,Watson, Andrew J. A.,Williams, Jonathan M. J.,Morrill, Louis C.
-
p. 6716 - 6719
(2017/12/26)
-
- Ruthenium-catalyzed transfer hydrogenation of amino- and amido-substituted acetophenones
-
The ruthenium-catalyzed transfer hydrogenation of electron-rich amino-substituted acetophenones is reported. Variation of the reductant, ligands, base, and solvent allowed reaction optimization. A key discovery was the use of 1,4-butanediol as an irreversible reducing agent, which significantly improved the conversion. A range of amino- and amido-substituted aryl ketones were explored, and they all gave the corresponding alcohols in good yield, which demonstrates the wider applicability of this process. The ruthenium-catalyzed reduction of electron-rich amino-substituted acetophenones with 1,4-butanediol as an irreversible reducing agent is reported. Optimization of the conditions and variation of the amino substituent are explored as is the use of amido- and sulfonamidoacetophenones with varying results. Copyright
- Watson, Andrew J. A.,Fairbanks, Antony J.
-
supporting information
p. 6784 - 6788
(2013/11/06)
-
- Antimalarial Activity of Newly Synthesized Chalcone Derivatives In Vitro
-
Twenty-seven novel chalcone derivatives were synthesized using Claisen-Schmidt condensation and their antimalarial activity against asexual blood stages of Plasmodium falciparum was determined. Antiplasmodial IC50 (half-maximal inhibitory concentration) activity of a compound against malaria parasites in vitro provides a good first screen for identifying the antimalarial potential of the compound. The most active compound was 1-(4-benzimidazol-1-yl-phenyl)-3-(2, 4-dimethoxy-phenyl)-propen-1-one with IC50 of 1.1μg/mL, while that of the natural phytochemical, licochalcone A is 1.43μg/mL. The presence of methoxy groups at position 2 and 4 in chalcone derivatives appeared to be favorable for antimalarial activity as compared to other methoxy-substituted chalcones. Furthermore, 3, 4, 5-trimethoxy groups on chalcone derivative probably cause steric hindrance in binding to the active site of cysteine protease enzyme, explaining the relative lower inhibitory activity.
- Yadav, Neesha,Dixit, Sandeep K.,Bhattacharya, Amit,Mishra, Lokesh C.,Sharma, Manish,Awasthi, Satish K.,Bhasin, Virendra K.
-
experimental part
p. 340 - 347
(2012/08/29)
-
- Inhibitors of protein kinases
-
Compounds of general Formula (I): wherein R1, R2, R3, Ra, A, B and x are as defined herein are inhibitors of protein kinases in particular members of the cyclin-dependent kinase family and/or the glycogen synthase kinase 3 family and are useful in preventing and/or treating any type of pain, inflammatory disorders, cancer, immunological diseases, proliferative diseases, infectious diseases, cardiovascular diseases, metabolic disorders, renal diseases, neurologic and neuropsychiatric diseases and neurodegenerative diseases.
- -
-
Page/Page column 29; 30
(2011/10/04)
-
- ARYLPYRAZOLES AND ARYLISOXAZOLES AND THEIR USE AS PKD MODULATORS
-
The present invention provides novel organic compounds of formula (I) or (Ia): which may be inhibitors of a selective subset of kinases belonging to the AGC or calmodulin kinase family, such as for example PKD-1/2/3, inhibitors of histone deacetylase (HDA
- -
-
Page/Page column 64
(2011/02/24)
-
- KINASE INHIBITORS
-
A compound of the general formula (I) or pharmaceutically acceptable salts, hydrates, solvates, crystal forms or diastereomers thereof is described. A method of treating protein kinase-associated disease states using the compound of formula (I) is also de
- -
-
-
- Structure-affinity relationships of a unique nicotinic ligand: N1-dimethyl-N4-phenylpiperazinium iodide (DMPP)
-
DMPP is a well-known nicotinic agonist that does not fit any proposed pharmacophore for nicotinic binding and represents a unique ligand among the hundreds of nicotinic agonists studied in the past decades. A systematic modulation of the chemical structure of DMPP, aimed to establish its structure-affinity relationships, is reported. The research has allowed to identify molecules such as 11c, 13c, 14c, and 28c, with affinities for α4β2 receptors in the low nanomolar range, some 2 orders of magnitude lower than the lead compound. The agonistic properties of the most interesting compounds have been assessed by measuring their analgesic activity on mice (hot-plate test). Another result of the research was the identification of DMPP analogues, such as 3a (Ki = 90 nM) and 14b (Ki = 180 nM), that maintain affinity for the central nicotinic receptor when the ammonium function is changed into an aminic one and are therefore possible leads for drug development in neurodegenerative diseases.
- Romanelli,Manetti,Scapecchi,Borea,Dei,Bartolini,Ghelardini,Gualtieri,Guandalini,Varani
-
p. 3946 - 3955
(2007/10/03)
-
- Trialkylsilyl esters of 6(substituted amino)phenyl-1,-dihydro-2-oxonicotinic acid, methods for their production and conversion to the corresponding acid chlorides
-
Trialkylsilyl esters of 6-(substituted amino)phenyl-1,2-dihydro-2-oxonicotinic acid and acid addition salts thereof are disclosed. The compounds are useful intermediates in the preparation of pharmacological agents, especially antimicrobials of the penicillin or cephalosporin type. The compounds can be produced by reacting a 6-(substituted amino)phenyl-1,2-dihydro-2-oxonicotinic acid with a silylating agent and are converted to the useful corresponding acid chloride by reaction with thionyl chloride.
- -
-
-
- Novel antibacterial amide compounds and process means for producing the same
-
Novel organic amide compounds which are N-[6-[(substituted amino)phenyl]-1,2-dihydro-2-oxonicotinyl]penicillin and cephalosporin type compounds having broad spectrum antibacterial utility are provided by (a) reacting the free amino acid of the appropriate penicillin or cephalosporin or the acid salt or silylated derivative thereof with a reactive derivative of the corresponding N-6-[(substituted amino)phenyl]-1,2-dihydro-2-oxonicotinic acid or (b) reacting the free amino acid 6-amino-penicillanic acid, 7-aminocephalosporanic acid, 7-amino-3-methylceph-3-em-4-carboxylic acid or a related compound or the acid salt or silylated derivative thereof with a reactive derivative of the corresponding D-N-[6-[(substituted amino)phenyl]-1,2-dihydro-2-oxonicotinyl]-2-substituted glycine. Pharmaceutical compositions containing said compounds and methods for treating infections using said compositions are also disclosed.
- -
-
-