- Discovery of Resorcinol-Based Polycyclic Structures as Tyrosinase Inhibitors for Treatment of Parkinson’s Disease
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Tyrosinase is involved in the synthesis of neuromelanin in the substantia nigra, which is closely correlated with the pathogenesis of Parkinson’s disease. Herein, we identified S05014 (l-Tyr, IC50 = 6.25 ± 1.43 nM; l-Dopa, IC50 = 0.6
- Li, Qi,Mo, Jun,Xiong, Baichen,Liao, Qinghong,Chen, Ying,Wang, Yuanyuan,Xing, Shuaishuai,He, Siyu,Lyu, Weiping,Zhang, Ning,Sun, Haopeng
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- Synthesis of Functionalized Cyclobutenes and Spirocycles via Asymmetric P(III)/P(V) Redox Catalysis
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An enantioselective phosphine-catalyzed transformation has been developed for the synthesis of chiral cyclobutene triesters and fluorinated spirocyclic compounds. The strategy involved a P(III)/P(V) redox cycling process, via in situ reduction of phosphin
- Lorton, Charlotte,Roblin, Antoine,Retailleau, Pascal,Voituriez, Arnaud
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supporting information
p. 4805 - 4810
(2021/09/08)
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- Synthesis, characterization, antioxidant activity of β-diketonates, and effects of coordination to copper(Ii) ion on their activity: Dna, bsa interactions and molecular docking study
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Background: In order to make some progress in discovering the more effective way to eliminate ROS which cause the oxidative stress in organism in humans and bearing in mind the fact that ethyl-2-hydroxy-4-aryl(alkyl)-4-oxo-2-butenoates (β-diketonates) belong to a class of biologically active compounds, series of β-diketonates were synthesized, characterized, and tested to evaluate there antioxidant activity. Further, to investigate how coordination to copper(II) ion affects the activity of β-diketonates, appropriate complexes were synthesized and characterized. Methods: All complexes were characterized by UV-Vis, IR, and EPR spectroscopy, MS spectrometry, and elemental analysis. Fluorescence spectroscopic method was used for investigations of the interactions between biomacromolecules (DNA or BSA) and compound 2E. Viscosity measurements and molecular docking study were performed to confirm the mode of interactions between DNA and BSA and compound 2E. Results: Scavenging activity on DPPH radical revealed that compounds 2A, 2B, and 2E possess largest free radical scavenging, comparable to standard while results of superoxide anion scavenging activities of tested samples showed that maximum scavenging activity (IC50=168.92 μg/mL) was found for 2E, very similar to standard ascorbic acid, followed by 2B and 2G. Results of the interactions between biomacromolecules and 2E indicated that 2E has the affinity to displace EB from the EB-DNA complex through intercalation [Ksv = (3.7 ± 0.1) × 103 M-1], while Ka value obtained via titration of BSA with 2E [Ka = (4.2 ± 0.2) × 105 M-1], support the fact that the significant amount of the drug could be transported and distributed through the cells. Conclusions: All β-diketonates exhibited better scavenging activities than their corresponding copper complexes. Among all the tested compounds, 2E gave the highest reducing power, even higher than standard ascorbic acid, while reducing power for compounds 2A and 2B was also good but lower than standard. DNA and BSA binding study for 2E showed that this compound has the potential to be used as medicament.
- Joksimovi?, Nenad,Petronijevi?, Jelena,Jankovi?, Nenad,Kosani?, Marijana,Milivojevi?, Du?an,Vrane?, Milan,Tot, Aleksandar,Bugar?i?, Zorica
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p. 519 - 532
(2021/03/26)
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- Discovery of Membrane-Bound Pyrophosphatase Inhibitors Derived from an Isoxazole Fragment
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Membrane-bound pyrophosphatases (mPPases) regulate energy homeostasis in pathogenic protozoan parasites and lack human homologues, which makes them promising targets in e.g. malaria. Yet only few nonphosphorus inhibitors have been reported so far. Here, w
- Johansson, Niklas G.,Turku, Ainoleena,Vidilaseris, Keni,Dreano, Lo?c,Khattab, Ayman,Ayuso Pérez, Daniel,Wilkinson, Aaron,Zhang, Yuezhou,Tamminen, Matti,Grazhdankin, Evgeni,Kiriazis, Alexandros,Fishwick, Colin W. G.,Meri, Seppo,Yli-Kauhaluoma, Jari,Goldman, Adrian,Boije Af Genn?s, Gustav,Xhaard, Henri
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supporting information
p. 605 - 610
(2020/03/10)
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- Discovery of novel urea-diarylpyrazole hybrids as dual COX-2/sEH inhibitors with improved anti-inflammatory activity and highly reduced cardiovascular risks
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Herein we describe our efforts to develop novel anti-inflammatory/analgesic agents devoid of known cardiovascular drawbacks. In doing so, two 1,5-diarylpyrazole series of urea linked (9a-f) and amide linked (11a-f) compounds were synthesized and evaluated
- Abdelazeem, Ahmed H.,Safi El-Din, Asmaa G.,Abdel-Fattah, Maha M.,Amin, Noha H.,El-Moghazy, Samir M.,El-Saadi, Mohammed T.
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- Development of a continuous flow photoisomerization reaction converting isoxazoles into diverse oxazole products
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A continuous flow process is presented, which directly converts isoxazoles into their oxazole counterparts via a photochemical transposition reaction. This results in the first reported exploitation of this transformation to establish its scope and synthe
- Bracken, Cormac,Baumann, Marcus
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p. 2607 - 2617
(2020/03/11)
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- Design, synthesis and antimycobacterial activity of benzoxazinone derivatives and open-ring analogues: Preliminary data and computational analysis
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This study examines in depth benzoxazine nucleus for antimycobacterial property. We synthesized some benzoxazin-2-one and benzoxazin-3-one derivatives, which were tested for activity against a panel of Mycobacterium tuberculosis (Mtb) strains, including H37Ra, H37Rv and some resistant strains. Several compounds displayed a high antimycobacterial activity and the three isoniazid analogue derivatives 8a-c exhibited a MIC range of 0.125–0.250 μg/mL (0.37–0.75 μM) against strain H37Ra, therefore lower than the isoniazid reference drug. Two benzoxazin-2-one derivatives, 1c and 5j, together with isoniazid-analogue compound 8a, also revealed low MIC values against resistant strains and proved highly selective for mycobacterial cells, compared to mammalian Vero cells. To predict whether molecule 8a is able to interact with the active site of InhA, we docked it into the crystal structure; indeed, during the molecular dynamic simulation the compound never left the protein pocket. The more active compounds were predicted for ADME properties and all proved to be potentially orally active in humans.
- Zampieri, Daniele,Mamolo, Maria Grazia,Filingeri, Julia,Fortuna, Sara,De Logu, Alessandro,Sanna, Adriana,Zanon, Davide
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supporting information
p. 2468 - 2474
(2019/07/30)
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- PYRADAZINONE DERIVATIVES AND THE COMPOSITIONS AND METHODS OF TREATMENT REGARDING THE SAME
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The present disclosure is directed to pyridazin-3(2H)-one compounds of formula (I), pharmaceutical compositions thereof and methods for modulating or activating a Parkin ligase The present disclosure is also directed to methods of treating and/or reducing the incidence of diseases or conditions related to the activation of Parkin ligase, R21, R22, R23, R24 and R25 are as defined herein.
- -
-
Paragraph 498-500
(2018/01/17)
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- Diketo acids and their amino acid/dipeptidic analogues as promising scaffolds for the development of bacterial methionine aminopeptidase inhibitors
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Using diketoesters as the template, various derivatives were designed and the selected compounds were synthesized as bacterial methionine aminopeptidase (MetAP) inhibitors. The results of in vitro antibacterial screening revealed fifteen compounds (1a-c,
- Masood, Mir Mohammad,Pillalamarri, Vijay K.,Irfan, Mohammad,Aneja, Babita,Jairajpuri, Mohamad Aman,Zafaryab,Rizvi, M. Moshahid A.,Yadava, Umesh,Addlagatta, Anthony,Abid, Mohammad
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p. 34173 - 34183
(2015/04/27)
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- NMDA RECEPTOR MODULATORS AND USES RELATED THERETO
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This disclosure relates to NMDA modulators and used related thereto such as for treatment of central nervous system disorders. In certain embodiments, compounds disclosed herein are NR2C subunit-selective NMDA potentiators. In certain embodiments, the disclosure contemplates compounds and pharmaceutical compositions. In certain embodiments, the disclosure contemplates compounds disclosed herein as prodrugs, optionally substituted with one or more substituents, derivatives, or salts thereof. In certain embodiments, the disclosure relates to methods of treating or preventing nervous system disorders comprising administering an effective amount of a composition comprising compound disclosed herein to a subject in need thereof.
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Page/Page column 28; 43; 55
(2014/03/21)
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- Design, synthesis, and structure-activity relationship of a novel series of GluN2C-selective potentiators
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NMDA receptors are tetrameric complexes composed of GluN1 and GluN2A-D subunits that mediate a slow Ca2+-permeable component of excitatory synaptic transmission. NMDA receptors have been implicated in a wide range of neurological diseases and thus represent an important therapeutic target. We herein describe a novel series of pyrrolidinones that selectively potentiate only NMDA receptors that contain the GluN2C subunit. The most active analogues tested were over 100-fold selective for recombinant GluN2C-containing receptors over GluN2A/B/D-containing NMDA receptors as well as AMPA and kainate receptors. This series represents the first class of allosteric potentiators that are selective for diheteromeric GluN2C-containing NMDA receptors.
- Zimmerman, Sommer S.,Khatri, Alpa,Garnier-Amblard, Ethel C.,Mullasseril, Praseeda,Kurtkaya, Natalie L.,Gyoneva, Stefka,Hansen, Kasper B.,Traynelis, Stephen F.,Liotta, Dennis C.
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p. 2334 - 2356
(2014/04/17)
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- 'One-pot' synthesis of 4-substituted 1,5-diaryl-1H-pyrazole-3-carboxylates via lithium tert-butoxide-mediated sterically hindered Claisen condensation and Knorr reaction
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A concise 'one-pot' synthesis of a variety of 4-substituted 1,5-diaryl-1H-pyrazole-3-carboxylates has been developed in moderate to good yields with excellent regioselectivity. Less cost lithium tert-butoxide has been identified as a base for sterically hindered Claisen condensation to efficiently generate the labile 3-substituted 4-aryl-2,4-diketoesters. Furthermore, extensive studies lead to a 'one-pot' process by combination of the Claisen condensation and the Knorr reaction for the synthesis of highly valuable 4-substituted 1,5-diaryl-1H-pyrazole-3-carboxylates.
- Jiang, Jian-An,Huang, Wei-Bin,Zhai, Jiao-Jiao,Liu, Hong-Wei,Cai, Qi,Xu, Liu-Xin,Wang, Wei,Ji, Ya-Fei
-
supporting information
p. 627 - 635
(2013/07/25)
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- 3-Carboxamido-5-aryl-isoxazoles as new CB2 agonists for the treatment of colitis
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Recent investigations showed that anandamide, the main endogenous ligand of CB1 and CB2 cannabinoid receptors, possesses analgesic, antidepressant and anti-inflammatory effects. In the perspective to treat inflammatory bowel disease (IBD), our approach was to develop new selective CB2 receptor agonists without psychotropic side effects associated to CB1 receptors. In this purpose, a new series of 3-carboxamido-5- aryl-isoxazoles, never described previously as CB2 receptor agonists, was designed, synthesized and evaluated for their biological activity. The pharmacological results have identified great selective CB2 agonists with in vivo anti-inflammatory activity in a DSS-induced acute colitis mouse model.
- Tourteau, Aurélien,Andrzejak, Virginie,Body-Malapel, Mathilde,Lemaire, Lucas,Lemoine, Amélie,Mansouri, Roxane,Djouina, Madjid,Renault, Nicolas,El Bakali, Jamal,Desreumaux, Pierre,Muccioli, Giulio G.,Lambert, Didier M.,Chavatte, Philippe,Rigo, Beno?t,Leleu-Chavain, Natascha,Millet, Régis
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p. 5383 - 5394
(2013/09/02)
-
- New selective carbonic anhydrase IX inhibitors: Synthesis and pharmacological evaluation of diarylpyrazole-benzenesulfonamides
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Carbonic anhydrase (CA) IX expression is increased upon hypoxia and has been proposed as a therapeutic target since it has been associated with poor prognosis, tumor progression and pH regulation. We report the synthesis and the pharmacological evaluation
- Rogez-Florent, Tiphaine,Meignan, Samuel,Foulon, Catherine,Six, Perrine,Gros, Abigaelle,Bal-Mahieu, Christine,Supuran, Claudiu T.,Scozzafava, Andrea,Frederick, Raphael,Masereel, Bernard,Depreux, Patrick,Lansiaux, Amelie,Goossens, Jean-Francois,Gluszok, Sebastien,Goossens, Laurence
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p. 1451 - 1464
(2013/04/10)
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- 3-aroylmethylene-2,3,6,7-tetrahydro-1 H -pyrazino[2,1- a ]isoquinolin-4(11b H)-ones as potent Nrf2/ARE inducers in human cancer cells and AOM-DSS treated mice
-
Nrf2-mediated activation of ARE regulates expression of cytoprotective enzymes against oxidative stress, inflammation, and carcinogenesis. We have discovered a novel structure (1) as an ARE inducer via luciferase reporter assay to screen the in-house data
- Xi, Mei-Yang,Jia, Jian-Min,Sun, Hao-Peng,Sun, Zhong-Ying,Jiang, Jie-Wei,Wang, Ya-Jing,Zhang, Min-Ye,Zhu, Jun-Feng,Xu, Li-Li,Jiang, Zheng-Yu,Xue, Xin,Ye, Ming,Yang, Xi,Gao, Yuan,Tao, Lei,Guo, Xiao-Ke,Xu, Xiao-Li,Guo, Qing-Long,Zhang, Xiao-Jin,Hu, Rong,You, Qi-Dong
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p. 7925 - 7938
(2013/11/06)
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- Novel antiobesity agents: Synthesis and pharmacological evaluation of analogues of Rimonabant and of LH21
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Searching for novel antiobesity agents, a series of cannabinoid LH21 and of Rimonabant-fatty acid amide analogues have been prepared. Synthesis of pyrazoles 2a-2c was achieved by a two steps simple methodology via α,β-unsaturated ketones. Carboxamides 8a-8h were obtained in good yields from esters 7a-7c by a one-pot procedure which takes place under mild conditions. New compounds have been evaluated in vivo as anorectic agents. Some of them showed interesting properties reducing food intake in rats by a mechanism which does not involve the endocannabinoid system.
- Alvarado, Mario,Decara, Juan,Luque, María Jesús,Hernandez-Folgado, Laura,Gómez-Ca?as, María,Gómez-Ruiz, María,Fernández-Ruiz, Javier,Elguero, José,Jagerovic, Nadine,Serrano, Antonia,Goya, Pilar,De Fonseca, Fernando Rodríguez
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p. 1708 - 1716
(2013/05/09)
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- New FAAH inhibitors based on 3-carboxamido-5-aryl-isoxazole scaffold that protect against experimental colitis
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Growing evidence suggests a role for the endocannabinoid (EC) system, in intestinal inflammation and compounds inhibiting anandamide degradation offer a promising therapeutic option for the treatment of inflammatory bowel diseases. In this paper, we repor
- Andrzejak, Virginie,Muccioli, Giulio G.,Body-Malapel, Mathilde,El Bakali, Jamal,Djouina, Madjid,Renault, Nicolas,Chavatte, Philippe,Desreumaux, Pierre,Lambert, Didier M.,Millet, Regis
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experimental part
p. 3777 - 3786
(2011/08/03)
-
- Synthesis of 2,3 and 4,5-dihydro-hydroxy-isoxazoles and isoxazoles under different pH conditions
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Reaction between aryl 1,3-diketoesters 2a-e and hydroxylamine hydrochloride has been investigated under different experimental conditions. Whereas acid conditions gave principally 3,5-isoxazole esters (3a-e), reactions under neutral and basic conditions l
- Andrzejak, Virginie,Millet, Regis,Bakali, Jamal El,Guelzim, Abdelhalim,Gluszok, Sebastien,Chavatte, Philippe,Bonte, Jean-Paul,Vaccher, Claude,Lipka, Emmanuelle
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experimental part
p. 32 - 38
(2010/08/05)
-
- INHIBITORS OF MYCOBACTERIUM TUBERCULOSIS MALATE SYNTHASE, METHODS OF MARKING AND USES THEREOF
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The present invention provides aryl- or heteroaryl- diketo acid compounds effective to inhibit an activity of a Mycobacterial malate synthase enzyme or to inhibit a malate synthase activity in other bacteria having the enzyme. The compounds may be phenyl-
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Page/Page column 31
(2010/05/13)
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- A new chemo-enzymatic route to chiral 2-hydroxy-4-phenylbutyrates by combining lactonase-mediated resolution with hydrogenation over Pd/C
-
A new chemo-enzymatic route to both isomers of 2-hydroxy-4-phenylbutyric acid is reported. The key step is the lactonase-catalyzed hydrolysis of cis- and trans-2-hydroxy-4-phenyl-4-butyrolactones followed by hydrogenation over Pd/C to afford optically pure 2-hydroxy-4-phenylbutyric acid.
- Chen, Bing,Yin, Hai-Feng,Wang, Zhen-Sheng,Liu, Jia-Ying,Xu, Jian-He
-
scheme or table
p. 2754 - 2756
(2010/09/04)
-
- Synthesis of novel 2,3-substituted-2,4-dihydro-pyrazolo[4,3-d]pyrimidine-5,7-diones
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Novel 2,3-substituted-2,4-dihydro-pyrazolo[4,3-d]pyrimidine-5,7-diones were successfully synthesized with moderate to good yields using a new synthetic approach. The structures of the regio-isomers in this series were determined by single crystal X-ray an
- Brady, Thomas,Vu, Khang,Barber, Jack R.,Ng, Shi Chung,Zhou, Yuefen
-
experimental part
p. 6223 - 6227
(2010/01/18)
-
- Facile synthesis of enantiopure 4-substituted 2-hydroxy-4butyrolactones using a robust Fusarium lactonase
-
A facile chemo-enzymatic process has been developed for producing stereoisomers of 4substituted 2-hydroxy-4-butyrolactones with good to excellent enantioselectivity. This process involves an easy separation of the diastereoisomers by column chromatography
- Chen, Bing,Yin, Hai-Feng,Wang, Zhen-Sheng,Xu, Jian-He,Fan, Li-Qiang,Zhao, Jian
-
experimental part
p. 2959 - 2966
(2010/03/26)
-
- Analogs of 4-hydroxyisoleucine and uses thereof
-
The invention relates to analogs of 4-hydroxyisoleucine, and to lactones, pharmaceutically acceptable salts, and prodrugs thereof, to processes for their preparation, and to pharmaceutical compositions comprising the same. The analogs of the invention stimulate both glucose uptake and insulin secretion, and may thus be useful for the prevention and treatment of disorders of carbohydrate or lipid metabolism, including diabetes mellitus (type 1 and type 2 diabetes), pre-diabetes, and Metabolic Syndrome.
- -
-
Page/Page column 44
(2008/06/13)
-
- Compounds and compositions for use in the prevention and treatment of obesity and related syndromes
-
The invention relates to 4-hydroxyisoleucine, isomers, analogs, lactones, salts, and prodrugs thereof, to processes for their preparation, and to pharmaceutical compositions comprising the same. More particularly, the invention relates to the use of those compounds in the prevention and treatment of obesity and related syndromes.
- -
-
Page/Page column 57
(2010/11/24)
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- Synthesis of new potential HIV-1 integrase inhibitors
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A synthesis of some 1,2-(hetero)arylsubstituted ethanone and 1,3-(hetero)arylsubstituted3-hydroxypropenone derivatives, designed as potential HIV-1 integrase inhibitors, is reported. The microwave-assisted synthesis was applied in several reactions achiev
- Ferro, Stefania,Rao, Angela,Zappala, Maria,Chimirri, Alba,Letizia Barreca, Maria,Witvrouw, Myriam,Debyser, Zeger,Monforte, Pietro
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p. 2727 - 2734
(2007/10/03)
-
- New COX-2/5-LOX inhibitors: Apoptosis-inducing agents potentially useful in prostate cancer chemotherapy
-
The arachidonic acid metabolizing enzymes cyclooxygenase-2 (COX-2) and lipoxygenases (LOXs) have been found to be implicated in a variety of cancers, including prostate cancer. To develop new therapeutic treatments, it therefore seemed interesting to design dual COX-2/5-LOX inhibitors. We report here the synthesis and in vitro pharmacological properties of diarylpyrazole derivatives that have in their structure key pharmacophoric elements to obtain optimal interaction with subsites of active pockets in both enzyme systems. Using a molecular modeling approach, a set of SAR data is proposed, highlighting the importance of the sulfonyl group of one of the aryl moieties in terms of proliferation inhibition and/or apoptosis induction.
- Pommery, Nicole,Taverne, Thierry,Telliez, Aurélie,Goossens, Laurence,Charlier, Caroline,Pommery, Jean,Goossens, Jean-Fran?ois,Houssin, Raymond,Durant, Fran?ois,Hénichart, Jean-Pierre
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p. 6195 - 6206
(2007/10/03)
-
- Structure activity of 3-Aryl-1,3-diketo-containing compounds as HIV-1 integrase inhibitors
-
The 4-aryl-2-hydroxy-4-oxo-2-butenoic acids and their isosteric tetrazoles are among an emerging class of aryl β-diketo (ADK)-based agents which exhibit potent inhibition of HIV-1 integrase (IN)-catalyzed strand transfer (ST) processes, while having much
- Pais, Godwin C. G.,Zhang, Xuechun,Marchand, Christophe,Neamati, Nouri,Cowansage, Kiriana,Svarovskaia, Evguenia S.,Pathak, Vinay K.,Tang, Yun,Nicklaus, Marc,Pommier, Yves,Burke Jr., Terrence R.
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p. 3184 - 3194
(2007/10/03)
-
- Substituted γ-Lactones. XXX (1). Reactions of α-Keto-β-Substituted-γ-butyrolactones with Diamines
-
The condensation reaction between α-keto-β-aroyl (or acyl)-γ-butyrolactones, 4a-4e and o-phenylenediamine or 2,3-diaminonaphthalene leads under retrograde aldol condensation involving loss of formaldehyde to formation of 3-substituted-3,4-dihydro-2(1H)quinoxalinones or benzoquinoxalinones, 7a-7g, respectively as a new convenient synthesis of this type of heterocyclic systems.The reaction of type 4 compound with 4,5-diaminopyrimidine, 8, was found to proceed differently. 2--4-oxo-3-(hydroxymethyl)-4-phenyl-2-butenoic acid 9 was the only product formed when the reaction between 4a and 8 was run in ethanol.The same reaction in glacial acetic acid proceeds with loss of formaldehyde, to afford 7-phenacylidene-7,8-dihydro-6(1H)-pteridinone 10.The reaction between type 4 compounds and ethylenediamine or 1,4-phenylenediamine leads to the formation of the bis-condensation products 13-15, respectively.
- Amer, Adel,Ventura, Montserrat,Zimmer, Hans
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p. 359 - 364
(2007/10/02)
-