4479-70-3Relevant articles and documents
Design, synthesis, molecular modeling and anti-hyperglycemic evaluation of phthalimide-sulfonylurea hybrids as PPARγ and SUR agonists
El-Zahabi, Mohamed Ayman,Elbendary, Eman R.,Bamanie, Faida H.,Radwan, Mohamed F.,Ghareib, Salah A.,Eissa, Ibrahim H.
, (2019/07/16)
New series of phthalimide-sulfonylurea hybrids were prepared and examined for their in vivo anti-hyperglycemic activities in STZ-induced hyperglycemic rats using glibenclamide as a reference drug. Compounds 6c, 6d, 6g, 6h, 6j and 6k induced significant reduction in the blood glucose levels of diabetic rats ranging from 24.43 to 21.43%. Moreover, molecular docking and pharmacophore approaches were carried out to examine binding modes and fit values of the prepared compounds against PPARγ and SUR, respectively. Compounds 6c, 6d, 6j and 6m exhibited the highest binding free energies against PPARγ. Compounds 6c, 6j, 6k, 6l, and 6n showed the highest fit values against the generated pharmacophore model. Also, QSAR technique was carried out to estimate the proposed PPARγ binding affinities and insulin-secreting abilities. The synthesized compounds showed promising estimated activities. In-silico ADMET studies were performed to investigate pharmacokinetics of the synthesized compounds. They showed considerable human intestinal absorption with low BBB penetration.
PLATELET ADP RECEPTOR INHIBITORS
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Paragraph 0095, (2016/08/17)
no abstract published
Synthesis and molecular modelling studies of novel sulphonamide derivatives as dengue virus 2 protease inhibitors
Timiri, Ajay Kumar,Subasri, Selvarasu,Kesherwani, Manish,Vishwanathan, Vijayan,Sinha, Barij Nayan,Velmurugan, Devadasan,Jayaprakash, Venkatesan
, p. 74 - 82 (2015/08/11)
Abstract Development of antivirals for dengue is now based on rational approach targeting the enzymes involved in its life cycle. Among the targets available for inhibition of dengue virus, non-structural protein NS2B-NS3 protease is considered as a promising target for the development of anti-dengue agents. In the current study we have synthesized a series of 4-(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)benzene-1-sulphonamide derivatives and screened for DENV2 protease activity. Compounds 16 and 19 showed IC50 of DENV2 Protease activity with 48.2 and 121.9 μM respectively. Molecular docking and molecular dynamic simulation studies were carried out to know the binding mode responsible for the activity. MD simulations revealed that, NS2B/NS3 protease was more stable when it binds with the active compound. Structure optimization of the lead compounds 16 and 19 and their co-crystallization studies are underway.
COMPOUNDS AND METHODS FOR INDUCING CHONDROGENESIS
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Paragraph 0741, (2014/09/29)
Described herein are compounds and compositions for the amelioration of arthritis or joint injuries by inducing mesenchymal stem cells into chondrocytes.
Synthesis and evaluation of novel dapsone-thalidomide hybrids for the treatment of type 2 leprosy reactions
Yamasaki, Paulo Renato,Do Nascimento, Dejair Caetano,Chelucci, Rafael Consolin,De Faria Fernandes Belone, Andréa,Rosa, Patrícia Sammarco,Diório, Suzana Madeira,De Melo, Thais Regina Ferreira,Barbieri, Karina Pereira,Placeres, Marisa Campos Polési,Carlos, Iracilda Zepone,Chung, Man Chin,Dos Santos, Jean Leandro
, p. 3084 - 3087 (2014/06/24)
We synthesized a series of novel dapsone-thalidomide hybrids (3a-i) by molecular hybridization and evaluated their potential for the treatment of type 2 leprosy reactions. All of the compounds had analgesic properties. Compounds 3c and 3h were the most active antinociceptive compounds and reduced acetic acid-induced abdominal constrictions by 49.8% and 39.1%, respectively. The hybrid compounds also reduced tumor necrosis factor-α levels in lipopolysaccharide-stimulated L929 cells. Compound 3i was the most active compound; at concentrations of 15.62 and 125 μM, compound 3i decreased tumor necrosis factor-α levels by 86.33% and 87.80%, respectively. In nude mice infected with Mycobacterium leprae in vivo, compound 3i did not reduce the number of bacilli compared with controls. Compound 3i did not have mutagenic effects in Salmonella typhimurium strains TA100 and TA102, with or without metabolic activation (S9 mixture). Our results indicate that compound 3i is a novel lead compound for the treatment of type 2 leprosy reactions.
Synthesis and evaluation of novel dapsone-thalidomide hybrids for the treatment of type 2 leprosy reactions
Yamasaki, Paulo Renato,Do Nascimento, Dejair Caetano,Chelucci, Rafael Consolin,De Faria Fernandes Belone, Andra,Rosa, Patrcia Sammarco,Dirio, Suzana Madeira,De Melo, Thais Regina Ferreira,Barbieri, Karina Pereira,Placeres, Marisa Campos Polsi,Carlos, Iracilda Zepone,Chung, Man Chin,Dos Santos, Jean Leandro
, p. 3084 - 3087 (2015/02/19)
We synthesized a series of novel dapsone-thalidomide hybrids (3a-i) by molecular hybridization and evaluated their potential for the treatment of type 2 leprosy reactions. All of the compounds had analgesic properties. Compounds 3c and 3h were the most active antinociceptive compounds and reduced acetic acid-induced abdominal constrictions by 49.8% and 39.1%, respectively. The hybrid compounds also reduced tumor necrosis factor-α levels in lipopolysaccharide-stimulated L929 cells. Compound 3i was the most active compound; at concentrations of 15.62 and 125 μM, compound 3i decreased tumor necrosis factor-α levels by 86.33% and 87.80%, respectively. In nude mice infected with Mycobacterium leprae in vivo, compound 3i did not reduce the number of bacilli compared with controls. Compound 3i did not have mutagenic effects in Salmonella typhimurium strains TA100 and TA102, with or without metabolic activation (S9 mixture). Our results indicate that compound 3i is a novel lead compound for the treatment of type 2 leprosy reactions.
Docking, synthesis, and pharmacological evaluation of isoindoline derivatives as anticonvulsant agents
Davood, Asghar,Amini, Mohsen,Azimidoost, Leila,Rahmatpour, Somaieh,Nikbakht, Ali,Iman, Maryam,Shafaroodi, Hamed,Ansari, Abdollah
, p. 3177 - 3184 (2013/07/19)
Eleven analogs of N-arylisoindoline pharmacophore were synthesized and evaluated for their anticonvulsant activities. The in vivo screening data acquired indicate that all the analogs have the ability to protect against pentylenetetrazole-induced seizure. Compounds 2, 6, and 11 elevated clonic seizure thresholds at 30 min which were more active than reference drug phenytoin, and compounds 2, 7, and 11 showed marked anticonvulsant activity on tonic seizure. The most potent compounds were 2 and 11 which had comparative activity to the phenytoin. Using a model of the open pore of the Na channel, we have docked all compounds. Docking studies have revealed that these compounds interacted mainly with residues II-S6 of NaV1.2 by making hydrogen bonds and have additional hydrophobic interactions with other domains in the channel's inner pore.
Molecular design, synthesis and biological evaluation of cyclic imides bearing benzenesulfonamide fragment as potential COX-2 inhibitors. Part 2
Al-Suwaidan, Ibrahim A.,Alanazi, Amer M.,El-Azab, Adel S.,Al-Obaid, Abdulrahman M.,Eltahir, Kamal E.H.,Maarouf, Azza R.,Abu El-Enin, Mohamed A.,Abdel-Aziz, Alaa A.-M.
, p. 2601 - 2605 (2013/06/27)
A group of cyclic imides (1-10) was designed for evaluation as a selective COX-2 inhibitors and investigated in vivo for their anti-inflammatory activity. Compounds 6a, 6b, 8a, 8b, 9a, 9b, 10a and 10b were proved to be potent COX-2 inhibitors with IC50 range of 0.1-4.0 μM. In vitro COX-1/COX-2 inhibition structure-activity studies identified compound 8a as a highly potent (IC50 = 0.1 μM), and an extremely selective [COX-2 (SI) > 1000] comparable to celecoxib [COX-2 (SI) > 384], COX-2 inhibitor that showed superior anti-inflammatory activity (ED50 = 72.4 mg/kg) relative to diclofenac (ED50 = 114 mg/kg). Molecular modeling was carried out through docking the designed compounds into the COX-2 binding site to predict if these compounds have analogous binding mode to the COX-2 inhibitors. The study showed that the homosulfonamide fragment of 8a inserted deep inside the 2 -pocket of the COX-2 active site, where the SO2NH2 group underwent H-bonding interaction with Gln192(2.95 A?), Phe 518(2.82 A?) and Arg513(2.63 and 2.73 A?). Docking study of the synthesized compound 8a into the active site of COX-2 revealed a similar binding mode to SC-558, a selective COX-2 inhibitor.
Synthesis and in vitro anti Mycobacterium tuberculosis activity of a series of phthalimide derivatives
Santos, Jean L.,Yamasaki, Paulo R.,Chin, Chung Man,Takashi, Celio H.,Pavan, Fernando R.,Leite, Clarice Q.F.
experimental part, p. 3795 - 3799 (2009/09/30)
New phthalimide derivatives were easily prepared through condensation of phthalic anhydride and selected amines with variable yields (70-90%). All compounds (3a-l) were evaluated against Mycobacterium tuberculosis H37Rv using Alamar Blue susceptibility. The compounds 3c, 3i, and 3l have the minimum inhibitory concentrations (MICs) of 3.9, 7.8, and 5.0 μg/mL, respectively, and could be considered new lead compounds in the treatment of tuberculosis and multi-drug resistant tuberculosis. Crown Copyright
Platelet ADP receptor inhibitors
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, (2008/06/13)
Novel compounds of formulae (I) to (VIII), which more particularly include sulfonylurea derivatives, sulfonylthiourea derivatives, sulfonylguanidine derivatives, sulfonylcyanoguanidine derivatives, thioacylsulfonamide derivatives, and acylsulfonamide derivatives which are effective platelet ADP receptor inhibitors. These derivatives may be used in various pharmaceutical compositions, and are particularly effective for the prevention and/or treatment of cardiovascular diseases, particularly those diseases related to thrombosis. The invention also relates to a method for preventing or treating thrombosis in a mammal comprising the step of administering a therapeutically effective amount of a compound of formulae (I) to (VIII), or a pharmaceutically acceptable salt thereof.
