26226-72-2Relevant articles and documents
Selective cyclooxygenase inhibition and ulcerogenic liability of some newly prepared anti-inflammatory agents having thiazolo[4,5-d]pyrimidine scaffold
Bakr, Rania B.,Ghoneim, Amira A.,Azouz, Amany A.
, (2019)
Novel candidates of thiazolo[4,5-d]pyrimidines (9a-l)were synthesized and their structures were elucidated by spectral and elemental analyses. All the novel derivatives were screened for their cyclooxygenase inhibitory effect, anti-inflammatory activity and ulcerogenic liability. All the new compounds exhibited anti-inflammatory activity, especially 1-(4-[7-(4-nitrophenyl)-5-thioxo-5,6-dihydro-3H-thiazolo[4,5-d]pyrimidin-2-ylideneamino]phenyl)ethanone (9g)was the most active derivative with 57%, 88% and 88% inhibition of inflammation after 1, 3 and 5h, respectively. Furthermore, this derivative 9g recorded higher anti-inflammatory activity than celecoxib which showed 43%, 43% and 54% inhibition after 1, 3 and 5h, sequentially. Moreover, the target derivatives 9a-l demonstrated moderate to high potent inhibitory action towards COX-2 (IC50 = 0.87–3.78 μM), in particular, the derivatives 9e (IC50 = 0.92 μM), 9g (IC50 = 0.87 μM)and 9k (IC50 = 1.02 μM)recorded higher COX-2 inhibitory effect than the selective COX-2 inhibitor drug celecoxib (IC50 = 1.11 μM). The in vivo potent compounds (9e, 9g and 9k)caused variable ulceration effect (ulcer index = 5–12.25)in comparison to that of celecoxib (ulcer index = 3). Molecular docking was performed to the most potent COX-2 inhibitors (9e, 9g and 9k)to explore the binding mode of these derivatives with Cyclooxygenase-2 enzyme.
Design, synthesis, 99mTc labeling, and biological evaluation of a novel pyrrolizine derivative as potential anti-inflammatory agent
Attallah,Gouda,Ibrahim,Abouzeid
, p. 630 - 638 (2017)
The design and synthesis of ethyl 4-(6-amino-7-cyano-2,3-dihydro-1H-pyrrolizine-5-carboxamido)-benzoate (KH16) were discussed, and its structure was determined. The anti-inflammatory activity of a new compound was evaluated using in vitro cyclooxygenase (
New 4-(2-Furyl)-1,4-dihydronicotinonitriles and 1,4,5,6-Tetrahydronicotinonitriles: Synthesis, Structure, and Analgesic Activity
Aksenov, N. A.,Aksenova, I. V.,Bibik, E. Yu.,Dotsenko, V. V.,Frolov, K. A.,Krivokolysko, D. S.,Krivokolysko, S. G.,Pankov, A. A.,Samokish, A. A.,Vasilin, V. K.,Venidiktova, Yu. S.
, p. 1646 - 1660 (2021/11/01)
Abstract: A series of new hybrid molecules containing 2-furyl and partially saturated pyridine fragments was obtained based on the reaction of cyanothioacetamide with furfural and 1,3-dicarbonyl compounds. The resulting compounds were tested in vivo for analgesic activity (rats) in the orofacial trigeminal pain test. Some the tested compounds showed an antinociceptive effect, superior to that of the reference drug (metamizole sodium).
Design, synthesis, kinetic, molecular dynamics, and hypoglycemic effect characterization of new and potential selective benzimidazole derivatives as Protein Tyrosine Phosphatase 1B inhibitors
Campos-Almazán, Mara Ibeth,Flores-Ramos, Miguel,Hernández-Campos, Alicia,Castillo, Rafael,Sierra-Campos, Erick,Torgeson, Kristiane,Peti, Wolfgang,Valdez-Solana, Mónica,Oria-Hernández, Jesús,Méndez, Sara T.,Castillo-Villanueva, Adriana,Jiménez-de Jesús, Hugo,Avitia-Domínguez, Claudia,Téllez-Valencia, Alfredo
, (2021/09/28)
Protein-tyrosine phosphatase 1B (PTP1B) is a negative regulator of insulin signaling pathway and has been validated as a therapeutic target for type 2 diabetes. A wide variety of scaffolds have been included in the structure of PTP1B inhibitors, one of them is the benzimidazole nucleus. Here, we report the design and synthesis of a new series of di- and tri- substituted benzimidazole derivatives including their kinetic and structural characterization as PTP1B inhibitors and hypoglycemic activity. Results show that compounds 43, 44, 45, and 46 are complete mixed type inhibitors with a Ki of 12.6 μM for the most potent (46). SAR type analysis indicates that a chloro substituent at position 6(5), a β-naphthyloxy at position 5(6), and a p-benzoic acid attached to the linker 2-thioacetamido at position 2 of the benzimidazole nucleus, was the best combination for PTP1B inhibition and hypoglycemic activity. In addition, molecular dynamics studies suggest that these compounds could be potential selective inhibitors from other PTPs such as its closest homologous TCPTP, SHP-1, SHP-2 and CDC25B. Therefore, the compounds reported here are good hits that provide structural, kinetic, and biological information that can be used to develop novel and selective PTP1B inhibitors based on benzimidazole scaffold.
Ethyl benzoate bearing pyrrolizine/indolizine moieties: Design, synthesis and biological evaluation of anti-inflammatory and cytotoxic activities
Attalah, Khalid M.,Abdalla, Ashraf N.,Aslam, Akhmed,Ahmed, Muhammad,Abourehab, Mohammed A.S.,ElSawy, Naser A.,Gouda, Ahmed M.
, (2019/11/26)
Two new series of ethyl benzoate bearing pyrrolizine and indolizine moieties 8–11 were synthesized and evaluated for their anti-inflammatory and anticancer activities. Among these derivatives, compounds 9a, 10b and 11b displayed in vivo anti-inflammatory
INHIBITORS TO TARGET HIV-1 NEF-CD80/CD86 INTERACTIONS FOR THERAPEUTIC INTERVENTION
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Paragraph 000162, (2020/03/05)
The compounds of Formula I, II, and III along with their stereoisomers, pharmaceutically acceptable salts, polymorphs, solvates and hydrates thereof are described in the present disclosure. The said compounds restore immune activation in case of infections or a disease associated with an HIV infection in a subject in need thereof.
Pharmacological and physicochemical profile of arylacetamides as tools against human cancers
Ferreira, Paulo Michel Pinheiro,Machado, Kátia da Concei??o,Lavorato, Stefania Neiva,de Oliveira, Fátima de Cássia Evangelista,Silva, Jurandy do Nascimento,de Almeida, Antonia Amanda Cardoso,Santos, Luciano de Souza,Silva, Valdenizia Rodrigues,Bezerra, Daniel Pereira,Soares, Milena Botelho Pereira,Pessoa, Cláudia,de Moraes Filho, Manoel Odorico,Ferreira, José Roberto de Oliveira,Sousa, Jo?o Marcelo de Castro e,Maltarollo, Vinícius Gon?alves,Alves, Ricardo José
, (2019/08/02)
Arylacetamides are widely used as synthetic intermediates to obtain medicinal substances. This work evaluated in vitro antiproliferative activity of ten 2-Chloro-N-arylacetamides on human normal and cancer cells and detailed in vivo toxicological and anticancer investigations. Initially, cytotoxic colorimetric assays were performed using tumor lines, peripheral blood mononuclear cells (PBMC) and erythrocytes. Compounds 2, 3 and 4 were tested for acute toxicity (50, 150 and 300 mg/kg) and for subacute antitumoral capacity in HCT-116 colon carcinoma-bearing xenograft mice for 15 days at 25 mg/kg/day. Most compounds revealed cytotoxic action on tumor lines and PBMC, but activity on human erythrocytes were not detected. Molecular dipole moment, lipophilicity and electronic constant of aryl substituents had effects upon in vitro antiproliferative capacity. More common in vivo acute behavioral signals with compounds 2, 3 and 4 were muscle relaxation, reduction of spontaneous locomotor activity and number of entries in closed arms and increased number of falls andtime spent in open arms, suggesting diazepam-like anxiolytic properties. Decrease of grabbing strength and overall activity were common, but palpebral ptosis and deaths occurred at 300 mg/kg only. Compounds 2 and 3 reduced colon carcinoma growth (21.2 and 27.5%, respectively, p 0.05) without causing apparent signals of organ-specific toxicity after subacute exposure. The structural chemical simplicity of arylacetamides make them cost-effective alternatives and justifies further improvements to enhance activity, selectivity and the development of pharmaceutical formulations.
SMALL MOLECULE ACTIVATORS OF NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE (NAMPT) AND USES THEREOF
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Paragraph 00759, (2018/08/03)
Provided herein are small molecule activators of Nicotinamide Phosphoribosyltransferase (NAMPT), compositions comprising the compounds, and methods of using the compounds and compositions.
COMPOSITONS AND METHODS FOR MODULATING UBA5
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Paragraph 0619; 0621; 0625, (2018/08/26)
Disclosed herein, inter alia, are compositions and methods useful for inhibiting ubiquitin-like modifier activating enzyme 5.
COMPOSITIONS AND METHODS FOR MODULATING PPP2R1A
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Paragraph 0599; 0600; 0601; 0604, (2018/08/26)
Disclosed herein, inter alia, are compositions and methods useful for modulating PPP2R1 A and for the treatment of cancer.
