Category: 85070-57-1

Rabal, Obdulia; Sanchez-Arias, Juan A.; Cuadrado-Tejedor, Mar; de Miguel, Irene; Perez-Gonzalez, Marta; Garcia-Barroso, Carolina; Ugarte, Ana; Estella-Hermoso de Mendoza, Ander; Saez, Elena; Espelosin, Maria; Ursua, Susana; Tan, Haizhong; Wu, Wei; Xu, Musheng; Garcia-Osta, Ana; Oyarzabal, Julen published the artcile< Design, synthesis, biological evaluation and in vivo testing of dual phosphodiesterase 5 (PDE5) and histone deacetylase 6 (HDAC6)-selective inhibitors for the treatment of Alzheimer's disease>, Quality Control of 85070-57-1, the main research area is phosphodiesterase PDE5 histone deacetylase HDAC6 inhibitor Alzheimer disease; Alzheimer; Dual inhibitors; HDAC6 selective; In-vivo test; PDE5 inhibition; Pharmacological tool compound; Tg2576 mice.

The authors have identified chem. probes that act as dual phosphodiesterase 5 (PDE5) and histone deacetylase 6 (HDAC6)-selective inhibitors (>1 log unit difference vs. class I HDACs) to decipher the contribution of HDAC isoforms to the pos. impact of dual-acting PDE5 and HDAC inhibitors on mouse models of Alzheimer’s disease (AD) and fine-tune this systems therapeutics approach. Structure- and knowledge-based approaches led to the design of first-in-class mols. with the desired target compound profile: dual PDE5 and HDAC6-selective inhibitors. Compound 44b (5-[[4-ethoxy-3-(1-methyl-7-oxo-3-propyl-6H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl]methyl]thiophene-2-carbohydroxamic acid), which fulfilled the biochem., functional and ADME-Tox profiling requirements and exhibited adequate pharmacokinetic properties, was selected as pharmacol. tool compound and tested in a mouse model of AD (Tg2576) in vivo.

European Journal of Medicinal Chemistry published new progress about Alzheimer disease. 85070-57-1 belongs to class bromides-buliding-blocks, and the molecular formula is C9H8BrFO2, Quality Control of 85070-57-1.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Mo, Di-Wei; Dong, Shuai; Sun, Haiyan; Chen, Jia-Sheng; Pang, Jian-Xin; Xi, Bao-Min; Chen, Wen-Hua published the artcile< Synthesis and potent inhibitory activities of carboxybenzyl-substituted 8-(3-(R)-aminopiperidin-1-yl)-7-(2-chloro/cyanobenzyl)-3-methyl-3,7-dihydro-purine-2,6-diones as dipeptidyl peptidase IV (DPP-IV) inhibitors>, Quality Control of 85070-57-1, the main research area is dihydropurinedione derivative preparation dipeptidyl peptidase IV inhibitory activity; 3-Methyl-3,7-dihydro-purine-2,6-dione; Diabetes; Dipeptidyl peptidase IV inhibitor; Inhibitory activity; Synthesis.

Fourteen 3-methyl-3,7-dihydro-purine-2,6-dione derivatives bearing carboxybenzyl and 2-chloro/cyanobenzyl groups at the N-1 and N-7 positions, resp., were synthesized as dipeptidyl peptidase IV (DPP-IV) inhibitors. These compounds were characterized on the basis of NMR (1H and 13C) and ESI MS data. In vitro bioassay indicates that most of these compounds showed moderate to good inhibitory activities against DPP-IV. Among them, compound I (IC50 = 36 nM) exhibited comparable activity with a pos. control, Sitagliptin (IC50 = 16 nM). In addition, the structure-activity relationship of these compounds is also briefly discussed.

Bioorganic & Medicinal Chemistry Letters published new progress about Antidiabetic agents. 85070-57-1 belongs to class bromides-buliding-blocks, and the molecular formula is C9H8BrFO2, Quality Control of 85070-57-1.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Gaisina, Irina N.; Lee, Sue H.; Kaidery, Navneet A.; Ben Aissa, Manel; Ahuja, Manuj; Smirnova, Natalya N.; Wakade, Sushama; Gaisin, Arsen; Bourassa, Megan W.; Ratan, Rajiv R.; Nikulin, Sergey V.; Poloznikov, Andrey A.; Thomas, Bobby; Thatcher, Gregory R. J.; Gazaryan, Irina G. published the artcile< Activation of Nrf2 and Hypoxic Adaptive Response Contribute to Neuroprotection Elicited by Phenylhydroxamic Acid Selective HDAC6 Inhibitors>, Formula: C9H8BrFO2, the main research area is phenylhydroxamic acid derivative preparation HDAC6 inhibitor neuroprotectant; HIF-1 activators; Nrf2 activators; Phenylhydroxamates; histone deacetylase inhibitors; neuroprotection; oxidative stress.

Activation of HIF-1α and Nrf2 is a primary component of cellular response to oxidative stress, and activation of HIF-1α and Nrf2 provides neuroprotection in models of neurodegenerative disorders, including ischemic stroke, Alzheimer’s and Parkinson’s diseases. Screening a library of CNS-targeted drugs using novel reporters for HIF-1α and Nrf2 elevation in neuronal cells revealed histone deacetylase (HDAC) inhibitors as potential activators of these pathways. We report the identification of phenylhydroxamates as single agents exhibiting tripartite inhibition of HDAC6, inhibition of HIF-1 prolyl hydroxylase (PHD), and activation of Nrf2. Two superior tripartite agents, ING-6 and ING-66, showed neuroprotection against various cellular insults, associated with stabilization of both Nrf2 and HIF-1, and expression of their resp. target genes in vitro and in vivo. Discovery of the innate ability of phenylhydroxamate HDAC inhibitors to activate Nrf2 and HIF provides a novel route to multifunctional neuroprotective agents and cautions against HDAC6 selective inhibitors as chem. probes of specific HDAC isoform function.

ACS Chemical Neuroscience published new progress about Histone deacetylase inhibitors. 85070-57-1 belongs to class bromides-buliding-blocks, and the molecular formula is C9H8BrFO2, Formula: C9H8BrFO2.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Schmidt, Jurema; Rotter, Marco; Weiser, Tim; Wittmann, Sandra; Weizel, Lilia; Kaiser, Astrid; Heering, Jan; Goebel, Tamara; Angioni, Carlo; Wurglics, Mario; Paulke, Alexander; Geisslinger, Gerd; Kahnt, Astrid; Steinhilber, Dieter; Proschak, Ewgenij; Merk, Daniel published the artcile< A Dual Modulator of Farnesoid X Receptor and Soluble Epoxide Hydrolase To Counter Nonalcoholic Steatohepatitis>, COA of Formula: C9H8BrFO2, the main research area is benzylbenzamide dual modulator analog preparation nonalcoholic steatohepatitis; dual modulator analog FXR sEH benzylbenzamide analog pharmacokinetics.

Nonalcoholic steatohepatitis arising from Western diet and lifestyle is characterized by accumulation of fat in liver causing inflammation and fibrosis. It evolves as serious health burden with alarming incidence, but there is no satisfying pharmacol. therapy to date. Considering the disease’s multifactorial nature, modulation of multiple targets might provide superior therapeutic efficacy. In particular, farnesoid X receptor (FXR) activation that revealed antisteatotic and antifibrotic effects in clin. trials combined with inhibition of soluble epoxide hydrolase (sEH) as anti-inflammatory strategy promises synergies. To exploit this dual concept, we developed agents exerting partial FXR agonism and sEH inhibitory activity. Merging known pharmacophores and systematic exploration of the structure-activity relationship on both targets produced dual modulators with low nanomolar potency. Extensive in vitro characterization confirmed high dual efficacy in cellular context combined with low toxicity, and pilot in vivo data revealed favorable pharmacokinetics as well as engagement on both targets in vivo.

Journal of Medicinal Chemistry published new progress about Antifibrotic agents. 85070-57-1 belongs to class bromides-buliding-blocks, and the molecular formula is C9H8BrFO2, COA of Formula: C9H8BrFO2.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Armani, Elisabetta; Rizzi, Andrea; Capaldi, Carmelida; De Fanti, Renato; Delcanale, Maurizio; Villetti, Gino; Marchini, Gessica; Pisano, Anna Rita; Pitozzi, Vanessa; Pittelli, Maria Gloria; Trevisani, Marcello; Salvadori, Michela; Cenacchi, Valentina; Puccini, Paola; Amadei, Francesco; Pappani, Alice; Civelli, Maurizio; Patacchini, Riccardo; Baker-Glenn, Charles A. G.; Van de Poel, Herve; Blackaby, Wesley P.; Nash, Kevin; Amari, Gabriele published the artcile< Discovery of M3 Antagonist-PDE4 Inhibitor Dual Pharmacology Molecules for the Treatment of Chronic Obstructive Pulmonary Disease>, Quality Control of 85070-57-1, the main research area is M3 antagonist PDE4 inhibitor chronic obstructive pulmonary disease.

In this paper, we report the discovery of dual M3 antagonist-PDE4 inhibitor (MAPI) compounds for the inhaled treatment of pulmonary diseases. The identification of dual compounds was enabled by the intuition that the fusion of a PDE4 scaffold derived from our CHF-6001 series with a muscarinic scaffold through a common linking ring could generate compounds active vs. both the transmembrane M3 receptor and the intracellular PDE4 enzyme. Two chem. series characterized by two different muscarinic scaffolds were investigated. SAR optimization was aimed at obtaining M3 nanomolar affinity coupled with nanomolar PDE4 inhibition, which translated into anti-bronchospastic efficacy ex vivo (inhibition of rat trachea contraction) and into anti-inflammatory efficacy in vitro (inhibition of TNFα release). Among the best compounds, compound 92a achieved the goal of demonstrating in vivo efficacy and duration of action in both the bronchoconstriction and inflammation assays in rat after intratracheal administration.

Journal of Medicinal Chemistry published new progress about Anti-inflammatory agents. 85070-57-1 belongs to class bromides-buliding-blocks, and the molecular formula is C9H8BrFO2, Quality Control of 85070-57-1.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Lu, Dehua; Qu, Lailiang; Wang, Cheng; Luo, Heng; Li, Shang; Yin, Fucheng; Liu, Xingchen; Chen, Xinye; Luo, Zhongwen; Cui, Ningjie; Peng, Wan; Ji, Limei; Kong, Lingyi; Wang, Xiaobing published the artcile< Harmine-based dual inhibitors targeting histone deacetylase (HDAC) and DNA as a promising strategy for cancer therapy>, SDS of cas: 85070-57-1, the main research area is cancer therapy histone deacetylase harmine DNA damage; Cancer; DNA; DNA damage; HDAC; Harmine.

Overexpression of histone deacetylases (HDACs) are observed in different types of cancers, but histone deacetylase inhibitors (HDACIs) have not shown significant efficacy as monotherapy against solid tumors. Recently, studies demonstrated that it is promising to combine HDACIs with DNA damage agents to improve DNA damage level to gain better effect on treating solid tumor. Harmine has been demonstrated to cause DNA damage by intercalating DNA. Therefore, we designed a series of harmine-based inhibitors targeting HDAC and DNA with multi-target strategy, the most potential compound 27 could bind to DNA and cause DNA damage. Furthermore 27 caused cells apoptosis through p53 signaling pathway, and exhibited significant anti-proliferation effects against HCT-116 cells (IC50 = 1.41 μM). As a DNA damage agent, 27 displayed low toxicity in normal cells. Compound 27 was demonstrated as a dual inhibitor targeting HDAC (HDAC1 IC50 = 0.022 μM and HDAC6 IC50 = 0.45 μM) and DNA, and had the potential in the treatment of solid tumor.

Bioorganic Chemistry published new progress about Acetylation. 85070-57-1 belongs to class bromides-buliding-blocks, and the molecular formula is C9H8BrFO2, SDS of cas: 85070-57-1.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Getter, Tamar; Margalit, Raanan; Kahremany, Shirin; Levy, Laura; Blum, Eliav; Khazanov, Netaly; Keshet-Levy, Nimrod Y.; Tamir, Tigist Y.; Ben Major, M.; Lahav, Ron; Zilber, Sofia; Senderowitz, Hanoch; Bradfield, Paul; Imhof, Beat A.; Alpert, Evgenia; Gruzman, Arie published the artcile< Novel inhibitors of leukocyte transendothelial migration>, Safety of Methyl 4-(bromomethyl)-2-fluorobenzoate, the main research area is benzylidene trioxotetrahydropyrimidine preparation leukocyte transendothelial migration inhibitor docking human; Arthritis; Fatty liver; IBD/Crohn’s disease; Leukocyte transmigration; Multiple sclerosis; Trioxotetrahydropyrimidin derivatives.

In this study, based on previous trioxotetrahydropyrimidine based integrin inhibitors that suboptimally blocked leukocyte adhesion, twelve mols. with a modified scaffold were designed, synthesized, and tested in vitro for their capacity to block the transendothelial migration of immune cells. One of the mols. I, completely blocked leukocyte transendothelial migration, without any toxic effects on immune or endothelial cells (IC50 = 2.4 μM). In vivo, compound I exhibited significant therapeutic effects in inflammatory bowel disease (IBD)/Crohn’s disease, multiple sclerosis, fatty liver disease, and rheumatoid arthritis models. A detailed acute and chronic toxicity profile of the lead compound in vivo did not reveal any toxic effects. Such a type of mol. might therefore provide a unique starting point for designing a novel class of leukocyte transmigration blocking agents with broad therapeutic applications in inflammatory and auto-immune pathologies.

Bioorganic Chemistry published new progress about Anti-inflammatory agents. 85070-57-1 belongs to class bromides-buliding-blocks, and the molecular formula is C9H8BrFO2, Safety of Methyl 4-(bromomethyl)-2-fluorobenzoate.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary