keyword
MENU ▼
Read by QxMD icon Read
search

oxazolone

keyword
https://www.readbyqxmd.com/read/28818461/discovery-and-process-development-of-a-novel-tace-inhibitor-for-the-topical-treatment-of-psoriasis
#1
Jean-Guy Boiteau, Gilles Ouvry, Jean-Marie Arlabosse, Stéphanie Astri, Audrey Beillard, Yushma Bhurruth-Alcor, Laetitia Bonnary, Claire Bouix-Peter, Karine Bouquet, Marilyne Bourotte, Isabelle Cardinaud, Catherine Comino, Benoît Deprez, Denis Duvert, Angélique Féret, Feriel Hacini-Rachinel, Craig S Harris, Anne-Pascale Luzy, Arnaud Mathieu, Corinne Millois, Nicolas Orsini, Jonathan Pascau, Artur Pinto, David Piwnica, Gaëlle Polge, Arnaud Reitz, Kevin Reversé, Nicolas Rodeville, Patricia Rossio, Delphine Spiesse, Samuel Tabet, Nathalie Taquet, Loïc Tomas, Emmanuel Vial, Laurent F Hennequin
Targeting the TNFα pathway is a validated approach to the treatment of psoriasis. In this pathway, TACE stands out as a druggable target and has been the focus of in-house research programs. In this article, we present the discovery of clinical candidate 26a. Starting from hits plagued with poor solubility or genotoxicity, 26a was identified through thorough multiparameter optimisation. Showing robust in vivo activity in an oxazolone-mediated inflammation model, the compound was selected for development. Following a polymorph screen, the hydrochloride salt was selected and the synthesis was efficiently developed to yield the API in 47% overall yield...
August 2, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28807557/the-role-of-toll-like-receptor-3-in-chronic-contact-hypersensitivity-induced-by-repeated-elicitation
#2
Risa Yasuike, Risa Tamagawa-Mineoka, Mayumi Ueta, Naomi Nakamura, Shigeru Kinoshita, Norito Katoh
BACKGROUND: Accumulating evidence suggests that Toll-like receptor (TLR)-3 signaling is involved in non-infectious immune and inflammatory reactions as well as in viral infections. The skin of patients with atopic dermatitis (AD) is often infected with virus and bacteria, leading to the aggravation of atopic symptoms. These findings suggest TLR3 signaling may be involved in the pathogenesis of AD, but the exact role of TLR3 in AD remains to be defined. OBJECTIVE: The purpose of this study was to investigate the role of TLR3 in chronic contact hypersensitivity reactions induced by repeated elicitation, resembling the features of AD...
August 4, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28781714/generation-repair-and-replication-of-guanine-oxidation-products
#3
REVIEW
Katsuhito Kino, Masayo Hirao-Suzuki, Masayuki Morikawa, Akane Sakaga, Hiroshi Miyazawa
Guanine is the most readily oxidized of the four DNA bases, and guanine oxidation products cause G:C-T:A and G:C-C:G transversions through DNA replication. 8-Oxo-7,8-dihydroguanine (8-oxoG) causes G:C-T:A transversions but not G:C-C:G transversions, and is more readily oxidized than guanine. This review covers four major findings. (i) 2,2,4-Triamino-5(2H)-oxazolone (Oz) is produced from guanine and 8-oxoG under various oxidative conditions. Guanine is incorporated opposite Oz by DNA polymerases, except REV1...
2017: Genes and Environment: the Official Journal of the Japanese Environmental Mutagen Society
https://www.readbyqxmd.com/read/28748525/topically-applied-azaphenothiazines-inhibit-contact-sensitivity-to-oxazolone-in-mice
#4
Jolanta Artym, Maja Kocięba, Ewa Zaczyńska, Michał Zimecki, Małgorzata Jeleń, Beata Morak-Młodawska, Krystian Pluta, Katarzyna Kaleta-Kuratewicz, Jan P Madej, Piotr Kuropka, Jan Kuryszko
In this work we investigated the efficacy of two topically applied azaphenothiazine derivatives, 9-chloro-6-acetylaminobutylquinobenzo[3,2-b][1,4]thiazine (compound 4) and 6-chloroethylureidoethyldiquino[3,2-b;2';3'-e][1,4]thiazine (compound 5), in the amelioration of inflammatory symptoms of contact sensitivity (CS) to oxazolone in mice, in relation to the commercial ointment Protopic® (tacrolimus), the reference drug. The compounds were administered 24 h following elicitation of CS and, 24 h later, the parameters of inflammation, such as ear edema, blood composition, leukocyte level, numbers of cells in the draining lymph nodes, histological picture of the inflamed tissue, and the morphometric analysis, were analyzed...
July 27, 2017: Histology and Histopathology
https://www.readbyqxmd.com/read/28667471/topical-application-of-dermatophagoides-farinae-or-oxazolone-induces-symptoms-of-atopic-dermatitis-in-the-rabbit-ear
#5
Jingling Zhao, Shengxian Jia, Ping Xie, Gabriel A Arenas, Robert D Galiano, Seok Jong Hong, Thomas A Mustoe
Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disease characterized by hyperproliferation and abnormal differentiation of the epidermis, and dermal infiltration of inflammatory cells. Appropriate animal models that recapitulate human AD and allow the analysis of disease processes in a reliable manner are essential to the study of AD. In this study, we established two AD models in rabbits by applying an allergen, Dermatophagoides farinae (Der f), or a hapten, oxazolone (OXZ). Application of the allergen or hapten induced a rapid onset and a chronically sustained AD-like skin lesion...
June 30, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28607110/the-bile-acid-receptor-gpbar1-regulates-the-m1-m2-phenotype-of-intestinal-macrophages-and-activation-of-gpbar1-rescues-mice-from-murine-colitis
#6
Michele Biagioli, Adriana Carino, Sabrina Cipriani, Daniela Francisci, Silvia Marchianò, Paolo Scarpelli, Daniele Sorcini, Angela Zampella, Stefano Fiorucci
GPBAR1 (TGR5 or M-BAR) is a G protein-coupled receptor for secondary bile acids that is highly expressed in monocytes/macrophages. In this study, we aimed to determine the role of GPBAR1 in mediating leukocyte trafficking in chemically induced models of colitis and investigate the therapeutic potential of BAR501, a small molecule agonist for GPBAR1. These studies demonstrated that GPBAR1 gene ablation enhanced the recruitment of classically activated macrophages in the colonic lamina propria and worsened the severity of inflammation...
June 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28583370/prostaglandin-e2-stimulates-adaptive-il-22-production-and-promotes-allergic-contact-dermatitis
#7
Calum T Robb, Henry J McSorley, Jinju Lee, Tomohiro Aoki, Cunjing Yu, Siobhan Crittenden, Anne Astier, Jennifer M Felton, Nicholas Parkinson, Adane Ayele, Richard M Breyer, Stephen M Anderton, Shuh Narumiya, Adriano G Rossi, Sarah E Howie, Emma Guttman-Yassky, Richard B Weller, Chengcan Yao
BACKGROUND: Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are both forms of eczema and are common inflammatory skin diseases with a central role of T cell-derived IL-22 in their pathogenesis. Although prostaglandin (PG) E2 is known to promote inflammation, little is known about its role in processes related to AD and ACD development, including IL-22 upregulation. OBJECTIVES: We sought to investigate whether PGE2 has a role in IL-22 induction and development of ACD, which has increased prevalence in patients with AD...
June 3, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28569761/chemically-induced-mouse-models-of-acute-and-chronic-intestinal-inflammation
#8
Stefan Wirtz, Vanessa Popp, Markus Kindermann, Katharina Gerlach, Benno Weigmann, Stefan Fichtner-Feigl, Markus F Neurath
Inflammatory bowel diseases (IBDs) result in diarrhea and abdominal pain with further potential complications such as tissue fibrosis and stenosis. Animal models help in understanding the immunopathogenesis of IBDs and in the design of novel therapeutic concepts. Here we present an updated version of a protocol we published in 2007 for key models of acute and chronic forms of colitis induced by 2,4,6-trinitro-benzene sulfonic acid (TNBS), oxazolone and dextran sulfate sodium (DSS). This protocol update describes an adaptation of the existing protocol that modifies the technique...
July 2017: Nature Protocols
https://www.readbyqxmd.com/read/28505514/tlr4-supports-the-expansion-of-fasl-cd5-cd1d-hi-regulatory-b-cells-which-decreases-in-contact-hypersensitivity
#9
Keng Wang, Lei Tao, Jianbing Su, Yueyang Zhang, Binhua Zou, Yiyuan Wang, Min Zou, Nana Chen, Linsheng Lei, Xiaojuan Li
Certain B cells termed as "regulatory B cells" (Bregs) can suppress the ongoing immune responses and a splenic CD5(+)CD1d(hi) Breg subset identified earlier was shown to exert its regulatory functions through secretion of IL-10. Though FasL expression is an alternative mechanism of immune suppression used by B cells, little is known about the FasL expressing CD5(+)CD1d(hi) Bregs. In this study, we isolated splenocytes or splenic CD19(+) B cells and compared the efficiency of toll-like receptor(TLR)4 ligand (lipopolysaccharide) with TLR9 ligand (CpG), anti-CD40 and TLR9 ligand (CpG) plus anti-CD40 on the FasL expression of splenic CD5(+)CD1d(hi) Bregs by flow cytometry...
May 12, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28500957/design-synthesis-of-novel-oxazolone-triazinone-derivatives-and-their-biological-evaluation-as-cox-2-inhibitors
#10
Lamia W Mohamed, Osama M El-Badry, Afaf K El-Ansary, Ahmed Ismael
A new series of oxazolones and triazinones were designed and synthesized and evaluated against both COX-1 and COX-2 enzymes. Full structure elucidation of the new derivatives was performed using microanalyses, IR, 1H NMR, 13C NMR and mass spectra. Most of the derivatives showed good inhibitory activity against COX-2 enzyme specifically compounds IIIc, IIIe, IVd and IVg with IC50 values 0.024, 0.019, 0.011 and 0.014µM compared to celecoxib as reference drug with IC50 value of 0.05µM. Altogether, these results indicate that these derivatives can be effective anti-inflammatory agents...
June 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28482341/indigo-naturalis-ameliorates-oxazolone-induced-dermatitis-but-aggravates-colitis-by-changing-the-composition-of-gut-microflora
#11
Soichiro Adachi, Namiko Hoshi, Jun Inoue, Eiichiro Yasutomi, Takafumi Otsuka, Ramesh Dhakhwa, Zi Wang, Yuna Koo, Toshihiro Takamatsu, Yuriko Matsumura, Haruka Yamairi, Daisuke Watanabe, Makoto Ooi, Toshihito Tanahashi, Shin Nishiumi, Masaru Yoshida, Takeshi Azuma
BACKGROUND: Indigo naturalis (IND) is an herbal medicine that has been used as an anti-inflammatory agent to treat diseases including dermatitis and inflammatory bowel disease in China. However, the mechanism by which IND exerts its immunomodulatory effect is not well understood. METHODS: A murine model of dermatitis and inflammatory bowel disease, both induced by oxazolone (OXA), was treated with IND. The severity of dermatitis was evaluated based on ear thickness measurements and histological scoring...
2017: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/28429299/participation-of-c-h-protons-in-the-dissociation-of-a-proton-deficient-dipeptide
#12
Damodar Koirala, Sabyasachy Mistry, Paul G Wenthold
The dissociation of anionic dipeptides Phe*Gly and GlyPhe*, where Phe* refers to sulfonated phenyl alanine, has been investigated by using ion trap mass spectrometry. The dipeptides undergo collision-induced dissociation (CID) to give the same products, indicating that they rearrange to a common structure before dissociation. The rearrangement does not occur with the dipeptide methyl esters. The structures of the b2 ions were investigated to determine the effect that having a remote, anionic site has on product formation...
July 2017: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/28424989/t-lymphocyte-derived-enkephalins-reduce-th1-th17-colitis-and-associated-pain-in-mice
#13
Lilian Basso, Laure Garnier, Arnaud Bessac, Jérôme Boué, Catherine Blanpied, Nicolas Cenac, Sophie Laffont, Gilles Dietrich
BACKGROUND: Endogenous opioids, including enkephalins, are fundamental regulators of pain. In inflammatory conditions, the local release of opioids by leukocytes at the inflammatory site inhibits nociceptor firing, thereby inducing analgesia. Accordingly, in chronic intestinal Th1/Th17-associated inflammation, enkephalins released by colitogenic CD4(+) T lymphocytes relieve inflammation-induced visceral pain. The present study aims to investigate whether mucosal T-cell-derived enkephalins also exhibit a potent anti-inflammatory activity as described for exogenous opioid drugs in Th1/Th17-associated colitis...
April 19, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28418286/external-application-of-nf-%C3%AE%C2%BAb-inhibitor-dhmeq-suppresses-development-of-atopic-dermatitis-like-lesions-induced-with-dncb-ox-in-balb-c-mice
#14
Xiaoxue Jiang, Yi Lan, Bing Wei, Cailing Dai, Yaru Gu, Jun Ma, Xiaoyan Liu, Kazuo Umezawa, Yuyang Zhang
CONTEXT: Dehydroxymethylepoxyquinomicin (DHMEQ) which is originally developed as an analog of antibiotic epoxyquinomicin C is a specific and potent inhibitor of NF-κB and has been shown to possess promising potential as an anti-inflammatory and anti-tumor agent. OBJECTIVE: This study examines DHMEQ's effect on therapeutic potential for atopic dermatitis (AD)-like lesions. MATERIALS AND METHODS: AD lesions were chronically induced by the repetitive and alternative application of 2,4-dinitrochlorobenzene (DNCB) and oxazolone (OX) on ears in BALB/c mice...
June 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28378889/the-prebiotic-c-terminal-elongation-of-peptides-can-be-initiated-by-n-carbamoyl-amino-acids
#15
Ninette Abou Mrad, Ghinwa Ajram, Jean-Christophe Rossi, Laurent Boiteau, Fabrice Duvernay, Robert Pascal, Grégoire Danger
The formation of peptides upon 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)-promoted activation of N-carbamoylamino acids (CAA), was considered in the scope of our recent works on carbodiimide promoted C-terminus elongation of peptides in a prebiotic context. Thus EDC promoted activation of CAA derivatives of Tyr(Me) or Ala in dilute aqueous medium pH 5.5-6.5 in the presence of excess of AA, resulted in peptide formation by C-terminus activation/elongation. Kinetic results similar to those of EDC-mediated activation of N-acyl-AA lead us to postulate the formation of a 2-amino-5(4H)-oxazolone intermediate by cyclization of the activated CAA, in spite of the absence of epimerization occurred at CAA residues...
April 5, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28374317/infrared-multiple-photon-dissociation-action-spectroscopy-of-the-b2-ion-from-ppg-evidence-of-third-residue-affecting-b2-fragment-structure
#16
John C Poutsma, Jonathan Martens, Jos Oomens, Phillipe Maitre, Vincent Steinmetz, Matthew Bernier, Mengxuan Jia, Vicki Wysocki
Infrared multiple-photon dissociation (IRMPD) action spectroscopy was performed on the b2(+) fragment ion from the protonated PPG tripeptide. Comparison of the experimental infrared spectrum with computed spectra for both oxazolone and diketopiperazine structures indicates that the majority of the fragment ion population has an oxazolone structure with the remainder having a diketopiperazine structure. This result is in contrast with a recent study of the IRMPD action spectrum of the PP b2(+) fragment ion from PPP, which was found to be nearly 100% diketopiperazine (Martens et al...
July 2017: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/28357423/polyfluoroarylation-of-oxazolones-access-to-non-natural-fluorinated-amino-acids
#17
Kip A Teegardin, Jimmie D Weaver
Herein, conditions are provided for the formation and use of the oxazolone enolate for the nucleophilic substitution of highly fluorinated (hetero)arenes, which after unmasking yield highly fluorinated non-natural amino acids and derivatives. In addition, the properties and chemical behavior of this new class of amino acids are explored. The utility is demonstrated in the one pot synthesis of medicinally relevant 2-aminohydantoins.
April 27, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28342759/activation-of-epithelial-signal-transducer-and-activator-of-transcription-1-by-interleukin-28-controls-mucosal-healing-in%C3%A2-mice-with-colitis-and-is-increased-in-mucosa-of-patients-with%C3%A2-inflammatory-bowel-disease
#18
Mircea T Chiriac, Barbara Buchen, Alexandra Wandersee, Gheorghe Hundorfean, Claudia Günther, Yvonne Bourjau, Sean E Doyle, Benjamin Frey, Arif B Ekici, Christian Büttner, Benno Weigmann, Raja Atreya, Stefan Wirtz, Christoph Becker, Jürgen Siebler, Markus F Neurath
BACKGROUND & AIMS: We investigated the roles of interleukin 28A (also called IL28A or interferon λ2) in intestinal epithelial cell (IEC) activation, studying its effects in mouse models of inflammatory bowel diseases (IBD) and intestinal mucosal healing. METHODS: Colitis was induced in C57BL/6JCrl mice (controls), mice with IEC-specific disruption of Stat1 (Stat1IEC-KO), mice with disruption of the interferon λ receptor 1 gene (Il28ra(-/-)), and mice with disruption of the interferon regulatory factor 3 gene (Irf3(-/-)), with or without disruption of Irf7 (Irf7(-/-))...
March 23, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28290578/pd-cu-catalyzed-tandem-head-to-tail-dimerization-cycloisomerization-of-terminal-ynamides-for-the-synthesis-of-5-vinyloxazolones
#19
Luning Tang, Hai Huang, Yang Xi, Guangke He, Hongjun Zhu
An attractive and novel methodology involving Pd/Cu-catalyzed tandem head-to-tail dimerization/cycloisomerization of terminal ynamides for the synthesis of 3,5-disubstituted oxazolones was developed. Under Pd(PPh3)2Cl2/CuI cooperative catalyzed reaction conditions, it provided efficient access to 5-vinyloxazolones with exceptional functional group tolerance and good chemoselectivity. The control experiments demonstrated that Pd(PPh3)2Cl2 serves a key role in the dimerization of terminal ynamides and shows low catalytic activity in the intramolecular cyclization...
March 14, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28290517/sensitivity-to-oxazolone-induced-dermatitis-is-transferable-with-gut-microbiota-in-mice
#20
Line Fisker Zachariassen, Lukasz Krych, Kåre Engkilde, Dennis Sandris Nielsen, Witold Kot, Camilla Hartmann Friis Hansen, Axel Kornerup Hansen
Atopic Dermatitis (AD) has been associated with gut microbiota (GM) dysbiosis in humans, indicating a causative role of GM in AD etiology. Furthermore, the GM strongly correlates to essential disease parameters in the well-known oxazolone-induced mouse model of AD. Here, we demonstrate that it is possible to transfer both a high-responding and a low-responding AD phenotype with GM from conventional mice to germ-free mice. The mice inoculated with the high-responding GM had significantly higher clinical score, increased ear thickness, and increased levels of IL-1β, TNFα, IL-4, IL-5, and IL-6 compared to the mice inoculated with the low-responding GM...
March 14, 2017: Scientific Reports
keyword
keyword
69240
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"