82659-59-4Relevant academic research and scientific papers
C-MANNOSIDE COMPOUNDS USEFUL FOR THE TREATMENT OF URINARY TRACT INFECTIONS
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Page/Page column 21; 22-23, (2020/02/06)
Disclosed herein are new C-mannoside compounds and compositions and their application as pharmaceuticals for the treatment of human disease. Methods of inhibition of FimH activity in a human subject are also provided for the treatment diseases such as urinary tract infection.
C-Mannosyl Lysine for Solid Phase Assembly of Mannosylated Peptide Conjugate Cancer Vaccines
Bruijns, Sven C. M.,Codée, Jeroen D. C.,Filippov, Dmitri V.,Hogervorst, Tim P.,Li, R. J. Eveline,Marino, Laura,Meeuwenoord, Nico J.,Overkleeft, Herman S.,Van Der Marel, Gijsbert A.,Van Kooyk, Yvette,Van Vliet, Sandra J.
, (2020/03/04)
Dendritic cells (DCs) are armed with a multitude of Pattern Recognition Receptors (PRRs) to recognize pathogens and initiate pathogen-tailored T cell responses. In these responses, the maturation of DCs is key, as well as the production of cytokines that help to accomplish T cell responses. DC-SIGN is a frequently exploited PRR that can effectively be targeted with mannosylated antigens to enhance the induction of antigen-specific T cells. The natural O-mannosidic linkage is susceptible to enzymatic degradation, and its chemical sensitivity complicates the synthesis of mannosylated antigens. For this reason, (oligo)mannosides are generally introduced in a late stage of the antigen synthesis, requiring orthogonal conjugation handles for their attachment. To increase the stability of the mannosides and streamline the synthesis of mannosylated peptide antigens, we here describe the development of an acid-stable C-mannosyl lysine, which allows for the inline introduction of mannosides during solid-phase peptide synthesis (SPPS). The developed amino acid has been successfully used for the assembly of both small ligands and peptide antigen conjugates comprising an epitope of the gp100 melanoma-associated antigen and a TLR7 agonist for DC activation. The ligands showed similar internalization capacities and binding affinities as the O-mannosyl analogs. Moreover, the antigen conjugates were capable of inducing maturation, stimulating the secretion of pro-inflammatory cytokines, and providing enhanced gp100 presentation to CD8+ and CD4+ T cells, similar to their O-mannosyl counterparts. Our results demonstrate that the C-mannose lysine is a valuable building block for the generation of anticancer peptide-conjugate vaccine modalities.
Mild cu(Otf)2-mediated C-glycosylation with chelation-assisted picolinate as a leaving group
Tang, Weiping,Ye, Wenjing,Stevens, Christopher M.,Wen, Peng,Simmons, Christopher J.
, p. 16218 - 16225 (2021/01/19)
C-Glycosylation reactions of glycosyl picolinates with allyltrimethylsilane or silyl enol ethers were developed. Picolinate as a chelation-assisted leaving group could be activated by Cu(OTf)2 and avoided the use of harsh Lewis acids. The glycosylations were operated under mild neutral conditions and gave the corresponding C-glycosides in up to 95% yield with moderate to excellent stereoselectivities.
Deciphering the conformation of C-linked α-D-mannopyranosides and their application toward the synthesis of low nanomolar E. Coli FimH ligands
Mousavifar, Leila,Vergoten, Gérard,Roy, René
, p. 384 - 397 (2019/01/03)
C-Allyl –D-mannopyranosides were prepared via a variety of routes to determine an optimal route to the - anomers. The relative conformational energies of the key intermediate was evaluated by molecular modeling which showed the conventional4Cs
C-GLYCOSIDE COMPOUNDS USEFUL FOR TREATING DISEASE
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Paragraph 00198, (2017/10/06)
The present invention relates to mannoside derivative compounds useful as inhibitors of FimH and methods for the treatment or prevention of urinary tract infection.
MANNOSE DERIVATIVES USEFUL FOR TREATING PATHOLOGIES ASSOCIATED WITH ADHERENT E. COLI
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Page/Page column 51, (2017/02/28)
The present invention relates to mannose derivatives of formula (I): wherein R1 represents H, CO-(C1-C6)-alkyl or CO-alkylaryl, Y represents a single bond, CH2, O, NR3, S, A represents O, NH or S, X represents H and X' represents OH or X and X' taken together with the carbon atom bearing them form a CO group, R2 represents H, a linear or branched (C1-C6 )-alkyl or CF3, R3 represents H, a C1-C6 alkyl, a CO-(C1-C6 )-alkyl, CF3 or COCF3, and R is as described in claim 1. The mannose derivatives of formulae (I) are useful for treating pathologies associated with the presence of adherent Escherichia coli (AEC), in particular inflammatory bowel diseases (IBD), such as Crohn's disease and ulcerative colitis; a urinary tract infection, in particular painful bladder syndrome and cystitis, more particularly interstitial cystitis; irritable bowel syndrome; metabolic diseases such as metabolic obesity, diabetes, hypercholesterolemia; autoimmune inflammatory diseases; and colorectal cancer, in particular colon cancer.
GLUCOSE-RESPONSIVE INSULIN CONJUGATES
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Page/Page column 138; 148, (2016/10/31)
Insulin conjugates comprising an insulin analog molecule covalently attached to at least one bi-dentate linker having two arms, each arm independently attached to a ligand comprising a saccharide and wherein the saccharide for at least one ligand of the linker is fucose are disclosed. The insulin conjugates display a pharmacokinetic (PK) and/or pharmacodynamic (PD) profile that is responsive to the systemic concentrations of a saccharide such as glucose or alpha-methylmannose even when administered to a subject in need thereof in the absence of an exogenous multivalent saccharide-binding molecule such as Con A.
Second generation of thiazolylmannosides, FimH antagonists for E. coli-induced Crohn's disease
Chalopin,Alvarez Dorta,Sivignon,Caudan,Dumych,Bilyy,Deniaud,Barnich,Bouckaert,Gouin
, p. 3913 - 3925 (2016/05/19)
The anti-adhesive strategy, consisting of disrupting bacterial attachment to the host cells, is widely explored as an alternative to antibiotic therapies. Recently, thiazolylmannosides (TazMans) have been identified as strong anti-adhesives of E. coli strains implied in the gut inflammation of patients with Crohn's disease. In this work, we developed a second generation of TazMans with improved chemical stability. The anomeric nitrogen was substituted by short linkers and the compounds were assessed against the bacterial adhesin FimH and the clinically isolated LF82 E. coli strain in four in vitro assays. The results obtained on the FimH adhesin alone and the whole bacteria enabled the identification of a candidate for further in vivo evaluations.
Adaptable synthesis of C-glycosidic multivalent carbohydrates and succinamide-linked derivatization
Miller, Gavin J.,Gardiner, John M.
supporting information; experimental part, p. 5262 - 5265 (2011/02/24)
A modular approach to the synthesis of trivalent C-glycosidic carbohydrates is described. The approach is illustrated employing carboxylate-terminated C-glycosidic d-mannose, d-glucose, and d-galactose derivatives with different length C1-linked spacer un
Domino heck/lactonization-catalyzed synthesis of 3-C-linked mannopyranosyl coumarins
Giguere, Denis,Cloutier, Philipe,Roy, Rene
scheme or table, p. 8480 - 8483 (2010/02/28)
(Chemical Equation Presented). Selective syntheses of methyl α- (8) and β-C-mannopyranosyl acrylates (9) were obtained from α-C-allyl mannopyranoside (3) by ozonolysis to 4 followed by α-methylenation to provide intermediate aldehydes 5 and 6. The β-anomer 6 was obtained by in situ anomeric epimerization. The acrylates and the homologous α-anomer 16, obtained by oxidative hydroboration, oxidation, and α-methylenation, were converted into 3-C-linked mannopyranosyl coumarins 11, 12, and 19 in good yields under one-pot Heck/lactonization conditions. 2009 American Chemical Society.
