Indium-Catalyzed Reductive Dithioacetalization of Carboxylic Acids with Dithiols: Scope, Limitations, and Application to Oxidative Desulfurization

In this study an InI₃-TMDS (1,1,3,3-tetramethyl­disiloxane) reducing system effectively catalyzed the reductive dithioacetalization of a variety of aromatic and aliphatic carboxylic acids with 1,2-ethanedithiol or 1,3-propanedithiol leading to the one-pot preparation of either 1,3-dithiolane derivatives or a 1,3-dithiane derivative. Also, the intact indium catalyst continuously catalyzed the subsequent oxidative desulfurization of an in situ formed 1,3-dithiolane derivative, which led to the preparation of the corresponding aldehydes

Single-Step Thioetherification by Indium-Catalyzed Reductive Coupling of Carboxylic Acids with Thiols

Direct thioetherification from a variety of aromatic carboxylic acids and thiols using a reducing system combined with InBr₃ and 1,1,3,3-teramethyldisiloxane (TMDS) in a one-pot procedure is demonstrated. It was also found that a system combined with InI₃ and TMDS underwent thioetherification of aliphatic carboxylic acids with thiols

Additional file 3: Figure S2. of Identification of definitive serum biomarkers associated with disease activity in primary Sjögren’s syndrome

Serum levels of five proteins in pSS, sSS, sicca syndrome and HCs. The five proteins were CXCL13, TNF-R2, CD48, BAFF and PD-L2. Primary SS (pSS), n = 58; secondary SS (sSS), n = 6; other sicca syndrome, n = 13; healthy controls (HCs), n = 38. Differences in quantitative variables were analyzed by the Mann-Whitney U test when comparing two groups and by the Kruskal-Wallis test when comparing multiple groups. *P value <0.05, which was considered significant. (TIF 33972 kb

Additional file 2: Figure S1. of Identification of definitive serum biomarkers associated with disease activity in primary Sjögren’s syndrome

Functional annotation of differentially expressed proteins in pSS patient sera. Nodes indicate molecular concepts or set of biologically related genes. Name of each node is indicated in black text on the node. The node size represents the proportion of differentially expressed gene symbols in the concepts (e.g., the “chemokine signaling pathway” and “extracellular region” concepts contain 14 and 58 genes, respectively). Length of lines between nodes represents degree of overlap between symbols. Colored lines indicate strength of functional relationship from strong to weak, as follows: red, yellow, green and gray. Green nodes indicate immune response-related molecular concepts, and red nodes indicate platelet-related molecular concepts. (TIF 9752 kb

Additional file 1: Figure S1. of Enhanced IgG4 production by follicular helper 2 T cells and the involvement of follicular helper 1 T cells in the pathogenesis of IgG4-related disease

Flow cytometric analysis of the percentage of circulating follicular helper T (Tfh) cells and activated Tfh cells. The percentage of Tfh cells (A) and activated Tfh cells (B) from patients with IgG4-related disease (IgG4-RD) (n = 17), primary Sjögren’s syndrome (pSS) (n = 20), multicentric Castleman’s disease (MCD) (n = 5), and healthy controls (HC) (n = 12). *P < 0.05; **P < 0.0001 for analysis using the Kruskal-Wallis test, followed by group-wise comparisons using the Mann-Whitney U test. (TIF 42 kb

Structure-Based Design and Synthesis of 3‑Amino-1,5-dihydro‑4<i>H</i>‑pyrazolopyridin-4-one Derivatives as Tyrosine Kinase 2 Inhibitors

We report herein the discovery and optimization of 3-amino-1,5-dihydro-4<i>H</i>-pyrazolopyridin-4-one TYK2 inhibitors. High-throughput screening against TYK2 and JAK1–3 provided aminoindazole derivative <b>1</b> as a hit compound. Scaffold hopping of the aminoindazole core led to the discovery of 3-amino-1,5-dihydro-4<i>H</i>-pyrazolopyridin-4-one derivative <b>3</b> as a novel chemotype of TYK2 inhibitors. Interestingly, initial SAR study suggested that this scaffold could have a vertically flipped binding mode, which prompted us to introduce a substituent at the 7-position as a moiety directed toward the solvent-exposed region. Introduction of a 1-methyl-3-pyrazolyl moiety at the 7-position resulted in a dramatic increase in TYK2 inhibitory activity, and further optimization led to the discovery of <b>20</b>. Compound <b>20</b> inhibited IL-23-induced IL-22 production in a rat PD assay, as well as inhibited IL-23 signaling in human PBMC. Furthermore, <b>20</b> showed selectivity for IL-23 signaling inhibition against GM-CSF, demonstrating the unique cytokine selectivity of the novel TYK2 inhibitor