686736-60-7

Upstream product

• 87223-77-6 ethyl 3-amino-1H-indole-2-carboxylate 
• 2284-20-0 4-Methoxyphenyl isothiocyanate 

Downstream Products

• 1341207-25-7 C₁₇H₁₇N₃O₂S 
• 1341207-31-5 2-(4-methoxyphenylimino)-1,3-thiazino[5,4-b]indole 

Relevant academic research and scientific papers

Identification of biologically active pyrimido[5, 4-b]indoles that prolong NF-κB activation without intrinsic activity

Most vaccine adjuvants directly stimulate and activate antigen presenting cells but do not sustain immunostimulation of these cells. A high throughput screening (HTS) strategy was designed to identify compounds that would sustain NF-κB activation by a stimulus from the Tolllike receptor (TLR)4 ligand, lipopolysaccharide (LPS). Several pilot studies optimized the parameters and conditions for a cell based NF-κB reporter assay in human monocytic THP-1 cells. The final assay evaluated prolongation of LPS induced NF-κB activation at 12 h. The dynamic range of the assay was confirmed in a pilot screen of 14 631 compounds and subsequently in a main extensive screen with 166 304 compounds. Hit compounds were identified using an enrichment strategy based on unsupervised chemoinformatic clustering, and also by a na?ve "Top X" approach. A total of 2011 compounds were then rescreened for levels of coactivation with LPS at 5 h and 12 h, which provided kinetic profiles. Of the 407 confirmed hits, compounds that showed correlation of the kinetic profiles with the structural similarities led to identification of four chemotypes: pyrimido[5, 4-b]indoles, 4H-chromene-3-carbonitriles, benzo[d][1, 3]dioxol- 2-ylureas, and tetrahydrothieno[2, 3-c]pyridines, which were segregated by 5 h and 12 h kinetic characteristics. Unlike the TLR4 agonistic pyrimidoindoles identified in previous studies, the revealed pyrimidoindoles in the present work did not intrinsically stimulate TLR4 nor induce NF-κB but rather prolonged NF-κB signaling induced by LPS. A 42-member combinatorial library was synthesized which led to identification of potent N3-alkyl substituted pyrimidoindoles that were not only active in vitro but also enhanced antibody responses in vivo when used as a coadjuvant. The novel HTS strategy led to identification of compounds that are intrinsically quiescent but functionally prolong stimulation by a TLR4 ligand and thereby potentiate vaccine efficacy.

One-step ring-closure procedure for 4,5-dihydro-1,3-thiazino[5,4-b]indole derivatives with Lawesson's reagent. the fifth dihydro-1,3-thiazino[b]indole isomer

We report a convenient approach for the synthesis of a new ring system: 4,5-dihydro-1,3-thiazino[5,4-b]indoles. The procedure involves the use of Lawesson's reagent in the presence of silica to achieve the one-step ring-closure reactions of 2-benzoylamino-3-hydroxymethylindole intermediates to furnish 4,5-dihydro-2-aryl-1,3-thiazino[5,4-b]indoles. 2-Phenylimino-1,3- thiazino[5,4-b]indoles were obtained via the corresponding 3-phenylthiourea-2- carboxylic acid ester derivatives by chemoselective reduction of the ester group, followed by ring closure under acidic conditions. The structures of the novel products were elucidated by IR, 1H-NMR, and 13C-NMR spectroscopy, including 2D-HMQC, 2D-HMBC, and DEPT measurements.