59898-49-6Relevant academic research and scientific papers
Design, Synthesis, and Structure-Activity Relationship of N-Aryl- N′-(thiophen-2-yl)thiourea Derivatives as Novel and Specific Human TLR1/2 Agonists for Potential Cancer Immunotherapy
Chen, Zhipeng,Zhang, Lina,Yang, Junjie,Zheng, Lu,Hu, Fanjie,Duan, Siqin,Nandakumar, Kutty Selva,Liu, Shuwen,Yin, Hang,Cheng, Kui
, p. 7371 - 7389 (2021/06/28)
The previous virtual screening of ten million compounds yielded two novel nonlipopeptide-like chemotypes as TLR2 agonists. Herein, we present the chemical optimization of our initial hit, 1-phenyl-3-(thiophen-2-yl)urea, which resulted in the identification of SMU-C80 (EC50 = 31.02 ± 1.01 nM) as a TLR2-specific agonist with a 370-fold improvement in bioactivity. Mechanistic studies revealed that SMU-C80, through TLR1/2, recruits the adaptor protein MyD88 and triggers the NF-κB pathway to release cytokines such as TNF-α and IL-1β from human, but not murine, cells. To the best of our knowledge, it is the first species-specific TLR1/2 agonist reported until now. Moreover, SMU-C80 increased the percentage of T, B, and NK cells ex vivo and activated the immune cells, which suppressed cancer cell growth in vitro. In summary, we obtained a highly efficient and specific human TLR1/2 agonist that acts through the MyD88 and NF-κB pathway, facilitating cytokine release and the simultaneous activation of immune cells that in turn affects the apoptosis of cancer cells.
Synthesis of novel substituted 2-lactosylthiothieno[2,3-d]pyrimidin-4(3H)-one derivatives
Dai, Qiu-Hong,Yan, Kai,Liu, Ming-Guo
, p. 1390 - 1394 (2015/04/27)
The title compounds substituted 2-lactosylthiothieno[2,3-d]pyrimidin-4-ones 6 were synthesized by the glycosyl reaction and alcoholysis reaction of substituted 2-thioxo-thieno[2,3-d]pyrimidin-4-ones 4,which is formed by the base catalytic and acetic acidify reaction of amino esters 2 with alkyl or arylisothiocyanates and hepta-O-acetyl-lactosyl bromide in good yields. All of the compounds were confirmed by NMR, ESI-MS, and elemental analysis.
Synthesis and pharmacological activities of some 3-substituted thienopyrimidin-4-one-2-thiones
Cannito, A.,Perrissin, M.,Luu-Duc, C.,Huguet, F.,Gaultier, C.,Narcisse, G.
, p. 635 - 639 (2007/10/02)
The condensation of substituted 2-amino-3-carbethoxy-thiophenes with methyl, ethyl and phenyl isothiocyanate yields the corresponding thienylthioureas which cyclize in ethanol saturated with dry hydrochloric acid to form 3-substituted thienopyrimid
Synthesis of 3 substituted thieno[2,3 d]pyrimidin 4(3H) one 2 mercaptoacetic acids and their ethyl esters for pharmacological screening
Devani,Shishoo,Pathak,Parikh,Shah,Padhya
, p. 660 - 664 (2007/10/08)
3 Substituted thieno[2,3 d]pyrimidin 4(3H) one 2 mercaptoacetic acids and their ethyl esters were synthesized from 2 mercaptothieno[2,3 d]pyrimidin 4 (3H) ones, which were obtained by cyclization of thienylthioureas in acidic medium. Analgesic, anti inflammatory, and anticonvulsant activities were found in some of these compounds. Significant antimicrobial activity was exhibited by thienylthioureas.
