59898-55-4Relevant 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.
Structure-activity relationship analysis of a novel necroptosis inhibitor, Necrostatin-5
Wang, Ke,Li, Jinfeng,Degterev, Alexei,Hsu, Emily,Yuan, Junying,Yuan, Chengye
, p. 1455 - 1465 (2007/10/03)
Necrostatin-5 (Nec-5) is a novel potent small-molecule inhibitor of necroptosis structurally distinct from previously described Necrostatin-1 (Nec-1), and therefore, represents a new direction for the inhibition of this cellular caspase-independent necrot
Synthesis and transformations of 3-ethoxycarbonyl-2-(N-R-thioreido)thiophenes
Chumakova,Demchenko,Krasovsky,Dolishnyak,Lozinskii
, p. 1002 - 1012 (2007/10/03)
3-Ethoxycarbonyl-2-N-R-thioureido)-4,5,6,7-tetrahydrobenzo[b]thiophenes were obtained by the reaction of 2- amino-3-ethoxycarbonyl-4,5,6,7-tetrahydrobenzo[b]thiophene with isothiocyanates and of 3-ethoxycarbonyl-2-isothiocyanato-4,5,6,7-tetrahydrobenzo[b]
Synthesis and antimicrobial activity of some thiazolinyl tetrahydrobenzo[b]thiophenes and thiazolinyl tetrahydrobenzothieno[2,3-d]pyrimidin-4-ones
Aboulwafa,Ismail,Koreish
, p. 631 - 642 (2007/10/02)
Two series of novel 3-carbethoxy-2-(3',4'-disubstituted-2',3'-dihydrothiazol-2'-ylidenamin o)-4,5,6,7-tetrahydrobenzo[b]thiophenes (3a-o) and 2-methyl-3-(3',4'-disubstituted-2',3'-dihydrothiazol-2'-ylidenamino-5, 6,7,8-tetrahydrobenzothieno[2,3-d]pyrimidi
METHYL N-ARYLDITHIOCARBAMATES: USEFUL REAGENTS FOR THE ANNELATION OF PYRIMIDINES AND 1,3-OXAZINES TO FIVE-MEMBERED HETEROCYCLIC RINGS
Garin, Javier,Loscertales, Maria Pilar,Melendez, Enrique,Merchan, Francisco L.,Rodriguez, Ricardo,Tejero, Tomas
, p. 1303 - 1312 (2007/10/02)
The reaction of methyl N-aryldithiocarbamates with ?-excessive heteroaromatic o-amino acid derivatives leads to the annelation of 4-oxo-2-thioxopyrimidines, 2,4-dioxopyrimidines or 2-arylamino-1,3-oxazines, depending on the reaction conditions.
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.
