42076-12-0Relevant articles and documents
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.
Discovery of new apoptosis-inducing agents for breast cancer based on ethyl 2-amino-4,5,6,7-tetra hydrobenzo[b]thiophene-3-carboxylate: Synthesis, in vitro, and in vivo activity evaluation
Barakat, Assem,Boraei, Ahmed T. A.,Eltamany, Elsayed H.,Gad, Emad M.,Hammad, Magdy S. A. G.,Nafie, Mohamed S.
, (2020/06/29)
A multicomponent synthesis was empolyed for the synthesis of ethyl 2-amino-4,5,6,7- tetrahydrobenzo[b]thiophene-3-carboxylate 1. An interesting cyclization was obtained when the amino-ester 1 reacted with ethyl isothiocyanate to give the benzo[4,5]thieno[
Enterovirus inhibitory activity of C-8-tert-butyl substituted 4-aryl-6,7,8,9-tetrahydrobenzo[4,5]thieno[3,2-e][1,2,4]triazolo[4,3-a]pyrimidin-5(4H)-ones
Kumar Biswas, Bishyajit,Malpani, Yashwardhan R.,Ha, Neul,Kwon, Do-Hyun,Soo Shin, Jin,Kim, Hae-Soo,Kim, Chonsaeng,Bong Han, Soo,Lee, Chong-Kyo,Jung, Young-Sik
, p. 3582 - 3585 (2017/07/07)
Members of a series of 4-aryl-6,7,8,9-tetrahydrobenzo[4,5]thieno[3,2-e][1,2,4]triazolo[4,3-a]pyrimidin-5(4H)-ones (1, Fig. 2) were prepared and tested against representative enteroviruses including Human Coxsackievirus B1 (Cox B1), Human Coxsackievirus B3 (Cox B3), human Poliovirus 3 (PV3), human Rhinovirus 14 (HRV14), human Rhinovirus 21 (HRV 21) and human Rhinovirus 71 (HRV 71). The C-8-tert-butyl group on the tetrahydrobenzene ring in these substances was found to be crucial for their enterovirus activity. One member of this group, 1e, showed single digit micromolar activities (1.6–8.85?μM) against a spectrum of viruses screened, and the highest selectivity index (SI) values for Cox B1 (>11.2), for Cox B3 (>11.5), and for PV3 (>51.2), respectively. In contrast, 1p, was the most active analog against the selected HRVs (1.8–2.6?μM), and showed the highest selectivity indices among the group of compounds tested. The SI values for 1p were 11.5 for HRV14, 8.4 for HRV21, and 12.1 for HRV71, respectively.
Tetrahydrobenzothiophene derivatives, preparation method thereof and pharmaceutical composition for prevention or treatment of the viral diseases containing the same
-
Paragraph 0211-0213, (2017/04/03)
The present invention relates to tetrahydrobenzothiophene derivatives, a pharmaceutically allowable salt thereof or an optical isomer thereof, to a preparation method thereof and to a pharmaceutical composition for preventing or treating viral diseases co
Design, synthesis, molecular docking and biological evaluation of thiophen-2-iminothiazolidine derivatives for use against Trypanosoma cruzi
Silva-Júnior,Silva,Fran?a,Silva,Barreto,Silva,Ferreira,Gatto,Moreira,Siqueira-Neto,Mendon?a-Júnior,Lima,Bortoluzzi,Scotti,Scotti,Meneghetti,Aquino,Araújo-Júnior
, p. 4228 - 4240 (2016/08/23)
In this study, we designed and synthesized a series of thiophen-2-iminothiazolidine derivatives from thiophen-2-thioureic with good anti-Trypanosoma cruzi activity. Several of the final compounds displayed remarkable trypanocidal activity. The ability of the new compounds to inhibit the activity of the enzyme cruzain, the major cysteine protease of T. cruzi, was also explored. The compounds 3b, 4b, 8b and 8c were the most active derivatives against amastigote form, with significant IC50values between 9.7 and 6.03?μM. The 8c derivative showed the highest potency against cruzain (IC50?=?2.4?μM). Molecular docking study showed that this compound can interact with subsites S1 and S2 simultaneously, and the negative values for the theoretical energy binding (Eb?=??7.39?kcal·mol?1) indicates interaction (via dipole–dipole) between the hybridized sulfur sp3atom at the thiazolidine ring and Gly66. Finally, the results suggest that the thiophen-2-iminothiazolidines synthesized are important lead compounds for the continuing battle against Chagas disease.
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.
Hyperbolic mixed-type inhibition of acetylcholinesterase by tetracyclic thienopyrimidines
Gonzalez Tanarro,Guetschow
scheme or table, p. 350 - 358 (2012/02/14)
A series of tetracyclic thienopyrimidines (7-14) was prepared and investigated as inhibitors of acetylcholinesterase from Electrophorus electricus acetylcholinesterase (EeAChE), as well as human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBChE). A new synthetic procedure was employed for the synthesis of the angularly fused heterocycles 7-10. Among them, the presence of a tetrahydropyrido ring with a benzyl rest at the basic nitrogen was required for EeAChE inhibition. A detailed kinetic analysis of the hyperbolic mixed-type inhibition of EeAChE by 9-14 was performed. These heterocyclic compounds inhibited EeAChE with Ki values of less than 3 μM. Most α values were relatively close to 1, indicating a similar affinity of the inhibitor to the free enzyme and the enzyme-substrate complex. Inhibitor 10 displayed a rather uncompetitive pattern of inhibition (α=0.47) and a relatively high residual activity of a postulated ternary enzyme-substrate- inhibitor complex (β=0.24).
Synthesis, characterization and biological studies of some novel thieno[2,3-d]pyrimidines
Al-Taisan, Khulud M.,Al-Hazimi, Hassan M. A.,Al-Shihry, Shar S.
experimental part, p. 3932 - 3957 (2010/09/18)
Several 2-unsubstituted thieno[2,3-d]pyrimidines have been prepared from 2-aminothiophene-3-carboxylic acid esters and their carbonitrile analogs. Some triazolothienopyrimidine and 2-thioxothienopyrimidine representatives have also been synthesized using
Title studies on the reaction of N-(3-carbethoxy-4,5,6,7-tetrahydrobenzo[b] thien-2-yl)-N′-phenylthiourea with hydrazine hydrate (Part 1)
El-Sherief, Hassan A. H.,El-Naggar, Galal M.,Hozien, Zeinab A.,El-Sawaisi, Suliman M.
, p. 467 - 473 (2008/09/19)
(Chemical Equation Presented) The reaction of N-(3-carbethoxy-4,5,6,7- tetrahydrobenzo[b]thien-2-yl)-N′-phenylthiourea (1) with hydrazine hydrate in 1-butanol afforded a mixture of compounds 2, 3 and 4. Treatment of 3 and 4 with nitrous acid gave 6 and 8 respectively, while reactions of 3 with acetylacetone gave 7. Synthesis of tetracyclic compounds 9a-f and 11 from the reactions of 3 with ethyl orthoformate or appropriate acids, acid chloride, carbon disulphide and/or ethyl chloroformate. Also its reaction with isothiocyanate derivatives gave the corresponding thiosemicarbzides 12a,b which on, refluxing in alcoholic KOH gave the unexpected tetracyclic products 14a,b. Similarly the tetracyclic compounds 16a-e and 19 were obtained by cyclization of 4 and 18 respectively.
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
