cas 1736-72-7, 1-[4-(TRIFLUOROMETHYL)PHENYL]-2-THIOUREA

Articles about 1736-72-7Total 21 be found

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Discovery of aminothiazole derivatives as novel human enterovirus A71 capsid protein inhibitors
Enterovirus A71 (EV-A71), one of the major pathogens that causes hand, foot and mouth disease (HFMD), has seriously threatened the health and safety of young children. In this study, aminothiazole derivatives were synthesized and screened against EV-A71 in Rhabdomyosarcoma (RD) cells. The best compound (12s), with a biphenyl group, showed activity against EV-A71 (EC50: 0.27 μM) but also against a series of different human enteroviruses without significant cytotoxicity (CC50 > 56.2 μM). Mechanistic studies including time-of-drug-addition assays, viral entry assays and microscale thermophoresis (MST) experiments, showed that 12s binds to EV-A71 capsid and blocks the binding between the viral protein VP1 and the relevant human scavenger receptor class B member 2 (hSCARB2).
Cai, Yang,Chen, Yinuo,Dong, Chune,Lan, Ke,Lei, Ping,Tang, Qi,Wu, Shuwen,Xu, Ting,Xu, Zhichao,Zhou, Hai-Bing,Zou, Wenting
(2022/03/15)

4-PHENYL-N-(PHENYL)THIAZOL-2-AMINE DERIVATIVES AND RELATED COMPOUNDS AS ARYL HYDROCARBON RECEPTOR (AHR) AGONISTS FOR THE TREATMENT OF E.G. ANGIOGENESIS IMPLICATED OR INFLAMMATORY DISORDERS
4-phenyl-N-(phenyl)thiazol-2-amine and 4-(pyridin-3-yl)-N-( phenyl) thiazol-2-amine derivatives and the corresponding thiadiazole, thiophene, oxazole, oxadiazole, imidazole and triazole derivatives and related compounds as aryl hydrocarbon receptor (AHR) agonists for the treatment of angiogenesis implicated disorders, such as e.g. retinopathy, psoriasis, rheumatoid arthritis, obesity and cancer, or inflammatory disorders.
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Paragraph 00221; 00237; 00423-00424

(2021/06/26)

Novel arylimino thiazole compound, preparation method and uses thereof
The present invention relates to a compound with antibacterial synergy activity, a preparation and uses thereof, particularly to a novel arylimino thiazole compound, a preparation method and uses thereof, and specifically discloses a class of compounds represented by a formula (I) or optical isomers, cis-trans isomers or pharmaceutically acceptable salts thereof, a preparation method and uses thereof. The invention further discloses a pharmaceutical composition containing the compound. The compound of the present invention can effectively enhance the antibacterial activity of antibiotics, andcan be used for treating antibiotic-resistant bacteria. The formula (I) is defined in the specification.
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Paragraph 0125; 0126; 0127; 0128

(2018/03/28)

Synergism of fused bicyclic 2-aminothiazolyl compounds with polymyxin B against: Klebsiella pneumoniae
A series of fused bicyclic 2-aminothiazolyl compounds were synthesized and evaluated for their synergistic effects with polymyxin B (PB) against Klebsiella pneumoniae (SIPI-KPN-1712). Some of the synthesized compounds exhibited synergistic activity. When 4 μg ml-1 compound B1 was combined with PB, it showed potent antibacterial activity, achieving 64-fold reduction of the MIC of PB. Furthermore, compound B1 showed prominent synergistic efficacy in both concentration gradient and time-kill curves in vitro. In addition, B1 combined with PB also exhibited synergistic and partial synergistic effect against E. coli (ATCC25922 and its clinical isolates), Acinetobacter baumannii (ATCC19606 and its clinical isolates), and Pseudomonas aeruginosa (Pae-1399).
Wang, Rong,Hou, Shuang,Dong, Xiaojing,Chen, Daijie,Shao, Lei,Qian, Liujia,Li, Zhong,Xu, Xiaoyong
supporting information
p. 2060 - 2066
(2017/11/22)

Aminothiazole derivatives
The invention relates to aminothiazole heterocyclic derivatives, a preparation method thereof and an application of the aminothiazole heterocyclic derivatives in preparation of drugs for treating or preventing progressive cognitive disorder and/or amnesia diseases.
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Paragraph 0074; 0075; 0076

(2018/01/04)

2-(4-trifluoromethyl-phenylimino)-5-(2-naphthyl)methylene-thiazolidin-4-one compound and application thereof
The invention discloses a thiazole heterocyclic compound. The thiazole heterocyclic compound is 2-(4-trifluoromethyl-phenylimino)-5-(2-naphthyl) methylene-thiazolidin-4-one compound, which is referred as TNTO and has a chemical structure as shown in a general formula (I). The invention further discloses an application of the compound as an aromatic hydrocarbon receptor stimulant. Experiments prove that the thiazole heterocyclic compound under the concentration of 10 muM can remarkably up-regulate the gene, protein expression of the related exogenous substance metabolic enzyme CYP1A1 of the downstream target gene of the aromatic hydrocarbon receptor in the mouse liver cancer cells, the compound is prompted to be an agonist of an aromatic hydrocarbon receptor, and is expected to become a potential medicine which takes the aromatic hydrocarbon receptor as the tumor target, and has wide clinical application prospect and economic development value.
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Paragraph 0022; 0023; 0028

(2017/07/22)

Synthesis and antitumor evaluation of 5-(benzo[: D] [1,3]dioxol-5-ylmethyl)-4-(tert -butyl)- N -arylthiazol-2-amines
A series of novel N-aryl-5-(benzo[d][1,3]dioxol-5-ylmethyl)-4-(tert-butyl)thiazol-2-amines (C1-C31) were synthesized and evaluated for their antitumor activities against HeLa, A549 and MCF-7 cell lines. Some tested compounds showed potent growth inhibition properties with IC50 values generally below 5 μM against the three human cancer cells lines. Compound C27 showed potent activities against HeLa and A549 cell lines with IC50 values of 2.07 ± 0.88 μM and 3.52 ± 0.49 μM, respectively. Compound C7 (IC50 = 2.06 ± 0.09 μM) was the most active compound against A549 cell line, while compound C16 (IC50 = 2.55 ± 0.34 μM) showed the best inhibitory activity against the MCF-7 cell line. The preliminary mechanism of the inhibitory effect was investigated via further experiments, such as morphological analysis by dual AO/EB staining and Hoechst 33342 staining, and cell apoptosis and cycle assessment by FACS analysis. The results illustrated that compound C27 could induce apoptosis and cause both S-phase and G2/M-phase arrests in HeLa cell line. Therefore, compound C27 could be developed as a potential antitumor agent.
Wu,Fang,Tang,Xiao,Ye,Li,Hu
p. 1768 - 1774
(2016/09/28)

Probing the ATP-Binding Pocket of Protein Kinase DYRK1A with Benzothiazole Fragment Molecules
DYRK1A has emerged as a potential target for therapies of Alzheimer's disease using small molecules. On the basis of the observation of selective DYRK1A inhibition by firefly d-luciferin, we have explored static and dynamic structural properties of fragment sized variants of the benzothiazole scaffold with respect to DYRK1A using X-ray crystallography and NMR techniques. The compounds have excellent ligand efficiencies and show a remarkable diversity of binding modes in dynamic equilibrium. Binding geometries are determined in part by interactions often considered "weak", including "orthogonal multipolar" types represented by, for example, F-CO, sulfur-aromatic, and halogen-aromatic interactions, together with hydrogen bonds that are modulated by variation of electron withdrawing groups. These studies show how the benzothiazole scaffold is highly promising for the development of therapeutic DYRK1A inhibitors. In addition, the subtleties of the binding interactions, including dynamics, show how full structural studies are required to fully interpret the essential physical determinants of binding.
Rothweiler, Ulli,Stensen, Wenche,Brandsdal, Bj?rn Olav,Isaksson, Johan,Leeson, Frederick Alan,Engh, Richard Alan,Svendsen, John S. Mj?en
p. 9814 - 9824
(2016/11/19)

Design, synthesis, X-ray crystallographic analysis, and biological evaluation of thiazole derivatives as potent and selective inhibitors of human dihydroorotate dehydrogenase
Human dihydroorotate dehydrogenase (HsDHODH) is a flavin-dependent mitochondrial enzyme that has been certified as a potential therapeutic target for the treatment of rheumatoid arthritis and other autoimmune diseases. On the basis of lead compound 4, which was previously identified as potential HsDHODH inhibitor, a novel series of thiazole derivatives were designed and synthesized. The X-ray complex structures of the promising analogues 12 and 33 confirmed that these inhibitors bind at the putative ubiquinone binding tunnel and guided us to explore more potent inhibitors, such as compounds 44, 46, and 47 which showed double digit nanomolar activities of 26, 18, and 29 nM, respectively. Moreover, 44 presented considerable anti-inflammation effect in vivo and significantly alleviated foot swelling in a dose-dependent manner, which disclosed that thiazole-scaffold analogues can be developed into the drug candidates for the treatment of rheumatoid arthritis by suppressing the bioactivity of HsDHODH.
Zhu, Junsheng,Han, Le,Diao, Yanyan,Ren, Xiaoli,Xu, Minghao,Xu, Liuxin,Li, Shiliang,Li, Qiang,Dong, Dong,Huang, Jin,Liu, Xiaofeng,Zhao, Zhenjiang,Wang, Rui,Zhu, Lili,Xu, Yufang,Qian, Xuhong,Li, Honglin
p. 1123 - 1139
(2015/03/04)

Multi-dimensional target profiling of N,4-diaryl-1,3-thiazole-2-amines as potent inhibitors of eicosanoid metabolism
Eicosanoids like leukotrienes and prostaglandins play a considerable role in inflammation. Produced within the arachidonic acid (AA) cascade, these lipid mediators are involved in the pathogenesis of pain as well as acute and chronic inflammatory diseases like rheumatoid arthritis and asthma. With regard to the lipid cross-talk within the AA pathway, a promising approach for an effective anti-inflammatory therapy is the development of inhibitors targeting more than one enzyme of this cascade. Within this study, thirty N-4-diaryl-1,3-thiazole-2- amine based compounds with different substitution patterns were synthesized and tested in various cell-based assays to investigate their activity and selectivity profile concerning five key enzymes involved in eicosanoid metabolism (5-, 12-, 15-lipoxygenase (LO), cyclooxygenase-1 and -2 (COX-1/-2)). With compound 7, 2-(4-phenyl)thiazol-2-ylamino)phenol (ST-1355), a multi-target ligand targeting all tested enzymes is presented, whereas compound 9, 2-(4-(4-chlorophenyl)thiazol-2-ylamino)phenol (ST-1705), represents a potent and selective 5-LO and COX-2 inhibitor with an IC50 value of 0.9 ± 0.2 μM (5-LO) and a residual activity of 9.1 ± 1.1% at 10 μM (COX-2 product formation). The promising characteristics and the additional non-cytotoxic profile of both compounds reveal new lead structures for the treatment of eicosanoid-mediated diseases.
R?dl, Carmen B.,Vogt, Dominik,Kretschmer, Simon B.M.,Ihlefeld, Katja,Barzen, Sebastian,Brüggerhoff, Astrid,Achenbach, Janosch,Proschak, Ewgenij,Steinhilber, Dieter,Stark, Holger,Hofmann, Bettina
p. 302 - 311
(2014/08/05)

Design, synthesis and evaluation of 2-aminothiazole derivatives as sphingosine kinase inhibitors
Sphingosine kinases (SphK1, SphK2) are main regulators of sphingosine-1-phosphate (S1P), which is a pleiotropic lipid mediator involved in numerous physiological and pathophysiological functions. SphKs are targets for novel anti-cancer and anti-inflammatory agents that can promote cell apoptosis and modulate autoimmune diseases. Herein, we describe the design, synthesis and evaluation of an aminothiazole class of SphK inhibitors. Potent inhibitors have been discovered through a series of modifications using the known SKI-II scaffold to define structure-activity relationships. We identified N-(4-methylthiazol-2-yl)-(2,4′-bithiazol)-2′-amine (24, ST-1803; IC50values: 7.3 μM (SphK1), 6.5 μM (SphK2)) as a promising candidate for further in vivo investigations and structural development.
Vogt, Dominik,Weber, Julia,Ihlefeld, Katja,Brüggerhoff, Astrid,Proschak, Ewgenij,Stark, Holger
p. 5354 - 5367
(2014/12/11)

Structure-activity relationships of 2-aminothiazoles effective against Mycobacterium tuberculosis
A series of 2-aminothiazoles was synthesized based on a HTS scaffold from a whole-cell screen against Mycobacterium tuberculosis (Mtb). The SAR shows the central thiazole moiety and the 2-pyridyl moiety at C-4 of the thiazole are intolerant to modification. However, the N-2 position of the aminothiazole exhibits high flexibility and we successfully improved the antitubercular activity of the initial hit by more than 128-fold through introduction of substituted benzoyl groups at this position. N-(3-Chlorobenzoyl)-4-(2-pyridinyl) -1,3-thiazol-2-amine (55) emerged as one of the most promising analogues with a MIC of 0.024 μM or 0.008 μg/mL in 7H9 media and therapeutic index of nearly ～300. However, 55 is rapidly metabolized by human liver microsomes (t1/2 = 28 min) with metabolism occurring at the invariant aminothiazole moiety and Mtb develops spontaneous low-level resistance with a frequency of ～10-5.
Meissner, Anja,Boshoff, Helena I.,Vasan, Mahalakshmi,Duckworth, Benjamin P.,Barry III, Clifton E.,Aldrich, Courtney C.
p. 6385 - 6397
(2013/10/22)

Environmentally benign one-pot synthesis of cyanamides from dithiocarbamates using I2 and H2O2
An environmentally benign reaction is devised for the synthesis of cyanamides from dithiocarbamate salts using iodine and H2O 2. Taylor & Francis Group, LLC.
Jamir, Latonglila,Sinha, Upasana Bora,Nath, Jayashree,Patel, Bhisma K.
experimental part
p. 951 - 958
(2012/02/01)

4-Pyridylanilinothiazoles that selectively target von Hippel - Lindau deficient renal cell carcinoma cells by inducing autophagic cell death
Renal cell carcinomas (RCC) are refractory to standard therapy with advanced RCC having a poor prognosis; consequently treatment of advanced RCC represents an unmet clinical need. The von Hippel-Lindau (VHL) tumor suppressor gene is mutated or inactivated in a majority of RCCs. We recently identified a 4-pyridyl-2-anilinothiazole (PAT) with selective cytotoxicity against VHL-deficient renal cells mediated by induction of autophagy and increased acidification of autolysosomes. We report exploration of structure-activity relationships (SAR) around this PAT lead. Analogues with substituents on each of the three rings, and various linkers between rings, were synthesized and tested in vitro using paired RCC4 cell lines. A contour map describing the relative spatial contributions of different chemical features to potency illustrates a region, adjacent to the pyridyl ring, with potential for further development. Examples probing this domain validated this approach and may provide the opportunity to develop this novel chemotype as a targeted approach to the treatment of RCC. 2009 American Chemical Society.
Hay, Michael P.,Turcotte, Sandra,Flanagan, Jack U.,Bonnet, Muriel,Chan, Denise A.,Sutphin, Patrick D.,Nguyen, Phuong,Giaccia, Amato J.,Denny, William A.
supporting information; experimental part
p. 787 - 797
(2010/07/05)

Novel selective thiazoleacetic acids as CRTH2 antagonists developed from in silico derived hits. Part 1
Structure-activity relationships of three related series of 4-phenylthiazol-5-ylacetic acids, derived from two hits emanating from a focused library obtained by in silico screening, have been explored as CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells) antagonists. Several compounds with double digit nanomolar binding affinity and full antagonistic efficacy for human CRTH2 receptor were obtained in all subclasses. The most potent compound was [2-(4-chloro-benzyl)-4-(4-phenoxy-phenyl)-thiazol-5-yl]acetic acid having an binding affinity of 3.7 nM and functional antagonistic effect of 66 nM in a BRET and 12 nM in a cAMP assay with no functional activity for the other PGD2 DP receptor (27 μM in cAMP).
Rist, ystein,Grimstrup, Marie,Receveur, Jean-Marie,Frimurer, Thomas M.,Ulven, Trond,Kostenis, Evi,Hoegberg, Thomas
scheme or table
p. 1177 - 1180
(2010/06/15)

HETEROARYL COMPOUNDS, COMPOSITIONS, AND METHODS OF USE IN CANCER TREATMENT
Provided herein are novel heteroaryl compounds, compositions comprising the compounds, and methods of treatment or prevention comprising administration of the compounds. The compounds are effective in the targeting of cells defective in the von Hippel-Lindau gene and in inducing autophagic cell death. The methods are directed to treating or preventing diseases such as cancer, and in particular cancers resulting from von Hippel-Lindau disease. The compounds of the invention may be administered in combination with another therapeutic agent.
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Page/Page column 149

(2009/10/22)

THIAZOLES DERIVATIVES AS AMPK ACTIVATOR
The present application provides novel thiazole derivatives that are useful as activators of Adenosine 5'-Monophosphate-Activated Protein Kinase and pharmaceutical compositions containing such compounds.
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Page/Page column 29-30

(2008/06/13)

Synthesis of 7-chloro-5-trifluoromethyl/7-fluoro/7-trifluoromethyl-4H-1,4-benzothiazines as antimicrobial agents
7-Chloro-5-trifluoromethyl/7-fluoro/7-trifluoromethyl-4H-1,4-benzothiazines have been synthesized by 2-amino-5-fluoro/5-trifluoromethyl/5-chloro-3-trifluoromethyl benzenethiols condensed with β-diketone/β-ketoesters in the presence of DMSO involving oxidative cyclization. Pharmacological activities have also been included.
Rathore, Bhawani Singh,Kumar
p. 5678 - 5682
(2007/10/03)

NOVEL GLUCAGON ANTAGONISTS/INVERSE AGONISTS
Novel compounds that act to antagonize the action of the glucagon peptide hormone on the glucagon receptor. More particularly, it relates to glucagon antagonists or inverse agonists.
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Page/Page column 150

(2008/06/13)

Substituted N-phenylisothioureas: Potent inhibitors of human nitric oxide synthase with neuronal isoform selectivity
S-Ethyl N-phenylisothiourea (4) has been found to be a potent inhibitor of both the human constitutive and inducible isoforms of nitric oxide synthase. A series of substituted N-phenylisothiourea analogues was synthesized to investigate the structure-activity relationship of this class of inhibitor. Each analogue was evaluated for human isoform selectivity. One analogue, S-ethyl N-[4-(trifluoromethyl)phenyl]isothiourea (39), exhibited 115-fold and 29-fold selectivity for the neuronal isoform versus the inducible and endothelial derived constitutive isoforms, respectively. Studies have shown the substituted N-phenylisothiourea 39 binds competitively with L,-arginine.
Shearer, Barry G.,Lee, Shuliang,Oplinger, Jeffrey A.,Frick, Lloyd W.,Garvey, Edward P.,Furfine, Eric S.
p. 1901 - 1905
(2007/10/03)

Improved Procedures for the Preparation of Cycloalkyl-, Arylalkyl-, and Arylthioureas
An improved procedure for the preparation of arylthioureas consists of the reaction of benzoyl isothiocyanate with anilines in acetone and debenzoylation of the resultant N-aryl-N'-benzoylthioureas with 5percent aqueous sodium hydroxide.Bicycloalkylthioureas and N-(arylalkyl)thioureas (e.g. 9H-9-fluorenylthiourea) are directly prepared from the corresponding isothiocyanates and ammonia.
Rasmussen, C. R.,Villani, F. J.,Weaner, L. E.,Reynolds, B. E.,Hood, A. R.,et al.
p. 456 - 459
(2007/10/02)