30162-37-9Relevant academic research and scientific papers
Synergism of fused bicyclic 2-aminothiazolyl compounds with polymyxin B against: Klebsiella pneumoniae
Wang, Rong,Hou, Shuang,Dong, Xiaojing,Chen, Daijie,Shao, Lei,Qian, Liujia,Li, Zhong,Xu, Xiaoyong
supporting information, p. 2060 - 2066 (2017/11/22)
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).
Design, synthesis and biological evaluation of novel HSP70 inhibitors: N, N′-disubstituted thiourea derivatives
Zeng, Yan-Qun,Cao, Rui-Yuan,Yang, Jian-Ling,Li, Xing-Zhou,Li, Song,Zhong, Wu
, p. 83 - 95 (2016/05/24)
As novel heat shock protein 70 (HSP70) inhibitors, N, N′-disubstituted thiourea derivatives were designed and synthesized based on the X-ray structure of the ATPase domain (nucleotide binding domain, NBD). An ATPase activity inhibition assay revealed that these compounds effectively inhibited HSP70 ATPase activity. The results revealed that the compounds 370/371/374/379/380//392/394/397/404/405 and 407 can inhibit the HSP70 ATPase turnover with high percentages of inhibition: 50.42, 38.46, 50.45, 44.12, 47.13, 50.50, 40.95, 65.36, 46.23, 35.78, and 58.37 in 200 μM, respectively. Significant synergies with lapatinib were observed for compound 379 and compound 405 in the BT474 breast cancer cell line. A structure-function analysis revealed that most of the thiourea derivatives exhibited cooperative action with lapatinib in the BT474 cancer cell line and the BT/LapR1.0 lapatinib-resistant cell line. HSP70 inhibitors may be developed as synergetic drugs in drug-resistant cancer therapy.
NOVEL ANTIPRION COMPOUNDS
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Paragraph 0648; 0649; 0703, (2013/03/28)
Described herein are novel compositions and methods of treatment addressing diseases such as neurodegenerative diseases, including prion diseases and Alzheimer's disease.
New imidazoline/α2-adrenoceptors affecting compounds-4(5)-(2-aminoethyl)imidazoline (dihydrohistamine) derivatives. Synthesis and receptor affinity studies
Treder, Adam P.,Andruszkiewicz, Ryszard,Zgoda, W?odzimierz,Walkowiak, Aleksandra,Ford, Celeste,Hudson, Alan L.
scheme or table, p. 156 - 167 (2011/03/18)
Compilation of agmatine structure and imidazoline moiety leads to a new group of imidazoline/α2-adrenoceptor ligands, 4(5)-(2-aminoethyl)imidazoline derivatives. In this study the exploration of previously unknown 4(5)-(2-aminoethyl)imidazolines including the analogues of reported imidazoline and α2-aderenoceptors ligands: clonidine, rilmenidine, idazoxan, efaroxan, antazoline, tracizoline is described. The synthesis of a variety of novel 4(5)-(2-aminoethyl)imidazolines and their I 1, I2, α2-adrenoceptors affinities are reported.
2-aminothiazoles as therapeutic leads for prion diseases
Gallardo-Godoy, Alejandra,Gever, Joel,Fife, Kimberly L.,Silber, B. Michael,Prusiner, Stanley B.,Renslo, Adam R.
experimental part, p. 1010 - 1021 (2011/04/25)
2-Aminothiazoles are a new class of small molecules with antiprion activity in prion-infected neuroblastoma cell lines (J. Virol. 2010, 84, 3408). We report here structure-activity studies undertaken to improve the potency and physiochemical properties of 2-aminothiazoles, with a particular emphasis on achieving and sustaining high drug concentrations in the brain. The results of this effort include the generation of informative structure-activity relationships (SAR) and the identification of lead compounds that are orally absorbed and achieve high brain concentrations in animals. The new aminothiazole analogue (5-methylpyridin-2-yl)-[4-(3-phenylisoxazol-5-yl)-thiazol-2-yl]-amine (27), for example, exhibited an EC50 of 0.94 μM in prion-infected neuroblastoma cells (ScN2a-cl3) and reached a concentration of ～25 μM in the brains of mice following three days of oral administration in a rodent liquid diet. The studies described herein suggest 2-aminothiazoles as promising new leads in the search for effective therapeutics for prion diseases.
Synthesis and anticonvulsant activity of some substituted 1,2,4-thiadiazoles
Gupta, Arun,Mishra, Pradeep,Pandeya,Kashaw, Sushil K.,Kashaw, Varsha,Stables, James P.
experimental part, p. 1100 - 1105 (2009/08/10)
A series of new substituted 1,2,4-thiadiazoles were synthesized by appropriate route and screened for anticonvulsant, neurotoxic and sedative-hypnotic activity. The structures of the synthesized compounds were confirmed by IR spectroscopy, 13C NMR and elemental (nitrogen and sulphur) analysis. After i.p. injection of the compounds to mice or rate at doses of 30, 100, and 300 mg/kg, body weights were examined in the maximal electroshock-induced seizures (MES) and subcutaneous pentylenetetrazole (scPTZ)-induced seizure models after 0.5 and 4 h. Rotorod method and phenobarbitone-induced hypnosis potentiation study were employed to examine neurotoxicity and sedative-hypnotic activity, respectively. All the compounds except 4g showed protection against MES screen after 0.5 h. Compounds 3a-c, 4a-c were active at 100 mg/kg dose i.p., whereas remaining compounds showed activity at 300 mg/kg. All 14 compounds except 3 g showed neurotoxicity at 100 and 300 mg/kg after 0.5 h. Compounds 3b and 4b showed NT after 4 h. Two compounds 3b and 4g showed significant (p 0.05) percentage increase in sleeping time i.e. 67% and 59%, respectively. It may be concluded that the synthesized compounds were potent against MES-induced seizures than ScPTZ induced and showed low potency as sedative-hypnotic agent which is advantageous.
Synthesis and anticonvulsant activity of some novel 3-aryl amino/amino-4-aryl-5-imino-Δ2-1,2,4-thiadiazoline
Gupta, Arun,Mishra, Pradeep,Kashaw, Sushil K.,Jatav, Varsha,Stables
, p. 749 - 754 (2008/09/20)
A series of 3-aryl amino/amino-4-aryl-5-imino-Δ2-1,2,4-thiadiazoline have been synthesized using an appropriate synthetic route and characterized by elemental analyses and spectral data. The anticonvulsant activity of all the synthesized compounds was evaluated against maximal electroshock induced seizures (MES) and subcutaneous pentylenetetrazole (ScPTZ) induced seizure models in mice. The neurotoxicity was assessed using the rotorod method. All the test compounds were administered at doses of 30, 100, and 300 mg/kg body weight and the anticonvulsant activity was noted at 0.5 and 4 h time intervals after the drug administration. Some of the compounds were evaluated for the Phenobarbitone induced hypnosis potentiation test. Among the compounds tested, all except 2h showed protection from MES seizures, whereas only 3b was found to be active in the ScPTZ test.
Discovery and SAR of 2-amino-5-(thioaryl)thiazoles as potent and selective Itk inhibitors
Das, Jagabandhu,Furch, Joseph A.,Liu, Chunjian,Moquin, Robert V.,Lin, James,Spergel, Steven H.,McIntyre, Kim W.,Shuster, David J.,O'Day, Kathleen D.,Penhallow, Becky,Hung, Chen-Yi,Doweyko, Arthur M.,Kamath, Amrita,Zhang, Hongjian,Marathe, Punit,Kanner, Steven B.,Lin, Tai-An,Dodd, John H.,Barrish, Joel C.,Wityak, John
, p. 3706 - 3712 (2007/10/03)
A series of structurally novel aminothiazole based small molecule inhibitors of Itk were prepared to elucidate their structure-activity relationships (SARs), selectivity, and cell activity in inhibiting IL-2 secretion in a Jurkat T-cell assay. Compound 3 is identified as a potent and selective Itk inhibitor which inhibits anti-TCR antibody induced IL-2 production in mice in vivo and was previously reported to reduce lung inflammation in a mouse model of ovalbumin induced allergy/asthma.
A new orally bioavailable dual adenosine A2B/A3 receptor antagonist with therapeutic potential
Press, Neil J.,Taylor, Roger J.,Fullerton, Joseph D.,Tranter, Pamela,McCarthy, Clive,Keller, Thomas H.,Brown, Lyndon,Cheung, Robert,Christie, Julie,Haberthuer, Sandra,Hatto, Julia D.I.,Keenan, Mark,Mercer, Mark K.,Press, Nicola E.,Sahri, Helene,Tuffnell, Andrew R.,Tweed, Morris,Fozard, John R.
, p. 3081 - 3085 (2007/10/03)
The synthesis and SAR of 5-heterocycle-substituted aminothiazole adenosine receptor antagonists is described. Several compounds show high affinity and selectivity for the A2B and A3 receptors. One compound (5f) shows good ADME properties in the rat and as such may be an important new compound in testing the current hypotheses proposing a therapeutic role for a dual A2B/A3 antagonist in allergic diseases.
Pyrimidinone antibiotics - Heterocyclic analogues with improved antibacterial spectrum
Brands, Michael,Grande, Yolanda Cancho,Endermann, Rainer,Gahlmann, Reinhold,Krueger, Jochen,Raddatz, Siegfried
, p. 2641 - 2645 (2007/10/03)
We report the synthesis and pharmacological evaluation of new derivatives of the natural dipeptide antibiotic TAN 1057 A,B containing heterocycles either in the β-amino acid side chain or as mimics of the urea function. In the course of this program, we identified novel analogues that display activity towards a broader panel of Gram-positive bacteriae.
