- Pyrrolopyrrole aza-BODIPY near-infrared photosensitizer for dual-mode imaging-guided photothermal cancer therapy
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A NIR photosensitizer pyrrolopyrrole aza-BODIPY (PPAB) was synthesized in a straightforward manner. Through the use of PPAB NPs as a photothermal agent, photoacoustic imaging (PAI) and NIR fluorescence imaging (NIR-FI) can be achieved in vivo. In addition, the photothermal ablation of tumor cells can be realized both in vitro and in vivo, even at a low concentration (0.5 mg kg?1).
- Wu, Chaolong,Huang, Xiaoyu,Tang, Yunyun,Xiao, Wanyue,Sun, Liguo,Shao, Jinjun,Dong, Xiaochen
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Read Online
- Iodine-catalyzed amination of benzothiazoles with KSeCN in water to access primary 2-aminobenzothiazoles
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A facile and sustainable approach for the amination of benzothiazoles with KSeCN using iodine as the catalyst in water has been disclosed under transition-metal free conditions. The reaction proceeded smoothly to afford various primary 2-amino benzothiazoles in up to 96% yield. A series of control experiments were performed, suggesting a ring-opening mechanism was involved via a radical process. This protocol provides efficient synthesis of primary 2-aminobenzothiazoles
- Zhu, Yu-Shen,Shi, Linlin,Fu, Lianrong,Chen, Xiran,Zhu, Xinju,Hao, Xin-Qi,Song, Mao-Ping
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supporting information
p. 1497 - 1500
(2021/09/09)
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- An efficient one-pot synthesis of 2-aminobenzothiazoles from substituted anilines using benzyltrimethylammonium dichloroiodate and ammonium thiocyanate in DMSO:H2O
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Treatment of a variety of substituted anilines with benzyltrimethylammonium dichloroiodate (1.2 equiv) and ammonium thiocyanate (1.0 equiv) in DMSO:H2O (9:1) at 70 °C gave the corresponding 2-aminobenzothiazoles in excellent isolated yields (75–97%; ave. yield for all substrates = 90%). The reaction worked well for 2(4)-mono-, 2,4-di-, or 3,4,5-tri-substituted anilines, and a wide range of both electron donating groups (MeO, HO, CF3O, Me) and electron withdrawing groups (NO2, CN, CO2Et, CO2H, Cl, F) were well tolerated. This method provides a useful alternative to other methods that are either less efficient (requiring 3–7 fold equivalents of reagents) or utilize highly toxic and corrosive liquid Br2 as the oxidizing agent.
- Dass, Reuben,Peterson, Matt A.
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supporting information
(2021/10/04)
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- Benzo imidazo [2, 1-b] thiazole compound and application thereof (by machine translation)
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The invention discloses a benzoimidazo [2, 1-b] thiazole compound and application thereof, and belongs to the technical field of medicines. The inhibitory activity of the synthesized benzimidazo [2, 1-b] thiazole analogues on FLTT3 is more than 90%, wherein the compounds (compounds 2 , 4, 6, 8 and 10) are IC of FLTT3-ITD kinase. 50 Lower value, in particular compound 2, IC IC50 The value is only 5.60 nm, and therefore the compound of the present invention may be used as an inhibitor FLTT3, or for preparing a drug capable of modulating or suppressing diseases associated with abnormal cell proliferation by affecting the enzymatic activity of one or more tyrosine kinases and interfering with aberrant cell proliferation, having a wide application prospect. (by machine translation)
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Paragraph 0060-0062
(2020/07/15)
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- Benzothiazolyl ureas are low micromolar and uncompetitive inhibitors of 17Β-HSD10 with implications to Alzheimer’s disease treatment
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Human 17β-hydroxysteroid dehydrogenase type 10 is a multifunctional protein involved in many enzymatic and structural processes within mitochondria. This enzyme was suggested to be involved in several neurological diseases, e.g., mental retardation, Parkinson’s disease, or Alzheimer’s disease, in which it was shown to interact with the amyloid-beta peptide. We prepared approximately 60 new compounds based on a benzothiazolyl scaffold and evaluated their inhibitory ability and mechanism of action. The most potent inhibitors contained 3-chloro and 4-hydroxy substitution on the phenyl ring moiety, a small substituent at position 6 on the benzothiazole moiety, and the two moieties were connected via a urea linker (4at, 4bb, and 4bg). These compounds exhibited IC50 values of 1–2 μM and showed an uncompetitive mechanism of action with respect to the substrate, acetoacetyl-CoA. These uncompetitive benzothiazolyl inhibitors of 17β-hydroxysteroid dehydrogenase type 10 are promising compounds for potential drugs for neurodegenerative diseases that warrant further research and development.
- Aitken, Laura,Benek, Ondrej,Chribek, Matej,Dolezal, Rafael,Gunn-Moore, Frank,Hrabinova, Martina,Hroch, Lukas,Jun, Daniel,Kralova, Vendula,Kuca, Kamil,Lycka, Antonin,Musilek, Kamil,Prchal, Lukas,Schmidt, Monika,Vinklarova, Lucie,Zemanova, Lucie
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- Enhancement of Benzothiazoles as Pteridine Reductase-1 Inhibitors for the Treatment of Trypanosomatidic Infections
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2-Amino-benzo[d]thiazole was identified as a new scaffold for the development of improved pteridine reductase-1 (PTR1) inhibitors and anti-trypanosomatidic agents. Molecular docking and crystallography guided the design and synthesis of 42 new benzothiazoles. The compounds were assessed for Trypanosoma brucei and Leishmania major PTR1 inhibition and in vitro activity against T. brucei and amastigote Leishmania infantum. We identified several 2-amino-benzo[d]thiazoles with improved enzymatic activity (TbPTR1 IC50 = 0.35 μM; LmPTR1 IC50 = 1.9 μM) and low μM antiparasitic activity against T. brucei. The ten most active compounds against TbPTR1 were able to potentiate the antiparasitic activity of methotrexate when evaluated in combination against T. brucei, with a potentiating index between 1.2 and 2.7. The compound library was profiled for early ADME toxicity, and 2-amino-N-benzylbenzo[d]thiazole-6-carboxamide (4c) was finally identified as a novel potent, safe, and selective anti-trypanocydal agent (EC50 = 7.0 μM). Formulation of 4c with hydroxypropyl-β-cyclodextrin yielded good oral bioavailability, encouraging progression to in vivo studies.
- Linciano, Pasquale,Pozzi, Cecilia,Iacono, Lucia Dello,Di Pisa, Flavio,Landi, Giacomo,Bonucci, Alessio,Gul, Sheraz,Kuzikov, Maria,Ellinger, Bernhard,Witt, Gesa,Santarem, Nuno,Baptista, Catarina,Franco, Caio,Moraes, Carolina B.,Müller, Wolfgang,Wittig, Ulrike,Luciani, Rosaria,Sesenna, Antony,Quotadamo, Antonio,Ferrari, Stefania,P?hner, Ina,Cordeiro-Da-Silva, Anabela,Mangani, Stefano,Costantino, Luca,Costi, Maria Paola
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p. 3989 - 4012
(2019/05/06)
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- Benzothiazole compound with anti-tumor activity and preparation method and application of compound
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The invention discloses a benzothiazole compound with the anti-tumor activity and a preparation method and application of the compound and belongs to the technical field of anti-tumor medicine synthesis. The benzothiazole compound is characterized in that
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Paragraph 0022-0028
(2019/09/05)
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- Design, synthesis, and apoptosis-promoting effect evaluation of novel pyrazole with benzo[d]thiazole derivatives containing aminoguanidine units
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New pyrazole with benzo[d]thiazoles containing hydrazinecarboximidamide substituent was synthesised and evaluated for cytotoxicity and apoptotic activity using the MTT assay, flow cytometry, and Western blot analysis. Among the compounds studied, (E)-2-((1-(6-((4-fluorobenzyl)oxy)benzo[d]thiazol-2-yl)-3-phenyl-1H- pyrazol-4-yl)methylene) hydrazinecarboximidamide (8l) was potent, with IC50 values of 2.41 μM, 2.23 μM, 3.75 μM and 2.31 μM in vitro anti-proliferative activity testing against triple-negative breast cancer cell line MDA-MB-231, non-triple-negative breast cancer MCF-7 cells, and human hepatocarcinoma HepG2 cells, and SMMC-7721 cells, respectively. Especially, the activity against MDA-MB-231 was similar to that of Doxorubicin, which was used as a positive control in this study. Next, the Annexin V/PI flow cytometry assay was used at different concentrations of compound 8l to demonstrate that compound 81 induced apoptosis of MDA-MB-231 cells in a concentration-dependent manner. Finally, these results were further verified by Western blot analysis. Taken together, the results of this study revealed that compound 8l may be a potential anticancer compound play a significant role in the subsequent researches.
- Liu, Da Chuan,Gao, Mei Jia,Huo, Qiang,Ma, Tao,Wang, Ying,Wu, Cheng Zhu
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p. 829 - 837
(2019/04/03)
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- Enhancing Antiproliferative Activity and Selectivity of a FLT-3 Inhibitor by Proteolysis Targeting Chimera Conversion
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The receptor tyrosine kinase FLT-3 is frequently mutated in acute myeloid leukemia; however, current small molecule inhibitors suffer from limited efficacy in the clinic. Conversion of a FLT-3 inhibitor (quizartinib) into a proteolysis targeting chimera (
- Burslem, George M.,Song, Jayoung,Chen, Xin,Hines, John,Crews, Craig M.
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supporting information
p. 16428 - 16432
(2018/12/11)
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- Synthesis, spectroscopic characterization, and computational studies of 2-cyano-6-hydroxybenzothiazole: A key synthetic intermediate of firefly luciferin
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Firefly luciferin is widely applied as a biotechnological tool for visualizing various biological processes in vitro and in vivo. Chemically, 2-cyano-6-hydroxybenzothiazole, as a key synthetic intermediate of firefly luciferin, is obtained from 2-cyano-6-methoxybenzothiazole by changing the methoxy with a hydroxy group. However, this approach is costly and not suited for large-scale synthesis. Here we report cost-effective and efficient syntheses of 2-cyano-6-hydroxybenzothiazole through the catalytic Sandmeyer-type cyanation reaction. Our approach employs diazonium tetrafluoroborate salt of 2-amino-6-hydroxybenzothiazole as a cyanation substrate. The cyanation reaction proceeds efficiently under mild conditions by using Cu(I)/Cu(II)/N,N,N',N'-tetramethylethylenediamine as a catalyst. In addition, computational studies of the 2-cyano-6-hydroxybenzothiazole structure were performed based on the density functional theory method. The theoretical parameters of the optimized geometry were derived from the B3LYP/6-311 ++ G(d, p) method. Time-dependent density functional theory was applied to assign the electronic absorption bands observed experimentally and the1 H NMR chemical shifts were computed using the GIAO method. There was a significant relationship between computational studies and experimental results.
- Shahmoradi, Ghasem,Amani, Saeid
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p. 1499 - 1517
(2019/01/03)
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- TYROSINE KINASE INHIBITOR AND PHARMACEUTICAL COMPOSITION COMPRISING SAME
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The present invention relates to a tyrosine kinase inhibitor and a pharmaceutical composition comprising same. The tyrosine kinase inhibitor of the present invention has the structures as shown in the following formula (I) or (II):
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Paragraph 0352; 0353
(2018/03/25)
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- Synthesis and biological evaluation of 2-(3,4-dimethoxyphenyl)-6-(2-[18F]fluoroethoxy)benzothiazole ([18F]FEDBT) for PET imaging of breast cancer
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Given the ever-present demand for improved PET radiotracer in oncology imaging, we have synthesized 2-(3,4-dimethoxyphenyl)-6-(2-[18F]fluoroethoxy)benzothiazole ([18F]FEDBT), a fluorine-18-containing fluoroethylated benzothiazole to explore its utility as a PET imaging tracer. [18F]FEDBT was prepared via kryptofix-mediated nucleophilic substitution of the tosyl group precursor. Fractionated ethanol-based solid-phase (SPE cartridge-based) purification afforded [18F]FEDBT in 60% radiochemical yield (EOB), with radiochemical purity in excess of 98% and the specific activity was 35?GBq/μmol. The radiotracer displayed clearly higher cellular uptake ratio in various breast cancer cell lines MCF7, MDA-MB-468 and MDA-MB-231. However, both biodistribution and microPET studies have showed an higher abdominal accumulation of [18F]FEDMBT and the tumor/muscle ratio of 1.8 was observed in the MDA-MB-231 xenograft tumors mice model. Further the lipophilic improvement is needed for the reducement of hepatobilliary accumulation and to promote the tumor uptake for PET imaging of breast cancer.
- Li, Geng-Ying,Vaulina, Daria D.,Li, Jia-Je,Fedorova, Olga S.,Wang, Hsin-Ell,Liu, Ren-Shyan,Krasikova, Raisa N.,Chen, Chuan-Lin
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supporting information
p. 3460 - 3463
(2017/07/07)
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- HEMOGLOBIN MODIFIER COMPOUNDS AND USES THEREOF
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Described herein are compounds, including pharmaceutically acceptable salts thereof, methods of making such compounds, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat, prevent or diagnose blood-based diseases, disorders or conditions.
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Paragraph 00456
(2018/02/28)
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- INFRARED SENSOR, NEAR-INFRARED ABSORBING COMPOSITION, CURED FILM, NEAR-INFRARED ABSORBING FILTER, IMAGE SENSOR, CAMERA MODULE, AND COMPOUND
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Provided are an infrared sensor, a near-infrared absorbing composition, a cured film, a near-infrared absorbing filter, an image sensor, a camera module, and a compound. An infrared sensor 100 which has an infrared transmitting filter 113 and a near-infra
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Paragraph 0477; 0478; 0479
(2017/01/31)
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- Optimization and biological evaluation of 2-aminobenzothiazole derivatives as Aurora B kinase inhibitors
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A strong relationship between abnormal functions of Aurora kinases and tumorigenesis has been reported for decades. Consequently, Aurora kinases serve as potential targets for anticancer agents. Here, we identified aminobenzothiazole derivatives as novel inhibitors of Aurora B kinase through bioisosteric replacement of the previous inhibitors, aminobenzoxazole derivatives. Most of the urea-linked aminobenzothiazole derivatives showed potent and selective inhibitory activity against Aurora B kinase over Aurora A kinase. Molecular modeling indicated that compound 15g bound well to the active site of Aurora B kinase and formed the essential hydrogen bonds. The potent compounds, 15g and 15k, were selected, and their biological effects were evaluated using HeLa cell lines. It was found that these compounds inhibited the phosphorylation of histone H3 at Ser10 and induced G2/M cell cycle arrest. We suggest that the reported compounds have the potential to be further developed as anticancer therapeutics.
- Lee, Eun,An, Ying,Kwon, Junhee,Kim, Keun Il,Jeon, Raok
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p. 3614 - 3622
(2017/06/13)
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- Probing the ATP-Binding Pocket of Protein Kinase DYRK1A with Benzothiazole Fragment Molecules
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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
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p. 9814 - 9824
(2016/11/19)
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- Design and synthesis of new potent anticancer benzothiazole amides and ureas featuring pyridylamide moiety and possessing dual B-RafV600E and C-Raf kinase inhibitory activities
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A new series of benzothiazole amide and urea derivatives tethered with the privileged pyridylamide moiety by ether linkage at the 6-position of benzothiazole (22 final compounds) has been designed and synthesized as potent anticancer sorafenib analogs. A selected group of twelve derivatives was appraised for its antiproliferative activity over a panel of 60 human cancer cell lines at a single dose concentration of 10 1/4M at National Cancer Institute (NCI, USA). Compounds 4b, 5a, 5b and 5d exhibited promising growth inhibitions and thus were further tested in advanced 5-dose testing assay to determine their GI50 values. The cellular based assay results revealed that 3,5-bis-trifluoromethylphenyl (5b) urea member is the best derivative with superior potency and efficacy compared to sorafenib as well as notable extended spectrum activity covering 57 human cancer cell lines. Kinase screening of compound 5b showed its kinase inhibitory effect against both B-RafV600E and C-Raf. Moreover, the most potent derivatives in cells were investigated for their RAF inhibitory activities, and the results were rationalized with the molecular docking study. Profiling of CYP450 and hERG channel inhibitory effects for the active compounds revealed their low possibilities to exhibit undesirable drug-drug interactions and cardiac side effects.
- El-Damasy, Ashraf Kareem,Lee, Ju-Hyeon,Seo, Seon Hee,Cho, Nam-Chul,Pae, Ae Nim,Keum, Gyochang
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p. 201 - 216
(2016/04/05)
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- Synthesis and biological evaluation of novel benzothiazole derivatives as potential anticonvulsant agents
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New benztriazoles with a mercapto-triazole and other heterocycle substituents were synthesized and evaluated for their anticonvulsant activity and neurotoxicity by using the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ), and rotarod neurotoxicity (TOX) tests. Among the compounds studied, compound 2-((1H-1,2,4-triazol-3-yl)thio)-N-(6-((3-fluorobenzyl) oxy)benzo[d]thiazol-2-yl)acetamide (5i) and 2-((1H-1,2,4-triazol-3-yl)thio)-N-(6-((4-fluorobenzyl)oxy) benzo[d] thiazol-2-yl)acetmide (5j) were the most potent, with an ED50 value of 50.8 mg/kg and 54.8 mg/kg in the MES test and 76.0 mg/kg and 52.8 mg/kg in the scPTZ seizures test, respectively. They also showed lower neurotoxicity and, therefore a higher protective index. In particular, compound 5j showed high protective index (PI) values of 8.96 in the MES test and 9.30 in the scPTZ test, which were better than those of the standard drugs used as positive controls in this study.
- Liu, Da-Chuan,Zhang, Hong-Jian,Jin, Chun-Mei,Quan, Zhe-Shan
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- Synthesis and biological evaluation of novel benzothiazole derivatives as potential anticonvulsant agents
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New benztriazoles with a mercapto-triazole and other heterocycle substituents were synthesized and evaluated for their anticonvulsant activity and neurotoxicity by using the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ), and rotarod neurotoxicity (TOX) tests. Among the compounds studied, compound 2-((1H-1,2,4-triazol-3-yl)thio)-N-(6-((3-fluorobenzyl) oxy)benzo[d]thiazol-2-yl)acetamide (5i) and 2-((1H-1,2,4-triazol-3-yl)thio)-N-(6-((4-fluorobenzyl)oxy) benzo[d] thiazol-2-yl)acetmide (5j) were the most potent, with an ED50 value of 50.8 mg/kg and 54.8 mg/kg in the MES test and 76.0 mg/kg and 52.8 mg/kg in the scPTZ seizures test, respectively. They also showed lower neurotoxicity and, therefore a higher protective index. In particular, compound 5j showed high protective index (PI) values of 8.96 in the MES test and 9.30 in the scPTZ test, which were better than those of the standard drugs used as positive controls in this study.
- Liu, Da-Chuan,Zhang, Hong-Jian,Jin, Chun-Mei,Quan, Zhe-Shan
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- Rational molecular design towards Vis/NIR absorption and fluorescence by using pyrrolopyrrole aza-BODIPY and its highly conjugated structures for organic photovoltaics
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Pyrrolopyrrole aza-BODIPY (PPAB) developed in our recent study from diketopyrrolopyrrole by titanium tetrachloride-mediated Schiff-base formation reaction with heteroaromatic amines is a highly potential chromophore due to its intense absorption and fluor
- Shimizu, Soji,Iino, Taku,Saeki, Akinori,Seki, Shu,Kobayashi, Nagao
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supporting information
p. 2893 - 2904
(2015/02/05)
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- PHENYLIMIDE-CONTAINING BENZOTHIAZOLE DERIVATIVE OF ITS SALT AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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Provided is a phenylimide-containing benzothiazole derivative or its pharmaceutically acceptable salt, a process for the preparation thereof, and a pharmaceutical composition comprising the same. The phenylimide-containing benzothiazole derivative or its pharmaceutically acceptable salt can selectively inhibit the protein-protein interaction between KRS and a laminin receptor (LR), thereby inhibiting migration of cancer cells. Therefore, the phenylimide-containing benzothiazole derivative or its pharmaceutically acceptable salt may be usefully applied for preventing or treating the diseases associated with cancer cell metastasis.
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Paragraph 0608
(2015/02/18)
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- Synthesis and anticonvulsant activity evaluation of 7-alkoxy[1,2,4] triazolo[3,4-b]benzothiazol-3(2H)-ones
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A new series of 7-alkoxy[1,2,4]triazolo[3,4-b]benzothiazol-3(2H)-ones were synthesized and evaluated for their anticonvulsant activities. Among these compounds, 7-propoxy[1,2,4]triazolo[3,4-b]benzothiazol-3(2H)-one (4c) and 7-butoxy[1,2,4]triazolo[3,4-b]benzothiazol-3(2H)-one (4d) showed the highest activity against maximal electroshock (MES)-induced tonic extension [effective dose (ED)50: 11.4 and 13.6 mg/kg, respectively]. It is worth mentioning that compound 4d showed especially low neurotoxicity, which led to a high protective index (PI >51). The orally anticonvulsant activity data of compound 4d further confirmed its efficacy, in an MES test, and its high safety with a PI value of 50.2. In addition, the potency of compound 4h against seizures induced by pentylenetetrazole, 3-mercaptopropionic acid, and bicuculline in the chemical-induced seizure tests suggested that compound 4d may exert its anticonvulsant activity through affecting the GABAergic system.
- Liu, Da-Chuan,Deng, Xian-Qing,Wang, Shi-Ben,Quan, Zhe-Shan
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p. 268 - 275
(2014/04/17)
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- Design, synthesis and anticonvulsant evaluation of N-(benzo[d]thiazol-2- ylcarbamoyl)-2-methyl-4-oxoquinazoline-3(4H)-carbothioamide derivatives: A hybrid pharmacophore approach
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Novel N-(benzo[d]thiazol-2-ylcarbamoyl)-2-methyl-4-oxoquinazoline-3(4H)- carbothioamide derivatives were synthesized and evaluation of their anticonvulsant effects was done using various models of experimental epilepsy. Initial anticonvulsant activities of the compounds were investigated using intraperitoneal (i.p.) maximal electroshock shock (MES), subcutaneous pentylenetetrazole (scPTZ) seizure models in mice. The quantitative assessment after oral administration in rats showed that the most active was 2-methyl-4-oxo-N-(6-(trifluoromethoxy)benzo[d]thiazol-2-ylcarbamoyl) quinazoline-3(4H)-carbothioamide (SA 24) with ED50 values of 82.5 μmol/kg (MES) and 510.5 μmol/kg (scPTZ). This molecule was more potent than phenytoin and ethosuximide which were used as reference antiepileptic drugs. To explain the possible mechanism for anticonvulsant action, some of the selected active compounds were subjected to GABA (γ-amino butyric acid) assay and AMPA ((S)-2-amino-3-(3-hydroxyl-5-methyl-4-isoxazolyl) propionic acid) induced seizure test.
- Malik, Sachin,Bahare, Radhe Shyam,Khan, Suroor Ahmad
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supporting information
p. 1 - 13
(2013/10/01)
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- PHENYLIMIDE-CONTAINING BENZOTHIAZOLE DERIVATIVE OR ITS SALT AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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The present invention provides a phenylimide-containing benzothiazole derivative or its pharmaceutically acceptable salt, a process for the preparation thereof, and a pharmaceutical composition comprising the same. The phenylimide-containing benzothiazole derivative or its pharmaceutically acceptable salt can selectively inhibit the protein-protein interaction between KRS and a laminin receptor (LR), thereby inhibiting migration of cancer cells. Therefore, the phenylimide-containing benzothiazole derivative or its pharmaceutically acceptable salt may be usefully applied for preventing or treating the diseases associated with cancer cell metastasis.
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Paragraph 1082; 1083
(2013/04/10)
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- QSAR modeling of synthesized 3-(1,3-benzothiazol-2-yl) 2-phenyl quinazolin-4(3H)-ones as potent antibacterial agents
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Present communication elicits the designing and synthesis of 3-(1,3-benzothiazol-2-yl) 2-phenyl quinazolin-4(3H)-ones as potential antibacterial agents. A number of substituted 2-amino benzothiazoles, 2-amino-5-[(E)-phenyl diazenyl] benzoic acid, and 2-phenyl-4H benzo[d] [1,3] oxazin-4-one were synthesized as the precursor substrates. The compounds were synthesized in excellent yields and the structures were corroborated on the basis of IR, 1H NMR, Mass, and elemental analysis data. These compounds were screened in vitro for their antibacterial activity against a representative panel of Gram positive and Gram negative bacteria and models were generated through quantitative structure-activity relationship (QSAR).The activity contributions due to structural and substituent effects were determined using sequential regression procedure. The antimicrobial assay data show that the synthesized compounds are found to manifest profound antimicrobial activity. Springer Science+Business Media, LLC 2011.
- Sharma, Pratibha,Kumar, Ashok,Kumari, Prerna,Singh, Jitendra,Kaushik
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p. 1136 - 1148
(2012/08/28)
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- 18F-labeled phenyldiazenyl benzothiazole for in vivo imaging of neurofibrillary tangles in Alzheimer's disease brains
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We synthesized and evaluated (E)-4-((6-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy) benzo[d]thiazol-2-yl)diazenyl)-N,N-dimethylaniline (FPPDB) as a probe for the imaging of neurofibrillary tangles (NFTs) in patients with Alzheimer's disease (AD). In assays using thioflavin S (ThS) as a competitive ligand, FPPDB competed with ThS well and showed high affinity for both tau and Aβ1-42 aggregates (Ki = 13.0 and 20.0 nM, respectively). The results of saturation binding assays also verified that FPPDB bound to both tau and Aβ1-42 aggregates with high affinity (Kd = 44.8 nM and Bmax = 45.8 pmol/nmol protein for tau aggregates and K d = 45.4 nM and Bmax = 38.9 pmol/nmol protein for Aβ1-42 aggregates). Furthermore, [18F]FPPDB substantially labeled NFTs and senile plaques in AD brain sections but not control brain sections. In biodistribution experiments using normal mice, [ 18F]FPPDB displayed higher uptake (4.28% ID/g at 2 min postinjection) into and washout (2.53% ID/g at 60 min postinjection) from the brain with time. On the basis of the chemical structure of FPPDB, further increases in selective binding to tau aggregates may lead to the development of more useful probes for the imaging of NFTs in AD brains.
- Matsumura, Kenji,Ono, Masahiro,Kimura, Hiroyuki,Ueda, Masashi,Nakamoto, Yuji,Togashi, Kaori,Okamoto, Yoko,Ihara, Masafumi,Takahashi, Ryosuke,Saji, Hideo
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supporting information; experimental part
p. 58 - 62
(2012/04/10)
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- PROCESS FOR THE PREPARATION OF IMIDAZO[2,1-B][1,3]BENZOTHIAZOLE DERIVATIVES
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Provided herein are process for the preparation of N-(5-ferf-butyl-isoxazol-3-yl)- N'-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,l-fe][l,3]benzothiazol-2-yl]phenyl}urea, or a pharmaceutically acceptable salt, solvate, hydrate, or polymorph thereof. N-(5-tert- Butyl-isoxazol-3-yl)-N'-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,l-and][l,3]benzo- thiazol-2-yl]phenyl}urea is useful for treating, preventing, and/or managing diseases or conditions, including but not limited to, proliferative diseases, FLT-3 mediated diseases, and cancers. N-(5-ferf-Butyl-isoxazol-3-yl)-N'-{4-[7-(2-morpholin-4-yl- ethoxy)imidazo[2,l-and][l,3]benzothiazol-2-yl]phenyl}urea is represented by the structure:
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Page/Page column 69-71
(2011/06/11)
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- IMIDAZOLOTHIAZOLE COMPOUNDS AS MODULATORS OF PROTEIN KINASE
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Compounds, compositions and methods are provided for modulating the activity of receptor kinases and for the treatment, prevention, or amelioration of one or more symptoms of disease or disorder mediated by receptor kinases.
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Page/Page column 73-75
(2010/06/11)
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- HETEROCYCLIC COMPOUND AND USE THEREOF
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Disclosed is a heterocyclic compound having a strong Raf inhibitory activity. Specifically disclosed is a compound represented by the formula (I), (II) or (III) below, or a salt thereof. (In the formulae, the symbols are as defined in the description.)
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Page/Page column 66
(2010/06/11)
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- SOLID FORMS COMPRISING N-(5-TERT-BUTYL-ISOXAZOL-3-YL)-N'-{4-[7-(2-MORPHOLIN-4-YL-ETHOXY)IMIDAZO[2,1-B][1,3]BENZOTHIAZOL-2-YL]PHENYL}UREA, COMPOSITIONS THEREOF, AND USES THEREWITH
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Solid forms comprising N-(5-tert-butyl-isoxazol-3-yl)-N'-{4-[7-(2-morpholin- 4-yl-ethoxy)imidazo[2,l-b][l,3]benzothiazol-2-yl]phenyl}urea, compositions comprising the solid forms, methods of making the solid forms and methods of their use for the treatmen
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Page/Page column 84
(2009/04/25)
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- Novel Benzimidazole and Benzothiazole Derivatives, Method for Preparing Same, Use Thereof as Drugs, Pharmaceutical Compositions and Novel Use Especially as c-MET Inhibitors
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This invention relates to benzimidazole and benzothiazole compounds of formula (I) to methods of preparing such compounds, pharmaceutical compositions comprising such compounds, and to methods of treatment comprising administering of such compounds.
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Page/Page column 20
(2008/12/07)
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- Imidazolothiazole compounds for the treatment of disease
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Compounds, compositions and methods are provided for modulating the activity of receptor kinases and for the treatment, prevention, or amelioration of one or more symptoms of disease or disorder mediated by receptor kinases.
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Page/Page column 39
(2008/06/13)
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- Novel Benzothiazoles And The Use Thereof As Medicaments
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The invention especially relates to novel chemical compounds, especially novel benzothiazole derivatives, to compositions containing said compounds, and to the use thereof as medicaments.
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Page/Page column 7
(2008/06/13)
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- Inhibitors of histone deacetylase
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The invention relates to the inhibition of histone deacetylase. The invention provides compounds and methods for inhibiting histone deacetylase enzymatic activity. The invention also provides compositions and methods for treating cell proliferative diseases and conditions.
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- Inhibitors of histone deacetylase
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The invention relates to the inhibition of histone deacetylase. The invention provides compounds and methods for inhibiting histone deacetylase enzymatic activity. The invention also provides compositions and methods for treating cell proliferative diseases and conditions.
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- INHIBITORS OF HISTONE DEACETYLASE
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The invention relates to the inhibition of histone deacetylase. The invention provides compounds and methods for inhibiting histone deacetylase enzymatic activity. The invention also provides compositions and methods for treating cell proliferative diseases and conditions.
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Page/Page column 152
(2010/02/11)
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- Inhibitors of histone deacetylase
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The invention relates to the inhibition of histone deacetylase. The invention provides compounds and methods for inhibiting histone deacetylase enzymatic activity. The invention also provides compositions and methods for treating cell proliferative diseases and conditions.
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- Substituted 2-benzothiazolamines as sodium flux inhibitors: Quantitative structure-activity relationships and anticonvulsant activity
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Thirty-two aryl-substituted 2-benzothiazolamines have been tested for their ability to modulate sodium flux in rat cortical slices. A QSAR analysis, applied to these derivatives, showed a trend toward increasing potency as sodium flux inhibitors with increasing lipophilicity, decreasing size, and increasing electron withdrawal of the benzo ring substitutents. Additionally, 4- or 5-substitution of the benzo ring was found to decrease potency. The combination of increased lipophilicity, small size, and electron withdrawal severely limited which groups were tolerated on the benzo ring, thus suggesting that the optimal substitution patterns have been prepared within this series. Nine of these compounds were potent inhibitors of veratridine-induced sodium flux (NaFl). These nine compounds also proved to be anticonvulsant in the maximal electroshock (MES) assay. Fourteen additional 2-benzothiazolamines demonstrated activity in the MES screen, yet exhibited no activity in the NaFl assay. These derivatives may be interacting at the sodium channel in a manner not discernible by the flux paradigm, or they may be acting by an alternative mechanism in vivo.
- Hays,Rice,Ortwine,Johnson,Schwarz,Boyd,Copeland,Vartanian,Boxer
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p. 1425 - 1432
(2007/10/02)
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- Nucleophilic Aromatic Substitution: Transmission of Substituent Effects in Alkaline Hydrolysis of 4-Aminophenylazobenzothiazolium Dyes
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Alkaline fading of 2'-, 5-, and 6-substitued 2(4'-aminophenyl)azobenzothiazolium dyes (I) possesses a second-order rate constant (kOH).The value of kOH is shown to predicted by equation (i) where ?N is log kOH = 0.76?n + 0.24?s + 1.69 ?+ + log-0.15(pK-9.5)/(1 + 100.25(pK-9.5)> + 0.74 (i) ?+ for 6- and ? for 5-substituents, ?s is ?- for 5- and ? for 6-substituents, ?+ is for 2'-substituents, and the pK is that of the leaving 4'-amine.The dye fading is not very sensitive to substituents in the benzothiazole phenyl ring but the charge is transmitted more effectively through nitrogen than through sulphur.
- D'Rozario, Augustine P.,Williams, Andrew,Parton, Brian
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p. 1781 - 1784
(2007/10/02)
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