- An efficient one-pot synthesis of 2-aminobenzothiazoles from substituted anilines using benzyltrimethylammonium dichloroiodate and ammonium thiocyanate in DMSO:H2O
-
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.
-
supporting information
(2021/10/04)
-
- Visible-light photoredox catalytic approach for the direct synthesis of 2-aminobenzothiazoles from anilines
-
A novel, highly efficient and convenient approach for the visible-light-promoted direct synthesis of 2-aminobenzothiazoles from anilines and ammonium thiocyanate is presented. The reaction involves addition/cyclization cascade of SCN radical and anilines under photoredox catalysis with Ru(bpy)3Cl2. The salient features of the protocol include the utilization of atmospheric oxygen and visible light as clean, inexpensive and sustainable resources at room temperature.
- Dhar S. Yadav, Lal,Krishna Pal Singh, Rana,Singh, Manjula
-
-
- Benzo[4,5]thiazolo[3,2-c][1,3,5,2]oxadiazaborinines: Synthesis, Structural, and Photophysical Properties
-
A family of highly emissive benzo[4,5]thiazolo[3,2-c][1,3,5,2]oxadiazaborinines, conjugated with the donor 4-dimethylaminophenyl group, was designed and synthesized. Their photophysical, both in solution and in the solid state, and structural properties were investigated. The influence of donor and acceptor substituents (R) in the benzothiazole unit on photophysical properties of complexes was found out. The tetrafluorobenzothiazole analogue exhibits nonbonded nuclear spin-spin coupling between fluorines from the BF2 group and α-fluorine atom at the benzene ring. Additionally, this boron complex demonstrates a comparatively high solid-state fluorescence quantum yield (φ = 0.34).
- Potopnyk, Mykhaylo A.,Volyniuk, Dmytro,Ceborska, Magdalena,Cmoch, Piotr,Hladka, Iryna,Danyliv, Yan,Gra?ulevi?ius, Juozas Vidas
-
p. 12129 - 12142
(2018/09/25)
-
- Synthesis and molecular docking of new roflumilast analogues as preferential-selective potent PDE-4B inhibitors with improved pharmacokinetic profile
-
In the present work, we designed and synthesized new roflumilast analogues with preferential-selective PDE-4B inhibition activity and improved pharmacokinetic properties. The unsubstituted benzo[d]thiazol-2-yl and -6-yl benzamide derivatives (4a and 6a) showed both good potency and preferential selectivity for PDE-4B. More remarkably, 6c revealed 6 times preferential PDE-4B/4D selectivity with a significant increase of in vitro cAMP and good % inhibition of TNF-α concentration. In addition, the in vitro pharmacokinetics of 6c showed good metabolic stability with in vitro CLint (5.67 mL/min/kg) and moderate % plasma protein binding (53.71%). This was reflected onto increased in vivo exposure with a half-life greater than roflumilast by 3 folds (21 h) and a Cmax value of 113.958 ng/mL. Molecular docking attributed its good activity to its key binding interactions in PDE-4B active site with additional hydrogen bonding with amino acids lining the metal pocket. Summing up, 6c can be considered as suitable candidate for further investigation for the treatment of COPD.
- Moussa, Bahia A.,El-Zaher, Asmaa A.,El-Ashrey, Mohamed K.,Fouad, Marwa A.
-
p. 477 - 486
(2018/02/28)
-
- Copper-Catalyzed Aerobic Oxidative Regioselective Thiocyanation of Aromatics and Heteroaromatics
-
A copper-catalyzed aerobic oxidative reaction between aromatics or heteroaromatics with KSCN is developed by using O2 as the oxidant. The combination of Cu(OTf)2, N,N,N′,N′-tetramethylethylenediamine (TMEDA) and BF3·Et2O provides an efficient catalytic system, affording substituted thiocyanation products and 2-aminobenzothiazoles in excellent yields. The reaction also possesses a good functional group tolerance for both strong electron-withdrawing and electron-donating groups.
- Jiang, Huanfeng,Yu, Wentao,Tang, Xiaodong,Li, Jianxiao,Wu, Wanqing
-
p. 9312 - 9320
(2017/09/22)
-
- IMIDAZO[2,1-B]THIAZOLE AND 5,6-DIHYDROIMIDAZO[2,1-B]THIAZOLE DERIVATIVES USEFUL AS S100-INHIBITORS
-
A compound of formula (I) or a pharmaceutically acceptable salt thereof. The compound is useful for use in the treatment of cancer, an inflammatory disorder,an autoimmunity disorder or a neurodegenerative disorder.
- -
-
Page/Page column 78; 79
(2016/04/09)
-
- 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)
-
- PHENYLIMIDE-CONTAINING BENZOTHIAZOLE DERIVATIVE OF ITS SALT AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
-
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.
- -
-
Paragraph 0168; 0190
(2015/02/18)
-
- Chrysin-benzothiazole conjugates as antioxidant and anticancer agents
-
7-(4-Bromobutoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one, obtained from chrysin with 1,4-dibromobutane, was combined with a wide range of 6-substituted 2-aminobenzthiazoles, which had been prepared from the corresponding anilines with potassium thiocyanate. Free radical scavenging efficacies of newer analogues were measured using DPPH and ABTS assays, in addition to the assessment of their anticancer activity against cervical cancer cell lines (HeLa and CaSki) and ovarian cancer cell line (SK-OV-3) implementing the SRB assay. Cytotoxicity of titled compounds was checked using Madin-Darby canine kidney (MDCK) non-cancer cell line. Overall, 6a-r indicated remarkable antioxidant power as DPPH and ABTS+ scavengers; particularly the presence of halogen(s) (6g, 6h, 6j-6l) was favourable with IC50 values comparable to the control ascorbic acid. Unsubstituted benzothiazole ring favored the activity of resultant compounds (6a and 6r) against HeLa cell line, whereas presence of chlorine (6g) or a di-fluoro group (6k) was a key to exert strong action against CaSki. Moreover, a mono-fluoro (6j) and a ketonic functionality (6o) were beneficial to display anticipated anticancer effects against ovarian cancer cell line SK-OV-3. The structural assignments of the new products were done on the basis of IR, 1H NMR, 13C NMR spectroscopy and elemental analysis.
- Mistry, Bhupendra M.,Patel, Rahul V.,Keum, Young-Soo,Kim, Doo Hwan
-
supporting information
p. 5561 - 5565
(2015/11/17)
-
- PHENYLIMIDE-CONTAINING BENZOTHIAZOLE DERIVATIVE OR ITS SALT AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
-
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.
- -
-
Paragraph 247; 248
(2013/04/10)
-
- A novel system for the synthesis of 2-aminobenzthiazoles using sodium dichloroiodate
-
2-Aminobenzthiazole is a privileged scaffold with a range of biological activities. However, to date, an efficient protocol for the synthesis of this ring system using aniline as a starting material has been lacking. Herein, for the first time, we describe a highly efficient and mild protocol for the synthesis of 2-aminiobenzthiazole using NaICl Georg Thieme Verlag Stuttgart ? New York.
- Telvekar, Vikas N.,Bachhav, Harshal M.,Bairwa, Vinod Kumar
-
p. 2219 - 2222
(2012/10/30)
-
- Pyrrolopyrrole cyanines: Effect of substituents on optical properties
-
To tune their optical properties, a large variety of pyrrolopyrrole cyanines (PPCys) were synthesized with substitutedheteroaromatics such as quinoline, benzothiazole, and oxazole derivatives as terminal groups. Thus, a broad range of stable, highly fluorescing near-infrared (NIR) dyes with high absorptivities between 690 to 845 nm is accessible. The large number of newly synthesized compounds allows a detailed discussion of the correlation between molecular structure and the optical properties of the first electronic transition. Syntheses and optical properties of pyrrolopyrrole cyanines (PPCys) with different substituents at the terminal heteroaromatic moieties are described. The relationship between molecular structure and optical properties is discussed. By suitable substitution, the absorption and fluorescence maxima of the chromophore can be tuned in a range between 690 and 845 nm. Copyright
- Fischer, Georg M.,Klein, Matthias K.,Daltrozzo, Ewald,Zumbusch, Andreas
-
scheme or table
p. 3421 - 3429
(2011/09/12)
-
- 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)
-
- Riluzole series. synthesis and in vivo 'antiglutamate' activity of 6- substituted-2-benzothiazolamines and 3-substituted-2-imino-benzothiazolines
-
Two series of analogues of riluzole, a blocker of excitatory amino acid mediated neurotransmission, have been synthesized: monosubstituted 2- benzothiazolamines and 3-substituted derivatives. Of all the compounds prepared in the first series, only 2-benzothiazolamines bearing alkyl, polyfluoroalkyl, or polyfluoroalkoxy substituents in the 6-position showed potent anticonvulsant activity against administration of glutamic acid in rats. The most active compounds displaying in vivo 'antiglutamate' activity were the 6-OCF3 (riluzole), 6-OCF2CF3, 6-CF3, and 6-CF2CF3 substituted derivatives with ED50 values between 2.5 and 3.2 mg/kg i.p. Among the second series of variously substituted benzothiazolines, compounds as active as riluzole or up to 3 times more potent were identified in two series: benzothiazolines bearing a β-dialkylaminoethyl moiety and compounds with an alkylthioalkyl chain and their corresponding sulfoxides and sulfones. The most potent derivatives were 2-imino-3-(2-methylthio)- and 2-imino-3-(2- methylsulfinyl)-ethyl-6-trifluoromethoxybenzothiazolines (61 and 64, ED50 = 1.0 and 1.1 mg/kg i.p., respectively). In addition, intraperitoneal administration of some of the best benzothiazolines protected mice from mortality produced by hypobaric hypoxia.
- Jimonet, Patrick,Audiau, Fran?ois,Barreau, Michel,Blanchard, Jean-Charles,Boireau, Alain,Bour, Yvette,Coléno, Marie-Annick,Doble, Adam,Doerflinger, Gilles,Do Huu, Claudine,Donat, Marie-Hélène,Duchesne, Jean Marie,Ganil, Pierre,Guérémy, Claude,Honoré, Eliane,Just, Bernard,Kerphirique, Roselyne,Gontier, Sylvie,Hubert, Philippe,Laduron, Pierre M.,Blevec, Joseph Le,Meunier, Mireille,Miquet, Jean-Marie,Nemecek, Conception,Pasquet, Martine,Piot, Odile,Pratt, Jeremy,Rataud, Jean,Reibaud, Michel,Stutzmann, Jean-Marie,Mignani, Serge
-
p. 2828 - 2843
(2007/10/03)
-
- Substituted 2-benzothiazolamines as sodium flux inhibitors: Quantitative structure-activity relationships and anticonvulsant activity
-
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
-
p. 1425 - 1432
(2007/10/02)
-
- Substituted 2-aminobenzothiazoles and derivatives useful as cerebrovascular agents
-
A series of substituted 2-aminobenzothiazoles and derivatives useful for treating cerebrovascular disorders are disclosed. Also disclosed is a new method for treating such disorders.
- -
-
-