cas 1747-60-0, 2-Amino-6-methoxybenzothiazole

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Pharmacological profile of 6,12-dihydro-3-methoxy-1-benzopyrano[3,4-b] [1,4]benzothiazin-6-one, a novel human estrogen receptor agonist
Pharmacological studies were carried out to characterize further the endocrinological profile and the binding mode to the estrogen receptor (ER) of 6,12-dihydro-3-methoxy-l-benzopyrano[3,4-b][1,4]benzothiazin-6-one (1). Binding experiments were conducted with highly purified recombinant human estrogen receptors hERα and β. Potent estrogenic activity of compound 1 was assessed by testing its ability to down-regulate ERs and to enhance estrogen receptor element (ERE)-dependent transcription. The latest step of our work dealt with the synthesis of the 9-fluorinated derivative 15 for ionic microscopy experiments to determine the intracellular localization of compound 1. Although 1 failed to compete with [3H]E2 for binding to both ER isoforms, evidence was reported that it interacted with hERα in MCF-7 cells (ER down-regulation/ERE-dependent luciferase induction). Hence, an appropriate conformation of the hormone binding domain, most probably conferred by co-regulators of ER, is required for the onset of an activity of the compound 1. Estrogenic activity was weak but on the order of magnitude of that of coumestrol (slightly weaker). The synthesis of the 9-methoxylated derivative 16 and its pharmacological evaluation led us to propose a binding mode of 1 on hERα. Compound 1 appears to interact with ERα mainly through interactions of its 3-methoxy substituent with the residue His-524 of the hormone binding domain.
Jacquot, Yves,Cleeren, Anny,Laios, Ioanna,Ma, Yan,Boulahdour, Athem,Bermont, Laurent,Refouvelet, Bernard,Adessi, Gerard,Leclercq, Guy,Xicluna, Alain
p. 335 - 341
(2002)
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Rubin et al.
(1974)
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Design, synthesis, and AChE inhibitory activity of new benzothiazole–piperazines
In the current study, 14 new benzothiazole–piperazine compounds were designed to meet the structural requirements of acetylcholine esterase (AChE) inhibitors. The target compounds were synthesised in three steps. Structures of the newly synthesised compounds (7–20) were confirmed using IR,1H NMR,13C NMR, and HRMS methods. The inhibitory potential of the compounds on AChE (E.C.3.1.1.7, from electric eel) was then investigated. Among the compounds, 19 and 20 showed very good activity on AChE enzyme. Kinetics studies were performed to observe the effects of the most active compounds on the substrate–enzyme relationship. Cytotoxicity studies, genotoxicity studies, and theoretical calculation of pharmacokinetics properties were also carried out. The compounds 19 and 20 were found to be nontoxic in both of the toxicity assays. A good pharmacokinetics profile was predicted for the synthesised compounds. Molecular docking studies were performed for the most active compounds, 19 and 20, and interaction modes with enzyme active sites were determined. Docking studies indicated a strong interaction between the active sites of AChE enzyme and the analysed compounds.
Demir ?zkay, ümide,Can, ?zgür Devrim,Sa?l?k, Begüm Nurpelin,Acar ?evik, Ulviye,Levent, Serkan,?zkay, Yusuf,Ilg?n, Sinem,Atl?, ?zlem
p. 5387 - 5394
(2016)
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Synthesis, characterization and computational studies of 2-cyano-6-methoxybenzothiazole as a firefly-luciferin precursor
A novel approach to the synthesis of 2-cyano-6-methoxybenzothiazole via the Cu-catalyzed cyanation of 2-iodo-6-methoxybenzothiazole was developed. K4[Fe(CN)6] was used as a source of cyanide, and a Cu/N,N,N′,N′-tetramethylethylenediamine (TMEDA) system was utilized as a catalyst. This approach is scalable and can be practiced with operational benign. The most stable conformation of 2-cyano-6-methoxybenzothiazole was delineated using the density functional theory (DFT)/B3LYP method with 6-311++G(d, p) basis set.
Shahmoradi, Ghasem,Amani, Saeid
p. 255 - 258
(2018)
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Stuckwisch
p. 3417
(1949)
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New Benzo[d]thiazol-2-yl-aminoacetamides as Potential Anticonvulsants: Synthesis, Activity and Prediction of Molecular Properties
A series of N-(substituted-2-oxo-4-phenylazetidin-1-yl)-2-((6-substitutedbenzo[d]thiazol-2-yl)amino)-acetamide derivatives were synthesized using pharmacophoric features with aromatic hydrophobic aryl ring (A), NH-C=O as hydrogen bonding domain, the nitrogen atom as electron donor (D), and phenyl as distal aryl ring (C). The synthesized molecules were initially screened for anticonvulsant activity using the maximal electroshock seizure (MES) test and the subcutaneous pentylenetetrazole test in albino mice. An acute neurotoxicity study on the synthesized molecules was also carried out using the rotarod test. The results of these tests revealed that two compounds, 5b and 5q, showed promising activity with ED50 values of 15.4 and 18.6 mg/kg and protective indices of 20.7 and 34.9 in the MES test, respectively, which are found to be approximately fourfold higher than those of the standard drugs phenytoin (6.9) and carbamazepine (8.1). These molecules may act as lead of the designed scheme. The pharmacokinetic profiles of all the synthesized compounds were estimated using Molinspiration software. None of the compounds violated Lipinski's "rule of five". The possible structure-activity relationship was discussed. In conclusion, this manuscript shows that the developed model has a highly prognostic power for the further investigation of better benzothiazole derivatives for future discovery and development.
Ali, Ruhi,Siddiqui, Nadeem
p. 254 - 265
(2015)
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Anticonvulsant and neurotoxicity evaluation of some 6-substituted benzothiazolyl-2-thiosemicarbazones
Various 6-substituted benzothiazolyl-2-thiosemicarbazones were synthesized and screened for anticonvulsant activity in maximal electroshock induced seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. The neurotoxicity was assessed using the rotorod method. The 6-methyl benzothiazolyl-2-thiosemicarbazones showed anticonvulsant activity in both mice i.p. and rat oral MES screen. The 6-nitro benzothiazolyl thiosemicarbazone derivative 1a emerged as the most promising one with anti-MES activity in mice i.p., rat i.p. and rat p.o. evaluations. All the compounds exhibited lesser or no neurotoxicity compared to phenytoin. The isatinimino derivatives had shown better activity when compared to the benzylidene or acetophenone derivatives.
Yogeeswari,Sriram,Mehta,Nigam,Kumar, M. Mohan,Murugesan,Stables
p. 1 - 5
(2005)
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Condensation of 2-Amino-1,3-thiazole Salts and Benzo Analogs with Trifluoroacetylacetone
Abstract: The condensation of 2-amino-1,3-thiazolium perchlorates and their benzo analogs with trifluoro-acetyl-acetone in acetic acid afforded the corresponding [1,3]thiazolo[3,2-a]pyrimidinium, pyrimido[2,1-b][1,3]benzothiazolium, and naphtho[2′,1′:4,5][1,3]thiazolo[3,2-a]pyrimidinium salts as a single isomer in which the trifluoromethyl group is located in the γ-position with respect to the bridgehead nitrogen atom. The structure of the synthesized compounds was confirmed by 1H NMR spectra and elemental analyses.
Shulga,Simurova,Shulga
p. 364 - 368
(2021/04/13)

Discovery of Potent Carbonic Anhydrase Inhibitors as Effective Anticonvulsant Agents: Drug Design, Synthesis, and in Vitro and in Vivo Investigations
Two sets of benzenesulfonamide-based effective human carbonic anhydrase (hCA) inhibitors have been developed using the tail approach. The inhibitory action of these novel molecules was examined against four isoforms: HCA I, hCA II, hCA VII, and hCA XII. Most of the molecules disclosed low to medium nanomolar range inhibition against all tested isoforms. Some of the synthesized derivatives selectively inhibited the epilepsy-involved isoforms hCA II and hCA VII, showing low nanomolar affinity. The anticonvulsant activity of selected sulfonamides was assessed using the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (sc-PTZ) in vivo models of epilepsy. These potent CA inhibitors effectively inhibited seizures in both epilepsy models. The most effective compounds showed long duration of action and abolished MES-induced seizures up to 6 h after drug administration. These sulfonamides were found to be orally active anticonvulsants, being nontoxic in neuronal cell lines and in animal models.
Mishra, Chandra Bhushan,Kumari, Shikha,Angeli, Andrea,Bua, Silvia,Mongre, Raj Kumar,Tiwari, Manisha,Supuran, Claudiu T.
p. 3100 - 3114
(2021/04/12)

Iodine-catalyzed amination of benzothiazoles with KSeCN in water to access primary 2-aminobenzothiazoles
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
Chen, Xiran,Fu, Lianrong,Hao, Xin-Qi,Shi, Linlin,Song, Mao-Ping,Zhu, Xinju,Zhu, Yu-Shen
supporting information

(2021/09/09)

CT-DNA/HSA binding interactions and cytotoxicity activity of a new copper(II) complex
We designed and synthesized a novel copper (II) complex, [Cu(ambt)2(cnbz)2], using 2-amino-6-methoxybenzothiazole (ambt) and 2-chloro-5-nitrobenzoic acid (cnbz) as ligands. Single-crystal X-ray diffraction (XRD), IR (infrared) spectra along with elemental analysis were employed to characterize its structure. Single-crystal XRD analysis illustrated the copper (II) complex belonged to the triclinic crystal system, space group P-1 and formed mononuclear hexa-coordinated structure. Electronic absorption, fluorescence spectrum and viscosity analysis were employed to assess the binding properties of the complex with CT-DNA (calf thymus DNA), as well as HSA (human serum albumin). The calculated binding constants Ka were 5.89 × 104 M?1 and 3.31 × 106 M?1 for CT-DNA and HSA, respectively, implying that complex [Cu(ambt)2(cnbz)2] displays intercalative bindings with CT-DNA and HSA. It also statically quenched CT-DNA/HSA fluorescence. CCK-8 assay revealed that compared to cisplatin, the complex exerts greater anti-proliferative influence against HepG2, HeLa and A549 cell lines. Flow cytometry revealed that [Cu(ambt)2(cnbz)2] arrested the cycle of HepG2 cells at G0/G1 phase, inducing apoptosis / necrosis. The degree of apoptosis / necrosis and inhibition of cell cycle is dose-, as well as time-dependent.
Cai, Jie-Hui,Huang, Qiu-Chan,Huang, Qiu-Ping,Qin, Li-Jin,Wei, You-Huan,Zeng, Zhen-Fang,Zheng, Guang-Jin
(2021/09/20)

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)

Design, synthesis and antimicrobial study of novel 1-(1,3-benzothiazol-2-yl)-3-chloro-4H-spiro[azetidine-2,3'-indole]-2',4(1'H)-diones through ketene–imine cycloaddition reaction
The present study deals with the synthesis of novel 1-(1,3-benzothiazol-2-yl)-3-chloro-4H-spiro[azetidine-2,3'-indole]-2',4(1'H)-dione derivatives from the reaction of 3-(1,3-benzothiazol-2-ylimino)-1,3-dihydro-2H-indol-2-one derivatives with chloroacetyl chloride in the presence of triethyl-amine (TEA). The mechanism involved simple acid or base catalysed reaction through the formation of Schiff base followed by cyclisation via ketene–imine cycloaddition reaction. All synthesized compounds were characterized by FT-IR,1H-NMR,13C-NMR, and elemental analysis. The antimicrobial activities of the synthesized derivatives 5a-5g were examined via Micro Broth Dilution method against bacterial strains Bacillius subtilis, Staphylcoccus aureus, E. coli, P. aeruginosa, and fungal strain Candida albicans for determining MIC values. Ampicillin, chloramphenicol, and griseofulvin were used as standard drugs. The MIC values for antimicrobial activity of synthesized compounds were examined using Micro Broth Dilution method. Compounds 5a, 5b, and 5c were found effective against E. coli (MTCC 442) and P.aeruginosa (MTCC 441) and all compounds showed moderate to excellent activity against Streptococcus aureus (MTCC 96) and Bacillius subtilis (MTCC 441). Regarding the antifungal screening, compounds 5a, 5b, and 5c exhibited excellent activity against Candida albicans MTCC 227. 1-(1,3-benzothiazol-2-yl)-3-chloro-4H-spiro[azetidine-2,3'-indole]-2',4(1'H)-dione derivatives may be used as potential lead molecules as effective antimicrobial agents.
Agarwal, Dinesh Kr.,Agarwal, Shikha,Gandhi, Divyani,Prajapat, Prakash,Sethiya, Ayushi
p. 141 - 148
(2020/02/04)

Identification of: N -benzothiazolyl-2-benzenesulfonamides as novel ABCA1 expression upregulators
ATP binding cassette transporter A1 (ABCA1) is a critical transporter that mediates cellular cholesterol efflux from macrophages to apolipoprotein A-I (ApoA-I). Therefore, increasing the expression level of ABCA1 is anti-atherogenic and ABCA1 expression upregulators have become novel choices for atherosclerosis treatment. In this study, a series of N-benzothiazolyl-2-benzenesulfonamides, based on the structure of WY06 discovered in our laboratory, were designed and synthesized as novel ABCA1 expression upregulators. Based on an in vitro ABCA1 upregulatory cell model, ABCA1 upregulation of target compounds was evaluated. Compounds 6c, 6d, and 6i have good upregulated ABCA1 expression activities, with EC50 values of 0.97, 0.37, and 0.41 ΜM, respectively. A preliminary structure-activity relationship is summarized. Replacing the methoxy group on the benzothiazole moiety of WY06 with a fluorine or chlorine atom and exchanging the ester group with a cyano group resulted in more potent ABCA1 upregulating activity. Moreover, compound 6i increased ABCA1 mRNA and protein expression and significantly promoted cholesterol efflux in RAW264.7 cells. In conclusion, N-benzothiazolyl-2-benzenesulfonamides were identified as novel ABCA1 expression upregulators.
Cao, Feng,Gao, Xinfeng,Jiang, Xinhai,Li, Wenyan,Liu, Hongtao,Tian, Wenhua,Wang, Ruizhi,Wei, Liping,Xu, Chen,Xu, Yanni
p. 411 - 418
(2020/04/15)

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
(2020/02/13)

A Novel Difluoroacetic Acid Derivatives Compound, and Composition Comprising the Same
The present invention relates to a novel difluoroacetic acid derivative compound and a composition for various uses containing the same, wherein the difluoroacetic acid derivative compound can not only act as an agonist activating one among PPARandalpha;, andbeta; or andgamma;, but also can exhibit double efficacy or triple efficacy. Therefore, the difluoroacetic acid derivative compound can more effectively prevent, alleviate or treat metabolic diseases in which PPARs involves, and further exhibits whitening and wrinkle alleviation activity, and anti-inflammatory and antioxidant effects, thereby being able to be usefully utilized as various compositions.COPYRIGHT KIPO 2020
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Paragraph 0086-0091; 0094; 0095

(2020/04/23)

Visible-light-initiated malic acid-promoted cascade coupling/cyclization of aromatic amines and KSCN to 2-aminobenzothiazoles without photocatalyst
By using ambient air as the oxidant and malic acid as the promoter, a practical method for the preparation of 2-aminobenzothiazoles through visible-light-initiated cascade reaction of aromatic amines and KSCN in eco-friendly bis(methoxypropy)ether under metal-, hazardous additive-, photocatalyst-free conditions was established.
He, Wei-Bao,Gao, Lan-Qing,Chen, Xin-Jie,Wu, Zhi-Lin,Huang, Ying,Cao, Zhong,Xu, Xin-Hua,He, Wei-Min
supporting information
p. 1895 - 1898
(2020/02/27)

Design, synthesis, characterization and biological evaluation of 6- methoxy-2-aminobenzothioate derivatives against certain bacterial strains
The current work reports the synthesized and biological evaluation of 6-methoxy-2-amino benzothiazole (A1), which was prepared via reaction p-Ansidine with ammonium thiocyanate followed by the oxidative ring closure of the resultant thiourea with a catalytic amount of bromine, in the alkaline medium. The resulting compound(A1) underwent condensation reactions with various kinds of aldehydes to produce Hydrazones (A3ad). 6-methoxy2-hydrazinobenzothiazole (A2) was prepared through the reaction of the compound (A1) with 99.9 % hydrazine hydrate in the presence of concentrated HCl and ethylene glycol solution. After that, the compound (A2) was reacted with ethyl acetoacetate in alcohol to yield corresponding pyrazole-6- methoxybenzothiazole (A4). Moreover, the compound (A2) was reacted with 4- substituted aromatic aldehydes in absolute ethanol to create Hydrazones (A5a-d). Synthesized compounds were investigated as anti-bacterial activity against five microorganisms: (Gram-positive: Bacillus subtilis & Staphylococcus aurea). (Gramnegative: Pseudomonas aeruginous Escherichia coli and Enterobacter)
Juber, Ahmood K.,Hamed, Ahmed Solaiman,Khalil, Ahmed Moussa
p. 4131 - 4139
(2020/11/18)

Synthesis, Type II diabetes inhibitory activity, antimicrobial evaluation and docking studies of indeno[1,2-c]pyrazol-4(1H)-ones
We report a convenient and efficient synthesis of indeno[1,2-c]pyrazol-4(1H)-ones (4a?o) by the reaction of a variety of 2-acyl-(1H)-indene-1,3(2H)-diones (1) and 2-hydrazinylbenzo[d]thiazole/2-hydrazinyl-6-substitutedbenzo[d]thiazoles (2) in the presence of glacial acetic acid in good yields. The structure of the compounds thus prepared were confirmed by analytical and spectral (FT-IR, 1H NMR, 13C NMR, and HRMS) techniques. All the synthesized indeno[1,2-c]pyrazol-4(1H)-ones (4a?o) were assayed for their in vitro Type II diabetes inhibitory activity by using Acarbose as standard drug and in vitro antimicrobial activity utilizing Streptomycin and Fluconazole as reference drugs. Among the synthesized derivatives, 4e (IC50 = 6.71 μg/mL) was found to be more potent against α-glucosidase enzyme as compared with the standard Acarbose (IC50 = 9.35 μg/mL) and 4i (IC50 = 11.90 μg/mL) exhibited good inhibitory activity against α-amylase enzyme as compared with the standard Acarbose (IC50 = 22.87 μg/mL). Also, all the titled compounds showed good antimicrobial activity. In addition, in vitro α-glucosidase and α-amylase inhibition were supported by docking studies performed on the derivatives 4e and 4o, respectively. [Figure not available: see fulltext.].
Mor, Satbir,Sindhu, Suchita
p. 46 - 62
(2019/11/13)

Discovery of novel pyrimidine-based benzothiazole derivatives as potent cyclin-dependent kinase 2 inhibitors with anticancer activity
To develop novel CDK2 inhibitors as anticancer agents, a series of novel pyrimidine-based benzothiazole derivatives were designed and synthesized. Initial biological evaluation demonstrated some of target compounds displayed potent antitumor activity in vitro against five cancer cell lines. Especially, the analogue 10s exhibited approximately potency with AZD5438 toward four cells including HeLa, HCT116, PC-3, and MDA-MB-231 with IC50 values of 0.45, 0.70, 0.92, 1.80 μM, respectively. More interestingly, the most highly active compound 10s in this study also possessed promising CDK2/cyclin A2 inhibitory activities with IC50 values of 15.4 nM, which was almost 3-fold potent than positive control AZD5438, and molecular docking studies revealed that the analogue bound efficiently with the CDK2 binding site. Further studies indicated that compound 10s could induce cell cycle arrest and apoptosis in a concentration-dependent manner. These observations suggest that pyrimidine-benzothiazole hybrids represent a new class of CDK2 inhibitors and well worth further investigation aiming to generate potential anticancer agents.
Diao, Peng-Cheng,Lin, Wei-Yuan,Jian, Xie-Er,Li, Yan-Hong,You, Wen-Wei,Zhao, Pei-Liang
p. 196 - 207
(2019/07/02)

Novel Triapine Derivative Induces Copper-Dependent Cell Death in Hematopoietic Cancers
Triapine, an iron chelator that inhibits ribonucleotide reductase, has been evaluated in clinical trials for cancer treatment. Triapine in combination with other chemotherapeutic agents shows promising efficacy in certain hematologic malignancies; however, it is less effective against many advanced solid tumors, probably due to the unsatisfactory potency and pharmacokinetic properties. In this report, we developed a triapine derivative IC25 (10) with potent antitumor activity. 10 Preferentially inhibited the proliferation of hematopoietic cancers by inducing mitochondria reactive oxygen species production and mitochondrial dysfunction. Unlike triapine, 10 executed cytotoxic action in a copper-dependent manner. 10-Induced up-expression of thioredoxin-interacting protein resulted in decreased thioredoxin activity to permit c-Jun N-terminal kinase and p38 activation and ultimately led to the execution of the cell death program. Remarkedly, 10 showed good bioavailability and inhibited tumor growth in mouse xenograft models. Taken together, our study identifies compound 10 as a copper-dependent antitumor agent, which may be applied to the treatment of hematopoietic cancers.
Chen, Ge,Niu, Chunyi,Yi, Jianhua,Sun, Lin,Cao, Hengyi,Fang, Yanjia,Jin, Taijie,Li, Ying,Lou, Chunli,Kang, Jingwu,Wei, Wanguo,Zhu, Jidong
(2019/04/01)

Novel Triapine Derivative Induces Copper-Dependent Cell Death in Hematopoietic Cancers
Triapine, an iron chelator that inhibits ribonucleotide reductase, has been evaluated in clinical trials for cancer treatment. Triapine in combination with other chemotherapeutic agents shows promising efficacy in certain hematologic malignancies; however, it is less effective against many advanced solid tumors, probably due to the unsatisfactory potency and pharmacokinetic properties. In this report, we developed a triapine derivative IC25 (10) with potent antitumor activity. 10 Preferentially inhibited the proliferation of hematopoietic cancers by inducing mitochondria reactive oxygen species production and mitochondrial dysfunction. Unlike triapine, 10 executed cytotoxic action in a copper-dependent manner. 10-Induced up-expression of thioredoxin-interacting protein resulted in decreased thioredoxin activity to permit c-Jun N-terminal kinase and p38 activation and ultimately led to the execution of the cell death program. Remarkedly, 10 showed good bioavailability and inhibited tumor growth in mouse xenograft models. Taken together, our study identifies compound 10 as a copper-dependent antitumor agent, which may be applied to the treatment of hematopoietic cancers.
Chen, Ge,Niu, Chunyi,Yi, Jianhua,Sun, Lin,Cao, Hengyi,Fang, Yanjia,Jin, Taijie,Li, Ying,Lou, Chunli,Kang, Jingwu,Wei, Wanguo,Zhu, Jidong
p. 3107 - 3121
(2019/04/01)

Convenient and efficient synthesis of novel 11: H -benzo[5,6][1,4]thiazino[3,4- a] isoindol-11-ones derived from 2-bromo-(2/3-substitutedphenyl)-1 H -indene-1,3(2 H)-diones
An unprecedented formation of 11H-benzo[5,6][1,4]thiazino[3,4-a]isoindol-11-ones through a one-step reaction of differently substituted 2-aminobenzenethiols and 2-bromo-(2/3-substitutedphenyl)-1H-indene-1,3(2H)-diones in freshly dried ethanol under reflux conditions has been investigated. This unique transformation probably occurs through an initial nucleophilic substitution followed by ring opening and subsequent intramolecular cyclization. The structures of all the synthesized benzo[1,4]thiazino isoindolinones were established by FTIR, 1H NMR, 13C NMR, HRMS, and X-ray crystallographic analysis. This approach was found to be simple and convenient and provides several advantages such as substantial atom economy, short reaction time and operational simplicity.
Mor, Satbir,Sindhu, Suchita
p. 12784 - 12792
(2019/05/10)

Enhancement of Benzothiazoles as Pteridine Reductase-1 Inhibitors for the Treatment of Trypanosomatidic Infections
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
p. 3989 - 4012
(2019/05/06)

Design, synthesis, and apoptosis-promoting effect evaluation of novel pyrazole with benzo[d]thiazole derivatives containing aminoguanidine units
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
p. 829 - 837
(2019/04/03)

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)

Design, synthesis, docking studies and biological evaluation of 2-phenyl-3-(Substituted benzo[d] thiazol-2-ylamino)-quinazoline-4(3H)-one derivatives as antimicrobial agents
Objective: A new series 2-phenyl-3-(substituted benzo[d] thiazol-2-ylamino)-quinazoline-4(3H)-one was prepared by the fusion method by reacting 2-phenyl benzoxazine with 2-hydrazino benzothiazole and it was evaluated for their antimicrobial activity against gram positive, gram negative bacteria and fungi. Methods: Titled compounds were synthesized by fusion reactions. These compounds were evaluated by in vitro antibacterial and antifungal activity using the minimum inhibitory concentration and zone of inhibition methods. The synthesized compounds were characterized with the help of infrared, NMR and mass spectral studies. The benzothiazole moiety and the quinazoline ring have previously shown DNA gyrase inhibition and target related antibacterial activity. Thus, molecular docking studies of synthesized compounds were carried out (PDB: 3G75) to study the possible interaction of compounds with the target. The batch grid docking was performed to determine the probable. Results: These compounds showed significant activity against gram positive and gram negative bacteria as well against the fungi. The compound A5 was found to be active against B. subtilis, P aeruginosa and C. albican at 12.5 μg/ml MIC. The compound A3 was found to be active against all microbial strains selected at 25 and 12.5 μg/ml MIC. Conclusion: Though the relationship between the activities shown by these compounds in, the antimicrobial study is still to be established, the docking studies conducted found to be consistent with antimicrobial results. Thus the results indicate that the designed structure can be a potential lead as an antimicrobial agent.
Pisal, Pooja,Deodhar, Meenakshi,Kale, Amol,Nigade, Ganesh,Pawar, Smita
p. 57 - 61
(2018/10/31)

Design, synthesis, and molecular docking study of benzothiazolotriazine derivatives for anticonvulsant potential
A series of newer benzothiazolotriazine derivatives (4a–k) was designed, synthesized, and characterized as anticonvulsant agents against the two classically used MES and scPTZ animal models. The synthesized derivatives were tested in vivo in both the animal models, followed by a neurotoxicity study by the rotarod method. Compound 4e, 8-chloro-4-(2-chlorocyclohexa-1,5-dien-1-yl)-2-((4-methoxybenzyl)thio)-10aH-benzo[4,5]thiazolo[3,2a][1,3,5]triazine was found most promising among the series in both the animal models, with no neurotoxicity. From this it may be confirmed that the presence of a methoxy (OCH3) group at the lipophilic aryl ring was showing high anticonvulsant potency. In the molecular modeling study, compound 4e (docking score = ?8.70) showed important hydrogen bond interaction with the amino acids LYS 329, SER 137, GLY 136 and π–π interactions with PHE 189 at the active site of GABA-AT. These derivatives can be further explored for the development of newer/novel anticonvulsant agents.
Firdaus, Jannat Ul,Habib, Anwar,Siddiqui, Nadeem,Alam, Ozair,Naim, Mohd. Javed,Partap, Sangh,Sahu, Meeta
(2018/12/04)

Discovery of 18β-glycyrrhetinic acid conjugated aminobenzothiazole derivatives as Hsp90-Cdc37 interaction disruptors that inhibit cell migration and reverse drug resistance
A series of 18β-glycyrrhetinic acid (GA) conjugated aminobenzothiazole derivatives were designed, synthesized and evaluated for disruption activity of Hsp90-Cdc37 as well as the effects of in vitro cell migration. These compounds exhibited relatively good disruption activity against Hsp90-Cdc37 with IC50 values in low micromolar range. A docking study of the most active compound 11g revealed key interactions between 11g and Hsp90-Cdc37 complex in which the benzothiazole moiety and the amine chain group were important for improving activity. It is noteworthy that further antitumor activity screening revealed that some compounds exhibited better inhibitory activity than the commercial anticancer drug 5-FU and showed potent suppression activity against drug-resistant cancer cells. In particular, compound 11 g appeared to be the most potent compound against the A549 cell line, at least partly, by inhibition of the activity of Hsp90 and apoptosis induction. The treatment of A549 cells with compound 11g resulted in inhibition of in vitro cell migration through wound healing assay and S phase of cell cycle arrested. In addition, 11g-induced apoptosis was significantly facilitated in A549 cells. Thus, we conclude that GA aminobenzothiazole derivatives may be the potential Hsp90-Cdc37 disruptors with the ability to suppress cells migration and reversed drug-resistant.
Jin, Le,Huang, Rizhen,Huang, Xiaochao,Zhang, Bin,Ji, Min,Wang, Hengshan
p. 1759 - 1775
(2018/03/01)

Rapid and efficient thiocyanation of phenols, indoles, and anilines in 1,1,1,3,3,3-hexafluoro-2-propanol under ultrasound irradiation
An efficient ultrasound-promoted thiocyanation of phenols, indoles, and anilines in the presence of N-chlorosuccinimide and NH4SCN using 1,1,1,3,3,3-hexafluoro-2-propanol as the solvent has been developed. The major features of the present protocol include the mild reaction conditions, short reaction times, good to excellent yields, and broad substrate scope. Moreover, scale-up synthesis can be achieved and the solvent can be easily recovered and reused.
Wang, Zhonghao,Wang, Liang,Chen, Qun,He, Ming-yang
supporting information
p. 76 - 84
(2017/12/28)

Efficient Synthesis and Biological Activity of Novel Indole Derivatives as VEGFR-2 Tyrosine Kinase Inhibitors
A series of novel indole derivatives were synthesized as potent inhibitors for the vascular endothelial growth factor receptor 2 (VEGFR-2) tyrosine kinase. Among those, compound 10b demonstrated the highest growth inhibition rate of 66.7% against the VEGFR-2 tyrosine kinase at 10 μM which indicates that indole-benzothiazole might be the favorable structure. The binding mode of compound 10b with VEGFR-2 tyrosine kinase was evaluated by molecular docking.
Zhang,Xu,Wang,Kang
p. 3006 - 3016
(2018/02/21)

Synthesis of 2-arylbenzothiazoles via direct condensation between in situ generated 2-aminothiophenol from disulfide cleavage and carboxylic acids
In this work we describe a simple and efficient general methodology for 2-arylbenzothiazole preparation employing disulfides and carboxylic acids. The reaction is promoted by tributylphosphine that acts both in disulfide bond cleavage and as activating agent for coupling with carboxylic acids. The reaction scope was studied using bis(2-aminophenyl)disulfide and different carboxylic acids with donor/withdrawing substituents, which resulted in the desired 2-arylbenzothiazole with moderate to good yields. The method was tested with success in preparation of the amyloid probe 2-(4-aminophenyl)-6-methoxybenzothiazole that employed a substituted bis(2-aminophenyl)disulfide.
Coelho, Felipe L.,Campo, Leandra F.
supporting information
p. 2330 - 2333
(2017/05/29)

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)

Regioselective Synthesis, Antimicrobial Evaluation and QSAR Studies of Some 3-Aryl-1-heteroarylindeno[1,2-c]pyrazol-4(1H)-ones
A series of seventeen 3-aryl-1-heteroarylindeno[1,2-c]pyrazol-4(1H)-ones (4a, 4b, 4c, 4d, 4e, 4f, 4g, 4h, 4i, 4j, 4k, 4l, 4m, 4n, 4o, 4p, 4q) has been synthesized and characterized by spectral (IR, 1H NMR, and mass), X-ray crystallography and analytical results. All the indenopyrazoles (4a, 4b, 4c, 4d, 4e, 4f, 4g, 4h, 4i, 4j, 4k, 4l, 4m, 4n, 4o, 4p, 4q) were tested for their in vitro antimicrobial activity against two Gram-positive bacteria viz. Bacillus subtilis (MTCC 441) and Staphylococcus aureus (MTCC 7443), two Gram-negative bacteria, viz. Escherichia coli (MTCC 42) and Pseudomonas aeruginosa (MTCC 741) and two fungi, viz. Candida albicans (MTCC 183) and Aspergillus niger (MTCC 282) using ceftriaxone and fluconazole as standard references against bacterial and fungal strains, respectively. Among the synthesized derivatives, 4f against B. subtilis and S. aureus, 4e against E. coli, 4g and 4j against P. aeruginosa, 4k and 4l against C. albicans, and 4k against A. niger were found to exhibit appreciable antimicrobial activities. However, 4g (minimum inhibitory concentration, 0.0036 μmol/mL) was found to be more potent than the reference, that is, fluconazole (minimum inhibitory concentration, 0.0050 μmol/mL) against A. niger. Moreover, both antibacterial and antifungal activities were found to be prolific. The radial distribution function parameters were found to be important for description of activities against the modeled strains in quantitative structure–activity relationship studies.
Mor, Satbir,Mohil, Rajni,Nagoria, Savita,Kumar, Ashwani,Lal, Kashmiri,Kumar, Devinder,Singh, Virender
p. 1327 - 1341
(2017/03/27)

Synthesis of Indane-Based 1,5-Benzothiazepines Derived from 3-Phenyl-2,3-dihydro-1H-inden-1-one and Antimicrobial Studies Thereof
In the present study, a series of 20 indane-based 1,5-benzothiazepines (5a–t) has been prepared derived from 3-phenyl-2,3-dihydro-1H-inden-1-one (1). All the synthesized 1,5-benzothiazepines (5a–t) were screened for their in vitro antimicrobial activities against four bacteria [Bacillus subtilis (MTCC 441), Staphylococcus epidermidis (MTCC 6880), Escherichia coli (MTCC 1652), and Pseudomonas aeruginosa (MTCC 424)] and two fungi [Candida albicans (MTCC 227) and Aspergillus niger (MTCC 8189)]. Among all the tested derivatives, 5n and 5o against E.?coli displayed more inhibitory activity than that of the reference drug, ciprofloxacin, while the derivatives 5c, 5m–o, 5s, and 5t against C.?albicans, and 5d, 5e, 5n, 5o, 5s, and 5t against A.?niger were found to be more potent than the standard drug, that is, fluconazole.
Mor, Satbir,Nagoria, Savita,Sindhu, Suchita,Khatri, Mohini,Sidhu, Gurdeep,Singh, Virender
p. 3282 - 3293
(2017/10/06)

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.
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Page/Page column 78; 79

(2016/04/09)

Fluoroboron fluorescent dye and its preparation method and application
The invention discloses a fluoroboron fluorescent dye and a preparation method and an application thereof, wherein the structure of the fluoroboron fluorescent dye is shown in a formula (III) or a formula (IV); in the formulae (III) and (IV), R1 is H or halogen, R2 is CN, R7 and R8 are independently H or C1-C6 alkyl, R9 is H, C1-C6 alkyl or C1-C6 alkoxyl, V is CH or N, and when V is N, no substituents are available on N. According to the fluoroboron fluorescent dye provided by the invention, the maximum fluorescent emission wavelength of the fluoroboron fluorescent dye prepared by the method provided by the invention ranges from 518nm to 600nm. Meanwhile, the fluoroboron fluorescent dye further has excellent fluorescence quantum yield and Stokes displacement, which means that the fluoroboron fluorescent dye has a good application prospect in the bioanalysis field such as fluorescence labeling and bioimaging. Meanwhile, the preparation method has simple steps and uses easily available raw materials.
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Paragraph 0059; 0061; 0062

(2017/02/09)

Novel Piperine Derivatives with Antidiabetic Effect as PPAR-γ Agonists
Piperine is an alkaloid responsible for the pungency of black pepper. In this study, piperine isolated from Piper nigrum L. was hydrolyzed under basic condition to obtain piperic acid and was used as precursor to carry out the synthesis of twenty piperine derivatives containing benzothiazole moiety. All the benzothiazole derivatives were evaluated for their antidiabetic potential by OGT test followed by assessment of active derivatives on STZ-induced diabetic model. It was observed that nine of twenty novel piperine analogues (5b, 6a-h), showed significantly higher antidiabetic activity in comparison with rosiglitazone (standard). Furthermore, these active derivatives were evaluated for their action as PPAR-γ agonists demonstrating their mechanism of action. The effects on body weight, lipid peroxidation, and hepatotoxicity after administration with active derivatives were also studied to further establish these derivatives as lead molecules for treatment of diabetes with lesser side-effects.
Kharbanda, Chetna,Alam, Mohammad Sarwar,Hamid, Hinna,Javed, Kalim,Bano, Sameena,Ali, Yakub,Dhulap, Abhijeet,Alam, Perwez,Pasha, M. A. Qadar
p. 354 - 362
(2016/10/19)

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)

Efficient and convenient synthesis, characterization, and antimicrobial evaluation of some new tetracyclic 1,4-benzothiazines
In the present study, 20 new tetracyclic 1,4-benzothiazines (4a-4 t) were conveniently synthesized in good yields and characterized by different spectral and physical techniques. The in vitro antimicrobial evaluation of the synthesized benzothiazine derivatives was performed by serial dilution against two Gram-positive bacteria [Bacillus subtilis (MTCC 441) and Staphylococcus epidermidis (MTCC 6880)], two Gram-negative bacteria [Escherichia coli (MTCC 1652) and Pseudomonas aeruginosa (MTCC 424)], and two fungal strains [Candida albicans (MTCC 227) and Aspergillus Niger (MTCC 8189)]. The derivatives 4 l and 4 t were found to be more potent than standard drug, i.e., fluconazole, against A. Niger and C. albicans, respectively.
Mor, Satbir,Nagoria, Savita
supporting information
p. 169 - 178
(2016/02/23)

Synthesis, anti-inflammatory, analgesic, 5-lipoxygenase (5-LOX) inhibition activities, and molecular docking study of 7-substituted coumarin derivatives
In the present study, 7-subsituted coumarin derivatives were synthesized using various aromatic and heterocyclic amines, and evaluated in vivo for anti-inflammatory and analgesic activity, and for ulcerogenic risk. The most active compounds were evaluated in vitro for 5-lipoxygenase (5-LOX) inhibition. Docking study was performed to predict the binding affinity, and orientation at the active site of the enzyme. In vivo anti-inflammatory and analgesic activity, and in vitro 5-LOX enzyme inhibition study revealed that compound 33 and 35 are the most potent compounds in all the screening methods. In vitro kinetic study of 35 showed mixed or non-competitive type of inhibition with 5-LOX enzyme. Presence of [Formula presented]3 group in 35 and [Formula presented] in 33 at C6-position of benzothiazole ring were found very important substitutions for potent activity.
Srivastava, Pavan,Vyas, Vivek K.,Variya, Bhavesh,Patel, Palak,Qureshi, Gulamnizami,Ghate, Manjunath
supporting information
p. 130 - 138
(2016/07/11)

Graphene oxide: A promising carbocatalyst for the regioselective thiocyanation of aromatic amines, phenols, anisols and enolizable ketones by hydrogen peroxide/KSCN in water
Graphene oxide (GO), as a heterogeneous carbocatalyst, catalyzes the direct thiocyanation of a variety of arenes including aromatic amines, phenols, anisols and carbonyl compounds that possessing α-hydrogen in the presence of hydrogen peroxide and KSCN in water as a green media. This procedure is chemoselective, avoids the use of precious metals and toxic solvents and has a broad substrate scope. Easy removal from the reaction mixture and recyclability with no loss of activity are the key features of graphene oxide in this catalytic system.
Khalili, Dariush
p. 2547 - 2553
(2016/03/19)

Catalytic Thiourea Promoted Electrophilic Thiocyanation of Indoles and Aromatic Amines with NCS/NH4SCN
A simple and efficient protocol for the electrophilic thiocyanation of indoles and aromatic amines with thiourea/NCS/NH4SCN system has been developed. The major features of the present procedure are the mild conditions, good yields, short reaction times, and the use of inexpensive and readily available organocatalyst. Moreover, N-chlorosuccinimide (NCS) was found to be indispensable, and thiourea could greatly promote the reaction.
Wang, Cancan,Wang, Zhonghao,Wang, Liang,Chen, Qun,He, Mingyang
supporting information
p. 1081 - 1085
(2016/11/25)

Synthesis and biological evaluation of novel benzothiazole derivatives as potential anticonvulsant agents
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
(2016/04/20)

Synthesis and biological evaluation of novel benzothiazole derivatives as potential anticonvulsant agents
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
(2016/04/20)

Synthesis of bioactive substituted pyrazolylbenzothiazinones
Abstract Pyrazolylbenzothiazinones have been synthesized in good yields by the reaction of 2-hydrazinocarbonymethyl-3,4-dihydro-2H-1,4-benzothiazin-3-ones with β-diketone in the presence of ethanol. The structures of synthesized pyrazolylbenzothiazinones were confirmed on the basis of their analytical and spectral data. The antimicrobial activities of the synthesized compounds have also been included.
Sharma, Praveen Kumar,Kumar
p. 6141 - 6148
(2015/08/18)

Design, synthesis and biological evaluation of benzimidazolyl and benzothiazolyl picolinamide derivatives as antimicrobial agents
A series of benzothiazolyl amides and benzimidazolyl amides (6a-f) has been synthesized from the coupling reaction of substituted picolinic acid with benzothiazole and benzimidazoles, respectively. The newly synthesized compounds were evaluated for their efficacy as antimicrobial agents against various Gram-positive and Gram-negative strains of bacteria and fungal strains. Amongst these compounds 6f was found to be the most potent against Bacillus subtilis and Candida albicans. Moreover, other compounds also found to be potential antibacterial agents in comparison to the standard drugs.
Namani, Vasu,Bharath Kumar Goud,Bharathi Kumari,Kumbham, Ramesh,Balakrishna, Kannoju,Bhima, Bhukya
p. 4575 - 4578
(2015/11/27)

Catalytic N-formylation for synthesis of 6-substituted-2-benzothiazolylimino-5-piperazinyl-4-thiazolidinone antimicrobial agents
A new class of piperazine-based 2-benzothiazolylimino-4-thiazolidinones has been efficiently prepared via highly accelerated N-formylation of N-isopropylpiperazine by the use of a mild heterogeneous catalyst, sulfated tungstate. Heterocyclization of N-(benzo[d]thiazol-2-yl)-2-chloroacetamides (3a-j) by use of NH4SCN in ethanol under reflux efficiently furnished the intermediates 2-benzothiazolyliminothiazolidin-4-ones (4a-j). These were treated with 4-isopropylpiperazine-1-carbaldehyde (2) to prepare the final products 5a-j. The structures of the new derivatives were confirmed by elemental analysis and use of spectroscopic data (FTIR and 1H NMR). Their pharmacological potential as promising antimicrobial agents was determined in vitro against bacteria and a fungus; the lowest minimum inhibitory concentrations (MIC) observed were in the range 4-8 μg/mL.
Patel, Rahul V.,Park, Se Won
p. 5599 - 5609
(2015/07/08)

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)

Access to a new class of biologically active quinoline based 1,2,4-triazoles
As an aspect of our ongoing research in search of new antimicrobial armamentarium, a series of 1,2,4-triazol-3-ylthio-acetamides was constructed and in vitro analyzed for their antimicrobial activity against several bacteria and fungi. Aiming to establish an increased potency, the bioassay results were matched to those of 1,3,4-oxadiazoles, utilized previously. Remarkably, 1,2,4-triazoles were found to possess a good spectrum of antifungal potency, which eventually suggested the azole template as an essential pharmacophore to diversify the biological occupations of the attendant molecules. However, it was noticed that the potency of final analogs against each strain placed reliance on the type of substituent present on benzothiazole ring. The structures of final compounds were confirmed with the aid of IR, 1H NMR, 13C NMR spectroscopy and CHN analysis.
Patel, Rahul V.,Park, Se Won
p. 24 - 30
(2013/12/04)

A facile and efficient synthesis of 2-(5-(4-substitutedphenyl)-4, 5-dihydro-3-phenylpyrazol-1-yl)-6-substitutedbenzothiazoles and their biological studies
A series of new 1-substituted 3, 5-diarylpyrazolines (10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25) were synthesized in good yield by both conventional and microwave-assisted synthesis from α, β- unsaturated ketones (6, 7, 8, 9) in n-butanol and benzothiazole hydrazines (2, 3, 4, 5). All the new compounds were characterized by IR, NMR, and mass spectral data. The synthesized compounds (10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25) were evaluated for antibacterial and anthelmintic activities. The compounds showed potent anthelmintic activity against earthworm species (Eudrilus eugeniae) and moderate antibacterial activity against bacterial strains such as Gram positive bacteria, Enterococcus faecalis, Staphylococcus aureus, and Bacillus subtilis, and Gram negative bacteria, Escherichia coli and Proteus mirabilis.
Munirajasekhar,Himaja,Mali, Sunil V.
p. 459 - 465
(2014/04/17)

Discovery of the highly potent Fluoroquinolone-based Benzothiazolyl-4- thiazolidinone hybrids as antibacterials
A new series of fluoroquinolone-based benzothiazolyl-4-thiazolidinone hybrids has been yielded via sulfated tungstate-promoted highly accelerated N-formylation at a piperazine residue of ciprofloxacin and norfloxacin entities. The formylated fluoroquinolone moieties were then coupled with substituted 2-aminobenzothiazoles, which were generated from their respective para-substituted amines to form corresponding Schiff base intermediates. The Schiff bases were then treated with thioglycolic acid to equip a new class of 4-thiazolidinones to be analyzed for their antibacterial effects against two Gram-positive (Staphylococcus aureus and Bacillus subtilis) and two Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacterial strains and were found highly potent with lowest Minimum inhibitory concentrations (MIC), 1-2 μg/mL, that is, more potent than control drugs ciprofloxacin (3.12-6.25 μg/mL). Initial outcomes provided for these novel molecular systems will aid researchers to design and develop new antibacterial drugs. The structural assignments of the new products were done on the basis of FT-IR, 1H NMR and 13C NMR spectroscopy, and elemental analysis. A truly rationalized design of a new class of 4-thiazolidinones revealed potent antibacterial efficacies with lowest MICs 1-2 μg/mL when compared to control drug ciprofloxacin at 3.12-6.25 μg/mL. Combination of electron-withdrawing substituent on the benzothiazole ring and norfloxacin entity furnished anti-Gram-positive effects, as well as combination of electron-releasing substituent with ciprofloxacin entity furnished anti-Gram-negative potency. Two thiazole rings positively enhanced the potency of the final scaffolds.
Patel, Rahul V.,Park, Se Won
p. 123 - 129
(2014/07/07)

Different heterocycles functionalized s-triazine analogues: Design, synthesis and in vitro antimicrobial, antituberculosis, and anti-HIV assessment
Some new quinolone condensed s-triazine derivatives endowed with different heterocycles and 4-aminobenzonitrile moiety has been synthesized and examined for their bioactivities against eight bacteria (Staphylococcus aureus, Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhi, Proteus vulgaris, and Shigella flexneri), two fungi (Aspergillus niger, Candida albicans) by using agar streak dilution method, and Mycobacterium tuberculosis H37Rv by using Lowenstein and Jensen MIC method. Upon preliminary biological screening, it was observed that the majority of the compounds were found to possess a significant broad spectrum antimicrobial (MICs: 6.25-25 μg/mL) and antitubercular (MIC: 12.5 μg/mL) potential. Hence, anti-HIV activity against two types of HIV viral strains [HIV-1 (IIIB) and HIV-2 (ROD)] has been carried out using the MTT assay. From this bioassay, we have identified some potent inhibitors acting as anti-HIV-1 agents (IC50: 4.45g/mL) with promising therapeutic index of 16 for analogue 7 h. The structural assignments of the new products were carried out on the basis of IR, 1HNMR, 13CNMR spectroscopy, and elemental analysis.
Patel, Paresh K.,Patel, Rahul V.,Mahajan, Dharmesh H.,Parikh, Parimal A.,Mehta, Girish N.,Pannecouque, Christophe,De Clercq, Erik,Chikhalia, Kishor H.
p. 1641 - 1658
(2015/01/09)