- Synthesis of Emodin Amide Derivatives Containing 1,3,4-Thiadiazole and Their Inhibitory Activity on Vibrio harveyi
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A series of new 1,3,4-thiadiazole Emodin amide derivatives were synthesized through the connection of 5-substituted-1,3,4-thiadiazole-2-amine and Emodin carboxylic acids which were obtained by a two-step procedure starting from Emodin. Vibrio harveyi inhibition activities of the newly prepared compounds were evaluated. Results revealed that all compounds showed different degrees of inhibition on V. harveyi. Among them, compound 7a showed the best V. harveyi inhibition effect and the minimum inhibitory concentration (MIC) was 0.0625 mg/mL.
- Cao, Lian-Gong,Cao, Zhi-Ling,Chen, Chao,Jiang, Kai-Jun,Liu, Shu-Hao,Liu, Wei-Wei,Ruan, Xin-Chi,Shao, Zhong-Bai,Shi, Da-Hua,Su, Zi-Qin,Wang, You-Xian,Wu, Yu-Ran,Wu, Yu-Yu
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p. 281 - 286
(2021/08/05)
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- N-thiadiazole-4-hydroxy-2-quinolone-3-carboxamides bearing heteroaromatic rings as novel antibacterial agents: Design, synthesis, biological evaluation and target identification
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Due to the occurrence of antibiotic resistance, bacterial infectious diseases have become a serious threat to public health. To overcome antibiotic resistance, novel antibiotics are urgently needed. N-thiadiazole-4-hydroxy-2-quinolone-3-carboxamides are a potential new class of antibacterial agents, as one of its derivatives was identified as an antibacterial agent against S. aureus. However, no potency-directed structural optimization has been performed. In this study, we designed and synthesized 37 derivatives, and evaluated their antibacterial activity against S. aureus ATCC29213, which led to the identification of ten potent antibacterial agents with minimum inhibitory concentration (MIC) values below 1 μg/mL. Next, we performed bacterial growth inhibition assays against a panel of drug-resistant clinical isolates, including methicillin-resistant S. aureus, and cytotoxicity assays with HepG2 and HUVEC cells. One of the tested compounds named 1-ethyl-4-hydroxy-2-oxo-N-(5-(thiazol-2-yl)-1,3,4-thiadiazol-2-yl)-1,2-dihydroquinoline-3-carboxamide (g37) showed 2 to 128-times improvement compared with vancomycin in term of antibacterial potency against the tested strains (MICs: 0.25–1 μg/mL vs. 1–64 μg/mL) and an optimal selective toxicity (HepG2/MRSA, 110.6 to 221.2; HUVEC/MRSA, 77.6–155.2). Further, comprehensive evaluation indicated that g37 did not induce resistance development of MRSA over 20 passages, and it has been confirmed as a bactericidal, metabolically stable, orally active antibacterial agent. More importantly, we have identified the S. aureus DNA gyrase B as its potential target and proposed a potential binding mode by molecular docking. Taken together, the present work reports the most potent derivative of this chemical series (g37) and uncovers its potential target, which lays a solid foundation for further lead optimization facilitated by the structure-based drug design technique.
- Xue, Wenjie,Li, Xueyao,Ma, Guixing,Zhang, Hongmin,Chen, Ya,Kirchmair, Johannes,Xia, Jie,Wu, Song
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- Discovery of novel nonpeptide small-molecule NRP1 antagonists: Virtual screening, molecular simulation and structural modification
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Multifaceted roles of vascular endothelial growth factor (VEGF)-neuropilin-1 (NRP1) interaction have been implicated in cancer, but reports on small-molecule inhibitors of VEGF-NRP1 interaction are scarce. Herein, we describe the identification of 1, a novel nonpeptide small-molecule NRP1 antagonist with moderate activity via structure-based virtual screening. Ensemble docking and molecular dynamics (MD) simulations of 1 were carried out and an interesting binding model was obtained. We found that the “aromatic box” enclosed by Tyr297, Trp301 and Tyr353 of NRP1 is critical for NRP1-1 binding. Further structure modification of 1 based on the binding model derived from MD simulations resulted in the identification of 12a with significantly improved activity.
- Peng, Kewen,Li, Yu,Bai, Ying,Jiang, Teng,Sun, Huiyong,Zhu, Qihua,Xu, Yungen
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- Metal-free synthesis of 2-aminothiadiazoles via TBHP-Mediated oxidative C-S bond formation
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An efficient one-pot synthesis of 2-amino-1,3,4-thiadiazoles from easily available aldehydes and thiosemicarbazide using TBHP as an oxidant has been described. Notably, these reactions were carried out at room temperature using ethanol as solvent. This is the first example for one-pot synthesis of 2-amino-1,3,4-thiadiazole derivatives from aldehydes. This new synthetic methodology provides a simple procedure utilizing a safer oxidizing system that affords the target products in mild reaction condition with satisfactory yields and wide substrate scope.
- Hatvate, Navnath T.,Ghodse, Shrikant M.,Telvekar, Vikas N.
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supporting information
p. 285 - 290
(2018/02/09)
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- 2-n-propyl-6-ferrocenyl-imidazo[2,1-b]-1,3,4-thiadiazole preparation method
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The present invention discloses a 2-n-propyl-6-ferrocenyl-imidazo[2,1-b]-1,3,4-thiadiazole preparation method, which comprises: carrying out stirring mixing on 2-amino-5-n-propyl-1,3,4-thiadiazole, alpha-bromo-acetylferrocene and ethanol; placing the mixed solution in a microwave oven, and carrying out microwave irradiation; after the alpha-bromo-acetylferrocene completely reacts, carrying out a microwave reaction; adding water to the reaction solution, and adjusting the pH value of the reaction solution to 7-8 with a saturated sodium carbonate solution; carrying out suction filtration, washing the filter cake with water, and drying to obtain a crude product; and re-crystallizing with DMF to obtain the target product. According to the present invention, the microwave-assisted synthesis reaction is used so as to substantially shorten the reaction time and improve the reaction efficiency.
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Paragraph 0033; 0043; 0053; 0063; 0073
(2018/01/12)
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- Preparation of 2-amino-5-alkyl -1, 3, 4-thiadiazole
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The invention discloses a method for preparing 2-amino-5-alkyl-1,3,4-thiadiazole. The method comprises the following steps of adding A mol of thiosemicarbazide, B mol of carboxylic acid, C mol of phosphorus oxychloride and D mol of silica gel in a dry reaction container, grinding at a room temperature until the raw materials are completely reacted, and standing to obtain a crude product, wherein A: B: C = 1: (1 to 1.2): (1 to 1.2), and A: D = 1: (5 to 10); then adding alkaline solution in the crude product until the pH value of the obtained mixed solution is 8-8.2, then carrying out suction filtration on the mixed solution, dissolving the filter cake by a solvent and then further carrying out suction filtration, removing silica gel, then carrying out reduced pressure concentration on the finally-obtained filtrate, and removing the solvent to obtain 2-amino-5-alkyl-1,3,4-thiadiazole. The method disclosed by the invention is a solid-phase reaction, silica gel is used as a carrier, the operation process is simple, the reaction time is short, the reaction conditions are moderate, the equipment requirements are low, and the yield of the target product is up to more than 91%.
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Paragraph 0024-0026; 0052-0054
(2017/04/19)
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- Synthesis, characterization and biological evaluation of some novel fluoroquinolones
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Different derivatives of fluoroquinolones were synthesized by combining it with different thiadiazoles. The synthesized compounds were characterized by infrared spectroscopy, proton nuclear magnetic resonance and mass spectral data. The compounds were screened for their antibacterial and antifungal activity. Ciprofloxacin derivatives with thiadiazoles 7c showed good antibacterial as well as antifungal activities, whereas 13c and 13e showed antibacterial and antifungal activity respectively. Sparfloxacin derivative 8c showed both antibacterial and antifungal activity. Sparfloxacin derivatives 14b and 14e showed antibacterial and antifungal activity respectively.
- Pandit, Neelanjana,Shah, Kamal,Agrawal, Neetu,Upmanyu, Neeraj,Shrivastava, Sushant K.,Mishra, Pradeep
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p. 843 - 851
(2016/04/20)
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- Synthesis and antibacterial activities of thiadiazole maneb
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Summary: Four novel maneb derivatives containing 1, 3, 4-thiadiazole were successfully synthesized and characterized by FT-IR, electrochemical analysis and 1H-NMR and 13C-NMR. And their antibacterial activities were screened for Paddy fusarium, Borrytis cinerea, Cucumber fusarium, Tomato gibberella, Grape white rot in vitro by filter paper disc diffusion technique. The target compounds exhibited moderate to excellent activity in comparison to maneb.
- Yuting, Liu,Gangtao, Liang,Dawei, Yin
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p. 115 - 121
(2015/05/20)
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- Design of new phenothiazine-thiadiazole hybrids via molecular hybridization approach for the development of potent antitubercular agents
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A new library of phenothiazine and 1,3,4-thiadiazole hybrid derivatives (5a-u) was designed based on the molecular hybridization approach and the molecules were synthesized in excellent yields using a facile single-step chloro-amine coupling reaction between 2-chloro-1-(10H-phenothiazin-10-yl)ethanones and 2-amino-5-subsituted-1,3,4-thiadiazoles. The compounds were evaluated for their in vitro inhibition activity against Mycobacterium tuberculosis H37Rv (MTB). Compounds 5g and 5n were emerged as the most active compounds of the series with MIC of 0.8 μg/mL (～1.9 μM). Also, compounds 5a, 5b, 5c, 5e, 5l and 5m (MIC = 1.6 μg/mL), and compounds 5j, 5k and 5o (MIC = 3.125 μg/mL) showed significant inhibition activity. The structure-activity relationship demonstrated that an alkyl (methyl/npropyl) or substituted (4-methyl/4-Cl/4-F) phenyl groups on the 1,3,4-thiadiazole ring enhance the inhibition activity of the compounds. The cytotoxicity study revealed that none of the active molecules are toxic to a normal Vero cell line thus proving the lack of general cellular toxicity. Further, the active molecules were subjected to molecular docking studies with target enzymes InhA and CYP121.
- Ramprasad, Jurupula,Nayak, Nagabhushana,Dalimba, Udayakumar
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- Synthesis and biological activity of acylthiourea derivatives contain 1,2,3-thiadiazole and 1,3,4-thiadiazole
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In order to investigate the biological activity of novel thiourea compounds, some novel 1,2,3-thiadiazole derivatives containing 1,3,4-thiadiazole were synthesized under phase transfer catalyzed condition(PEG-600)by multi-step reactions. The chemical structures of all compounds were established by 1H NMR, FTIR, MS, and elemental analysis, and some of these compounds were investigated for fungicidal activity and plant growth regulatory activity. The bioassay results indicated that some of these compound exhibited moderate activities.
- Yang, Ming-Yan,Zhao, Wen,Sun, Zhao-Hui,Tan, Cheng-Xia,Weng, Jian-Quan,Liu, Xing-Hai
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p. 314 - 318
(2015/04/14)
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- Mild and convenient one-pot synthesis of 2-amino-1,3,4-thiadiazoles using trimethylsilyl isothiocyanate (TMSNCS)
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A novel and efficient one-pot method has been developed for the synthesis of 2-amino-1,3,4-thiadiazoles using various carboxylic acid hydrazides with trimethylsilyl isothiocyanate (TMSNCS). In situ preparation of various thiosemicarbazides by the reaction
- Guda, Dinneswara Reddy,Cho, Hyeon Mo,Lee, Myong Euy
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p. 6813 - 6816
(2013/05/22)
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- Synthesis, crystal structure and bioactivity of N-(5-propyl-1,3,4- thiadiazol-2-yl)cyclopropanecarboxamide
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A new 1,3,4-thiadiazole compound with m.f. C9H 13N3OS, has been synthesized and confirmed by 1H NMR and HRMS. The single crystal structure of the 1,3,4-thiadiazole compound was determined by a single crystal X-ray diffraction study. The crystal belongs to the triclinic system, space group P-1 with a = 10.238(2), b = 10.325(2), c = 10.560(2) ?, α = 104.09(3), β = 109.50(3), γ = 93.40(3)°, Z = 4, V = 1008.4(3)?3, Mr = 211.28, Dc = 1.392 g/cm3, S = 0.98, μ = 0.29 mm-1, F(000) = 448, the final R1 = 0.0970 and wR2 = 0.2147 for 1776 were observed with I > 2Σ(I). X-ray indicated that two intermolecular hydrogen bonds N1-H1···N5, N4-H4···N2 were observed. The preliminary biological test shown that the synthesized compound has moderate herbicidal activity against Brassica campestris.
- Sun, Na-Bo,Jin, Jian-Zhong,Lei, Chao,He, Fang-Yue
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p. 7820 - 7822
(2013/09/23)
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- Synthesis of 5-alkyl-2-amino-1,3,4-thiadiazoles and α,ω-bis(2- amino-1,3,4-thiadiazol-5-yl)alkanes in ionic liquids
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Reaction of thiosemicarbazide with carboxylic acids, including N-substituted amino acids, in ionic liquids with H2SO4 as a catalyst affords 5-R-2-amino-1,3,4-thiadiazoles. On using alkanedicarboxylic acids, α,ω-bis(2-amino-1,3,4,-thiadiazol-5-yl)alkanes were obtained.
- Epishina, Margarita A.,Kulikov, Alexander S.,Ignat'Ev, Nikolai V.,Schulte, Michael,Makhova, Nina N.
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experimental part
p. 331 - 333
(2012/02/02)
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- Synthesis, antifungal activities and 3D-QSAR study of N-(5-substituted-1,3,4-thiadiazol-2-yl)cyclopropanecarboxamides
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A series of cyclopropanecarboxamide were prepared and tested for antifungal activity in vivo. The preliminary bioassays indicated that some compounds are comparable to the commercial fungicides. To further explore the comprehensive structure-activity relationship on the basis of fungicidal activity data, comparative molecular field analysis (CoMFA) was performed, and a statistically reliable model with good predictive power (r2 = 0.8, q2 = 0.516) was achieved. Based on the CoMFA, compound 7p was designed and synthesized, which was found to display a good antifungal activity (79.38%) as 7g and 7h.
- Liu, Xing-Hai,Shi, Yan-Xia,Ma, Yi,Zhang, Chuan-Yu,Dong, Wei-Li,Pan, Li,Wang, Bao-Lei,Li, Bao-Ju,Li, Zheng-Ming
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scheme or table
p. 2782 - 2786
(2009/10/19)
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- Some novel 2-methyl-3-(1′3′4′-thiadiazoyl)-4-(3H) quinazolinones with anticonvulsant and CNS depressant activity
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A series comprising six novel 2-methyl-3-(1′3′4′- thiadiazoyl)-4(3H)quinazolinones have been synthesized by condensing different 2-amino-1,3,4-thiadiazoles with 2-methyl benzoxazin-2-one and evaluated for anticonvulsant and CNS depressant activity. Compound 5f exhibited both anticonvulsant and CNS depressant activity.
- Mishra, Pradeep,Jatav, Varsha,Kashaw
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p. 1165 - 1170
(2008/02/07)
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- Polymer-supported dichlorophosphate: A recoverable new reagent for synthesis of 2-amino-1,3,4-thiadiazoles
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Poly(ethylene glycol) (PEG) supported dichlorophosphate was efficiently used as a recoverable new dehydration reagent for rapid synthesis of 2-amino-5-substituted-1,3,4-thiadiazoles under microwave irradiation and solvent-free condition by reactions of thiosemicarbazide with aliphatic acids, benzoic acid, aryloxyacetic acids or furan-2-carboxylic acids.
- Li, Zheng,Yu, Jin-Lan,Yang, Jing-Ya,Shi, Sheng-Yi,Wang, Xi-Cun
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p. 341 - 343
(2007/10/03)
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- Thiadiazolyl quinazolones as potential antiviral and antihypertensive agents
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Phthalic anhydride on treatment with β-ethanol amine gives N-hydroxy ethyl phthalimide I which reacts with anthranilic acid in presence of ethanol containing concentrated hydrochloric acid affording 5-(N-ethylphthalimido)- anthranilic acid 2. This on treatment with benzoyl chloride in pyridine gives 6-(N-ethyl phthalimido)-2-phenyl-4-oxo-3, 4-dihydrobenzoxazine 3 which on reaction with 2-amino-5-aralkyl-1, 3, 4-thiadiazoles 4 in pyridine results in the formation of 6-(N-ethylphthalimido)-3-[2′-(5′-aralkyl-1′, 3′, 4′-thiadiazolyl)]-2-phenyl-4-oxo-(3H)-quinazolines 5. The antiviral and antihypertensive activities of 5 have been reported.
- Pandey,Tusi, Sarah,Tusi, Zehra,Raghubir,Dixit,Joshi,Bajpai
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p. 180 - 183
(2007/10/03)
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- Synthesis of thiadiazolo-s-triazines for their antiviral activity based on QSAR studies
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2-Amino-5-aralkyl-1,3,4-thiadiazole 1 on treatment with benzaldehyde yields 5-aralkyl-2-benzylideno-imino-1,3,4-thiadiazole 2 which on reaction with ammonium thiocyanate cyclises to give 2-phenyl-7-aralkyl-1,3,4-thiadiazolo-[3,2-a]-s-triazine-5-[6H,7H]-thione 3. Reaction of 3 with p-toluene sulphonyl chloride in anhydrous chloroform gives 2-phenyl-3-(p-toluenesulphonyl)-7-aralkyl-1,3,4-thiadiazolo-[3, 2-al-s-triazine-5-[6H,7H]-thiones 4g-I. Benzoyl chloride also reacts with 3 in anhydrous pyridine giving 2-phenyl-3-(benzoyl)-7-aralkyl-1,3,4-thiadiazolo-[3,2-a]-s-triazine-5-[6H,7H] -thiones 4a-f in quantitative yields. The antiviral activities of 4 based on QSAR studies have been reported using physicochemical method.
- Pandey,Tusi,Tandon,Joshi,Bajpai
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p. 2583 - 2588
(2007/10/03)
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- Derives de la dihydro-2,4 triazole-1,2,4 thione-3 et de l'amino-2 thiadiazole-1,3,4 a partir de nouvelles thiosemicarbazones d'esters
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A new general synthesis of 4,5-disubstituted 2,4-dihydro-1,2,3-triazole-3-thiones is proposed.These heterocycles are obtained by the action of primary amines, aralhydrazines or aroylhydrazines on the thiosemicarbazones of esters.These last compounds are prepared by action of chlorhydrates of iminoesters on thiosemicarbazide in dimethylformamide.These thiosemicarbazones react also with strong acids, acid anhydrides and chlorides; by thermolysis and they give 2-amino-1,3,4-thiadiazole derivatives.Also, two derivatives of 1,2,4-triazolo-1,3,4-thiadiazole have been prepared.
- Malbec, Frederique,Milcent, Rene,Barbier, Geo
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p. 1689 - 1698
(2007/10/02)
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