- Preparation of 1,3,4-oxadiazoles and 1,3,4-thiadiazoles via chemoselective сyclocondensation of electrophilically activated nitroalkanes to (thio)semicarbazides or thiohydrazides
-
[Figure not available: see fulltext.] Unusual reaction proceeding via the electrophilic activation of nitroalkanes in the presence of polyphosphoric acid has been discovered. Subsequent nucleophilic attack with semicarbazides or thiosemicarbazides allows
- Aksenov, Alexander V.,Aksenov, Dmitrii A.,Aksenov, Nicolai A.,Arutiunov, Nikolai A.,Kirillov, Nikita K.,Rubin, Michael
-
p. 1067 - 1072
(2020/10/02)
-
- N-thiadiazole-4-hydroxy-2-quinolone-3-carboxamides bearing heteroaromatic rings as novel antibacterial agents: Design, synthesis, biological evaluation and target identification
-
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
-
-
- Discovery of novel nonpeptide small-molecule NRP1 antagonists: Virtual screening, molecular simulation and structural modification
-
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
-
-
- 2-ethyl-6-ferrocenyl-imidazo[2,1-b]-1,3,4-thiadiazole preparation method
-
The present invention discloses a 2-ethyl-6-ferrocenyl-imidazo[2,1-b]-1,3,4-thiadiazole preparation method, which comprises: carrying out stirring mixing on 2-amino-5-ethyl-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.
- -
-
Paragraph 0027; 0037
(2018/01/12)
-
- Preparation of 2-amino-5-alkyl -1, 3, 4-thiadiazole
-
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%.
- -
-
Paragraph 0028-0030
(2017/04/19)
-
- Synthesis, biological evaluation and molecular modeling study of thiadiazolo[3,2-a][1,3]diazepine analogues of HIE-124 as a new class of short acting hypnotics
-
A new series of 6,7-dihydro-[1,3,4]thiadiazolo[3,2-a][1,3]diazepine analogues were synthesized, and biological evaluated. Compound GS-62 (33) exhibited potent in?vivo short acting hypnotic activity with onset time, duration of sleep and therapeutic index of 6.4?±?0.2, 94.8?±?5.3?min, 6.62, respectively), in comparison to thiopental sodium (6). Compounds 33 did not show any sign of acute tolerance reported with the maintenance dose of 6. Meanwhile 33 potentiated the in?vivo hypnotic effect of 6 in an equimolar amounts (0.06?mmol) combination showing an onset and duration of 7.5?±?1.3, 62.5?±?5.9?min, respectively. This combination allowed the use of lower doses of both drugs to avoid the undesirable side effects. Docking studies revealed favorable interactions and binding to BDZ binding site of the GABAAreceptor especially with Arg87, Arg149, and Thr151 amino acid residues.
- El-Subbagh, Hussein I.,Hassan, Ghada S.,El-Taher, Kamal E.H.,El-Messery, Shahenda M.,El-Azab, Adel S.,Abdelaziz, Alaa A.-M.,Hefnawy, Mohamed M.
-
p. 237 - 247
(2016/09/09)
-
- Synthesis and antibacterial activities of thiadiazole maneb
-
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
-
p. 115 - 121
(2015/05/20)
-
- Fe3+-selective naked-eye 'off-on' fluorescent probe: Its crystal structure and imaging in living cells
-
Four novel rhodamine-active probes L1-L4 have been proposed and characterized as fluorescent chemosensors for Fe3+. An 'off-on' type fluorescent enhancement was observed, which was induced by the interactions between Fe3+ and the probe, proven to adopt a 1:1 binding stoichiometry. The recognition properties of the target compounds with metal ions have been investigated in methanol-water (1:1, v/v) solution by the fluorescence and ultraviolet spectrum. In addition, a plausible application of probes in the imaging of HepG2 (liver cells) under the condition of reoxygenation (95% air, 5% CO2) exposed to Fe3+ ions was also demonstrated.
- Meng, Wen-Fei,Yang, Mei-Pan,Li, Bo,Cheng, Zhao,Yang, Bing-Qin
-
p. 8577 - 8581
(2014/12/10)
-
- Rapid synthesis, characterization, anticancer and antimicrobial activity studies of substituted thiadiazoles and their dinucleating ligand metal complexes
-
Synthesis of 2,5-disubstituted thiadiazoles was accomplished via a conventional method as well as microwave irradiation method. These substituted thiadiazoles were diazotized and coupled with 2,4-pentanedione (AcAc), ethylcyanoacetate (ECA) and malanodinitrile (MN) to get dinucleating ligands. The ligands were isolated, characterized and condensed with Ni (II), Cu (II) and Ru(III) chlorides. These compounds were screened on HL-60 Human leukemia cell Line and U-937 Lymphoma cell lines for anticancer activities. The antimicrobial activity of the ligands and their complexes against bacteria and fungi was also investigated. The effect of metal on the ligand activity is discussed. Springer Science+Business Media, LLC 2011.
- Jha, Anjali,Murthy,Sanyal,Durga
-
p. 2548 - 2556
(2012/11/07)
-
- Synthesis of novel aryloxy propanoyl thiadiazoles as potential antihypertensive agents
-
2-Amino-5-aryl/alkyl-1,3,4-thiadiazoles 3a-e were synthesized from aliphatic and aromatic acids and thiosemicarbazide. These 2-amino-5-aryl/alkyl- 1,3,4-thiadiazoles 3a-e were condensed with 2-(naphthalenyloxymethyl) oxirane 4a-b to prepare some naphthalenyloxy-propanol amine derivatives 5a-j. These compounds were synthesized as potential antihypertensive agents.
- Samel, Amarish B.,Pai, Nandini R.
-
experimental part
p. 1327 - 1330
(2011/10/07)
-
- AMINOACID DERIVATIVES CONTAINING A DISULFANYL GROUP IN THE FORM OF MIXED DISULFANYL AND AMINOPEPTIDASE N INHIBITORS
-
The invention relates to novel compounds of formula (I): H2N-CH(R1)-CH2-S-S-CH2-CH(R2)-CONH-R5, wherein R1 is a hydrocarbon chain, phenyl or benzyl radical, methylene radical substituted by a 5 or 6 atom heterocycle; R2 is a phenyl or benzyl radical, a 5 or 6 atom aromatic heterocycle, methylene group substituted by a 5 or 6 atom heterocycle; R5 is a CH(R3)-COOR4 radical, wherein R3 is hydrogen, an OH or OR group, a saturated hydrocarbon group, a phenyl or benzyl radical and OR4 is hydrophile ester, or 5 or 6 membered heterocycle comprising several heteroatoms selected from a group consisting of nitrogen, sulphur and oxygen, with at least two nitrogene atoms, wherein said heterocycle is substitutable by an alkyl C1-C6, phenyl or benzyl radical. The use of the inventive compounds in the form of drugs, a pharmaceutical composition comprising said compounds, a pharmaceutically acceptable excipient, the use in conjunction of at least one type of cannabinoid derivative for potentiating the analgesic and antidepressant effect of the novel compounds of formula (I) and/or morphine or the derivatives thereof are also disclosed.
- -
-
Page/Page column 12
(2009/01/24)
-
- Synthesis, antifungal activities and 3D-QSAR study of N-(5-substituted-1,3,4-thiadiazol-2-yl)cyclopropanecarboxamides
-
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
-
scheme or table
p. 2782 - 2786
(2009/10/19)
-
- Phase transfer catalysts promoting the one-pot synthesis under ultrasonic irradiation and biological activity of n-(5-substituted-1,3,4-thiadiazole-2-yl)- N'-(5-methylisoxazoyl)-thiourea derivatives
-
Reaction of 2-amino-5-substitute-1,3,4-thiadiazoles with 5-methylisoxazoyl chloride and ammonium thiocyanate under the condition of solid-liquid phase-transfer catalysis using polyethylene glycol-600 (PEG-600) as the catalyst under ultrasonic irradiation yielded N-(5-substituted-1,3,4-thiadiazole-2-yl)- N'-(5-methylisoxazoyl)-thiourea derivatives 3a-1 in good-to-excellent yield. The chemical structure of all compounds was established by 1H NMR, FTIR, MS, and elemental analysis studies. Some of the compounds were investigated for fungicidal activity. The bioassay results indicated that some of these compounds exhibit moderate fungicidal activities.
- Xiaodong, Yang
-
p. 387 - 392
(2008/09/19)
-
- Polymer-supported dichlorophosphate: A recoverable new reagent for synthesis of 2-amino-1,3,4-thiadiazoles
-
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
-
p. 341 - 343
(2007/10/03)
-
- Thiadiazolyl quinazolones as potential antiviral and antihypertensive agents
-
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
-
p. 180 - 183
(2007/10/03)
-
- Pharmaceutically active pyrrolidine derivatives as bax inhibitors
-
The present invention is related to new substituted pyrrolidine derivatives of formula (I). Said compounds are preferably for use as pharmaceutically active compounds. Specifically, pyrrolidine derivatives of formula (I) are useful in the treatment and/or prevention of neurodegenerative disorders, diseases associated with polygultamine tracts, epilepsy, ischemia, infertility, cardiovascular disorders renal hypoxia, hepatitis and AIDS. Said pyrrolidine derivatives display a modulatory and most notably a down-regulating-up to an inhibitory-activity with respect to the cellular death agonist Bax and/or the activation pathways leading to Bax and allows therefore to block the release of cytochrome (c). The present invention is furthermore related to novel pharmaceutically activity substituted pyrrolidine derivatives as well as to methods of their preparation, wherein X is selected from the group consisting of O, S, CRR, NOR, NNRR; A is selected from the group consisting of —(C═O)—, —(C═O)—O—, —C(═NH)—, —(C═O)—NH—, —(C═S)—NH, —SO2-, —SO2NH—; —CH2-; B is either a group —(C═O)—NRR or represents a heterocyclic residue having the formula (II) wherein Q is NR, O or S; n is an integer selected of 0, 1 or 2; Y, Z and E form together with the 2 carbons to which they are attached a 5-6 membered aryl or heteroaryl ring.
- -
-
-
- Pharmaceutically active pyrrolidine derivatives
-
The present invention is related to pyrrolidine derivatives of formula (I). Said compounds are preferably for use as pharmaceutically active compounds. Specifically, pyrrolidine derivatives of formula (I) are useful in the treatment and/or prevention of premature labor, premature birth and dysmenorrhea. In particular, the present invention is related to pyrrolidine derivatives displaying a substantial modulatory, notably an antagonist activity of the oxytocin receptor. More preferably, said compounds are useful in the treatment and/or prevention of disease states mediated by oxytocin, including premature labor, premature birth and dysmenorrhea. The present invention is furthermore related to novel pyrrolidine derivatives as well as to methods of their preparation, wherein X is selected from the group consisting of CR6R7, NOR6, NNR6R7; A is selected from the group consisting of —(C═O)—, —(C═O)—O—, —C(═NH)—, —(C═O)—NH—, —(C═S)—NH, —SO22—, —SO2NH—, —CH2—,B is either a group —(C═O)—NR8R9 or represents a heterocyclic residue having the formula (a) wherein Q is NR10, O or S; n is an integer selected of 0, 1 or 2; Y, Z and E form together with the 2 carbons to which they are attached a 5-6 membered aryl or heteroaryl ring.
- -
-
-
- Synthesis of thiadiazolo-s-triazines for their antiviral activity based on QSAR studies
-
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
-
p. 2583 - 2588
(2007/10/03)
-
- Synthesis and biological activity of some new benzophenothiazines
-
Condensation of carboxylic acids with thiosemicarbazide in presence of conc. H2SO4 gives 2-amino-5-aralkyl-1,3,4-thiadiazoles 1 which on diazotization afford 5-aralkyl-1,3,4-thiadiazolyl-2-diazonium chlorides 2. Reaction of 2 with cold solution of β-naphthol in dilute NaOH furnishes α-(2-diazo-5-aralkyl-1,3,4-thiadiazolyl)-β-sodionaphthoxides 3 which on acidification with conc. HCl gives α-(2-diazo-5-aralkyl-1,3,4-thiadiazolyl)-β-naphthols 4. Reaction of 4 with p-anisidine gives α-(2-diazo-5-aralkyl-1,3,4-thiadiazolyl)-β-(p-anisidino) naphthalenes 5. Fusion of 5 with sulphur in presence of iodine results in 1-(2′-diazo-5′-aralkyl-1′,3′,4′- thiadiazolyl)-6-methoxy benzophenothiazines 6 in yields varying from 48% to 59%. The new compounds 6 have been screened for their antiviral and antifungal activities.
- Pandey,Negi,Joshi,Bajpai
-
p. 206 - 210
(2007/10/03)
-
- Process for producing N-biphenylmethylthiadiazoline derivative or salt thereof and intermediate for producing the same
-
Described is a process for producing an N-biphenyl-methylthiadiazoline derivative (7) in accordance with the reaction formula described below. According to the process of the present invention, it is possible to produce a compound (7) advantageously from the industrial viewpoint. STR1
- -
-
-
- Process for producing tetrazolylated biphenylmethane derivatives
-
The present invention relates to a process for producing a tetrazolylated biphenylmethane derivatives (6) or salts thereof in accordance with the below-described reaction scheme wherein R 1 represents an alkyl; R 2 represents H, etc.; Z represents a halogen, etc.; and A represents a cycloalkene, etc. According to the above process, a tetrazolylated biphenylmethane derivative can be industrially and advantageously produced with short steps.
- -
-
-
- LIQUID-CRYSTALLINE IMIDAZO-1,3,4-THIADIAZOLES. I. SYNTHESIS OF 2,6-DISUBSTITUTED IMIDAZO-1,3,4-THIADIAZOLES AND THEIR MESOMORPHOUS AND SPECTRAL CHARACTERISTICS
-
Derivatives of imidazo-1,3,4-thiadiazole possessing a wide temperature range of smectic mesophase were obtained.The introduction of the cyclohexane fragment into the imidazole part of the molecule promotes the appearance of the nematic mesophase.The structure of the new mesogens and of the intermediates in their synthesis were confirmed by the data from IR and (13)C and (1)H NMR spectroscopy.
- Torgova, S. I.,Abolin, A. G.,Karamysheva, L. A.,Ivashchenko, A. V.
-
p. 172 - 178
(2007/10/02)
-
- 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
-
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
-
p. 1689 - 1698
(2007/10/02)
-
- Convenient Synthesis of 2,7-Disubstituted 5H-1,3,4-Thiadiazolopyrimidin-5-ones and Related Compounds
-
2,7-Disubstituted 5H-1,3,4-thiadiazolopyrimidin-5-ones were synthesized from the reaction of 3-amino-6-methyl-2-thiouracil with carboxylic acid or from that of thiosemicarbazide with carboxylic acid and β-keto ester in the presence of phosphorus pentaoxide and methanesulfonic acid.The synthesis of related compounds is also described.
- Tsuji, Tadakazu,Takenaka, Keiko
-
p. 637 - 638
(2007/10/02)
-