1014-25-1

Basic information

• Product Name: 2-AMINO-5-(4-METHOXYPHENYL)-1,3,4-THIADIAZOLE
• Synonyms: 2-AMINO-5-(4-METHOXYPHENYL)-1,3,4-THIADIAZOLE;AKOS B014673;5-(4-METHOXYPHENYL)-1,3,4-THIADIAZOL-2-AMINE;5-(4-METHOXY-PHENYL)-[1,3,4]THIADIAZOL-2-YLAMINE;IFLAB-BB F1386-0072;BUTTPARK 24\04-30;ART-CHEM-BB B014673;TIMTEC-BB SBB000467
• CAS NO: 1014-25-1
• Molecular Formula: C₉H₉N₃OS
• Molecular Weight: 207.25
• Product Categories: Amines;Oxadiazoles & Thiadiazoles;API intermediates;Oxadiazoles & Thiadiazoles;Building Blocks;Heterocyclic Building Blocks;Thiadiazoles
• Mol File: 1014-25-1.mol
• Article Data: 73

Chemical Properties

• Melting Point: 185-187 °C
• Boiling Point: 393.1 °C at 760 mmHg
• Flash Point: 191.6 °C
• Appearance: /
• Density: 1.32 g/cm³
• Vapor Pressure: 2.18E-06mmHg at 25°C
• Refractive Index: 1.636
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• PKA: 3.37±0.10(Predicted)
• CAS DataBase Reference: 2-AMINO-5-(4-METHOXYPHENYL)-1,3,4-THIADIAZOLE(CAS DataBase Reference)
• NIST Chemistry Reference: 2-AMINO-5-(4-METHOXYPHENYL)-1,3,4-THIADIAZOLE(1014-25-1)
• EPA Substance Registry System: 2-AMINO-5-(4-METHOXYPHENYL)-1,3,4-THIADIAZOLE(1014-25-1)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 1014-25-1(Hazardous Substances Data)

Usage

Uses

2-Amino-5-(4-methoxyphenyl)-1,3,4-thiadiazole is a thiadiazole derivative that is potent and selective human adenosine A3 receptor antagonist. It is also used as a reactant in the synthesis of substituted thiadiazolyl(styryl)quinazolinones with anticonvulsant, sedative-hypnotic, and CNS depressant activities.

Synthesis Reference(s)

Journal of the American Chemical Society, 73, p. 906, 1951 DOI: 10.1021/ja01147a007

InChI:InChI=1/C9H9N3OS/c1-13-7-4-2-6(3-5-7)8-11-12-9(10)14-8/h2-5H,1H3,(H2,10,12)

Upstream product

• 54998-29-7 ethyl 4-methoxybenzimidate hydrochloride 
• 79-19-6 thiosemicarbazide 
• 96134-01-9 4-methoxy-N'-thiocarbamoyl-benzohydrazonic acid ethyl ester 
• 123-11-5 4-methoxy-benzaldehyde 
• 4334-74-1 (2E)-2-[(4-methoxyphenyl)methylidene]hydrazine-1-carbothioamide 
• 99-96-7 4-hydroxy-benzoic acid 
• 333-20-0 potassium thioacyanate 
• 19350-72-2 N'-(4-methoxybenzylidene)-4-methylbenzenesulfonohydrazide 
• 100-09-4 4-methoxybenzoic acid 
• 121-98-2 methyl 4-methoxybenzoate 
• 3290-99-1 4-methoxybenzoic acid hydrazide 
• 2290-65-5 trimethylsilyl isothiocyanate 
• 833-84-1 C₉H₁₁N₃O₂S 
• 100-07-2 4-methoxy-benzoyl chloride 

Downstream Products

• 16430-16-3 2-[5-(4-methoxy-phenyl)-[1,3,4]thiadiazol-2-ylamino]-ethanol 
• 109321-41-7 2-Chloro-N-[5-(4-methoxy-phenyl)-[1,3,4]thiadiazol-2-yl]-nicotinamide 
• 141421-47-8 7-Hydroxy-2-(4-methoxy-phenyl)-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one 
• 81516-40-7 7-methyl-2-(4-nitrophenyl)-5H-1,3,4-thiadiazolo<3,2-a>pyrimidin-5-one 
• 107125-28-0 N-(5-p-anisylthiadiazol-2-yl)benzoylacetamide 
• 92537-72-9 2-(4-Methoxy-phenyl)-7-oxo-7H-[1,3,4]thiadiazolo[3,2-a]pyrimidine-5-carboxylic acid ethyl ester 
• 83760-32-1 2-(p-anisyl)-6-carbethoxy-1,3,4-thiadiazolo<3,2-a>pyrimidin-5(H)-one 
• 107125-21-3 diethyl 5-p-anisylthiadiazol-2-ylaminomethylenemalonate 
• 158980-01-9 3-(4-Chloro-phenyl)-4-hydroxy-5-{(4-hydroxy-phenyl)-[5-(4-methoxy-phenyl)-3H-[1,3,4]thiadiazol-(2E)-ylideneamino]-methyl}-3H-thiazole-2-thione 
• 158980-05-3 3-(4-Chloro-phenyl)-4-hydroxy-5-{(4-methoxy-phenyl)-[5-(4-methoxy-phenyl)-3H-[1,3,4]thiadiazol-(2E)-ylideneamino]-methyl}-3H-thiazole-2-thione 
• 158979-99-8 4-Hydroxy-5-{(2-hydroxy-phenyl)-[5-(4-methoxy-phenyl)-3H-[1,3,4]thiadiazol-(2E)-ylideneamino]-methyl}-3-(4-methoxy-phenyl)-3H-thiazole-2-thione 
• 96425-18-2 2-(2'-hydroxyacetophenoneimino)-5-(p-anisyl)-1,3,4-thiadiazole 
• 201343-27-3 [1,3]dithiolan-2-ylidene-[5-(4-methoxy-phenyl)-[1,3,4]thiadiazol-2-yl]-amine 
• 103989-36-2 N-[(4-methoxy-phenyl)-[1,3,4]thiadiazol-2-yl]-acetamide 

Relevant articles and documents

Schiff base derivatives containing thiodiazole: Twisted molecular conformation avoiding π … π stacking promotion aggregation-induced emission enhancement

Three novel 2-(4-methoxyphenyl)-1, 3, 4-thiadiazole based Schiff base derivatives (T1-T3) had been synthesized and characterized by1H NMR,13C NMR, MS and IR. The spectroscopic properties of T1-T3 were investigated by UV–vis absorptio

Cyclization–oxidation of Benzylidenehydrazinecarbothioamides by FeCl3.6H2O or ZnCl2.6H2O Catalysts and Synthesis of New 1,3,4-Thiadiazolo-[3,2- α]Pyrimidines

We report new method for preparation of 2-amino-5-aryl-1,3,4-thiadiazoles by reaction of arylaldehyde with thiosemicarbazide and in the next step via cyclization of 2-aryl hydrazinecarbothioamide in the presence of ZnCl2.6H2O or FeCl3.6H2O. Also, in this research, new substituted 1,3,4-thiadiazolo-[3,2-α]pyrimidines were synthesized by the reaction of 2-amino-5-aryl-1,3,4-thiadiazoles derivatives with DMAD or DEAD in the presence of K2CO3 under reflux conditions. The FT-IR, 1H-NMR, 13C-NMR, elemental analysis and single- crystal X-ray analysis confirm the structures of the products.

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.

1,2,4-Triazole-conjugated 1,3,4-thiadiazole hybrid scaffolds: A potent ameliorant of carrageenan-induced inflammation by lessening proinflammatory mediators

Inflammation acts as an alarming signal for the progression of various biological complications. Various reports in the literature have revealed that heterocycle-containing synthetic compounds have a restorative capability against acute and chronic inflammatory stages. In the current study, we synthesized a series of 1,2,4-triazole-conjugated 1,3,4-thiadiazole hybrid scaffolds and evaluated their impacts against carrageenan-induced paw edema and proinflammatory markers in Wistar rats. Further, 3D QSAR study (three-dimensional quantitative structure–activity relationships), ADMET (absorption, distribution, metabolism, and excretion) profiling, and docking studies were performed to determine the possible mechanism of the action of the derivatives. The study shows that the most active derivatives, 13f and 13g, have optimal logP, a higher anti-inflammatory activity score, and poor metabolism at various sites of cytochrome P450. The docking studies recommended that the synthesized compounds have a similar affinity as the ligands A307, 63X, and S58 to interact with tumor necrosis factor-α, COX-1, and COX-2. So, these molecules will definitely hold a promise for the future drug development initiative.

Synthesis of 2-amino-5-aryl-1,3,4-thiadiazoles and their condensed analogs with the use of aromatic nitriles

Aromatic nitriles are found to readily react with thiosemicarzide and 4-amino-3-methyl-1,2,4-triazol-5-thione in a solution of polyphosphoric acid to give corresponding 2-amino-5-aryl-1,3,4-thiadiazoles. - Keywords: aromatic nitriles, polyphosphoric acid,

Synthesis, bioevaluation and docking study of 5-substitutedphenyl-1,3,4-thiadiazole-based hydroxamic acids as histone deacetylase inhibitors and antitumor agents

Since the first histone deacetylase (HDAC) inhibitor (Zolinza, widely known as suberoylanilide hydroxamic acid; SAHA) was approved by the Food and Drug Administration for the treatment of T-cell lymphoma in 2006, the search for newer HDAC inhibitors has attracted a great deal of interest of medicinal chemists worldwide. As a continuity of our ongoing research in this area, we designed and synthesized a series of 5-substitutedphenyl-1,3,4-thiadiazole-based hydroxamic acids as analogues of SAHA and evaluated their biological activities. A number of compounds in this series, for example, N1-hydroxy-N8-(5-(2-chlorophenyl)-1,3,4-thiadiazol-2-yl)octandiamide (5b), N1-hydroxy-N8-(5-(3-chlorophenyl-1,3,4-thiadiazol-2-yl)octandiamide (5c) and N1-hydroxy-N8-(5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl)octandiamide (5d), were found to possess potent anticancer cytotoxicity and HDAC inhibition effects. Compounds 5b-d were generally two- to five-fold more potent in terms of cytotoxicity compared to SAHA against five cancer cell lines tested. Docking studies revealed that these hydroxamic acid displayed higher affinities than SAHA toward HDAC8.

Synthesis and antiviral activity of novel 1,3,4-thiadiazole inhibitors of DDX3x

The human ATPase/RNA helicase X-linked DEAD-box polypeptide 3 (DDX3X) emerged as a novel therapeutic target in the fight against both infectious diseases and cancer. Herein, a new family of DDX3X inhibitors was designed, synthesized, and tested for its inhibitory action on the ATPase activity of the enzyme. The potential use of the most promising derivatives it has been investigated by evaluating their anti-HIV-1 effects, revealing inhibitory activities in the low micromolar range. A preliminary ADME analysis demonstrated high metabolic stability and good aqueous solubility. The promising biological profile, together with the suitable in vitro pharmacokinetic properties, make these novel compounds a very good starting point for further development.

Aryl or heteroaryl substituted thiadiazole compound and antibacterial application thereof

The invention belongs to the technical field of medicines, and particularly relates to an aryl or heteroaryl substituted thiadiazole compound, a preparation method and application thereof as an antibacterial drug. The compound is represented by formula (1

Diversity-Oriented Synthesis of 1,2,4-Triazols, 1,3,4-Thiadiazols, and 1,3,4-Selenadiazoles from N-Tosylhydrazones

The diversity-oriented synthesis of 1,2,4-triazols, 1,3,4-thiadiazols, and 1,3,4-selenadiazoles from N-tosylhydrazones was developed, and the reactions were general for a wide range of substrates, in which NH2CN, KOCN, KSCN, and KSeCN were used as odorless sources. Two different pathways were proposed, and N-tosylhydrazonoyl chlorides were formed in situ in the presence of NCS.

1,3,4-Thiadiazole-Containing Azo Dyes: Synthesis, Spectroscopic Properties and Molecular Structure

Three series of azo dyes derived from 2-amino-5-aryl-1,3,4-thiadiazoles and aniline, N,N-dimethylaniline and phenol were synthesized in high yields by a conventional diazotization-coupling sequence. The chemical structures of the prepared compounds were confirmed by 1H-NMR, 13C-NMR, IR, UV-Vis spectroscopy, mass spectrometry and elemental analysis. In addition, the X-ray single crystal structure of a representative azo dye was presented. For explicit determination of the influence of a substituent on radiation absorption in UV-Vis range, time-dependent density functional theory calculations were performed.