18686-81-2

Basic information

• Product Name: 1H-Tetrazole-5(4H)-thione
• Synonyms: 1,2-Dihydro-5H-tetrazole-5-thione;1H-Tetrazole-5(4H)-thione;1H-Tetrazole-5-thiol
• CAS NO: 18686-81-2
• Molecular Formula: CH₂N₄S
• Molecular Weight: 102.1184
• Mol File: 18686-81-2.mol
• Article Data: 6

Chemical Properties

• Boiling Point: 105.866 °C at 760 mmHg
• Flash Point: 17.828 °C
• Appearance: /
• Density: 2.172 g/cm³
• Vapor Pressure: 28.99mmHg at 25°C
• Refractive Index: 2.041
• CAS DataBase Reference: 1H-Tetrazole-5(4H)-thione(CAS DataBase Reference)
• NIST Chemistry Reference: 1H-Tetrazole-5(4H)-thione(18686-81-2)
• EPA Substance Registry System: 1H-Tetrazole-5(4H)-thione(18686-81-2)

Safety Data

• Hazardous Substances Data: 18686-81-2(Hazardous Substances Data)

Usage

Uses

2H-Tetrazole-5-thiol is an intermediate for the synthesis of (6R-trans)-7-Amino-8-oxo-3-[(1H-tetrazol-5-ylthio)methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic Acid (A618830), which is an impurity of Cefoperazone (C242900). Cefoperazone impurity D.

InChI:InChI=1/CH2N4S/c6-1-2-4-5-3-1/h(H2,2,3,4,5,6)

Upstream product

• 29515-99-9 5-methylsulfanyl-1H-tetrazole 

Downstream Products

• 1359835-06-5 C₂₃H₁₅N₅O₃S₂ 
• 1359834-33-5 N-(3-(1H-tetrazol-5-ylthio)-4-hydroxynaphthalen-1-yl)biphenyl-4-sulfonamide 
• 1359835-08-7 C₂₁H₁₃N₅O₃S₃ 
• 1359834-34-6 N-(3-(1H-tetrazol-5-ylthio)-4-hydroxynaphthalen-1-yl)-5-phenylthiophene-2-sulfonamide 
• 1359835-18-9 C₂₃H₁₅N₅O₄S₂ 
• 1359834-39-1 N-(3-(1H-tetrazol-5-ylthio)-4-hydroxynaphthalen-1-yl)-4-phenoxybenzenesulfonamide 
• 1359835-16-7 C₂₃H₁₄FN₅O₃S₂ 
• 1359834-38-0 N-(3-(1H-tetrazol-5-ylthio)-4-hydroxynaphthalen-1-yl)-4'-fluorobiphenyl-4-sulfonamide 
• 1359835-12-3 C₂₃H₂₁N₅O₃S₂ 
• 1359834-36-8 N-(3-(1H-tetrazol-5-ylthio)-4-hydroxynaphthalen-1-yl)-4-cyclohexylbenzenesulfonamide 
• 1359835-14-5 C₂₄H₁₇N₅O₄S₂ 
• 1359834-37-9 N-(3-(1H-tetrazol-5-ylthio)-4-hydroxynaphthalen-1-yl)-4'-methoxybiphenyl-4-sulfonamide 
• 1359835-22-5 C₂₂H₂₁N₅O₃S₂ 
• 1359834-41-5 N-(3-(1H-tetrazol-5-ylthio)-4-hydroxynaphthalen-1-yl)-4-pentylbenzenesulfonamide 

Relevant articles and documents

HINDERED DISULFIDE DRUG CONJUGATES

The invention relates generally to disulfide drug conjugates wherein a linker comprising a sulfur-bearing carbon atom substituted with at least one hydrocarbyl or substituted hydrocarbyl is conjugated by a disulfide bond to a cysteine sulfur atom of a targeting carrier, and wherein the linker is further conjugated to a drug moiety. The invention further relates to activated linker-drug conjugates suitable for conjugation to a targeting carrier by a disulfide bond. The invention further relates to methods for preparing hindered disulfide drug conjugates.

Discovery and synthesis of hydronaphthoquinones as novel proteasome inhibitors

Screening efforts led to the identification of PI-8182 (1), an inhibitor of the chymotrypsin-like (CT-L) activity of the proteasome. Compound 1 contains a hydronaphthoquinone pharmacophore with a thioglycolic acid side chain at position 2 and thiophene sulfonamide at position 4. An efficient synthetic route to the hydronaphthoquinone sulfonamide scaffold was developed, and compound 1 was synthesized in-house to confirm the structure and activity (IC50 = 3.0 ± 1.6 μM [n = 25]). Novel hydronaphthoquinone derivatives of 1 were designed, synthesized, and evaluated as proteasome inhibitors. The structure-activity relationship (SAR) guided synthesis of more than 170 derivatives revealed that the thioglycolic acid side chain is required and the carboxylic acid group of this side chain is critical to the CT-L inhibitory activity of compound 1. Furthermore, replacement of the carboxylic acid with carboxylic acid isosteres such as tetrazole or triazole greatly improves potency. Compounds with a thio-tetrazole or thio-triazole side chain in position 2, where the thiophene was replaced by hydrophobic aryl moieties, were the most active compounds with up to 20-fold greater CT-L inhibition than compound 1 (compounds 15e, 15f, 15h, 15j, IC50 values around 200 nM, and compound 29, IC50 = 150 nM). The synthetic iterations described here not only led to improving potency in vitro but also resulted in the identification of compounds that are more active such as 39 (IC50 = 0.44 to 1.01 μM) than 1 (IC50 = 3.54 to 7.22 μM) at inhibiting the proteasome CT-L activity in intact breast cancer cells. Treatment with 39 also resulted in the accumulation of ubiquitinated cellular proteins and inhibition of tumor cell proliferation of breast cancer cells. The hit 1 and its analogue 39 inhibited proteasome CT-L activity irreversibly.

Cephalosporin displacement reaction

The present invention is directed to a process for the displacement of the acetoxy group of a cephalosporanic acid by a sulfur nucleophile, in an organic solvent and under essentially anhydrous conditions.