98-75-9

Usage

InChI:InChI=1/C5H8N4O3S2/c1-2-3(10)7-4-8-9-5(13-4)14(6,11)12/h2H2,1H3,(H2,6,11,12)(H,7,8,10)

Upstream product

• 14949-00-9 5-amino-1, 3, 4-thiadiazole-2-sulfonamide 
• 123-62-6 propionic acid anhydride 
• 32873-56-6 2-acetylamino-5-mercapto-1,3,4-thiadiazole 
• 120208-98-2 5-amino-2-sulfamoyl-1,3,4-thiadiazole monohydrochloride 
• 79-03-8 propionyl chloride 

Relevant academic research and scientific papers

CARBONIC ANHYDRASE INHIBITORS AND ANTIBIOTICS AGAINST MULTIDRUG RESISTANT BACTERIA

The invention described herein generally relates to novel therapeutic compounds, and in particular to carbonic anhydrase inhibitors as a narrow spectrum antibiotics against drug resistant bacteria and methods for treating those infection diseases in mammals using the described carbonic anhydrase inhibitors or a pharmaceutical formulation thereof.

Structural Basis of Nanomolar Inhibition of Tumor-Associated Carbonic Anhydrase IX: X-Ray Crystallographic and Inhibition Study of Lipophilic Inhibitors with Acetazolamide Backbone

This study provides a structure-Activity relationship study of a series of lipophilic carbonic anhydrase (CA) inhibitors with an acetazolamide backbone. The inhibitors were tested against the tumor-expressed CA isozyme IX (CA IX), and the cytosolic CA I, CA II, and membrane-bound CA IV. The study identified several low nanomolar potent inhibitors against CA IX, with lipophilicities spanning two log units. Very potent pan-inhibitors with nanomolar potency against CA IX and sub-nanomolar potency against CA II and CA IV, and with potency against CA I one order of magnitude better than the parent acetazolamide 1 were also identified in this study, together with compounds that displayed selectivity against membrane-bound CA IV. A comprehensive X-ray crystallographic study (12 crystal structures), involving both CA II and a soluble CA IX mimetic (CA IX-mimic), revealed the structural basis of this particular inhibition profile and laid the foundation for further developments toward more potent and selective inhibitors for the tumor-expressed CA IX.

Optimization of Acetazolamide-Based Scaffold as Potent Inhibitors of Vancomycin-Resistant Enterococcus

Vancomycin-resistant enterococci (VRE) are the second leading cause of hospital-acquired infections (HAIs) attributed to a drug-resistant bacterium in the United States, and resistance to the frontline treatments is well documented. To combat VRE, we have repurposed the FDA-approved carbonic anhydrase drug acetazolamide to design potent antienterococcal agents. Through structure-activity relationship optimization we have arrived at two leads possessing improved potency against clinical VRE strains from MIC = 2 μg/mL (acetazolamide) to MIC = 0.007 μg/mL (22) and 1 μg/mL (26). Physicochemical properties were modified to design leads that have either high oral bioavailability to treat systemic infections or low intestinal permeability to treat VRE infections in the gastrointestinal tract. Our data suggest the intracellular targets for the molecules are putative α-carbonic and γ-carbonic anhydrases, and homology modeling and molecular dynamics simulations were performed. Together, this study presents potential anti-VRE therapeutic options to provide alternatives for problematic VRE infections.

Acetazolamide-based fungal chitinase inhibitors

Chitin is an essential structural component of the fungal cell wall. Chitinases are thought to be important for fungal cell wall remodelling, and inhibition of these enzymes has been proposed as a potential strategy for development of novel anti-fungals. The fungal pathogen Aspergillus fumigatus possesses two distinct multi-gene chitinase families. Here we explore acetazolamide as a chemical scaffold for the inhibition of an A. fumigatus 'plant-type' chitinase. A co-crystal structure of AfChiA1 with acetazolamide was used to guide synthesis and screening of acetazolamide analogues that yielded SAR in agreement with these structural data. Although acetazolamide and its analogues are weak inhibitors of the enzyme, they have a high ligand efficiency and as such are interesting leads for future inhibitor development.

Combination of two active substances

The invention concerns the use of a compound with diuretic properties and of a magnesium supplementation in the form of magnesium monoaspartate hydrochloride, magnesium oxide, magnesium hydroxide or magnesium carbonate, and optionally of a potassium supplementation, and pharmaceutical preparations comprising a compound with diuretic properties and a magnesium supplementation in the form of magnesium monoasparate hydrochloride, magnesium oxide, magnesium hydroxide, or magnesium carbonate and optionally a potassium supplementation.

Non-classical topical treatment for glaucoma

A topical composition for eye treatment of glaucoma, comprising a small but pharmaceutically effective amount of a non-classical carbonic anhydrase inhibitor. The most preferred compound is methyl acetazolamide. The invention also relates to a method of topically treating glaucoma with eye drops of a non-classical carbonic anhydrase inhibitor to reduce intraocular pressure.

Non-classical topical treatment for glaucoma using n-substituted sulfonamides

A topical composition for eye treatment of glaucoma, comprising a small but pharmaceutically effective amount of a non-classical carbonic anhydrase inhibitor. The most preferred compound is methyl acetazolamide. The invention also relates to a method of topically treating glaucoma with eye drops of a non-classical carbonic anhydrase inhibitor to reduce intraocular pressure.

Non-classical topical treatment for glaucoma

A topical composition for eye treatment of glaucoma, comprising a small but pharmaceutically effective amount of a non-classical carbonic anhydrase inhibitor. The most preferred compound is methyl acetazolamide. The invention also relates to a method of topically treating glaucoma with eye drops of a non-classical carbonic anhydrase inhibitor to reduce intraocular pressure.

5-Acylamino-1,3,4-thiadiazole-2-sulfonamides and use as herbicides

Compounds which are useful as selective herbicides have the general structural formula STR1 in which R1 and R2 are selected from hydrogen, and lower alkyl, alkenyl, alkylene and alkoxy structures and together possess a total of 1 to 6 carbon atoms when R3 is ethyl, propyl, isopropyl, cyclopropyl, methoxy or tert-butyl.