Protionamide (prothionamide) is a drug /medication of the antiarrhythmic class used in the treatment of cardiac arrhythmias and tuberculosis; has also been tested for use in the treatment of leprosy. It is classified by the Vaughan Williams classification system as class Ia; thus it is a sodium channel blocker of cardiomyocytes. In addition to blocking the INa current, it inhibits the IKr rectifier K+ current.

Physicochemical Properties

Molecular Formula	C9H12N2S
Molecular Weight	180.27
Exact Mass	180.072
Elemental Analysis	C, 59.97; H, 6.71; N, 15.54; S, 17.78
CAS #	14222-60-7
Related CAS #	Prothionamide-d5;1330261-26-1
PubChem CID	666418
Appearance	Light yellow to yellow solid powder
Density	1.1±0.1 g/cm3
Boiling Point	310.4±44.0 °C at 760 mmHg
Melting Point	140ºC
Flash Point	141.5±28.4 °C
Vapour Pressure	0.0±0.7 mmHg at 25°C
Index of Refraction	1.607
LogP	1.75
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	2
Rotatable Bond Count	3
Heavy Atom Count	12
Complexity	159
Defined Atom Stereocenter Count	0
SMILES	S=C(C1=CC(CCC)=NC=C1)N
InChi Key	VRDIULHPQTYCLN-UHFFFAOYSA-N
InChi Code	InChI=1S/C9H12N2S/c1-2-3-8-6-7(9(10)12)4-5-11-8/h4-6H,2-3H2,1H3,(H2,10,12)
Chemical Name	2-propylpyridine-4-carbothioamide
Synonyms	2-Propyl-4-pyridinecarbothioamide; 2-Propyl-4-thiocarbamoylpyridine
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

References

[1]. Mechanism of thioamide drug action against tuberculosis and leprosy.J Exp Med. 2007 Jan 22;204(1):73-8. [2]. . A clinical trial of ethionamide and prothionamide for\ntreatment of lepromatous leprosy. Am J Trop Med Hyg. 2006\nMar;74(3):457-61.

Additional Infomation

Prothionamide is a member of pyridines. Prothionamide has been used in trials studying the treatment of MDR-TB and HIV Infections. Protionamide is a thioamide derivative with antitubercular activity. Protionamide forms a covalent adduct with bacterial nicotinamide adenine dinucleotide (NAD), PTH-NAD, which competitively inhibits 2-trans-enoyl-ACP reductase (inhA), an enzyme essential for mycolic acid synthesis. This results in increased cell wall permeability and decreased resistance against cell injury eventually leading to cell lysis. Mycolic acids, long-chain fatty acids, are essential mycobacterial cell wall components and play a key role in resistance to cell injury and mycobacterial virulence. Antitubercular agent similar in action and side effects to ETHIONAMIDE. It is used mostly in combination with other agents.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~554.72 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (13.87 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (13.87 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	5.5472 mL	27.7362 mL	55.4723 mL
	5 mM	1.1094 mL	5.5472 mL	11.0945 mL
	10 mM	0.5547 mL	2.7736 mL	5.5472 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.