Tasisulam

Tasisulam is a small molecule antitumor agent that inhibits mitotic progression and induces vascular normalization. Tasisulam induces apoptosis via the intrinsic pathway[1].

Tasisulam has been used in trials studying the treatment and basic science of Melanoma, Lymphoma, Solid Tumors, Breast Cancer, and Ovarian Cancer, among others.|Tasisulam is an acyl-sulfonamide with potential antineoplastic activity. Selectively toxic towards tumor cells, tasisulam appears to induce tumor cell apoptosis by a mitochondrial-targeted mechanism involving the loss of mitochondrial membrane potential and induction of reactive oxygen species (ROS). In combination with an angiogenesis inhibitor, this agent may exhibit synergistic antiangiogenic activity.

0.5 mmol (0.0955 g) of 2, 5-dichlorobenzoic acid, 0.75 mmol (0.2011 g) of 2-bromothiophenesulfonyl azide and 0.025 mmol (0.0086 g) of octacarbyldicobalt were weighed, respectively.Add to a 25 mL reaction tube;Then, 4 mL of acetonitrile solvent, 100 μl of t-butyl isocyanide measured by a micro syringe was sequentially added to the above reactor, and the whole reaction system was stirred at 80 ° C for 4 hours;After the completion of the reaction, the mixture was concentrated by rotary evaporation, and the mixture was applied and separated by column chromatography (column separation conditions: 200-300 mesh silica gel powder, mobile phase ethyl acetate: petroleum ether = 1:4, yielding 0.1583 g The object product was obtained as a white solid in a yield of 76percent.DCM (2.0 mL) was added to a 20 mL vial containing DMAP (3.81 mg, 0.031 mmol), 2-chloro-1-methylpyridin-1-ium iodide (0.191 g, 0.748 mmol), 2, 4-dichlorobenzoic acid (0.119 g, 0.623 mmol), 5-bromothiophene-2-sulfonamide (0.302 g, 1.25 mmol) at rt. After stirring for 5 min, TEA (0.261 ml, 1.869 mmol) was slowly added to the reaction mixture. The reaction was stirred at rt for 1 h. The reaction solvent was concentrated under vacuum and the crude residue was taken up in ethyl acetate, washed with 1N HCl (1 mL), water, and brine. The ethyl acetate layer was separated, dried (Na2SO4), filtered and concentrated. The crude material was purified by silica gel flash column chromatography eluting with ethyl acetate in hexane from 0 to 30percent to give the desired product (0.168 g, 65percent) as colorless crystals:

Molecular Weight:415.1
XLogP3:4.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:412.83495
Monoisotopic Mass:412.83495
Topological Polar Surface Area:99.9
Heavy Atom Count:20
Complexity:471
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes