37098-75-2Relevant articles and documents
Nucleophilic Aromatic Substitutions of 2-Halo-5-(sulfamoyl)benzoic Acids and N, O-Bis-alkylation via Phase Transfer Catalysis: Synthesis of RoRγInverse Agonist GSK2981278A
Barcan, Gregg A.,Conde, Jose J.,Mokhallalati, Mohamed K.,Nilson, Mark G.,Xie, Shiping,Allen, C. Liana,Andemichael, Yemane W.,Calandra, Nicholas A.,Leitch, David C.,Li, Ling,Morris, Michael J.
, p. 1396 - 1406 (2019/07/04)
GSK2981278A (1) is a RORγinverse agonist used as a potential topical nonsteroidal therapy for psoriasis. New synthesis of 1 was developed based on a SNAr reaction of (tetrahydro-2H-pyran-4-yl)methanol with an aryl halide intermediate, prepared from 2-halobenzoic acids. The dianion underwent in situ N,O-bis-isobutylation, followed by a reduction to provide 1. The new route eliminated a genotoxic tosylate of (tetrahydro-2H-pyran-4-yl)methanol and a difficult reductive amination from the original synthesis starting from methyl salicylate. A primary version of the route has been scaled up to deliver 125 kg of 1. However, the heating of a strong base in DMSO for an extended period during the bis-alkylation was found to be a safety concern for manufacturing. A safer and greener process was then developed utilizing a facile N,O-bis-alkylation, which was conducted under phase transfer conditions with mild bases such as potassium carbonate and in green solvents such as water. The concise four stage sequence from 2-halobenzoic acids to GSK2981278A (1) had an overall yield of 41%.
Synthesis of sulfamoylbenzamide derivatives as HBV capsid assembly effector
Sari, Ozkan,Boucle, Sebastien,Cox, Bryan D.,Ozturk, Tugba,Russell, Olivia Ollinger,Bassit, Leda,Amblard, Franck,Schinazi, Raymond F.
, p. 407 - 421 (2017/07/10)
The synthesis of novel series of sulfamoylbenzamides as HBV capsid assembly effector is reported. The structure was divided into five parts which were independently modified as part of our lead optimization. All synthesized compounds were evaluated for their anti-HBV activity and toxicity in human hepatocytes, lymphocytes and other cells. Additionally, we assessed their effect on HBV cccDNA formation in an HBeAg reporter cell-based assay. Among the 27 compounds reported, several analogs exhibited submicromolar activities and significant reduction of HBeAg secretion. Selected compounds were studied under negative-stain electron microscopy for their ability to disrupt the HBV capsid formation. Structures were modeled into a binding site recently identified in the HBV capsid protein for similar molecules to rationalize the structure-activity relationships for this family of compounds.
ELIMINATION OF HEPATITIS B VIRUS WITH ANTIVIRAL AGENTS
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Page/Page column 84; 85, (2017/09/27)
The present invention is directed to compounds, compositions and methods for preventing, treating or curing Hepatitis B (HBV) infection in human subjects or other animal hosts. The compounds are as also pharmaceutically acceptable, salts, prodrugs, and other derivatives thereof as pharmaceutical compositions and methods for treatment, prevention or eradication of HBV infection.
