137-64-4Relevant 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%.
TRIAZOLONE COMPOUNDS AS mPGES-1 INHIBITORS
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Page/Page column 98; 99, (2014/01/08)
The present disclosure is directed to compounds of formula (I), and pharmaceutically acceptable salts thereof, as mPGES-1 inhibitors. These compounds are inhibitors of the microsomal prostaglandin E synthase-1 (mPGES-1) enzyme and are therefore useful in the treatment of pain and/or inflammation from a variety of diseases or conditions, such as asthma, osteoarthritis, rheumatoid arthritis, acute or chronic pain and neurodegenerative diseases.
PIPERAZINE DERIVATIVES AS GLYT1 INHIBITORS
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Page/Page column 45, (2010/11/23)
The invention provides a compound of formula (I) or a salt or solvate thereof: wherein R1, n, X, Y and Z are as defined in the specification, and uses of such compounds. The compounds inhibit GlyT1 transporters and are useful in the treatment of certain neurological and neuropsychiatric disorders, including schizophrenia.
