81721-87-1Relevant articles and documents
Synthesis of N-(3,4,10,10a-Tetrahydro-2H-1,9-dioxa-4aazaphenanthrene- 6-yl)alkyl and Aryl Sulfonamides
Rajachandrasekhar,Vineel, B. George,Venkataiaha,Dubey
, p. 5263 - 5267 (2014)
Commercially available 2-amino-4-nitrophenol (1) was treated with chloroacetyl chloride to obtain 6-nitro-4H-benzo[1,4]oxazine-3,2- one (2). The latter was reacted with ethyl 3-bromopropionate to obtain 3-(6-nitro-3-oxo-2,3-dihydrobenzo[1,4]oxazine-4-yl)propionic acid ethyl ester (3), which on treatment with lithium aluminiumhydride gave 6-nitro-3,4,10,10a-tetrahydro-2H-1,9-dioxo-4aazaphenanthrene (4) by reductive cyclization. Compound, 4 was treated with H2/Pd-C containing di-tert-butyldicarbonate (Boc)2O in THF to obtain the (3,4,10,10a-tetrahydro-2H-1,9-dioxa-4a-azaphenanthrene-6-yl)carbamic acid tert-butyl ester (5). The latter, on treatment with alkyl or arylsulfonyl chlorides in the presence of NaH gave N-(3,4,10,10a-tetrahydro-2H-1,9-dioxa-4a-azaphenanthrene-6-yl) alkyl or aryl sulfonamide-N1-carbamic acid tert-butyl ester (6). N-Boc group of 6 was de-protected with Cs2CO3/imidazole in acetonitrile to give the title compounds N-(3,4,10,10a-tetrahydro-2H-1,9-dioxa-4a-azaphenanthrene-6-yl) alkyl or aryl sulfonamides (7) as potential antibacterial agents. All the new products obtained in the above sequences of reactions have been adequately characterized by spectral data.
Discovery of selective and orally bioavailable protein kinase Cθ (PKCθ) inhibitors from a fragment hit
George, Dawn M.,Breinlinger, Eric C.,Friedman, Michael,Zhang, Yang,Wang, Jianfei,Argiriadi, Maria,Bansal-Pakala, Pratima,Barth, Martine,Duignan, David B.,Honore, Prisca,Lang, Qingyu,Mittelstadt, Scott,Potin, Dominique,Rundell, Lian,Edmunds, Jeremy J.
supporting information, p. 222 - 236 (2015/03/03)
Protein kinase Cθ (PKCθ) regulates a key step in the activation of T cells. On the basis of its mechanism of action, inhibition of this kinase is hypothesized to serve as an effective therapy for autoimmune diseases such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis. Herein, the discovery of a small molecule PKCθ inhibitor is described, starting from a fragment hit 1 and advancing to compound 41 through the use of structure-based drug design. Compound 41 demonstrates excellent in vitro activity, good oral pharmacokinetics, and efficacy in both an acute in vivo mechanistic model and a chronic in vivo disease model but suffers from tolerability issues upon chronic dosing.
Identification of 3-hydroxy-4[3,4-dihydro-3-oxo-2H-1,4-benzoxazin-4-yl]-2,2-dimethyldihydro-2H-benzopyran derivatives as potassium channel activators and anti-inflammatory agents
Bano, Mohsina,Barot, Kuldipsinh P.,Jain, Shailesh V.,Ghate, Manjunath D.
, p. 3008 - 3020 (2015/03/18)
The present study described the design, synthesis and identification of 3-hydroxy-4[3,4-dihydro-3-oxo-2H-1,4-benzoxazin-4-yl]-2,2-dimethyldihydro-2H-benzopyran derivatives. Their biological activity was tested for KATP channel opener as antihypertensives, COX-1 and COX-2 activity. The results were compared with the activity of cromakalim, ibuprofen and celecoxib. The study aimed at exploring the influence of introduction of a benzoxazine substituent at position 6 of various derivatives of benzopyrans in order to improve biological activity. Several compounds were found to be equipotent or even more potent than cromakalim. Out of these nitro-substituted benzopyrans, nitro substitution at benzoxazino group possessed potent antihypertensive activity in the R/S isomers. With amino derivatives, activity remains constant when compared with standard cromakalim. Similarly, compounds 17b, 17c, 17e and 17h have exhibited around 40 % inhibition of COX-1 as compared to the inhibition of COX-2. Only two compounds 17g and 17i exhibited effective inhibition more than 50 % of COX-2 compared with the inhibition of COX-1 at a concentration of 0.3 mg/ml.
