- PYRIDINYL BASED APOPTOSIS SIGNAL-REGULATION KINASE INHIBITORS
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Apoptosis signal-regulating kinase 1 (ASK1) activation and signaling have been reported to play an important role in a broad range of diseases including neurodegenerative, cardiovascular, inflammatory, autoimmunity and metabolic disorders. Disclosed herein is the synthesis of pyridinyl derived therapeutic agents that function as inhibitors of ASK 1 as well as their pharmaceutical compositions and methods of use.
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Paragraph 0445
(2018/09/12)
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- Concise synthesis of 22-hydroxyacuminatine, cytotoxic camptothecinoid from Camptotheca acuminata, by pyridone benzannulation
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A short, efficient synthesis of 22-hydroxyacuminatine, starting from a readily accessible hydroxy pyridone, is presented; key steps include a Heck coupling with methyl pentadienoate, a flash vacuum pyrolytic cyclization, and a Friedlaender condensation. The Royal Society of Chemistry 2006.
- Babjak, Matej,Kanazawa, Alice,Anderson, Regan J.,Greene, Andrew E.
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p. 407 - 409
(2007/10/03)
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- 1,3-Dipolar cycloaddition chemistry for the preparation of novel indolizinone-based compounds
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Starting from methyl 5-oxo-6-trifluoromethanesulfonyloxy-1,2,3,5- tetrahydroindolizine-8-carboxylate, obtained by a Rh(II)-catalyzed 1,3-dipolar cycloaddition reaction of 1-(2-benzenesulfonyl-2-diazoacetyl)pyrrolidin-2-one and methyl acrylate, several indolo- and furano-fused indolizinones were efficiently prepared. In the first case, a palladium-mediated C-N coupling of the triflate with a variety of substituted anilines provided the desired methyl 5-oxo-6-(arylamino)-1,2,3,5-tetrahydroindolizine-8-carboxylates in high yield. Methyl 6-(2-bromophenylamino)-5-oxo-1,2,3,5-tetrahydroindolizine-8-carboxylate as well as its decarboxylated analogue, 6-(2-bromophenylamino)-2,3-dihydro-1H- indolizin-5-one, were synthesized in excellent yield and were found to undergo an intramolecular Heck cyclization to give 1,2,3,6-tetrahydroindolizino[6,7-b] indol-5-ones. To prepare furano-fused indolizinones, methyl 6-hydroxy-5-oxo-1,2, 3,5-tetrahydroindolizine-8-carboxylate was etherified with different allyl halides, and the resultant allyl ethers were subjected to a thermal Claisen rearrangement to give the corresponding methyl 7-allyl-6-hydroxy-5-oxo-1,2,3,4- tetrahydroindolizine-8-carboxylates. Cyclization under Wacker oxidation conditions afforded methyl 2-methyl-8-oxo-5,6,7,8-tetrahydro-1-oxa-7a-aza-s- indacene-4-carboxylates in near-quantitative yield.
- Mmutlane, Edwin M.,Harris, Joel M.,Padwa, Albert
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p. 8055 - 8063
(2007/10/03)
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