4355-15-1Relevant articles and documents
A 2, 4 - dioxo -3 - aza spiro - [5, 5] undecane - 1, 5 - dinitrile preparation method (by machine translation)
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Paragraph 0009; 0035; 0036; 0038; 0040; 0041; 0043; 0045, (2019/03/08)
The present invention provides a 2, 4 - dioxo - 3 - aza-spiro - [5, 5] undecane - 1, 5 - dinitrile preparation method, comprises the following steps: ammonia methanol solution dropping to cyclohexanone and cyanoacetic acid methyl ester in the mixed solution of, thermal insulation reaction, a 2, 4 - dioxo - 3 - aza-spiro - [5, 5] undecane - 1, 5 - [...] solution; then adding water mix, dropping a sulfuric acid solution, thermal insulation reaction, separation, washing, shall be 2, 4 - dioxo - 3 - aza-spiro - [5, 5] undecane - 1, 5 - a dinitrile. The invention provides a 2, 4 - dioxo - 3 - aza-spiro - [5, 5] undecane - 1, 5 - dinitrile preparation method, the process is simple, low in energy consumption, less side reaction, the product yield can reach 98.5% or more, the product of the ammonia nitrogen in the content of less than 0.3%, cyanoacetate of methyl acetate and the unit consumption of 0.85 - 1.1 t/t, is suitable for large-scale industrial production. (by machine translation)
Synthesis of 4-substituted 3,5-dicyano-2,6-piperidinediones using lithium nitride as a convenient source of ammonia
Wu, Liqiang,Yang, Chunguang,Yang, Liming,Yang, Lijuan
experimental part, p. 977 - 982 (2009/09/30)
A simple and efficient one-pot synthesis of 4-substituted-3,5-dicyano-2,6-piperidinediones was achieved in good yields via the three-component reaction of aldehyde or ketone, ethyl cyanoacetate, lithium nitride (Li3N) as a convenient source of ammonia in MeOH.
Antiarthritic and suppressor cell inducing activity of azaspiranes: Structure-function relationships of a novel class of immunomodulatory agents
Badger,Schwartz,Picker,Dorman,Bradley,Cheeseman,DiMartino,Hanna,Mirabelli
, p. 2963 - 2970 (2007/10/02)
Spirogermanium (1;8,8-diethyl-N,N-dimethyl-2-aza-8-germaspiro[4.5]decane-2-propanamin e dihydrochloride) is a potent cytotoxic agent in vitro which has demonstrated limited activity in experimental animal tumor models. Subsequently, it has been reported that spirogermanium has antiarthritic and suppressor cell-inducing activity. We have synthesized a series of substituted 8-hetero-2-azaspiro[4.5]decane and 9-hetero-3-azaspiro[5.5]undecane analogues of spirogermanium to identify the heteroatom requirements for in vivo antiarthritic and suppressor cell-inducing activity. This structure-activity relationship study has identified that appropriately substituted silicon and carbon analogues of spirogermanium retain both antiarthritic and immunosuppressive activity, with the 8,8-dipropyl (carbon) analogue being among the most active. Following the identification of N,N-dimethyl-8,8-dipropyl-2-azaspiro[4,5]decane-2-propanamine dihydrochloride (9) as more active analogue than spirogermanium, a series of 8,8-dipropyl analogues with various amine substituents were synthesized. A number of these analogues had activity similar to that of 9. A correlation between activity in the adjuvant arthritic rat and the ability to induce suppressor cells (r = 0.894, p0.001) suggests an association between the two pharmacologic effects. While the precise biochemical mechanism(s) for the pharmacological activity is unclear, these data suggest that compounds within this series, e.g., N,N-dimethyl-8,8-dipropyl-2-azaspiro[4.5]decane-2-propanamine dihydrochloride, may provide effective therapy in diseases of autoimmune origin and/or the prevention of rejection in tissue transplantation.
