Amide compound as well as preparation method and application thereof
An amide compound and compound technology, applied in the field of drug preparation, can solve the problems of damage to the nervous system, low biological activity, reduction of animal leukocytes, etc., and achieve the effect of overcoming adverse effects
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[0057] The present invention also provides a preparation method for the above-mentioned amides, comprising the following steps:
[0058] S101: providing a compound shown in formula (I-1);
[0059]
[0060] Wherein, the compound represented by formula (I-1) can be synthesized using commercially available raw materials or using existing methods.
[0061] It is preferably prepared by the following method:
[0062] S1011: Substituting 5-nitro-6-hydroxy-nicotinic acid and thionyl chloride to prepare 5-nitro-6-chloro-nicotinic acid;
[0063]
[0064] Further, it is preferred that the solvent in step S1011 is DMF, and the amount of thionyl chloride added is 10eq-20eq, more preferably 14eq-16eq.
[0065] Further, the preferred operation of step S1011 is: dissolve 5-nitro-6-hydroxy-nicotinic acid in the solvent, slowly add thionyl chloride dropwise under ice bath, and after the dropwise addition, raise the temperature to 75°C-85°C (preferably 80° C.), after the reaction is com...
Embodiment 1
[0093] Embodiment 1: the preparation of interferon inducer (II)
[0094]Synthesis of 5-nitro-6-chloro-nicotinic acid
[0095]
[0096] At 0-10°C, the compound 5-nitro-6-hydroxy-nicotinic acid (20g, 108.63mmol, 1eq) and SOCl 2 (196.80g, 1.65mol, 120.00mL, 15.23eq) was added dropwise to a mixture of DMF (30mL), and after the addition was complete, the reaction was heated to 80°C and stirred for 1h. After LCMS and TLC (ethyl acetate:methanol=10:1) monitoring reaction is complete, rotary evaporation removes most of SOCl 2 , and then carefully poured into ice water (200mL) to quench, extracted with ethyl acetate (100mL*2) and spin-dried to obtain the compound 5-nitro-6-chloro-nicotinic acid (20g). MS: 203(M+1)
[0097] Synthesis of 5-nitro-6-chloro-nicotinamide
[0098]
[0099] The compound 5-nitro-6-chloro-nicotinic acid (18g, 88.87mmol, 1eq) and SOCl 2 (147.60g, 1.24mol, 90.00mL, 13.96eq) mixture was heated to 80°C and stirred for 1 hour. Rotary evaporation removes m...
Embodiment 2
[0109] Embodiment 2: The experimental research that compound (II) induces piglet to produce interferon
[0110] Materials and methods:
[0111] A total of 24 4-week-old one-time weaned piglets were selected as experimental piglets, and randomly divided into 3 groups with 8 piglets in each group, which were respectively designated as X group, Y group and Z group. Wherein group X is a negative control group, and the test substance is normal saline; Group Y, the test substance is an interferon-inducing agent experimental group, and injects compound (II) at a dose of 0.3 mg / kg; Z group is a positive drug group, and the test substance For polycytidine, a 0.7 mg / kg dose of polycytidine solution was injected. After continuous injection for 2 days, the blood samples of piglets were collected to test the interferon alpha (IFN-α) level in the blood.
[0112] Statistical method:
[0113] SPSS11.5 statistical software was used for statistical analysis, the experimental data was tested ...
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