Compound or salt thereof as well as application and synthesis method thereof
A synthesis method and compound technology, which are applied in the field of drug synthesis, can solve the problems of unsatisfactory early diagnosis results of Alzheimer's disease and low binding ability of PET imaging agents to cross the brain-blood barrier, and achieve a simple labeling method, which is beneficial to Large-scale production, good stability
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Embodiment 1
[0041] 4,4'-((1E,1'E)-(1-methyl-1H-pyrazole-3,5-diyl)bis(ethylene-2,1-diyl))bis(2-methoxy phenol), its structural formula is:
[0042]
[0043] The pharmaceutically acceptable salts of the above compounds are carbonate, hydrochloride, sulfate, phosphate, phosphite, formate, acetate, citrate, lactate, fumarate, tartaric acid salt or gluconate;
[0044] The synthetic method of above-mentioned compound 1 is: take curcumin as raw material, carry out cyclization reaction with curcumin and hydrazine hydrate to generate pyrazole curcumin, after the phenolic hydroxyl group of pyrazole curcumin is protected, on the N atom of pyrazole ring The R group is introduced, and then the protected phenolic hydroxyl group is deprotected to obtain the compound 1; the specific synthesis process is:
[0045] 1) Cyclization reaction between curcumin and hydrazine hydrate to generate pyrazole curcumin: Weigh 0.88g of curcumin into a 100mL round bottom flask, add 10mL of glacial acetic acid to dis...
Embodiment 2
[0072] 3,5-bis((E)-4-((tert-butyldimethylsilyl)oxy)-3-methoxystyryl)-1-(2-fluoroethyl), whose structural formula is :
[0073]
[0074] The pharmaceutically acceptable salts of the above compound 2 are carbonates, hydrochlorides, sulfates, phosphates, phosphites, formates, acetates, citrates, lactates, fumarates, tartrate or gluconate;
[0075] The synthetic method of above-mentioned compound 2 is:
[0076] Introduce a fluoroethyl group on the N atom of the pyrazole ring: Weigh 1.09 g of the white solid obtained in step 2) of Example 1, and put 10 mL of DMF into a 50 mL round bottom flask to dissolve it, and add a mass fraction of 60% to the reaction solution. 0.081 g of NaH, after stirring at room temperature for 20 min, add 0.153 mL of BrCH 2 CH 2 F, stir at room temperature for 12 hours, after the reaction is completed, add 10 mL of water to quench the reaction, then extract with 20 mL of ethyl acetate, and repeat the extraction 3 times, combine the organic phases, t...
Embodiment 3
[0093] Calculate the Log P and Clog P values of compounds 1 and 2 and the carbonate, hydrochloride, formate and lactate of compounds 1 and 2 by Chemdraw, and the four Alzheimer's diseases that have entered clinical diagnostic applications The diagnostic PET tracers [11C]PIB, [18F]Amyvid, [11C]PBB3 and [18F]T807 were compared, and the results are shown in the table below:
[0094] compound Log P CLog P Compound 1 4.20 4.01 Compound 2 4.39 4.26 [ 11 C] PIB
3.41 3.99 [ 18 F] Amyvid
3.16 3.91 [ 11 C] PBB3
4.09 4.05 [ 18 F]T807
2.25 3.18
[0095] .
[0096] Comparing the experimental results, it can be seen that the Log P values of compounds 1 and 2 are similar to four existing PET tracers. Therefore, compounds 1 and 2 and their pharmacologically acceptable salts have better lipophilicity and better spanning Brain-blood barrier capacity.
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