Radioligands for the 5 -ht1b receptor
A technology of 5-HT1B and pharmaceutical carriers, which can be applied to in vivo radioactive preparations, preparations for in vivo experiments, medical preparations containing active ingredients, etc., and can solve problems such as difficult replication
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Embodiment 1
[0033] Embodiment 1: the synthesis of radioligand precursor (8-(1-piperazinyl)-5-methyl chroma-2-en-4-ketone-2-(4-morpholinophenyl) formamide)
[0034]
[0035] A portion of 12.82 g (89.9 mmol) of 2-chloro-5-methylphenol was dissolved in 75 mL of ether. A portion of 10.9 g (107.9 mmol) of triethylamine was added dropwise with stirring, followed by the dropwise addition of 14.04 g (98.9 mmol) of dimethyl acetylenedicarboxylate, causing a gentle rise in temperature. The reaction mixture was stirred at room temperature overnight, then rinsed with ether and a little THF to dissolve some residue, transferred to a separatory funnel. The mixture was washed twice with 200 mL of 1N NaOH, once with water, then twice with saturated NaCl, and finally washed with MgSO 4 dry. Filtration and removal of solvent by rotary evaporation afforded a light yellow transparent oil which was directly carried on to the next reaction.
[0036]
[0037]The oil from the previous step was taken up ...
Embodiment 2
[0048] Example 2: Tritiated radioligand [ 3 H] Synthesis of 8-(4-methylpiperazin-1-yl)-5-methylchromo-2-en-4-one-2-(4-morpholinophenyl)formamide
[0049] To 1.6mg (3.57μmol) precursor 8-piperazin-1-yl-5-methylchromo-2-en-4-one-2-(4-morpholinophenyl)formamide in 0.3ml DMF solution, add 100mCi of C 3 h 3 I (100 μl DMF solution, Amersham), and finally 100 μl DMF was used as wash to give a total reaction volume of 0.5 mL. The reaction mixture was sealed and placed in an oil bath at 100-110° C., heated with stirring for 50 minutes. The reaction mixture was cooled and 6mg of Boc anhydride (Boc anhydride) was added, sealed and heated for 60 minutes. The volatiles were removed and the product was dissolved in acetonitrile and 0.1% TFA / water 50 / 50. The product was separated on a HPLC C18 Phenomex Luna column (10x50 cm; gradient 20-60% acetonitrile (0.1% TFA) over 10 min (retention time = 8.1 min). The main fractions from the separation were combined, evaporated and redissolved in ...
Embodiment 3
[0050] Embodiment 3: 11 C Radioligand: [ 11 C] Synthesis of 8-(4-methylpiperazin-1-yl)-5-methylchromo-2-en-4-one-2-(4-morpholinophenyl)formamide
[0051] [ 11 C] 8-(4-methylpiperazin-1-yl)-5-methylchrom-2-en-4-one-2-(4-morpholinophenyl)formamide was prepared as follows: using trifluoro Methanesulfonic acid [ 11 C] methyl ester, to the corresponding demethylated precursor 8-piperazin-1-yl-5-methylchrom-2-en-4-one-2-(4-morpholinophenyl)methyl Amides were prepared by methylation and purification by HPLC. Fractions collected by HPLC were evaporated and the residue was redissolved in 8 mL of sterile physiological phosphate buffer (pH=7.4). After filter sterilization, the formulated product solution is sterilized and freed from pyrogens.
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