Background and overview of application examples of 2-bromo-3-chloro-5-methylpyridine
2-Bromo-3-chloro-5-methylpyridyl aminoguanidine bicarbonate is used as a pharmaceutical synthesis intermediate. There are reports in the literature that it can be used as a raw material to synthesize a class of phenylpyrrolidine compounds that can effectively inhibit PDE4 and PCSK9. Inhibitors.
Application examples of 2-bromo-3-chloro-5-methylpyridine
Example report on the application of 2-bromo-3-chloro-5-methylpyridine 1.
2-Bromo-3-chloro-5-methylpyridine can be used as a starting material to prepare the target compound (S)-1-((3S, 4S)-4-(3-((1-(3- Chloro-5-methylpyridin-2-yl)azetidin-3-yl)oxy)-4-methoxyphenyl)-3-((R)-1-hydroxyethyl)-3-methyl pyrrolidin-1-yl)-2,3-dihydroxypropyl-1-one. This compound is a potent inhibitor of PDE4. Phosphodiesterase (abbreviated as PDE), also known as 3′,5′-cyclic nucleotide phosphodiesterase, can catalyze the hydrolysis reaction of cAMP (cyclic adenosine monophosphate) to generate 5′-AMP (5′ -adenosine monophosphate), or catalyze the hydrolysis reaction of cGMP (cyclic guanosine monophosphate) to generate 5′-GMP (5′-guanosine monophosphate). It is known that PDE4 is divided into four subtypes: PDE4A, PDE4B, PDE4C, and PDE4D. Among them, inhibiting PDE4D will lead to side effects such as vomiting, while selective inhibition of PDE4B can improve the occurrence of side effects such as vomiting.
Example report on the application of 2-bromo-3-chloro-5-methylpyridine 2.
2-Bromo-3-chloro-5-methylpyridine can also be used to prepare PCSK9 inhibitors with the above structure. PCSK9 has a powerful effect on lowering LDL-C. Placebo-controlled studies have shown that PCSK9 inhibitors can reduce LDL-C levels by 50%-70% from baseline.
References
[1] [Chinese invention] CN201911303362.7 Phenylpyrrolidine compounds and their uses
[2] [Invented in China] CN20 trichloropyridine 1811407344.9 A method for in vitro screening of PCSK9 inhibitors
