1005402-40-3

Upstream product

• 501-94-0 p-hydroxyphenethyl alcohol 
• 955359-96-3 2-[4-(3-chloropropoxy)phenyl]ethanol 
• 1005402-39-0 [4-(3-chloropropoxy)phenyl]acetaldehyde 
• 298-12-4 Glyoxilic acid 

Downstream Products

• 1005402-42-5 5-[4-(3-chloropropoxy)phenyl]-2H-pyridazin-3-one 
• 1353387-78-6 5-[4-(3-chloropropoxy)phenyl]-2-isopropyl-2H-pyridazin-3-one 

Relevant academic research and scientific papers

Optimization of 5-pyridazin-3-one phenoxypropylamines as potent, selective histamine H3 receptor antagonists with potent cognition enhancing activity

Previous studies have shown that (5-{4-[3-(R)-2-methylpyrrolin-1-yl- propoxy]phenyl}-2H-pyridazin-3-one) 2 had high affinity for both the human (hH3R Ki = 2.8 nM) and rat H3Rs (rH 3R Ki = 8.5 nM) but displayed low oral bioavailability in the rat. Optimization of the 5-pyridazin-3-one R2 and R6 positions to improve the pharmacokinetic properties over 2 led to the identification of 5-{4-[3-(R)-2-methylpyrrolidin-1-yl)propoxy]phenyl}-2-pyridin- 2-yl-2H-pyridazin-3-one 29. Compound 29 displayed high affinity for both human and rat H3Rs (hH3R Ki = 1.7 nM, rH3R Ki = 3.7 nM) with a greater than 1000-fold selectivity over the other histamine receptor subtypes and favorable pharmacokinetic properties across species (F = 78% rat, 92% dog, 96% monkey). It showed low binding to human plasma proteins, weakly inhibited cytochrome P450 isoforms, and displayed an excellent safety profile for a CNS-active compound. 29 displayed potent H3R antagonist activity in the brain in a rat dipsogenia model and demonstrated enhancement of cognitive function in a rat social recognition model at low doses. However, the development of compound 29 was discontinued because of genotoxicity.

Pyridizinone derivatives

The present invention provides compounds of formula (I*): their use as H3 inhibitors, processes for their preparation, and pharmaceutical compositions thereof.