Patent Evaluation: The use of Pyridazines in the Treatment of Cognitive Disorders

Summary

Novelty: New derivatives of alkyl-6-pyridazine are disclosed and are reported to be ACh agonists. These compounds may be useful for the treatment of memory loss, cognitive disorders and senility.

Biology: It is stated that the present compounds are ligands for M₁ cholinergic receptors and hence, they do not resemble previously disclosed pyridazines which give rise to anti-depres sive effects. In vitro M₁ receptor activity was assessed by the method of Potter et al (IC₅₀ = 0.04 mM) and in vitro M₂ activity, as assessed by the method of Hammer, showed good specificity (IC₅₀ = 0.9 mM). In vivo pirenzepine induced worm rotation was 71% for compound 6 (3 mg/kg). Toxicity is said to be negligible for therapeutic doses.

Chemistry: Twenty-six compounds are given as preparative examples. Characterization is by mp. Compound 1 is the dichlorohydrate of (2-diethylamino-2-methyl-1-propylamino(4-fluoro-phenyl)-6-propylpyridazine, and is typical of the claim.

Structure: