CL-218,872 is a sedative and hypnotic drug used in scientific research. It has similar effects to sedative-hypnotic benzodiazepine drugs such as

triazolam Triazolam, sold under the brand name Halcion among others, is a central nervous system (CNS) depressant tranquilizer of the triazolobenzodiazepine (TBZD) class, which are benzodiazepine (BZD) derivatives. It possesses pharmacological properties ...

, but is structurally distinct and so is classed as a nonbenzodiazepine hypnotic. CL-218,872 is a GABA_A

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. They may also be considered ligands which display both agonistic and antagonis ...

which is selective for the α1 subtype. It has a range of effects including sedative, hypnotic,

anxiolytic An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxiet ...

, anticonvulsant and

amnestic Amnesia is a deficit in memory caused by brain damage or disease,Gazzaniga, M., Ivry, R., & Mangun, G. (2009) Cognitive Neuroscience: The biology of the mind. New York: W.W. Norton & Company. but it can also be caused temporarily by the use o ...

actions, however the most prominent actions are sedation and amnesia, and CL-218,872 produces effects very similar to those of the hypnotic

imidazopyridine An imidazopyridine is a nitrogen containing heterocycle that is also a class of drugs that contain this same chemical substructure. In general, they are GABAA receptor agonists, however recently proton pump inhibitors, aromatase inhibitors, NSA ...

derivative

zolpidem Zolpidem, sold under the brand name Ambien, among others, is a medication primarily used for the short-term treatment of sleeping problems. Guidelines recommend that it be used only after cognitive behavioral therapy for insomnia and behavior ...

in animal studies.

Synthesis

Strecker type condensation between 3-(Trifluoromethyl)Benzaldehyde 54-89-7(1), morpholine 10-91-8(2), and potassium cyanide gives 6548-59-2(3). Conjugate addition of Ethyl acrylate 40-88-5(4) led t
CID:12449509
(5). Treatment with hydrazine went on to give 6548-61-6(6). Dehydrohalogenation with molecular bromine yields 6- -(Trifluoromethyl)phenylyridazin-3-ol 6548-62-7(7). Treatment with phophorus oxychloride gave 3-chloro-6- -(trifluoromethyl)phenylyridazine 6548-63-8(8). Reaction with Acetylhydrazine 068-57-1(9) completed the synthesis of CL-218,872 (10).

References

{{GABAAR PAMs Sedatives Triazolopyridazines Trifluoromethyl compounds GABAA receptor positive allosteric modulators