Umespirone (KC-9172) is a

drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insuffla ...

of the

azapirone Azapirones are a class of drugs used as anxiolytics, antidepressants, and antipsychotics. They are commonly used as add-ons to other antidepressants, such as selective serotonin reuptake inhibitors (SSRIs). Medical uses Azapirones have shown ...

class which possesses

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 anxi ...

and

antipsychotic Antipsychotics, also known as neuroleptics, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but ...

properties. It behaves as a 5-HT_1A receptor

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 antagonistic e ...

(K_i = 15 nM), D₂ receptor partial agonist (K_i = 23 nM), and α₁-adrenoceptor

receptor antagonist A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of rece ...

(K_i = 14 nM), and also has weak

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Par ...

for the

sigma receptor Sigma receptors (σ-receptors) are protein cell surface receptors that bind ligands such as 4-PPBP (4-phenyl-1-(4-phenylbutyl) piperidine), SA 4503 (cutamesine), ditolylguanidine, dimethyltryptamine, and siramesine. There are two subtypes, ...

(K_i = 558 nM). Unlike many other anxiolytics and antipsychotics, umespirone produces minimal

sedation Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure. Examples of drugs which can be used for sedation include isoflurane, diethyl ether, ...

, cognitive/memory impairment,

catalepsy Catalepsy (from Ancient Greek , , "seizing, grasping") is a nervous condition characterized by muscular rigidity and fixity of posture regardless of external stimuli, as well as decreased sensitivity to pain. Signs and symptoms Symptoms inc ...

, and

extrapyramidal symptom Extrapyramidal symptoms (EPS) are symptoms that are archetypically associated with the extrapyramidal system of the brain's cerebral cortex. When such symptoms are caused by medications or other drugs, they are also known as extrapyramidal side ...

Synthesis

The condensation between ethyl cyanoacetate (1) and

acetone Acetone (2-propanone or dimethyl ketone), is an organic compound with the formula . It is the simplest and smallest ketone (). It is a colorless, highly volatile and flammable liquid with a characteristic pungent odour. Acetone is miscib ...

gives ethylisopropylidenecyanoacetate 59-58-0(2). This product is reacted with N-butylcyanoacetamide 9581-21-0(3) in sodium methoxide solution to give N-butyl-2,4-dicyano-3,3-dimethylglutarimide
CID:10681941
(4). The

glutarimide Glutarimide is the organic compound with the formula (CH2)3(CO)2NH. It is a white solid. The compound forms upon dehydration of the amide of glutaric acid. Glutarimide is sometimes called 2,6-piperidinedione. It is the core of a variety of medi ...

is cyclized with phosphoric acid to yield 3-butyl-9,9-dimethyl-3,7-diazabicyclo .3.1onane-2,4,6,8-tetraone, https://pubchem.ncbi.nlm.nih.gov/compound/10825633 CID:10825633 (5). The reaction between 1-(o-anisyl)piperazine 5386-24-4(6) and 1,4-dibromobutane 10-52-1(7) gives the

Quat salt In chemistry, quaternary ammonium cations, also known as quats, are positively charged polyatomic ions of the structure , R being an alkyl group or an aryl group. Unlike the ammonium ion () and the primary, secondary, or tertiary ammonium catio ...

br>CID:15895413
8).

Convergent synthesis In chemistry a convergent synthesis is a strategy that aims to improve the efficiency of multistep synthesis, most often in organic synthesis. In this type of synthesis several individual pieces of a complex molecule are synthesized in stage one, ...

(in the presence of potassium carbonate) affords ' (KC-9172) (9).

References

Azapirones N-(2-methoxyphenyl)piperazines {{Anxiolytic-stub

Synthesis

See also

References