Umespirone

Umespirone (KC-9172) is a drug of the azapirone class which possesses anxiolytic and antipsychotic properties.^[2][3][4][5] It behaves as a 5-HT_1A receptor partial agonist (K_i = 15 nM), D₂ receptor partial agonist (K_i = 23 nM), and α₁-adrenoceptor receptor antagonist (K_i = 14 nM), and also has weak affinity for the sigma receptor (K_i = 558 nM).^[2][6][7] Unlike many other anxiolytics and antipsychotics, umespirone produces minimal sedation, cognitive/memory impairment, catalepsy, and extrapyramidal symptoms.^[1][5][6]

Umespirone

Clinical data
Routes of administration	By mouth
ATC code	none
Legal status
Legal status	In general: uncontrolled
Pharmacokinetic data
Elimination half-life	Unknown but effects last much longer than other azapirones, up to 23 hours after a single dose in human clinical studies.[1]
Identifiers
IUPAC name 3-butyl-7-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]-9,9-dimethyl-3,7-diazabicyclo[3.3.1]nonane-2,4,6,8-tetrone
CAS Number	107736-98-1
PubChem CID	65902
ChemSpider	59311
UNII	FG0A3VRL5K
CompTox Dashboard (EPA)	DTXSID30869480
Chemical and physical data
Formula	C28H40N4O5
Molar mass	512.651 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=C1N(C(=O)C2C(=O)N(C(=O)C1C2(C)C)CCCCN4CCN(c3ccccc3OC)CC4)CCCC

Synthesis

Synthesis:^[8] Patent:^[9]

The condensation between ethyl cyanoacetate (1) and acetone gives ethylisopropylidenecyanoacetate [759-58-0] (2). This product is reacted with N-butylcyanoacetamide [39581-21-0] (3) in sodium methoxide solution to give N-butyl-2,4-dicyano-3,3-dimethylglutarimide, CID:10681941 (4). The glutarimide is cyclized with phosphoric acid to yield 3-butyl-9,9-dimethyl-3,7-diazabicyclo[3.3.1]nonane-2,4,6,8-tetraone, https://pubchem.ncbi.nlm.nih.gov/compound/10825633 CID:10825633 (5).

The reaction between 1-(o-anisyl)piperazine [35386-24-4] (6) and 1,4-dibromobutane [110-52-1] (7) gives the Quat salt CID:15895413(8).

Convergent synthesis (in the presence of potassium carbonate) affords Umespirone (KC-9172) (9).

See also

• Azapirone