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Umespirone

From Wikipedia, the free encyclopedia
Anxiolytic and antipsychotic drug

Pharmaceutical compound
Umespirone
Clinical data
Routes of
administration		By mouth
ATC code
  • none
Legal status
Legal status
  • In general: uncontrolled
Pharmacokinetic data
Eliminationhalf-lifeUnknown but effects last much longer than other azapirones, up to 23 hours after a single dose in human clinical studies.[1]
Identifiers
  • 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
PubChemCID
ChemSpider
UNII
CompTox Dashboard(EPA)
Chemical and physical data
FormulaC28H40N4O5
Molar mass512.651 g·mol−1
3D model (JSmol)
  • O=C1N(C(=O)C2C(=O)N(C(=O)C1C2(C)C)CCCCN4CCN(c3ccccc3OC)CC4)CCCC

Umespirone (KC-9172) is adrug of theazapirone class which possessesanxiolytic andantipsychotic properties.[2][3][4][5] It behaves as a5-HT1A receptorpartial agonist (Ki = 15 nM),D2 receptor partial agonist (Ki = 23 nM), andα1-adrenoceptorreceptor antagonist (Ki = 14 nM), and also has weakaffinity for thesigma receptor (Ki = 558 nM).[2][6][7] Unlike many other anxiolytics and antipsychotics, umespirone produces minimalsedation,cognitive/memory impairment,catalepsy, andextrapyramidal symptoms.[1][5][6]

Synthesis

[edit]
Synthesis:[8] Patent:[9]

The condensation betweenethyl cyanoacetate (1) andacetone 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). Theglutarimide 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) and1,4-dibromobutane [110-52-1] (7) gives theQuat saltCID:15895413(8).

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

See also

[edit]

References

[edit]
  1. ^abHolland RL, Wesnes K, Dietrich B (1994). "Single dose human pharmacology of umespirone".European Journal of Clinical Pharmacology.46 (5):461–8.doi:10.1007/bf00191912.PMID 7957544.S2CID 12117650.
  2. ^abBarnes NM, Costall B, Domeney AM, et al. (September 1991). "The effects of umespirone as a potential anxiolytic and antipsychotic agent".Pharmacology Biochemistry and Behavior.40 (1):89–96.doi:10.1016/0091-3057(91)90326-W.PMID 1685786.S2CID 9762359.
  3. ^Ruhland M, Krähling H, Fuchs A, Schön U (November 1988). "KC 9172 (free base of KC 7218)--an antipsychotic/anxiolytic compound. I. Antipsychotic and anxiolytic activity in comparison with chlorpromazine, clozapine, diazepam and buspirone".Pharmacopsychiatry.21 (6):396–8.doi:10.1055/s-2007-1017024.PMID 2907649.S2CID 260241523.
  4. ^Krähling H, Fuchs A, Ruhland M, Schön U, Mol F, Tulp M (November 1988). "KC 9172 (free base of KC 7218)--an antipsychotic/anxiolytic compound. II. Discrimination from typical neuroleptics and benzodiazepine-like minor tranquilizers".Pharmacopsychiatry.21 (6):399–401.doi:10.1055/s-2007-1017025.PMID 2907650.S2CID 260241655.
  5. ^abSchmidt WJ, Krähling H, Ruhland M (1991). "Antagonism of AP-5-induced sniffing stereotypy links umespirone to atypical antipsychotics".Life Sciences.48 (6):499–505.doi:10.1016/0024-3205(91)90464-M.PMID 1671523.
  6. ^abAhlenius S, Wijkström A (November 1992). "Mixed agonist-antagonist properties of umespirone at neostriatal dopamine receptors in relation to its behavioral effects in the rat".European Journal of Pharmacology.222 (1):69–74.doi:10.1016/0014-2999(92)90464-F.PMID 1361441.
  7. ^Itzhak Y, Ruhland M, Krähling H (February 1990)."Binding of umespirone to the sigma receptor: evidence for multiple affinity states".Neuropharmacology.29 (2):181–4.doi:10.1016/0028-3908(90)90058-Y.PMID 1970425.S2CID 54326248.
  8. ^Kr鋒ling, H.; Krijzer, F. Drugs Fut 1991,16(5),437.
  9. ^DE3529872 idem Uwe Schoen, Wolfgang Kehrbach, Werner Benson, Andreas Fuchs, Michael Ruhland,U.S. patent 4,771,044 (1988 to Kali-Chemie Pharma Gmbh).
Typical
Disputed
Atypical
Others
5-HT1ARTooltip 5-HT1A receptoragonists
GABAARTooltip GABAA receptorPAMsTooltip positive allosteric modulators
Gabapentinoids
(α2δVDCCblockers)
Antidepressants
Sympatholytics
(Antiadrenergics)
Others
SSRIsTooltip Selective serotonin reuptake inhibitors
SNRIsTooltip Serotonin–norepinephrine reuptake inhibitors
NRIsTooltip Norepinephrine reuptake inhibitors
NDRIsTooltip Norepinephrine–dopamine reuptake inhibitors
NaSSAsTooltip Noradrenergic and specific serotonergic antidepressants
SARIsTooltip Serotonin antagonist and reuptake inhibitors
SMSTooltip Serotonin modulator and stimulators
Others
TCAsTooltip Tricyclic antidepressants
TeCAsTooltip Tetracyclic antidepressants
Others
Non-selective
MAOATooltip Monoamine oxidase A-selective
MAOBTooltip Monoamine oxidase B-selective
Miscellaneous
α1
Agonists
Antagonists
α2
Agonists
Antagonists
β
Agonists
Antagonists
D1-like
Agonists
PAMs
Antagonists
D2-like
Agonists
Antagonists
σ1
σ2
Unsorted
5-HT1
5-HT1A
5-HT1B
5-HT1D
5-HT1E
5-HT1F
5-HT2
5-HT2A
5-HT2B
5-HT2C
5-HT3–7
5-HT3
5-HT4
5-HT5A
5-HT6
5-HT7
Phenylpiperazines
Benzylpiperazines
Naphthylpiperazines
Quinolinylpiperazines
Diphenylalkylpiperazines
Pyrimidinylpiperazines
Pyridinylpiperazines
Benzo(iso)thiazolylpiperazines
Tricyclic-linked piperazines
Others/uncategorized


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