Zalospirone

Zalospirone (WY-47,846) is a selective 5-HT1A partial agonist of the azapirone chemical class.[1][2] It was found to be effective in the treatment of anxiety and depression in clinical trials, but a high proportion of subjects dropped out due to side effects and development was subsequently never completed.[3]

Zalospirone
Clinical data
Routes of
administration		Oral
ATC code
  • none
Legal status
Legal status
  • In general: uncontrolled
Pharmacokinetic data
Elimination half-life1-4 hours
Identifiers
IUPAC name
  • (3aα,4α,4aβ,6aβ,7α,7aα)-Hexahydro-2-(4-(4-(2-pyrimidinyl)-1-piperazinyl)butyl)-4,7-etheno-1H-cyclobut[f]isoindole-1,3(2H)-dione
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
Chemical and physical data
FormulaC24H29N5O2
Molar mass419.529 g·mol−1
3D model (JSmol)
SMILES
  • O=C1N(C(=O)[C@@H]4[C@H]1[C@@H]2\C=C/[C@H]4[C@H]3\C=C/[C@@H]23)CCCCN6CCN(c5ncccn5)CC6
InChI
  • InChI=1S/C24H29N5O2/c30-22-20-18-6-7-19(17-5-4-16(17)18)21(20)23(31)29(22)11-2-1-10-27-12-14-28(15-13-27)24-25-8-3-9-26-24/h3-9,16-21H,1-2,10-15H2/t16-,17+,18-,19+,20-,21+
  • Key:AERLHOTUXIJQFV-RCPZPFRWSA-N
  (verify)

Zalospirone was patented for the treatment of alcoholism, sleep disorders,Alzheimer's disease:[4]

Synthesis
Synthesis:[5] Patent:[6]

An internal electrocyclic rearrangement means that cyclooctatetraene [629-20-9] (1) is in equilibrium with bicyclo[4.2.0]octa-2,4,7-triene, CID:12676027 (2). Diels-Alder reaction with the very reactive dienophile maleimide [541-59-3] (3) leads to the bridged bicyclic adduct [114298-16-7] (4). Alkylation with [87789-48-8] (5) completed the synthesis of Zalospirone (6).

See also

References
  1. Gleeson S, Barrett JE (October 1990). "5-HT1A agonist effects on punished responding of squirrel monkeys". Pharmacology, Biochemistry, and Behavior. 37 (2): 335–7. doi:10.1016/0091-3057(90)90344-H. PMID 1981937. S2CID 23488390.
  2. Singh A, Lucki I (April 1993). "Antidepressant-like activity of compounds with varying efficacy at 5-HT1A receptors". Neuropharmacology. 32 (4): 331–40. doi:10.1016/0028-3908(93)90153-T. PMID 8497336. S2CID 38611829.
  3. Rickels K, Derivan A, Kunz N, Pallay A, Schweizer E (June 1996). "Zalospirone in major depression: a placebo-controlled multicenter study". Journal of Clinical Psychopharmacology. 16 (3): 212–7. doi:10.1097/00004714-199606000-00004. PMID 8784652.
  4. Magid A. M. Abou-Gharbia & John A. Moyer, U.S. Patent 5,183,819 (1993 to Wyeth LLC).
  5. Abou-Gharbia, M., Patel, U. R., Webb, M. B., Moyer, J. A., Andree, T. H., Muth, E. A. (July 1988). "Polycyclic aryl- and heteroarylpiperazinyl imides as 5-HT1A receptor ligands and potential anxiolytic agents: synthesis and structure-activity relationship studies". Journal of Medicinal Chemistry. 31 (7): 1382–1392. doi:10.1021/jm00402a023. ISSN 1520-4804 0022-2623, 1520-4804. {{cite journal}}: Check |issn= value (help)
  6. Magid A. Abou-Gharbia, U.S. Patent 4,892,943 (1990 to Wyeth LLC).
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