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GSK1360707F
Identifiers
  • (1R,6S)-1-(3,4-Dichlorophenyl)-6-(methoxymethyl)-4-azabicyclo[4.1.0]heptane
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC14H17Cl2NO
Molar mass286.20 g·mol−1
3D model (JSmol)
  • COC[C@@]12C[C@@]1(CCNC2)c3ccc(c(c3)Cl)Cl
  • InChI=1S/C14H17Cl2NO/c1-18-9-13-7-14(13,4-5-17-8-13)10-2-3-11(15)12(16)6-10/h2-3,6,17H,4-5,7-9H2,1H3/t13-,14-/m0/s1
  • Key:ICXJGCSEMJXNQF-KBPBESRZSA-N
  (verify)

GSK1360707F is a potent and selective triple reuptake inhibitor.[1] It is chemically related to amitifadine and NS-2359 (GSK-372,475). Until recently,[when?] it was under development for the treatment of major depressive disorder; its development was put on hold for strategic reasons.[citation needed]

Synthesis

Synthesis of GSK1360707F[2]
  1. BOC Protecting group.
  2. Enolization and trapping with triflate group (cf Comins' reagent).
  3. Suzuki reaction
  4. Reduction (only 1 mol eq. LAH because N-BOC can be reduced to N-Me)
  5. Trifluoroacetic acid (TFA) removal of protecting group.
  6. Simmons–Smith reaction cyclopropanation.
  7. Williamson ether synthesis (c.f. NS patents & paxil).

Transporter occupancy

GSK1360707F has recently (2013) been tested on baboons (Papio anubis) & humans for transporter occupancy using PET.[3]

See also

References

  1. ^ Micheli F, Cavanni P, Andreotti D, Arban R, Benedetti R, Bertani B, et al. (July 2010). "6-(3,4-dichlorophenyl)-1-[(methyloxy)methyl]-3-azabicyclo[4.1.0]heptane: a new potent and selective triple reuptake inhibitor". Journal of Medicinal Chemistry. 53 (13): 4989–5001. doi:10.1021/jm100481d. PMID 20527970.
  2. ^ WO 2008031772, Bertani, Barbara; Di Fabio, Romano & Micheli, Fabrizio et al., "Azabicyclic compounds as inhibitors of monoamines reuptake", published 2008-03-20, assigned to Glaxo Group Ltd. 
  3. ^ Comley RA, Salinas CA, Slifstein M, Petrone M, Marzano C, Bennacef I, et al. (August 2013). "Monoamine transporter occupancy of a novel triple reuptake inhibitor in baboons and humans using positron emission tomography". The Journal of Pharmacology and Experimental Therapeutics. 346 (2): 311–7. doi:10.1124/jpet.112.202895. PMID 23685546. S2CID 2964324.
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