GSK1360707F

GSK1360707F is a potent and selective triple reuptake inhibitor.[1] structurally related to amitifadine and NS-2359 (GSK-372,475).

GSK1360707F

Identifiers
IUPAC name (1R,6S)-1-(3,4-Dichlorophenyl)-6-(methoxymethyl)-4-azabicyclo[4.1.0]heptane
CAS Number	1013098-04-8
PubChem CID	24802841
ChemSpider	32739425
UNII	9DE44WJ46X
Chemical and physical data
Formula	C14H17Cl2NO
Molar mass	286.20 g·mol^−1
3D model (JSmol)	Interactive image
SMILES COC[C@@]12C[C@@]1(CCNC2)c3ccc(c(c3)Cl)Cl
InChI 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
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Synthesis

Synthesis of GSK1360707F: WO 2008031772

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.[2]

until recently was under development for the treatment of major depressive disorder; its development was put on hold for strategic reasons.

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. 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.