PMC

Structures of compounds 1–8.

SmartCube^® signatures of 5 selected hybrids.

A: Time course for the effects of sertraline and 21 on time immobile in the FS test in mice. Data represent mean ± SEM. B: Effects of sertraline and 21 in mice on total time immobile in the forced swim test. Data were summed over the 6-min test and represent mean ± SEM. *p < 0.05 indicates statistical significance compared to water. C: Baseline body-weights of all treatment groups tested in FS. Data are presented as mean ± SEM.

^a Reagents and conditions: (a) BnOH, NaH, DMF; (b) n-butyl acrylate, 1 % Pd(OAc)₂, 2 % PhNHCONH₂, K₂CO₃, 130 °C; (c) 2N NaOH, MeOH/THF (1:1); (d) MeNH₂ ⁺OMeCl⁻, EDCI, DMAP, CH₂Cl₂; (e) Me₃S(O)⁺I⁻, NaH, DMSO; (f) (I) DIBAL-H, THF, −78 °C to −20 °C; (II) NaBH₄, MeOH; (g) ChiralPak AD, EtOH; (h) (I) (COCl)₂, DMSO, Et₃N, CH₂Cl₂, −78 °C; (II) Ph₃P=CHOCH₃, THF, 0 °C; (i) PtO₂, H₂, CH₂Cl₂; (j) 10 % Pd/C, H₂; (k) (CF₃SO₂)₂O, pyridine; (l) tert-butyl 1,4-diazepane-1-carboxylate or 1-methyl-1,4-diazepane or tert-butyl (1S,4S)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate, tris-(dibenzylideneacetone)dipalladium, 2-(dicyclohexylphosphino)-2’,4’,6’-triisopropylbiphenyl, K₃PO₄, 1,4-dioxane, microwave, 160 °C, 10 min; (m) CF₃CO₂H, CH₂Cl₂; (n) (I) ethynyl(trimethyl)silane, CuI, PdCl₂(PPh₃)₂, PPh₃, Et₃N, 60 °C, (II) TBAF, THF; (o) O₂N(CH₂)₂OTBS, PhNCO, Et₃N, PhMe.