2,3,4,4a,5,9b-Hexahydro-1H-indeno[1,2-b]pyridines: potential antidepressants

Abstract

The synthesis of various diastereoisomeric H4a,H5-cis,H4a,H9b-cis- and H4a,H5-trans,H4a,H9b-cis-2,3,4,4a,5,9b-hexahydro -1H-indeno[1,2-b]pyridines is described, as well as the evaluation of their antidepressant potency. Elucidation of structure-activity relationships revealed the H4a,H5-trans compounds as being by far the more active of the two series of diastereoisomers. Pharmacological and biochemical data suggest that these compounds are potential antidepressants with central stimulating properties, which are characterized by strong norepinephrine and dopamine reuptake inhibition.

Third‐generation antidepressants

“…Several derivatives were devoid of effects on the 5-HT carrier, but showed insufficient dissociation from direct stimulating effects which resulted from their mixed NE-/DA-reuptake inhibitory action. 244 Citalopram (Fig. 9), was developed from series of alkylamino-substituted isobenzofurans and thiophenes that featured affinity for 5-HT-and NE-reuptake carriers (e. g., talopram and t a l s~p r a m~~~) and currently is introduced on several European markets after a launch in Denmark in 1988.…”

Target-directed discovery and production of pharmaceuticals in transgenic mutant plant cells

“…Others contain complex alkaloids, with similarity to known synthetic DAT inhibitors (e.g. Kunstmann et al 1984), but the MS match is only partial. Methanol extracts from all these cultures were separated by preparative HPLC (Kesting et al 2009).…”

Efficient synthesis of hexahydroindenopyridines and their potential as melatoninergic ligands

“…High resolution (HRESIMS) data were recorded on a Waters Xevo quadrupole time-of-flight (Q-TOF) spectrometer (Waters Corp., Milford, MA, USA) coupled to an Acquity UPLC system (Waters Corp., Milford, MA, USA) via an electrospray ionization (ESI) interface operating in positive mode and using a Waters Acquity BEH C18 column (50 Â 2.1 mm i.d., 1.7 mm); 1 H NMR and 13 C NMR spectra were recorded with CDCl 3 as solvent on a Bruker AC-500. Multiplicities of 13 C NMR resonances were assigned by DEPT experiments. COSY, HSQC and HMBC correlations were recorded at 400 MHz and 500 MHz (Bruker AC-400 or AC-500).…”

“…Some authors achieved the synthesis of HHIPs via a tricyclic lactam intermediate. Kunstmann et al carried out the synthesis through the condensation of aldehydes and 6-phenyl-3,4-dihydropyridin-2-ones which were prepared from 5-oxo-5-phenylvaleronitriles [13]. Van Emelen et al did so by an intramolecular Ritter reaction of a hydroxynitrile [20] whereas Hong et al obtained 4-azafluorenes, onychine-type ( Fig.…”

“…3), 1.24 (m, 3H, CH 3 );13 C NMR (125 MHz, CDCl 3 ) d 173.6 (CONH), 171.6 (COO), 158.7 (C-8), 144.1 (C-9a), 132.7 (C-5a), 125.5 (CH-6), 113.2 (CH-7), 110.5 (CH-9), 70.2 (CH-9b), 60.8 (CO 2 CH 2 ), 55.8 (OCH 3 ), 48.5 (CH 2 -2), 46.0 (CH-4a), 34.9 (CH 2 -5), 29.9 (2 Â C, NCOCH 2 CH 2 ), 29.8 (CH 2 -4), 25.9 (CH 2 -3), 14.6 (CH 3 ). EIMS m/z (%) 331 [M] þ (30), 286 (25), 202 (100), 186 (40), 174 (40); HRESIMS m/z 332.1877 [M þ H] þ (332.1862, calc for C 19 H 26 NO 4 ).…”