Potential antidepressants: 2-(Methoxy- and hydroxyphenylthio)benzylamines as selective inhibitors of 5-hydroxytryptamine re-uptake in the brain

Abstract

ChemInform Abstract A large variety of title compounds such as (VI) and (VIII) are synthesized using reaction sequences generally exemplified in the scheme for (VI). Some of the 2-(methoxy-and hydroxy-phenylthio)benzylamines prepared, especially compounds (VIIIa), indicate properties of potential antidepressants being highly active and selective inhibitors of 5-hydroxytryptamine reuptake in the brain structures and having the typical antireserpine activity. The most interesting compound of the series is (VI) (hydrogen maleate VUFB-15468) which is undergoing preclinical studies. On the basis of its structure, some further compounds are prepared.

Substituted Diphenyl Sulfides as Selective Serotonin Transporter Ligands: Synthesis and In Vitro Evaluation

“…After the solvent was evaporated, the crude product was purified by flash chromatography (EtOAc/petroleum ether/ Et3N: 4/5/1 for N,N-dimethyl derivatives and EtOAc/MeOH/ Et3N: 8/1/1 for N-methyl derivatives). 11), 293 (12), 291 (15), 227 (25), 197 (21), 165 (22), 164 (20), 132 (26), 58 (62), 46 (100), 42 (27). Anal.…”

“…Anal. (C15H17BrN2S) C, H, N. 4), 212 (19), 152 (11), 151 (42), 150 (26), 120 (100), 118 (25), 44 (29). Anal.…”

“…However, human studies with this ligand have not been reported. More recently, on the basis of a structure described as a novel antidepressant, , several substituted diphenyl sulfides have been described as potent and selective SERT derivatives (Figure ). These diphenyl sulfide derivatives (IDAM, ADAM, DAPP, and DASB) have been labeled with I-125 and C-11 and displayed high in vitro and in vivo affinities and selectivities for SERT relative to the dopamine and the norepinephrine transporters (DAT, NET). − Moreover, preliminary studies with IDAM and ADAM in nonhuman primates , or with DAPP or DASB in human brains showed that these ligands have promising characteristics for imaging SERT.…”

Development of Potent Type I Protein Arginine Methyltransferase (PRMT) Inhibitors of Leukemia Cell Proliferation

“…The synthesis of the compound 13a derivatives depicted in Scheme was performed following a five-step reaction pathway. Coupling of commercially available 2-mercaptobenzoic acid with acyl halides yielded compounds 21a – 21d according to the known literature and successively reacted with oxalyl dichloride in the presence of DMF to give the aroyl chloride; the resultant 22a – 22d were then reacted with N 1 , N 1 -dimethylethane-1,2-diamine to generate the target 23a – 23d analogues by amidation reaction under standard conditions with good yield. Sodium tetrahydroborate, boron trifluoride diethyl etherate was used to reduce 23a – 23d analogues to obtain the target 24a – 24d analogues in tetrahydrofuran.…”

Novel Radiotracers for Imaging the Serotonin Transporter by Positron Emission Tomography: Synthesis, Radiosynthesis, and in Vitro and ex Vivo Evaluation of 11C-Labeled 2-(Phenylthio)araalkylamines

“…A novel radioiodinated SERT radiotracer for SPECT imaging, [ 123 I]IDAM, has been described recently which was based on the 2-(phenylthio)araalkylamine structure, originally developed as nontricyclic antidepressants. [12][13][14] IDAM was shown to have high specificity and selectivity for SERT in vitro and ex vivo in rat biodistribution studies, 15 while SPECT studies on baboons using [ 123 I]IDAM demonstrated that a transient equilibrium was quickly reached with midbrain-to-cerebellum ratios of 1.8:1 obtained at 120 min postinjection. 16 Recently we reported the radiosynthesis of a 11 Clabeled potential SERT ligand in the 2-(phenylthio)-araalkylamines series (5-trifluoromethyl-2-(2-dimethylaminomethylphenylsulfanyl)phenylamine) and showed that it readily crossed the blood-brain barrier (BBB).…”