25109-08-4

Upstream product

• 3569-21-9 1H-indole-3-propanol 
• 98-59-9 p-toluenesulfonyl chloride 
• 59-88-1 phenylhydrazine hydrochloride 
• 100-63-0 phenylhydrazine 
• 141972-19-2 3-(indol-3'-yl)propyl trichloroacetate 

Downstream Products

• 13117-35-6 N-Dimethylhomotryptamine 
• 1158201-42-3 N-1-[3-(1H-indol-3-yl)propyl]-4-methyl-1-benzenesulfonamide 
• 1587712-74-0 3-[3-(3-{4-fluorophenyl}-1H-1-pyrazolyl)propyl]-1H-indole 
• 1587712-67-1 3-[3-(4-phenylethyl-1-piperazinyl)propyl]-1H-indole 
• 1587712-65-9 3-[3-(4-{2-fluorobenzyl}-1-piperazinyl)propyl]-1H-indole 
• 1587712-63-7 3-[3-(4-{4-(trifluoromethyl)phenyl}-1-piperazinyl)propyl]-1H-indole 
• 1394129-54-4 3-{3-[4-(2-fluorophenyl)-1-piperazinyl]-propyl}-1H-indole 
• 1394129-55-5 3-{3-[4-(4-fluorophenyl)-1-piperazinyl]-propyl}-1H-indole 

Relevant academic research and scientific papers

Synthesis and biological evaluation of potential acetylcholinesterase inhibitors based on a benzoxazine core

With the purpose of expanding the structural variety of chemical compounds available as pharmacological tools for the treatment of Alzheimer's disease, we synthesized and evaluated a novel series of indole-benzoxazinones (Family I) and benzoxazine-arylpiperazine derivatives (Family II) for potential human acetylcholinesterase (hAChE) inhibitory properties. The most active compounds 7a and 7d demonstrated effective inhibitory profiles with Ki values of 20.3 ± 0.9 μM and 20.2 ± 0.9 μM, respectively. Kinetic inhibition assays showed non-competitive inhibition of AChE by the tested compounds. According to our docking studies, the most active compounds from both series (Families I and II) showed a binding mode similar to donepezil and interact with the same residues.

Indole derivatives and its application on the medicament

The invention provides indole derivatives or stereisomers, tautomers, nitrogen oxides, solvate, metabolic products, pharmaceutically acceptable salts or prodrugs thereof for treating the alzheimer disease. The invention further discloses a pharmaceutical composition containing the compounds and a method of using the compounds or the pharmaceutical composition thereof to treat the alzheimer disease.

Synthesis and Docking of Novel 3-Indolylpropyl Derivatives as New Polypharmacological Agents Displaying Affinity for 5-HT1AR/SERT

A series of novel 3-indolylpropyl derivatives was synthesized and evaluated for their binding affinities at the serotonin-1A receptor subtype (5-HT1AR) and the 5-HT transporter (SERT). Compounds 11b and 14b exhibited the highest affinities at the 5-HT1AR (Ki = 43 and 56 nM), whereas compounds 11c and 14a were the most potent analogs at the SERT (Ki = 34 and 17 nM). On the other hand, compounds 14b and 11d showed potent activity at both targets, displaying a profile that makes them promising leads for the search for novel potent ligands with a dual mechanism of action. Molecular docking studies in all the compounds unveiled relevant drug–target interactions, which allowed rationalizing the observed affinities.

Radical-Mediated Dearomatization of Indoles with Sulfinate Reagents for the Synthesis of Fluorinated Spirocyclic Indolines

The dearomative introduction of trifluoromethyl and 1,1-difluoroethyl radicals, generated from their corresponding sulfinate salts, into the C2 position of indole derivatives allows the diastereoselective synthesis of three-dimensional 3,3-spirocyclic indolines over C-H functionalized indoles.

SUBSTITUTED HETEROARYL COMPOUNDS AND METHODS OF USE THEREOF

Provided herein are novel heteroaryl compounds, pharmaceutically acceptable salts and pharmaceutical formulations thereof for selectively inhibiting serotonin reuptake and/or acting as 5-HT1A receptor agonists. Also provided herein are pharmaceutical compositions comprising the heteroaryl compounds and methods of using the pharmaceutical compositions in treating central nervous system (CNS) dysfunction in a mammal, especially a human being.

SUBSTITUTED PIPERAZINE COMPOUNDS AND METHODS AND USE THEREOF

Provided herein are novel piperazine compounds acting as selective serotonin reuptake inhibitors and/or the 5-HT1A receptor agonists. The invention also relates to the methods of preparing the compound and pharmaceutical composition, and the use of treating central nervous system dysfunction in mammals especially in humans.

Synthesis and biological screening of novel indolalkyl arenes targeting the serotonine Transporter

A series of functionalized indolylalkylarenes 3-16(a and b) were synthesized and their affinities for the serotonin transporter were investigated in vitro. Compounds 3-12(a and b) were obtained by nucleophilic substitution of 3-(1H-indol-3-yl)propyl-4-methylbenzenesulfonates 2(a and b) with a series of azaheterocycles. Compounds 14-16(a and b) were prepared in a two-step sequence by reaction of 3-(1H-indol-3-yl)-2-methylpropanal with substituted 1,2-phenylenediamines. Compounds 3b, 4b, and 5b showed good binding affinities (Ki = 33.0, 48.0, and 17 nM, respectively). The other synthesized compounds showed moderate or no affinity in the binding studies. The affinities for the serotonin transporter of a new series of functionalized indolylalkylarenes 3-16(a and b) were investigated in vitro. With Ki values of 33.0, 48.0, and 17 nM, compounds 3b, 4b, and 5b, respectively, showed good binding affinities. The other synthesized compounds showed moderate or no affinity in the binding studies.

Synthesis, docking and pharmacological evaluation of novel homo- and hetero-bis 3-piperazinylpropylindole derivatives at SERT and 5-HT1A receptor

A series of 3-(3-(4-(3-(1H-indol-3-yl)propyl)piperazin-1-yl)propyl)-1H- indole derivatives (3a-d and 5a-f) as homo- and hetero-bis-ligands, were synthesized and evaluated for in vitro affinity at the serotonin transporter (SERT) and the 5-HT1A receptor. Compounds 5b and 5f showed nanomolar affinities for both targets. The experimental data were rationalized according to results obtained from docking experiments. These findings are in agreement with our proposal that bis-indole derivatives can bind both targets, and might serve as leads in the quest of ligands endowed with a dual mechanism of action.

Synthesis, 5-hydroxytryptamine1A receptor affinity and docking studies of 3-[3-(4-aryl-1-piperazinyl)-propyl]-1H-indole derivatives

A series of 3-[3-(4-aryl-1-piperazinyl)-propyl]-1H-indole derivatives (12a-h) was synthesized and evaluated for binding affinity at the human 5-hydroxytryptamine1A receptor (5-HT1AR) compounds (12b) and (12h) showed the highest 5-HT1A receptor affinity (IC 50-=15 nM). Molecular docking studies with all the compounds in a homology model of 5-HT1A showed that the main interaction anchoring the ligand in the receptor was a charge-reinforced bond between the protonated nitrogen atom (N-4) of the piperazine ring and Aspartate3.32.

Design, synthesis, and melatoninergic activity of new azido- and isothiocyanato-substituted indoles

To develop irreversibly binding ligands for the melatonin receptor(s) as tools for tracing the primary melatonin binding site, we report on the design and synthesis of new melatoninergic azido- and isothiocyanato-substituted indoles. All active compounds were partial agonists or antagonists in the Xenopus melanophore assay, the most potent being the 5-OMe C3-substituted azido 45 and isothiocyanato 46 analogues.