81347-68-4

Upstream product

• 21763-00-8 1-bromo-3-chloro-1-phenylpropane 
• 402-45-9 4-hydroxybenzotrifluoride 
• 18776-12-0 3-chloro-1-phenyl-propan-1-ol 
• 2687-12-9 cinnamyl chloride 
• 104-52-9 phenylpropyl chloride 
• 936-59-4 3-chloropropiophenone 

Downstream Products

• 54910-89-3 FLUOXETINE 
• 56225-81-1 N,N-dimethyl-3-phenyl-3-(4-(trifluoromethyl)phenoxy)-1-propylamine 
• 83891-03-6 norfluoxetine 

Relevant academic research and scientific papers

Dual Cobalt and Photoredox Catalysis Enabled Intermolecular Oxidative Hydrofunctionalization

A general protocol has been developed for the Markovnikov-selective intermolecular hydrofunctionalization based on visible-light-mediated Co/Ru dual catalysis. The key feature involves the photochemical oxidation of an organocobalt(III) intermediate deriv

Molecular basis for selective serotonin reuptake inhibition by the antidepressant agent fluoxetine (Prozac)

Inhibitors of the serotonin transporter (SERT) are widely used antidepressant agents, but the structural mechanism for inhibitory activity and selectivity over the closely related norepinephrine transporter (NET) is not well understood. Here we use a combination of chemical, biological, and computational methods to decipher the molecular basis for high-affinity recognition in SERT and selectivity over NET for the prototypical antidepressant drug fluoxetine (Prozac; Eli Lilly, Indianapolis, IN). We show that fluoxetine binds within the central substrate site of human SERT, in agreement with recent X-ray crystal structures of LeuBAT, an engineered monoamine-like version of the bacterial amino acid transporter LeuT. However, the binding orientation of fluoxetine is reversed in our experimentally supported model comparedwith the LeuBAT structures, emphasizing the need for careful experimental verification when extrapolating findings from crystal structures of bacterial transporters to human relatives. We find that the selectivity of fluoxetine and nisoxetine, a NET selective structural congener of fluoxetine, is controlled by residues in different regions of the transporters, indicating a complex mechanism for selective recognition of structurally similar compounds in SERT and NET. Our findings add important new information on the molecular basis for SERT/NET selectivity of antidepressants, and provide the first assessment of the potential of LeuBAT as a model system for antidepressant binding in human transporters, which is essential for future structure-based drug development of antidepressant drugs with fine-tuned transporter selectivity. Copyright

MODULATORS OF CENTRAL NERVOUS SYSTEM NEUROTRANSMITTERS

Disclosed are agents having pharmacological activity against cellular receptors and intracellular singaling, particularly receptors and sigaling pathways of central nervous system (CNS) neurotransmitters. Also disclosed are related methods and compositions for the treatment or prevention of diseases or disorders using the agents.

Imidazole analogues of fluoxetine, a novel class of anti-Candida agents

Imidazole analogues of fluoxetine have been obtained by replacing the methylamino terminus of aminopropane chain with the imidazole ring. The newly designed imidazoles showed potent anti-Candida activity, superior to those of miconazole and other antifungal agents of clinical interest. 1-(4-Chlorophenyl)-l-(2,4-dichlorophenoxy)-3-(1H-imidazol-1-yl)propane (16), the most active among test imidazoles, Was about 2-fold more active and as much less cytotoxic than miconazole. High increase of activity was observed with methyl, nitro, fluorine, and chlorine (Cl > F > CH3 > NO2 > CF3).

Identification and comparison of impurities in fluoxetine hydrochloride synthesized by seven different routes

Fluoxetine HCl was prepared by seven different synthetic routes, all previously reported. The major impurities in each route were identified by GC/MS, HPLCMS, and gradient HPLC analysis. Impurities were classified as being derived from impurities in 4-chlorobenzotrifluoride, those arising during the SNAr reaction of this compound and 3-methylamino-1-phenyl-propanol, and those arising during the synthesis of this alcohol. Fifteen impurities belonging to the latter two categories were identified, and their structures were confirmed by synthesis of authentic material for most of the compounds. It was found that a variety of analytical tools was needed for complete characterization of the impurity profile of fluoxetine HCl and that purification of the intermediate and recrystallization of the drug itself are highly effective in minimizing the levels of the impurities.

Aryloxyphenylpropylamines

3-Aryloxy-3-phenylpropylamines and acid addition salts thereof, useful as psychotropic agents, particularly as anti-depressants.