63625-94-5

Upstream product

• 867-13-0 diethoxyphosphoryl-acetic acid ethyl ester 
• 530-93-8 1,2,3,4-tetrahydronaphthalen-2-one 
• 154935-59-8 2-ethoxycarbonylmethyl-1,2,3,4-tetrahydronaphthalen-2-ol 

Downstream Products

• 91524-14-0 Napamezole 

Relevant academic research and scientific papers

Catalytic Enantioselective Bromoaminocyclization and Bromocycloetherification

We apply a chiral anionic phase-transfer system for the catalytic asymmetric bromoaminocyclization and bromocycloetherification of momo-functional benzo-cyclic alkenes. Various brominated tricyclic benzo-heterocycles were produced with up to 99% yields and 99% enantiomeric excess. The resulting enantioenriched hexahydro-benzoindoles are key building blocks of bioactive molecules. (Figure presented.).

Amination of arenes through electron-deficient reaction cascades of aryl epoxyazides

(Matrix presented) Aryl epoxyazides undergo efficient electron-deficient reaction cascades mediated by Lewis acids, leading to regiospecific amination of the aromatic ring.

Construction of functionalized indans by thallium(III) promoted ring contraction of 3-alkenols

An efficient four step protocol for the construction of functionalized indans was developed. 1-Tetralones were transformed into unsaturated esters by Reformatsky reaction with bromo-esters (ethyl 2-bromopropionate, ethyl bromoacetate or ethyl 2-bromobutyrate), followed by dehydration of the β-hydroxy-ester formed. Reduction of the ester moiety led to homoallylic alcohols bearing an endocyclic double bond. The oxidative rearrangement of these 3-alkenols was performed by thallium trinitrate (TTN) in a 2:1 mixture of AcOH/H2O, leading to the ring contraction products in moderate to very good yield. Fourteen examples of this sequence were studied. The oxidation of 3-alkenols prepared from 2-tetralones with TTN was also investigated. With these substrates the ring contraction reaction was not observed.

Potential antidepressants displayed combined α2-adrenoceptor antagonist and monoamine uptake inhibitor properties

Classical antidepressants are thought to act by raising monoamine (serotonin and noradrenaline) levels in the brain. This action is generally accomplished either by inhibition of monoamine metabolism (MAO inhibitors) or by blockade of monoamine uptake (tricyclic antidepressants and selective serotonin or noradrenaline reuptake inhibitors). However, all such agents suffer from a time lag (3-6 weeks) before robust clinical efficacy can be demonstrated. This delay may reflect inhibitory actions of noradrenaline at presynaptic α2A-adrenergic auto- or heteroreceptors which gradually down-regulate upon prolonged exposure. Blockade of presynaptic α2A-adrenoceptors by an antagonist endowed with monoamine uptake inhibition properties could lead to new antidepressants with greater efficacy and a shorter time lag. In the literature, only two molecules-have been described with such a pharmacological profile. Of these, napamezole (2) was chosen as a point of departure for the design of 4(5)-[(3,4-dihydro-2-naphthalenyl)methyl]-4,5-dihydroimidazole (4a), which displayed the desired profile: α2A-adrenoceptor antagonist properties and serotonin/noradrenaline uptake inhibition. From this original molecule, a series of derivatives was designed and synthesized, encompassing substituted as well as rigid analogues. Structure-activity relationships permitted the selection of 14c (4(5)-[(5-fluoroindan-2-yl)methyl]-4,5-dihydroimidazole) as a development candidate.

Synthesis and antidepressant properties of novel 2-substituted 4,5-dihydro-1H-imidazole derivatives

A unique combination of α2-adrenoreceptor antagonist and serotonin-selective reuptake inhibitory activities has been identified in a series of 2-substituted 4,5-dihydro-1H-imidazole derivatives. This combination of blocking activities has provided one of these derivatives, napamezole hydrochloride (2), with potential as an antidepressant. A discussion of the syntheses of these compounds includes a convenient method for the conversion of nitriles to imidazolines with ethylenediamine and trimethylaluminum.

Antidepressant imidazolines and related compounds

2-(2-Naphthalenyl)alkyl-4,5-dihydro-1H-imidazoles and -tetrahydropyrimidines, the corresponding 3,4-dihydronaphthalenyl and 1,2,3,4-tetrahydronaphthalenyl compounds; and the corresponding indene and indane derivatives, useful as antidepressant or diuretic agents, are prepared by reacting the appropriate 2-(cyanoalkyl)naphthalene or -indane derivative (or the corresponding ester or imino-ether) with an alkylenediamine.