80272-06-6

Usage

InChI:InChI=1/C15H12Cl2O2/c16-13-7-6-11(8-14(13)17)12(9-15(18)19)10-4-2-1-3-5-10/h1-8,12H,9H2,(H,18,19)

Upstream product

• 5653-29-2 2-(1,3-dithiolan-2-yl)-1-phenylethan-1-one 
• 1198097-88-9 methyl 3-(3,4-dichlorophenyl)-3-phenylpropanoate 
• 7312-27-8 3,4-Dichlorocinnamic acid 
• 6287-38-3 3,4-dichlorobenzaldehyde 
• 55417-50-0 ethyl 2-cyano-3-(3,4-dichlorophenyl)-prop-2-enecarboxylate 
• 108-86-1 bromobenzene 
• 71-43-2 benzene 
• 203317-12-8 2-Cyano-3-(3,4-dichloro-phenyl)-3-phenyl-propionic acid ethyl ester 

Downstream Products

• 1198097-89-0 1-diazo-4-(3,4-dichlorophenyl)-4-phenylbutan-2-one 
• 96850-13-4 trans-3-(3,4-dichlorophenyl)-2,3-dihydro-N-methyl-1H-inden-1-amine hydrochloride 
• 96850-13-4 LNK 131 hydrochloride 
• 748724-48-3 LNK 131 
• 85663-59-8 1-[(1R,3R)-3-(3,4-Dichloro-phenyl)-indan-1-yl]-4-((E)-3-phenyl-allyl)-piperazine 
• 85663-58-7 1-[(1S,3R)-3-(3,4-Dichloro-phenyl)-indan-1-yl]-4-((E)-3-phenyl-allyl)-piperazine 
• 85663-57-6 3-{4-[(1S,3S)-3-(3,4-Dichloro-phenyl)-indan-1-yl]-piperazin-1-yl}-propan-1-ol 
• 80273-19-4 3-{4-[(1R,3S)-3-(3,4-Dichloro-phenyl)-indan-1-yl]-piperazin-1-yl}-propan-1-ol 
• 85663-56-5 2-{4-[(1S,3S)-3-(3,4-Dichloro-phenyl)-indan-1-yl]-piperazin-1-yl}-ethanol 
• 85663-55-4 2-{4-[(1R,3S)-3-(3,4-Dichloro-phenyl)-indan-1-yl]-piperazin-1-yl}-ethanol 
• 85663-54-3 (+)-cis-1-<3-(3,4-dichlorophenyl)indan-1-yl>-4-methylpiperazine 
• 85663-53-2 (+)-trans-1-<3-(3,4-dichlorophenyl)indan-1-yl>-4-methylpiperazine 
• 86939-07-3 1-Chloro-3-(3,4-dichloro-phenyl)-indan 
• 80272-59-9 cis-3-(3,4-dichlorophenyl)-2,3-dihydro-1H-inden-1-ol 

Relevant academic research and scientific papers

Slow-onset, long-duration 3-(3′,4′-dichlorophenyl)-1-indanamine monoamine reuptake blockers as potential medications to treat cocaine abuse

A series of 3-(3′,4′-dichlorophenyl)-1-indanamine monoamine reuptake blockers have been synthesized in an effort to develop a compound that could be used as a maintenance therapy to treat cocaine abuse. Since the effects of cocaine on dopamine (DA) and serotonin (5HT) transporters are important components of its pharmacological activity, the focus was on nonselective inhibitors of monoamine transport. To reduce or eliminate the abuse potential of a DA reuptake blocker, the compounds were designed to be slow-onset, long-duration prodrugs whose N-demethylated metabolites would have increased activity over the parent compound with the ideal being a parent compound that has little or no activity. To achieve this, pairs of compounds with different groups on the amine nitrogen and with and without an additional N-methyl group were synthesized. All of the synthesized compounds were screened for binding and reuptake at the cloned human DA, 5HT, and norepinephrine (NE) transporters. As previously found, trans isomers are nonselective blockers of DA, 5HT, and NE reuptake, cis isomers with small N-alkyl groups are selective blockers of 5HT reuptake, and tertiary amines of the trans compounds are less potent than the corresponding N-demethylated secondary amines as blockers of DA reuptake. Larger N-alkyl groups in both the trans and cis series were found to reduce activity for the 5HT and NE transporters with less effect at DA transporters. Selected trans compounds were also screened for locomotor activity in mice and generalization to a cocaine-like profile in rats. With intraperitoneal administration, all of the trans isomers showed a slow onset of at least 20 min and an extremely long duration of action in the locomotor assays. Several of the trans compounds also fully generalized to a cocaine-like pharmacological profile. An initial lead compound, the N,N-dimethyl analogue trans-1b, was resolved into chirally pure enantiomers. Surprisingly, both enantiomers were found to have significant affinity for the DA transporter and to cause locomotor activation. This is in contrast to the N-methyl compound in which only the (+)-enantiomer had significant activity. The absolute configuration of the more active enantiomer was determined by X-ray crystallography to be 3R,1S.

Enantiopurity determination of the enantiomers of the triple reuptake inhibitor indatraline

The present study describes the development of two approaches for the determination of the enantiopurity of both enantiomers of indatraline. Initially, a method was developed using different chiral solvating agents (CSAs) for diastereomeric discrimination regarding signal separation in 1H nuclear magnetic resonance (NMR) spectroscopy, revealing MTPA as a promising choice for the differentiation of the indatraline enantiomers. This CSA was also tested for its ideal molar ratio, temperature, and solvent. Optimized conditions could be achieved that made determination of enantiopurity for (1R,3S)-indatraline up to 98.9% enantiomeric excess (ee) possible. To quantify even higher enantiopurities, a high-performance liquid chromatography (HPLC) method based on a modified β-cyclodextrine phase was established. The influence of buffer type, concentration, pH value, percentage and kind of organic modifier, temperature, injection volume as well as sample solvent on chromatographic parameters was investigated. Afterwards, the reliability of the established HPLC method was demonstrated by validation according to the ICH guideline Q2(R1) regarding specificity, accuracy, precision, linearity, and quantitation limit. The developed method proved to be strictly linear within a concentration range of 1.25-1000 μM for the (1R,3S)-enantiomer and 1.25-750 μM for its mirror image that enables a reliable determination of enantiopurities up to 99.75% ee for the (1R,3S)-enantiomer and up to 99.67% ee for the (1S,3R)-enantiomer.

NEW DIFLUOROKETAMIDE DERIVATIVES

The invention provides novel compounds having the general formula (I) wherein R1, R2, R3, R4, R5, R6, R7, R8 and R9 are as described herein, compositions including the compounds and methods of using the compounds.

A Weinreb Amide Based Building Block for Convenient Access to β,β-Diarylacroleins: Synthesis of 3-Arylindanones

Towards the synthesis of symmetrical and unsymmetrical β,β-diarylacroleins for assembling diarylmethine fragments present in biologically important molecules, we have developed a new Weinreb amide (WA) based building block, derived from propiolic acid. The WA functionality present in this compound allowed the sequential addition of various arylmagnesium bromide reagents in a controlled manner. The developed methodology for the access to β,β-diarylacroleins has been utilised for the synthesis of biologically important 3-arylindanone molecules. Synthesis of both symmetrical and unsymmetrical β,β-diarylacrolein and diarylmethine fragments, have been achieved via easily accessible and hitherto unknown Weinreb Amide (WA) based building block 11. The WA functionality allowed the sequential addition of nucleophiles such as arylmagnesium bromide in a controlled manner, which has enabled the synthesis of an important 3-arylindanone molecule.

Remarkable electronic effect on the diastereoselectivity of the Heck reaction of methyl cinnamate with arenediazonium salts: Formal total synthesis of (±)-indatraline and (±)-sertraline

An efficient and stereoselective protocol for the preparation of β,β-disubstituted acrylates in good to high yields by means of a Heck-Matsuda arylation was accomplished. The method employs a base- and ligand-free Heck arylation reaction of methyl cinnamate using both electron-deficient and electron-rich arenediazonium salts as electrophiles. The Heck reaction displays a remarkable electronic dependence regarding the diastereoselectivity of the arylation process, which correlates with the electronic nature of the arenediazonium salts employed. A rationale for the observed diastereoselectivity is presented. The overall methodology provides a convenient route to 3-arylindanones and 4aryltetralones allowing the concise formal total syntheses of the therapeutically important psychoactive compounds (± )-indatraline and (± )-sertraline.

TREATMENT OF NEURODEGENERATIVE DISEASES USING INDATRALINE ANALOGS

Methods and compositions useful in the treatment or prevention of synucleinopathies, such as Parkinson''s disease, diffuse Lewy body disease, and multiple system atrophy, or other neurodegenerative diseases (e.g., amyotrophic lateral sclerosis, Huntington''s disease, and Alzheimer''s disease) are provided. The treatment including administering to a subject an indatraline derivative that inhibits the aggregation of a-synuclein.

Synthesis of 3-aryl-1-indanamines

The present invention is a method of preparing a 3-aryl-1-indanamine represented by structural formula I: and physiologically acceptable salts thereof. In structure I, phenyl ring A can be unsubstituted or substituted with 1-4 substitutents. R1is an aromatic group which can be substituted or unsubstituted. R2and R3are each, independently, hydrogen, an aliphantic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, an aralkyl group, or a substituted aralkyl group. Alternatively, R2and R3, taken together with the nitrogen substitutent on the indan ring, form a non-aromatic ring system having 1-2 heteroatoms.

Neuroleptic activity and dopamine-uptake inhibition in 1-piperazino-3-phenylindans

A series of 1-piperazino-3-phenylindans was synthesized and tested for neuroleptic and thymoleptic activity. Neuroleptic activity was found only in trans racemates and was associated with one of the enantiomers only. The potent and long-acting neuroleptic compound trans-4-[3-(4-fluorophenyl)-6-(trifluoromethyl)indan-1-yl]-1-piperazineeth anol (Lu 18-012, tefludazine) was developed by systematic variation of structural components. Thymoleptic activity was optimized, especially with respect to dopamine-uptake inhibition. No geometrical stereoselectivity was found with regard to dopamine-uptake inhibition, but a high enantioselectivity could be demonstrated for both cis and trans racemates. The most potent compounds were 1-piperazino-3-(3,4-dichlorophenyl)indans with IC50 values of about 2 nM for inhibition of dopamine uptake.