569686-87-9

Upstream product

• 569687-12-3 (+)-(1R,2R,3R,5R,6R)-2-amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid diethyl ester 
• 1805-32-9 3,4-dichlorobenzyl alcohol 
• 260353-79-5 ethyl (-)-(1R,5R,6R)-6-fluoro-2-oxobicyclo[3.1.0]hexane-6-carboxylate 
• 748780-77-0 3,4-dichlorobenzyl-2,2,2-trichloroacetoimidate 
• 748780-69-0 (+)-(1R,5R,6R)-6-fluorobicyclo[3.1.0]hex-2-ene-2,6-dicarboxylic acid diethyl ester 
• 748780-68-9 (1R,5R,6R)-6-fluoro-2-trifluoromethane-sulfonyloxobicyclo[3.1.0]hex-2-ene-6-carboxylic acid ethyl ester 
• 748780-71-4 (-)-(1R,2S,3R,5R,6R)-6-fluoro-2,3-dihydroxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid diethyl ester 
• 748780-75-8 (-)-(1R,2R,3R,5R,6R)-2-azido-6-fluoro-3-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid diethyl ester 
• 748780-73-6 (+)-(1R,1aR,1bS,4aR,5aR)-1-fluoro-3,3-dioxotetrahydro-2,4-dioxa-3λ⁶-thiacyclopropa[a]pentalene-1,1b-dicarboxylic acid diethyl ester 
• 748780-78-1 (-)-(1R,2R,3R,5R,6R)-2-azido-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid diethyl ester 
• 1308835-38-2 ethyl (1R,5R,6R)-6-fluoro-2-[(trimethylsilyl)oxy]bicyclo[3.1.0]hex-2-ene-6-carboxylate 
• 1308835-40-6 ethyl (1R,3R,5R,6R)-6-fluoro-3-hydroxy-2-oxo bicyclo[3.1.0]hexane-6-carboxylate 
• 1308835-50-8 ethyl (1R,3R,5R,6R)-3-[(3,4-dichloro benzyl)oxy]-6-fluoro-2-oxo bicyclo[3.1.0]hexane-6-carboxylate 
• 1308835-55-3 (1R,2S,3R,5R,6R)-2-amino-2-cyano-3-[(3,4-dichloro benzyl)oxy]-6-fluoro bicyclo[3.1.0]hexane-6-carboxamide citrate 

Downstream Products

• 820244-79-9 (1R,2R,3R,5R,6R)-2-allyloxycarbonylamino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid 

Relevant academic research and scientific papers

PROCESS FOR PRODUCING 3-ALKOXY-2-AMINO-6-FLUOROBICYCLO [3.1.0] HEXANE-2,6-DICARBOXYLIC ACID DERIVATIVE AND INTERMEDIATE THEREOF

A process for producing a 3-alkoxy-2-amino-6-fluoro bicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivative represented by the formula (I) or a salt thereof, which includes converting a compound represented by the formula (VI) or a salt thereof to the compound represented by the formula (I) or a salt thereof.

2-AMINOBICYCLO 3.1.0 HEXANE-2,6-DICARBOXYLIC ESTER DERIVATIVE

A drug effective for the treatment and prevention of psychiatric disorders such as schizophrenia, anxiety and related ailments thereof, depression, bipolar disorder and epilepsy. The drug antagonizes the action of group II metabotropic glutamate receptors

Synthesis, in vitro pharmacology, structure - Activity relationships, and pharmacokinetics of 3-alkoxy-2-amino-6-fluorobicyclo[3.1.0]hexane-2,6- dicarboxylic acid derivatives as potent and selective group II metabotropic glutamate receptor antagonists

Novel group II metabotropic glutamate receptor (mGluR) antagonists, 3-alkoxy-2-amino-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivatives 11 and 12, were discovered by the incorporation of a hydroxy or alkoxyl group onto the C-3 portion of selective and potent group II mGluR agonist 5, (1R,2S,5R,6R)-2-amino-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid. Among these compounds, (1R,2R,3R,5R,6R)-2-amino-3-(3,4-dichlorobenzyloxy)-6- fluorobicyclo-[3.1.0]hexane-2,6-dicarboxylic acid (-)-11be (MGS0039) was a highly selective and potent group II mGluR antagonist with the best pharmacokinetic profile. Compound (-)-11be exhibited high affinities for mGlu 2 (Ki = 2.38 ± 0.40 nM) and mGlu 3 (4.46 ± 0.31 nM) but low affinity for mGluR 7 (Ki = 664 ± 106 nM), and potent antagonist activities for mGlu 2 (IC50 = 20.0 ± 3.67nM) and mGluR 3 (IC50 = 24.0 ± 3.54 nM) but much less potent antagonist activities for mGlu 4 (IC50 = 1740 ± 1080 nM), mGlu 6 (IC50 = 2060 ± 1270 nM), mGlu 1 (IC50 = 93300 ± 14600 nM), and mGluR 5 (IC50 = 117000 ± 38600 nM). No significant agonist activities of (-)-11be were found for mGluRs 2, 3, 4, 6, 1, and 5 (EC50 > 100000 nM). Furthermore, (-)-11be exhibited dose-dependent oral absorption (plasma Cmax: 214 ± 56.7, 932 ± 235, and 2960 ± 1150 ng/mL for 3 mg/kg, 10 mg/kg, and 30 mg/kg, po, respectively) and acceptable blood-brain barrier penetration (brain C max: 13.2 ng/mL for 10 mg/kg, po 6 h). In this paper, we report the synthesis, in vitro pharmacological profile, and structure-activity relationships (SARs) of 3-alkoxy-2-amino-6-fluorobicyclo[3.1.0]hexane-2,6- dicarboxylic acid derivatives 11 and 12, and pharmacokinetic profiles of several typical compounds.

6-FLUOROBICYCLO 3.1.0 HEXANE DERIVATIVES

An antidepressant comprising, as an active ingredient, a compound having an antagonistic effect on group II metabotropic glutamate receptors, as well as a 2-amino-3-alkoxy-6-fluoro-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivative of Formula [I]: [whe