70449-94-4

Usage

Biological Activity

(+)-mk 801 is a potent antagonist of nmda with ki value of 30.5nm [1].mk 801 is a potent anticonvulsant exhibits both anxiolytic and sympathomimetic properties. it is found to be a noncompetitive antagonist of nmda. mk 801 can penetrate into the central nervous system. in the in vitro assay, mk 801 binds to rat cerebral cortical membrane with high affinity in a saturable manner. this binding is reversible even when the concentration of mk 801 is up to 100μm. it is also found that the binding shows a regional specificity. most of these binding sites are located in the hippocampus. in rat cortical-slice preparations, mk 801 causes a potent blockade of depolarizing responses to nmda with a high selectivity. this effect is persistent. the blockade can also cause a suppression of the epileptiform activity induced by tetrodotoxin or other neurotoxin [1].

InChI:InChI=1/C16H15N/c1-16-13-8-4-2-6-11(13)10-15(17-16)12-7-3-5-9-14(12)16/h2-9,15,17H,10H2,1H3

Upstream product

• 24167-43-9 5-methyl-10,11-dihydro-5H-dibenzo[a,d][7]annulene 
• 2732-90-3 5-methylene-10,11-dihydro-5H-dibenzo[a,d]cycloheptene 
• 1210-35-1 10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-one 
• 124070-07-1 C₂₀H₂₂N₂ 
• 50537-17-2 (+/-)-des-methyl MK-801 
• 124070-25-3 C₂₁H₂₄N₂ 
• 3433-80-5 1-Bromo-2-bromomethyl-benzene 
• 28272-96-0 2-vinylbenzaldehyde 
• 125025-17-4 3-bromo-5-methyl-5H-dibenzocyclohepten-5-ol 
• 124070-07-1 (+/-)-N-<(tert-butylimino)methyl>-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine 
• 125025-21-0 3-bromo-5-methyl-5-(hydroxyamino)-5H-dibenzocycloheptane 
• 3979-65-5 3-bromo-5H-dibenzo[a,d]cyclohepten-5-one 
• 50537-17-2 10,11-dihydro-5H-dibenzocyclohepten-5,10-imine 
• 87747-42-0 12-hydroxy-3-bromo-5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine 

Downstream Products

• 125134-28-3 (5S,10R)-(+)-3-bromo-10,11-dihydro-5-methyl-5H-dibenzocyclohepten-5,10-imine 
• 70450-22-5 12-benzyl-10,11-dihydro-5-methyl-5H-dibenzo[a,d]cyclohepten-5,10-imine 

Relevant academic research and scientific papers

A BRIDGEHEAD α-AMINO CARBANION: FACILE PREPARATION OF C5(BRIDGEHEAD)-SUBSTITUTED ANALOGUES OF (+/-)-5H-DIBENZOCYCLOHEPTEN-5,10-IMINE INCLUDING A STABLE α-IODO SECONDARY AMINE

The preparation of C5(bridgehead)-substituted analogues of (+/-)-5H-dibenzocyclohepten-5,10-imine via α-lithiation of a tert-butylformamidine precursor is presented.

Convergent Strategy to Dizocilpine MK-801 and Derivatives

A convergent total synthesis of MK-801 has been achieved. Key synthetic transformations include a multicomponent Barbier-type reaction to construct the α-branched amine, a selective Heck α-coupling tactic to generate the exocyclic alkene skeleton, and a late-stage intramolecular hydroamination reaction between the exocyclic alkene and the secondary protected amine. The efficacy of this method was demonstrated by the synthesis of two news analogues substituted on the aromatic rings.

Intermolecular Radical C(sp3)?H Amination under Iodine Catalysis

The direct amination of aliphatic C?H bonds has remained one of the most tantalizing transformations in organic chemistry. Herein, we report on a unique catalyst system, which enables the elusive intermolecular C(sp3)?H amination. This practical synthetic strategy provides access to aminated building blocks and fosters innovative multiple C?H amination within a new approach to aminated heterocycles. The synthetic utility is demonstrated by the synthesis of four relevant pharmaceuticals.

Benzyne addition to N-alkyl-4-hydroxy-1-methylisoquinolinium salts; a new and convenient synthesis of (±)-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]cyclohepten-5,10-imine (MK801)

Addition of benzyne, generated by three different methods, to N-benzyl-4-hydroxy-1-methylisoquinolinium betaine provides N-benzyl-5-methyl-11-oxo-5H-dibenzo[a,d] cyclohepten-5,10-imine which can be converted to MK801.

Synthesis and structure-activity relationship of C5-substituted analogues of (±)-10,11-dihydro-5H-dibenzo[a, d]cyclohepten-5,10-imine [(±)-desmethyl-MK801]: Ligands for the NMDA receptor-coupled phencyclidine binding site

A series of eight C5-substituted analogues of (±)-10,11-dihydroy-5H-dibenzo[a,d]cyclohepten-5,10-imine (1) have been prepared by the directed lithiation-alkylation (and acylation) of its (±)-N-tert-butylformamidinyl derivative 2 followed by formamidine solvolysis. An additional 10 analogues were prepared by elaboration of the C5-ethyl ester derivative. Analogues possessing large (e.g. propyl and larger) lipophilic substituents displace [3H]-1-(1-thienylcyclohexyl)piperidine ([3H]TCP) from the high-affinity phencyclidine (PCP) binding site in rat brain homogenates only at high concentrations (K(i) > 1000 nM); however, the presence of a polar amino functionality (e.g. 2-aminoethyl) offsets this effect (K(i) = 20 nM). Thus, the boundary condition for lipophilic substituents larger than ethyl appears to be polar in nature. Interaction of the 11 relatively small (MR 14) C5-substituted analogues of 1 with the high-affinity PCP binding site associated with the N-methyl-D-aspartate (NMDA) receptor is best described by the equation log (1/K(i)) = -5.83J + 0.64π + 7.41 (r = 0.90).

Synthesis and Pharmacological Evaluation of a Series of Dibenzocycloalkenimines as N-Methyl-D-aspartate Antagonists

A series of 73 dibenzocycloalkenimines were synthesized and evaluated for their ability to displace (+)-10,11-dihydro-5-methyl-5H-dibenzocyclohepten-5,10-imine (-(+)-10) from its specific binding site on rat cortical membranes.A number of the more active compounds (Ki ranging from 0.006 to 0.21 μM) were evaluated for N-methyl-D-aspartate (NMDA) antagonist activity in the rat cortical slice (Kb ranging from 0.08 to 0.9 μM) and anticonvulsant activity in the mouse against NMDA induced convulsions.The ED50 values ranged from 0.22 to 7.76 mg/kg and correlated reasonably well with the Kb determination.In the dibenzocyclohepten-5,10-imine series, the (+)-5S,10R enantiomer displayed consistently higher leves of biological activity.While substitution at the 3-position of (+)-10 with electronegative atoms generally increased in vitro activity, a loss of potency relative to (+)-10 (MK-801) was observed in vivo for all of the compounds tested.

Process for 5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine

(+)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine, and its pharmaceutically acceptable salts is useful as an anxiolytic, antidepressant, anticonvulsant, muscle relaxant and in the treatment of mixed anxiety-depression, minimal brain dysfunction and extrapyramidal disorders such as Parkinson's disease. The racemate of the compound is produced by a four-step synthetic process in about 65% yield from 5H-dibenzo[a,d]cyclohepten-5-one.

5-Alkyl or hydroxyalkyl substituted-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imines and anticonvulsant use thereof

5-Substituted-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imines, derivatives and pharmaceutically acceptable salts thereof are useful as anticonvulsants.