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Inhibition of [3H]dopamine uptake into striatal synaptosomes by isoquinoline derivatives structurally related to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Isoquinoline derivatives structurally related to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 1-methyl-4-phenylpyridinium (MPP+) may be endogenous neurotoxins causing nigral cell death in Parkinson’s disease. These compounds inhibit mitochondrial function but, like MPP+, require accumulation in dopaminergic neurones via the dopamine reuptake system to exert toxicity. We, now, examine the substrate affinity of 14 neutral and quaternary isoquinoline derivatives (7 isoquinolines, 2 dihydroisoquinolines and 5 1,2,3,4-tetrahydroisoquinolines) for the dopamine reuptake system by their ability to inhibit the uptake of [3H]dopamine into rat striatal synaptosomes. Ten isoquinoline derivatives and MPP+ inhibited [3H]dopamine uptake in a concentration-dependent manner. Only 5 isoquinoline derivatives produced 50% inhibition of [3H]dopamine uptake (IC50 = 8.0-50.0 muM), none of which were as potent as MPP+ (IC50 = 0.33 muM). These findings suggest that isoquinoline derivatives are moderate to poor substrates for the dopamine reuptake system and that high concentrations of, or prolonged exposure to, isoquinoline derivatives may be necessary to cause neurodegeneration.

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Reference£º
Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

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Silicon Polonovski Reaction. Formation and Synthetic Application of alpha-Siloxy Amines

A new and versatile synthetic intermediate, alpha-siloxy amine was prepared in situ by the base-promoted rearrangement of a siloxyammonium salt obtained by treatment of a tertiary amine N-oxide with trialkylsilyl trifluoromethanesulfonate.The best combination of the base and silylating reagent was found to be methyllithium and t-butyldimethylsilyl trifluoromethanesulfonate.The reactions of alpha-siloxy amines with acyl halides and haloformates gave the corresponding amides and carbamates in moderate to good yields, respectively.Treatment of alpha-siloxy amines with acetic acid resulted in a direct dealkylation to free secondary amines.Fluoride induced alkylation of alpha-siloxy amines using alkyl halides as electrophiles leading to tertiary amines was also examined and demonstrated to be a new transalkylation method of amines.

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Reference£º
Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

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SELECTIVE REDUCTION OF THE N-O BOND IN N-OXIDES AND NITRONES BY SODIUM HYDROGEN TELLURIDE

Sodium hydrogen telluride reduces tert.-amine N-oxides to the corresponding amines in very high yield, but does not reduce sulphoxides.This reagent also reduces nitrones to sec.-amines at pH6 and to imines at alkaline pH (10-11).

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Reference£º
Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

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N-Methylation of Amines with Methanol Catalyzed by a Cp?Ir Complex Bearing a Functional 2,2?-Bibenzimidazole Ligand

A new type of Cp?Ir complex bearing a functional 2,2?-bibenzimidazole ligand was designed, synthesized, and found to be a highly effective and general catalyst for the N-methylation of a variety of amines with methanol in the presence of a weak base (0.3 equiv of Cs2CO3).

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Reference£º
Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

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Direct and Efficient C(sp3)-H Bond Alkylation of Tetrahydroisoquinolines and Isochroman with Alkylzinc Reagents

An efficient C(sp3)?H bond alkylation of tetrahydroisoquinolines and isochroman with alkylzinc reagents was demonstrated. This transformation could be readily performed under mild conditions in the absence of a heavy metal catalyst, affording a wide range of potentially biologically active compounds. In addition, this approach exhibited excellent compatibility with various sensitive functional groups such as a cyano group, an ester group as well as a boronic acid pinacol ester group. (Figure presented.).

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Reference£º
Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

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Concurrent Biocatalytic Oxidation and C-C Bond Formation via Gold Catalysis: One-Pot Alkynylation of N-Alkyl Tetrahydroisoquinolines

A cross-dehydrogenative coupling process has been developed involving the enzymatic oxidation of tetrahydroisoquinolines (THIQ) together with gold-catalyzed C-C bond-formation. The transformation demonstrates the compatibility of gold-mediated chemocatalysis and monoamine oxidase biocatalysis which act co-operatively in one vessel. A range of N-alkyl THIQs were functionalized in this manner at C-(1) position in high yields.

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Reference£º
Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

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Methylation of amines, nitrobenzenes and aromatic nitriles with carbon dioxide and molecular hydrogen

CO2/H2 was successfully employed in alkylation reactions by performing CO2 reduction and amine N-methylation in one-pot. In the presence of a simple CuAlOx catalyst, N-methyl or N,N-dimethyl amines with different structures can be selectively synthesized with up to 96% yields by applying amine, nitrobenzene and nitrile as starting materials.

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Reference£º
Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

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Selective trifluoromethylation and alkynylation of tetrahydroisoquinolines using visible light irradiation by Rose Bengal

A convenient and efficient method for oxidative coupling of tetrahydroisoquinoline derivatives with trimethyl(trifluoromethyl)silane and terminal alkynes to 1-trifluoromethylated or 1-alkynylated tetrahydroisoquinolines via CH activation was developed using visible light irradiation. The protocol uses Rose Bengal as the catalyst, air as terminal oxidant, and the trifluoromethylation or alkynylation was selectively performed at the alpha-position of nitrogen under extremely mild conditions.

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Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

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Nitrogen-containing remote functionalised organolithium compounds by reductive opening of five- and six-membered heterocycles

The reaction of different five- or six-membered nitrogen- containing heterocycles such as N-isopropyl-2-phenylpyrrolidine (1), N-phenyl-3-pyrroline (6), N-phenylisoindoline (10), N- phenyltetrahydroisoquinoline (13) and N- methyltetrahydroisoquinoline (19) with an excess of lithium powder ad a catalytic amount of DTBB (4.5 mol %), followed by treatment with electrophiles [H2O, D2O, MeI, CH2=CHCH2Br, Pr(i)CHO,Bu(t)CHO, PhCHO, Me2CO, Pr(n)COMe, PhCOMe, (CH2)4CO, (CH2)5CO, CO2] and final hydrolysis gives a wide series of functionalised amines 3, 8, 9, 12 and 19, the key step in the process, being the reductive opening of the starting material giving a dianionic remote functionalised organolithium compound.

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Reference£º
Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

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A Mild and Chemoselective Reduction of Cyclic Iminium Salts

N-Substituted cyclic iminium salts are conveniently reduced to the corresponding tertiary amines in good yields by reaction with tributylstannane in methanol at room temperature.A variety of functional groups (such as ketonic groups) present in the molecule are not affected under these conditions.

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Reference£º
Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem