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Method for preparing tetrahydroisoquinolines

A method for preparing 1,2,3,4-tetrahydroisoquinolines comprising heating N-halo or hydroxyethyl-N-benzylamines in an aluminum chloride melt at 160-210.

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

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Nitrogen heterocyclic derivatives, its preparation method and medical use thereof (by machine translation)

The invention relates to a nitrogen heterocyclic derivatives, its preparation method and medical use thereof. In particular, the invention relates to the general formula (I) indicated by the nitrogen heterocyclic derivatives, their preparation, pharmaceutical compositions containing the same, and as SMO antagonists, in particular for treating with the Hedgehog signal pathway-related diseases such as cancer in use. Wherein the general formula (I) with each group in the definition as defined in the specification. (by machine translation)

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

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A Direct Synthesis of alpha-Keto Five- and Six-Membered Cyclic Ethers

A simple synthesis of tetrahydro-2H-pyran-2-yl and tetrahydrofuran-2-yl ketones from their corresponding carboxylic acids was studied.A comparison was made of organolithium and Grignard alkylating reagents as a means of reducing the formation of byproducts and improving the yields.

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Tetrahydroisoquinoline – Wikipedia,
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Catalytic Asymmetric Electrochemical Oxidative Coupling of Tertiary Amines with Simple Ketones

Catalytic asymmetric electrochemical C-H functionalization of simple ketones has been developed. The transformation is realized by the combination of electrochemical oxidation and chiral primary amine catalysis. This metal- and oxidant-free method furnishes diverse C1-alkylated tetrahydroisoquinolines in high yields and with excellent enantioselectivities under very mild conditions.

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Tetrahydroisoquinoline – Wikipedia,
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Studies on cerebral protective agents. IX. Synthesis of novel 1,2,3,4-tetrahydroisoquinolines as N-methyl-D-aspartate antagonists

A series of 1,2,3,4-tetrahydroisoquinoline derivatives were synthesized and evaluated for anticonvulsant activity against intracerebro-ventriculas (i.c.v.) N-methyl-D-aspartate (NMDA)-induced seizures in mice. Among these compounds, (+)-1-methyl-1-phenyl-1,2,3,4-tetrahydroisoquinoline hydrochloride ((+)-1a, FR115427) was the most effective anticonvulsant, and also protected CA1 hippocampal neurons from ischemia-induced neuronal degeneration in rats at 32mg/kg i.p. In addition, (+)-1a showed anti-hypoxic activity in mice at 3.2-32mg/kg i.p. The absolute configuration at the C-1 position of the isoquinoline ring was determined to be 5 by a single-crystal X-ray analysis of (+)-1a (+)-di-p-toluoyl-D-tartrate. Structure-activity relationships with regard to the anticonvulsant activity of this series of compounds are discussed, and the three-dimensional structures of (S)-(+)-1a and MK801 are compared.

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Tetrahydroisoquinoline – Wikipedia,
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Structure-activity relationships of 7-substituted dimethyltyrosine-tetrahydroisoquinoline opioid peptidomimetics

The opioid receptors modulate a variety of biological functions, including pain, mood, and reward. As a result, opioid ligands are being explored as potential therapeutics for a variety of indications. Multifunctional opioid ligands, which act simultaneously at more than one type of opioid receptor, show promise for use in the treatment of addiction, pain, and other conditions. Previously, we reported the creation of bifunctional kappa opioid receptor (KOR) agonist/mu opioid receptor (MOR) partial agonist ligands from the classically delta opioid receptor (DOR) antagonist selective dimethyltyrosine-tetrahydroisoquinoline (Dmt-Tiq) scaffold through the addition of a 7-benzyl pendant on the tetrahydroisoquinoline ring. This study further explores the structure-activity relationships surrounding 7-position pendants on the Dmt-Tiq scaffold. Some analogues maintain a KOR agonist/MOR partial agonist profile, which is being explored in the development of a treatment for cocaine addiction. Others display a MOR agonist/DOR antagonist profile, which has potential to be used in the creation of a less addictive pain medication. Ultimately, we report the synthesis and in vitro evaluation of novel opioid ligands with a variety of multifunctional profiles.

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

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Synthesis, structure-activity relationships, and pharmacokinetic properties of dihydroorotate dehydrogenase inhibitors: 2-cyano-3-cyclopropyl- 3-hydroxy. N-[3′-methyl-4′-(trifluoromethyl)phenyl]propenamide and related compounds

The active metabolite (2) of the novel immunosuppressive agent leflunomide (1) has been shown to inhibit the enzyme dihydroorotate dehydrogenase (DHODH). This enzyme catalyzes the fourth step in de novo pyrimidine biosynthesis. A series of analogues of the active metabolite 2 have been synthesized. Their in vivo biological activity determined in rat and mouse delayed type hypersensitivity has been found to correlate well with their in vitro DHODH potency. The most promising compound (3) has shown activity in rat and mouse collagen (II)-induced arthritis models (ED50 = 2 and 31 mg/kg, respectively) and has shown a shorter half-life in man when compared with leflunomide. Clinical studies in rheumatoid arthritis are in progress.

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

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A Series of Analogues to the AT2R Prototype Antagonist C38 Allow Fine Tuning of the Previously Reported Antagonist Binding Mode

We here report on our continued studies of ligands binding to the promising drug target angiotensin II type 2 receptor (AT2R). Two series of compounds were synthesized and investigated. The first series explored the effects of adding small substituents to the phenyl ring of the known selective nonpeptide AT2R antagonist C38, generating small but significant shifts in AT2R affinity. One compound in the first series was equipotent to C38 and showed similar kinetic solubility, and stability in both human and mouse liver microsomes. The second series was comprised of new bicyclic derivatives, amongst which one ligand exhibited a five-fold improved affinity to AT2R as compared to C38. The majority of the compounds in the second series, including the most potent ligand, were inferior to C38 with regard to stability in both human and mouse microsomes. In contrast to our previously reported findings, ligands with shorter carbamate alkyl chains only demonstrated slightly improved stability in microsomes. Based on data presented herein, a more adequate, tentative model of the binding modes of ligand analogues to the prototype AT2R antagonist C38 is proposed, as deduced from docking redefined by molecular dynamic simulations.

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Direct vinylogous oxidative cross-dehydrogenative coupling of 4-nitroisoxazoles with N-aryl tetrahydroisoquinolines in water under air conditions

A direct vinylogous cross-dehydrogenative coupling (CDC) reaction of N-aryl tetrahydroisoquinolines with 3,5-dialkyl-4-nitroisoxazoles catalysed by CuBr using air as the oxidant in water has been developed. This new strategy provides an efficient and environmentally benign way to access medicinally important isoxazole substituted tetrahydroisoquinoline derivatives under mild conditions.

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Tetrahydroisoquinoline – Wikipedia,
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Synthesis and biological evaluation of benzothiazole derivatives as potent antitumor agents

Based on 2-methyl-4-nitro-2H-pyrazole-3-carboxylic acid[2- (cyclohexanecarbonylamino)benzothiazol-6-yl]amide (1), which shows selective cytotoxicity against tumorigenic cell lines, 2,6-dichloro-N-[2- (cyclopropanecarbonylamino)benzothiazol-6-yl]benzamide (13b) was designed and synthesized as a biologically stable derivative containing no nitro group. The highly potent derivative 13b exhibited excellent in vivo inhibitory effect on tumor growth.

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Tetrahydroisoquinoline – Wikipedia,
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