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TRPV1 receptor is an important analgesia target. Its antagonists are expected to prevent pain perception by blocking the receptor directly. In this letter, eight dihydroisoquinoline-2(1H)-carbothioamide derivatives were designed and synthesized as TRPV1 antagonists. The benzene ring was modified with different substitutional groups. Preliminary biological tests suggested that the new compounds exhibited TRPV1 antagonist activity and different analgesia effects, some of which were promising as analgesia drugs.

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This report describes a highly enantioselective oxidative sp3 C-H arylation of N-aryltetrahydroisoquinolines (THIQs) through a dual catalysis platform. The combination of the photoredox catalyst, [Ir(ppy)2(dtbbpy)]PF6, and chiral copper catalysts provide a mild and highly effective sp3 C-H asymmetric arylation of THIQs.

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

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S-Adenosyl-L-methionine (SAM): coclaurine N-methyltransferase (CNMT), which catalyzes the transfer of a methyl group from S-adenosyl-L-methionine to the amino group of the tetrahydrobenzylisoquinoline alkaloid coclaurine, was purified 340-fold from Coptis japonica cells in 1% yield to give an almost homogeneous protein. The purified enzyme, which occurred as a homotetramer with a native Mr of 160 kDa (gel-filtration chromatography) and a subunit Mr of 45 kDa (SDS-polyacrylamide gel electrophoresis), had an optimum pH of 7.0 and a pI of 4.2. Whereas (R)-coclaurine was the best substrate for enzyme activity, Coptis CNMT had broad substrate specificity and no stereospecificity; CNMT methylated norlaudanosoline, 6,7-dimethoxyl-1,2,3,4-tetrahydroisoquinoline and 1-methyl-6,7-dihydroxy-1,2,3,4,-tetrahydroisoquinoline. The enzyme did not require any metal ion. p-Chloromercuribenzoate and iodoacetamide did not inhibit CNMT activity, but the addition of Co2+, Cu2+ or Mn2+ at 5 mM severely inhibited such activity by 75, 47 and 57%, respectively. The substrate-saturation kinetics of CNMT for norreticuline and SAM were of the typical Michaelis-Menten-type with respective Km values of 0.38 and 0.65 mM.

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Tetrahydroisoquinoline – Wikipedia,
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The development of small molecules as P-gp modulating agents and SAR studies on these ligands represented the aim of the present work. A series of 6,7-dimethoxytetrahydroisoquinoline derivatives was prepared and their ability to inhibit P-gp activity has been evaluated. The basic nucleus of these compounds, common to the best P-gp inhibitors such as Tariquidar and Elacridar, has been functionalized with no-basic moiety from our studied sigma receptor ligands displaying potent P-gp inhibition. The best results were obtained for compounds 3c and 3a (EC50 = 1.64 and 4.86 muM, respectively) and these results were remarkable because Elacridar showed in the same biological evaluation similar inhibitory activity (EC50 = 2 muM). SAR studies displayed that the removal of double bond on the spacer or its shifting into tetraline ring decreased the P-gp inhibiting activity. Moreover, the P-gp inhibition mechanism of tested compounds was investigated by three selected biological experiments. The results displayed that only compound 3c was P-gp inhibitor as Elacridar, while compound 3a and reference compounds Cyclosporin A and Verapamil modulated P-gp activity saturating the efflux pump as substrates. Flow cytometry studies carried out in Doxorubicin resistant breast cancer cell line (MCF7/Adr) confirmed that compound 3c increased Doxorubicin cell accumulation 5.7-fold. In addition, in MCF7/Adr, antiproliferative effect of 5 muM Doxorubicin shifted from 5% to 95% when co-administered with compound 3c (20 muM). The present study suggested a new class of small molecules displaying P-gp inhibitor activity differing from reference compounds Elacridar and Tariquidar for a simplified, and in the meantime, efficacious no-basic moiety.

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

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A novel method for the synthesis of cyanomethylated tetrahydroisoquinolines has been developed with mild reaction conditions, good yields and a broad substrate scope. Acetonitrile, a common solvent, is for the first time used as a pronucleophile for this type of two sp3C?H bonds cross-dehydrogenative coupling (CDC) reaction. A new oxidative system (CuCl2/TEMPO/Cs2CO3) has been established by our group, in which the mild TEMPO reagent was found to be a highly efficient oxidant. (Figure presented.).

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Tetrahydroisoquinoline – Wikipedia,
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We have previously described the discovery of poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors based on a phthalazinone scaffold. Subsequent optimisation of inhibitory activity, metabolic stability and pharmacokinetic parameters has led to a novel series of meta-substituted 4-benzyl-2H-phthalazin-1-one PARP-1 inhibitors which retain low nM cellular activity and show good stability in vivo and efficacy in cell based models.

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3,3-Pentamethylene oxaziridine 1 forms an N-N bond with secondary isoquinoline bases 2a-f to give the cyclohexylidene hydrazines 3a-f.In some cases nitrogen elimination yielding indane derivatives 13b, 13e competes with hydrazone formation.The cyclic Schiff’base 14 and the beta-carboline derivative 16 can also be aminated.

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An electrochemically promoted coupling of benzoxazoles and amines has been developed, leading directly to the formation of 2-aminobenzoxazoles. The chemistry utilizes catalytic quantities of a tetraalkylammonium halide redox catalyst and is carried out under constant current conditions in a simple undivided cell. The use of excess chemical oxidant or large amounts of supporting electrolyte is avoided. This greatly simplifies the workup and isolation process and leads to a reduction in waste. (Chemical Equation Presented).

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Tetrahydroisoquinoline – Wikipedia,
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A series of pyrrolo[2,1-a]isoquinoline and coumarin-fused pentacyclic derivatives were synthesized via base-mediated divergent annulation of 4-chloro-3-formylcoumarin and tetrahydroisoquinoline as a key step. This method was then extended to the preparation of isolamellarins A and B (isolamellarin G trimethyl ether). When exposed to UV light, the pyrrolo[2,1-a]isoquinoline- and coumarin-fused pentacycles B were found to undergo aerobic oxidation to give the corresponding hydroxypyrrolones.

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This review focuses on the coordination chemistry of alpha-hydroxycarboxylates with first-row transition cations. It takes in both mono- and polycarboxylates, surveying their bonding modes in these complexes (with and without other ligands) and summarizing important chemical and physical properties of these metal compounds.

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Tetrahydroisoquinoline – Wikipedia,
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