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T-type calcium channel inhibitor

The present invention addresses the problem of providing novel compounds that have T-type voltage-gated calcium channel-blocking activity and are useful particularly in treating pain, chronic kidney disease, and atrial fibrillation. Provided are novel triazinone compounds represented by formula (I) (the various substituents in the formula are defined in detail in the description but R1 denotes a hydrogen atom, C1-C6 alkyl group, etc., E denotes a 7- to 14-membered non-aromatic condensed heterocyclic group, L3 denotes a C1-C6 alkylene group, etc., and D denotes a C6-C14 aryl group that may be substituted, a 5- to 10-membered heteroaryl group that may be substituted, etc.), tautomers or pharmaceutically permissible salts of said compounds, and solvates thereof.

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

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HETEROBICYCLIC METALLOPROTEASE INHIBITORS

The present invention relates generally to heterobicyclic containing pharmaceutical agents, and in particular, to heterobicyclic metalloprotease inhibitor compounds. More particularly, the present invention provides a new class of heterobicyclic metalloprotease inhibiting compounds that exhibit an increased potency in relation to currently known metalloprotease inhibitors.

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

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Structure-Activity Study of N -((trans)-4-(2-(7-Cyano-3,4-dihydroisoquinolin-2(1 H)-yl)ethyl)cyclohexyl)-1 H -indole-2-carboxamide (SB269652), a Bitopic Ligand That Acts as a Negative Allosteric Modulator of the Dopamine D2 Receptor

We recently demonstrated that SB269652 (1) engages one protomer of a dopamine D2 receptor (D2R) dimer in a bitopic mode to allosterically inhibit the binding of dopamine at the other protomer. Herein, we investigate structural determinants for allostery, focusing on modifications to three moieties within 1. We find that orthosteric “head” groups with small 7-substituents were important to maintain the limited negative cooperativity of analogues of 1, and replacement of the tetrahydroisoquinoline head group with other D2R “privileged structures” generated orthosteric antagonists. Additionally, replacement of the cyclohexylene linker with polymethylene chains conferred linker length dependency in allosteric pharmacology. We validated the importance of the indolic NH as a hydrogen bond donor moiety for maintaining allostery. Replacement of the indole ring with azaindole conferred a 30-fold increase in affinity while maintaining negative cooperativity. Combined, these results provide novel SAR insight for bitopic ligands that act as negative allosteric modulators of the D2R.

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

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Electrochemical Approach for Direct C-H Phosphonylation of Unprotected Secondary Amine

Direct alpha-phosphonylation of an unprotected secondary amine in a single step is of practical importance to amino phophophates. However, this protocol is limited due to the high redox barrier of unprotected amine. In this paper, we report C-H phosphonylation of an unprotected secondary amine via an electrochemical approach in the presence of catalytic carboxylate salt. This metal-free and exogenous oxidant-free method furnishes diverse target molecules with satisfactory yield under mild reaction conditions. Successful application of the protocol in a gram-scale experiment demonstrates the potential utility for further functionalization.

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

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Electric Literature of 149355-52-2, A catalyst don’t appear in the overall stoichiometry of the reaction it catalyzes, but it must appear in at least one of the elementary reactions in the mechanism for the catalyzed reaction. 149355-52-2, Name is 1,2,3,4-Tetrahydroisoquinoline-7-carbonitrile, molecular formula is C10H10N2. In a Article£¬once mentioned of 149355-52-2

NHC-catalyzed Redox-Neutral Aza-Benzoin Reaction of Aldehydes with Tetrahydroisoquinolines

Tetrahydroisoquinoline derivatives are useful synthetic intermediates, which play an important role in the preparation of natural products, pharmaceuticals and other materials. Herein, we report an unprecedented redox-neutral aza-benzoin protocol to construct such scaffold. Upon exposure of tetrahydroisoquinolines to aromatic aldehydes in the presence of an NHC catalyst, the C-1 acylated tetrahydroisoquinolines were obtained in moderate to good yields.

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

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TRIAZOLE OXADIAZOLES DERIVATIVES

The invention relates to compounds of formula (I), wherein R1, R2, Ra, Rb, X have the meanings given in claim 1. The compounds are useful e.g. in the treatment of autoimmune disorders, such as multiple sclerosis.

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

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In homogeneous catalysis, the catalyst is in the same phase as the reactant. The number of collisions between reactants and catalyst is at a maximum.In a patent, 149355-52-2, name is 1,2,3,4-Tetrahydroisoquinoline-7-carbonitrile, introducing its new discovery. SDS of cas: 149355-52-2

BROAD SPECTRUM ANTIVIRAL COMPOSITIONS AND METHODS

Novel thiazole- and isoquinoline- containing compounds are presented that are useful for treating and/or preventing broad-spectrum viral infections. Methods of treating and/or preventing broad-specturm viral infections are also presented. These compounds have shown inhibitio of HCMV, influenza viruses, Zika virus, BK Virus and RSV replication in cell-based assays.

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

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We¡¯ll also look at important developments in the pharmaceutical industry because understanding organic chemistry is important in understanding health, medicine, the role of 149355-52-2, and how the biochemistry of the body works.Synthetic Route of 149355-52-2

Synthetic Route of 149355-52-2, The reaction rate of a catalyzed reaction is faster than the reaction rate of the uncatalyzed reaction at the same temperature.149355-52-2, Name is 1,2,3,4-Tetrahydroisoquinoline-7-carbonitrile, molecular formula is C10H10N2. In a Patent£¬once mentioned of 149355-52-2

BICYCLIC BENZAMIDE COMPOUNDS AS HISTAMINE H3 RECEPTOR LIGAND USEFUL IN THE TREATMENT OF NEUROLOGICAL DISEASES

The present invention relates to novel bicyclic benzamide derivatives having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of neurological and psychiatric disorders.

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

Discovery of 1,2,3,4-Tetrahydroisoquinoline-7-carbonitrile

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Electric Literature of 149355-52-2, The reaction rate of a catalyzed reaction is faster than the reaction rate of the uncatalyzed reaction at the same temperature.149355-52-2, Name is 1,2,3,4-Tetrahydroisoquinoline-7-carbonitrile, molecular formula is C10H10N2. In a Article£¬once mentioned of 149355-52-2

Comparative molecular field analysis (CoMFA) models of phenylethanolamine N-methyltransferase (PNMT) and the alpha2-adrenoceptor: The development of new, highly selective inhibitors of PNMT

As a guide to the development of new and more selective inhibitors of phenylethanolamine N-methyltransferase (PNMT) vs the alpha2-adrenoceptor, we have performed a comparative molecular field analysis (CoMFA) on a series of 80 benzylamine analogues. Using the models obtained, we have proposed a series of 3-trifluoromethyl-1,2,3,4-tetrahydroisoquinolines and predicted the activity of other analogues.

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

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Discovery of a Novel Class of Negative Allosteric Modulator of the Dopamine D2 Receptor Through Fragmentation of a Bitopic Ligand

Recently, we have demonstrated that N-((trans)-4-(2-(7-cyano-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)-1H-indole-2-carboxamide (SB269652) (1) adopts a bitopic pose at one protomer of a dopamine D2 receptor (D2R) dimer to negatively modulate the binding of dopamine at the other protomer. The 1H-indole-2-carboxamide moiety of 1 extends into a secondary pocket between the extracellular ends of TM2 and TM7 within the D2R protomer. To target this putative allosteric site, we generated and characterized fragments that include and extend from the 1H-indole-2-carboxamide moiety of 1. N-Isopropyl-1H-indole-2-carboxamide (3) displayed allosteric pharmacology and sensitivity to mutations of the same residues at the top of TM2 as was observed for 1. Using 3 as an “allosteric lead”, we designed and synthesized an extensive fragment library to generate novel SAR and identify N-butyl-1H-indole-2-carboxamide (11d), which displayed both increased negative cooperativity and affinity for the D2R. These data illustrate that fragmentation of extended compounds can expose fragments with purely allosteric pharmacology.

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