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7-Substituted-1,2,3,4-tetrahydroisoquinolines (7-substituted-THIQs) are potent inhibitors of phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28), the enzyme involved in the biosynthesis of epinephrine. Unfortunately, most of these compounds also exhibit strong affinity for the alpha2-adrenoceptor. To design a selective (PNMT vs alpha2-adrenoceptor affinity) inhibitor of PNMT, the steric and electrostatic factors responsible for PNMT inhibitory activity and alpha2-adrenoceptor affinity were investigated by evaluating a number of 7-substituted-THIQs. A classical quantitative structure-activity relationship (QSAR) study resulted in a three-parameter equation for PNMT (PNMT pK(i) = 0.599pi – 0.0725MR + 1.55sigma(m) + 5.80; n = 27, r = 0.885, s = 0.573) and a three-parameter equation for the alpha2- adrenoceptor (alpha2 pK(i) = 0.599pi – 0.0542MR – 0.951sigma(m) + 6.45; n = 27, r = 0.917, s = 0.397). These equations indicated that steric effects and lipophilicity play a similar role at either active site but that electronic effects play opposite roles at either active site. Two binding orientations for the THIQs were postulated such that lipophilic and hydrophilic 7- substituents would not occupy the same region of space at either binding site. Using these two binding orientations, based on the lipophilicity of the 7-substituent, comparative molecular field analysis (CoMFA) models were developed that showed that the steric and electrostatic interactions at both sites were similar to those previously elaborated in the QSAR analyses. Both the QSAR and the CoMFA analyses showed that the steric interactions are similar at the PNMT active site and at the alpha2-adrenoceptor and that the electrostatic interactions were different at the two sites. This difference in electrostatic interactions might be responsible for the selectivity of THIQs bearing a nonlipophilic electron-withdrawing group at the 7-position. These QSAR and CoMFA results will be useful in the design of potent and selective (PNMT vs alpha2-adrenoceptor affinity) inhibitors of PNMT.

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

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A high-throughput screen identified 3-(3,4-dihydroisoquinolin-2(1H)- ylsulfonyl)benzoic acid as a novel, highly potent (low nM), and isoform-selective (1500-fold) inhibitor of aldo-keto reductase AKR1C3: a target of interest in both breast and prostate cancer. Crystal structure studies showed that the carboxylate group occupies the oxyanion hole in the enzyme, while the sulfonamide provides the correct twist to allow the dihydroisoquinoline to bind in an adjacent hydrophobic pocket. SAR studies around this lead showed that the positioning of the carboxylate was critical, although it could be substituted by acid isosteres and amides. Small substituents on the dihydroisoquinoline gave improvements in potency. A set of “reverse sulfonamides” showed a 12-fold preference for the R stereoisomer. The compounds showed good cellular potency, as measured by inhibition of AKR1C3 metabolism of a known dinitrobenzamide substrate, with a broad rank order between enzymic and cellular activity, but amide analogues were more effective than predicted by the cellular assay.

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

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The present invention relates generally to bis-amide group containing pharmaceutical agents, and in particular, to multicyclic bis-amide MMP-13 inhibitor compounds. More particularly, the present invention provides a new class of MMP-13 inhibiting compounds, containing a pyrimidinyl bis-amide group in combination with a heterocyclic moiety, that exhibit an increased potency and solubility in relation to currently known bis-amide group containing MMP-13 inhibitors.

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Provided are modulators of TLRs of Formula II: pharmaceutically acceptable salts thereof, compositions containing such compounds, and therapeutic methods that include the administration of such compounds

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It is an object to provid a novel compound that has an excellent T-type calcium channel inhibitory activity and is specifically useful for prevention or treatment of pain, chronic kidney disease and atrial fibrillation. The present invention provides a novel triazinone compound of Formula (I): where each substituent in the formula is defined in detail in the description, and R1 means a hydrogen atom, or a C1-6 alkyl group, etc., E means a 7 to 14-membered non-aromatic fused heterocyclic group, L3 means a C1-6 alkylene group, etc., D means a C6-14 aryyl group or a 5 to 10-membered heteroaryl group each of which is optionally substituted, etc., a tautomer of the compound, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

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The present invention provides novel compounds having the general formula (I): wherein R1, R 2, R 3, U, V, W, X and Y are as described herein, compositions including the compounds and methods of using the compounds.

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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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New Advances in Chemical Research, May 2021.Redox catalysis has been broadly utilized in electrochemical synthesis due to its kinetic advantages over direct electrolysis. Quality Control of 1,2,3,4-Tetrahydroisoquinoline-7-carbonitrile, At least one of the reactants interacts with the solid surface in a physical process called adsorption in such a way. 149355-52-2, name is 1,2,3,4-Tetrahydroisoquinoline-7-carbonitrile. In an article,Which mentioned a new discovery about 149355-52-2

Provided are 4?-arylmethoxy isoindoline compounds, and pharmaceutically acceptable salts, solvates, clathrates, stereoisomers, and prodrugs thereof. Methods of use, and pharmaceutical compositions of these compounds are disclosed.

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The invention relates to cyclic imino derivatives of general formula wherein A, B, E, X2 to X5 and Y are defined as in claim 1, the stereoisomers, tautomers, mixtures and salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, which have valuable pharmacological properties, preferably aggregation-inhibiting effects, pharmaceutical compositions which contain these compounds and processes for preparing them.

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Chemical Research Letters, May 2021. COA of Formula: C10H10N2, 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

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