Final Thoughts on Chemistry for 7-Bromo-1,2,3,4-tetrahydroisoquinoline

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THIENOPYRIDINE CARBOXAMIDES AS UBIQUITIN-SPECIFIC PROTEASE INHIBITORS

The disclosure relates to inhibitors of USP28 and/or USP25 useful in the treatment of cancers, inflammation, autoimmune diseases, and infectious diseases, having the Formula (I), where R1, R2, R3, R4, R5, R5′, R6, R7, X, m, and n are described herein.

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

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A non-catalyst in the reaction transfers the amine of preparation carboxamide derivatives (by machine translation)

The present invention discloses a non-catalyst of solvent-free low reaction activity of the aliphatic tertiary amide and transfers the amine reaction to synthesize carboxamide derivatives. The method directly to N, N – dimethyl formamide (DMF) is […], get the yield of carboxamide derivatives. The method has the raw materials and the acylation reagent is easy cheap, the reaction yield is high, one-step reaction, low cost, high reaction selectivity, simple operation and the like. To overcome the existing technologies such as the reaction reagent toxicity is large, the need to use different type catalyst, synthesis method and the cost is high, more reaction steps, more byproducts and the like. (by machine translation)

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

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Effects of a 3-alkyl-, 4-hydroxy- and/or 8-aromatic-substituent on the phenylethanolamine N-methyltransferase inhibitor potency and alpha2-adrenoceptor affinity of 2,3,4,5-tetrahydro-1H-2-benzazepines

2,3,4,5-Tetrahydro-1H-2-benzazepine (THBA; 1) is nearly 100-fold more selective an inhibitor of phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28) versus the alpha2-adrenoceptor than is 1,2,3,4-tetrahydroisoquinoline (THIQ; 2) (1: PNMT Ki = 3.3 muM, alpha2-adrenoceptor Ki = 11 muM, selectivity [alpha2 Ki/PNMT Ki] = 3.3; 2: PNMT Ki = 9.7 muM, alpha2 Ki = 0.35 muM, selectivity = 0.036;). Since the PNMT inhibitory activity and selectivity of THIQ were enhanced by the introduction of a hydrophilic electron-withdrawing 7-substituent and a 3-alkyl-substituent, a similar study was conducted on THBA. 8-Nitro-THBA (3) was found to be as potent an inhibitor of PNMT as its THIQ analogue (21) and to be more selective due to its reduced alpha2-adrenoceptor affinity (3: PNMT Ki = 0.39 muM, alpha2 Ki = 66 muM, selectivity = 170; 21: PNMT Ki = 0.41 muM, alpha2 Ki = 4.3 muM, selectivity = 10). Introduction of a 3-alkyl substituent on the THBA nucleus decreased both the alpha2-adrenoceptor affinity and the PNMT inhibitory activity, suggesting an area of steric bulk intolerance at both sites. 4-Hydroxy-THBA (15), which can be considered a conformationally-restricted analogue of 3-hydroxymethyl-THIQ (30), exhibited poorer PNMT inhibitory activity and less selectivity than 30 (15: PNMT Ki = 58 muM, alpha2 Ki = 100 muM, selectivity = 1.7; 30: PNMT Ki = 1.1 muM, alpha2 Ki = 6.6 muM, selectivity = 6.0). While the addition of an 8-nitro group to 15 increased the selectivity of 16 as compared to its THIQ analogue (31), it was not as potent at PNMT nor as selective as 8-nitro-THBA (3) (16, PNMT Ki = 5.3 muM, alpha2 Ki = 680 muM, selectivity = 130; 31: PNMT Ki = 0.29 muM, alpha2 Ki = 19 muM, selectivity = 66). Compound 3 is the most selective (PNMT/alpha2) and one of the more potent at PNMT compounds yet reported in the benzazepine series, and should have sufficient lipophilicity to penetrate the blood-brain barrier (CLogP = 1.8).

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

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PROCESS FOR THE PREPARATION OF PYRROLO[2,3-C]PYRIDINE DERIVATIVES OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF

The present invention provides an improved process for preparing pyrrolo[2,3-c]pyridine derivatives or pharmaceutically acceptable salts thereof having excellent and reversible proton pump inhibitory activity. And also, the present invention provides novel intermediates useful for the process and processes for preparing the same.

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

Discovery of 7-Bromo-1,2,3,4-tetrahydroisoquinoline

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N-formylation of amine using graphene oxide as a sole recyclable metal-free carbocatalyst

Abstract: Graphene oxide (GO), an inexpensive, environment-friendly, and metal-free carbocatalyst, used for the N-formylation of amines is developed. In this reaction, GO shows good activity, selectivity, and recyclability. This strategy has an array of advantages, such as being metal free, without additive, wide-scope protocol, scalable with a low catalyst loading of 3?wt%, use of readily available and recyclable carbocatalyst, and DMF as a readily available formyl source. Furthermore, this strategy provides an avenue for the convenient hydroformylation of various amines. Graphical abstract: [Figure not available: see fulltext.].

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

Extended knowledge of 17680-55-6

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HETEROCYCLIC CYCLOPENTYL TETRAHYDROISOQUINOLINE AND TETRAHYDROPYRIDOPYRIDINE MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY

The present invention is directed to compounds of formula (I), wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, X, n and the broken lines are as defined herein which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptor CCR-2.

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

Properties and Exciting Facts About 7-Bromo-1,2,3,4-tetrahydroisoquinoline

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EBNA1 INHIBITORS AND METHODS USING SAME

The present invention provides EBNA1 inhibitors, and/or pharmaceutical compositions comprising the same, that are useful for the treatment of diseases caused by EBNA1 activity, such as, but not limited to, cancer, infectious mononucleosis, chronic fatigue syndrome, multiple sclerosis, systemic lupus erythematosus and/or rheumatoid arthritis. The present invention further provides EBNA1 inhibitors, and/or pharmaceutical compositions comprising the same, that are useful for the treatment of diseases caused by latent Epstein-Barr Virus (EBV) infection and/or lytic EBV infection.

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

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NOVEL MORPHOLINYL AMINE COMPOUNDS FOR THE TREATMENT OF AUTOIMMUNE DISEASE

The present invention relates to compounds of formula (I), wherein R1, R2 and R3 are as described herein, and their pharmaceutically acceptable salt, enantiomer or diastereomer thereof, and compositions including the compounds and methods of using the compounds.

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

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Identification of 2-[2-(4-tert-Butylphenyl)ethyl]-N-[4-(3-cyclopentylpropyl)- 2-fluorophenyl]-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide as an Orally Active MGAT2 Inhibitor

We previously reported 2-[2-(4-tert-butylphenyl)ethyl]-N-(4-fluorophenyl)-1,2,3,4-tetrahydroisoquinoline- 6-sulfonamide 2 as on orally available monoacylglycerol acyltransferase 2 (MGAT2) inhibitor which exhibited an in vivo efficacy at an oral dose of 100 mg/kg in a mouse oral lipid tolerance test. Further optimization of compound 2 to improve the intrinsic potency culminated in the identification of compound 11. Compound 11 showed a >50-fold lower IC50 against human MGAT2 enzyme than 2. Oral administration of 11 at a dose of 3 mg/kg in the oral lipid tolerance test resulted in significant suppression of triglyceride synthesis.

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