Category: 115955-90-3

Meyer, Michael E.; Doshi, Arpit; Yasuda, Dennis; Zaveri, Nurulain T. published the artcile< Structure-Based SAR in the Design of Selective or Bifunctional Nociceptin (NOP) Receptor Agonists>, Name: 1,2,3,4-Tetrahydroisoquinolin-5-amine, the main research area is nociceptin receptor agonist binding interaction structural modification; active-state; homology model; nociceptin receptor; pharmacophore; selective or bifunctional nociceptin agonist; structure-based drug design.

The nociceptin opioid receptor (NOP), the fourth member of the opioid receptor family, and its endogenous peptide ligand, nociceptin or orphanin FQ (N/OFQ), play a vital role in several central nervous system pathways regulating pain, reward, feeding, anxiety, motor control and learning/memory. Both selective NOP agonists as well as bifunctional agonists at the NOP and mu opioid receptor (MOP) have potential therapeutic applications in CNS disorders related to these processes. Using Surflex-Dock protocols, we conducted a computational structure-activity study of four scaffold classes of NOP ligands with varying NOP-MOP selectivity. By docking these compounds into the orthosteric binding sites within an active-state NOP homol. model, and an active-state MOP crystal structure, the goal of this study was to use a structure-based drug design approach to modulate NOP affinity and NOP vs.MOP selectivity. We first docked four parent compounds (no side chain) to determine their binding interactions within the NOP and MOP binding pockets. Various polar sidechains were added to the heterocyclic A-pharmacophore to modulate NOP ligand affinity. The substitutions mainly contained a 1-2 carbon chain with a polar substituent such as an amine, alc., sulfamide, or guanidine. The SAR anal. is focused on the impact of structural changes in the sidechain, such as chain length, hydrogen bonding capability, and basic vs neutral functional groups on binding affinity and selectivity at both NOP and MOP receptors. This study highlights structural modifications that can be leveraged to rationally design both selective NOP and bifunctional NOP-MOP agonists with different ratios of functional efficacy.

AAPS Journal published new progress about Alcohols Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 115955-90-3 belongs to class tetrahydroisoquinoline, and the molecular formula is C9H12N2, Name: 1,2,3,4-Tetrahydroisoquinolin-5-amine.

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

Mach, Ulrich R.; Hackling, Anneke E.; Perachon, Sylvie; Ferry, Sandrine; Wermuth, Camille G.; Schwartz, Jean-Charles; Sokoloff, Pierre; Stark, Holger published the artcile< Development of novel 1,2,3,4-tetrahydroisoquinoline derivatives and closely related compounds as potent and selective dopamine D3 receptor ligands>, Product Details of C9H12N2, the main research area is tetrahydroisoquinoline derivative dopamine D3 receptor ligand.

Based on N-alkylated 1,2,3,4-tetrahydroisoquinoline derivatives which are structurally related to the partial agonist BP 897, a series of novel, selective dopamine D3 receptor antagonists has been synthesized. Derivatization included changes in the arylamide moiety and the tetrahydroisoquinoline substructure leading to compounds with markedly improved selectivities and affinities in the low nanomolar concentration range. From the 55 structures presented here, (E)-3-(4-iodophenyl)-N-(4-(1,2,3,4-tetrahydroisoquinolin-2-yl)butyl)acrylamide (51) has high affinity (Ki(hD3) = 12 nM) and a 123-fold preference for the D3 receptor relative to the D2 receptor subtype. Its pharmacol. profile offers the prospect of a novel radioligand as a tool for various dopamine D3-receptor-related in vitro and in vivo investigations.

ChemBioChem published new progress about Dopamine D3 receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 115955-90-3 belongs to class tetrahydroisoquinoline, and the molecular formula is C9H12N2, Product Details of C9H12N2.

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

Jamieson, Stephen M. F.; Brooke, Darby G.; Heinrich, Daniel; Atwell, Graham J.; Silva, Shevan; Hamilton, Emma J.; Turnbull, Andrew P.; Rigoreau, Laurent J. M.; Trivier, Elisabeth; Soudy, Christelle; Samlal, Sharon S.; Owen, Paul J.; Schroeder, Ewald; Raynham, Tony; Flanagan, Jack U.; Denny, William A. published the artcile< 3-(3,4-Dihydroisoquinolin-2(1H)-ylsulfonyl)benzoic Acids: Highly Potent and Selective Inhibitors of the Type 5 17-β-Hydroxysteroid Dehydrogenase AKR1C3>, Application of C9H12N2, the main research area is isoquinolinylsulfonylbenzoic acid preparation AKR1C3 enzyme inhibitor structure activity; sulfonylbenzoic acid isoquinolinyl preparation AKR1C3 enzyme inhibitor structure activity.

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””, e.g., I (R = CO2H, R1 = H; R = H, R1 = CO2H), 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 analogs were more effective than predicted by the cellular assay.

Journal of Medicinal Chemistry published new progress about Enzyme inhibitors. 115955-90-3 belongs to class tetrahydroisoquinoline, and the molecular formula is C9H12N2, Application of C9H12N2.

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

Xue, Xiuru; Zeng, Min; Wang, Yanhua published the artcile< Highly active and recyclable Pt nanocatalyst for hydrogenation of quinolines and isoquinolines>, Computed Properties of 115955-90-3, the main research area is platinum nanocatalyst quinoline isoquinoline hydrogenation.

Thermoregulated phase-transfer Pt nanocatalyst was shown to be highly active, selective and recyclable in the hydrogenation of quinolines and isoquinolines. The catalyst could be easily separated from the product by simple phase separation and directly reused in the next cycle without evident loss in catalytic activity and selectivity, even after ten recycles. Importantly, for quinoline, the TON of 10,474 is the highest value ever reported among Pt catalysts. More remarkably, for isoquinoline, the TON of 5340 is far ahead of the highest record among transition metal catalysts.

Applied Catalysis, A: General published new progress about Hydrogenation. 115955-90-3 belongs to class tetrahydroisoquinoline, and the molecular formula is C9H12N2, Computed Properties of 115955-90-3.

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

Kobayashi, Masakazu; Retra, Kim; Figaroa, Francis; Hollander, Johan G.; Ab, Eiso; Heetebrij, Robert J.; Irth, Hubertus; Siegal, Gregg published the artcile< Target immobilization as a strategy for NMR-based fragment screening: comparison of TINS, STD, and SPR for fragment hit identification>, Safety of 1,2,3,4-Tetrahydroisoquinolin-5-amine, the main research area is enzyme immobilization biosensor SPR FBDD TINS STD NMR spectroscopy.

Fragment-based drug discovery (FBDD) has become a widely accepted tool that is complementary to high-throughput screening (HTS) in developing small-mol. inhibitors of pharmaceutical targets. Because a fragment campaign can only be as successful as the hit matter found, it is critical that the first stage of the process be optimized. Here the authors compare the 3 most commonly used methods for hit discovery in FBDD: high concentration screening (HCS), solution ligand-observed NMR, and surface plasmon resonance (SPR). They selected the commonly used saturation transfer difference (STD) NMR spectroscopy and the proprietary target immobilized NMR screening (TINS) as representative of the array of possible NMR methods. Using a target typical of FBDD campaigns, the authors find that HCS and TINS are the most sensitive to weak interactions. They also find a good correlation between TINS and STD for tighter binding ligands, but the ability of STD to detect ligands with affinity weaker than 1 mM KD is limited. Similarly, they find that SPR detection is most suited to ligands that bind with KD better than 1 mM. However, the good correlation between SPR and potency in a bioassay makes this a good method for hit validation and characterization studies.

Journal of Biomolecular Screening published new progress about Drug discovery. 115955-90-3 belongs to class tetrahydroisoquinoline, and the molecular formula is C9H12N2, Safety of 1,2,3,4-Tetrahydroisoquinolin-5-amine.

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

Madacsi, Ramona; Kanizsai, Ivan; Feher, Liliana Z.; Gyuris, Mario; Ozsvari, Bela; Erdelyi, Andras; Wolfling, Janos; Puskas, Laszlo G. published the artcile< Aromatic Sulfonamides Containing a Condensed Piperidine Moiety as Potential Oxidative Stress-Inducing Anticancer Agents>, Computed Properties of 115955-90-3, the main research area is N arylsulfonamide derivative anticancer agent oxidative stress cancer cell.

A 30-membered piperidine ring-fused aromatic sulfonamide library was synthesized, including N-arylsulfonyl 1,2,3,4-tetrahydroquinolines, 1,2,3,4-tetrahydroisoquinolines and 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indoles. The compounds induced oxidative stress and glutathione depletion in HT168 melanoma and K562 leukemia cells and in micromolar concentrations exerted cytotoxic effects. Among the tested sulfonamides, compounds 21, 22, 23, 35 and 41 exhibited 100% cytotoxic effects with low (< 10 μM) EC50 values on K562 cells. The cytotoxicity of lead compound 22 was investigated in 24 different cancer cell lines, and it was found to be active against leukemia, melanoma, glioblastoma, and liver, breast and lung cancer cells, as confirmed by classical biochem. and holog. microscopic analyses. Medicinal Chemistry (Sharjah, United Arab Emirates) published new progress about Antitumor agents. 115955-90-3 belongs to class tetrahydroisoquinoline, and the molecular formula is C9H12N2, Computed Properties of 115955-90-3.

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

Chan, W. N.; Hadley, M. S.; Harling, J. D.; Herdon, H. J.; Orlek, B. S.; Riley, G. J.; Stead, R. E. A.; Stean, T. O.; Thompson, M.; Upton, N.; Ward, R. W. published the artcile< Evaluation of a series of anticonvulsant 1,2,3,4-tetrahydroisoquinolinyl-benzamides>, Formula: C9H12N2, the main research area is tetrahydroisoquinolinylbenzamide preparation anticonvulsant structure activity.

SAR studies around a series of N-(tetrahydroisoquinolinyl)-2-methoxybenzamides, identified by high-throughput screening at the novel SB-204269 binding site, have provided compounds with high affinity and excellent anticonvulsant activity in animal models.

Bioorganic & Medicinal Chemistry published new progress about Anticonvulsants. 115955-90-3 belongs to class tetrahydroisoquinoline, and the molecular formula is C9H12N2, Formula: C9H12N2.

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

Resende, Diana I. S. P.; Almeida, Joana R.; Pereira, Sandra; Campos, Alexandre; Lemos, Agostinho; Plowman, Jeffrey E.; Thomas, Ancy; Clerens, Stefan; Vasconcelos, Vitor; Pinto, Madalena; Correia-da-Silva, Marta; Sousa, Emilia published the artcile< From Natural Xanthones to Synthetic C-1 Aminated 3,4-Dioxygenated Xanthones as Optimized Antifouling Agents>, Recommanded Product: 1,2,3,4-Tetrahydroisoquinolin-5-amine, the main research area is aminated dioxygenated xanthone preparation antifouling antibacterial; anti-settlement; antifouling; eco-friendly alternatives; molecular targets; xanthones.

In this work, the antifouling activity of a series of 24 xanthones I [R1 = Me, CH2Br, 4-ClC6H4CH2NHCH2, etc.; R2 = H, Cl; R3 = OMe; R4 = OH, OMe; R5 = H, OMe], with chem. similarities to natural products, was exploited. Nine of the tested xanthones presented highly significant anti-settlement responsed against the settlement of mussel Mytilus galloprovincialis larvae and low toxicity to this macrofouling species. Addnl., xanthone I [R1 = piperidinylmethyl; R2 = H; R3 = OMe; R4 = OMe; R5 = H] exhibited a therapeutic ratio (LC50/EC50) >15, as required by the US Navy program attesting its suitability as natural antifouling agents. From the nine tested xanthones, none of the compounds were found to significantly inhibit the growth of the marine biofilm-forming bacterial strains tested. Insights on the antifouling mode of action suggested that these two compounds affected similar mol. targets and cellular processes in mussel larvae, including that related to mussel adhesion capacity. This work exposed for the first time the relevance of C-1 aminated xanthones with a 3,4-dioxygenated pattern of substitution as new non-toxic products to prevent marine biofouling.

Marine Drugs published new progress about Antibacterial agents. 115955-90-3 belongs to class tetrahydroisoquinoline, and the molecular formula is C9H12N2, Recommanded Product: 1,2,3,4-Tetrahydroisoquinolin-5-amine.

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

Ruel, Rejean; L’Heureux, Alexandre; Thibeault, Carl; Lapointe, Philippe; Martel, Alain; Qiao, Jennifer X.; Hua, Ji; Price, Laura A.; Wu, Qimin; Chang, Ming; Zheng, Joanna; Huang, Christine S.; Wexler, Ruth R.; Rehfuss, Robert; Lam, Patrick Y. S. published the artcile< Potent P2Y1 urea antagonists bearing various cyclic amine scaffolds>, Application of C9H12N2, the main research area is isoindolinyloxypyridyl trifluoromethoxyphenylurea preparation purinergic P2Y1 inhibitor; piperidinyloxypyridyl trifluoromethoxyphenylurea preparation purinergic P2Y1 inhibitor; Isoindolines; P2Y(1) antagonists; Piperidines; Purinergic receptors; Tetrahydroisoquinolines.

A number of new amine scaffolds with good inhibitory activity in the ADP-induced platelet aggregation assay have been found to be potent antagonists of the P2Y1 receptor. SAR optimization led to the identification of isoindoline and piperidine derivatives which showed good in vitro binding and functional activities, as well as improved aqueous solubility Among them, the piperidine I showed the best overall profile with favorable PK parameters.

Bioorganic & Medicinal Chemistry Letters published new progress about Cyclic amines Role: PAC (Pharmacological Activity), RCT (Reactant), SPN (Synthetic Preparation), THU (Therapeutic Use), BIOL (Biological Study), RACT (Reactant or Reagent), PREP (Preparation), USES (Uses). 115955-90-3 belongs to class tetrahydroisoquinoline, and the molecular formula is C9H12N2, Application of C9H12N2.

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

Clark, Robin D.; Berger, Jacob; Garg, Pushkal; Weinhardt, Klaus K.; Spedding, Michael; Kilpatrick, Andrew T.; Brown, Christine M.; MacKinnon, Alison C. published the artcile< Affinity of 2-(tetrahydroisoquinolin-2-ylmethyl)- and 2-(isoindolin-2-ylmethyl)imidazolines for α-adrenoceptors. Differential affinity of imidazolines for the [3H]idazoxan-labeled α2-adrenoceptor vs. the [3H]yohimbime-labeled site [Erratum to document cited in CA112(7):55713w>, Safety of 1,2,3,4-Tetrahydroisoquinolin-5-amine, the main research area is Erratum imidazoline tetrahydroisoquinolinylmethyl isoindolinylmethyl adrenoreceptor affinity; adrenoreceptor affinity tetrahydroisoquinolinylmethylimidazoline isoindolinylmethylimidazoline Erratum.

An error in Table I has been corrected The error was not reflected in the abstract or the index entries.

Journal of Medicinal Chemistry published new progress about α1-Adrenoceptors Role: RCT (Reactant), RACT (Reactant or Reagent). 115955-90-3 belongs to class tetrahydroisoquinoline, and the molecular formula is C9H12N2, Safety of 1,2,3,4-Tetrahydroisoquinolin-5-amine.

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