Tag: M.W=100-150

Palmeira, Andreia; Vasconcelos, M. Helena; Paiva, Ana; Fernandes, Miguel X.; Pinto, Madalena; Sousa, Emilia published the artcile< Dual inhibitors of P-glycoprotein and tumor cell growth: (Re)discovering thioxanthones>, Category: tetrahydroisoquinoline, the main research area is thioxanthone preparation antitumor glycoprotein SAR.

For many pathologies, there is a crescent effort to design multiple ligands that interact with a wide variety of targets. 1-Aminated thioxanthone derivatives were synthesized and assayed for their in vitro dual activity as antitumor agents and P-glycoprotein (P-gp) inhibitors. The approach was based on mol. hybridization of a thioxanthone scaffold, present in known antitumor drugs, and an amine, described as an important pharmacophoric feature for P-gp inhibition. A rational approach using homol. modeling and docking was used, to select the mols. to be synthesized by conventional or microwave-assisted Ullmann C-N cross-coupling reaction. The obtained aminated thioxanthones were highly effective at inhibiting P-gp and/or causing growth inhibition in a chronic myelogenous leukemia cell line, K562. Six of the aminated thioxanthones had GI50 values in the K562 cell line below 10 μM and 1-{[2-(diethylamino)ethyl]amino}-4-propoxy-9H-thioxanthen-9-one (37) had a GI50 concentration (1.90 μM) 6-fold lower than doxorubicin (11.89 μM) in the K562Dox cell line. The best P-gp inhibitor found was 1-[2-(1H-benzimidazol-2-yl)ethanamine]-4-propoxy-9H-thioxanthen-9-one (45), which caused an accumulation rate of rhodamine-123 similar to that caused by verapamil in the K562Dox resistant cell line, and a decrease in ATP consumption by P-gp. At a concentration of 10 μM, compound 45 caused a decrease of 12.5-fold in the GI50 value of doxorubicin in the K562Dox cell line, being 2-fold more potent than verapamil. From the overall results, the aminated thioxanthones represent a new class of P-gp inhibitors with improved efficacy in sensitizing a resistant P-gp overexpressing cell line (K562Dox) to doxorubicin.

Biochemical Pharmacology published new progress about Antitumor agents. 115955-90-3 belongs to class tetrahydroisoquinoline, and the molecular formula is C9H12N2, Category: tetrahydroisoquinoline.

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

Lemos, Agostinho; Gomes, Ana Sara; Loureiro, Joana B.; Brandao, Pedro; Palmeira, Andreia; Pinto, Madalena M. M.; Saraiva, Lucilia; Sousa, Maria Emilia published the artcile< Synthesis, biological evaluation, and in silico studies of novel aminated xanthones as potential p53-activating agents>, Safety of 1,2,3,4-Tetrahydroisoquinolin-5-amine, the main research area is aminated xanthone preparation antitumor human docking p53 activator; dimethoxy oxo xanthene carbaldehyde preparation; MDM2-p53 interaction; antitumor activity; computational docking; xanthones; yeast-based assays.

In this work, a series of eleven aminated xanthones possessing a 3,4-dioxygenated pattern of substitution e.g., I was efficiently constructed in moderate to good yields. From this group of compounds, xanthone I was identified for the first time as a putative p53-activating agent, using a yeast-based screening assay. Xanthone I was revealed to inhibit the growth of human HCT116 p53+/+ colon cancer cells, being that this effect was associated with cell cycle arrest through activation of the p53 pathway. Nevertheless, further studies were required to confirm the mechanism of action of compound I, which may lead to the identification of a novel xanthone derivative with promising antitumor activity. These results demonstrated the potential usefulness of coupling amine-containing structural motifs of known MDM2-p53 disruptors into the 3,4-dioxygenated xanthone scaffold as a starting point for the design of novel and improved p53-activating agents with antitumor activity and drug like properties.

Molecules published new progress about Amines Role: PAC (Pharmacological Activity), PRP (Properties), 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, Safety of 1,2,3,4-Tetrahydroisoquinolin-5-amine.

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

Long, Solida; Loureiro, Joana B.; Carvalho, Carla; Gales, Lu Is; Saraiva, Lucilia; Pinto, Madalena M. M.; Puthongking, Ploenthip; Sousa, Emilia published the artcile< Semi-synthesis of small molecules of aminocarbazoles: tumor growth inhibition and potential impact on p53>, Formula: C9H12N2, the main research area is aminocarbazole derivative preparation antitumor p53 activator; alkaloids; aminocarbazoles; heptaphylline; mutant; p53; tumor.

The tumor cell growth inhibitory activity of aminocarbazole derivatives, I [R = H, OMe; R1 = H, CH2CHC(Me)2; R2 = NH(CH2)3N(Me)2, pipridin-1-yl, 4-ClC6H4NH, etc.] as well as their potential activation of p53 was reported. Compounds I was synthesized from naturally-occurring carbazoles II [R3 = H, OMe; R4 = H, CH2CHC(Me)2] with amine precursors and isolated from Clausena harmandiana, using a reductive amination protocol. Compounds I and II were evaluated for their potential effect on wild-type and mutant p53 activity using a yeast screening assay and on human tumor cell lines. Naturally-occurring carbazoles II showed the most potent growth inhibitory effects on wild-type p53-expressing cells, being heptaphylline II [R3 = H; R4 = CH2CHC(Me)2] the most promising in all the investigated cell lines. However, compound II [R3 = H; R4 = CH2CHC(Me)2] also showed growth inhibition against non-tumor cells. Conversely, semi-synthetic aminocarbazole I [R = H; R1 = CH2CHC(Me)2; R2 = 4-FC6H4NH] showed an interesting growth inhibitory activity in tumor cells expressing both wild-type and mutant p53, exhibiting low growth inhibition on non-tumor cells. The yeast assay showed a potential reactivation of mutant p53 by heptaphylline derivatives, including compound I [R = H; R1 = CH2CHC(Me)2; R2 = 4-FC6H4NH].

Molecules published new progress about Amines Role: PAC (Pharmacological Activity), PRP (Properties), 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, Formula: C9H12N2.

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

Zhang, Wen-Xiong; Nishiura, Masayoshi; Hou, Zhaomin published the artcile< Catalytic addition of amine N-H bonds to carbodiimides by half-sandwich rare-earth metal complexes: efficient synthesis of substituted guanidines through amine protonolysis of rare-earth metal guanidinates>, Reference of 115955-90-3, the main research area is half sandwich rare earth catalyst guanidine synthesis carbodiimide amine.

Reaction of [Ln(CH2SiMe3)3(thf)2] (Ln = Y, Yb, and Lu) with one equivalent of Me2Si(C5Me4H)NHR’ (R’ = Ph, 2,4,6-Me3C6H2, tBu) affords straightforwardly the corresponding half-sandwich rare-earth metal alkyl complexes [{Me2Si(C5Me4)(NR’)}Ln(CH2SiMe3)(thf)n] (1: Ln = Y, R’ = Ph, n = 2; 2: Ln = Y, R’ = C6H2Me3-2,4,6, n = 1; 3: Ln = Y, R’ = tBu, n = 1; 4: Ln = Yb, R’ = Ph, n = 2; 5: Ln = Lu, R’ = Ph, n = 2) in high yields. These complexes, especially the yttrium complexes 1-3, serve as excellent catalyst precursors for the catalytic addition of various primary and secondary amines to carbodiimides, efficiently yielding a series of guanidine derivatives with a wide range of substituents on the nitrogen atoms. Functional groups such as CN, CCH, and aromatic C-X (X: F, Cl, Br, I) bonds can survive the catalytic reaction conditions. A primary amino group can be distinguished from a secondary one by the catalyst system, and therefore, the reaction of 1,2,3,4-tetrahydro-5-aminoisoquinoline with iPrN=C=NiPr can be achieved stepwise first at the primary amino group to selectively give the monoguanidine, and then at the cyclic secondary amino unit to give the biguanidine. Some key reaction intermediates or true catalyst species, such as the amido complexes [{Me2Si(C5Me4)(NPh)}Y(NEt2)(thf)2] and [{Me2Si(C5Me4)(NPh)}Y(NHC6H4Br-4)(thf)2], and the guanidinate complexes [{Me2Si(C5Me4)(NPh)}Y{iPrNC(NEt2)(NiPr)}(thf)] and [{Me2Si(C5Me4)(NPh)}Y{iPrN}C(NC6H4Br-4)(NHiPr)(thf)] have been isolated and structurally characterized. Reactivity studies on these complexes suggest that the present catalytic formation of a guanidine compound proceeds mechanistically through nucleophilic addition of an amido species, formed by acid-base reaction between a rare-earth metal alkyl bond and an amine N-H bond, to a carbodiimide, followed by amine protonolysis of the resultant guanidinate species.

Chemistry – A European Journal published new progress about Amines, triamines Role: PEP (Physical, Engineering or Chemical Process), RCT (Reactant), PROC (Process), RACT (Reactant or Reagent). 115955-90-3 belongs to class tetrahydroisoquinoline, and the molecular formula is C9H12N2, Reference of 115955-90-3.

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

Duan, Xiaonan; Wang, Xuepeng; Chen, Xingkun; Zhang, Jisong published the artcile< Continuous and Selective Hydrogenation of Heterocyclic Nitroaromatics in a Micropacked Bed Reactor>, Quality Control of 115955-90-3, the main research area is nitroisoquinoline nickel silica palladium aluminumoxide catalyst continous flow hydrogentaion; aminoisoquinoline regioselective preparation.

A continuous flow system based on a micropacked bed reactor was developed for the selective hydrogenation of heterocyclic nitroaroms. and the reductions of 5-nitroisoquinoline to 5-aminoisoquinoline and 5-amino-1,2,3,4-tetrahydroisoquinoline are selected as the model reactions. With the optimal reaction conditions, maximal yields of 99.9% (5-aminoisoquinoline) and 99.3% (5-amino-1,2,3,4-tetrahydroisoquinoline) were obtained successfully. Moreover, this system exhibits remarkable performance for the selective hydrogenation of relevant heterocyclic nitroaroms. with all yields beyond the level of 97.5%. The continuous flow system enables efficient hydrogenation of heterocyclic nitroaroms. and remarkable selectivity of target products with shorter reaction time and safer operation compared with batch reactors.

Organic Process Research & Development published new progress about Hydrogenation catalysts, regioselective. 115955-90-3 belongs to class tetrahydroisoquinoline, and the molecular formula is C9H12N2, Quality Control of 115955-90-3.

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

Liu, Li-Kai; Finzel, Barry C. published the artcile< Fragment-Based Identification of an Inducible Binding Site on Cell Surface Receptor CD44 for the Design of Protein-Carbohydrate Interaction Inhibitors>, SDS of cas: 115955-90-3, the main research area is CD44 binding site protein carbohydrate inhibitor design crystal structure.

Selective inhibitors of hyaluronan (HA) binding to the cell surface receptor CD44 will have value as probes of CD44-mediated signaling and have potential as therapeutic agents in chronic inflammation, cardiovascular disease, and cancer. Using biophys. binding assays, fragment screening, and crystallog. characterization of complexes with the CD44 HA binding domain, we have discovered an inducible pocket adjacent to the HA binding groove into which small mols. may bind. Iterations of fragment combination and structure-driven design have allowed identification of a series of 1,2,3,4-tetrahydroisoquinolines as the first nonglycosidic inhibitors of the CD44-HA interaction. The affinity of these mols. for the CD44 HA binding domain parallels their ability to interfere with CD44 binding to polymeric HA in vitro. X-ray crystallog. complexes of lead compounds are described and compared to a new complex with a short HA tetrasaccharide, to establish the tetrahydroisoquinoline pharmacophore as an attractive starting point for lead optimization.

Journal of Medicinal Chemistry published new progress about CD44 antigens Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 115955-90-3 belongs to class tetrahydroisoquinoline, and the molecular formula is C9H12N2, SDS of cas: 115955-90-3.

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

Xie, Feng; Chen, Qing-Hua; Xie, Rong; Jiang, Huan-Feng; Zhang, Min published the artcile< MOF-Derived Nanocobalt for Oxidative Functionalization of Cyclic Amines to Quinazolinones with 2-Aminoarylmethanols>, COA of Formula: C9H12N2, the main research area is MOF nanocobalt catalysis oxidative functionalization cyclic amine aminoarylmethanol; quinazolinone preparation.

By employing a MOF-templated method, we have developed a highly dispersed and ultralow loading cobalt nanocatalyst, which has been applied in the oxidative functionalization of easily available cyclic amines with 2-aminoarylmethanols to ring-fused quinazolinones, the core structures of numerous valuable products. The developed catalytic transformation proceeds with the merits of broad substrate scope, good functional group tolerance and chemoselectivity, high step- and atom-efficiency, and use of the naturally abundant Co/O2 system, which offers a practical way for the preparation of quinazolinones with structural diversity. The work presented has built an important basis for direct conversion of cyclic amine motifs into functional frameworks.

ACS Catalysis published new progress about Atom economy. 115955-90-3 belongs to class tetrahydroisoquinoline, and the molecular formula is C9H12N2, COA of Formula: C9H12N2.

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

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

Liu, Li-Kai; Finzel, Barry C. published the artcile< Fragment-Based Identification of an Inducible Binding Site on Cell Surface Receptor CD44 for the Design of Protein-Carbohydrate Interaction Inhibitors>, SDS of cas: 115955-90-3, the main research area is CD44 binding site protein carbohydrate inhibitor design crystal structure.

Selective inhibitors of hyaluronan (HA) binding to the cell surface receptor CD44 will have value as probes of CD44-mediated signaling and have potential as therapeutic agents in chronic inflammation, cardiovascular disease, and cancer. Using biophys. binding assays, fragment screening, and crystallog. characterization of complexes with the CD44 HA binding domain, we have discovered an inducible pocket adjacent to the HA binding groove into which small mols. may bind. Iterations of fragment combination and structure-driven design have allowed identification of a series of 1,2,3,4-tetrahydroisoquinolines as the first nonglycosidic inhibitors of the CD44-HA interaction. The affinity of these mols. for the CD44 HA binding domain parallels their ability to interfere with CD44 binding to polymeric HA in vitro. X-ray crystallog. complexes of lead compounds are described and compared to a new complex with a short HA tetrasaccharide, to establish the tetrahydroisoquinoline pharmacophore as an attractive starting point for lead optimization.

Journal of Medicinal Chemistry published new progress about CD44 antigens Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 115955-90-3 belongs to class tetrahydroisoquinoline, and the molecular formula is C9H12N2, SDS of cas: 115955-90-3.

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

Xie, Feng; Chen, Qing-Hua; Xie, Rong; Jiang, Huan-Feng; Zhang, Min published the artcile< MOF-Derived Nanocobalt for Oxidative Functionalization of Cyclic Amines to Quinazolinones with 2-Aminoarylmethanols>, COA of Formula: C9H12N2, the main research area is MOF nanocobalt catalysis oxidative functionalization cyclic amine aminoarylmethanol; quinazolinone preparation.

By employing a MOF-templated method, we have developed a highly dispersed and ultralow loading cobalt nanocatalyst, which has been applied in the oxidative functionalization of easily available cyclic amines with 2-aminoarylmethanols to ring-fused quinazolinones, the core structures of numerous valuable products. The developed catalytic transformation proceeds with the merits of broad substrate scope, good functional group tolerance and chemoselectivity, high step- and atom-efficiency, and use of the naturally abundant Co/O2 system, which offers a practical way for the preparation of quinazolinones with structural diversity. The work presented has built an important basis for direct conversion of cyclic amine motifs into functional frameworks.

ACS Catalysis published new progress about Atom economy. 115955-90-3 belongs to class tetrahydroisoquinoline, and the molecular formula is C9H12N2, COA of Formula: C9H12N2.

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