Category: tetrahydroisoquinoline

Quinolizidines. XXXI. A synthesis of the dibenzo[a,h]quinolizidine ring system: an application of the mercuric acetate-edetic acid oxidation method to 1,2,3,4-tetrahydroisoquinoline was written by Ohba, Masashi;Shinbo, Yoko;Ohashi, Takako;Toda, Mitsuhiro;Fujii, Tozo. And the article was included in Heterocycles in 1992.Application of 2328-12-3 This article mentions the following:

A formal synthesis of 2,3-dimethoxydibenzo[a,h]quinolizidine (I) has been achieved through a route including mercuric acetate-edetic acid oxidation of a benzene-fused piperidine. The route started with an initial condensation of 1,2,3,4-tetrahydroisoquinoline with 3,4-dimethoxyphenacyl bromide and proceeded through the amino ketone, amino alc. II, lactam alc., and the lactam III. A parallel sequence of reactions concluded a formal synthesis of the 2,3,11,12-tetramethoxy analog. In the mercuric acetate-edetic acid oxidations of the amino alcs. II under acidic or alk. conditions gave oxazoloisoquinoline derivatives besides the desired lactam alcs. In the experiment, the researchers used many compounds, for example, 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (cas: 2328-12-3Application of 2328-12-3).

6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (cas: 2328-12-3) belongs to tetrahydroisoquinoline derivatives. There has been increasing research interest and speculation since 1968 in the potential formation of tetrahydroisoquinoline (TIQ) alkaloids in mammalian cells via such interactions, and in the role such TIQs may have in alcohol dependence. An efficient CuCl2-catalyzed coupling of nonfunctionalized tetrahydroisoquinolines with organozinc reagents under aerobic conditions proceeds in high yields under mild reaction conditions and is broadly applicable to a wide range of substrates. The reaction involves an iminium ion intermediate that is formed via a SET process.Application of 2328-12-3

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

Synthesis and Structure Activity Relationship of Tetrahydroisoquinoline-Based Potentiators of GluN2C and GluN2D Containing N-Methyl-D-aspartate Receptors [Erratum to document cited in CA159:150256] was written by Santangelo Freel, Rose M.;Ogden, Kevin K.;Strong, Katie L.;Khatri, Alpa;Chepiga, Kathryn M.;Jensen, Henrik S.;Traynelis, Stephen F.;Liotta, Dennis C.. And the article was included in Journal of Medicinal Chemistry in 2014.Category: tetrahydroisoquinoline This article mentions the following:

The description of the model shown in Figure 3 predicts the wrong stereochem. of the amine resulting from the stereoselective reduction of the imine; the corrected stereochem. is given, along with a discussion of the effects. In the experiment, the researchers used many compounds, for example, 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (cas: 2328-12-3Category: tetrahydroisoquinoline).

6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (cas: 2328-12-3) belongs to tetrahydroisoquinoline derivatives. Tetrahydroisoquinoline motif is often present in natural products with a broad range of biological and pharmacological activities. An intramolecular Friedel-Crafts cyclization of an in situ generated tosylate intermediate enables an efficient construction of 3-substituted 1,2,3,4-tetrahydroisoquinolines from N,N-dibenzyl-伪-aminols.Category: tetrahydroisoquinoline

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

Discovery of Antiglioma Activity of Biaryl 1,2,3,4-Tetrahydroisoquinoline Derivatives and Conformationally Flexible Analogues was written by Mohler, Michael L.;Kang, Gyong-Suk;Hong, Seoung-Soo;Patil, Renukadevi;Kirichenko, Oleg V.;Li, Wei;Rakov, Igor M.;Geisert, Eldon E.;Miller, Duane D.. And the article was included in Journal of Medicinal Chemistry in 2006.Application In Synthesis of 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride This article mentions the following:

Cultured rat astrocytes and C6 rat glioma were used as a differential screen for a variety of 1,2,3,4-tetrahydroisoquinoline (THI) derivatives Compound (I) selectively blocked the growth of C6 glioma leaving normal astrocytes relatively unaffected. The potential for clin. utility of I was further substantiated in human gliomas and other tumor cell lines. Preliminary SAR of this activity was characterized by synthesis and testing of several THI and conformationally flexible variants. In the experiment, the researchers used many compounds, for example, 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (cas: 2328-12-3Application In Synthesis of 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride).

6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (cas: 2328-12-3) belongs to tetrahydroisoquinoline derivatives. The tetrahydroisoquinoline skeleton is present in a number of drugs, such as tubocurarine, one of the quaternary ammonium muscle relaxants. An intramolecular Friedel-Crafts cyclization of an in situ generated tosylate intermediate enables an efficient construction of 3-substituted 1,2,3,4-tetrahydroisoquinolines from N,N-dibenzyl-伪-aminols.Application In Synthesis of 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride

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

Discovery of Potent and Selective Inhibitors for ADAMTS-4 through DNA-Encoded Library Technology (ELT) was written by Ding, Yun;O’Keefe, Heather;DeLorey, Jennifer L.;Israel, David I.;Messer, Jeffrey A.;Chiu, Cynthia H.;Skinner, Steven R.;Matico, Rosalie E.;Murray-Thompson, Monique F.;Li, Fan;Clark, Matthew A.;Cuozzo, John W.;Arico-Muendel, Christopher;Morgan, Barry A.. And the article was included in ACS Medicinal Chemistry Letters in 2015.Electric Literature of C11H16ClNO2 This article mentions the following:

The aggrecan degrading metalloprotease ADAMTS-4 has been identified as a novel therapeutic target for osteoarthritis. Here, the authors use DNA-encoded Library Technol. (ELT) to identify novel ADAMTS-4 inhibitors from a DNA-encoded triazine library by affinity selection. Structure-activity relationship studies based on the selection information led to the identification of potent and highly selective inhibitors. For example I has IC₅₀ of 10 nM against ADAMTS-4, with >1000-fold selectivity over ADAMT-5, MMP-13, TACE, and ADAMTS-13. These inhibitors have no obvious zinc ligand functionality. In the experiment, the researchers used many compounds, for example, 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (cas: 2328-12-3Electric Literature of C11H16ClNO2).

6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (cas: 2328-12-3) belongs to tetrahydroisoquinoline derivatives. Tetrahydroisoquinoline, as a secondary amine, tetrahydroisoquinoline has weakly basic properties and forms salts with strong acids. An oxidative C1 arylation of tetrahydroisoquinolines with aryl Grignard reagents is mediated by diethyl azodicarboxylate (DEAD). This C-H activation under metal-free conditions delivers target compounds, including some naturally occurring alkaloids, in good yields.Electric Literature of C11H16ClNO2

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

New tetrahydroisoquinoline-based P-glycoprotein modulators: decoration of the biphenyl core gives selective ligands was written by Contino, Marialessandra;Guglielmo, Stefano;Perrone, Maria Grazia;Giampietro, Roberta;Rolando, Barbara;Carrieri, Antonio;Zaccaria, Daniele;Chegaev, Konstantin;Borio, Vanessa;Riganti, Chiara;Zabielska-Koczywas, Katarzyna;Colabufo, Nicola A.;Fruttero, Roberta. And the article was included in MedChemComm in 2018.Application In Synthesis of 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride This article mentions the following:

P-glycoprotein (P-gp, MDR1) is a membrane transporter expressed in several regions of our v. It plays a crucial defense role as it mediates the efflux of hundreds of potentially toxic substances. However, P-gp is one of the main causes of failure in cancer chemotherapy, as a number of chemotherapeutic agents are P-gp substrates. Another interesting implication concerns the correlation between P-gp expression impairment and the onset of several central nervous system pathologies such as Alzheimer’s and Parkinson’s diseases. In view of these considerations, in the present study, a new series of P-gp modulators have been designed, synthesized and evaluated for their activity towards P-gp and two other sister proteins (BCRP and MRP1). The compounds, structurally correlated to the potent but non-selective P-gp inhibitor MC70 [4′-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-ylmethyl)biphenyl-4-ol], proved fairly selective towards P-gp, with a potency in the micromolar range. Compounds 5a, 5d and 12d proved capable of restoring doxorubicin toxicity in resistant cancer cells. In the experiment, the researchers used many compounds, for example, 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (cas: 2328-12-3Application In Synthesis of 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride).

6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (cas: 2328-12-3) belongs to tetrahydroisoquinoline derivatives. Tetrahydroisoquinoline motif is often present in natural products with a broad range of biological and pharmacological activities. In particular, 1-benzyl1,2,3,4-tetrahydroisoquinolines are dopamine receptor antagonists. Because of the high biological relevance of compounds possessing the 1,2,3,4-tetrahydroisoquinoline framework, a large number of synthetic approaches towards the creation of an isoquinoline or 1,2,3,4-tetrahydroisoquinoline core are presently known. However, synthetic routes to tetrahydroisoquinoline derivatives containing fluorine atom(s) in their structure are not particularly abundant.Application In Synthesis of 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride

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

The effect and mechanistic study of encequidar on reversing the resistance of SW620/AD300 cells to doxorubicin was written by Zhang, Hang;Bian, Shaopan;Xu, Zhihao;Gao, Ming;Wang, Han;Zhang, Junwei;Zhang, Mingkun;Ke, Yu;Wang, Weijia;Chen, Zhe-Sheng;Xu, Haiwei. And the article was included in Biochemical Pharmacology (Amsterdam, Netherlands) in 2022.Application In Synthesis of 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride This article mentions the following:

Encequidar, a gut-specific P-glycoprotein (P-gp) inhibitor, makes oral paclitaxel possible, and has been used in clin. treatment of metastatic breast cancer, however, its pharmacol. effect and mechanism of reversal of drug resistance in drug-resistant colon cancer cells SW620/AD300 are still unknown. Herein, we first synthesized encequidar and demonstrated that it could inhibit the transport activity of P-gp, reduced doxorubicin (DOX) efflux, enhanced DOX cytotoxicity and promoted tumor-apoptosis in SW620/AD300 cells. Metabolomic anal. of cell samples was performed using liquid chromatog. Q-Exactive mass spectrometer, the results of metabolite enrichment anal. and pathway anal. showed that the combination of encequidar and DOX could: i. significantly affect the citric acid cycle (TCA cycle) and reduce the energy supply required for P-gp to exert its transport activity; ii. affect the metabolism of glutathione, which is the main component of the anti-oxidative stress system, and reduce the ability of cells to resist oxidative stress; iii. increase the intracellular reactive oxygen species (ROS) production and enhance ROS-induced cell damage and lipid peroxidation, which in turn restore the sensitivity of drug-resistant cells to DOX. In conclusion, these results provide sufficient data support for the therapeutical application of the P-gp inhibitor encequidar to reverse MDR, and are of great significance to further understand the therapeutic advantages of encequidar in anti-tumor therapy and guide clin. rational drug use. In the experiment, the researchers used many compounds, for example, 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (cas: 2328-12-3Application In Synthesis of 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride).

6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (cas: 2328-12-3) belongs to tetrahydroisoquinoline derivatives. Tetrahydroisoquinoline, as a secondary amine, tetrahydroisoquinoline has weakly basic properties and forms salts with strong acids. Because of the high biological relevance of compounds possessing the 1,2,3,4-tetrahydroisoquinoline framework, a large number of synthetic approaches towards the creation of an isoquinoline or 1,2,3,4-tetrahydroisoquinoline core are presently known. However, synthetic routes to tetrahydroisoquinoline derivatives containing fluorine atom(s) in their structure are not particularly abundant.Application In Synthesis of 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride

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

Synthesis, Biochemical Evaluation, and Classical and Three-Dimensional Quantitative Structure-Activity Relationship Studies of 7-Substituted-1,2,3,4-tetrahydroisoquinolines and Their Relative Affinities toward Phenylethanolamine N-Methyltransferase and the 伪₂-Adrenoceptor was written by Grunewald, Gary L.;Dahanukar, Vilas H.;Jalluri, Ravi K.;Criscione, Kevin R.. And the article was included in Journal of Medicinal Chemistry in 1999.Electric Literature of C10H11ClF3N This article mentions the following:

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 伪₂-adrenoceptor. To design a selective (PNMT vs 伪₂-adrenoceptor affinity) inhibitor of PNMT, the steric and electrostatic factors responsible for PNMT inhibitory activity and 伪₂-adrenoceptor affinity were investigated by evaluating a number of 7-substituted-THIQs. A classical quant. structure-activity relationship (QSAR) study resulted in a three-parameter equation for PNMT (PNMT pK_i = 0.599蟺 – 0.0725MR + 1.55蟽_m + 5.80; n = 27, r = 0.885, s = 0.573) and a three-parameter equation for the 伪₂-adrenoceptor (伪₂ pK_i = 0.599蟺 – 0.0542MR – 0.951蟽_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 mol. field anal. (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 伪₂-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 伪₂-adrenoceptor affinity) inhibitors of PNMT. In the experiment, the researchers used many compounds, for example, 7-(Trifluoromethyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride (cas: 220247-87-0Electric Literature of C10H11ClF3N).

7-(Trifluoromethyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride (cas: 220247-87-0) belongs to tetrahydroisoquinoline derivatives. Tetrahydroisoquinoline, as a secondary amine, tetrahydroisoquinoline has weakly basic properties and forms salts with strong acids. Because of the high biological relevance of compounds possessing the 1,2,3,4-tetrahydroisoquinoline framework, a large number of synthetic approaches towards the creation of an isoquinoline or 1,2,3,4-tetrahydroisoquinoline core are presently known. However, synthetic routes to tetrahydroisoquinoline derivatives containing fluorine atom(s) in their structure are not particularly abundant.Electric Literature of C10H11ClF3N

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

Design, synthesis, and bioactivity study on Lissodendrins B derivatives as PARP1 inhibitor was written by Liu, Xinning;Wei, Xianfeng;Li, Xionghao;Yu, Rilei;Jiang, Tao;Zhao, Chenyang. And the article was included in Bioorganic & Medicinal Chemistry in 2022.Quality Control of 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride This article mentions the following:

Poly(ADP-ribose) polymerase-1 (PARP1) is an enzyme that catalyzes the polymerization of ADP-ribose units to target proteins, and it is a potential target for anti-cancer drug discovery, especially for BRAC1/2 mutated tumors. In this study, a series of 2-aminoimidazole Lissodendrins B derivatives were designed, synthesized, and evaluated as PARP1 inhibitors. We found that compound D3 is better due to its PARP enzyme inhibitory activity and in vitro anti-cancer activity compared with other tested compounds It could inhibit PARP1 enzymic activity (IC50 = 17.46渭M) in the non-cell system and BRCA1-deficient HCC1937 and MDA-MB-436 cells growth (IC50 = 17.81 and 12.63渭M, resp.). Further study demonstrated that compound D3 inhibits tumor growth through multiple mechanisms, such as reduction of PARylation, accumulation of cellular DNA double-strand breaks, induction of G2/M cell cycle arrest, and subsequent apoptosis of BRCA1-deficient cells. Besides, the mol. docking study also confirmed that compound D3 could effectively occupy the active pocket of PARP1. Our findings provide a new skeleton structure for PARP1 inhibitor, and the results suggested that the compound D3 may serve as a potential lead compound to develop novel PARP1 inhibitors for cancer therapy. In the experiment, the researchers used many compounds, for example, 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (cas: 2328-12-3Quality Control of 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride).

6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (cas: 2328-12-3) belongs to tetrahydroisoquinoline derivatives. Tetrahydroisoquinoline, as a secondary amine, tetrahydroisoquinoline has weakly basic properties and forms salts with strong acids. Arene/Ru/TsDPEN complexes bearing a heterocyclic group catalyze the asymmetric transfer hydrogenation (ATH) of 1-aryl dihydroisoquinolines (DHIQs) to provide tetrahydroisoquinolines of high enantiomeric excess.Quality Control of 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride

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

Photocatalyzed Csp³-Csp³ cross-dehydrogenative coupling of N-Boc-tetrahydroisoquinolines with 伪,尾-unsaturated ketones was written by Ao, Na-Ri-Mei;Zhu, Xue-Qing;Zhao, Chun-Xin;Gao, Ya-Ru;Wang, Yong-Qiang. And the article was included in Organic & Biomolecular Chemistry in 2021.Synthetic Route of C14H18BrNO2 This article mentions the following:

A novel photocatalyzed cross-dehydrogenative coupling reaction of N-Boc-tetrahydroisoquinolines I [R¹ = H, 5-Br, 7-O₂N, 5,6-(MeO)₂, etc.] with 伪,尾-unsaturated ketones MeC(O)CH:CHR² (R² = Ph, n-hexyl, PhCH₂CH₂, etc.) has been developed. This research provides an easy access to a variety of C1-substituted tetrahydroisoquinolines II, which could be further transformed into benzo[a]quinolizine-2-ones, the skeletons of natural products with a wide range of biol. activities. The load of the photocatalyst was low and the oxidant was inexpensive and less toxic. In the experiment, the researchers used many compounds, for example, tert-Butyl 5-bromo-3,4-dihydroisoquinoline-2(1H)-carboxylate (cas: 215184-78-4Synthetic Route of C14H18BrNO2).

tert-Butyl 5-bromo-3,4-dihydroisoquinoline-2(1H)-carboxylate (cas: 215184-78-4) belongs to tetrahydroisoquinoline derivatives. Tetrahydroisoquinoline, as a secondary amine, tetrahydroisoquinoline has weakly basic properties and forms salts with strong acids. Tetrahydroisoquinoline derivatives may be formed in the body as metabolites of some drugs, and this was once thought to be involved in the development of alcoholism.This is no longer generally accepted by the scientific community.Synthetic Route of C14H18BrNO2

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

Biodegradable neuromuscular blocking agents. Part 3. Bisquaternary esters was written by Stenlake, John B.;Waigh, Roger D.;Urwin, John;Dewar, George H.;Hughes, Roy;Chapple, Dennis J.. And the article was included in European Journal of Medicinal Chemistry in 1981.Electric Literature of C11H16ClNO2 This article mentions the following:

Alkylenebis[tetrahydroisoquinolinium] derivatives, e.g. I (n = 4, 6, 8, 10) and II [R = H, 2-cyclopenten-1-ylmethyl, 3,4-(MeO)₂C₆H₃CH₂] were prepared Thus, 3,4-(MeO)₂C₆H₃CH₂CH₂NHCO(CH₂)₄CONHCH₂CH₂C₆H₃(OMe)₂-3,4 was cyclized to a bisdihydroisoquinoline, which was reduced followed by treatment with H₂C:CHCO₂Me and MeI to give I (n = 4). The compounds were tested as potential neuromuscular blocking agents in cats. Variations in duration of action, potency and vagal block are reported and related to structure. In the experiment, the researchers used many compounds, for example, 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (cas: 2328-12-3Electric Literature of C11H16ClNO2).

6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (cas: 2328-12-3) belongs to tetrahydroisoquinoline derivatives. The tetrahydroisoquinoline skeleton is present in a number of drugs, such as tubocurarine, one of the quaternary ammonium muscle relaxants. Arene/Ru/TsDPEN complexes bearing a heterocyclic group catalyze the asymmetric transfer hydrogenation (ATH) of 1-aryl dihydroisoquinolines (DHIQs) to provide tetrahydroisoquinolines of high enantiomeric excess.Electric Literature of C11H16ClNO2

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