Heterocyclic Building Blocks-Tetrahydroisoquinoline

Grunewald, Gary L. et al. published their research in Journal of Medicinal Chemistry in 1999 | CAS: 207451-81-8

7-Methyl-1,2,3,4-tetrahydroisoquinoline (cas: 207451-81-8) belongs to tetrahydroisoquinoline derivatives. The tetrahydroisoquinoline skeleton is encountered in a number of bioactive compounds and drugs. The dopamine-derived tetrahydroisoquinolines (TIQ) synthesized endogeneously from aldehydes and catecholamines have shown to modulate neurotransmission, central metabolism and motor activity.Application In Synthesis of 7-Methyl-1,2,3,4-tetrahydroisoquinoline

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 α₂-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.Application In Synthesis of 7-Methyl-1,2,3,4-tetrahydroisoquinoline 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 α₂-adrenoceptor. To design a selective (PNMT vs α₂-adrenoceptor affinity) inhibitor of PNMT, the steric and electrostatic factors responsible for PNMT inhibitory activity and α₂-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 = 0.599π – 0.0725MR + 1.55σ_m + 5.80; n = 27, r = 0.885, s = 0.573) and a three-parameter equation for the α₂-adrenoceptor (α₂ pK_i = 0.599π – 0.0542MR – 0.951σ_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 α₂-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 α₂-adrenoceptor affinity) inhibitors of PNMT. In the experiment, the researchers used many compounds, for example, 7-Methyl-1,2,3,4-tetrahydroisoquinoline (cas: 207451-81-8Application In Synthesis of 7-Methyl-1,2,3,4-tetrahydroisoquinoline).

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

Xie, Yu et al. published their research in Youji Huaxue in 2010 | CAS: 207451-81-8

7-Methyl-1,2,3,4-tetrahydroisoquinoline (cas: 207451-81-8) 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. 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.Electric Literature of C10H13N

A novel synthesis of isoquinolone derivatives was written by Xie, Yu;Hu, Jingang;Hong, Xiaowei;Wei, Ya;Jia, Jie. And the article was included in Youji Huaxue in 2010.Electric Literature of C10H13N This article mentions the following:

Tetrahydroisoquinoline derivatives [i.e., δ-lactams] were designed and the synthesis of the target compounds was achieved by a nucleophilic substitution, cyclization reaction using Et chloroformate and benzeneethanamine derivatives as starting materials. The above-mentioned isoquinolinone derivatives are precursors for 1,2,3,4-tetrahydroisoquinoline derivatives (no data). The key step in this sequence, a cyclization reaction, was accomplished by using polyphosphoric acid (PPA) as a catalyst conveniently and effectively under solvent-free reaction conditions. In the experiment, the researchers used many compounds, for example, 7-Methyl-1,2,3,4-tetrahydroisoquinoline (cas: 207451-81-8Electric Literature of C10H13N).

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

Remsburg, Jeffrey W. et al. published their research in Journal of Liquid Chromatography & Related Technologies in 2008 | CAS: 151004-92-1

(S)-1,2,3,4-Tetrahydroisoquinoline-1-carboxylic acid (cas: 151004-92-1) belongs to tetrahydroisoquinoline derivatives. The tetrahydroisoquinoline skeleton is encountered in a number of bioactive compounds and drugs. Like other secondary amines, tetrahydroisoquinoline can be oxidized to the corresponding nitrone using hydrogen peroxide, catalyzed by selenium dioxide.Application of 151004-92-1

LC enantiomeric separation of unusual amino acids using cyclodextrin-based stationary phases was written by Remsburg, Jeffrey W.;Armstrong, Daniel W.;Peter, Antal;Toth, Geza. And the article was included in Journal of Liquid Chromatography & Related Technologies in 2008.Application of 151004-92-1 This article mentions the following:

The use of cyclodextrin based stationary phases was studied for the enantiomeric separation of 20 unusual amino acids. Mobile phase, pH effects, and flow rate were optimized for each separation Separations were limited to aqueous mobile phases. Nineteen of the amino acids were separated, with seven having a resolution ≥1.5. The highest selectivities came from the alpha, acetylated beta, and 2,6-dinitrophenyl-4-trifluoromethylphenyl derivitized beta-cyclodextrin stationary phases. Amino acids containing a 1,2,3,4 tetrahydroisoquinoline carboxylic acid structure showed great compatibility with the acetylated beta-cyclodextrin. Tyrosine analogs, due to lack of retention, were not well suited to the cyclodextrin stationary phases. In the experiment, the researchers used many compounds, for example, (S)-1,2,3,4-Tetrahydroisoquinoline-1-carboxylic acid (cas: 151004-92-1Application of 151004-92-1).

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

Grunewald, Gary L. et al. published their research in Bioorganic & Medicinal Chemistry Letters in 1999 | CAS: 82771-59-3

1-(1,2,3,4-Tetrahydroisoquinolin-7-yl)ethanone (cas: 82771-59-3) belongs to tetrahydroisoquinoline derivatives. The tetrahydroisoquinoline skeleton is present in a number of drugs, such as tubocurarine, one of the quaternary ammonium muscle relaxants. 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.Product Details of 82771-59-3

Comparative molecular field analysis (CoMFA) models of phenylethanolamine N-methyltransferase (PNMT) and the α₂-adrenoceptor: the development of new, highly selective inhibitors of PNMT was written by Grunewald, Gary L.;Caldwell, Timothy M.;Dahanukar, Vilas H.;Jalluri, Ravi K.;Criscione, Kevin R.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 1999.Product Details of 82771-59-3 The following contents are mentioned in the article:

As a guide to the development of new and more selective inhibitors of phenylethanolamine N-methyltransferase (PNMT) vs. the α₂-adrenoceptor, we have performed a comparative mol. field anal. (CoMFA) on a series of 80 benzylamine analogs. Using the models obtained, we have proposed a series of 3-trifluoromethyl-1,2,3,4-tetrahydroisoquinolines and predicted the activity of other analogs. This study involved multiple reactions and reactants, such as 1-(1,2,3,4-Tetrahydroisoquinolin-7-yl)ethanone (cas: 82771-59-3Product Details of 82771-59-3).

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

Liu, Li-Kai et al. published their research in Journal of Medicinal Chemistry in 2014 | CAS: 223700-11-6

2-Ethyl-1,2,3,4-tetrahydroisoquinolin-5-amine (cas: 223700-11-6) 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. Like other secondary amines, tetrahydroisoquinoline can be oxidized to the corresponding nitrone using hydrogen peroxide, catalyzed by selenium dioxide.Application of 223700-11-6

Fragment-Based Identification of an Inducible Binding Site on Cell Surface Receptor CD44 for the Design of Protein-Carbohydrate Interaction Inhibitors was written by Liu, Li-Kai;Finzel, Barry C.. And the article was included in Journal of Medicinal Chemistry in 2014.Application of 223700-11-6 The following contents are mentioned in the article:

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. This study involved multiple reactions and reactants, such as 2-Ethyl-1,2,3,4-tetrahydroisoquinolin-5-amine (cas: 223700-11-6Application of 223700-11-6).

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

Ali, Fadia El-Fehail et al. published their research in Journal of Medicinal Chemistry in 1982 | CAS: 82771-59-3

1-(1,2,3,4-Tetrahydroisoquinolin-7-yl)ethanone (cas: 82771-59-3) belongs to tetrahydroisoquinoline derivatives. Tetrahydroisoquinoline can be dehydrogenated to give isoquinoline and hydrogenated to decahydroisoquinoline. 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-α-aminols.HPLC of Formula: 82771-59-3

Imidodisulfamides. 2. Substituted 1,2,3,4-tetrahydroisoquinolinylsulfonic imides as antagonists of slow-reacting substance of anaphylaxis was written by Ali, Fadia El-Fehail;Gleason, John G.;Hill, David T.;Krell, Robert D.;Kruse, Carolyn H.;Lavanchy, Patricia G.;Volpe, Beth W.. And the article was included in Journal of Medicinal Chemistry in 1982.HPLC of Formula: 82771-59-3 The following contents are mentioned in the article:

Substituted 1,2,3,4-tetrahydroisoquinolinylsulfonic imides, e.g., I (R = H, 5-, 6-, 7-, 8-Cl, 7-MeO, 6,7,8-Cl₃) and 1,5-bis(arylcycloalkyl)imidodisulfamides, e.g. II, were prepared by condensation of the corresponding amine with ClSO₂NHSO₂Cl. In order to determine the influence of structural modifications of the imidodisulfamides on their ability to selectively antagonize SRS-A activity, a few conformationally constrained structures were examined Among these derivatives having a conformationally restricted alkylene side chain, substituted 1,2,3,4-tetrahydroisoquinolinylsulfonic imides produced optimum SRS-A antagonist activity and selectivity. These compounds were tested for antagonism of partially purified SRS-A induced contractions of isolated guinea pig ileum. In this series of tetrahydroisoquinolines, the effect of aromatic ring substitution, as well as substitution and variation of the size of the heterocyclic ring on SRS-A antagonist activity and selectivity, was studied. This study involved multiple reactions and reactants, such as 1-(1,2,3,4-Tetrahydroisoquinolin-7-yl)ethanone (cas: 82771-59-3HPLC of Formula: 82771-59-3).

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

Grunewald, Gary L. et al. published their research in Bioorganic & Medicinal Chemistry in 2008 | CAS: 82771-59-3

1-(1,2,3,4-Tetrahydroisoquinolin-7-yl)ethanone (cas: 82771-59-3) belongs to tetrahydroisoquinoline derivatives. Tetrahydroisoquinoline can be dehydrogenated to give isoquinoline and hydrogenated to decahydroisoquinoline. 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.Reference of 82771-59-3

Synthesis of 4,5,6,7-tetrahydrothieno[3,2-c]pyridines and comparison with their isosteric 1,2,3,4-tetrahydroisoquinolines as inhibitors of phenylethanolamine N-methyltransferase was written by Grunewald, Gary L.;Seim, Mitchell R.;Bhat, Seema R.;Wilson, Marc E.;Criscione, Kevin R.. And the article was included in Bioorganic & Medicinal Chemistry in 2008.Reference of 82771-59-3 The following contents are mentioned in the article:

A series of substituted 4,5,6,7-tetrahydrothieno[3,2-c]pyridines (THTPs) was synthesized and evaluated for their human phenylethanolamine N-methyltransferase (hPNMT) inhibitory potency and affinity for the α₂-adrenoceptor. The THTP nucleus was suggested as an isosteric replacement for the 1,2,3,4-tetrahydroisoquinoline (THIQ) ring system on the basis that 3-thienylmethylamine was more potent as an inhibitor of hPNMT and more selective toward the α₂-adrenoceptor than benzylamine. Although the isosterism was confirmed, with similar influence of functional groups and chirality in both systems on hPNMT inhibitory potency and selectivity, the THTP compounds proved, in general, to be less potent as inhibitors of hPNMT than their THIQ counterparts, with the drop in potency being primarily attributed to the electronic properties of the thiophene ring. A hypothesis for the reduced hPNMT inhibitory potency of these compounds has been formed on the basis of mol. modeling and docking studies using the x-ray crystal structures of hPNMT cocrystd. with THIQ-type inhibitors and S-adenosyl-L-homocysteine as a template. This study involved multiple reactions and reactants, such as 1-(1,2,3,4-Tetrahydroisoquinolin-7-yl)ethanone (cas: 82771-59-3Reference of 82771-59-3).

1-(1,2,3,4-Tetrahydroisoquinolin-7-yl)ethanone (cas: 82771-59-3) belongs to tetrahydroisoquinoline derivatives. Tetrahydroisoquinoline can be dehydrogenated to give isoquinoline and hydrogenated to decahydroisoquinoline. 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.Reference of 82771-59-3

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

Grunewald, Gary L. et al. published their research in Journal of Medicinal Chemistry in 1999 | CAS: 82771-59-3

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 α₂-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.HPLC of Formula: 82771-59-3 The following contents are mentioned in the article:

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 α₂-adrenoceptor. To design a selective (PNMT vs α₂-adrenoceptor affinity) inhibitor of PNMT, the steric and electrostatic factors responsible for PNMT inhibitory activity and α₂-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 = 0.599π – 0.0725MR + 1.55σ_m + 5.80; n = 27, r = 0.885, s = 0.573) and a three-parameter equation for the α₂-adrenoceptor (α₂ pK_i = 0.599π – 0.0542MR – 0.951σ_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 α₂-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 α₂-adrenoceptor affinity) inhibitors of PNMT. This study involved multiple reactions and reactants, such as 1-(1,2,3,4-Tetrahydroisoquinolin-7-yl)ethanone (cas: 82771-59-3HPLC of Formula: 82771-59-3).

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

Zhou, Nan’s team published research in Bioorganic & Medicinal Chemistry in 25 | CAS: 142335-42-0

Bioorganic & Medicinal Chemistry published new progress about 142335-42-0. 142335-42-0 belongs to tetrahydroisoquinoline, auxiliary class Tetrahydroisoquinoline,Chiral,Carboxylic acid,Amide,Alcohol, name is (S)-2-(tert-Butoxycarbonyl)-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, and the molecular formula is C9H6FNO, Application In Synthesis of 142335-42-0.

Zhou, Nan published the artcileDiscovery of a tetrahydroisoquinoline-based HDAC inhibitor with improved plasma stability, Application In Synthesis of 142335-42-0, the publication is Bioorganic & Medicinal Chemistry (2017), 25(17), 4614-4619, database is CAplus and MEDLINE.

Histone deacetylase inhibitors with desirable pharmacokinetic profiles which can be delivered to solid tumor tissues in large amount might be promising to treat solid tumor effectively. Herein, structural modification of a previously reported tetrahydroisoquinoline-based HDAC inhibitor 2-[(2S,3S)-2-[(3,3-dimethyl-1-oxobutyl)amino]-3-methyl-1-oxopentyl]-1,2,3,4-tetrahydro-7-[2-(hydroxyamino)-2-oxoethoxy]-N-(4-methoxyphenyl)-, (3S)-3-Isoquinolinecarboxamide [1314556-93-8] (I) was carried out to improve its plasma stability for more feasible drug delivery. Among three newly synthesized analogs, the in vitro rat plasma stability of compound (II) (t_1/2 = 630 min) was over 5-fold improved than its parent I (t_1/2 = I03 min). In vitro activity evaluation showed that compound II and I exhibited similar HDACs inhibitory activity, which was validated by western blot anal. and antiproliferative assay. Moreover, compared with I, compound II exhibited comparable, if not higher, in vivo antitumor activity in a human breast carcinoma (MDA-MB-231) xenograft model.

Referemce:
https://en.wikipedia.org/wiki/Tetrahydroisoquinoline,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

Tourwe, Dirk’s team published research in Biopolymers in 38 | CAS: 142335-42-0

Biopolymers published new progress about 142335-42-0. 142335-42-0 belongs to tetrahydroisoquinoline, auxiliary class Tetrahydroisoquinoline,Chiral,Carboxylic acid,Amide,Alcohol, name is (S)-2-(tert-Butoxycarbonyl)-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, and the molecular formula is C17H18N2O6, Product Details of C15H19NO5.

Tourwe, Dirk published the artcileConformational restriction of Tyr and Phe side chains in opioid peptides: information about preferred and bioactive side-chain topology, Product Details of C15H19NO5, the publication is Biopolymers (1996), 38(1), 1-12, database is CAplus and MEDLINE.

The side chain of Tyr and Phe was fixed into the gauche(-) or gauche(+) conformation by using 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) or 7-hydroxy-Tic (Htc) structures, and into the trans conformation by using aminobenzazepine-type structure I. When incorporated into dermorphin or deltorphin II, the Tic and Htc analogs all showed a large decrease in both μ and δ affinities and activities. Fixation of Phe³ in the trans rotamer resulted in a large increase in δ affinity in the dermorphin analog, whereas in the I-containing deltorphin II analog, good δ affinity is maintained despite the removal of the Glu side chain. Whereas several authors propose a gauche(-) preferred conformation for the Phe³ side chain, these results suggest a trans conformation at the δ receptor. The use of these conformationally constrained residues for evaluating the preferred solution conformation in the flexible N-terminal tripeptide Tyr-D-Ala-Phe is illustrated. The ¹H-NMR parameters-chem. shift, temperature dependence, and nuclear Overhauser effects to the D-Ala² Me protons in the different analogs-provide direct evidence to confirm the proposed sandwich conformation in the native peptides.

Referemce:
https://en.wikipedia.org/wiki/Tetrahydroisoquinoline,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem