Category: 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).

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. Like other secondary amines, tetrahydroisoquinoline can be oxidized to the corresponding nitrone using hydrogen peroxide, catalyzed by selenium dioxide.HPLC of Formula: 82771-59-3

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

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

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).

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

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

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).

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

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