Comparison of biological effects of N-alkylated congeners of .beta.-phenethylamine derived from 2-aminotetralin, 2-aminoindan, and 6-aminobenzocycloheptene

Cannon, Joseph G.; Pérez, Julio; Pease, Jonathan P.; Long, J. P.; Flynn, Jan R.; Rusterholz, David B.; Dryer, Stuart E.

doi:10.1021/jm00181a009

Cited by 29 publications

(17 citation statements)

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“…Propylaminoindane hydrochloride 2(54), which was readily prepared by reductive amination of indan-2-one 1, was substituted in a nucleophilic manner with 4-bromobutyronitrile to afford the (N-indan-2-yl-N-propyl)-4-aminobutyronitrile 4a. Reduction of the nitrile 4a resulted in the primary amine 4b, which could be transformed into the carboxamides 5a-c by taking HATU-promoted coupling with the respective carboxylic acids.…”

mentioning

confidence: 99%

Engineering a GPCR−Ligand Pair That Simulates the Activation of D_2L by Dopamine

Tschammer

Dörfler

Hübner

et al. 2009

ACS Chem. Neurosci.

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In the past decade, engineered G-protein-coupled receptors activated solely by synthetic ligands (RASSLs) have been implemented as a new means to study neurotransmission, which is controlled by G-protein-coupled receptors in vitro and in vivo. In this study, we report an engineered dopamine receptor D(2L) F390(6.52)W, which is the first identified RASSL for the dopamine receptor family. The mutant receptor is characterized by a disrupted ligand binding and complete loss of efficacy for the endogenous ligand, dopamine, which is putatively due to a sterically induced perturbation of H-bonding with conserved serine residues in TM5. Based on this model, we rationally developed an aminoindane-derived set of agonists. Because these agonists forgo analogous H-bonding functionalities, their binding energy does not depend on the respective interactions. Binding affinity and potency were optimized by ligand modifications bearing molecular appendages that obviously interact with a secondary recognition site provided by four hydrophobic residues in TM2 and TM3. Thus, the ferrocenyl carboxamide 5b (FAUC 185) was identified as a synthetic agonist that is able to stimulate the mutant receptor in a manner similar to that by which endogenous dopamine activates the D(2L) wild-type receptor. The engineered dopamine receptor D(2L) F390(6.52)W in combination with FAUC 185 (5b) provides a new tool to probe GPCR functions selectively in specific cell populations in vitro and in vivo.

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confidence: 99%

Engineering a GPCR−Ligand Pair That Simulates the Activation of D_2L by Dopamine

Tschammer

Dörfler

Hübner

et al. 2009

ACS Chem. Neurosci.

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“…After the addition was completed, the reaction mixture was stood overnight at room temperature. To the reaction mixture was added 5% aqueous citric acid (700 mL), and the precipitate solid was collected by filtration, washed with H 2 O, and dried under reduced pressure to give tert-butyl 1,3-dihydro-2H-isoindol-2-yl(methyl)carbamate (27) (126 g, 84%) as a pale pink solid. This compound was used in the next reaction without further purification.…”

Section: N 2 -[5-chloro-2-(4-chlorophenoxy)phenyl]-n 2 -{2-[23-dihydmentioning

confidence: 99%

Discovery and structural analyses of S-adenosyl-l-homocysteine hydrolase inhibitors based on non-adenosine analogs

Nakao

Suzuki

Ueno

et al. 2015

Bioorganic & Medicinal Chemistry

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“…2-ero-Amino-5,8-dimethoxy-1,2,3,4-tetrahydro-1,4ethanonaphthalene Hydrochloride (7). To a solution of 780 mg (206 mmol) of sodium borohydride in 50 mL of diglyme was added 10.8 g (50 mmol) of olefin 16.…”

Section: Methodsmentioning

confidence: 99%

.alpha.-Adrenergic agents. 1. Direct-acting .alpha.1 agonists related to methoxamine

DeMarinis¹,

Bryan²,

Shah³

et al. 1981

J. Med. Chem.

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A series of phenylethylamines related to methoxamine has been prepared and evaluated for direct alpha 1-receptor agonist activity. It has been observed that for open-chain compounds such as methoxamine, in which the amine-containing portion is free to adopt numerous conformations, an hydroxyl group is necessary for direct alpha 1-adrenergic activity. When the hydroxyl is removed, however, the direct component of activity is greatly reduced unless the amine is incorporated into a more sterically defined structure. From our studies we have concluded that in order for a phenylethylamine to be active as a direct alpha 1-receptor agonist it should have a beta nitrogen in a fully extended conformation relative to a substituted phenyl ring. For optimum potency, the nitrogen should be exocyclic to a saturated six-membered ring. It may be further incorporated exocyclic or endocyclic into an additional ring as long as the amine occupies a well-defined region of space relative to the aromatic portion of a molecule. The ED50 values of some of the more potent compounds as alpha 1-receptor agonists are on the order of 1 X 10(-7) M.

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Comparison of biological effects of N-alkylated congeners of .beta.-phenethylamine derived from 2-aminotetralin, 2-aminoindan, and 6-aminobenzocycloheptene

Cited by 29 publications

References 0 publications

Engineering a GPCR−Ligand Pair That Simulates the Activation of D_2L by Dopamine

Engineering a GPCR−Ligand Pair That Simulates the Activation of D_2L by Dopamine

Discovery and structural analyses of S-adenosyl-l-homocysteine hydrolase inhibitors based on non-adenosine analogs

.alpha.-Adrenergic agents. 1. Direct-acting .alpha.1 agonists related to methoxamine

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Comparison of biological effects of N-alkylated congeners of .beta.-phenethylamine derived from 2-aminotetralin, 2-aminoindan, and 6-aminobenzocycloheptene

Cited by 29 publications

References 0 publications

Engineering a GPCR−Ligand Pair That Simulates the Activation of D2L by Dopamine

Engineering a GPCR−Ligand Pair That Simulates the Activation of D2L by Dopamine

Discovery and structural analyses of S-adenosyl-l-homocysteine hydrolase inhibitors based on non-adenosine analogs

.alpha.-Adrenergic agents. 1. Direct-acting .alpha.1 agonists related to methoxamine

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Engineering a GPCR−Ligand Pair That Simulates the Activation of D_2L by Dopamine

Engineering a GPCR−Ligand Pair That Simulates the Activation of D_2L by Dopamine