Syntheses in the Direction of Morphine. I. 7-Methoxy- And 7,8-Dimethoxy-2-Tetralone.

Soffer, Milton D.; Cavagnol, J. C.; Gellerson, Hilda E.

doi:10.1021/ja01179a529

Cited by 9 publications

(4 citation statements)

References 2 publications

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“…Graphically, the conclusions could be represented by the three Markus formulae of Figure 2, where structure I represents mainly the selective ct2-adrenoceptor agonists, structure II the selective -adrenoceptor agonists, and structure III the nonselective partial a-adrenoceptor agonists of various efficacy. It is clear from this picture that the SARs so far described are in agreement with previous data from the literature since structure I can mimic the substitution pattern of clonidine (1), a partial <X2-adrenoceptor agonist, and structure II represents the kind of substitution prevailing in ST 587 (2) and SDV NVI 085 (42),24 two partial -adrenoceptor agonists. 25 A major goal of the present project was to detect compounds acting specifically on the veins while minimally affecting mean blood pressure.…”

Section: Resultssupporting

confidence: 88%

Design, synthesis, and structure-activity Relationships of a new series of .alpha.-adrenergic agonists: spiro[(1,3-diazacycylpent-1-ent)-5,2'-(1',2',3',4'-tetrahydronaphthalene)]

Cordi

Lacoste²,

Descombes³

et al. 1995

J. Med. Chem.

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The contractions induced by a partial alpha 1-adrenoceptor agonist in cutaneous veins, such as the saphenous vein, show a particular sensitivity to changes in local temperature: the contractility to a partial alpha 1-adrenoceptor agonist increases when the temperature is raised, a response that contrasts to that noted with full alpha 1- and alpha 2-adrenoceptor agonists. This observation may be of importance for the treatment of the symptoms of venous insuffiency, favored during warm summer days. A new series of full and partial alpha-adrenergic agonists was designed and synthesized, the spiro[(1,3-diazacyclopent-1-ene)-5,2'-(1',2',3',4'- tetrahydronaphthalene)] 7a-kk or spiro-imidazolines. Using in vitro (femoral artery and saphenous vein) and in vivo (pithed rat) biological evaluations, structure-activity relationships could be defined which allowed the discovery of a full alpha 2-agonist (34b), a full alpha 1-agonist (7s), and a nonselective partial alpha 1/alpha 2-agonist (7aa) endowed with an outstanding veinotonic selectivity as compared to its effect on mean arterial pressure. The latter compound is presently undergoing extensive pharmacological and toxicological evaluations, as a clinical candidate.

show abstract

Section: Resultssupporting

confidence: 88%

Design, synthesis, and structure-activity Relationships of a new series of .alpha.-adrenergic agonists: spiro[(1,3-diazacycylpent-1-ent)-5,2'-(1',2',3',4'-tetrahydronaphthalene)]

Cordi

Lacoste²,

Descombes³

et al. 1995

J. Med. Chem.

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“…mp 36 °C). Compound 3c : mp 26−27 °C [lit. , bp 130−136 °C (2.3 mmHg); mp 27−28 °C]. Compound 3d : mp 56−57 °C [lit. , mp 58−59 °C; bp 120−123 °C (1.0 mmHg)].…”

Section: Methodsmentioning

confidence: 99%

Synthesis and Antifungal Activities of Novel 2-Aminotetralin Derivatives

Bin

Cao

et al. 2007

J. Med. Chem.

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Novel 2-aminotetralin derivatives were synthesized as antifungal agents. The 2-aminotetralin scaffold was chemically designed to mimic the tetrahydroisoquinoline ring of the lead molecule described before. Their antifungal activities were evaluated in vitro by measuring the minimal inhibitory concentrations (MICs). Compounds 10a, 12a, 12c, 13b, and 13d are more potent than fluconazole against seven testing human fungal pathogens. Compound 10b exhibits much higher antifungal activities against all of the four fluconazole-resistant clinic Candida albicans strains than the control drugs including amphotericin B, terbinafine, ketoconazole, and itraconazole. The mode of action of some compounds to the potential receptor lanosterol 14alpha-demethylase (CYP51) was investigated by molecular docking. The studies presented here provide a new structural type for the development of novel antifungal compounds. Furthermore, 10b was evaluated in vivo by a rat vaginal candidiasis model, and it was found that 10b significantly decreases the number of fungal colony counts.

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“…Although this reaction sequence, via the reduction of 7-hydroxytetralin-2-one, proceeded in 88% ee as determined by methylation of the phenol followed by Mosher’s ester formation, in our hands the superacid reduction gave unpredictable conversions and was problematic on the multigram scale. Alternatively, dissolving metal reduction of the 2,7-dimethoxynaphthlene 3 followed by Noyori asymmetric reduction gave the chiral ( R )-7-methoxytetralin-2-ol, 4 , in good yield and excellent ee (92%; determined by chiral SFC). Direct demethylation of 4 with BBr 3 was unsuccessful, but protection of the alcohol as the acetate gave 5 , which was demethylated using BBr 3 .…”

mentioning

confidence: 99%

Synthesis and Bioactivity of a Brasilicardin A Analogue Featuring a Simplified Core

Jung¹,

Chamberlain²,

Koch³

et al. 2015

Org. Lett.

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An analogue 2 of Brasilicardin A, 1 (BraA), a potent immunosuppressive and cytotoxic agent, was synthesized in which the natural tricyclic skeleton was replaced with a synthetically more accessible substituted tetrahydronaphthalene core. BraA, this analogue (BraL), and cyclosporine A were tested for their ability to inhibit the proliferation of human T cells upon CD3/CD28 activation. Although BraL did not impact T cell activation over the dose range tested, this study shows the inhibitory activity of BraA on human T cells for the first time.

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Syntheses in the Direction of Morphine. I. 7-Methoxy- And 7,8-Dimethoxy-2-Tetralone.

Cited by 9 publications

References 2 publications

Design, synthesis, and structure-activity Relationships of a new series of .alpha.-adrenergic agonists: spiro[(1,3-diazacycylpent-1-ent)-5,2'-(1',2',3',4'-tetrahydronaphthalene)]

Design, synthesis, and structure-activity Relationships of a new series of .alpha.-adrenergic agonists: spiro[(1,3-diazacycylpent-1-ent)-5,2'-(1',2',3',4'-tetrahydronaphthalene)]

Synthesis and Antifungal Activities of Novel 2-Aminotetralin Derivatives

Synthesis and Bioactivity of a Brasilicardin A Analogue Featuring a Simplified Core

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