2-Substituted 4-(Thio)chromenone 6-<i>O</i>-Sulfamates:  Potent Inhibitors of Human Steroid Sulfatase

Nußbaumer, Peter; Lehr, Philipp; Billich, Andreas

doi:10.1021/jm020878w

Cited by 110 publications

(64 citation statements)

References 39 publications

(56 reference statements)

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“…20,22,[26][27][28][29][30] Thus, after the completion of the ketone forming reaction in BF 3 · Et 2 O [step (a) in Chart 1], the reaction mixture was cooled to room temperature. N,N-Dimethylformamide (DMF) was added as a one-carbon source, and the reaction mixture was stirred at 50°C for 10 min.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of Various Kinds of Isoflavones, Isoflavanes, and Biphenyl-Ketones and Their 1,1-Diphenyl-2-picrylhydrazyl Radical-Scavenging Activities

Goto

Terao

Akai

2009

CHEMICAL & PHARMACEUTICAL BULLETIN

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Isoflavones are a class of phenolic compounds produced by a variety of higher plants and especially very abundant in soybeans. The major components of soybeans include daidzein 1, genistein 2, and glycitein 3, 1) which are known to have some important biological activities such as estrogenlike activities 1) and antibacterial activities.2) Epidemiologic studies have also shown that the dietary intake of isoflavones is associated with some properties beneficial to human health such as the prevention of coronary heart disease and the reduced risk of breast, prostate, and colon cancers.3,4) Some of these effects are thought to be related to the antioxidant activities of the isoflavonoids 5) similar to that of the flavonoids such as catechins, 6) although the major soybean isoflavones (1-3) have been reported to have low antioxidant activities. 7)The metabolites of natural isoflavones generated by intestinal bacteria and/or enzymes, such as cytochrome P450, 8,9) are the key to understanding the net factors for the physiological efficiency of natural products, because cells are predominantly exposed to metabolites rather than the parent compounds.10,11) For example, equol 4 and O-desmethylangolensin 5 were isolated among the metabolites of 1 (Fig. 1), from which 4 was found to show a more potent estrogen activity than 1.12,13) Several other metabolites of 1 and 2, that have one or two additional hydroxy groups predominantly at the C6-, C8-and C3Ј-positions, have been identified in human urine and plasma.9,14-16) However, their biological activities have been scarcely reported probably due to their very low yields, and therefore, little is known about their structure-activity relationship.In 2004, Hirota et al. isolated the more oxygenated isoflavones, 6-hydroxydaidzein 6 and 8-hydroxyglycitein 7, from fermented soybean miso, which exhibited 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities (ED 50 ϭ24-37 mM) as high as that of a-tocopherol (Fig. 1). 17)Inspired by Hirota's report 17) and the isolation of the A-or B-ring hydroxylated metabolites as well as the C-ring reduced metabolites (4, 5), we started the synthesis of a wide range of isoflavones 8, isoflavanes 9, and the non-cyclic biphenyl-ketones (10, 10Ј) having oxygen-substituents on the A-and/or B-rings to systematically evaluate their DPPH radical scavenging activity. During the course of our research, the antioxidant activity of six kinds of isoflavones and nine metabolites, all of which are naturally available, were reported by two groups 7,18) ; however, the antioxidant activities of the synthetic isoflavones and their derivatives have never been reported. We now present the synthesis of forty-eight kinds of isoflavones 8, thirty-one isoflavanes 9, and fortyseven biphenyl-ketones (10, 10Ј), of which seventy-five compounds are new, and report some relationships of their struc- Suruga-ku, Shizuoka, Shizuoka 422-8526, Japan. Received November 13, 2008; accepted February 6, 2009 Forty-eight kinds of isoflavones (8), thirty-one isoflava...

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Section: Resultsmentioning

confidence: 99%

Synthesis of Various Kinds of Isoflavones, Isoflavanes, and Biphenyl-Ketones and Their 1,1-Diphenyl-2-picrylhydrazyl Radical-Scavenging Activities

Goto

Terao

Akai

2009

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…Batch Methods for the Synthesis of Compound I. According to Route 1, 2-chloro-1,3-benzothiazol-6-yl acetate (2) was prepared [9] from the corresponding phenol derivative (1) with acetyl chloride in the presence of AlCl 3 (Scheme 1).…”

Section: Resultsmentioning

confidence: 99%

Multistep Continuous-Flow Synthesis of Condensed Benzothiazoles

Lövei

Greiner²,

Éles³

et al. 2015

J Flow Chem

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In medicinal chemistry, the development of synthetic procedures for the access of new heterocyclic systems as potential scaffolds is elementary. Herein, we report our results on the formation of small drug-like heterocycles, utilizing flow chemistry. This approach enables the extension of the reaction parameter window, including high-pressure/high-temperature or hazardous chemistry. In our work, various novel condensed tricyclic benzothiazoles fused with furo-and thieno-rings were synthesized applying a multistep continuous-flow protocol. The process includes two ring closure steps and a nitro group reduction step. Batch and telescoped continuous-flow syntheses were also designed and performed.

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“…Wie die gute Inhibitorwirkung von 2-(1-Adamantyl)-4H-thiochromen-4-on-6-O-sulfamat (18, IC 50 = 340 pm, Abbildung 11) belegt, sind Moleküle mit hochverzweigten aliphatischen Substituenten am aktivsten. [249,250] Es wurden auch Benzophenonsulfamate hergestellt, unter anderem 4,4'-Benzophenon-O,O'-disulfamat (19, Abbildung 11) mit einem IC 50 -Wert von 190 nm. [251] Schließ-lich wurden Thiosemicarbazon-Derivate von Madurahydroxyaceton untersucht, einem Sekundärmetaboliten aus dem Bodenbakterium Nonomuria rubra.…”

Section: Angewandte Chemieunclassified

Sulfatasen: Struktur, Mechanismus, biologische Aktivität, Inhibition, Anwendung in Synthesen

2004

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Sulfatasen – d. h. Sulfatester spaltende Enzyme – spielen eine entscheidende Rolle bei der Regulierung von Sulfatierungszuständen, die über die Funktion vieler physiologischer Moleküle entscheiden. Die Substrate der Sulfatasen reichen von kleinen cytosolischen Steroiden wie dem Östrogensulfat bis hin zu komplexen Kohlenhydraten auf Zelloberflächen, etwa den Glycosaminoglycanen. Die Umwandlung dieser Moleküle wurde mit wichtigen zellulären Funktionen in Verbindung gebracht, z. B. mit der Hormonregulation, dem zellulären Abbau und der Modulation von Signalisierungsprozessen. Sulfatasen hängen mit dem Ausbruch etlicher pathophysiologischer Erscheinungen zusammen, etwa mit hormonabhängigen Krebsformen. Bis heute sind zwar zahlreiche Sulfatasen identifiziert worden, die Aufklärung des weitreichenden Spektrums ihrer biologischen Aktivitäten befindet sich aber erst am Anfang. Dieser Aufsatz gibt einen Überblick über den derzeitigen Wissensstand zu den Strukturen, Mechanismen und der Inhibition von Sulfatasen.

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2-Substituted 4-(Thio)chromenone 6-O-Sulfamates: Potent Inhibitors of Human Steroid Sulfatase

Cited by 110 publications

References 39 publications

Synthesis of Various Kinds of Isoflavones, Isoflavanes, and Biphenyl-Ketones and Their 1,1-Diphenyl-2-picrylhydrazyl Radical-Scavenging Activities

Synthesis of Various Kinds of Isoflavones, Isoflavanes, and Biphenyl-Ketones and Their 1,1-Diphenyl-2-picrylhydrazyl Radical-Scavenging Activities

Multistep Continuous-Flow Synthesis of Condensed Benzothiazoles

Sulfatasen: Struktur, Mechanismus, biologische Aktivität, Inhibition, Anwendung in Synthesen

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