Novel C-aryl glucoside SGLT2 inhibitors as potential antidiabetic agents: Pyridazinylmethylphenyl glucoside congeners

Kim, Min Ju; Lee, Jun–Won; Kang, Suk Youn; Lee, Sung-Han; Son, Eunjung; Jung, Myung Eun; Lee, Suk Ho; Song, Kwon‐Ho; Lee, Minwoo; Han, Ho-Kyun; Kim, Jeongmin; Lee, Jinhwa

doi:10.1016/j.bmcl.2010.04.006

Cited by 40 publications

(11 citation statements)

References 19 publications

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“…Ther ecurring theme in iron-catalyzed cross-couplings in medicinal-chemistry applications is the use of the Fe(acac) 3 / NMP catalytic system for the C(sp 2 ) À C(sp 3 )cross-coupling of alkyl Grignard reagents as an effective alternative to alkyl Negishi [53] and B-alkyl Suzuki [54] cross-couplings.T his is illustrated in the synthesis of SGLT2 inhibitors as potential antidiabetics by Lee and co-workers at Green Cross Corporation (Scheme 10). [55] Thecross-coupling of afunctionalized chloropyridazine bearing as ensitive glucoside moiety with ethylmagnesium bromide furnished the desired alkyl derivative in 67 %y ield. Thes electivity for ah eteroaromatic chloride in the presence of its aromatic congener is especially noteworthy.…”

Section: Angewandte Chemiementioning

confidence: 99%

Iron‐Catalyzed Cross‐Couplings in the Synthesis of Pharmaceuticals: In Pursuit of Sustainability

2018

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The scarcity of precious metals has led to the development of sustainable strategies for metal-catalyzed cross-coupling reactions. The establishment of new catalytic methods using iron is attractive owing to the low cost, abundance, ready availability, and very low toxicity of iron. In the last few years, sustainable methods for iron-catalyzed cross-couplings have entered the critical area of pharmaceutical research. Most notably, iron is one of the very few metals that have been successfully field-tested as highly effective base-metal catalysts in practical, kilogram-scale industrial cross-couplings. In this Minireview, we critically discuss the strategic benefits of using iron catalysts as green and sustainable alternatives to precious metals in cross-coupling applications for the synthesis of pharmaceuticals. The Minireview provides an essential introduction to the fundamental aspects of practical iron catalysis, highlights areas for improvement, and identifies new fields to be explored.

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Section: Angewandte Chemiementioning

confidence: 99%

Iron‐Catalyzed Cross‐Couplings in the Synthesis of Pharmaceuticals: In Pursuit of Sustainability

2018

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“…[54] Dies wird durch die Synthese des SGLT2-Inhibitors,e inem blutzuckersenkenden Wirkstoff, von Lee und Mitarbeitern bei Green Cross Corporation veranschaulicht (Schema 10). [55] Die Kreuzkupplung eines funktionalisierten Chlorpyridazins,d as eine empfindliche Glucosideinheit enthält, mit Ethylmagnesiumbromid lieferte das gewünschte Alkylderivat in 67 %A usbeute.B emerkenswert ist die Selektivitätfürein heteroaromatisches Chlorid in Gegenwart seines aromatischen Analogons.…”

Section: Medizinische Chemieunclassified

Eisenkatalysierte Kreuzkupplungen in der Synthese von Pharmazeutika: Streben nach Nachhaltigkeit

Piontek¹,

Bisz²,

Szostak

2018

Angewandte Chemie

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Der Mangel an Edelmetallen hat eine Suche nach nachhaltigen Strategien für metallkatalysierte Kreuzkupplungen ausgelöst. Die Entwicklung neuer Katalysemethoden unter Verwendung von Eisen ist wegen der geringen Kosten, leichten Verfügbarkeit und sehr geringen Toxizität von Eisen hoch attraktiv. In den letzten Jahren haben nachhaltige Methoden für eisenkatalysierte Kreuzkupplungen den kritischen Bereich der pharmazeutischen Forschung erreicht. Insbesondere ist Eisen eines der sehr wenigen unedlen Metalle, deren praktischer Einsatz in industriellen Kreuzkupplungen im Kilogrammmaßstab erfolgreich erprobt wurde. In diesem Kurzaufsatz wollen wir die strategischen Vorteile der Verwendung von Eisenkatalysatoren als umweltfreundliche und nachhaltige Alternative zu Edelmetallen in Kreuzkupplungen für die Synthese von Pharmazeutika kritisch beleuchten. Wir bieten eine Einführung in die grundlegenden Aspekte der Eisenkatalyse, heben Bereiche mit Verbesserungspotenzial hervor und zeigen neue Richtungen auf, die in Zukunft erforscht werden sollten.

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“…A set of 110 different SGLT2 inhibitors and 44 different SGLT1 inhibitors has been collected from different references [1,[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29]. Of those compounds, 25 SGLT2 inhibitors and 23 SGLT1 inhibitors, which achieve satisfactory diversity in both structural and activity ranges, were selected as the training set for pharmacophore models, respectively.…”

Section: Selection Of Moleculesmentioning

confidence: 99%

A specific pharmacophore model of sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors

et al. 2011

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Sodium-dependent glucose co-transporter 2 (SGLT2) plays a pivotal role in maintaining glucose equilibrium in the human body, emerging as one of the most promising targets for the treatment of diabetes mellitus type 2. Pharmacophore models of SGLT2 inhibitors have been generated with a training set of 25 SGLT2 inhibitors using Discovery Studio V2.1. The best hypothesis (Hypo1(SGLT2)) contains one hydrogen bond donor, five excluded volumes, one ring aromatic and three hydrophobic features, and has a correlation coefficient of 0.955, cost difference of 68.76, RMSD of 0.85. This model was validated by test set, Fischer randomization test and decoy set methods. The specificity of Hypo1(SGLT2) was evaluated. The pharmacophore features of Hypo1(SGLT2) were different from the best pharmacophore model (Hypo1(SGLT1)) of SGLT1 inhibitors we developed. Moreover, Hypo1(SGLT2) could effectively distinguish selective inhibitors of SGLT2 from those of SGLT1. These results indicate that a highly predictive and specific pharmacophore model of SGLT2 inhibitors has been successfully obtained. Then Hypo1(SGLT2) was used as a 3D query to screen databases including NCI and Maybridge for identifying new inhibitors of SGLT2. The hit compounds were subsequently subjected to filtering by Lipinski's rule of five. And several compounds selected from the top ranked hits have been suggested for further experimental assay studies.

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Novel C-aryl glucoside SGLT2 inhibitors as potential antidiabetic agents: Pyridazinylmethylphenyl glucoside congeners

Cited by 40 publications

References 19 publications

Iron‐Catalyzed Cross‐Couplings in the Synthesis of Pharmaceuticals: In Pursuit of Sustainability

Iron‐Catalyzed Cross‐Couplings in the Synthesis of Pharmaceuticals: In Pursuit of Sustainability

Eisenkatalysierte Kreuzkupplungen in der Synthese von Pharmazeutika: Streben nach Nachhaltigkeit

A specific pharmacophore model of sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors

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