Regioselective synthesis of 3-aryl-5-(1H-indole-3-carbonyl)-4-hydroxyfuroic acids as potential insulin receptor activators

Chou, Shan-Yen; Chen, Shieh-Shung Tom; Chen, Ching‐Hui; Chang, Lien-Shange

doi:10.1016/j.tetlet.2006.08.076

Cited by 6 publications

(1 citation statement)

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“…1 ) with an improved efficacy [ 20 , 21 ]. Combining these two features together, phenylindolylfuroic acid derivatives were synthesized [ 26 ], but for unknown reasons these compounds showed no observable insulin receptor activation efficacy (data not shown). Therefore, these phenylindolylfuroic acid derivatives were not pursued further, and the bisindolylfuroic acid scaffold is retained for further derivative development because of its absence of a quinone moiety.…”

Section: Introductionmentioning

confidence: 99%

A novel hydroxyfuroic acid compound as an insulin receptor activator structure and activity relationship of a prenylindole moiety to insulin receptor activation

Tsai

Chou

2009

J Biomed Sci

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BackgroundDiabetes Mellitus is a chronic disease and many patients of which require frequent subcutaneous insulin injection to maintain proper blood glucose levels. Due to the inconvenience of insulin administration, an orally active insulin replacement has long been a prime target for many pharmaceutical companies. Demethylasterriquinone (DMAQ) B1, extracted from tropical fungus, Pseudomassaria sp., has been reported to be an orally effective agent at lowering circulating glucose levels in diabetic (db/db) mice; however, the cytotoxicity associated with the quinone moiety has not been addressed thus far.MethodsA series of hydroxyfuroic acid compounds were synthesized and tested for their efficacies at activating human insulin receptor. Cytotoxicity to Chinese hamster ovary cells, selectivities over insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), and fibroblast growth factor (FGF) receptors were examined in this study.Result and ConclusionThis study reports a new non-quinone DMAQ B1 derivative, a hydroxyfuroic acid compound (D-410639), which is 128 fold less cytotoxic as DMAQ B1 and as potent as compound 2, a DMAQ B1 synthetic derivative from Merck, at activating human insulin receptor. D-410639 has little activation potential on IGF-1 receptor but is a moderate inhibitor to EGF receptor. Structure and activity relationship of the prenylindole moiety to insulin receptor activation is discussed.

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Section: Introductionmentioning

confidence: 99%

A novel hydroxyfuroic acid compound as an insulin receptor activator structure and activity relationship of a prenylindole moiety to insulin receptor activation

Tsai

Chou

2009

J Biomed Sci

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Iridium(I)‐Catalyzed Direct CH Bond Alkylation of the C‐7 Position of Indolines with Alkenes

2014

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A cationic iridium‐catalyzed C‐7 alkylation of N‐substituted indoline derivatives with various alkenes has been developed. A variety of 7‐alkylindolines were obtained in moderate to high yields. This protocol relies on the use of the carbonyl group on the nitrogen atom of indoline as a directing group and it is potentially applicable to the large‐scale synthesis of 7‐alkylindoles.magnified image

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