- 7-methylation of chenodeoxycholic acid derivatives yields a substantial increase in TGR5 receptor potency
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TGR5 agonists are potential therapeutics for a variety of conditions including type 2 diabetes, obesity, and inflammatory bowel disease. After screening a library of chenodeoxycholic acid (CDCA) derivatives, it was determined that a range of modifications could be made to the acid moiety of CDCA which significantly increased TGR5 agonist potency. Surprisingly, methylation of the 7-hydroxyl of CDCA led to a further dramatic increase in potency, allowing the identification of 5.6 nM TGR5 agonist 17.
- Nakhi, Ali,Mcdermott, Connor M.,Stoltz, Kristen L.,John, Kristen,Hawkinson, Jon E.,Ambrose, Elizabeth A.,Khoruts, Alexander,Sadowsky, Michael J.,Dosa, Peter I.
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- Decarbonated cholesteric aldehyde as well as preparation method and application thereof
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The invention provides decarbonated cholesteric aldehyde as well as a preparation method and application thereof. The decarbonated cholesteric aldehyde is a compound as shown in a formula (I), or a salt thereof, or a stereoisomer thereof. R1 and R2 are respectively and independently selected from hydrogen, C1-C6 alkyl, halogen, hydroxyl, carboxyl, aldehyde group, amino or nitro. The decarbonated cholesteric aldehyde has good antibacterial activity, especially has a good inhibition effect on clostridium difficile, and can be used for preparing drugs for inhibiting clostridium difficile. Meanwhile, carbon-loss chenodeoxycholic acid, carbon-loss cholesteric alcohol and chenodeoxycholic acid can be prepared by taking the carbon-loss cholesteric aldehyde as an initial raw material, and the yield is high and is superior to that in the prior art. Besides, the invention provides a preparation method of various decarbonated cholesteric aldehyde, the preparation method is high in yield and purity, the raw material duck cholic acid used in the preparation method is wide in source and low in cost, an industrial method for utilizing industrial waste duck cholic acid is developed, and the industrialization of the preparation method is more feasible.
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Paragraph 0131-0132
(2021/07/21)
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- ISOLATION OF (23R) 3α,7α,23-TRIHYDROXY-5β-CHOLAN-24-OIC (β-PHOCAECHOLIC) ACID FROM DUCK BILE. 1H NMR SPECTRA OF ITS DERIVATIVES
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(23R) 3α,7α,23-Trihydroxy-5β-cholan-24-oic acid (IV) - a bile acid typical of some marine mammals - was now isolated from duck bile.Acid IV was characterized as derivatives V - VIII, XI and XII and oxydatively degradated to derivatives of 24-nor-5β-cholan-23-oic acid, XIII - XVIII.The 1H NMR spectra of these compounds and (23S) methyl ester X are discussed and the effect of substitution in position 23 on the chemical shift of the methyl groups is summarized.
- Klinot, Jiri,Jirsa, Milan,Klinotova, Eva,Ubik, Karel,Protiva, Jiri
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p. 1722 - 1730
(2007/10/02)
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