1484-73-7Relevant articles and documents
Design, synthesis and biological evaluation of novel trimethylangelicin analogues targeting nuclear factor kB (NF-kB)
Marzaro, Giovanni,Lampronti, Ilaria,D'Aversa, Elisabetta,Sacchetti, Gianni,Miolo, Giorgia,Vaccarin, Christian,Cabrini, Giulio,Dechecchi, Maria Cristina,Gambari, Roberto,Chilin, Adriana
, p. 285 - 293 (2018)
A series of trimethylangelicin (TMA) derivatives were designed and synthesized to overcome the unwanted effects of TMA, promising agent for treatment of inflammation-related diseases and other pathologies, such as cystic fibrosis. The new generation TMA analogues bore hindered substituents at the 4 position in order to minimize or avoid the photoreactions with DNA. Among them, the 4-isopropyl-6-ethyl derivative 23 exhibited TMA-like inhibitory activity on NF-κB/DNA interactions but it proved unable to photoreact with pyrimidine bases of DNA, nor to induce any other DNA damage. The isopropyl analogue 23 was proven to lack mutagenicity when assayed through Ames test and exhibited no anti-proliferative activity on cystic fibrosis IB3-1 cells, displaying at the same time inhibition of the TNF-α induced release of the NF-κB regulated PDGF-B chain, IL-10, IL-15, IL-17 and IFN-γ. Therefore compound 23 deserves further assay to determine its anti-inflammatory properties, since it lacks photoreaction properties and mutagenicity-related side effects.
Establishing a flow process to coumarin-8-carbaldehydes as important synthetic scaffolds
Zak, Jaroslav,Ron, David,Riva, Elena,Harding, Heather P.,Cross, Benedict C. S.,Baxendale, Ian R.
supporting information; experimental part, p. 9901 - 9910 (2012/09/07)
Despite their usefulness as fluorophores and synthetic precursors, efficient and reliable routes to coumarin-8-carbaldehydes are lacking. We describe here a high-yielding continuous flow synthesis that requires no manual intermediate purification or work-up, giving access to multigram quantities of the aldehyde product. Aldehyde on tap: Despite their usefulness as fluorophores and synthetic precursors, efficient and reliable routes to coumarin-8- carbaldehydes are lacking. A high-yielding continuous flow synthesis that requires no manual intermediate purification or work-up is described, giving access to multigram quantities of aldehyde product (see scheme). Copyright
Na+-glucose cotransporter (SGLT) inhibitors as antidiabetic agents. 4. Synthesis and pharmacological properties of 4'- dehydroxyphlorizin derivatives substituted on the B ring
Tsujihara, Kenji,Hongu, Mitsuya,Saito, Kunio,Kawanishi, Hiroyuki,Kuriyama, Kayoko,Matsumoto, Mamoru,Akira, Oku,Ueta, Kiichiro,Tsuda, Minoru,Saito, Akira
, p. 5311 - 5324 (2007/10/03)
In our studies of Na+-glucose cotransporter (SGLT) inhibitors as antidiabetic agents, a series of novel 4'- dehydroxyphlorizin derivatives substituted on the B ring was prepared and their effects on urinary glucose excretion were evaluated in rats. Introduction of only a small alkyl group at the 4'-position increased the activity, and 3-(benzo[b]furan-5- yl)-2',6'-dihydroxy-4'-methylpropiophenone 2'-O-β-D- glucopyranoside (4) showed the most potent effect. To overcome hydrolysis of compound 4 by β-glucosidase in the digestive tract, the OH groups on the glucose moiety of compound 4 were modified. Three prodrugs (5, 42, and 55) were more potent than the parent compound 4 by oral administration, and finally 3- (benzo[b]furan-5-yl)-2',6'-dihydroxy-4'-methylpropiophenone 2'-O- (6-O-methoxycarbonyl-β-D-glucopyranoside) (5) was selected as a new promising candidate. Compound 5 was metabolized mainly by liver esterase to the active form (4), which was about 10 times more potent than 5 in inhibiting SGLT. In oral glucose tolerance test in db/db mice, compound 5 dose-dependently suppressed the elevation of glucose levels. Single administration of 5 reduced hyperglycemia concurrently with increase of glucose excretion into urine in diabetic KK-A(y) mice. Furthermore, compound 5 suppressed the elevation of blood glucose levels but did not lower it below the normal level even in fasted conditions in KK- A(y) mice. Additionally, long-term treatment with 5 dose- dependently reduced hyperglycemia and HbA1c in KK-A(y) mice. These pharmacological data strongly suggest that compound 5 has a therapeutic potential in the treatment of NIDDM.
