Lee, Sujin published the artcile4,8-Dimethylcoumarin Inhibitors of Intestinal Anion Exchanger slc26a3 (Downregulated in Adenoma) for Anti-Absorptive Therapy of Constipation, Quality Control of 1997-80-4, the publication is Journal of Medicinal Chemistry (2019), 62(17), 8330-8337, database is CAplus and MEDLINE.
The chloride/bicarbonate exchanger SLC26A3 (down-regulated in adenoma, DRA) is expressed mainly in colonic epithelium where it dehydrates the stool by facilitating the final step of chloride and fluid absorption. SLC26A3 inhibition has predicted efficacy in various types of constipation including that associated with cystic fibrosis. We previously identified, by high-throughput screening, 4,8-dimethylcoumarin inhibitors of murine slc26a3 with IC50 down to ∼150 nM. Here, we synthesized a focused library of forty-three 4,8-dimethylcoumarin analogs. Structure-activity studies revealed the requirement of 4,8-dimethylcoumarin-3-acetic acid for activity. The most potent inhibitors were produced by replacements at C7, including 3-iodo- (4az(I)) and 3-trifluoromethyl- (4be(II)), with IC50 of 40 nM and 25 nM, resp. Pharmacokinetics in mice showed predicted therapeutic concentrations of I for >72 h following a single 10 mg/kg oral dose. I at 10 mg/kg fully normalized stool water content in a loperamide-induced mouse model of constipation. The favorable inhibition potency, selectivity within the SLC26 family and pharmacol. properties of I support its further preclin. development.
Journal of Medicinal Chemistry published new progress about 1997-80-4. 1997-80-4 belongs to bromides-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Bromide,Benzene, name is 1-(2-Bromoethyl)-3-(trifluoromethyl)benzene, and the molecular formula is C9H8BrF3, Quality Control of 1997-80-4.
Referemce:
https://en.wikipedia.org/wiki/Bromide,
bromide – Wiktionary