Polyphosphoric acid (PPA) cyclization leads to 5-fluoro-2-methyl-3-indanone (4). A Reformatsky reaction with zinc amalgam and bromoacetic ester leads to carbinol (5), which is then dehydrated with tosic acid to indene 6. {Alternatively, this step can be performed in a Knoevenagel condensation with cyanoacetic acid, which is then further decarboxylated.} The active methylene group is condensed with p-methylthiobenzaldehyde, using sodium methoxide as catalyst, and then saponified to give Z (7) which in turn oxidized with sodium metaperiodate to sulfoxide 8, the antiinflammatory agent sulindac. References
External links
RxList information on Sulindac
Drug Profile
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Limited data also support its use for the treatment of fecal impaction.In those with chronic constipation it works better than lactulose.A 2007 comparison showed that people with constipation had a better response to macrogol than to tegaserod. Popular types include: macrogol 3350, macrogol 4000, and macrogol 6000. The number represents the average molecular mass. Combining different molecular masses provides some control over the consistency. Excipient
Macrogol is used as an excipient in pharmaceutical products. Lower-molecular-weight variants are used as solvents in oral liquids and soft capsules, whereas solid variants are used as ointment bases, tablet binders, film coatings, and lubricants.For example, PEG-2000 is one of the excipients in the Moderna COVID-19 vaccine. PEGylation
Macrogols are also attached to biopharmaceutical drugs to slow down their degradation in the human body and increase their duration of action, as well as to reduce immunogenicity. This process is called PEGylation. Contraindications
Contraindications for macrogol taken orally as a laxative are intestinal perforation, bowel obstruction, ileus, inflammatory bowel diseases, and toxic megacolon.The doses of macrogol as an excipient are too low to have relevant contraindications.Allergy to macrogol is rare, and usually appears as an allergy to an increasing number of seemingly unrelated products, including cosmetics, drugs that use it as an excipient, and peri-procedural substances such as ultrasound gel. Adverse effects
Oral macrogol is generally well tolerated. Possible side effects include headache, bloating, nausea, allergies, and electrolyte imbalance, mainly hypokalaemia (low blood potassium levels) and hyperkalaemia (high blood potassium levels).