81845-44-5Relevant academic research and scientific papers
Prodrug derivatives of carboxylic acid drugs
-
, (2008/06/13)
Novel ester derivatives of carboxylic acid medicaments of formula (I), wherein R--COO--represents the acyloxy residue of a carboxylic acid drug or medicament, n is an integrer from 1 to 3, and R1 and R2 are the same or different and are selected from a group consisting of an alkyl, an alkenyl, an aryl, an aralkyl, a cycloalkyl and which group may be unsubstituted or substituted, or R1 and R2 together with the N forms a 4-, 5-, 6- or 7-membered heterocyclic ring, which in addition to the nitrogen atom may contain one or two further heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and which heterocyclic group may be substituted. These compounds are highly biolabile prodrug forms of the corresponding carboxylic acid compounds and are highly susceptible to undergoing enzymatic hydrolysis in vivo whereas they are highly stable in aqueous solution. The novel derivatives are less irritating to mucosa than the parent carboxylic acids and may provide an improved bio-availability of the drugs.
Synthesis of 9-Substituted Carbacyclin Analogues
Aristoff, Paul A.,Johnson, Paul D.,Harrison, Allen W.
, p. 5341 - 5348 (2007/10/02)
The synthesis of a series of 9-substituted carbacyclin analogues with potent platelet antiaggregatory activity is described.The key step for the formation of 9-acetylene compounds (e. g., 8d) utilized a modification of the Schwartz procedure involving the nickel-catalyzed conjugate addition of the appropriate alkynyl aluminate to bicyclooct-1-en-3-one (2).It was found that 9-methylcarbacyclin (8b) could be prepared by a similar procedure.In addition, a novel alternative to the Wittig reaction for introducing the carbacyclin upper side chain in base-sensitive substrates was developed which involves the addition of the dianion of 6-((tert-butyldimethylsilyl)oxy)hexanoic acid to the appropriate ketone (e. g., 6f or 2) followed by decarboxylative dehydration of the resulting β-hydroxy acid.
