Discovery of an Orally Active Non-Peptide Fibrinogen Receptor Antagonist

From a peptide lead to an orally active peptidomimetic fibrinogen receptor antagonist

“…As has been reported elsewhere, the SS stereoisomers 20 proved to be the most potent fibrinogen receptor antagonist, inhibiting human platelet aggregation with an IC50 of 20 nM [13][14][15][16]. We found that the presence of a free carboxylic acid group of the aspartic acid unit is favorable for high activity in the platelet aggregation assay.…”

“…The drug 20 is a highly potent, competitive and selective fibrinogen receptor antagonist and a much more effective antithrombotic agent than aspirin, which is currently used to prevent arterial thrombosis [13][14][15][16]. The drug 20 is a highly potent, competitive and selective fibrinogen receptor antagonist and a much more effective antithrombotic agent than aspirin, which is currently used to prevent arterial thrombosis [13][14][15][16].…”

New amidines from intramolecular cyclization in triflic acid of nitroketene aminals with a tethered phenyl ring

“…7 They are also of interest as naturally occurring constituents of t-RNA 8 and show significant inhibition activity in oedema as well as anti-inflammatory and analgesic activities. 9 Consequently, a plethora of methods has been developed for preparation of amidines 10 from amides, nitriles or thioamides, and involve highly acidic, 11 alkaline 12 or strongly reducing reaction conditions. 13 Alternative mild methods involving the reduction of amidoximes 14 or the conversion of esters derivatives 15 have also been reported.…”

Prodrug Strategies Based on Intramolecular Cyclization Reactions

“…[1][2][3][4][5][6][7] This is particularly true when prodrugs involve the derivatization of carboxyl or hydroxyl groups to form ester functional groups, which readily hydrolyze in vivo, either chemically or enzymatically, to release the parent drugs. Applying similar strategies to the preparation of prodrugs of amine-containing drugs is somewhat more problematic because of the relative chemical and enzymatic stability of an amide bond in the biological system, which makes the regeneration of the original drug difficult.…”