4H-Thieno[3,2-b]pyrrole-5-carboxylic acid

Uses

DAO-IN-2 is a novel D-amino acid oxidase (DAO) inhibitor. DAO-IN-2 demonstrates moderate potency for DAO in vitro and ex vivo[1].

Synthesis Reference(s)

Journal of the American Chemical Society, 79, p. 2556, 1957 DOI: 10.1021/ja01567a053

General Description

A cell-permeable thienopyrrole compound that potently inhibits the cellular activity of transfected D-amino acid oxidase (DAO/DAAO/DAMOX/OXDA) in CHO cells (IC₅₀ against human and rat DAO = 145 and 114 nM, respectively), while exhibiting no activity towards D-aspartate oxidase (DDO; IC₅₀ >5 μM), P450 enzymes CYP3A4/2D6/3C9 (IC₅₀ >10 μM), and a panel of over 150 other enzymes, receptors, and ion channels. Although in vivo treatment of Compound 8 (200 mg/kg, i.p.) is shown to effectively inhibit DAO activity in rat brain and kidney (by 96% and 80%, respectively), the resulting D-serine concentration increase in the periphery and central nervous system appears to be far from sufficient to produce adequate antipsychotic and cognitive enhancing effects.

References

[1] Tim Sparey, et, al. The discovery of fused pyrrole carboxylic acids as novel, potent D-amino acid oxidase (DAO) inhibitors. Bioorg Med Chem Lett. 2008,18, 11. DOI:10.1016/j.bmcl.2008.04.020