874901-16-3Relevant academic research and scientific papers
Novel 1H-imidazol-2-amine derivatives as potent and orally active vascular adhesion protein-1 (VAP-1) inhibitors for diabetic macular edema treatment
Inoue, Takayuki,Morita, Masataka,Tojo, Takashi,Nagashima, Akira,Moritomo, Ayako,Miyake, Hiroshi
, p. 3873 - 3881 (2013/07/19)
Novel thiazole derivatives were synthesized and evaluated as vascular adhesion protein-1 (VAP-1) inhibitors. Although we previously identified a compound (2) with potent VAP-1 inhibitory activity in rats, the human activity was relatively weak. Here, to improve the human VAP-1 inhibitory activity of compound 2, we first evaluated the structure-activity relationships of guanidine bioisosteres as simple small molecules and identified a 1H-benzimidazol-2-amine (5) with potent activity compared to phenylguanidine (1). Based on the structure of compound 5, we synthesized a highly potent VAP-1 inhibitor (37b; human IC50 = 0.019 μM, rat IC50 = 0.0051 μM). Orally administered compound 37b also markedly inhibited ocular permeability in streptozotocin-induced diabetic rats after oral administration, suggesting it is a promising compound for the treatment of diabetic macular edema.
THIAZOLE DERIVATIVES HAVING VAP-1 INHIBITORY ACTIVITY
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Page/Page column 119, (2008/06/13)
A compound of the formula (I), (II), (III) or (IV): wherein each symbol is as defined in the specification,or a pharmaceutically acceptable salt thereof useful as a vascular adhesion protein-1 (VAP-1) inhibitor, a pharmaceutical composition, a method for preventing or treating a VAP-1 associated disease, especially macular edema, which method includes administering an effective amount of the compound or a pharmaceutically acceptable salt thereof to a subject, and the like.
