In the angiogenesis process, integrins, which are members of a family of cell surface transmembrane receptors, play a critical role particularly in blood vessel formation and the local release of vascular growth factors. Thyroid hormones such as L-thyroxine (T-4) and 3,5,30-triiodo-L-thyronine (T-3) promote angiogenesis and tumor cell proliferation via integrin alpha v beta 3 receptor. At or near an arginine-glycine-aspartate (RGD) recognition site on the binding pocket of integrin avb3, tetraiodothyroacetic acid (tetrac, a deaminated derivative of T-4) is a thyrointegrin receptor antagonist and blocks the actions of T-3 and T-4 as well as different growth factors-mediated angiogenesis. In this study, we synthesized novel tetrac analogs by modifying the phenolic moiety of tetrac and tested them for their anti-angiogenesis activity using a Matrigel plug model for angiogenesis in mice. Pharmacological activity results showed that tetrac can accommodate numerous modifications and maintain its anti-angiogenesis activity. (C) 2018 Elsevier Ltd. All rights reserved.