Application of Stereocontrolled Stepwise [3+2] Cycloadditions to the Preparation of Inhibitors of alpha_4beta_1-Integrin-Mediated Hepatic Melanoma Metastasis

摘要

Intravascular circulation of cancer cells represents a frequent event along neoplasic progression that seriously increases the probability of occurrence of metastasis.However,the adhesion of blood-borne cancer cells to the microvascular wall is a prerequisite for metastatic cell implantation at target organs.Similar to capillary homing of leukocytes,this process is proinflammatory cytokine-inducible and the mechanism involves specific binding between cancer and endothelial cell adhesion molecules.Previously,we and others reported that integrin "very late antigen 4" (VLA-4,alpha_4beta_1) accounts for melanoma cell adhesion to endothelium in metastasized organs.