Chemokine receptor type 4 (CXCR4) is overexpressed in cells associated with various disease pathways such as autoimmune disorders, inflammation, HIV-1 proliferation, and cancer. Healthy functions such as stem cell differentiation and migration are linked with the CXCR4/CXCL12 signaling pathway. Hence, the binding interaction of CXCR4 with its natural cognate CXCL12 ligand can be partially blocked with small molecules to hinder the mechanism of cancer metastasis or inflammation but still allow normal cell functions to occur. Various antagonists and modulators for CXCR4 have been synthesized and tested, but new compounds with better efficacy are necessary due to cardiotoxicity and/or poor oral bioavailability of these compounds. The overall goal for this research is to synthesize asymmetrical, pyridine-based and thiophene-based compounds as potential modulators of CXCR4-CXCL12 activity. A new research scheme is being investigated and tested using 2,5-thiophene as the central ring and modifications to the side chains with a different hit functional group on each side to yield an asymmetrical small molecule antagonist. After the synthesis process is completed, the analogues are analyzed through NMR and MS and proceed to be tested with further biological tests.