C-C Chemokine receptor 1 (CCR1) is a G-protein coupled cell surface receptor involved in the chemotaxis of leukocytes via ligand receptor binding. Our prior research has shown that CCR1 is expressed in the invasion of glioblastoma, a highly aggressive terminal carcinoma. This research aims to synthesize novel CCR1 antagonists for treatment of glioblastoma. Calculated properties were utilized to design compounds with improved predicted brain penetration. These compounds were synthesized by coupling various synthons to a pyrrolidine core. The compounds were tested in a CCR1 binding assay at three concentrations versus the natural ligand (CCL3). Thus far, changes that improved predicted brain penetration resulted in loss of potency for receptor binding. Early structure activity relationships will be discussed.

Synthesis of novel CCR1 antagonists for treatment of glioblastoma

255th National Meeting (2018)

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