Structural Requirements of Minoxidil Analogs for Enhancing Lysyl Hydroxylase Inhibitory Activity

The study explored the structural features of minoxidil analogs to enhance lysyl hydroxylase (LH) inhibitory activity using HQSAR and CoMSIA analyses. The HQSAR model indicated that the C2 atom of the pyrimidine ring and the C'3-C'4 bond of the 4-piperidinol group had the highest impact on LH inhibition. The CoMSIA model showed that inhibitory activity was mainly influenced by hydrophobic field contribution (36%) and hydrogen bond field contribution (49.2%). Functional groups that disfavor H-bond acceptors around the piperidinol group and favor H-bond acceptors at the C'4 (& C'5) atom in the $R_5$ group were predicted to increase inhibitory activity. This information could guide the design of novel candidates with improved hair growth inhibition.