The present application relates to a long-changma class derivative and its preparation method and application, belong to long-changma class derivative preparation technical field. The long-changma class derivative disclosed by the present application has the following advantages: (i) the modification of the
tail chain increases the
fat solubility of the long-changma class compound, and does not affect the brain
blood flow regulation of the long-changma class itself, helps to carry the
drug to penetrate the blood-brain barrier, and plays a
brain protection role, improves the brain
microcirculation disorder; (ii) the
tertiary amine group in the parent
nucleus structure of the long-changma class derivative has the property of
ionization under acidic conditions, can achieve efficient carrying and
lysosome escape of
nucleic acid drugs through charge adsorption, and improve
intracellular transport; (iii) the long-changma class derivative inherits the inherent various pharmacological activities of long-changma, and has high safety. Therefore, the long-changma class derivative disclosed by the present application has good application prospect in brain-targeted delivery of drugs for treating brain diseases.