Amphotericin B derivatives with improved therapeutic index

• Main Authors: PALYAM NAGARJUNA, KNAPP DAVID M, STRUBLE JUSTIN, DAVIS STEPHEN, DAILEY IAN, BURKE MARTIN D, GRAY KAITLYN C, UNO BRICE E, WANG PULIN
• Format: Patent
• Language: Chinese; English
• Published: 05.11.2019
• Subjects: CHEMISTRY; DERIVATIVES THEREOF; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; NUCLEIC ACIDS; NUCLEOSIDES; NUCLEOTIDES; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SUGARS

Provided are certain derivatives of amphotericin B (AmB) characterized by reduced toxicity and retained anti-fungal activity. Certain of the derivatives are C16 urea derivatives of AmB. Certain of thederivatives are C3, C5, C8, C9, C11, C13, or C15 deoxy derivatives of AmB. Certain of the derivatives include C3' or C4' modifications of the mycosamine appendage of AmB. Also provided are methods ofmaking AmB derivatives of the invention, pharmaceutical compositions comprising AmB derivatives of the invention, and methods of use of AmB derivatives of the invention. 提供了两性霉素B(AmB)的某些衍生物，其特征在于降低的毒性和保留的抗真菌活性。某些衍生物是AmB的C16脲衍生物。某些衍生物是AmB的C3、C5、C8、C9、C11、C13或C15脱氧衍生物。某些衍生物包括AmB的海藻糖胺附加基团的C3'或C4'修饰。还提供了制备本发明的AmB衍生物的方法，包含本发明的AmB衍生物的药物组合物，和本发明的AmB衍生物的使用方法。