[EN] UREA DERIVATIVES OF AMPHOTERICIN B DERIVED FROM SECONDARY AMINES<br/>[FR] DÉRIVÉS D'URÉE DE L'AMPHOTÉRICINE B DÉRIVÉE D'AMINES SECONDAIRES
申请人:UNIV ILLINOIS
公开号:WO2016112243A1
公开(公告)日:2016-07-14
Provided are certain urea derivatives of amphotericin B (AmB) having improved therapeutic index compared to AmB. The compounds of the invention are less toxic than AmB and are useful to treat fungal infections. In certain embodiments the urea derivative of AmB is a compound represented by formula (I) or a pharmaceutically acceptable salt thereof: wherein, independently for each occurrence: R represents methyl, ethyl, propyl, or isopropyl; R' represents methyl, ethyl, propyl, or isopropyl; or R and R', taken together with the nitrogen atom to which they are attached, represent a radical of a cyclic secondary amine. Also provided are methods for making the urea derivatives of AmB.
Disclosed is a noble &bgr;-hydroxyamide of general formula wherein R
1
is alkyl, alkoxyalkyl or hydroxyalkoxyalkyl derived from at least one hydroxyfunctional compound, R
2
is alkyl, aryl, alkylaryl or arylalkyl derived from at least one carboxyfunctional compound or at least one anhydride, halide or ester of at least one carboxyfunctional compound, R
3
is N-alkyl or N-cycloalkyl derived from at least one alkanolamine and wherein m and n are independent integers and at least 1. In a further aspect the present refers to a process for synthesis of said &bgr;-hydroxyamide. The process comprises the Steps of (i) subjecting a di, tri or polyalcohol to alcoholysis with at least one di, tri or polyalkyl ester of a di, tri or polyfunctional carboxylic acid and (ii) subjecting obtained reaction product to aminolysis with at least one alkanolamine.
1