POLYCATIONIC METHYL PHOSPHOLIPIDS FOR IMPROVEDDELIVERY OF NUCLEIC ACIDS TO EUKARYOTIC CELLS

摘要

New cationic lipids are provided that are useful for delivering macromolecules, such as nucleic acids, into eukaryotic cells. The lipids can be used alone, in combination with other lipids and/or in combination with other transfection enhancing reagents to prepare transfection complexes. The present invention is in the field of molecular biology, and more particularly in the field of transfection, which utilizes new compounds and methods for the introduction of nucleic acids into eukaryotic cells.

主权项

1. A compound of Formula I: or a pharmaceutically acceptable salt thereof, wherein:
each X independently is selected from —O—, —OC(O)O—, —C(O)O—, —O(O)C—, —N(R2)C(O)O—, —C(O)N(R2)—, —OC(O)N(R2)—, and —(R2)NCON(R2)—;Y is independently (C1-C6)alkyl;each R is independently selected from substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted aryl, and substituted or unsubstituted arylalkyl, wherein each R group is optionally independently substituted by 1-3 substituent groups, each substituent group independently selected from amino, hydroxyl, (CH2)jOR11, (CH2)jC(O)R11, (CH2)jC(O)OR11, (CH2)jOC(O)R11, (CH2)jNR12R13, (CH2)jC(O)NR12R13, (CH2)jOC(O)NR12R13, (CH2)jN14RC(O)R11, (CH2)jN14RC(O)OR11, (CH2)jN14RC(O)NR12R13, and (CH2)jN14RC(NH)NR12R13, wherein each j is independently an integer selected from 0 to 6;R1 is independently selected from alkyl, (CH2)jOR11, (CH2)jC(O)R11, and CH2CH(OH)CH2(OH);R2 is independently selected from hydrogen and (C1-C6)alkyl;R3 is independently selected from H, (CH2)jNR12R13, C(O)CH[(CH2)3NH(CH2)3NH2]—[NH(CH2)3NH2], C(O)CH(NH2)(CH2)3NH2; C(O)CH(NH2)(CH2)4NH2, C(O)CH(NH2)(CH2)3NHC(═NH)NH2, C(O)CH(NH2)(CH2)(C3H3N2), C(O)CH(NH2)(CH2)3NH2; C(O)CH(NH2)CH2NH2, —C(O)CH(NH2)(CH2)2NH2, and —C(O)CH(NH2)CHOH;R11, R12, R13 and R14 are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, perfluoroalkyl, and cycloalkyl, where the alkyl or alkenyl is optionally substituted with one or more substituent selected from the group consisting of amino, primary amino, secondary amino, hydroxy, alkoxy, and hydroxyalkyl.