| 摘要 |
NOVEL LIPIDS AND COMPOSITIONS FOR THE DELIVERY OF THERAPEUTICS Abstract: The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention provides lipids having the following structure (I) wherein R1 and R2 are each independently for each occurrence optionally substituted C10 -C30 alkyl, optionally substituted C10-C 30 alkenyl, optionally substituted C10 -C3 0 alkynyl, optionally substituted Ci1-C30 acyl, or -linker-ligand; R3 is H, optionally substituted C1 -C10 alkyl, optionally substituted C2 -Cio alkenyl, optionally substituted C2 -Cio alkynyl, alkylheterocycle, alkylphosphate, alkylphosphorothioate, alkylphosphorodithioate, alkylphosphonates, alkylamines, hydroxyalkyls, o-aminoalkyls, (o-(substituted)aminoalkyls, o-phosphoalkyls, to O thiophosphoalkyls, optionally substituted polyethylene glycol (PEG, mw 100-40K), optionally substituted mPEG (mw 120-40K), heteroaryl, heterocycle, or linker-ligand; E is 0, S, N(Q), C(O), N(Q)C(O), C(O)N(Q), (Q)N(CO)O, O(CO)N(Q), S(O), NS(O) 2N(Q), S(O) 2 , N(Q)S(O) 2, SS, O=N, aryl, heteroaryl, cyclic or heterocycle; and, Q is H, alkyl, o-aminoalkyl, o-(substituted)aminoalkyl, o-phosphoalkyl or o-thiophosphoalkyl. X, NH(GO), (CO)NH NH(CO)O O(CO)NH. 0, NH(CO)NH, S-S R=rCHa -(CH2)44o Y= ($ IfGrCi GNAc, Marmos Lactose. Qlucose Fucase Y= (CH 2hq (GaINAc)2 (Mannose},( Ladcoe), (Glucose)2 (Futose)h Y= (CJ-1n-i (Ga1NAc)3 . (Manwch,( Latose)3 . (Gwuoseh, (Fucose)1 Y- (OH Ciro- GiNAc, Mannose, Lactose, Glucose. Fueose Ya (CHr-CF1r~O)a- (GaINAc)?, (Mannose0,( tacts0sE (G, ume), (Fucos) 2 Ye (CttaA4hrOfl (GSNAch (Mrnoaseb( Lactos3h (Gincoea (Fuosm X= NH(CO), (CO)NH, NH(CO)O O(CO)KN, 0 NN(CO)NH, S-S R= CHy( CH1)fQ Y= (C1tn- GaNA:, Manncse, Glucost, Fucose Y= (Ci0-i- (GaNAc 2, (Mano)( Lactose)? (Glucose, (rucose), Y= (CHN2 n. (GWNAcr3, (Mannoe)3 ( Lacboe 3 (Giucee (Fucose Y= (CH2-CHaO V GdaNAc, rknnose, Lactose, Glucose, Fucose Y= (CHrCr-)a- (GalNAc, (Mannvse),( Lac'se 2 (Guicose)2 (Fucose) 2 Y= (CH2-CI-irO)a (GadNAc)3. (Mawnoeh( Lactose)3, (GLucoseh, (Fucose)3 a=N1-I0 |
