Small molecule conjugates for intracellular delivery of biologically active compounds

摘要

The invention provides novel compounds and conjugates of these compounds useful for the delivery of biologically active substances. Further novel design criteria for chemically stabilized siRNA particular useful when covalently attached to a delivery polymer to achieve in vivo mRNA knock down are disclosed therein.

主权项

1. A compound of formula (I):wherein
Y is a linker group selected from —(CH2)3— or —C(O)—NH—(CH2—CH2—O)p—CH2—CH2—; R1 is —(C1-6) alkyl;
—(CH2)-naphthyl; or—(CH2)m-phenyl, which phenyl is unsubstituted or up to four times substituted with a substituent independently selected from
—NO2,—CN,Halogen,—O—(CH2)-phenyl,—O—(C1-6) alkyl, or—C(O)—NH2; R2 is hydrogen;
—(CH2)k—NH—C(Ph)3, which phenyl rings are unsubstituted or independently substituted with —O—(C1-4)alkyl;—(CH2)k—C(O)—NH2;—(CH2)k-phenyl;—(C1-6) alkyl, which is unsubstituted or once substituted with —S—CH3; R3 is —NH-phenyl, which phenyl group is further substituted with a substituent independently selected from
—(CH2)—OH; or—(CH2)—O—C(O)—O-(4-nitro-phenyl); k is 1, 2, 3, 4, 5 or 6; m is 1, 2, 3 or 4; n is 0 or 1; and p is an integer from 1 to 20.