COMPOUNDS FOR TARGETING DRUG DELIVERY AND ENHANCING SIRNA ACTIVITY

• Main Authors: HOU, ZHENG, KARMALI, PRIYA, PAYNE, JOSEPH E, AKOPIAN, VIOLETTA, KNOPOV, VICTOR, AHMADIAN, MOHAMMAD, PERELMAN, LOREN A, WITTE, RICHARD P, SRIDHAR, C. NAGARAJAN, GAUDETTE, JOHN A, TANAKA, YASUNOBU, NIITSU, YOSHIRO
• Format: Patent
• Language: English; French; German
• Published: 24.02.2016
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; CHEMISTRY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

Here described are compounds of formula I: wherein R 1 and R 2 is independently selected from a group consisting of C 10 to C 18 alkyl, C 12 to C 18 alkenyl, and oleyl group; wherein R 3 and R 4 are independently selected from a group consisting of C 1 to C 6 alkyl, and C 2 to C 6 alkanol; wherein X is selected from a group consisting of -CH 2 -, -S-, and -O- or absent; wherein Y is selected from -(CH 2 ) n , -S(CH 2 ) n , - O(CH 2 ) n -, thiophene, -SO 2 (CH 2 ) n -, and ester, wherein n = 1-4; wherein a = 1-4; wherein b=1-4; wherein c=1-4; and wherein Z is a counterion; and compounds consisting of the structure (targeting molecule) m -linker-(targeting molecule) n , wherein the targeting molecule is a retinoid or a fat soluble vitamin having a specific receptor on the target cell; wherein m and n are independently 0, 1, 2 or 3; and wherein the linker comprises a polyethylene glycol (PEG) or PEG-like molecule, as well as compositions and pharmaceutical formulations including one or both of these compounds which are useful for the delivery of therapeutic agents; and methods of using these compositions and pharmaceutical formulations.