16-01-2020 дата публикации
Номер: US20200017440A1
Принадлежит:
Disclosed are dendritic anionic lipids which are compounds of Formula (I): wherein R and Rare non-polar groups, L is a linking moiety, and Dm is a dendritic moiety of m generations, each as defined herein. These dendritic anionic lipids are useful for delivery and expression of m RNA and encoded protein, e.g., as a component of liposomal delivery vehicle, and accordingly can be useful for treating various diseases, disorders and conditions, such as those associated with deficiency of one or more proteins. 2. The compound of claim 1 , wherein:{'sub': '3', 'sup': '−', 'A is —OSO.'}3. The compound of claim 1 , wherein:{'sup': '1', 'L is —X—;'}{'sup': 1', '3', '3', '3', '3', '3', '3, 'sub': '2', 'Xis —O—, —C(O)—, —S(O)—, —C(O)—O—, —O—C(O)—, —C(O)—N(R)—, —N(R)—C(O)—, —O—C(O)—N(R)—, —N(R)—C(O)—O— or —N(R)—C(O)—N(R)—; and'}{'sup': '3', 'sub': '1-4', 'each instance of Rindependently is H or Calkyl.'}4. The compound of claim 3 , wherein:{'sup': '1', 'Xis —C(O)—NH—, —NH—C(O)—, —O—C(O)—NH—, —NH—C(O)—O—, —NH—C(O)—NH—, —SS—, or —S.'}5. The compound of claim 1 , wherein:{'sup': 2', '2a', '3, 'L is —X—R—X—;'}{'sup': 2', '3', '3', '3', '3', '3', '3, 'sub': '2', 'Xis —O—, —C(O)—, —S(O)—, —C(O)—O—, —O—C(O)—, —C(O)—N(R)—, —N(R)—C(O)—, —O—C(O)—N(R)—, —N(R)—C(O)—O— or —N(R)—C(O)—N(R)—;'}{'sup': '2a', 'sub': '1-10', 'Ris Caliphatic;'}{'sup': 3', '3', '3', '3', '3', '3', '3, 'sub': '2', 'Xis —O—, —C(O)—, —S(O)—, —C(O)—O—, —O—C(O)—, —C(O)—N(R)—, —N(R)—C(O)—, —O—C(O)—N(R)—, —N(R)—C(O)—O— or —N(R)—C(O)—N(R)—; and'}{'sup': '3', 'sub': '1-4', 'each instance of Ris independently is —H or Calkyl.'}6. The compound of claim 1 , wherein:{'sup': 4', '2b', '2c', '2d', '5, 'L is —X—R—R—R—X—;'}{'sup': 4', '3', '3', '3', '3', '3', '3, 'sub': '2', 'Xis —O—, —C(O)—, —S(O)—, —C(O)—O—, —O—C(O)—, —C(O)—N(R)—, —N(R)—C(O)—, —O—C(O)—N(R)—, —N(R)—C(O)—O— or —N(R)—C(O)—N(R)—;'}{'sup': '2b', 'sub': '1-10', 'Ris Caliphatic;'}{'sup': '2c', 'Ris a polyethylene glycol linker having an average molecular weight of from ...
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