Lipid prodrugs of neurosteroids

A compound of formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• R1 and R2 are each independently hydrogen, an acid-labile group, a lipid, or —C(O)R3 each R3 independently is a saturated or unsaturated, straight or branched, optionally substituted C1-37 hydrocarbon chain;
• X is —O—, —NR—, or —S—;
• each R independently is hydrogen or an optionally substituted group selected from C1-6 aliphatic, a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic aromatic carbocyclic ring, a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• Y is —C(O)—, —C(NR)—, or —C(S)—;
• L is a bivalent, saturated C3-30 hydrocarbon chain optionally substituted with 1, 2, 3, or 4 R4 groups, wherein 0-4 methylene units of L are independently replaced by —O—, —OC(O)—, —C(O)O—, or —C(O)— and 1 methylene unit of L is optionally replaced with -M−:
• or
• L is
• wherein either the right-hand side or left-hand side of L is attached to ;
• each R4 and R5 independently is hydrogen, deuterium, halogen, —CN, —OR, —NR2, —SR, a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic aromatic carbocyclic ring, a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a C1-6 aliphatic group optionally substituted with —CN, —OR, —NR2, —SR, a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic aromatic carbocyclic ring, a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or the C1-6 aliphatic is optionally substituted with 1, 2, 3, 4, 5, or 6 deuterium or halogen atoms;
• or
• two instances of R4 or R5 attached to the same carbon atom, taken together with the carbon atom to which they are attached, form a 3-6 membered spirocyclic saturated monocyclic carbocyclic ring or 3-6 membered spirocyclic saturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• M- is a self-immolative group;
• n is 0-18;
• each m independently is 0-6;
• and
• is a therapeutic agent selected from a pregnane neurosteroid or an analogue or prodrug thereof.