Delivery of therapeutic alkaloid compounds

A compound of formula (I):

• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is C1-C7 alkyl or H;
• and
• ring A is
• wherein* denotes the attachment points of ring A to the compound of formula (I), and wherein
• each of W and Z is independently O, NH, or S;
• each R2 is independently C1-C3 alkyl, C2-C6 alkenyl, —COOH, —CONH2, phenyl, 5- to 7-membered heterocyclyl, or 5- to 7-membered heteroaryl, wherein each hydrogen atom in C1-C3 alkyl, C2-C6 alkenyl, phenyl, 5- to 7-membered heterocyclyl and 5- to 7-membered heteroaryl is optionally substituted by —OH, C1-C3 alkyl, C1-C3 alkoxy, aryloxy, C1-C3 alkanol, or —NO2, wherein each hydrogen atom in C1-C3 alkoxy and aryloxy is optionally substituted by C1-C3 alkoxy or phenyl;
• or two R2s on a single carbon atom combine to form ═O;
• or two adjacent R2s together with the carbon atoms to which they are attached combine to form 5- to 7-membered heteroaryl, wherein each hydrogen atom in 5- to 7-membered heteroaryl is optionally substituted by —OH, C1-C3 alkyl, or C1-C3 alkanol;
• m is 1 or 2;
• n is 0, 1, 2, or 3;
• R3 is —OSi(C1-C6 alkyl)3, —OC(O)C1-C6 alkyl, —OC(O)C2-C6 alkenyl, —OC(O)C3-C10 cycloalkyl, —OC(O)phenyl, —OC(O)-5- to 7-membered heteroaryl, wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C3-C1O cycloalkyl, phenyl, and 5- to 7-membered heteroaryl is optionally substituted by halogen, C1-C6 alkyl, C1-C3 alkoxy, nitro, —N(C1-C3 alkyl)2, C1-C3 haloalkyl, cyano, phenyl, or phenoxy;
• R4 is —OR5 or —N(R5)2;
• each R5 is H, C1-C6 alkyl, C3-C6 heterocycloalkyl, C3-C1O cycloalkyl, C1-C6 alkoxy, phenyl, 5- to 10-membered heteroaryl, —C(O)-5- to 7-membered heteroaryl, —C(O)—C1-C8alkyl, —C(O)—C3-C1O cycloalkyl, —C(O)-phenyl, —C(O)N(H)-phenyl, —C(O)N(H)-5- to 7-membered heteroaryl, —C(O)N(H)—C1-C6 alkyl, —C(O)C(O)OH, or —CONH2, wherein each hydrogen atom in C1-C6 alkyl, C3-C6 heterocycloalkyl, C3-C1O cycloalkyl, C1-C6 alkoxy, phenyl, 5- to 10-membered heteroaryl, —C(O)-5- to 7-membered heteroaryl, —C(O)—C1-C8 alkyl, —C(O)—C3-C1O cycloalkyl, —C(O)-phenyl, —C(O)N(H)-phenyl, —C(O)N(H)-5- to 7-membered heteroaryl, and —C(O)N(H)—C1-C6 alkyl is optionally substituted by halogen, OH, C1-C3 alkyl, C3-C10 cycloalkyl optionally substituted by —COOH, phenyl, 5- to 7-membered heteroaryl, aryloxy, C1-C6 alkoxy, C1-C3 alkanol, C3-C6 heterocycloalkyl optionally substituted with methyl, —COOH, —S(O)2CH3, —C(O)C1-C6 alkyl, or —C(O)OC1-C6 alkyl;
• and
• each of R6 and R7 is independently C1-C3 alkyl.

A compound of formula (V):

• or a pharmaceutically acceptable salt thereof, wherein
• ring A is
• wherein * denotes the attachment points of ring A to the compound of formula (V), and wherein
• R6 is C1-C3 alkyl;
• X1 is >L-R14, wherein L is absent or a linker and where > denotes the two single bonds to the cyclohexane ring such that the ring containing X1 forms a C3-C6 alkyl ring, which is optionally substituted by C1-C3 alkanol;
• X2 is =L-R14, wherein L is absent or a linker;
• X3 is -L-R14, wherein L is absent or a linker;
• and
• wherein -L-R14 is selected from
• and
• the * denotes the carbon of the cyclohexyl ring when L is absent.