Delivery of therapeutic alkaloid compounds
AssigneeSensorium Therapeutics, Inc.
InventorsJacob M. Hooker, Michael S. Placzek
Life of this patent
Estimating the term…
Abstract
Disclosed are prodrug compounds that can be converted to mesembrine under biologically relevant conditions, such as hydrolysis in vivo; and related methods of preparing and using these compounds. Stable preparations of isolated mesembrine stereoisomers are also provided.
Claims21
1-134. (canceled)
A compound of formula (I):
- or a pharmaceutically acceptable salt thereof, wherein
- R1 is or 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, C3-C10 cycloalkyl, 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 or phenyl, wherein each hydrogen atom in 5- to 7-membered heteroaryl or phenyl 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-C10 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, phenoxy or —O(CH2)pOCH3;
- p is 2, 3, or 4;
- R4 is —OR5 or —N(R5)2;
- each R5 is H, C1-C6 alkyl, C3-C6 heterocycloalkyl, C3-C10 cycloalkyl, C1-C6 alkoxy, phenyl, 5- to 10-membered heteroaryl, —C(O)-5- to 7-membered heteroaryl, —C(O)—C1-C5 alkyl, —C(O)—C3-C10 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-C10 cycloalkyl, C1-C6 alkoxy, phenyl, 5- to 10-membered heteroaryl, —C(O)-5- to 7-membered heteroaryl, —C(O)—C1-C5 alkyl, —C(O)—C3-C10 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;
- provided the compound of Formula (I) is not
The compound of claim 8, wherein R5 is —C(O)-5- to 6-membered heteroaryl, —C(O)—C1-C8 alkyl, —C(O)—C3-C10 cycloalkyl, —C(O)-phenyl, —C(O)N(H)-phenyl, —C(O)N(H)-5- to 6-membered heteroaryl, —C(O)N(H)—C1-C6 alkyl, —C(O)C(O)OH, or —CONH2,
A compound of Formula (XIII) or a pharmaceutically acceptable salt thereof:
- wherein R9 is C1-C6 alkyl, hydroxyl, methoxy, or —NH—C(O)-6-member nitrogen-containing heteroaryl.
A compound of formula (I):
- or a pharmaceutically acceptable salt thereof, wherein
- R1 is C1-C7 alkyl;
- ring A is
- wherein * denotes the attachment points of ring A to the compound of formula (I), and wherein
- R4 is —N(R5)2 and;
- one R5 is H and the other R5 is —C(O)N(H)-phenyl optionally substituted by —COOH.
Dependencies are inferred from the claim text.