Vasopressin receptor antagonists and products and methods related thereto
AssigneeBlackthorn Therapeutics, Inc.
InventorsRobert M. Jones, Mariangela Urbano, Gary Brandt, Mark Chambers, David Hardick, Chris Knight, Jason Tierney, Chris Lock
Life of this patent
Estimating the term…
Abstract
Compounds are provided that antagonize vasopressin receptors, particularly the V1a receptor products containing such compounds, as well as to methods of their use and synthesis. Such compounds have the structure of Formula (I), or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope, or salt thereof: wherein Q1, Q2, Q3, R2a, R2b, R3 and X are as defined herein.
Claims104
A compound having the structure of Formula (I) or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope, or salt thereof:
- wherein:
- X is —(CRxRy)nO(CRxRy)q—, —(CRxRy)nS(o)t(CRxRy)q—, —(CRxRy)nN(Rx)(CRxRy)q—, or —(CRxRy)n—,
- Rx is, at each occurrence, independently H, lower alkyl, lower haloalkyl, halo, or R6;
- Ry is, at each occurrence, independently H, —OH, lower alkyl, lower alkoxy, or halo;
- Q1 is N or CR1a, Q2 is N or CR1b, and Q3 is N or CR1c, wherein at least one Q1, Q2, or Q3 is not N;
- R1a, R1b, and R1c are each, independently, H, lower alkyl, lower haloalkyl, lower alkoxy, cyano, or halo;
- R2a and R2b are each, independently, H, lower alkyl, lower haloalkyl, or lower alkoxy;
- R3 is —(CHRz)m-Q-(R4)p, —S(═O)2R5, or —C(═O)R5;
- Rz is H or CH3
- Q is aryl or heteroaryl;
- R4 is, at each occurrence, independently H, —OH, ═O, cycloalkyl, lower alkyl, lower haloalkyl, lower alkoxy, lower haloalkoxy, halo, or cyano;
- R5 is H, cycloalkyl, lower alkyl, lower haloalkyl, lower alkoxy, aryl, heteroaryl, cycloalkylalkyl, heterocyclyl, or —O-heterocyclyl;
- R6 is cycloalkyl, heterocyclyl, or —C(═O)R7;
- R7 is H, lower alkyl, or lower haloalkyl;
- n is 0, 1, or 2;
- q is 0, 1, or 2;
- t is 0, 1, or 2;
- m is 0, 1, 2, 3, 4, 5, or 6;
- and
- p is 0, 1, or 2.
A substantially enantiomerically pure compound having the structure of Formula (XVII-S), or a pharmaceutically acceptable hydrate, solvate, isotope, or salt thereof:
- wherein:
- X is —(CRxRy)nO(CRxRy)q—, —(CRxRy)nS(o)t(CRxRy)q—, —(CRxRy)nN(Rx)(CRxRy)q—, or —(CRxRy)n—,
- Rx is, at each occurrence, independently H, lower alkyl, lower haloalkyl, halo, or R6;
- Ry is, at each occurrence, independently H, —OH, lower alkyl, lower alkoxy, or halo;
- Q1 is N or CR1a, Q2 is N or CR1b, and Q3 is N or CR1c, wherein at least one Q1, Q2, or Q3 is not N;
- R1a, R1b, and R1c are each, independently, H, lower alkyl, lower haloalkyl, lower alkoxy, cyano, or halo;
- R2a and R2b are each, independently, H, lower alkyl, lower haloalkyl, or lower alkoxy;
- R3 is —(CHRz)m-Q-(R4)p, —S(═O)2R5, or —C(═O)R5;
- Rz is H or CH3
- Q is aryl or heteroaryl;
- R4 is, at each occurrence, independently H, —OH, ═O, cycloalkyl, lower alkyl, lower haloalkyl, lower alkoxy, lower haloalkoxy, halo, or cyano;
- R5 is H, cycloalkyl, lower alkyl, lower haloalkyl, lower alkoxy, aryl, heteroaryl, cycloalkylalkyl, heterocyclyl, or —O-heterocyclyl;
- R6 is cycloalkyl, heterocyclyl, or —C(═O)R7;
- R7 is H, lower alkyl, or lower haloalkyl;
- n is 0, 1, or 2;
- q is 0, 1, or 2;
- t is 0, 1, or 2;
- m is 0, 1, 2, 3, 4, 5, or 6;
- and
- p is 0, 1, or 2.
A substantially enantiomerically pure compound having the structure of Formula (XVII-R), or a pharmaceutically acceptable hydrate, solvate, isotope, or salt thereof:
- wherein:
- X is —(CRxRy)nO(CRxRy)q—, —(CRxRy)nS(O)t(CRxRy)q—, —(CRxRy)nN(Rx)(CRxRy)q—, or —(CRxRy)n—,
- Rx is, at each occurrence, independently H, lower alkyl, lower haloalkyl, halo, or R6;
- Ry is, at each occurrence, independently H, —OH, lower alkyl, lower alkoxy, or halo;
- Q1 is N or CR1a, Q2 is N or CR1b, and Q3 is N or CR1c, wherein at least one Q1, Q2, or Q3 is not N;
- R1a, R1b, and R1c are each, independently, H, lower alkyl, lower haloalkyl, lower alkoxy, cyano, or halo;
- R2a and R2b are each, independently, H, lower alkyl, lower haloalkyl, or lower alkoxy;
- R3 is —(CHRz)m-Q-(R4)p, —S(═O)2R5, or —C(═O)R5;
- Rz is H or CH3
- Q is aryl or heteroaryl;
- R4 is, at each occurrence, independently H, —OH, ═O, cycloalkyl, lower alkyl, lower haloalkyl, lower alkoxy, lower haloalkoxy, halo, or cyano;
- R5 is H, cycloalkyl, lower alkyl, lower haloalkyl, lower alkoxy, aryl, heteroaryl, cycloalkylalkyl, heterocyclyl, or —O-heterocyclyl;
- R6 is cycloalkyl, heterocyclyl, or —C(═O)R7;
- R7 is H, lower alkyl, or lower haloalkyl;
- n is 0, 1, or 2;
- q is 0, 1, or 2;
- t is 0, 1, or 2;
- m is 0, 1, 2, 3, 4, 5, or 6;
- and
- p is 0, 1, or 2.
A substantially enantiomerically pure compound having the structure of Formula (XVIII-S), or a pharmaceutically acceptable hydrate, solvate, isotope, or salt thereof:
- wherein:
- X is —(CRxRy)nO(CRxRy)q—, —(CRxRy)nS(O)t(CRxRy)q—, —(CRxRy)nN(Rx)(CRxRy)q—, or —(CRxRy)n—,
- Rx is, at each occurrence, independently H, lower alkyl, lower haloalkyl, halo, or R6;
- Ry is, at each occurrence, independently H, —OH, lower alkyl, lower alkoxy, or halo;
- Q1 is N or CR1a, Q2 is N or CR1b, and Q3 is N or CR1c, wherein at least one Q1, Q2, or Q3 is not N;
- R1a, R1b, and R1c are each, independently, H, lower alkyl, lower haloalkyl, lower alkoxy, cyano, or halo;
- R2a and R2b are each, independently, H, lower alkyl, lower haloalkyl, or lower alkoxy;
- R3 is —(CHRz)m-Q-(R4)p, —S(═O)2R5, or —C(═O)R5;
- Rz is H or CH3
- Q is aryl or heteroaryl;
- R4 is, at each occurrence, independently H, —OH, ═O, cycloalkyl, lower alkyl, lower haloalkyl, lower alkoxy, lower haloalkoxy, halo, or cyano;
- R5 is H, cycloalkyl, lower alkyl, lower haloalkyl, lower alkoxy, aryl, heteroaryl, cycloalkylalkyl, heterocyclyl, or —O-heterocyclyl;
- R6 is cycloalkyl, heterocyclyl, or —C(═O)R7;
- R7 is H, lower alkyl, or lower haloalkyl;
- n is 0, 1, or 2;
- q is 0, 1, or 2;
- t is 0, 1, or 2;
- m is 0, 1, 2, 3, 4, 5, or 6;
- and
- p is 0, 1, or 2.
A substantially enantiomerically pure compound having the structure of Formula (XVIII-R), or a pharmaceutically acceptable hydrate, solvate, isotope, or salt thereof:
- wherein:
- X is —(CRxRy)nO(CRxRy)q—, —(CRxRy)nS(O)t(CRxRy)q—, —(CRxRy)nN(Rx)(CRxRy)q—, or —(CRxRy)n—,
- Rx is, at each occurrence, independently H, lower alkyl, lower haloalkyl, halo, or R6;
- Ry is, at each occurrence, independently H, —OH, lower alkyl, lower alkoxy, or halo;
- Q1 is N or CR1a, Q2 is N or CR1b, and Q3 is N or CR1c, wherein at least one Q1, Q2, Or Q3 is not N;
- R1a, R1b, and R1c are each, independently, H, lower alkyl, lower haloalkyl, lower alkoxy, cyano, or halo;
- R2a and R2b are each, independently, H, lower alkyl, lower haloalkyl, or lower alkoxy;
- R3 is —(CHRz)m-Q-(R4)p, —S(═O)2R5, or —C(═O)R5;
- Rz is H or CH3
- Q is aryl or heteroaryl;
- R4 is, at each occurrence, independently H, —OH, ═O, cycloalkyl, lower alkyl, lower haloalkyl, lower alkoxy, lower haloalkoxy, halo, or cyano;
- R5 is H, cycloalkyl, lower alkyl, lower haloalkyl, lower alkoxy, aryl, heteroaryl, cycloalkylalkyl, heterocyclyl, or —O-heterocyclyl;
- R6 is cycloalkyl, heterocyclyl, or —C(═O)R7;
- R7 is H, lower alkyl, or lower haloalkyl;
- n is 0, 1, or 2;
- q is 0, 1, or 2;
- t is 0, 1, or 2;
- m is 0, 1, 2, 3, 4, 5, or 6;
- and
- p is 0, 1, or 2.
A compound having a structure listed in Table 1, or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope, or salt thereof.
A substantially enantiomerically pure form of a compound having a structure listed in Table 2, or pharmaceutically acceptable hydrate, solvate, isotope, or salt thereof.
Dependencies are inferred from the claim text.