# US 2019/0169202 A1 · Vasopressin receptor antagonists and products and methods related thereto

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- Number: US 2019/0169202 A1
- Document ID: US20190169202A1
- Status: Published application
- Kind: A1
- Application number: 16/122,780
- Filed: 2018-09-05
- Published: 2019-06-06
- Earliest claimed: 2017-09-05
- Assignees: Blackthorn Therapeutics, Inc.
- Applicants: BlackThorn Therapeutics, Inc.
- Inventors: Robert M. Jones; Mariangela Urbano; Gary Brandt; Mark Chambers; David Hardick; Chris Knight; Jason Tierney; Chris Lock
- Web page: https://patentgrep.com/patent/US20190169202A1

## CPC

- C07D 487/10: Spiro-condensed systems
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A61P 25/20: Hypnotics; Sedatives
- A61P 25/22: Anxiolytics
- A61P 25/24: Antidepressants
- C07D 519/00: Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- C07B 2200/07: Optical isomers
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## 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.

## Claims

### Claim 1

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.

### Claim 2 (depends on 1)

The compound of claim 1 having the structure of Formula (II):
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;
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.

### Claim 3 (depends on 1)

The compound of claim 1 having the structure of Formula (II-a):
wherein:
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, cycloalkylalkyl, heterocyclyl, or —O-heterocyclyl;
m is 0, 1, 2, 3, 4, 5, or 6; and
p is 0, 1, or 2.

### Claim 4 (depends on 3)

The compound of claim 3, wherein R3 is —(CHRz)m-Q-(R4)p, m and p are both 0, and Q is heteroaryl.

### Claim 5 (depends on 1)

The compound of claim 1 having the structure of Formula (II-b):
wherein:
Rx is, at each occurrence, independently H, lower alkyl, lower haloalkyl, or halo;
Ry is, at each occurrence, independently H, —OH, lower alkyl, lower alkoxy, or halo;
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;
m is 0, 1, 2, 3, 4, 5, or 6; and
p is 0, 1, or 2.

### Claim 6 (depends on 1)

The compound of claim 1 having the structure of Formula (II-c):
wherein:
Rx is, at each occurrence, independently H, lower alkyl, lower haloalkyl, or halo;
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;
m is 0, 1, 2, 3, 4, 5, or 6; and
p is 0, 1, or 2.

### Claim 7 (depends on 1)

The compound of claim 1 having the structure of Formula (II-d):
wherein:
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;
m is 0, 1, 2, 3, 4, 5, or 6; and
p is 0, 1, or 2.

### Claim 8 (depends on 1)

The compound of claim 1 having the structure of Formula (II-e):
wherein:
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;
m is 0, 1, 2, 3, 4, 5, or 6; and
p is 0, 1, or 2.

### Claim 9 (depends on 1)

The compound of claim 1 having the structure of Formula (II-f):
wherein:
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;
m is 0, 1, 2, 3, 4, 5, or 6; and
p is 0, 1, or 2.

### Claim 10 (depends on 1)

The compound of claim 1 having the structure of Formula (II-g):
wherein:
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;
m is 0, 1, 2, 3, 4, 5, or 6; and
p is 0, 1, or 2.

### Claim 11 (depends on 1)

The compound of claim 1 having the structure of Formula (II-h):
wherein:
Rx is, at each occurrence, independently H, lower alkyl, lower haloalkyl, or halo;
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;
m is 0, 1, 2, 3, 4, 5, or 6; and
p is 0, 1, or 2.

### Claim 12 (depends on 1)

The compound of claim 1 having the structure of Formula (II-i):
wherein:
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;
m is 0, 1, 2, 3, 4, 5, or 6; and
p is 0, 1, or 2.

### Claim 13 (depends on 1)

The compound of claim 1 having the structure of Formula (II-j):
wherein:
Rx is, at each occurrence, independently H, lower alkyl, lower haloalkyl, or halo;
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;
m is 0, 1, 2, 3, 4, 5, or 6; and
p is 0, 1, or 2.

### Claim 14 (depends on 1)

The compound of claim 1 having the structure of Formula (II-k):
wherein:
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;
m is 0, 1, 2, 3, 4, 5, or 6; and
p is 0, 1, or 2.

### Claim 15 (depends on 1)

The compound of claim 1 having the structure of Formula (III):
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, or halo;
Ry is, at each occurrence, independently H, —OH, lower alkyl, lower alkoxy, or halo;
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;
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;
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.

### Claim at position 16

16-26. (canceled)

### Claim 27 (depends on 1)

The compound of claim 1 having the structure of Formula (IV):
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, or halo;
Ry is, at each occurrence, independently H, —OH, lower alkyl, lower alkoxy, or halo;
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;
Rz is H or CH3
J1, J2, J3, and J4 are each, independently, N, O, CH, or CR4;
R4 is, at each occurrence, independently H, —OH, ═O, cycloalkyl, lower alkyl, lower haloalkyl, lower alkoxy, lower haloalkoxy, halo, or cyano;
n is 0, 1, or 2;
q is 0, 1, or 2;
t is 0, 1, or 2;
p is 0, 1, or 2.

### Claim at position 18

28-38. (canceled)

### Claim 39 (depends on 1)

The compound of claim 1 having the structure of Formula (V):
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, or halo;
Ry is, at each occurrence, independently H, —OH, lower alkyl, lower alkoxy, or halo;
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;
J1, J2, J3, and J4 are each, independently, N, O, CH, or CR4;
R4 is, at each occurrence, independently H, —OH, ═O, cycloalkyl, lower alkyl, lower haloalkyl, lower alkoxy, lower haloalkoxy, halo, or cyano;
n is 0, 1, or 2;
q is 0, 1, or 2;
t is 0, 1, or 2;
p is 0, 1, or 2.

### Claim at position 20

40-50. (canceled)

### Claim 51 (depends on 1)

The compound of claim 1 having the structure of Formula (VI):
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, or halo;
Ry is, at each occurrence, independently H, —OH, lower alkyl, lower alkoxy, or halo;
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;
R4 is, at each occurrence, independently H, —OH, ═O, cycloalkyl, lower alkyl, lower haloalkyl, lower alkoxy, lower haloalkoxy, halo, or cyano;
n is 0, 1, or 2;
q is 0, 1, or 2;
t is 0, 1, or 2;
p is 0, 1, or 2.

### Claim at position 22

52-62. (canceled)

### Claim 63 (depends on 1)

The compound of claim 1 having the structure of Formula (VII):
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, or halo;
Ry is, at each occurrence, independently H, —OH, lower alkyl, lower alkoxy, or halo;
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;
R4 is, at each occurrence, independently H, —OH, ═O, cycloalkyl, lower alkyl, lower haloalkyl, lower alkoxy, lower haloalkoxy, halo, or cyano;
n is 0, 1, or 2;
q is 0, 1, or 2;
t is 0, 1, or 2;
p is 0, 1, or 2.

### Claim at position 24

64-74. (canceled)

### Claim 75 (depends on 1)

The compound of claim 1 having the structure of Formula (VIII):
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, or halo;
Ry is, at each occurrence, independently H, —OH, lower alkyl, lower alkoxy, or halo;
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;
R4 is, at each occurrence, independently H, —OH, ═O, cycloalkyl, lower alkyl, lower haloalkyl, lower alkoxy, lower haloalkoxy, halo, or cyano;
n is 0, 1, or 2;
q is 0, 1, or 2;
t is 0, 1, or 2;
p is 0, 1, or 2.

### Claim at position 26

76-86. (canceled)

### Claim 87 (depends on 1)

The compound of claim 1 having the structure of Formula (IX):
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, or halo;
Ry is, at each occurrence, independently H, —OH, lower alkyl, lower alkoxy, or halo;
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;
R4 is, at each occurrence, independently H, —OH, ═O, cycloalkyl, lower alkyl, lower haloalkyl, lower alkoxy, lower haloalkoxy, halo, or cyano;
n is 0, 1, or 2;
q is 0, 1, or 2;
t is 0, 1, or 2;
p is 0, 1, or 2.

### Claim at position 28

88-98. (canceled)

### Claim 99 (depends on 1)

The compound of claim 1 having the structure of Formula (X):
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, or halo;
Ry is, at each occurrence, independently H, —OH, lower alkyl, lower alkoxy, or halo;
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;
J1, J2, J3, and J4 are each, independently, N, O, CH, or CR4;
R4 is, at each occurrence, independently H, —OH, ═O, cycloalkyl, lower alkyl, lower haloalkyl, lower alkoxy, lower haloalkoxy, halo, or cyano;
n is 0, 1, or 2;
q is 0, 1, or 2;
t is 0, 1, or 2;
p is 0, 1, or 2.

### Claim at position 30

100-110. (canceled)

### Claim 111 (depends on 1)

The compound of claim 1 having the structure of Formula (XI):
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, or halo;
Ry is, at each occurrence, independently H, —OH, lower alkyl, lower alkoxy, or halo;
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;
R4 is, at each occurrence, independently H, —OH, ═O, cycloalkyl, lower alkyl, lower haloalkyl, lower alkoxy, lower haloalkoxy, halo, or cyano;
n is 0, 1, or 2;
q is 0, 1, or 2;
t is 0, 1, or 2; and
p is 0, 1, or 2.

### Claim at position 32

112-122. (canceled)

### Claim 123 (depends on 1)

The compound of claim 1 having the structure of Formula (XII):
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, or halo;
Ry is, at each occurrence, independently H, —OH, lower alkyl, lower alkoxy, or halo;
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;
R4 is, at each occurrence, independently H, —OH, ═O, cycloalkyl, lower alkyl, lower haloalkyl, lower alkoxy, lower haloalkoxy, halo, or cyano;
n is 0, 1, or 2;
q is 0, 1, or 2;
t is 0, 1, or 2; and
p is 0, 1, or 2.

### Claim at position 34

124-134. (canceled)

### Claim 135 (depends on 1)

The compound of claim 1 having the structure of Formula (XIII):
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, or halo;
Ry is, at each occurrence, independently H, —OH, lower alkyl, lower alkoxy, or halo;
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;
R4 is, at each occurrence, independently H, —OH, ═O, cycloalkyl, lower alkyl, lower haloalkyl, lower alkoxy, lower haloalkoxy, halo, or cyano;
n is 0, 1, or 2;
q is 0, 1, or 2;
t is 0, 1, or 2; and
p is 0, 1, or 2.

### Claim at position 36

136-146. (canceled)

### Claim 147 (depends on 1)

The compound of claim 1 having the structure of Formula (XIV):
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, or halo;
Ry is, at each occurrence, independently H, —OH, lower alkyl, lower alkoxy, or halo;
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;
R4 is, at each occurrence, independently H, —OH, ═O, cycloalkyl, lower alkyl, lower haloalkyl, lower alkoxy, lower haloalkoxy, halo, or cyano;
n is 0, 1, or 2;
q is 0, 1, or 2;
t is 0, 1, or 2; and
p is 0, 1, or 2.

### Claim at position 38

148-158. (canceled)

### Claim 159 (depends on 1)

The compound of claim 1 having the structure of Formula (XV):
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, or halo;
Ry is, at each occurrence, independently H, —OH, lower alkyl, lower alkoxy, or halo;
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;
R5 is H, cycloalkyl, lower alkyl, lower haloalkyl, lower alkoxy, aryl, heteroaryl, cycloalkylalkyl, heterocyclyl, or —O-heterocyclyl;
n is 0, 1, or 2;
q is 0, 1, or 2; and
t is 0, 1, or 2.

### Claim at position 40

160-170. (canceled)

### Claim 171 (depends on 1)

The compound of claim 1 having the structure of Formula (XVI):
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, or halo;
Ry is, at each occurrence, independently H, —OH, lower alkyl, lower alkoxy, or halo;
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;
R5 is H, cycloalkyl, lower alkyl, lower haloalkyl, lower alkoxy, aryl, heteroaryl, cycloalkylalkyl, heterocyclyl, or —O-heterocyclyl;
n is 0, 1, or 2;
q is 0, 1, or 2; and
t is 0, 1, or 2.

### Claim at position 42

172-182. (canceled)

### Claim 183

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.

### Claim 184

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.

### Claim 185

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.

### Claim 186

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.

### Claim 187 (depends on 1)

The compound of claim 1, wherein R1b is halogen.

### Claim 188 (depends on 187)

The compound of claim 187, wherein R1b is Cl.

### Claim 189 (depends on 1)

The compound of claim 1, wherein R1b is lower alkyl.

### Claim 190 (depends on 189)

The compound of claim 189, wherein R1b is methyl, ethyl, or isopropyl.

### Claim 191 (depends on 1)

The compound of claim 1, wherein R1b is lower haloalkyl.

### Claim 192 (depends on 191)

The compound of claim 191, wherein R1b is —CF3.

### Claim 193 (depends on 1)

The compound of claim 1, wherein R1b is lower alkoxy.

### Claim 194 (depends on 193)

The compound of claim 193, wherein R1b is methoxy, ethoxy, isopropoxy, or t-butoxy.

### Claim 195 (depends on 1)

The compound of claim 1, wherein R1b is cyano.

### Claim 196 (depends on 1)

The compound of claim 1, wherein at least one Rx is hydrogen.

### Claim 197 (depends on 1)

The compound of claim 1, wherein at least one Rx is lower alkyl.

### Claim 198 (depends on 197)

The compound of claim 197, wherein at least one Rx is methyl, ethyl, or isopropyl.

### Claim 199 (depends on 1)

The compound of claim 1, wherein at least one Ry is lower alkoxy.

### Claim 200 (depends on 199)

The compound of claim 199, wherein at least one Ry is methoxy, ethoxy, isopropoxy, or t-butoxy.

### Claim 201 (depends on 1)

The compound of claim 1, wherein at least one Rx is cycloalkyl.

### Claim 202 (depends on 201)

The compound of claim 201, wherein at least one Rx is cyclopropyl or cyclobutyl.

### Claim 203 (depends on 1)

The compound of claim 1, wherein R4 is halogen.

### Claim 204 (depends on 203)

The compound of claim 203, wherein R4 is F or Cl.

### Claim 205 (depends on 1)

The compound of claim 1, wherein R4 is lower alkyl.

### Claim 206 (depends on 205)

The compound of claim 205, wherein R4 is methyl or ethyl.

### Claim 207 (depends on 1)

The compound of claim 1, wherein R4 is lower alkoxy.

### Claim 208 (depends on 207)

The compound of claim 207, wherein R4 is methoxy or ethoxy.

### Claim 209 (depends on 1)

The compound of claim 1, wherein R4 is cyano.

### Claim 210 (depends on 1)

The compound of claim 1, wherein R4 is hydroxy.

### Claim 211 (depends on 1)

The compound of claim 1, wherein R5 is lower alkyl.

### Claim 212 (depends on 211)

The compound of claim 211, wherein R5 is methyl, ethyl, or isopropyl.

### Claim 213 (depends on 1)

The compound of claim 1, wherein R5 is lower alkoxy.

### Claim 214 (depends on 213)

The compound of claim 213, wherein R5 is t-butoxy.

### Claim 215

A compound having a structure listed in Table 1, or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope, or salt thereof.

### Claim 216

A substantially enantiomerically pure form of a compound having a structure listed in Table 2, or pharmaceutically acceptable hydrate, solvate, isotope, or salt thereof.

### Claim 217 (depends on 1)

A composition comprising a compound of claim 1, or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope, or salt thereof, and a pharmaceutically acceptable carrier, diluent, or excipient.

### Claim 218 (depends on 1)

A method for antagonizing the V1a receptor, comprising contacting the V1a receptor with an effective amount of a compound of claim 1, or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope, or salt thereof, or a composition comprising the same.

### Claim 219 (depends on 1)

A method for treating vasopressin-dependent conditions or conditions related to inappropriate secretion of vasopressin, comprising administering to a subject in need thereof an effective amount of a compound of claim 1, or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope, or salt thereof, or a composition comprising the same, at a frequency and for a duration sufficient to provide a beneficial effect to the subject.

### Claim 220 (depends on 1)

A method for treating a neuropsychological, comprising administering to a subject in need thereof an effective amount of a compound of claim 1, or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope, or salt thereof, or a composition comprising the same, at a frequency and for a duration sufficient to provide a beneficial effect to the subject.

### Claim 221 (depends on 220)

The method of claim 220, wherein the neuropsychological disorder is an autistic spectrum disorder.

### Claim 222 (depends on 220)

The method of claim 220, wherein the neuropsychological disorder is aggressive behavior.

### Claim 223 (depends on 220)

The method of claim 220, wherein the neuropsychological disorder is intermittent explosive disorder.

### Claim 224 (depends on 220)

The method of claim 220, wherein the neuropsychological disorder is an anxiety disorder.

### Claim 225 (depends on 224)

The method of claim 224, wherein the anxiety disorder is generalized anxiety disorder, panic disorder, stress-related disorder, obsessive compulsive disorder, phobia, social anxiety disorder, separation anxiety disorder, or post-traumatic stress disorder.

### Claim 226 (depends on 225)

The method of claim 225, wherein the anxiety disorder is social anxiety disorder.

### Claim 227 (depends on 225)

The method of claim 225, wherein the anxiety disorder is phobia.

### Claim 228 (depends on 225)

The method of claim 225, wherein the anxiety disorder is stress-related disorder.

### Claim 229 (depends on 225)

The method of claim 225, wherein the anxiety disorder is post-traumatic stress disorder.

### Claim 230 (depends on 225)

The method of claim 225, wherein the anxiety disorder is obsessive compulsive disorder.

### Claim 231 (depends on 220)

The method of claim 220, wherein the neuropsychological disorder is a depressive disorder, a mood disorder, or an affective disorder.

### Claim 232 (depends on 231)

The method of claim 231, wherein the depressive disorder is major depression, drug-resistant depression, dysthymia, and bipolar disorder.

### Claim 233 (depends on 232)

The method of claim 232, wherein the depressive disorder is major depression.

### Claim 234 (depends on 231)

The method of claim 231, wherein the mood disorder is anhedonia.

### Claim 235 (depends on 220)

The method of claim 220, wherein the neuropsychological disorder is a schizophrenia spectrum disorder.

### Claim 236 (depends on 235)

The method of claim 235, wherein the schizophrenia spectrum disorder is schizophrenia, schizoaffective disorder, psychotic state, or memory disorder.

### Claim 237 (depends on 1)

A method for treating a circadian rhythm related disorder, comprising administering to a subject in need thereof an effective amount of a compound of claim 1, or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope or salt thereof, or a pharmaceutical composition comprising the same, at a frequency and for duration sufficient to provide a beneficial effect to the subject.

### Claim 238 (depends on 237)

The method of claim 237, wherein the circadian rhythm related disorder is jetlag.

### Claim 239 (depends on 237)

The method of claim 237, wherein the circadian rhythm related disorder is a sleep disorder.

### Claim 240 (depends on 1)

A method for the therapeutic and/or prophylactic treatment of chronic stress related infertility, primary or secondary dysmenorrhea, male or female sexual dysfunction comprising administering to a subject in need thereof an effective amount of a compound of claim 1, or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope or salt thereof, or a composition comprising the same, at a frequency and for duration sufficient to provide a beneficial effect to the subject.