# US 10,118,902 B2 · Small molecule agonists of neurotensin receptor 1

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- Number: US 10,118,902 B2
- Document ID: US10118902B2
- Status: Granted
- Kind: B2
- Application number: 15/319,329
- Filed: 2015-06-24
- Published: 2017-08-24
- Granted: 2018-11-06
- Earliest claimed: 2014-06-25
- Assignees: Sanford Burnham Prebys Medical Discovery Institute
- Applicants: Sanford Burnham Prebys Medical Discovery Institute
- Inventors: Anthony B. Pinkerton; Paul M. Hershberger; Satyamaheshwar Peddibhotla; Patrick R. Maloney; Michael P. Hedrick
- Web page: https://patentgrep.com/patent/US10118902B2

## CPC

- C07D 239/94: Nitrogen atoms
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- A61P 25/16: Anti-Parkinson drugs
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 25/30: for treating abuse or dependence
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 401/14: containing three or more hetero rings
- C07D 403/04: directly linked by a ring-member-to-ring-member bond
- C07D 403/12: linked by a chain containing hetero atoms as chain links
- C07D 409/14: containing three or more hetero rings
- C07D 487/10: Spiro-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Provided herein are small molecule neurotensin receptor agonists, compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds.

## Claims

### Claim 1

A compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof:
wherein,
ring A is phenyl, C3-C6cycloalkyl, C2-C6heterocycloalkyl, or monocyclic heteroaryl;
A is CH or N;
R1 is halogen, C1-C4alkyl, C1-C4alkoxy, C1-C4haloalkyl, C1-C4haloalkoxy, —OH, or —N(Ra)2; and R3 is hydrogen, C1-C4alkyl, or C1-C4haloalkyl;
or
R1 is hydrogen, halogen, C1-C4alkyl, C1-C4alkoxy, C1-C4haloalkyl, C1-C4haloalkoxy, or —N(Ra)2; and R3 and R9 are taken together with the intervening atoms to form an optionally substituted C2-C6heterocycloalkyl;
each Ra is independently selected from the group consisting of hydrogen, C1-C4 alkyl, —C(═O)R11, —C(═O)—O—R11, —S(═O)2R11, —C(═O)R11, or 2 Ra taken together with the nitrogen to which they are attached form an optionally substituted C2-C6heterocycloalkyl;
L1 is absent, C1-C4alkylene, C1-C4alkenylene, C1-C4alkynylene, or —N(Rb)—;
Rb is hydrogen, C1-C4alkyl, C1-C4haloalkyl, —C(═O)R11, —C(═O)—O—R11, —S(═O)2R11, or —C(═O)R11;
R2 is hydrogen, halogen, —CN, —OH, —NO2, optionally substituted C1-C4alkyl, optionally substituted C1-C4alkoxy, optionally substituted C1-C4haloalkyl, optionally substituted C1-C4haloalkoxy, optionally substituted C3-C6cycloalkyl, optionally substituted C2-C6heterocycloalkyl, optionally substituted phenyl, or optionally substituted 5- or 6-membered heteroaryl;
R5 and R6 are each independently selected from hydrogen, halogen, —OH, and C1-C4alkyl, or when on the same carbon, R5 and R6 are taken together form an oxo;
R7 is hydrogen, halogen, —CN, —OH, —NO2, —N(R12)—R13, —C(═O)—N(R12)—R13, —NR12C(═O)R11, —C(═O)—O—R11, —O—C(═O)—R11, —SR12, —S(═O)R11, —S(═O)2R11, —N(R12)S(═O)2R11, —S(═O)2—N(R12)—R13, —C(═O)R11, optionally substituted C1-C4alkyl, optionally substituted C1-C4alkoxy, optionally substituted C1-C4haloalkyl, optionally substituted C1-C4haloalkoxy, optionally substituted C3-C6cycloalkyl, optionally substituted C2-C6heterocycloalkyl, optionally substituted phenyl, or optionally substituted 5- or 6-membered heteroaryl;
R8 is hydrogen, —OH, C1-C4alkyl, C1-C4fluoroalkyl, C1-C4alkoxy, C1-C4fluoroalkoxy, or —N(Ra)2;
R9 is hydrogen, C1-C4alkyl, or C1-C4fluoroalkyl;
X is —O— or —N(Rb)—;
R10 is hydrogen, C1-C4alkyl, C1-C4fluoroalkyl, —C(═O)R11, —C(═O)—O—R11, —C(═O)N(R12)R13, —S(═O)2R11, or —C(═O)R11;
each R11 is independently selected from the group consisting of optionally substituted C1-C4alkyl, optionally substituted C1-C4fluoroalkyl, optionally substituted C3-C6cycloalkyl, optionally substituted C2-C6heterocycloalkyl, optionally substituted phenyl, and optionally substituted 5- or 6-membered heteroaryl;
each of R12 and R13 is independently selected from the group consisting of hydrogen, optionally substituted C1-C4alkyl, optionally substituted C1-C4fluoroalkyl, optionally substituted C3-C6cycloalkyl, optionally substituted C2-C6heterocycloalkyl, optionally substituted phenyl, and optionally substituted 5- or 6-membered heteroaryl; or R12 and R13, when on the same nitrogen atom, are taken together with the nitrogen atom to which they are attached to form an optionally substituted C2-C6heterocycloalkyl;
n is 1, 2 or 3; and
m is 1, 2, 3 or 4.

### Claim 2 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein:
ring A is phenyl or C3-C6cycloalkyl.

### Claim 3 (depends on 2)

The compound of claim 2, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound of Formula (I) has the following structure:

### Claim 4 (depends on 3)

The compound of claim 3, or a pharmaceutically acceptable salt or solvate thereof, wherein L1 is absent and the compound of Formula (I) has the following structure of Formula (Ia):

### Claim 5 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein:
ring A is monocyclic heteroaryl.

### Claim 6 (depends on 4)

The compound of claim 4, a pharmaceutically acceptable salt or solvate thereof, wherein:
R1 is halogen, C1-C4alkyl, C1-C4alkoxy, C1-C4haloalkyl, C1-C4haloalkoxy, or —N(Ra)2; and
R3 is hydrogen or C1-C4alkyl.

### Claim 7 (depends on 4)

The compound of claim 4, or a pharmaceutically acceptable salt or solvate thereof, wherein:
R1 is hydrogen, halogen, C1-C4alkyl, C1-C4alkoxy, C1-C4haloalkyl, C1-C4haloalkoxy, or —N(Ra)2; and
R3 and R9 are taken together with the intervening atoms to form an optionally substituted C2-C6heterocycloalkyl.

### Claim 8 (depends on 7)

The compound of claim 7, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound of Formula (I) has the following structure of Formula (Ib):

### Claim 9 (depends on 8)

The compound of claim 8, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound of Formula (Ib) has one of the following structures:

### Claim 10 (depends on 8)

The compound of claim 8, or a pharmaceutically acceptable salt or solvate thereof, wherein:
A is CH;
R7 is hydrogen, halogen, —CN, —OH, C1-C4alkyl, C1-C4alkoxy, C1-C4haloalkyl, or C1-C4haloalkoxy;
R8 is C1-C4alkoxy or —N(Ra)2;
R10 is hydrogen or C1-C4alkyl;
m is 1 or 2; and
n is 1 or 2.

### Claim 11 (depends on 8)

The compound of claim 8, or a pharmaceutically acceptable salt or solvate thereof, wherein:
A is N;
R7 is hydrogen, halogen, —CN, —OH, C1-C4alkyl, C1-C4alkoxy, C1-C4haloalkyl, or C1-C4haloalkoxy;
R8 is C1-C4alkoxy or —N(Ra)2;
R10 is hydrogen or C1-C4alkyl;
m is 1 or 2; and
n is 1 or 2.

### Claim 12

A compound of Formula (VI), or a pharmaceutically acceptable salt or solvate thereof:
wherein,
ring A is C3-C6cycloalkyl, C2-C6heterocycloalkyl, or monocyclic heteroaryl;
ring B is an optionally substituted hetereocycloalkyl, wherein if ring B is substituted then it is substituted with R5 and R6;
R1 is hydrogen, halogen, C1-C4alkyl, C1-C4alkoxy, C1-C4haloalkyl, C1-C4haloalkoxy, or —N(Ra)2;
each Ra is independently selected from the group consisting of hydrogen, C1-C4 alkyl, —C(═O)R11, —C(═O)—O—R11, —S(═O)2R11, and —C(═O)R11, or 2 Ra taken together with the nitrogen to which they are attached form an optionally substituted C2-C6heterocycloalkyl;
L1 is absent, C1-C4alkylene, C1-C4alkenylene, C1-C4alkynylene, —O—, or —N(Rb)—;
Rb is hydrogen, C1-C4alkyl or C1-C4haloalkyl, —C(═O)R1, —C(═O)—O—R11, S(═O)2R11, or —C(═O)R11;
R2 is hydrogen, halogen, —CN, —OH, —NO2, optionally substituted C1-C4alkyl, optionally substituted C1-C4alkoxy, optionally substituted C1-C4haloalkyl, optionally substituted C1-C4haloalkoxy, optionally substituted C3-C6cycloalkyl, optionally substituted C2-C6heterocycloalkyl, optionally substituted phenyl, or optionally substituted 5- or 6-membered heteroaryl;
L2 is absent or an optionally substituted C1-C4alkylene;
R3 is hydrogen, C1-C4alkyl, or C1-C4haloalkyl;
R4 is hydrogen, optionally substituted C1-C4 alkyl, —C1-C4 alkylene-C(═O)OR11, —C1-C4 alkylene-OR10, or —C1-C4 alkylene-N(Rb)(R10);
R10 is hydrogen, C1-C4alkyl, C1-C4fluoroalkyl, —C(═O)R11, —C(═O)—O—R11, —C(═O)N(R12)R13, S(═O)2R11, or —C(═O)R11; or R10 and Rb are taken together with the N atom to which they are attached to form a C2-C6heterocycle;
or R3 and R4 taken together with the nitrogen to which they are attached form an optionally substituted C2-C6heterocycloalkyl;
R5 and R6 are each independently selected from hydrogen, halogen, —OH, and C1-C4alkyl, or when on the same carbon, R5 and R6 are taken together form an oxo;
R7 is hydrogen, halogen, —CN, —OH, —NO2, —N(R12)—R13, —C(═O)—N(R12)—R13, —NR12C(═O)R11, —C(═O)—O—R11, —O—C(═O)—R11, —SR12, —S(═O)R11, —S(═O)2R11, —N(R12)S(═O)2R11, —S(═O)2—N(R12)—R13, —C(═O)R11, optionally substituted C1-C4alkyl, optionally substituted C1-C4alkoxy, optionally substituted C1-C4haloalkyl, optionally substituted C1-C4haloalkoxy, optionally substituted C3-C6cycloalkyl, optionally substituted C2-C6heterocycloalkyl, optionally substituted phenyl, or optionally substituted 5- or 6-membered heteroaryl;
R8 is hydrogen, —OH, C1-C4alkyl, C1-C4fluoroalkyl, C1-C4alkoxy, C1-C4fluoroalkoxy, or —N(Ra)2;
each R11 is independently selected from the group consisting of optionally substituted C1-C4alkyl, optionally substituted C1-C4fluoroalkyl, optionally substituted C3-C6cycloalkyl, optionally substituted C2-C6heterocycloalkyl, optionally substituted phenyl, and optionally substituted 5- or 6-membered heteroaryl;
each of R12 and R13 is independently selected from the group consisting of hydrogen, optionally substituted C1-C4alkyl, optionally substituted C1-C4fluoroalkyl, optionally substituted C3-C6cycloalkyl, optionally substituted C2-C6heterocycloalkyl, optionally substituted phenyl, and optionally substituted 5- or 6-membered heteroaryl; or R12 and R13, when on the same nitrogen atom, are taken together with the nitrogen atom to which they are attached to form an optionally substituted C2-C6heterocycloalkyl;
n is 1, 2 or 3; and
m is 1, 2, 3 or 4.

### Claim 13 (depends on 12)

The compound of claim 12, or a pharmaceutically acceptable salt or solvate thereof, wherein:
ring A is monocyclic heteroaryl;
R1 is hydrogen, halogen, C1-C4alkyl, C1-C4haloalkyl, or —N(Ra)2;
L1 is absent;
L2 is absent or —CH2—;
R3 is hydrogen or C1-C4alkyl;
R4 is C1-C4 alkyl, —C1-C4 alkylene-OR10, or —C1-C4 alkylene-N(Rb)(R10);
or R3 and R4 taken together with the nitrogen to which they are attached form an optionally substituted C2-C5heterocycloalkyl;
R7 is hydrogen, halogen, —CN, —OH, C1-C4alkyl, C1-C4alkoxy, C1-C4haloalkyl, or C1-C4haloalkoxy; and
m is 1 or 2.

### Claim 14 (depends on 12)

The compound of claim 12, or a pharmaceutically acceptable salt or solvate thereof, wherein:
ring A is C3-C6cycloalkyl;
R1 is hydrogen, halogen, C1-C4alkyl, C1-C4haloalkyl, or —N(Ra)2;
L1 is absent;
L2 is absent or —CH2—;
R3 is hydrogen or C1-C4alkyl;
R4 is C1-C4 alkyl, —C1-C4 alkylene-OR10, or —C1-C4 alkylene-N(Rb)(R10);
or R3 and R4 taken together with the nitrogen to which they are attached form an optionally substituted C2-C5heterocycloalkyl;
R7 is hydrogen, halogen, —CN, —OH, C1-C4alkyl, C1-C4alkoxy, C1-C4haloalkyl, or C1-C4haloalkoxy; and
m is 1 or 2.

### Claim 15 (depends on 12)

The compound of claim 12, or a pharmaceutically acceptable salt or solvate thereof, wherein:
ring B is an N-containing optionally substituted monocyclic heterocycloalkyl.

### Claim 16 (depends on 15)

The compound of claim 15, or a pharmaceutically acceptable salt or solvate thereof, wherein:
ring B is
and
R5 and R6 are each independently selected from hydrogen, halogen, —OH, and C1-C4alkyl, or when on the same carbon, R5 and R6 are taken together form an oxo.

### Claim 17 (depends on 12)

The compound of claim 12, or a pharmaceutically acceptable salt or solvate thereof, wherein:
ring B is an N-containing optionally substituted bicyclic heterocycloalkyl or an N-containing optionally substituted tricyclic heterocycloalkyl.

### Claim 18 (depends on 17)

The compound of claim 17, or a pharmaceutically acceptable salt or solvate thereof, wherein:
ring B is

### Claim 19

A compound that is:
2-({2-(1-Fluoro-cyclopropyl)-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-quinazolin-6-yl}-methyl-amino)-ethanol;
{2-(1-fluoro-cyclopropyl)-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-quinazolin-6-yl}-(2-methoxy-ethyl)-methyl-amine;
{2-(1-fluoro-cyclopropyl)-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-quinazolin-6-yl}-methyl-propyl-amine;
{4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-2-[1-(methyl-propyl-amino)-cyclopropyl]-quinazolin-6-yl})-methyl-propyl-amine;
2-{[4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-2-(1-methyl-cyclopropyl)-quinazolin-6-yl]-methyl-amino)}-ethanol;
N-[4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-2-(1-methyl-cyclopropyl)-quinazolin-6-yl]-N,N′,N′-trimethyl-ethane-1,2-diamine;
2-{[4-[4-(2-dimethylamino-phenyl)-piperidin-1-yl]-2-(1-methyl-cyclopropyl)-quinazolin-6-yl]-methyl-amino}-ethanol;
[4-[4-(2-dimethylamino-phenyl)-piperidin-1-yl]-2-(1-methyl-cyclopropyl)-quinazolin-6-yl]-(2-methoxy-ethyl)-methyl-amine;
N-[4-[4-(2-dimethylamino-phenyl)-piperidin-1-yl]-2-(1-methyl-cyclopropyl)-quinazolin-6-yl]-N,N′,N′-trimethyl-ethane-1,2-diamine;
2-{[4-[4-(2-azetidin-1-yl-phenyl)-piperidin-1-yl]-2-(1-methyl-cyclopropyl)-quinazolin-6-yl]-methyl-amino}-ethanol;
[4-[4-(2-azetidin-1-yl-phenyl)-piperidin-1-yl]-2-(1-methyl-cyclopropyl)-quinazolin-6-yl]-(2-methoxy-ethyl)-methyl-amine;
N-(2-methoxyethyl)-4-(4-(2-methoxyphenyl)piperidin-1-yl)-N-methyl-2-(1-methylcyclopropyl)quinazolin-6-amine;
2-{[4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-2-(1-trifluoromethyl-cyclopropyl)-quinazolin-6-yl]-methyl-amino}-ethanol;
2-{[4-[4-(2-dimethylamino-phenyl)-piperidin-1-yl]-2-(1-trifluoromethyl-cyclopropyl)-quinazolin-6-yl]-methyl-amino}-ethanol;
2-{[4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-2-(1-methyl-cyclopentyl)-quinazolin-6-yl]-methyl-amino)}-ethanol;
{[4-[4-(2-Dimethylamino-phenyl)-piperidin-1-yl]-2-(1-methyl-cyclopentyl)-quinazolin-6-yl]-methyl-amino}-ethanol;
2-{[4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-2-(1-trifluoromethyl-cyclopentyl)-quinazolin-6-yl]-methyl-amino}-ethanol;
2-{[4-[4-(2-dimethylamino-phenyl)-piperidin-1-yl]-2-(1-trifluoromethyl-cyclopentyl)-quinazolin-6-yl]-methyl-amino}-ethanol;
2-({2-(1-fluoro-cyclobutyl)-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-quinazolin-6-yl}-methyl-amino)-ethanol;
2-{[4-[4-(2-dimethylamino-phenyl)-piperidin-1-yl]-2-(1-fluoro-cyclobutyl)-quinazolin-6-yl]-methyl-amino}-ethanol;
2-{[4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-2-(1-trifluoromethyl-cyclobutyl)-quinazolin-6-yl]-methyl-amino}-ethanol;
2-{[4-[4-(2-Dimethylamino-phenyl)-piperidin-1-yl]-2-(1-trifluoromethyl-cyclobutyl)-quinazolin-6-yl]-methyl-amino}-ethanol;
2-{[4-[4-(2-dimethylamino-phenyl)-piperidin-1-yl]-2-(1-methyl-cyclobutyl)-quinazolin-6-yl]-methyl-amino}-ethanol;
2-{[4-[4-(2-Methoxy-phenyl)-piperidin-1-yl]-2-(1-methyl-cyclobutyl)-quinazolin-6-yl]-methyl-amino)}-ethanol;
2-({2-(1-fluoro-cyclopentyl)-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-quinazolin-6-yl}-methyl-amino)-ethanol;
2-{[4-[4-(2-dimethylamino-phenyl)-piperidin-1-yl]-2-(1-fluoro-cyclopentyl)-quinazolin-6-yl]-methyl-amino}-ethanol;
1-{2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-quinazolin-6-yl}-piperidin-4-ol;
{2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-6-(4-methoxy-piperidin-1-yl)-quinazoline;
(1-{2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-quinazolin-6-yl})-piperidin-4-yl)-dimethyl-amine;
1-{2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-quinazolin-6-yl}-pyrrolidin-3-ol;
2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-6-(3-methoxy-pyrrolidin-1-yl)-quinazoline;
(R)-1-{2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-quinazolin-6-yl}-pyrrolidin-3-ol;
(S)-1-(2-cyclopropyl-4-(4-(2-methoxyphenyl)piperidin-1-yl)quinazolin-6-yl)pyrrolidin-3-ol;
(R)-2-cyclopropyl-4-(4-(2-methoxyphenyl)piperidin-1-yl)-6-(3-methoxypyrrolidin-1-yl)quinazoline;
(S)-2-cyclopropyl-4-(4-(2-methoxyphenyl)piperidin-1-yl)-6-(3-methoxypyrrolidin-1-yl)quinazoline;
[(1-{2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-quinazolin-6-yl}-piperidin-4-yl)-methyl-amino]-acetic acid ethyl ester;
4-(4-(2-methoxyphenyl)piperidin-1-yl)-N2,N2,N6-trimethyl-N6-propylquinazoline-2,6-diamine;
4-(4-(2-methoxyphenyl)piperidin-1-yl)-N2,N2-dimethyl-N6,N6-dipropylquinazoline-2,6-diamine;
N2-Cyclobutyl-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-N6-methyl-N6-propyl-quinazoline-2,6-diamine;
2-((2-(cyclobutylamino)-4-(4-(2-methoxyphenyl)piperidin-1-yl) quinazolin-6-yl)(methyl)amino)ethanol;
2-({2-cyclopropyl-4-[6-(2-methoxy-phenyl)-2,6-diaza-spiro [3.3]hept-2-yl]-quinazolin-6-yl}-methyl-amino)-ethanol;
2-((2-cyclopropyl-4-(4-(3-methoxythiophen-2-yl)piperidin-1-yl) quinazolin-6-yl)(methyl)amino)ethanol;
2-((4-(4-cyclohexylpiperidin-1-yl)-2-(1-fluorocyclopropyl) quinazolin-6-yl)(methyl)amino)ethanol;
2-(4-{2-cyclopropyl-6-[(2-hydroxy-ethyl)-methyl-amino]-quinazolin-4-yl}-piperazin-1-yl)-cyclopentanol;
2-{4-[2-cyclopropyl-6-(methyl-propyl-amino)-quinazolin-4-yl]-piperazin-1-yl}-cyclopentanol;
2-(4-{2-cyclopropyl-6-[methyl-(2-morpholin-4-yl-ethyl)-amino]-quinazolin-4-yl}-piperazin-1-yl)-cyclopentanol;
(1-Fluoro-cyclopropyl)-{7-fluoro-6-[(2-hydroxy-ethyl)-methyl-amino]-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-quinazolin-2-yl)}-methanone;
{7-Chloro-6-[(2-hydroxy-ethyl)-methyl-amino]-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-quinazolin-2-yl}-(1-fluoro-cyclopropyl)-methanone;
(S)-1-(2-cyclopropyl-4-(4-(2-methoxyphenyl)piperidin-1-yl)quinazolin-6-yl)pyrrolidin-3-ol;
(S)-2-cyclopropyl-4-(4-(2-methoxyphenyl)piperidin-1-yl)-6-(3-methoxypyrrolidin-1-yl)quinazoline;
(R)-1-{2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-quinazolin-6-yl}-pyrrolidin-3-ol;
(R)-2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-6-(3-methoxy-pyrrolidin-1-yl)-quinazoline;
(S)-1-{2-(1-Fluoro-cyclopropyl)-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-quinazolin-6-yl}-pyrrolidin-3-ol;
(R)-1-{2-(1-Fluoro-cyclopropyl)-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-quinazolin-6-yl}-pyrrolidin-3-ol;
2-((2-(1-fluorocyclopropyl)-4-(4-(2-methoxyphenyl)piperidin-1-yl)quinazolin-6-yl)(methyl)amino)acetic acid;
2-((8-chloro-2-(1-fluorocyclobutyl)-4-(4-(2-methoxyphenyl)piperidin-1-yl)quinazolin-6-yl)(methyl)amino)ethanol;
3-{8-Chloro-2-(1-fluoro-cyclobutyl)-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-quinazolin-6-yl)}-cyclopentanol;
3-{8-Chloro-2-(1-fluoro-cyclobutyl)-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-quinazolin-6-yl)}-cyclopentanol;
2-({2-Cyclopropyl-4-[4-(2-methoxy-cyclopentyl)-piperazin-1-yl]-quinazolin-6-yl)}-methyl-amino)-ethanol;
2-cyclopropyl-4-(4-(2-methoxycyclopentyl)piperazin-1-yl)-N-methyl-N-propylquinazolin-6-amine
2-{[4-(4-Cyclohexyl-piperidin-1-yl)-2-(1-fluoro-cyclopropyl)-quinazolin-6-yl]-methyl-amino}-ethanol
2-({2-(1-Fluoro-cyclopropyl)-4-[4-(2-methoxy-cyclohexyl)-piperidin-1-yl]-quinazolin-6-yl}-methyl-amino)-ethanol;
2-({2-Cyclopropyl-4-[4-(3-methoxy-thiophen-2-yl)-piperidin-1-yl]-quinazolin-6-yl}-methyl-amino)-ethanol;
2-({2-(1-Fluoro-cyclopropyl)-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-pyrido [3,4-d]pyrimidin-6-yl}-methyl-amino)-ethanol;
1-{2-(1-Fluoro-cyclopropyl)-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-pyrido[3,4-d]pyrimidin-6-yl}-pyrrolidin-3-ol;
1-{2-(1-Fluoro-cyclopropyl)-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-pyrido [3,4-d]pyrimidin-6-yl}-pyrrolidin-3-ol;
2-({2-(1-Fluoro-cyclobutyl)-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-pyrido[3,4-d]pyrimidin-6-yl}-methyl-amino)-ethanol;
1-{2-(1-Fluoro-cyclobutyl)-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-pyrido [3,4-d]pyrimidin-6-yl}-pyrrolidin-3-ol;
1-{2-(1-Fluoro-cyclobutyl)-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-pyrido [3,4-d]pyrimidin-6-yl}-pyrrolidin-3-ol;
2-({8-Chloro-2-(1-fluoro-cyclopropyl)-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-quinazolin-6-yl}-methyl-amino)-ethanol;
1-{8-Chloro-2-(1-fluoro-cyclopropyl)-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-quinazolin-6-yl}-pyrrolidin-3-ol;
1-{8-Chloro-2-(1-fluoro-cyclopropyl)-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-quinazolin-6-yl}-pyrrolidin-3-ol;
2-{[8-Fluoro-4-[4-(3-methoxy-pyrazin-2-yl)-piperidin-1-yl]-2-(1-methyl-cyclopropyl)-quinazolin-6-yl]-methyl-amino}-ethanol;
2-{[4-[4-(3-Methoxy-pyrazin-2-yl)-piperidin-1-yl]-2-(1-methyl-cyclopropyl)-quinazolin-6-yl]-methyl-amino}-ethanol;
2-{[2-(1-Fluoro-cyclopropyl)-4-(3-methoxy-3′,4′,5′,6′-tetrahydro-2′H-[2,4′]bipyridinyl-1′-yl)-quinazolin-6-yl]-methyl-amino}-ethanol;
2-{[2-(1-Fluoro-cyclopropyl)-4-(2-methoxy-3′,4′,5′,6′-tetrahydro-2′H-[3,4′]bipyridinyl-1′-yl)-quinazolin-6-yl]-methyl-amino}-ethanol;
2-({2-(1-Fluoro-cyclopropyl)-4-[4-(3-methoxy-pyrazin-2-yl)-piperidin-1-yl]-quinazolin-6-yl}-methyl-amino)-ethanol;
2-({2-(1-Fluoro-cyclopropyl)-4-[4-(3-methoxy-pyridin-2-yl)-piperazin-1-yl]-quinazolin-6-yl}-methyl-amino)-ethanol;
2-{[2-(1-Fluoro-cyclopropyl)-4-(4-methoxy-3′,4′,5′,6′-tetrahydro-2′H-[3,4′]bipyridinyl-1′-yl)-quinazolin-6-yl]-methyl-amino}-ethanol;
2-({2-(1-Fluoro-cyclopropyl)-4-[4-(5-methoxy-pyrimidin-4-yl)-piperidin-1-yl]-quinazolin-6-yl}-methyl-amino)-ethanol;
2-{[2-(1-Fluoro-cyclopropyl)-4-(3′-methoxy-3,4,5,6-tetrahydro-2H-[4,4′]bipyridinyl-1-yl)-quinazolin-6-yl]-methyl-amino}-ethanol;
2-({8-Fluoro-2-(1-fluoro-cyclopropyl)-4-[4-(3-methoxy-pyrazin-2-yl)-piperidin-1-yl]-quinazolin-6-yl}-methyl-amino)-ethanol;
2-{[8-Fluoro-2-(1-fluoro-cyclopropyl)-4-(2-methoxy-3′,4′,5′,6′-tetrahydro-2′H-[3,4′]bipyridinyl-1′-yl)-quinazolin-6-yl]-methyl-amino-}-ethanol;
2-({8-Fluoro-2-(1-fluoro-cyclopropyl)-4-[4-(3-methoxy-pyridin-2-yl)-piperazin-1-yl]-quinazolin-6-yl}-methyl-amino)-ethanol;
2-{[8-Fluoro-2-(1-fluoro-cyclopropyl)-4-(3-methoxy-3′,4′,5′,6′-tetrahydro-2′H-[2,4′]bipyridinyl-1′-yl)-quinazolin-6-yl]-methyl-amino}-ethanol;
2-({8-Fluoro-2-(1-fluoro-cyclopropyl)-4-[4-(5-methoxy-pyrimidin-4-yl)-piperidin-1-yl]-quinazolin-6-yl}-methyl-amino)-ethanol;
2-({2-(1-Fluoro-cyclopropyl)-4-[4-(4-iodo-2-methoxy-phenyl)-piperazin-1-yl]-quinazolin-6-yl}-methyl-amino)-ethanol;
2-({2-(1-Fluoromethyl-cyclopropyl)-4-[4-(3-methoxy-pyrazin-2-yl)-piperidin-1-yl]-quinazolin-6-yl}-methyl-amino)-ethanol;
2-({2-(1-Fluoro-cyclobutyl)-4-[4-(3-methoxy-pyrazin-2-yl)-piperidin-1-yl]-quinazolin-6-yl}-methyl-amino)-ethanol;
1-(6-((2-hydroxyethyl)(methyl)amino)-4-(4-(3-methoxypyrazin-2-yl)piperidin-1-yl)quinazolin-2-yl)cyclobutanol;
(2-(1-Fluoro-cyclopropyl)-4-{4-[2-(2-fluoro-ethoxy)-phenyl]-piperidin-1-yl)-quinazolin-6-yl)-[2-(2-fluoro-ethoxy)-ethyl]-methyl-amine;
{2-(1-Fluoro-cyclopropyl)-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-quinazolin-6-yl}-[2-(2-fluoro-ethoxy)-ethyl]-methyl-amine;
2-{1-[6-{[2-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-methyl-amino}-2-(1-fluoro-cyclopropyl)-quinazolin-4-yl]-piperidin-4-yl}-phenol;
2-[(2-(1-Fluoro-cyclopropyl)-4-{4-[2-(2-fluoro-ethoxy)-phenyl]-piperidin-1-yl}-quinazolin-6-yl)-methyl-amino]-ethanol;
or a pharmaceutically acceptable salt or solvate thereof.

### Claim 20 (depends on 1)

A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.

### Claim 21 (depends on 1)

A method of modulating neurotensin or neurotensin receptor 1 in a subject, comprising administering to the subject a compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof.