Small molecule agonists of neurotensin receptor 1

1. A compound of Formula I, or a pharmaceutically acceptable salt, solvate, or tautomer thereof:

wherein:

A is A 1 , —O-A 1 , —NH-A 1 , —C(═O)-A 1 , or —S(═O) 2 -A 1 ; A 1 is selected from the group consisting of optionally substituted phenyl, optionally substituted naphthyl, optionally substituted 5-membered heteroaryl, optionally substituted 6-membered heteroaryl, optionally substituted 9-membered heteroaryl and optionally substituted 10-membered heteroaryl; wherein optional substituents for A are selected from the group consisting of hydrogen, halogen, —CN, —OH, —NO 2 , —N(R 13 )—R 14 , C(═O)—N(R 13 )—R 14 NR 13 C(═O)R 15 , —C(═O)—O—R 13 , —O—C(═O)—R 15 , —SR 13 , —S(═O)R 15 , —S(═O) 2 R 15 , —N(R 3 )S(═O) 2 R 15 , —S(═O) 2 —N(R 13 )—R 14 , —C(═O)R 13 , optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted alkoxy, optionally substituted haloalkyl, optionally substituted haloalkoxy, optionally substituted phenyl, and optionally substituted 5- or 6-membered heteroaryl;

B is selected from the group consisting of optionally substituted alkyl, and optionally substituted cycloalkyl;

Y is selected from optionally substituted heterocyloalkyl, optionally substituted spiroheterocyloalkyl, and —NR 2 (CH 2 )NR 3 —;

n is 2, 3, 4, 5, or 6;

R 2 is H or alkyl;

R 3 is H or alkyl;

X 1 is N or C(R 1 );

X 2 is N or C(R 1 );

X 3 is N or C(R 4 );

X 4 is N or C(R 5 );

X 5 is N or C(R 6 );

X 6 is N or C(R 7 );

each R 1 is independently selected from the group consisting of hydrogen, halogen, —CN, —OH, —NO 2 , optionally substituted alkyl, optionally substituted alkoxy, optionally substituted haloalkyl, and optionally substituted haloalkoxy;

each of R 4 , R 5 , R 6 , and R 7 is independently selected from the group consisting of hydrogen, halogen, —CN, —OH, —NO 2 , —N(R 13 )—R 14 , —C(═O)—N(R 13 )—R 14 , —NR 13 C(═O)R 15 , —C(═O)—O—R 13 , —O—C(═O)—R 15 , —SR 13 , —S(═O)R 15 , —S(═O) 2 R 15 , —N(R 13 )S(═O) 2 R 15 , —S(═O) 2 —N(R 13 )—R 14 , —C(═O)R 13 , optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted alkoxy, optionally substituted haloalkyl, optionally substituted haloalkoxy, optionally substituted phenyl, and optionally substituted 5- or 6-membered heteroaryl;

or R 5 and R 6 are taken together with the atoms connecting R 5 and R 6 to form an optionally substituted heterocycloalkyl;

each of R 13 and R 14 is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted alkoxy, optionally substituted haloalkyl, optionally substituted haloalkoxy, optionally substituted phenyl, and optionally substituted 5- or 6-membered heteroaryl;

or R 13 and R 14 , when on the same nitrogen atom, are taken together with the nitrogen atom to which they are attached to form an optionally substituted heterocycloalkyl;

R 15 is selected from the group consisting of optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted alkoxy, optionally substituted haloalkyl, optionally substituted haloalkoxy, optionally substituted phenyl, and optionally substituted 5- or 6-membered heteroaryl;

wherein a heteroaryl comprises one to six heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur;

wherein a heterocycloalkyl comprises from 2 to 10 carbons in the ring and one to 6 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur.

2. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or tautomer thereof, wherein:

X 1 is C(R 1 ); and X 2 is C(R 1 ); or

X 1 is N; and X 2 is C(R 1 ); or

X 1 is C(R 1 ); and X 2 is N; or

X 1 is N; and X 2 is N; or

X 3 is N; X 4 is C(R 5 ); X 5 is C(R 6 ); and X 6 is N or C(R 7 ); or

X 3 is C(R 4 ); X 4 is N; X 5 is C(R 6 ); and X 6 is C(R 7 ); or

X 3 is C(R 4 ); X 4 is C(R 5 ); X 5 is N; and X 6 is C(R 7 ); or

X 3 is N or C(R 4 ); X 4 is C(R 5 ); X 5 is C(R 6 ); and X 6 is N; or

X 3 is C(R 4 ); X 4 is C(R 5 ); X 5 is C(R 6 ); and X 6 is C(R 7 ).

3. The compound of claim 1 , wherein the compound of Formula I has the following structure of Formula II, or a pharmaceutically acceptable salt, solvate, or tautomer thereof:

4. The compound of claim 3 , or a pharmaceutically acceptable salt, solvate, or tautomer thereof, wherein:

Y is selected from optionally substituted 5-, 6-, 7-, or 8-membered heterocyloalkyl, optionally substituted spiroheterocyloalkyl, and —NR 2 (CH 2 ) n NR 3 —.

5. The compound of claim 4 , or a pharmaceutically acceptable salt, solvate, or tautomer thereof, wherein:

Y is an optionally substituted 6-membered heterocyloalkyl that is an optionally substituted piperidinyl or optionally substituted piperazinyl.

6. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or tautomer thereof, wherein:

7. The compound of claim 3 , wherein the compound has the following structure of Formula III or Formula V, or a pharmaceutically acceptable salt, solvate, or tautomer thereof:

8. The compound of claim 7 , or a pharmaceutically acceptable salt, solvate, or tautomer thereof, wherein:

A is selected from the group consisting of optionally substituted phenyl, optionally substituted naphthyl, optionally substituted furanyl, optionally substituted pyrrolyl, optionally substituted oxazolyl, optionally substituted thiazolyl, optionally substituted imidazolyl, optionally substituted pyrazolyl, optionally substituted triazolyl, optionally substituted tetrazolyl, optionally substituted isoxazolyl, optionally substituted isothiazolyl, optionally substituted oxadiazolyl, optionally substituted thiadiazolyl, optionally substituted pyridinyl, optionally substituted pyrimidinyl, optionally substituted pyrazinyl, optionally substituted pyridazinyl, optionally substituted triazinyl, optionally substituted quinolinyl, optionally substituted isoquinolinyl, optionally substituted quinazolinyl, optionally substituted quinoxalinyl, optionally substituted naphthyridinyl, optionally substituted indolyl, optionally substituted indazolyl, optionally substituted benzoxazolyl, optionally substituted benzisoxazolyl, optionally substituted benzofuranyl, benzothienyl, optionally substituted benzothiazolyl, optionally substituted benzimidazolyl, optionally substituted purinyl, optionally substituted cinnolinyl, optionally substituted phthalazinyl, and optionally substituted pteridinylene.

9. The compound of claim 8 , wherein the compound has the following structure of Formula VII or Formula IX, or a pharmaceutically acceptable salt, solvate, or tautomer thereof:

wherein:

each of R 8 , R 9 , R 10 , R 11 , and R 12 is independently selected from the group consisting of hydrogen, halogen, —CN, —OH, —NO 2 , —N(R 13 )—R 14 , —C(═O)—N(R 13 )—R 14 , —NR 13 C(═O)R 15 , —C(═O)—O—R 13 , —O—C(═O)—R 15 , —SR 13 , —S(═O)R 15 , —S(═O) 2 R 15 , —N(R 13 )S(═O) 2 R 15 , —S(═O) 2 —N(R 13 )—R 14 , —C(═O)R 13 , optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted alkoxy, optionally substituted haloalkyl, optionally substituted haloalkoxy, optionally substituted phenyl, and optionally substituted 5- or 6-membered heteroaryl.

10. The compound of claim 7 , or a pharmaceutically acceptable salt, solvate, or tautomer thereof, wherein:

B is an optionally substituted cycloalkyl.

11. The compound of claim 10 , wherein the compound has the following structure of Formula XI or Formula XIII, or a pharmaceutically acceptable salt, solvate, or tautomer thereof:

wherein:

m is 1, 2, 3, 4, 5, 6, or 7.

12. The compound of claim 11 , or a pharmaceutically acceptable salt, solvate, or tautomer thereof, wherein:

m is 1 or 2;

R 4 is hydrogen;

R 7 is hydrogen; and

at least two of R 8 , R 9 , R 10 , R 11 , and R 12 is hydrogen.

13. The compound of claim 1 , wherein the compound is

2-cyclobutyl-6,7-dimethoxy-4-(4-(2-methoxyphenyl)piperazin-1-yl)quinazoline;

2-phenyl-6,7-dimethoxy-4-(4-(2-methoxyphenyl)piperazin-1-yl)quinazoline;

2-phenyl-6,7-dimethoxy-4-(4-(phenyl)piperazin-1-yl)quinazoline;

2-phenyl-6,7-dimethoxy-4-(4-(2-fluorophenyl)piperazin-1-yl)quinazoline;

2-phenyl-6,7-dimethoxy-4-(4-(4-fluorophenyl)piperazin-1-yl)quinazoline;

2-phenyl-6,7-dimethoxy-4-(4-(2-chlorophenyl)piperazin-1-yl)quinazoline;

2-phenyl-6-ethoxy-7-methoxy-4-(4-(2-methoxyphenyl)piperazin-1-yl)quinazoline;

2-phenyl-6-ethoxy-7-methoxy-4-(4-(phenyl)piperazin-1-yl)quinazoline;

2-phenyl-6-ethoxy-7-methoxy-4-(4-(2-fluorophenyl)piperazin-1-yl)quinazoline;

or a pharmaceutically acceptable salt, solvate, or tautomer thereof.

14. The compound of claim 1 , wherein the compound has the following structure, or a pharmaceutically acceptable salt, solvate, or tautomer thereof:

wherein,

A is phenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2,4-dimethoxyphenyl, 2-methylphenyl, 2,6-dimethylphenyl, 2-fluorophenyl, 2-chlorophenyl, pyridin-2-yl, or 2-nitrophenyl.

15. The compound of claim 1 , wherein the compound is

2-cyclobutyl-6,7-dimethoxy-4-(4-(2-methoxyphenyl)piperazin-1-yl)quinazoline;

2-cyclobutyl-6-methoxy-4-(4-(2-methoxyphenyl)piperazin-1-yl)quinazoline;

2-cyclobutyl-7-methoxy-4-(4-(2-methoxyphenyl)piperazin-1-yl)quinazoline;

2-cyclobutyl-4-(4-(2-methoxyphenyl)piperazin-1-yl)quinazoline;

6-cyclobutyl-8-(4-(2-methoxyphenyl)piperazin-1-yl)-[1,3]dioxolo [4,5-g]quinazoline;

2-cyclopropyl-6-methoxy-4-(4-(2-methoxyphenyl)piperazin-1-yl)quinazoline;

or a pharmaceutically acceptable salt, solvate, or tautomer thereof.

16. The compound of claim 1 , wherein the compound has the following structure, or a pharmaceutically acceptable salt, solvate, or tautomer thereof:

wherein,

A is 2-methoxyphenyl, 2-ethoxyphenyl, 2-chlorophenyl, —SO 2 -phenyl, 4-methylbenzyl, 2-methoxybenzyl, benzoyl, or 2-methoxybenzoyl.

17. A compound that is:

2-cyclopropyl-4-[4-(4-fluoro-2-methoxy-phenyl)-piperazin-1-yl]-6,7-dimethoxy-quinazoline;

2-cyclopropyl-6,7-dimethoxy-4-[4-(2-methoxy-4-trifluoromethoxy-phenyl)-piperazin-1-yl]-quinazoline;

4-[4-(4-chloro-2-methoxy-phenyl)-piperazin-1-yl]-2-cyclopropyl-6,7-dimethoxy-quinazoline;

2-cyclopropyl-6,7-dimethoxy-4-[4-(2-methoxy-4-nitro-phenyl)-piperazin-1-yl]-quinazoline;

4-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-3-methoxy-phenylamine;

4-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-3-methoxy-benzonitrile;

4-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-3-methoxy-benzoic acid;

4-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-3-methoxy-benzamide;

{4-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-3-methoxy-phenyl}-dimethyl-amine;

2-cyclopropyl-6,7-dimethoxy-4-[4-(2-methoxy-4-trifluoromethyl-phenyl)-piperazin-1-yl]-quinazoline;

2-cyclopropyl-4-[4-(2,4-dimethoxy-phenyl)-piperazin-1-yl]-6,7-dimethoxy-quinazoline;

2-cyclopropyl-6,7-dimethoxy-4-[4-(2-methoxy-5-methyl-phenyl)-piperazin-1-yl]-quinazoline;

2-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-benzonitrile;

2-cyclopropyl-6,7-dimethoxy-4-[4-(2-methoxy-5-nitro-phenyl)-piperazin-1-yl]-quinazoline;

3-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-4-methoxy-phenylamine;

N-{3-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-4-methoxy-phenyl}-acetamide;

N-{3-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-4-methoxy-phenyl}-methanesulfonamide;

{3-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-4-methoxy-phenyl}-dimethyl-amine;

{3-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-4-methoxy-phenyl}-methyl-amine;

2-cyclopropyl-4-[4-(2,3-dichloro-phenyl)-piperazin-1-yl]-6,7-dimethoxy-quinazoline;

2-cyclopropyl-4-[4-(2,4-dichloro-phenyl)-piperazin-1-yl]-6,7-dimethoxy-quinazoline;

3-chloro-4-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-benzonitrile;

4-[4-(2-chloro-4-nitro-phenyl)-piperazin-1-yl]-2-cyclopropyl-6,7-dimethoxy-quinazoline;

3-chloro-4-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-benzoic acid;

3-chloro-4-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-benzamide;

3-chloro-4-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-phenylamine;

N-{3-chloro-4-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-phenyl}-acetamide;

N-{3-chloro-4-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-phenyl}-methanesulfonamide;

3-chloro-4-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-benzoic acid;

4-[4-(2-chloro-4-fluoro-phenyl)-piperazin-1-yl]-2-cyclopropyl-6,7-dimethoxy-quinazoline;

4-[4-(2-chloro-4-trifluoromethyl-phenyl)-piperazin-1-yl]-2-cyclopropyl-6,7-dimethoxy-quinazoline;

4-[4-(2-chloro-4-methyl-phenyl)-piperazin-1-yl]-2-cyclopropyl-6, 7-dimethoxy-quinazoline;

4-[4-(2-chloro-4-methoxy-phenyl)-piperazin-1-yl]-2-cyclopropyl-6,7-dimethoxy-quinazoline;

2-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-benzonitrile;

2-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-5-methoxy-benzonitrile;

5-chloro-2-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-benzonitrile;

2-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-5-nitro-benzonitrile;

5-amino-2-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-benzonitrile;

2-cyclopropyl-6,7-dimethoxy-4-[4-(2-nitro-phenyl)-piperazin-1-yl]-quinazoline;

2-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-phenylamine;

2-(4-(2-cyclopropyl-6,7-dimethoxyquinazolin-4-yl)piperazin-1-yl)-N-ethylaniline;

{2-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-phenyl}-dimethyl-amine;

{2-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-phenyl}-diethyl-amine;

4-[4-(2-aziridin-1-yl-phenyl)-piperazin-1-yl]-2-cyclopropyl-6,7-dimethoxy-quinazoline;

4-[4-(4-benzyloxy-2-nitro-phenyl)-piperazin-1-yl]-2-cyclopropyl-6,7-dimethoxy-quinazoline;

3-amino-4-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-phenol;

2-cyclopropyl-6,7-dimethoxy-4-[4-(4-methoxy-2-nitro-phenyl)-piperazin-1-yl]-quinazoline;

2-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-5-fluoro-phenylamine;

2-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-5-methoxy-phenylamine;

{5-bromo-2-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-phenyl}-dimethyl-amine;

{2-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-5-fluoro-phenyl}-dimethyl-amine;

{5-chloro-2-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-phenyl}-dimethyl-amine;

{2-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-5-methoxy-phenyl}-dimethyl-amine;

4-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-3-dimethylamino-benzoic acid;

{2-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-phenyl)}-phenyl-amine;

2-cyclopropyl-6,7-dimethoxy-4-[4-(2-morpholin-4-yl-phenyl)-piperazin-1-yl]-quinazoline;

2-cyclopropyl-6,7-dimethoxy-4-[4-(2-pyrrolidin-1-yl-phenyl)-piperazin-1-yl]-quinazoline;

4-[4-(2-azetidin-1-yl-phenyl)-piperazin-1-yl]-2-cyclopropyl-6,7-dimethoxy-quinazoline;

2-cyclopropyl-6,7-dimethoxy-4-[4-(2-piperidin-1-yl-phenyl)-piperazin-1-yl]-quinazoline;

2-Cyclopropyl-6,7-dimethoxy-4-{4-[2-(4-methyl-piperazin-1-yl)-phenyl]-piperazin-1-yl}-quinazoline;

5-amino-2-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-phenol;

4-(4-(2-cyclopropyl-6,7-dimethoxyquinazolin-4-yl)piperazin-1-yl)-N,N-dimethylaniline;

{4-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-phenyl}-diethyl-amine;

3-(4-(2-cyclopropyl-6,7-dimethoxyquinazolin-4-yl)piperazin-1-yl)-N,N-dimethylaniline;

{3-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-phenyl}-diethyl-amine;

N-(2-cyclopropyl-6,7-dimethoxy-quinazolin-5-yl)-N′-(2-methoxy-phenyl)-ethane-1,2-diamine;

N′-(2-cyclopropyl-6,7-dimethoxy-quinazolin-5-yl)-N-(2-methoxy-phenyl)-N-methyl-ethane-1,2-diamine;

2-cyclopropyl-6,7-dimethoxy-4-[4-(2-methoxy-phenyl)-2-methyl-piperazin-1-yl]-quinazoline;

N-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-N′-phenyl-ethane-1,2-diamine;

N-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-N′-(2-methoxy-phenyl)-propane-1,3-diamine;

N-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-N′-(2-methoxy-phenyl)-N,N′-dimethyl-ethane-1,2-diamine;

2-cyclopropyl-6,7-dimethoxy-4-[4-(2-methoxy-phenyl)-[1,4]diazepan-1-yl]-quinazoline;

[1-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperidin-4-yl]-(2-methoxy-phenyl)-amine;

2-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-ylamino)-N-(2-methoxy-phenyl)-acetamide;

2-Cyclopropyl-6,7-dimethoxy-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-quinazoline;

{2-[1-(2-Cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperidin-4-yl]-phenyl}-dimethyl-amine;

2-cyclopropyl-6,7-dimethoxy-4-[4-(2-methoxy-phenyl)-3,6-dihydro-2H-pyridin-1-yl]-quinazoline;

2-cyclopropyl-6,7-dimethoxy-4-(3-phenyl-pyrrolidin-1-yl)-quinazoline;

2-cyclopropyl-6,7-dimethoxy-4-[3-(2-methoxy-phenyl)-pyrrolidin-1-yl]-quinazoline;

{2-[1-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-pyrrolidin-3-yl]-phenyl}-dimethyl-amine;

2-cyclopropyl-6, 7-dimethoxy-4-[3-(3-methoxy-phenyl)-cyclopentyl]-quinazoline;

{3-[1-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-pyrrolidin-3-yl]-phenyl}-dimethyl-amine;

1-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-3-phenyl-pyrrolidin-3-ol;

1-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-3-(2-dimethylamino-phenyl)-pyrrolidin-3-ol;

1-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-3-(3-methoxy-phenyl)-pyrrolidin-3-ol;

2-cyclopropyl-4-(3-fluoro-3-phenyl-pyrrolidin-1-yl)-6,7-dimethoxy-quinazoline;

{2-[1-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-3-fluoro-pyrrolidin-3-yl]-phenyl}-dimethyl-amine;

2-cyclopropyl-4-[3-fluoro-3-(3-methoxy-phenyl)-pyrrolidin-1-yl]-6,7-dimethoxy-quinazoline;

2-cyclopropyl-6,7-dimethoxy-4-(3-methyl-4-phenyl-piperazin-1-yl)-quinazoline;

2-cyclopropyl-6,7-dimethoxy-4-[1-(2-methoxy-phenyl)-piperidin-4-yl]-quinazoline;

6,7-dimethoxy-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-2-piperidin-4-yl-quinazoline;

6,7-dimethoxy-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-2-(1-methyl-piperidin-4-yl)-quinazoline;

6,7-dimethoxy-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-2-(4-methyl-cyclohexyl)-quinazoline;

4-{6,7-dimethoxy-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinazolin-2-yl}-piperidine-1-carboxylic acid benzyl ester;

6,7-dimethoxy-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-2-(tetrahydro-pyran-4-yl)-quinazoline;

6,7-dimethoxy-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-2-(tetrahydro-furan-3-yl)-quinazoline;

6,7-dimethoxy-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-2-(2-methyl-cyclopropyl)-quinazoline;

cis-6,7-dimethoxy-2-(4-methoxy-cyclohexyl)-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinazoline;

trans-6,7-dimethoxy-2-(4-methoxy-cyclohexyl)-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinazoline;

6,7-dimethoxy-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-2-(4-methyl-pyrrolidin-3-yl)-quinazoline;

2-(1,4-dimethyl-pyrrolidin-3-yl)-6,7-dimethoxy-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinazoline;

6,7-dimethoxy-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-2-pyrrolidin-3-yl-quinazoline;

6,7-dimethoxy-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-2-(1-methyl-pyrrolidin-3-yl)-quinazoline;

2-((1R,3R)-3-chloro-3-methylcyclobutyl)-6,7-dimethoxy-4-(4-(2-methoxyphenyl)piperazin-1-yl)quinazoline;

2-((1S,3S)-3-chloro-3-methylcyclobutyl)-6,7-dimethoxy-4-(4-(2-methoxyphenyl)piperazin-1-yl)quinazoline;

6,7-dimethoxy-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-2-(3-methyl-cyclobutyl)-quinazoline;

2-cyclohexyl-6,7-dimethoxy-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinazoline;

2-tert-Butyl-6,7-dimethoxy-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinazoline;

2-tert-Butyl-6,7-dimethoxy-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-quinazoline;

6,7-dimethoxy-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-2-(1-methyl-cyclopropyl)-quinazoline;

6,7-dimethoxy-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-2-(1-methyl-cyclopropyl)-quinazoline;

6,7-dimethoxy-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-2-(1-trifluoromethyl-cyclopropyl)-quinazoline;

6,7-dimethoxy-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-2-(1-trifluoromethyl-cyclopropyl)-quinazoline;

[4-[4-(2-Methoxy-phenyl)-piperidin-1-yl]-2-(1-methyl-cyclopropyl)-quinazolin-6-yl]-methyl-(2-morpholin-4-yl-ethyl)-amine;

7-chloro-2-cyclopropyl-6-methoxy-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinazoline;

2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-pyrido[2,3-d]pyrimidine;

2-cyclopropyl-6, 8-dimethoxy-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinazoline;

2-cyclopropyl-6-methoxy-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-7-methyl-quinazoline;

2-cyclopropyl-7-fluoro-6-methoxy-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinazoline;

6-bromo-2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinazoline;

2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinazolin-6-yl}-dimethylamine;

6-bromo-2-cyclopropyl-7-fluoro-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinazoline;

{2-cyclopropyl-7-fluoro-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinazolin-6-yl}-dimethyl-amine;

{2-cyclopropyl-7-fluoro-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinazolin-6-yl}-diethyl-amine;

6-bromo-7-chloro-2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinazoline;

{7-chloro-2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinazolin-6-yl}-dimethyl-amine;

{7-chloro-2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinazolin-6-yl}-diethyl-amine;

6-bromo-2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-7-methyl-quinazoline;

{2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-7-methyl-quinazolin-6-yl}-dimethyl-amine;

{2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-7-methyl-quinazolin-6-yl}-ethyl-methyl-amine;

6-bromo-2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-7-methyl-quinazoline;

{2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-7-methyl-quinazolin-6-yl}-diethyl-amine;

2-cyclopropyl-6-methoxy-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-pyrido [3,4-d]pyrimidine;

6-bromo-2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-7-methyl-quinazoline;

{2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-7-methyl-quinazolin-6-yl}-diethyl-amine;

{2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinazolin-7-yl)}-dimethyl-amine;

{2-cyclopropyl-4-[4-(2, 5-dimethoxy-phenyl)-piperazin-1-yl]-quinazolin-6-yl}-dimethyl-amine;

2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-6-piperidin-1-yl-quinazoline;

{2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinazolin-6-yl)}-diethyl-amine;

2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-6-morpholin-4-yl-quinazoline;

2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-6-pyrrolidin-1-yl-quinazoline;

{2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinazolin-6-yl)}-phenyl-amine;

{2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-quinazolin-6-yl)}-dimethyl-amine;

{2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-quinazolin-6-yl)}-ethyl-methyl-amine;

{7-chloro-2-cyclopropyl-4-[4-(2-methoxyphenyl)piperidyl]quinazolin-6-yl}dimethylamine;

2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-6-piperazin-1-yl-quinazoline;

2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-6-(4-methyl-piperazin-1-yl)-quinazoline;

2-cyclopropyl-6,7-difluoro-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinazoline;

{2-cyclopropyl-6-fluoro-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinazolin-7-yl}-dimethyl-amine;

{2-cyclopropyl-6-fluoro-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinazolin-7-yl}-diethyl-amine;

2-cyclopropyl-6-fluoro-7-methoxy-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinazoline;

{2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinazolin-6-yl}-methyl-propyl-amine;

{2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinazolin-6-yl)}-methyl-(2-morpholin-4-yl-ethyl)-amine;

2-cyclopropyl-4-(4-(2-methoxyphenyl)piperazin-1-yl)-N-methyl-N-(2-morpholinoethyl)quinazolin-6-amine;

2,2′-((2-cyclopropyl-4-(4-(2-methoxyphenyl)piperazin-1-yl)quinazolin-6-yl)azanediyl)diethanol;

2-({2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinazolin-6-yl)}-methyl-amino)-ethanol;

{2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinazolin-6-yl)}-(2-methoxy-ethyl)-methyl-amine;

2-({2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-quinazolin-6-yl)}-methyl-amino)-ethanol;

{2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-quinazolin-6-yl)}-(2-methoxy-ethyl)-methyl-amine;

{2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-quinazolin-6-yl}-methyl-propyl-amine;

{2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperidin-1-yl]-quinazolin-6-yl)}-methyl-(2-morpholin-4-yl-ethyl)-amine;

2-cyclopropyl-5, 8-dimethoxy-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinazoline;

2-cyclopropyl-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinazoline;

2-cyclopropyl-5,6-dimethoxy-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinazoline;

2-cyclopropyl-5-methoxy-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinazoline;

2-cyclopropyl-8-methoxy-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinazoline;

2-cyclopropyl-6,7-dimethoxy-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinoline;

3-cyclopropyl-6,7-dimethoxy-1-[4-(2-methoxy-phenyl)-piperazin-1-yl]-isoquinoline;

3-chloro-4-(4-(2-cyclopropyl-6-(dimethylamino)quinazolin-4-yl)piperazin-1-yl)benzonitrile;

3-chloro-4-[4-(2-cyclopropyl-6-dimethylamino-quinazolin-4-yl)-piperazin-1-yl]-benzamide;

3-{3-chloro-4-[4-(2-cyclopropyl-6-dimethylamino-quinazolin-4-yl)-piperazin-1-yl]-phenyl}-1,1-dimethyl-urea;

6-bromo-2-cyclopropyl-4-[4-(2, 5-dimethoxy-phenyl)-piperazin-1-yl]-quinazoline;

{2-cyclopropyl-4-[4-(2,5-dimethoxy-phenyl)-piperazin-1-yl]-quinazolin-6-yl}-dimethyl-amine;

6-bromo-2-cyclopropyl-4-[4-(2-methoxy-5-methyl-phenyl)-piperazin-1-yl]-quinazoline;

{2-cyclopropyl-4-[4-(2-methoxy-5-methyl-phenyl)-piperazin-1-yl]-quinazolin-6-yl}-dimethyl-amine;

6-bromo-2-cyclopropyl-4-[4-(4-fluoro-2-methoxy-phenyl)-piperazin-1-yl]-quinazoline;

{2-cyclopropyl-4-[4-(4-fluoro-2-methoxy-phenyl)-piperazin-1-yl]-quinazolin-6-yl}-dimethyl-amine;

4-[4-(6-bromo-2-cyclopropyl-quinazolin-4-yl)-piperazin-1-yl]-3-methoxy-benzonitrile;

4-[4-(2-cyclopropyl-6-dimethylamino-quinazolin-4-yl)-piperazin-1-yl]-3-methoxy-benzonitrile;

6-bromo-2-cyclopropyl-4-[4-(2-methoxy-4-trifluoromethoxy-phenyl)-piperazin-1-yl]-quinazoline;

{2-cyclopropyl-4-[4-(2-methoxy-4-trifluoromethoxy-phenyl)-piperazin-1-yl]-quinazolin-6-yl}-dimethyl-amine;

6-bromo-4-[4-(2-chloro-4-fluoro-phenyl)-piperazin-1-yl]-2-cyclopropyl-quinazoline;

{4-[4-(2-chloro-4-fluoro-phenyl)-piperazin-1-yl]-2-cyclopropyl-quinazolin-6-yl}-dimethyl-amine;

6-bromo-4-[4-(2-chloro-4-methyl-phenyl)-piperazin-1-yl]-2-cyclopropyl-quinazoline;

{4-[4-(2-chloro-4-methyl-phenyl)-piperazin-1-yl]-2-cyclopropyl-quinazolin-6-yl}-dimethyl-amine;

6-bromo-4-[4-(4-chloro-2-methoxy-phenyl)-piperazin-1-yl]-2-cyclopropyl-quinazoline;

{4-[4-(4-chloro-2-methoxy-phenyl)-piperazin-1-yl]-2-cyclopropyl-quinazolin-6-yl}-dimethyl-amine;

6-bromo-2-cyclopropyl-4-[4-(4-methoxy-phenyl)-piperazin-1-yl]-quinazoline;

{2-cyclopropyl-4-[4-(4-methoxy-phenyl)-piperazin-1-yl]-quinazolin-6-yl}-dimethyl-amine;

6-bromo-2-cyclopropyl-4-[4-(3-methoxy-phenyl)-piperazin-1-yl]-quinazoline;

{2-cyclopropyl-4-[4-(3-methoxy-phenyl)-piperazin-1-yl]-quinazolin-6-yl}-dimethyl-amine;

6-bromo-2-cyclopropyl-4-(4-o-tolyl-piperazin-1-yl)-quinazoline;

[2-cyclopropyl-4-(4-o-tolyl-piperazin-1-yl)-quinazolin-6-yl]-dimethyl-amine;

6-bromo-2-cyclopropyl-4-[4-(2-fluoro-phenyl)-piperazin-1-yl]-quinazoline;

6-bromo-4-[4-(2-chloro-phenyl)-piperazin-1-yl]-2-cyclopropyl-quinazoline;

{2-cyclopropyl-4-[4-(2-fluoro-phenyl)-piperazin-1-yl]-quinazolin-6-yl}-dimethyl-amine;

{4-[4-(2-chloro-phenyl)-piperazin-1-yl]-2-cyclopropyl-quinazolin-6-yl}-dimethyl-amine;

2-[4-(6-Bromo-2-cyclopropyl-quinazolin-4-yl)-piperazin-1-yl]-benzonitrile;

2-[4-(2-cyclopropyl-6-dimethylamino-quinazolin-4-yl)-piperazin-1-yl]-benzonitrile;

2-[4-(2-cyclopropyl-6-dimethylamino-quinazolin-4-yl)-piperazin-1-yl]-benzamide;

{4-[4-(2-azetidin-1-yl-phenyl)-piperazin-1-yl]-2-cyclopropyl-quinazolin-6-yl}-dimethyl-amine;

{4-[4-(2-azetidin-1-yl-phenyl)-piperazin-1-yl]-2-cyclopropyl-quinazolin-6-yl}-ethyl-methyl-amine;

{4-[4-(2-azetidin-1-yl-phenyl)-piperidin-1-yl]-2-cyclopropyl-quinazolin-6-yl}-dimethyl-amine;

2-cyclopropyl-6,7-dimethoxy-4-(4-(2-methoxyphenyl)piperazin-1-yl)quinazoline;

6,7-dimethoxy-4-(4-(2-methoxyphenyl)piperazin-1-yl)-2-methylquinazoline;

2-benzyl-6,7-dimethoxy-4-(4-(2-methoxyphenyl)piperazin-1-yl)quinazoline;

2-ethyl-6,7-dimethoxy-4-(4-(2-methoxyphenyl)piperazin-1-yl)quinazoline;

6,7-dimethoxy-4-(4-(2-methoxyphenyl)piperazin-1-yl)-2-propylquinazoline;

2-isopropyl-6,7-dimethoxy-4-(4-(2-methoxyphenyl)piperazin-1-yl)quinazoline;

2-isobutyl-6,7-dimethoxy-4-(4-(2-methoxyphenyl)piperazin-1-yl)quinazoline;

6,7-dimethoxy-4-(4-(2-methoxyphenyl)piperazin-1-yl)-2-vinylquinazoline;

6,7-dimethoxy-4-(4-(2-methoxyphenyl)piperazin-1-yl)-2-(2-(4-(2-methoxyphenyl)piperazin-1-yl)ethyl)quinazoline;

2-cyclopentyl-6,7-dimethoxy-4-(4-(2-methoxyphenyl)piperazin-1-yl)quinazoline;

2-(cyclopropylmethyl)-6,7-dimethoxy-4-(4-(2-methoxyphenyl)piperazin-1-yl)quinazoline;

2-(6,7-dimethoxy-4-(4-(2-methoxyphenyl)piperazin-1-yl)quinazolin-2-yl)-N,N-dimethylethanamine;

2-cyclobutyl-6,7-dimethoxy-4-(4-(2-methoxyphenyl)piperazin-1-yl)quinazoline;

2-cyclobutyl-6,7-dimethoxy-4-(4-phenylpiperazin-1-yl)quinazoline;

2-cyclobutyl-6,7-dimethoxy-4-(4-(o-tolyl)piperazin-1-yl)quinazoline;

2-cyclobutyl-4-(4-(2-fluorophenyl)piperazin-1-yl)-6,7-dimethoxyquinazoline;

4-(4-(2-chlorophenyl)piperazin-1-yl)-2-cyclobutyl-6,7-dimethoxyquinazoline;

2-cyclobutyl-6,7-dimethoxy-4-(4-(pyridin-2-yl)piperazin-1-yl)quinazoline;

2-cyclobutyl-6,7-dimethoxy-4-(4-(2-nitrophenyl)piperazin-1-yl)quinazoline;

2-cyclobutyl-6,7-dimethoxy-4-(4-(3-methoxyphenyl)piperazin-1-yl)quinazoline;

2-cyclobutyl-6,7-dimethoxy-4-(4-(4-methoxyphenyl)piperazin-1-yl)quinazoline;

2-cyclobutyl-4-(4-(2,4-dimethoxyphenyl)piperazin-1-yl)-6,7-dimethoxyquinazoline;

2-cyclobutyl-4-(4-(2, 6-dimethylphenyl)piperazin-1-yl)-6,7-dimethoxyquinazoline;

2-cyclobutyl-6-methoxy-4-(4-(2-methoxyphenyl)piperazin-1-yl)quinazoline;

2-cyclobutyl-7-methoxy-4-(4-(2-methoxyphenyl)piperazin-1-yl)quinazoline;

2-cyclobutyl-4-(4-(2-methoxyphenyl)piperazin-1-yl)quinazoline;

6-cyclobutyl-8-(4-(2-methoxyphenyl)piperazin-1-yl)-[1,3]dioxolo [4,5-g]quinazoline;

2-cyclopropyl-6-methoxy-4-(4-(2-methoxyphenyl)piperazin-1-yl)quinazoline;

2-cyclopropyl-4-(4-(2-ethoxyphenyl)piperazin-1-yl)-6,7-dimethoxyquinazoline;

4-(4-(2-chlorophenyl)piperazin-1-yl)-2-cyclopropyl-6,7-dimethoxyquinazoline;

2-cyclopropyl-6,7-dimethoxy-4-(4-(phenylsulfonyl)piperazin-1-yl)quinazoline;

2-cyclopropyl-6,7-dimethoxy-4-(4-(4-methylbenzyl)piperazin-1-yl)quinazoline;

2-cyclopropyl-6,7-dimethoxy-4-(4-(2-methoxybenzyl)piperazin-1-yl)quinazoline;

(4-(2-cyclopropyl-6,7-dimethoxyquinazolin-4-yl)piperazin-1-yl)(phenyl)methanone;

(4-(2-cyclopropyl-6,7-dimethoxyquinazolin-4-yl)piperazin-1-yl)(2-methoxyphenyl)methanone;

2-cyclopropyl-6,7-dimethoxy-4-(piperazin-1-yl)quinazoline trifluoroacetate;

2-cyclopropyl-6-methoxy-4-(4-(2-methoxyphenyl)piperazin-1-yl)-7-(trifluoromethyl)quinazoline;

or a pharmaceutically acceptable salt, solvate, or tautomer thereof.

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