Compounds and therapeutical use thereof

1. A compound represented by Formula VIb:

or pharmaceutically acceptable salt thereof, wherein:

R 1 is methyl or ethyl;

R 5 is H or F; and

R 2 is:

(i) cyano-C 1-6 alkyl, or tetrazolyl;

(ii) C 1-6 alkoxy substituted with either C 1-6 alkoxy or amino; or

(iii) —N(R a )(R b ) or —N(R a )( R b )—C 1-6 alkyl-, wherein R a is C 1-6 alkoxy, halo-C 1-6 alkyl, —C(═O)—C 1-6 alkyl (substituted with —C(═O)OH or amino), —C(═O)—pyridinyl, or —C 1-6 alkyl-C(═O)O—C 1-6 alkyl and R b is H or C 1-6 alkyl, or R a and R b together with the nitrogen atom to which they are both linked form either (a) a bicyclic heterocycle substituted with at least one oxo group or (b) piperidinyl or pyrrolidinyl substituted with at least one oxo group;

R 3 , R 4 , and R 6 -R 11 are independently H, halo, N 3 , OH, thiol, nitro, CN, NH 2 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylthiol, halo-C 1-6 alkyl, C 2-6 alkenyl-O—, C 2-6 alkynyl-O—, hydroxy-C 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl, C 1-6 acyl, C 1-6 acyloxy, —C 1-6 alkyl-C(O)O—C 1-6 alkyl, —C(O)O—C 1-6 alkyl, C 1-6 alkyl-C(O)O—C 1-6 alkyl-, C 1-6 acylamido, —N(R a )(R b ), —C 1-6 alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6 alkyl-, 3, 4, 5, or 6-membered carbocycle, heterocycle, aryl, or heteroaryl, wherein R a and R b are independently H, OH (R a and R b are not both OH), C 2-6 hydroxyalkyl, or C 1-6 alkyl, or R a and R b together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle; wherein any of the groups is optionally substituted with 1-3 substituents wherein each substituent is independently halo, N 3 , OH, thiol, nitro, CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylthiol, C 2-6 alkenyl-O—, C 2-6 alkynyl-O—, hydroxy-C 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl, C 1-6 acyl, C 1-6 acyloxy, C 1-6 alkyl-C(O)O—C 1-6 alkyl-, C 1-6 alkyl-OC(O)—C 1-6 alkyl-, C 1-6 acylamido, —N(R a )(R b ), —C 1-6 alkyl-C(O)N(Ra)(Rb), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6 alkyl-, wherein R a and R b are independently H, OH (R a and R b are not both OH), C 2-6 hydroxyalkyl, or C 1-6 alkyl or R a and R b together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle, wherein optionally any two adjacent R 7 R 11 groups together form a 3, 4, 5 or 6-membered carbocycle or heterocycle;

provided that R 9 is not —O(C 1-6 alkyl)C(O)O(C 1-6 alkyl), and when R 9 is H, then R 8 and R 10 are not both H, or one H and the other halo.

2. The compound of claim 1 , wherein when R 9 is H then at least one of R 8 and R 10 is not H or halo or C 1-6 alkyl.

3. The compound of claim 1 , wherein R 9 is selected from the group consisting of H, Cl, N 3 ;

C 1-6 alkyl optionally substituted with 1, 2 or 3 substituents, each substituent being independently OH, halo, C 1-3 alkoxy, (halo)C 1-3 alkoxy, —N(R a )(R b ) where R a and R b are independently H, OH (R a and R b are not both OH), C 2-4 hydroxyalkyl, or C 1-3 alkyl or R a and R b together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle;

—XR c wherein X is S or O and R c is C 1-6 alkyl optionally substituted with with 1, 2 or 3 substituents, each substituent being independently OH, halo, C 1-3 alkoxy, or (halo)C 1-3 alkoxy;

(C 0-3 alkyl)CO 2 R d where R d is C 1-6 alkyl;

—N(R a )(R b ) where R a and R b are independently H, OH (R a and R b are not both OH), C 2-4 hydroxyalkyl, C 1-3 alkyl, or —N(R e )(R f ) where R e and R f are independently H, OH (R e and R f are not both OH), or C 1-3 alkyl; wherein optionally R a and R b together with the N to which they are both linked form a 3, 4, 5 or 6-membered heterocycle, and optionally R e and R f together with the nitrogen atom to which they both are linked form a 3, 4, 5 or 6-membered heterocycle; or

—(C 0-3 alkyl)C(O)N(R a )(R b ) where R a and R b are independently H or C 1-3 alkyl;

and optionally R 9 and one of R 8 and R 10 together form a 3, 4, 5, or 6-membered heterocycle.

4. The compound of claim 1 , wherein R 9 is H; OH; Cl; N 3 ; C 1-3 alkyl; C 1-3 haloalkyl; —OR 9a where R 9a is C 1-4 alkyl or C 1-3 haloalkyl; —NH(R a ) or —N(R a )(R b ) where R a and R b are independently C 1-3 alkyl; or —COOR 9b where R 9b is C 1-3 alkyl; and optionally R 9 and one of R 8 and R 10 together form 3, 4, 5, or 6-membered heterocycle.

5. A compound according to claim 1 selected from:

[2-(2-Methoxy-ethoxy)-quinazolin-4-yl]-(4-methoxy-phenyl)-methyl-amine;

[2-(2-Dimethylamino-ethoxy)-quinazolin-4-yl]-(4-methoxy-phenyl)-methyl-amine;

N 2 -Ethoxymethyl-N 4 -(4-methoxy-phenyl)-N 2 ,N 4 -dimethyl-quinazoline-2,4-diamine;

{4-[(4-Methoxy-phenyl)-methyl-amino]-quinazolin-2-ylamino}-acetic acid ethyl ester;

N-{4-[(4-Methoxy-phenyl)-methyl-amino]-quinazolin-2-yl}-O-methyl-hydroxylamine;

N 2 -(2-Chloro-ethyl)-N 4 -(4-methoxy-phenyl)-N 4 -methyl-quinazoline-2,4-diamine;

({4-[(4-Methoxy-phenyl)-methyl-amino]-quinazolin-2-yl}-methyl-amino)-acetic acid methyl ester;

N-{4-[(4-Methoxy-phenyl)-methyl-amino]-quinazolin-2-ylmethyl}-acetamide;

{4-[(4-Methoxy-phenyl)-methyl-amino]-quinazolin-2-yl}-acetonitrile;

2-{4-[(4-Methoxy-phenyl)-methyl-amino]-quinazolin-2-yl}-2-methyl-propionitrile;

N-{4-[(4-Methoxy-phenyl)-methyl-amino]-quinazolin-2-ylmethyl}succinamic acid;

(S)-2-Amino-N-{4-[(4-methoxy-phenyl)-methyl-amino]-quinazolin-2-ylmethyl}-propionamide;

N-{4-[(4-Methoxy-phenyl)-methyl-amino]-quinazolin-2-ylmethyl}-nicotinamide;

(4-Methoxy-phenyl)-methyl-[2-(1H-tetrazol-5-yl)-quinazolin-4-yl]-amine;

(R)-2-Amino-N-{4-[(4-methoxy-phenyl)-methyl-amino]-quinazolin-2-ylmethyl}-propionamide;

1-{4-[(4-Methoxy-phenyl)-methyl-amino]-quinazolin-2-ylmethyl}-piperidin-2-one;

1-{4-[(4-Methoxy-phenyl)-methyl-amino]-quinazolin-2-ylmethyl}-pyrrolidin-2-one; and

2-{4-[(3-Chloro-4-ethoxy-phenyl)-methyl-amino]-quinazolin-2-ylmethyl}-isoindole-1,3-dione;

or a pharmaceutically acceptable salt thereof.

6. A compound selected from:

{4-[Methyl-(2-methyl-quinazolin-4-yl)-amino]-phenoxy}-acetic acid methyl ester;

{4-[Methyl-(2-methyl-quinazolin-4-yl)-amino]-phenoxy}-acetic acid;

Methyl 2-[({4-[methyl(2-methylquinazolin-4-yl)amino]phenyl}amino)carbonyl]hydrazine carboxylate;

4-{4-[Methyl-(2-methyl-quinazolin-4-yl)-amino]-phenyl}-[1,2,4]triazolidine-3,5-dione; and

N-{4-[Methyl-(2-methyl-quinazolin-4-yl)-amino]-phenyl}-methanesulfonamide;

or a pharmaceutically acceptable salt thereof.

7. A compound selected from:

Methyl-{4-[methyl-(2-methyl-quinazolin-4-yl)-amino]-phenyl}carbamic acid tent-butyl ester;

4-Methoxy-N-{4-[(4-methoxy-phenyl)-methyl-amino]-2-methyl-quinazolin-6-yl}-benzenesulfonamide;

N 2 -(3,7-Dimethyl-octa-2,6-dienyl)-N 4 -(4-methyl-phenyl)-N 4 -methyl-quinazoline-2,4-diamine;

(2-Chloro-quinazolin-4-yl)-(4-phenoxy-phenyl)-methyl-amine; and

(4-carboxy-phenyl)-(2-methyl-quinazolin-4-yl)-methyl-amine;

or a pharmaceutically acceptable salt thereof.

8. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of a compound according to claim 1 .