Tie-2 modulators and methods of use

1. A compound according to Formula IV

or a pharmaceutically acceptable salt thereof, wherein

X is selected from —H, —OR 6 , —S(O) 0-2 R 6 , —(R 6 )R 7 , —O—N(R 6 )R 7 , —N(R 6 )R 6 , —N(R 6 )N(R 6 )R 7 , absent, oxo, thiono, and imino;

R 1 and R 2 , at each occurance, are each independently selected from —H, halogen, —CN, —NH 2 , —NO 2 , —OR 6 , —N(R 6 )R 7 , —S(O) 0-2 R 7 , —SO 2 N(R 6 )R 7 , —CO 2 R 6 , —C(O)N(R 6 )R 7 , —N(R 6 )SO 2 R 7 , —N(R 6 )C(O)R 7 , —N(R 6 )CO 2 R 7 , —C(O)R 6 , optionally substituted lower alkyl, optionally substituted aryl, optionally substituted lower arylalkyl, optionally substituted heterocyclyl, absent, and optionally substituted lower heterocyclylalkyl;

optionally, two of R 1 are paired, together with the corresponding atom or atoms of the ring to which they are attached to form a second ring consisting of three and seven annular carbon atoms, said second ring optionally substituted with between zero and three of R 1 ;

R 3 is selected from —H and optionally substituted lower alkyl;

each of R 4 is independently selected from —H, halogen, —CN, —NH 2 , —NO 2 , —OR 6 , —N(R 6 )R 7 , —S(O) 0-2 R 7 , —SO 2 N(R 6 )R 7 , —CO 2 R 6 , —C(O)N(R 6 )R 7 , —N(R 6 )SO 2 R 7 , —N(R 6 )C(O)R 7 , —N(R 6 )CO 2 R 7 , —C(O )R 6 , optionally substituted lower alkyl, optionally substituted aryl, optionally substituted lower arylalkyl, optionally substituted heterocyclyl, and optionally substituted lower heterocyclylalkyl;

n is zero to four;

each R 5 is independently selected from —H, halogen, —CN, —NH 2 , —NO 2 , —OR 6 , —NR 6 R 7 , —S(O) 0-2 R 7 , —SO 2 NR 6 )R 7 , —CO 2 R 6 , —C(O)NR 6 R 7 , —N(R 6 )SO 2 R 7 , —N(R 6 )C(O)R 7 , —N(R 6 )CO 2 R 7 , —C(O)R 6 , optionally substituted lower alkyl, optionally substituted aryl, optionally substituted lower arylalkyl, optionally substituted heterocyclyl, and optionally substituted lower heterocyclylalkyl; and

R 6 is —H or optionally substituted lower alkyl;

R 7 is selected from optionally substituted lower alkyl, optionally substituted aryl, optionally substituted lower arylalkyl, optionally substituted heterocyclyl, and optionally substituted lower heterocyclylalkyl; and

R 6 and R 7 , when taken together with a common nitrogen to which they are attached, form an optionally substituted five- to seven-membered heterocyclyl ring, said optionally substituted five- to seven-membered heterocyclyl ring optionally containing at least one additional heteroatom selected from N, O, S, and P.

2. A compound according to Table 3:

TABLE 3

#

Name

Structure

1

N-cyclohexyl-2-pyridin-4-ylquinazolin-4- amine

3

3-cyclopentyl-2-pyridin-4-ylquinazolin-4- amine

4

N-(cyclohexylmethyl)-2-pyridin-4- ylquinazolin-4-amine

7

N-[(4-fluorophenyl)methyl]-2-pyridin-4- ylquinazolin-4-amine

9

N-(2,3-dihydro-1H-inden-1-yl)-2-pyridin- 4-ylquinazolin-4-amine

12

2-pyridin-4-yl-N-[(2R)-1,2,3,4- tetrahydronaphthalen-2-yl]quinazolin-4- amine

15

2-pyridin-4-yl-N-[(2S)-1,2,3,4- tetrahydronaphthalen-2-yl]quinazolin-4- amine

18

(1S,2R)-1-[(2-pyridin-4-ylquinazolin-4- yl)amino]-2,3-dihydro-1H-inden-2-ol

19

1,1-dimethylethyl 4-[(2-pyridin-4- ylquinazolin-4-yl)amino]piperidine-1- carboxylate

24

3-[(2-pyridin-4-ylquinazolin-4- yl)amino]naphthalen-2-ol

25

N-{-4-[(1-methylethyl)oxy]phenyl}-2- pyridin-4-ylquinazolin-4-amine

31

(1S,2R)-1-[(6-chloro-2-pyridin-4- ylquinazolin-4-yl)amino]-2,3-dihydro-1H- inden-2-ol

33

(1S,2R)-1-[(2-pyridin-3-ylquinazolin-4- yl)amino]-2,3-dihydro-1H-inden-2-ol

45

(1S,2R)-1-[(6-bromo-2-pyridin-4- ylquinazolin-4-yl)amino]-2,3-dihydro-1H- inden-2-ol

46

(1S,2R)-1-{[6,7-bis(methyloxy)-2- pyridin-4-ylquinazolin-4-yl]aminol-2,3- dihydro-1H-inden-2-ol

48

(1S,2R)-1-{[2-pyridin-4-yl-7- (trifluoromethyl)quinazolin-4-yl]amino}- 2,3-dihydro-1H-inden-2-ol

49

(1S,2R)-1-({2-[6-(methyloxy)pyridin-3- yl]quinazolin-4-yl}amino)-2,3-dihydro- 1H-inden-2-ol

51

(1S,2R)-1-[(7-methyl-2-pyridin-4- ylquinazolin-4-yl)amino]-2,3-dihydro-1H- inden-2-ol

54

(2S)-3-methyl-2-[(2-pyridin-4- ylquinazolin-4-yl)amino]butan-1-ol

55

(2S)-2-phenyl-2-[(2-pyridin-4- ylquinazolin-4-yl)amino]ethanol

56

(2R)-2-phenyl-2-[(2-pyridin-4- ylquinazolin-4-yl)amino]ethanol

61

(2S)-3-phenyl-2-[(2-pyridin-4- ylquinazolin-4-yl)amino]propan-1-ol

62

2-[(phenylmethyl)(2-pyridin-4- ylquinazolin-4-yl)amino]ethanol

63

(1S,2R)-1-{[2-(2-aminopyrimidin-4- yl)quinazolin-4-yl]amino}-2,3-dihydro- 1H-inden-2-ol

66

2-{-4-[(2-pyridin-4-ylquinazolin-4- yl)amino]piperazin-1-yl}ethanol

67

N-piperidin-1-yl-2-pyridin-4- ylquinazolin-4-amine

3. A pharmaceutical composition comprising the compound according to claim 1 and a pharmaceutically acceptable carrier.