Factor IXa inhibitors

1. A compound of formula I

or a pharmaceutically acceptable salt thereof, wherein

R 1 , R 2 , R 3 and R 4 are independently H or C 1-6 alkyl, provided that when R 1 , R 2 , and R 3 are H, R 4 is C 1-6 alkyl, and when R 1 , R 2 , and R 4 are H, R 3 is C 1-6 alkyl, and when R 1 , R 3 , and R 4 are H, R 2 is C 1-6 alkyl, and when R 2 , R 3 , and R 4 are H, R 1 is C 1-6 alkyl;

A is

1) a 9-10 membered bicyclic heterocycle having 2-3 heteroatoms independently selected from N, S and O, which 9-10 membered bicyclic heterocycle is substituted with pyrazole, or

2) a 12-, 13-, or 14-membered tricyclic heterocycle having 3-5 heteroatoms selected from N, S and O, which 12-, 13-, or 14-membered heterocycle is unsubstituted or substituted with ═O or NH 2 ;

B is

1) a 5-membered monocyclic heterocycle having 2 nitrogen atoms and 3 carbon atoms, where

one 5-membered monocyclic heterocycle nitrogen is substituted with 6-membered monocyclic heterocycle having one or two nitrogen atoms, C 1-6 alkyl, C 3-8 carbocycle, or aryl, wherein heterocycle, alkyl, carbocycle and aryl are unsubstituted, mono-substituted, or independently di-substituted with CF 3 , OCH 3 , F, CN, —CHF 2 , or ═O,

and one 5-membered monocyclic heterocycle carbon atom is unsubstituted or substituted with C 1-6 alkyl,

2) a 6-membered monocyclic heterocycle having 1 nitrogen atom and 5 carbon atoms, where one or two carbon atoms are independently unsubstituted or independently substituted with CF 3 , —C(CH 3 ) 2 OH, —OCHF 2 , —CH(CF 3 )OH, —C(CF 3 )(CH 3 )OH, F,

or

3) aryl, substituted with —C 1-6 alkyl.

2. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein

R 1 , R 2 , R 3 and R 4 are independently H or C 1-6 alkyl, provided that when R 1 , R 2 , and R 3 are H, R 4 is C 1-6 alkyl, and when R 1 , R 2 , and R 4 are H, R 3 is C 1-6 alkyl, and when R 1 , R 3 , and R 4 are H, R 2 is C 1-6 alkyl, and when R 2 , R 3 , and R 4 are H, R 1 is C 1-6 alkyl;

A has the formula (II)

wherein

W is N or CH;

E is S(O) 2 or C(O);

p is 0 or 1;

R 5 is H or, together with R 6 and the atoms to which they are attached, forms a 5- or 6-membered monocyclic heterocycle having 2 heteroatoms independently selected from N, S and O, which heterocycle is substituted at a carbon atom with NH 2 ;

R 6 is pyrazole, or, together with R 5 and the atoms to which they are attached, forms a 5- or 6-membered monocyclic heterocycle, having 2 heteroatoms independently selected from N, S and O, which heterocycle is substituted at a carbon atom with NH 2 , or, provided R 5 and R 6 do not form a heterocycle, forms, together with R 7 and the atoms to which they are attached, a 5-membered monocyclic heterocycle, having 2 heteroatoms independently selected from N, S and O, or forms, together with R 7 and the atoms to which they are attached, a 6-membered monocyclic heterocycle having 1 N atom, which 5- or 6-membered heterocycle is substituted at a carbon atom with NH 2 ;

R 7 is H, or, provided R 5 and R 6 do not form a heterocycle, forms, together with R 6 and the atoms to which they are attached, a 5-membered monocyclic heterocycle, having 2 heteroatoms independently selected from N, S and O, or forms, together with R 6 and the atoms to which they are attached, a 6-membered monocyclic heterocycle having 1 N atom, which 5- or 6-membered heterocycle is substituted at a carbon atom with NH 2 ; and

B is

1) a 5-membered monocyclic heterocycle having 2 nitrogen atoms and 3 carbon atoms, where

one 5-membered monocyclic heterocycle nitrogen is substituted with

and one 5-membered monocyclic heterocycle carbon atom is unsubstituted or substituted with

—CH 3 ,

2) a 6-membered monocyclic heterocycle having 1 nitrogen atom and 5 carbon atoms, where one or two carbon atoms are independently unsubstituted or independently substituted with CF 3 , —C(CH 3 ) 2 OH, —OCHF 2 , —CH(CF 3 )OH, —C(CF 3 )(CH 3 )OH, F,

or

3) aryl, substituted with —CH 3 .

3. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein

R 1 , R 2 , R 3 and R 4 are independently H or C 1-6 alkyl, provided that when R 1 , R 2 , and R 3 are H, R 4 is C 1-6 alkyl, and when R 1 , R 2 , and R 4 are H, R 3 is C 1-6 alkyl, and when R 1 , R 3 , and R 4 are H, R 2 is C 1-6 alkyl, and when R 2 , R 3 , and R 4 are H, R 1 is C 1-6 alkyl;

A is

and

B is

4. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 and R 4 are independently H or CH 3 , provided that when R 1 , R 2 , and R 3 are H, R 4 is CH 3 , and when R 1 , R 2 , and R 4 are H, R 3 is CH 3 , and when R 1 , R 3 , and R 4 are H, R 2 is CH 3 , and when R 2 , R 3 , and R 4 are H, R 1 is CH 3 .

5. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, which is

(R)-2-((S)-(3-Amino-9-oxo-6,9-dihydroisothiazolo[5,4-f]quinazolin-7-yl)(hydroxy)methyl)-4-(1-(1-(difluoromethyl)-6-oxo-1,6-dihydropyridin-3-yl)-1H-pyrazol-3-yl)-2-methylmorpholin-3-one,

(R)-2-((S)-(3-Amino-9-oxo-6,9-dihydroisothiazolo[5,4-f]quinazolin-7-yl)(hydroxy)methyl)-2-methyl-4-(1-(pyridazin-4-yl)-1H-pyrazol-3-yl)morpholin-3-one,

(R)-2-((S)-1-(3-Amino-9-oxo-6,9-dihydroisothiazolo[5,4-f]quinazolin-7-yl)-1-hydroxyethyl)-4-(6-(trifluoromethyl)pyridin-2-yl)morpholin-3-one,

(R)-2-((S)-(3-Amino-9-oxo-6,9-dihydroisothiazolo[5,4-f]quinazolin-7-yl)(hydroxy)methyl)-4-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-2-methylmorpholin-3-one,

(R)-2-((S)-(5-(1H-Pyrazol-4-yl)-1H-benzo[d]imidazol-2-yl)(hydroxy)methyl)-6,6-dimethyl-4-(1-(6-(trifluoromethyl)pyridazin-4-yl)-1H-pyrazol-3-yl)morpholin-3-one,

2-{(S)-hydroxy[(2R)-2-methyl-3-oxo-4-{1-[6-(trifluoromethyl)pyridazin-4-yl]-1H-pyrazol-3-yl}morpholin-2-yl]methyl}-6-(1H-pyrazol-4-yl)quinazolin-4(1H)-one,

(2R,6S)-2-((S)-(3-Amino-9-oxo-6,9-dihydroisothiazolo[5,4-f]quinazolin-7-yl)(hydroxy)methyl)-6-methyl-4-(1-(6-(trifluoromethyl)pyridazin-4-yl)-1H-pyrazol-3-yl)morpholin-3-one, or

(R)-2-((S)-(3-amino-9-oxo-6,9-dihydroisothiazolo[5,4-f]quinazolin-7-yl)(hydroxy)methyl)-4-(1-(6-methoxypyridazin-4-yl)-1H-pyrazol-3-yl)-6,6-dimethylmorpholin-3-one.

6. A composition for inhibiting thrombus formation in blood comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.