Factor IXa inhibitors

1. A compound of formula I

or a pharmaceutically acceptable salt thereof, wherein

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 unsubstituted or substituted with ═O, —C(═NH)NH 2 , or 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

a) 6-membered monocyclic heterocyle having one or two nitrogen atoms or one oxygen atom,

b) C 1-6 alkyl,

c) C carbocycle, or

d) 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, or

2) a 6-membered monocyclic heterocycle having 1 nitrogen atom and 5 carbon atoms, where three carbon atoms are unsubstituted, and 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,

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

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 H, —C(═NH)NH 2 , 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, —C(═NH)NH 2 , 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 ;

provided R 5 , R 6 and R 7 are not simultaneously H; 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 carbon atom in the 5-membered monocyclic heterocycle is unsubstituted or substituted with —CH 3 , or

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,

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

A is

and

B is

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

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

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

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

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

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

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

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

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

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

(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)morpholin-3-one,

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

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

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

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

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

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

(R)-2-((S)-(3-Amino-9-oxo-6,9-dihydroisothiazolo[5,4-f]quinazolin-7-yl)(hydroxy)methyl)-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-(3-fluoro-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-(difluoromethoxy)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-cyclopropylpyridin-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)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)-5-(trifluoromethyl)pyridin-2-yl)morpholin-3-one,

1-(6-((R)-2-((S)-(3-Amino-9-oxo-6,9-dihydroisothiazolo[5,4-f]quinazolin-7-yl)(hydroxy)methyl)-3-oxomorpholino)pyridin-2-yl)cyclobutyl acetate,

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

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

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

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

(R)-2-((S)-(6-Amino-4-oxo-1,4-dihydropyrido[3,4-g]quinazolin-2-yl)(hydroxy)methyl)-4-(1-(pyridin-4-yl)-1H-pyrazol-3-yl)morpholin-3-one,

2-((S)-Hydroxy((R)-3-oxo-4-(p-tolyl)morpholin-2-yl)methyl)-4-oxo-1,4-dihydroquinazoline-6-carboximidamide,

2-((S)-Hydroxy((R)-3-oxo-4-(p-tolyl)morpholin-2-yl)methyl)-1H-benzo[d]imidazole-6-carboximidamide,

3-((S)-Hydroxy((R)-3-oxo-4-(p-tolyl)morpholin-2-yl)methyl)-4H-benzo[e][1,2,4]thiadiazine-7-carboximidamide 1,1-dioxide,

(2R)-2-[(S)-(3-amino-7H-imidazo[4,5-f][1,2]benzisoxazol-6-yl)(hydroxy)methyl]-4-(1-pyridin-4-yl-1H-pyrazol-3-yl)morpholin-3-one,

(2R)-2-[(S)-(3-amino-7H-imidazo[4,5-f][1,2]benzisoxazol-6-yl)(hydroxy)methyl]-4-[1-(6-methoxypyridazin-4-yl)-1H-pyrazol-3-yl]morpholin-3-one,

(R)-2-((S)-(8-Amino-1,1-dioxido-4H-isoxazolo[4′,5′:4,5]benzo[1,2-e][1,2,4]thiadiazin-3-yl)(hydroxy)methyl)-4-(1-(pyridin-4-yl)-1H-pyrazol-3-yl)morpholin-3-one,

(2R)-2-[(S)-(8-amino-1,1-dioxido-4H-isoxazolo[5,4-g][1,2,4]benzothiadiazin-3-yl)(hydroxy)methyl]-4-[6-(trifluoromethyl)pyridin-2-yl]morpholin-3-one,

(R)-2-((S)-(7-Amino-1-oxo-1,4-dihydropyrido[4,3-f]quinazolin-3-yl)(hydroxy)methyl)-4-(1-(pyridin-4-yl)-1H-pyrazol-3-yl)morpholin-3-one,

(R)-2-((S)-hydroxy(4-oxo-6-(1H-pyrazol-4-yl)-1,4-dihydroquinazolin-2-yl)methyl)-4-(1-(pyridazin-4-yl)-1H-pyrazol-3-yl)morpholin-3-one,

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

2-[(S)-hydroxy{(2R)-4-[1-(2-methoxypyridin-4-yl)-1H-pyrazol-3-yl]-3-oxomorpholin-2-yl}methyl]-6-(1H-pyrazol-4-yl)quinazolin-4(1H)-one,

3-amino-7-{(S)-hydroxy[(2R)-3-oxo-4-{1-[2-(trifluoromethyl)pyridin-4-yl]-1H-pyrazol-3-yl}morpholin-2-yl]methyl}isoxazolo[5,4-f]quinazolin-9(6H)-one,

(R)-2-((S)-(6-amino-4-oxo-1,4-dihydropyrido[3,4-g]quinazolin-2-yl)(hydroxy)methyl)-4-(1-(pyridin-4-yl)-1H-pyrazol-3-yl)morpholin-3-one,

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

7-amino-3-{(S)-hydroxy[(2R)-3-oxo-4-(1-pyridin-4-yl-1H-pyrazol-3-yl)morpholin-2-yl]methyl}pyrido[4,3-f]quinazolin-1(4H)-one, or

6-(aminomethyl)-2-[(S)-hydroxy{(2R)-4-[1-(2-methoxypyridin-4-yl)-1H-pyrazol-3-yl]-3-oxomorpholin-2-yl}methyl]quinazolin-4(1H)-one.

5. 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.