Nitrogen containing heterobicycles as factor Xa inhibitors

1. A compound selected from the group:

or a sterioisomer or pharmaceutically acceptable salt thereof, wherein compounds of the above formulas are substituted with 0-2 R 3 ;

G is a group of formula I or II:

ring D is selected from —(CH 2 ) 3 —, —(CH 2 ) 4 —, —CH 2 N═CH—, —CH 2 CH 2 N═CH—, and a 5-6 membered aromatic system containing from 0-2 heteroatoms selected from the group N, O, and S, provided that from 0-1 O and S atoms are present;

ring D, when present, is substituted with 0-2 R;

E is selected from phenyl, pyridyl, pyrimidyl, pyrazinyl, and pyridazinyl, substituted with 0-1 R;

R is selected from Cl, F, Br, 1, OH, C 1-3 alkoxy, NH 2 , NH(C 1-3 alkyl), N(C 1-3 alkyl) 2 , CH 2 NH 2 , CH 2 NH(C 1-3 alkyl), CH 2 N(C 1-3 alkyl) 2 , CH 2 CH 2 NH 2 , CH 2 CH 2 NH(C 1-3 alkyl), and CH 2 CH 2 N(C 1-3 alkyl) 2 ;

alternatively, ring D is absent;

when ring D is absent, ring E is selected from phenyl, pyridyl, pyrimidyl, pyrazinyl, and pyridazinyl, and ring E is substituted with R″ and R′;

R″ is selected from F, Cl, Br, I, OH, C 1-3 alkoxy, CN, C(═NR 8 )NR 7 R 9 , NHC(═NR 8 )NR 7 R 9 , NR 8 CH(═NR 7 ), C(O)NR 7 RB, (CR 8 R 9 ) t NR 7 R 8 , SH, C 1-3 alkyl-S, S(O)R 3b , S(O) 2 R 3a , S(O) 2 NR 2 R 2a , and OCF 3 ;

R′ is selected from H, F, Cl, Br, I, SR 3 , CO 2 R 3 , NO 2 , (CH 2 ) t OR 3 , C 1-4 alkyl, OCF 3 , CF 3 , C(O)NR 7 R 8 , and (CR 8 R 9 ) t NR 7 R 8 ; alternatively, R″ and R′ combine to form methylenedioxy or ethylenedioxy;

Z is N or CR 1a ;

Z 1 is S, O, or NR 3 ;

Z 2 is selected from H, C 1-4 alkyl, phenyl, benzyl, C(O)R 3 , and S(O) p R 3c ;

R 1a is selected from H, —(CH 2 ) r -R 1 ′, —CH═CH-R 1 ′, NHCH 2 R 1 ″, OCH 2 R 1 ″, SCH 2 R 1 ″, NH(CH 2 ) 2 (CH 2 ) t R 1 ′, O(CH 2 ) 2 (CH 2 ) t R 1 ′, and S(CH 2 ) 2 (CH 2 ) t R 1 ′;

R 1 ′ is selected from H, C 1-3 alkyl, F, Cl, Br, I, —CN, —CHO, (CF 2 ) r CF 3 , (CH 2 ) r OR 2 , NR 2 R 2a , C(O)R 2c , OC(O)R 2 , (CF 2 ) r CO 2 R 2 C, S(O) p R 2b , NR 2 (CH 2 ) r OR 2 , C(═NR 2 C)NR 2 R 2a , NR 2 C(O)R 2b , NR 2 C(O)R 3 , NR 2 C(O)NHR 2b , NR 2 C(O) 2 R 2a , OC(O)NR 2a R 2b , C(O)NR 2 R 2a , C(O)NR 2 (CH 2 ) r OR 2 , SO 2 NR 2 R 2a , NR 2 SO 2 R 2b , C 3-6 carbocyclic residue substituted with 0-2 R 4a , and 5-10 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R 4a ;

R″ is selected from H, CH(CH 2 OR 2 ) 2 , C(O)R 2c , C(O)NR 2 R 2a , S(O)R 2b , S(O) 2 R 2b , and SO 2 NR 2 R 2a ;

R 2 , at each occurrence, is selected from H, CF 3 , C 1-6 alkyl, benzyl, C 3-6 carbocyclic residue substituted with 0-2 R 4b , a C 3-6 carbocyclic-CH 2 — residue substituted with 0-2 R 4b , and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R 4b ;

R 2a , at each occurrence, is selected from H, CF 3 , C 1-6 alkyl, benzyl, C 3-6 carbocyclic residue substituted with 0-2 R 4b , and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R 4b ;

R 2b , at each occurrence, is selected from CF 3 , C 1-4 alkoxy, C 1-6 alkyl, benzyl, C 3-6 carbocyclic residue substituted with 0-2 R 4b , and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R 4b ;

R 2c , at each occurrence, is selected from CF 3 , OH, C 1-4 alkoxy, C 1-6 alkyl, benzyl, C 3-6 carbocyclic residue substituted with 0-2 R 4b , and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R 4b ;

alternatively, R 2 and R 2a , together with the atom to which they are attached, combine to form a 5 or 6 membered saturated, partially saturated or unsaturated ring substituted with 0-2 R 4b and containing from 0-1 additional heteroatoms selected from the group consisting of N, O, and S;

R 3 , at each occurrence, is selected from H, C 1-4 alkyl, and phenyl;

R 3a , at each occurrence, is selected from H, C 1-4 alkyl, and phenyl;

R 3b , at each occurrence, is selected from H, C 1-4 alkyl, and phenyl;

R 3c , at each occurrence, is selected from C 1-4 alkyl, and phenyl;

A is selected from:

C 3-10 carbocyclic residue substituted with 0-2 R 4 , and

5-10 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R 4 ;

B is selected from:

Y, X-Y, C(═NR 2 )NR 2 R 2a , and NR 2 C(═NR 2 )NR 2 R 2a ;

X is selected from C 1-4 alkylene, —CR 2 (CR 2 R 2b )(CH 2 ) t —, —C(O)—, —C(═NR 1 ″)-, —CR 2 (NR 1 ″R 2 )—, —CR 2 (OR 2 )—, —CR 2 (SR 2 , —C(O)CR 2 R 2a —, —CR 2 R 2a C(O), —S(O) p —, —S(O) p CR 2 R 2a —, —CR 2 R 2a S(O) p —, —S(O) 2 NR 2 —, —NR 2 S(O) 2 —, —NR 2 S(O) 2 CR 2 R 2a , —CR 2 R 2a S(O) 2 NR 2 —, —NR 2 S(O) 2 NR 2 —, —C(O)NR 2 —, —NR 2 C(O), —C(O)NR 2 CR 2 R 2a —, —NR 2 C(O)CR 2 R 2a -, —CR 2 R 2a C(O)NR 2 —, —CR 2 R 2a NR 2 C(O)—, —NR 2 C(O)O—, —OC(O)NR 2 —, —NR 2 C(O)NR 2 —, —NR 2 —, —NR 2 CR 2 R 2a , CR 2 R 2a NR 2 , O, —CR 2 R 2a O—, and —OCR 2 R 2a —;

Y is selected from:

CH 2 NR 2 R 2a ;

CH 2 CH 2 NR 2 R 2a ;

C 3-10 carbocyclic residue substituted with 0-2 R 4a , and

5-10 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with O 2 R 4a ;

R 4 , at each occurrence, is selected from H, ═O, (CH 2 ) r OR 2 , F, Cl, Br, 1, C 1-4 alkyl, —CN, NO 2 , (CH 2 ) r NR 2 R 2a , (CH 2 ) r C(O)R 2c NR 2 C(O)R 2b , C(O)NR 2 R 2a , NR 2 C(O)NR 2 R 2a , C(═NR 2 )NR 2 R 2a , C(═NS(O) 2 R 5 )NR 2 R 2a , NHC(═NR 2 )NR 2 R 2a , C(O)NHC(═NR 2 )NR 2 R 2a , SO 2 NR 2 R 2a , NR 2 SO 2 NR 2 R 2a , NR 2 SO 2 —C 1-4 alkyl, NR 2 SO 2 R 5 , S(O) p R 5 , (CF 2 ) r CF 3 , NCH 2 R 1 ″, OCH 2 R 1 ″, SCH 2 R 1 ″, N(CH 2 ) 2 (CH 2 ) t R 1 ′, O(CH 2 ) 2 (CH 2 ) t R 1 ′, and S(CH 2 ) 2 (CH 2 ) t R 1 ′;

alternatively, one R 4 is a 5-6 membered aromatic heterocycle containing from 1-4 heteroatoms selected from the group consisting of N, O, and S;

R 4a , at each occurrence, is selected from H, ═O, (CH 2 ) r OR 2 , (CH 2 ) r —F, (CH 2 ) r -Br, (CH 2 ) r —Cl, Cl, Br, F, I, C 4 alkyl, —CN, NO 2 , (CH 2 ) r NR 2 R 2a , (CH 2 ) r C(O)R 2 C, NR 2 C(O)R 2b , C(O)NR 2 R 2a , (CH 2 ) r N═CHOR 3 , C(O)NH(CH 2 ) 2 NR 2 R 2a , NR 2 C(O)NR 2 R 2a , C(═NR 2 )NR 2 R 2a , SO 2 NR 2 R 2a , NR 2 SO 2 NR 2 R 2a , NR 2 SO 2 —C 1-4 alkyl, C(O)NHSO 2 —C 1-4 alkyl, NR 2 SO 2 R 5 , S(O) p R 5 , and (CF 2 ) r CF 3 ;

alternatively, one R 4a is a 5-6 membered aromatic heterocycle containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-1 R 5 ;

R 4b , at each occurrence, is selected from H, ═O, (CH 2 ) r OR 3 , F, Cl, Br, I, C 1-4 alkyl, —CN, NO 2 , (CH 2 ) r NR 3 R 3a , (CH 2 ) r C(O)R 3 , (CH 2 ) r C(O)OR 3c , NR 3 C(O)R 3a , C(O)NR 3 R 3a , NR 3 C(O)NR 3 R 3a , C(═NR 3 )NR 3 R 3a , NR 3 C(═NR 3 )NR 3 R 3a , SO 2 NR 3 R 3a , NR 3 SO 2 NR 3 R 3a , NR 3 SO 2 —C 1-4 alkyl, NR 3 SO 2 CF 3 , NR 3 SO 2 -phenyl, S(O) p CF 3 , S(O) p -C 1-4 alkyl, S(O) p -phenyl, and (CF 2 ) r CF 3 ;

R 5 , at each occurrence, is selected from CF 3 , C 1-6 alkyl, phenyl substituted with 0-2 R 6 , and benzyl substituted with 0-2 R 6 ;

R 6 , at each occurrence, is selected from H, OH, (CH 2 ) r OR 2 , halo, C 1-4 alkyl, CN, NO 2 , (CH 2 ) r NR 2 R 2a , (CH 2 ) r C(O)R 2b , NR 2 C(O)R 2b , NR 2 C(O)NR 2 R 2a , C(═NH)NH 2 , NHC(═NH)NH 2 , SO 2 NR 2 R 2a , NR 2 SO 2 NR 2 R 2a , and NR 2 SO 2 C 1-4 alkyl;

R 7 , at each occurrence, is selected from H, OH, C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxy, C 1-4 alkoxycarbonyl, (CH 2 ) n -phenyl, C 6-10 aryloxy, C 6-10 aryloxycarbonyl, C 6-10 arylmethylcarbonyl, C 1-4 alkylcarbonyloxy C 1-4 alkoxycarbonyl, C 6-10 arylcarbonyloxy C 1-4 alkoxycarbonyl, C 1-6 alkylanocarbonyl, phenylaminocarbonyl, and phenyl C 1-4 alkoxycarbonyl;

R 8 , at each occurrence, is selected from H, C 1-6 alkyl and (CH 2 ) n -phenyl;

alternatively, R 7 and R 8 combine to form a 5 or 6 membered saturated, ring which contains from 0-1 additional heteroatoms selected from the group consisting of N, O, and S;

R 9 , at each occurrence, is selected from H, C 1-6 alkyl and (CH 2 ) n -phenyl;

n, at each occurrence, is selected from 0, 1, 2, and 3;

m, at each occurrence, is selected from 0, 1, and 2;

p, at each occurrence, is selected from 0, 1, and 2;

r, at each occurrence, is selected from 0, 1, 2, and 3;

s, at each occurrence is selected from 0, 1, and 2; and,

t, at each occurrence is selected from 0, 1, 2, and 3.

2. A compound of claim 1 , wherein the compound is selected from the group:

wherein compounds of the above formulas are substituted with 0-2 R 3 ;

G is selected from the group:

A is selected from one of the following carbocyclic and heterocyclic systems which are substituted with 0-2 R 4 ;

phenyl, piperidinyl, piperazinyl, pyridyl, pyrirnidyl, furanyl, morpholinyl, thiophenyl, pyrrolyl, pyrrolidinyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, triazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, benzofuranyl, benzothiofuranyl, indolyl, benzioidazolyl, benzoxazolyl, benzthiazolyl, indazolyl, benzisoxazolyl, benzisothiazolyl, and isoindazolyl;

B is selected from: Y and X-Y;

X is selected from C 1-4 alkylene, —C(O)—, —C(═NR 1 ″)—, —CR 2 (NR 1 ″R 2 )—, —C(O)CR 2 R 2a —, —CR 2 R 2a C(O), —C(O)NR 2 —, —NR 2 C(O)—, C(O)NR 2 CR 2 R 2a , —NR 2 C(O)CR 2 R 2a , —CR 2 R 2a C(O)NR 2 —, CR 2 R 2a NR 2 C(O), —NR 2 C(O)NR 2 —, —NR 2 —, —NR 2 CR 2 R 2a , CR 2 R 2a NR 2 , O, CR 2 R 2a O—, and —OCR 2 R 2a —;

Y is C 2 NR 2 R 2a or CH 2 CH 2 N 2 R 2a ;

alternatively, Y is selected from one of the following carbocyclic and heterocyclic systems that are substituted with 0-2 R 4a ;

cyclopropyl, cyclopentyl, cyclohexyl, phenyl, piperidinyl, piperazinyl, pyridyl, pyrimidyl, furanyl, morpholinyl, thiophenyl, pyrrolyl, pyffolidinyl, oxazolyl, isoxazolyl, isoxazolinyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, triazolyl, 1,2,3-oxadiazolyl, 1,2,4 oxadiazolyl, 1,2,5 oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thliadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 11,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, benzofuranyl, benzothiofuranyl, indolyl, benzimidazolyl, benzoxazolyl, benzthiazolyl, indazolyl, benzisoxazolyl, benzisothiazolyl, and isoindazolyl;

alternatively, Y is selected from the following bicyclic heteroaryl ring systems:

K is selected from O, S, NH, and N; and,

s is 0.

3. A compound of claim 2 , wherein

G is selected from the group:

4. A compound of claim 3 , wherein:

G is selected from:

5. A compound of claim 4 , wherein:

A is selected from phenyl, pyridyl, and pyrimidyl, and is substituted with 0-2 R 4 ; and,

B is selected from X-Y, phenyl, pyrrolidino, morpholino, 1,2,3-triazolyl, and imidazolyl, and is substituted with 0-1 R 4a ;

R 2 , at each occurrence, is selected from H, CH 3 , CH 2 CH 3 , cyclopropylmethyl, cyclobutyl, and cyclopentyl;

R 2a , at each occurrence, is H or CH 3 ; alternatively, R 2 and R 2a , together with the atom to which they are attached, combine to form pyrrolidine substituted with O 2 R 4b ;

R 4 , at each occurrence, is selected from OH, (CH 2 ) r OR 2 , halo, C 1-4 alkyl, (CH 2 ) r NR 2 R 2a , and (CF 2 ) r CF 3 ;

R 4a is selected from CIA alkyl, CF 3 , (CH 2 ) r OR 2 , (CH 2 ) r NR 2 R 2a , S(O) p R 5 , SO 2 NR 2 R 2a , and 1-CF 3 -tetrazol-2-yl;

R 4b , at each occurrence, is selected from H, CH 3 , and OH;

R 5 , at each occurrence, is selected from CF 3 , C 1-6 alkyl, phenyl, and benzyl;

X is CH 2 or C(O);

Y is selected from pyrrolidino and morpholino; and,

r, at each occurrence, is selected from 0, 1, and 2.

6. A compound of claim 5 , wherein:

A is selected from the group: phenyl, 2-pyridyl, 3-pyridyl, 2-pyrimidyl, 2-Cl-phenyl, 3-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 2-methylphenyl, 2-aminophenyl, and 2-methoxyphenyl; and,

B is selected from the group: 2-(aminosulfonyl)phenyl, 2-(methylaminosulfonyl)phenyl, 1-pyrrolidinocarbonyl, 2-(methylsulfonyl)phenyl, 2-(N,N-dimethylaminomethyl)phenyl, dimethylaminomethyl)phenyl, 2-(N-pyrrolidinylmethyl)phenyl, 1-methyl-2-imidazolyl, 2-methyl-1-imidazolyl, 2-(dimethylaminomethyl)-1-imidazolyl, 2-(N-(cyclopropylmethyl)aminomethyl)phenyl, 2-(N-(cyclobutyl)aminomethyl)phenyl, 2-(N-(cyclopentyl)aminomethyl)phenyl, and 2-(N-(3-hydroxypyrrolidinyl)methyl)phenyl.

7. A compound of claim 1 , wherein the compound is selected from:

1-[4-Methoxyphenyl]-3-cyano-6-[2′-methylsulfonyl-3-fluoro-[1,1′]-biphen-4-yl]-1,4-dihydropyrazolo-[4,3-d]-pyrimidine-5,7-dione;

1-[4-Methoxyphenyl]-3-(methoxycarbonyl)-6-[2′-aminosulfonyl-3-fluoro-[1, 1′]-biphen-4-yl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[4-Methoxyphenyl]-3-(aminocarbonyl)-6-[2′-aminosulfonyl-3-fluoro-[1,1]-biphen-4-yl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[4-Methoxyphenyl]-3-(methoxycarbonyl)-6-[2′-aminosulfonyl-[1,1′]-biphen-4-yl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[4-Methoxyphenyl]-6-[2′-aminosulfonyl-[1,1′]-biphen-4-yl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one-3-carboxylic acid;

1-[4-Methoxyphenyl]-3-(aminocarbonyl) 6 -[2′-aminosulfonyl-[1,1′]-biphen-4-yl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[4-Methoxyphenyl]-3-cyano-6-[2′-aminosulfonyl-[1,1′]-biphen-4-yl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[4-Methoxyphenyl]-3-(aminomethyl)-6-[2′-aminosulfonyl-[1,1′]-biphen-4-yl-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[4-Methoxyphenyl]-3-(ethoxycarbonyl)-6[4-(2-methylimidazol-1′-yl)phenyl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[4-Methoxyphenyl]-3-(aminocarbonyl)-6-[4-(2-methylimidazol-1′-yl)phenyl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[4-Methoxyphenyl]-3-(ethoxycarbonyl)-6-[2′-N-pyrrolidinylmethyl-[1,1′ ]-biphen-4-yl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[4-Methoxyphenyl]-3-(ethoxycarbonyl)-6-[2′-N-pyrrolidinylmethyl-[1,1′ ]-biphen-4-yl]-1,4,5,6-tetrahydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[4-Methoxyphenyl]-3-(aminocarbonyl)-6-12′-N-pyrrolidinylmethyl-[1,1′]-biphen-4-yl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[4-Methoxyphenyl]-3-cyano-6-[2′-N-pyrrolidinylmethyl-[1,1′]-biphen-4-yl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[4-Methoxyphenyl]-3-(ethoxycarbonyl)-6-[2-fluoro-4-(2-dimethylaminomethylimidazol-1′-yl)phenyl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[2-Aminomethylphenyl]-3-(ethoxycarbonyl)-6-[2′-methylsulfonyl-[1,1′]-biphen-4-yl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[4-Methoxyphenyl] 3-cyano-6-[2′-N,N-dimethylaminomethyl-[1,1′]-biphen-4-yl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[4-Methoxyphenyl]-3-cyano-5-methyl-6-[2′-N,N-dimethylaminomethyl-[1,1′]-biphen-4-yl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[2-Aminomethylphenyl]-3-cyano-6-[2′-methylsulfonyl-3-fluoro-[1,1′]-biphen-4-yl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[3-Aminobenzisoxazol-5′-yl]-3-trifluoromethyl-6-[4-(1-methylimidazol-2′-yl)phenyl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[4-Methoxyphenyl]-3-(ethoxycarbonyl)-6-[2′-hydroxymethyl-3-fluoro-[1,1′ ]-biphen-4-yl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[4-Methoxyphenyl]-3-(ethoxycarbonyl)-6-[2′-N-pyrrolidinylmethyl-3-fluoro-[1,1′]-biphen-4-yl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[4-Methoxyphenyl]-3-(aminocarbonyl)-6-[2′-N-pyrrolidinylmethyl-3-fluoro-[1,1′]-biphen-4-yl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[4-Methoxyphenyl]-3-(aminocarbonyl)-6-[2′-(3-(R)-hydroxy-N-pyrrolidinylmethyl)-3-fluoro-[1,1′ ]-biphen-4-yl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[4-Methoxyphenyl]-3-(N-formylaminomethyl)-6-[2′-methylsulfonyl-3-fluoro-[1,1′]-biphen-4-yl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[3-Aminobenzisoxazol-5′-yl]-3-(ethoxycarbonyl)-6-[2′-hydroxymethyl-[1,1′]-biphen-4-yl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[3-Aminobenzisoxazol-5′-yl]-3-(ethoxycarbonyl)-6-[2′-N-pyrrolidinylmethyl-[1,1′]-biphen-4-yl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[4-Methoxyphenyl]-3-[(imidazol-1-yl)methyl]-5-methyl-6-[(2′-N-pyrrolidinylmethyl-[1,1′]-biphen-4-yl)]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[4-Methoxyphenyl]-3-[(tetrazol-1-yl)methyl]-5-methyl-6-[(2′-N-pyrrolidinylmethyl-[1,1′ ]-biphen-4-yl)]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[4-Methoxyphenyl]-3-[(tetrazol-2-yl)methyl]-5-methyl-6-[(2′-N-pyrrolidinylmethyl-[1,1′]-biphen-4-yl)]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[3-Aminobenzisoxazol-5′-yl]-3,5-dimethyl-6-[2′-N-dimethylaminomethyl-[1,1′]-biphen-4-yl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[3-Aminobenzisoxazol-5′-yl]-3-methyl-6-[2′-N,N-dimethylaminomethyl-[1,1′]-biphen-4-yl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[3-Aminobenzisoxazol-5′-yl]-3-methyl-6-[2′-N-isopropylaminomethyl-[1,1′]-biphen-4-yl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[3-Aminobenzisoxazol-5′-yl]-3-methyl-6-[2′-(3-(R)-hydroxy-N-pyrrolidinyl)methyl-[1,1′]-biphen-4-yl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[3-Aminobenzisoxazol-5′-yl]-3-methyl-6-[4-(4,5-dihydroimidazol-1′-yl)phenyl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[3-Aminobenzisoxazol-5′-yl]-3-methyl-6-[2′-N-(cyclopropylmethyl)aminomethyl-[1,1′]-biphen-4-yl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[3-Aminobenzisoxazol-5′-yl]-3-methyl-6-[2′-N-pyrrolidinylmethyl-[1,1′]-biphen-4-yl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[3-Aminobenzisoxazol-5′-yl]-3-methyl-6-[2′-(N-methyl-N-isopropyl)aminomethyl-[1,1′ ]-biphen-4-yl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[3-Aminobenzisoxazol-5′-yl]-3,5-dimethyl-[2′-(3-(R)-hydroxy-N-pyrrolidinyl)methyl-[1,1′]-biphen-4-yl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[3-Aminobenzisoxazol-5′-yl]-3-trifluoromethyl-6-[2′-N,N-dimethylaminomethyl-[1,1′]-biphen-4-yl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[3-Aminobenzisoxazol-5′-yl]-3-trifluoromethyl-6-[2′-N,N-dimethylaminomethyl-[1,1′ 1-biphen-4-yl]-1,4,5,6-tetrahydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-3-Aminobenzisoxazol-5′-yl]-3-trifluoromethyl-6-[2′-(3-(R)-hydroxy-N-pyrrolidinyl)methyl-[1,1′]-biphen-4-yl]-1,4,5,6-tetrahydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[3-Aminobenzisoxazol-5′-yl]-3-methyl6-[4(2-methylimidazol-1′-yl)phenyl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

1-[3-Aminobenzisoxazol-5′-yl]-3-methyl-6-[4-(2-(dimethylaminomethyl)imidazol-1′-yl)-2-fluorophenyl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one; and,

1-[3-Aminobenzisoxazol-5′-yl]-3-trifluoromethyl-6-[4-(2-(dimethylaminomethyl)imidazol-1′-yl)phenyl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one;

or a pharmaceutically acceptable salt form thereof.

8. A pharmaceutical compositions, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt form thereof.

9. A pharmaceutical compositions, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 2 or a pharmaceutically acceptable salt form thereof.

10. A pharmaceutical compositions, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 3 or a pharmaceutically acceptable salt form thereof.

11. A pharmaceutical compositions, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 4 or a pharmaceutically acceptable salt form thereof.

12. A pharmaceutical compositions, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 5 or a pharmaceutically acceptable salt form thereof.

13. A pharmaceutical compositions, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 6 or a pharmaceutically acceptable salt form thereof.

14. A pharmaceutical compositions, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 7 or a pharmaceutically acceptable salt form thereof.

15. A method for treating a thromboembolic disorder, comprising: administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt form thereof.

16. A method for treating a thromboembolic disorder, comprising:

administering to a patient in need thereof a therapeutically effective amount of a compound of claim 2 or a pharmaceutically acceptable salt form thereof.

17. A method for treating a thromboembolic disorder, comprising:

administering to a patient in need thereof a therapeutically effective amount of a compound of claim 3 or a pharmaceutically acceptable salt form thereof.

18. A method for treating a thromboembolic disorder, comprising:

administering to a patient in need thereof a therapeutically effective amount of a compound of claim 4 or a pharmaceutically acceptable salt form thereof.

19. A method for treating a thromboembolic disorder, comprising:

administering to a patient in need thereof a therapeutically effective amount of a compound of claim 5 or a pharmaceutically acceptable salt form thereof.

20. A method for treating a thromboembolic disorder, comprising:

administering to a patient in need thereof a therapeutically effective amount of a compound of claim 6 or a pharmaceutically acceptable salt form thereof.

21. A method for treating a thromboembolic disorder, comprising:

administering to a patient in need thereof a therapeutically effective amount of a compound of claim 7 or a pharmaceutically acceptable salt form thereof.