Details for Patent: 6,858,616

Title:	Nitrogen containing heterobicycles as factor Xa inhibitors
Abstract:	The present application describes nitrogen containing heterobicyclics and derivatives thereof, or pharmaceutically acceptable salt forms thereof, which are useful as inhibitors of factor Xa.
Inventor(s):	Fevig; John M. (Lincoln University, PA), Cacciola; Joseph (Newark, DE), Clark; Charles G. (Cherry Hill, NJ), Han; Qi (Hockessin, DE), Lam; Patrick Yuk Sun (Chadds Ford, PA), Pinto; Donald J. P. (Kennett Square, PA), Pruitt; James R. (Landenberg, PA), Quan; Mimi L. (Newark, DE), Rossi; Karen A. (Boothwyn, PA)
Assignee:	Bristol-Myers Squibb Pharma Company (Princeton, NJ)
Filing Date:	Apr 26, 2002
Application Number:	10/133,998
Claims:	1. A compound selected from the group: ##STR238## or a sterioisomer or pharmaceutically acceptable salt thereof, wherein compounds of the above formulas are substituted with 0-2 R.sup.3 ; G is a group of formula I or II: ##STR239## ring D is selected from --(CH.sub.2).sub.3 --, --(CH.sub.2).sub.4 --, --CH.sub.2 N.dbd.CH--, --CH.sub.2 CH.sub.2 N.dbd.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.sub.1-3 alkoxy, NH.sub.2, NH(C.sub.1-3 alkyl), N(C.sub.1-3 alkyl).sub.2, CH.sub.2 NH.sub.2, CH.sub.2 NH(C.sub.1-3 alkyl), CH.sub.2 N(C.sub.1-3 alkyl).sub.2, CH.sub.2 CH.sub.2 NH.sub.2, CH.sub.2 CH.sub.2 NH(C.sub.1-3 alkyl), and CH.sub.2 CH.sub.2 N(C.sub.1-3 alkyl).sub.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.sub.1-3 alkoxy, CN, C(.dbd.NR.sup.8)NR.sup.7 R.sup.9, NHC(.dbd.NR.sup.8)NR.sup.7 R.sup.9, NR.sup.8 CH(.dbd.NR.sup.7), C(O)NR.sup.7 RB, (CR.sup.8 R.sup.9).sub.t NR.sup.7 R.sup.8, SH, C.sub.1-3 alkyl-S, S(O)R.sup.3b, S(O).sub.2 R.sup.3a, S(O).sub.2 NR.sup.2 R.sup.2a, and OCF.sub.3 ; R' is selected from H, F, Cl, Br, I, SR.sup.3, CO.sub.2 R.sup.3, NO.sub.2, (CH.sub.2).sub.t OR.sup.3, C.sub.1-4 alkyl, OCF.sub.3, CF.sub.3, C(O)NR.sup.7 R.sup.8, and (CR.sup.8 R.sup.9).sub.t NR.sup.7 R.sup.8 ; alternatively, R" and R' combine to form methylenedioxy or ethylenedioxy; Z is N or CR.sup.1a ; Z.sup.1 is S, O, or NR.sup.3 ; Z.sup.2 is selected from H, C.sub.1-4 alkyl, phenyl, benzyl, C(O)R.sup.3, and S(O).sub.p R.sup.3c ; R.sup.1a is selected from H, --(CH.sub.2).sub.r -R.sup.1 ', --CH.dbd.CH-R.sup.1 ', NHCH.sub.2 R.sup.1 ", OCH.sub.2 R.sup.1 ", SCH.sub.2 R.sup.1 ", NH(CH.sub.2).sub.2 (CH.sub.2).sub.t R.sup.1 ', O(CH.sub.2).sub.2 (CH.sub.2).sub.t R.sup.1 ', and S(CH.sub.2).sub.2 (CH.sub.2).sub.t R.sup.1 '; R.sup.1 ' is selected from H, C.sub.1-3 alkyl, F, Cl, Br, I, --CN, --CHO, (CF.sub.2).sub.r CF.sub.3, (CH.sub.2).sub.r OR.sup.2, NR.sup.2 R.sup.2a, C(O)R.sup.2c, OC(O)R.sup.2, (CF.sub.2).sub.r CO.sub.2 R.sup.2 C, S(O).sub.p R.sup.2b, NR.sup.2 (CH.sub.2).sub.r OR.sup.2, C(.dbd.NR.sup.2 C)NR.sup.2 R.sup.2a, NR.sup.2 C(O)R.sup.2b, NR.sup.2 C(O)R.sup.3, NR.sup.2 C(O)NHR.sup.2b, NR.sup.2 C(O).sub.2 R.sup.2a, OC(O)NR.sup.2a R.sup.2b, C(O)NR.sup.2 R.sup.2a, C(O)NR.sup.2 (CH.sub.2).sub.r OR.sup.2, SO.sub.2 NR.sup.2 R.sup.2a, NR.sup.2 SO.sub.2 R.sup.2b, C.sub.3-6 carbocyclic residue substituted with 0-2 R.sup.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.sup.4a ; R" is selected from H, CH(CH.sub.2 OR.sup.2).sub.2, C(O)R.sup.2c, C(O)NR.sup.2 R.sup.2a, S(O)R.sup.2b, S(O).sub.2 R.sup.2b, and SO.sub.2 NR.sup.2 R.sup.2a ; R.sup.2, at each occurrence, is selected from H, CF.sub.3, C.sub.1-6 alkyl, benzyl, C.sub.3-6 carbocyclic residue substituted with 0-2 R.sup.4b, a C.sub.3-6 carbocyclic-CH.sub.2 -- residue substituted with 0-2 R.sup.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.sup.4b ; R.sup.2a, at each occurrence, is selected from H, CF.sub.3, C.sub.1-6 alkyl, benzyl, C.sub.3-6 carbocyclic residue substituted with 0-2 R.sup.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.sup.4b ; R.sup.2b, at each occurrence, is selected from CF.sub.3, C.sub.1-4 alkoxy, C.sub.1-6 alkyl, benzyl, C.sub.3-6 carbocyclic residue substituted with 0-2 R.sup.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.sup.4b ; R.sup.2c, at each occurrence, is selected from CF.sub.3, OH, C.sub.1-4 alkoxy, C.sub.1-6 alkyl, benzyl, C.sub.3-6 carbocyclic residue substituted with 0-2 R.sup.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.sup.4b ; alternatively, R.sup.2 and R.sup.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.sup.4b and containing from 0-1 additional heteroatoms selected from the group consisting of N, O, and S; R.sup.3, at each occurrence, is selected from H, C.sub.1-4 alkyl, and phenyl; R.sup.3a, at each occurrence, is selected from H, C.sub.1-4 alkyl, and phenyl; R.sup.3b, at each occurrence, is selected from H, C.sub.1-4 alkyl, and phenyl; R.sup.3c, at each occurrence, is selected from C.sub.1-4 alkyl, and phenyl; A is selected from: C.sub.3-10 carbocyclic residue substituted with 0-2 R.sup.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.sup.4 ; B is selected from: Y, X-Y, C(.dbd.NR.sup.2)NR.sup.2 R.sup.2a, and NR.sup.2 C(.dbd.NR.sup.2)NR.sup.2 R.sup.2a ; X is selected from C.sub.1-4 alkylene, --CR.sup.2 (CR.sup.2 R.sup.2b)(CH.sub.2).sub.t --, --C(O)--, --C(.dbd.NR.sup.1 ")-, --CR.sup.2 (NR.sup.1 "R.sup.2)--, --CR.sup.2 (OR.sup.2)--, --CR.sup.2 (SR.sup.2, --C(O)CR.sup.2 R.sup.2a --, --CR.sup.2 R.sup.2a C(O), --S(O).sub.p --, --S(O).sub.p CR.sup.2 R.sup.2a --, --CR.sup.2 R.sup.2a S(O).sub.p --, --S(O).sub.2 NR.sup.2 --, --NR.sup.2 S(O).sub.2 --, --NR.sup.2 S(O).sub.2 CR.sup.2 R.sup.2a, --CR.sup.2 R.sup.2a S(O).sub.2 NR.sup.2 --, --NR.sup.2 S(O).sub.2 NR.sup.2 --, --C(O)NR.sup.2 --, --NR.sup.2 C(O), --C(O)NR.sup.2 CR.sup.2 R.sup.2a --, --NR.sup.2 C(O)CR.sup.2 R.sup.2a -, --CR.sup.2 R.sup.2a C(O)NR.sup.2 --, --CR.sup.2 R.sup.2a NR.sup.2 C(O)--, --NR.sup.2 C(O)O--, --OC(O)NR.sup.2 --, --NR.sup.2 C(O)NR.sup.2 --, --NR.sup.2 --, --NR.sup.2 CR.sup.2 R.sup.2a, CR.sup.2 R.sup.2a NR.sup.2, O, --CR.sup.2 R.sup.2a O--, and --OCR.sup.2 R.sup.2a --; Y is selected from: CH.sub.2 NR.sup.2 R.sup.2a ; CH.sub.2 CH.sub.2 NR.sup.2 R.sup.2a ; C.sub.3-10 carbocyclic residue substituted with 0-2 R.sup.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.sub.2 R.sup.4a ; R.sup.4, at each occurrence, is selected from H, .dbd.O, (CH.sub.2).sub.r OR.sup.2, F, Cl, Br, 1, C.sub.1-4 alkyl, --CN, NO.sub.2, (CH.sub.2).sub.r NR.sup.2 R.sup.2a, (CH.sub.2).sub.r C(O)R.sup.2c NR.sup.2 C(O)R.sup.2b, C(O)NR.sup.2 R.sup.2a, NR.sup.2 C(O)NR.sup.2 R.sup.2a, C(.dbd.NR.sup.2)NR.sup.2 R.sup.2a, C(.dbd.NS(O).sub.2 R.sup.5)NR.sup.2 R.sup.2a, NHC(.dbd.NR.sup.2)NR.sup.2 R.sup.2a, C(O)NHC(.dbd.NR.sup.2)NR.sup.2 R.sup.2a, SO.sub.2 NR.sup.2 R.sup.2a, NR.sup.2 SO.sub.2 NR.sup.2 R.sup.2a, NR.sup.2 SO.sub.2 --C.sub.1-4 alkyl, NR.sup.2 SO.sub.2 R.sup.5, S(O).sub.p R.sup.5, (CF.sub.2).sub.r CF.sub.3, NCH.sub.2 R.sup.1 ", OCH.sub.2 R.sup.1 ", SCH.sub.2 R.sup.1 ", N(CH.sub.2).sub.2 (CH.sub.2).sub.t R.sup.1 ', O(CH.sub.2).sub.2 (CH.sub.2).sub.t R.sup.1 ', and S(CH.sub.2).sub.2 (CH.sub.2).sub.t R.sup.1 '; alternatively, one R.sup.4 is a 5-6 membered aromatic heterocycle containing from 1-4 heteroatoms selected from the group consisting of N, O, and S; R.sup.4a, at each occurrence, is selected from H, .dbd.O, (CH.sub.2).sub.r OR.sup.2, (CH.sub.2).sub.r --F, (CH.sub.2).sub.r -Br, (CH.sub.2).sub.r --Cl, Cl, Br, F, I, C.sub.4 alkyl, --CN, NO.sub.2, (CH.sub.2).sub.r NR.sup.2 R.sup.2a, (CH.sub.2).sub.r C(O)R.sup.2 C, NR.sup.2 C(O)R.sup.2b, C(O)NR.sup.2 R.sup.2a, (CH.sub.2).sub.r N.dbd.CHOR.sup.3, C(O)NH(CH.sub.2).sub.2 NR.sup.2 R.sup.2a, NR.sup.2 C(O)NR.sup.2 R.sup.2a, C(.dbd.NR.sup.2)NR.sup.2 R.sup.2a, SO.sub.2 NR.sup.2 R.sup.2a, NR.sup.2 SO.sub.2 NR.sup.2 R.sup.2a, NR.sup.2 SO.sub.2 --C.sub.1-4 alkyl, C(O)NHSO.sub.2 --C.sub.1-4 alkyl, NR.sup.2 SO.sub.2 R.sup.5, S(O).sub.p R.sup.5, and (CF.sub.2).sub.r CF.sub.3 ; alternatively, one R.sup.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.sup.5 ; R.sup.4b, at each occurrence, is selected from H, .dbd.O, (CH.sub.2).sub.r OR.sup.3, F, Cl, Br, I, C.sub.1-4 alkyl, --CN, NO.sub.2, (CH.sub.2).sub.r NR.sup.3 R.sup.3a, (CH.sub.2).sub.r C(O)R.sup.3, (CH.sub.2).sub.r C(O)OR.sup.3c, NR.sup.3 C(O)R.sup.3a, C(O)NR.sup.3 R.sup.3a, NR.sup.3 C(O)NR.sup.3 R.sup.3a, C(.dbd.NR.sup.3)NR.sup.3 R.sup.3a, NR.sup.3 C(.dbd.NR.sup.3)NR.sup.3 R.sup.3a, SO.sub.2 NR.sup.3 R.sup.3a, NR.sup.3 SO.sub.2 NR.sup.3 R.sup.3a, NR.sup.3 SO.sub.2 --C.sub.1-4 alkyl, NR.sup.3 SO.sub.2 CF.sub.3, NR.sup.3 SO.sub.2 -phenyl, S(O).sub.p CF.sub.3, S(O).sub.p -C.sub.1-4 alkyl, S(O).sub.p -phenyl, and (CF.sub.2).sub.r CF.sub.3 ; R.sup.5, at each occurrence, is selected from CF.sub.3, C.sub.1-6 alkyl, phenyl substituted with 0-2 R.sup.6, and benzyl substituted with 0-2 R.sup.6 ; R.sup.6, at each occurrence, is selected from H, OH, (CH.sub.2).sub.r OR.sup.2, halo, C.sub.1-4 alkyl, CN, NO.sub.2, (CH.sub.2).sub.r NR.sup.2 R.sup.2a, (CH.sub.2).sub.r C(O)R.sup.2b, NR.sup.2 C(O)R.sup.2b, NR.sup.2 C(O)NR.sup.2 R.sup.2a, C(.dbd.NH)NH.sub.2, NHC(.dbd.NH)NH.sub.2, SO.sub.2 NR.sup.2 R.sup.2a, NR.sup.2 SO.sub.2 NR.sup.2 R.sup.2a, and NR.sup.2 SO.sub.2 C.sub.1-4 alkyl; R.sup.7, at each occurrence, is selected from H, OH, C.sub.1-6 alkyl, C.sub.1-6 alkylcarbonyl, C.sub.1-6 alkoxy, C.sub.1-4 alkoxycarbonyl, (CH.sub.2).sub.n -phenyl, C.sub.6-10 aryloxy, C.sub.6-10 aryloxycarbonyl, C.sub.6-10 arylmethylcarbonyl, C.sub.1-4 alkylcarbonyloxy C.sub.1-4 alkoxycarbonyl, C.sub.6-10 arylcarbonyloxy C.sub.1-4 alkoxycarbonyl, C.sub.1-6 alkylanocarbonyl, phenylaminocarbonyl, and phenyl C.sub.1-4 alkoxycarbonyl; R.sup.8, at each occurrence, is selected from H, C.sub.1-6 alkyl and (CH.sub.2).sub.n -phenyl; alternatively, R.sup.7 and R.sup.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.sup.9, at each occurrence, is selected from H, C.sub.1-6 alkyl and (CH.sub.2).sub.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: ##STR240## wherein compounds of the above formulas are substituted with 0-2 R.sup.3 ; G is selected from the group: ##STR241## ##STR242## ##STR243## A is selected from one of the following carbocyclic and heterocyclic systems which are substituted with 0-2 R.sup.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.sub.1-4 alkylene, --C(O)--, --C(.dbd.NR.sup.1 ")--, --CR.sup.2 (NR.sup.1 "R.sup.2)--, --C(O)CR.sup.2 R.sup.2a --, --CR.sup.2 R.sup.2a C(O), --C(O)NR.sup.2 --, --NR.sup.2 C(O)--, C(O)NR.sup.2 CR.sup.2 R.sup.2a, --NR.sup.2 C(O)CR.sup.2 R.sup.2a, --CR.sup.2 R.sup.2a C(O)NR.sup.2 --, CR.sup.2 R.sup.2a NR.sup.2 C(O), --NR.sup.2 C(O)NR.sup.2 --, --NR.sup.2 --, --NR.sup.2 CR.sup.2 R.sup.2a, CR.sup.2 R.sup.2a NR.sup.2, O, CR.sup.2 R.sup.2a O--, and --OCR.sup.2 R.sup.2a --; Y is C.sub.2 NR.sup.2 R.sup.2a or CH.sub.2 CH.sub.2 N.sup.2 R.sup.2a ; alternatively, Y is selected from one of the following carbocyclic and heterocyclic systems that are substituted with 0-2 R.sup.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: ##STR244## 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: ##STR245## ##STR246## 4. A compound of claim 3, wherein: G is selected from: ##STR247## 5. A compound of claim 4, wherein: A is selected from phenyl, pyridyl, and pyrimidyl, and is substituted with 0-2 R.sup.4 ; and, B is selected from X-Y, phenyl, pyrrolidino, morpholino, 1,2,3-triazolyl, and imidazolyl, and is substituted with 0-1 R.sup.4a ; R.sup.2, at each occurrence, is selected from H, CH.sub.3, CH.sub.2 CH.sub.3, cyclopropylmethyl, cyclobutyl, and cyclopentyl; R.sup.2a, at each occurrence, is H or CH.sub.3 ; alternatively, R.sup.2 and R.sup.2a, together with the atom to which they are attached, combine to form pyrrolidine substituted with O.sub.2 R.sup.4b ; R.sup.4, at each occurrence, is selected from OH, (CH.sub.2).sub.r OR.sup.2, halo, C.sub.1-4 alkyl, (CH.sub.2).sub.r NR.sup.2 R.sup.2a, and (CF.sub.2).sub.r CF.sub.3 ; R.sup.4a is selected from CIA alkyl, CF.sub.3, (CH.sub.2).sub.r OR.sup.2, (CH.sub.2).sub.r NR.sup.2 R.sup.2a, S(O).sub.p R.sup.5, SO.sub.2 NR.sup.2 R.sup.2a, and 1-CF.sub.3 -tetrazol-2-yl; R.sup.4b, at each occurrence, is selected from H, CH.sub.3, and OH; R.sup.5, at each occurrence, is selected from CF.sub.3, C.sub.1-6 alkyl, phenyl, and benzyl; X is CH.sub.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-y l]-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]-bi phen-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-dihydropyra zolo-[4,3-d]-pyrimidin-7-one-3-carboxylic acid; 1-[4-Methoxyphenyl]-3-(aminocarbonyl).sub.6 -[2'-aminosulfonyl-[1,1']-biphen-4-yl]-1,6-dihydropyrazolo-[4,3-d]-pyrimid in-7-one; 1-[4-Methoxyphenyl]-3-cyano-6-[2'-aminosulfonyl-[1,1']-biphen-4-yl]-1,6-dih ydropyrazolo-[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']-bip hen-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-dimethylaminomethyl imidazol-1'-yl)phenyl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one; 1-[2-Aminomethylphenyl]-3-(ethoxycarbonyl)-6-[2'-methylsulfonyl-[1,1']-biph en-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-dihydropyraz olo-[4,3-d]-pyrimidin-7-one; 1-[4-Methoxyphenyl]-3-cyano-5-methyl-6-[2'-N,N-dimethylaminomethyl-[1,1']-b iphen-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'-y l)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-pyrrolidinylme thyl)-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-pyrrolidiny lmethyl-[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-pyrrolidiny lmethyl-[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-pyrrolidiny lmethyl-[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)phen yl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one; 1-[3-Aminobenzisoxazol-5'-yl]-3-methyl-6-[2'-N-(cyclopropylmethyl)aminometh yl-[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']-bi phen-4-yl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one; 1-[3-Aminobenzisoxazol-5'-yl]-3-methyl-6-[2'-(N-methyl-N-isopropyl)aminomet hyl-[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-pyrrolidiny l)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-dimethylaminometh yl-[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-dimethylaminometh yl-[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-pyrro lidinyl)methyl-[1,1']-biphen-4-yl]-1,4,5,6-tetrahydropyrazolo-[4,3-d]-pyrim idin-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)imidazo l-1'-yl)-2-fluorophenyl]-1,6-dihydropyrazolo-[4,3-d]-pyrimidin-7-one; and, 1-[3-Aminobenzisoxazol-5'-yl]-3-trifluoromethyl-6-[4-(2-(dimethylaminomethy l)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.