Phenyl-isoxazoles as factor XA Inhibitors

A compound of formula Ib:

• or a stereoisomer or pharmaceutically acceptable salt thereof, wherein;
• J is O
• D is selected from C(═NR8)NR7R9, and CR8R9NR7R8, provided that D is substituted meta on E;
• E is phenyl substituted with 1 R;
• R is selected from H, halogen, OR3, (CH2)OR3, C1-4 alkyl, OCF3, and CF3;
• Z is C(O)NH, provided that Z does not form a N—N bond with group A;
• R1a is absent or selected from —(CH2)r-R1′, NCH2R1″, OCH2R1″, SCH2R1″, N(CH2)2(CH2)tR1′, O(CH2)2(CH2)tR1′, and S(CH2)2(CH2)tR1′;
• R1′ is selected from H, C1-3 alkyl, halo, (CF2)rCF3, OR2, NR2R2a, C(O)R2c, OC(O)R2, (CF2)rCO2R2c, S(O)pR2b, NR2(CH2)rOR2, NR2C(O)R2b, NR2C(O)NHR2b, NR2C(O)2R2a, OC(O)NR2b, C(O)NR2R2a, SO2NR2R2a, NR2SO2R2b, and C3-6 carbocyclic residue substituted with 0-2 R4;
• R1″ is selected from H, C(O)R2b, C(O)NR2R2a, S(O)R2b, S(O)2R2b, and SO2NR2R2a;
• R2, at each occurrence, is selected from H, CF3, C1-6 alkyl, benzyl, and C3-6 carbocyclic residue substituted with 0-2 R4b;
• R2a, at each occurrence, is selected from H, CF3, C1-6 alkyl, benzyl, and C3-6 carbocyclic residue substituted with 0-2 R4b;
• R2b, at each occurrence, is selected from CF3, C1-4 alkoxy, C1-6 alkyl, benzyl, and C3-6 carbocyclic residue substituted with 0-2 R4b;
• R2c, at each occurrence, is selected from CF3, OH, C1-4 alkoxy, C1-6 alkyl, benzyl, and C3-6 carbocyclic residue substituted with 0-2 R4b;
• R3, at each occurrence, is selected from H, C1-4 alkyl, and phenyl;
• R3a, at each occurrence, is selected from H, C1-4 alkyl, and phenyl;
• A is selected from:
• C3-10 carbocyclic residue substituted with 0-2 R4, and
• pyridyl substituted with 0-2 R4;
• B is selected from:
• Y, X—Y, NR2R2a, C(═NR2)NR2R2a, NR2C(═NR2)NR2R2a,
• C3-10 carbocyclic residue substituted with 0-2 R4a, and
• pyridyl substituted with 0-2 R4a;
• X is selected from C1-4 alkylene, —CR2(CR2R2b)(CH2)t—, —C(O)—, —C(═NR)—, —CR2(NR1″R2)—, —CR2(OR2)—, —CR2(SR2)—, —C(O)CR2R2a—, —CR2R2aC(O), —S(O)p—, —S(O)pCR2R2a—, —CR2R2aS(O)p—, —S(O)2NR2—, —NR2S(O)2—, —NR2S(O)2CR2R2a—, —CR2R2aS(O)2NR2—, —NR2S(O)2NR2—, —C(O)NR2—, —NR2C(O)—, —C(O)NR2CR2R2a—, —NR2C(O)CR2R2a—, —CR2R2aC(O)NR2—, —CR2R2aNR2C(O)—, —NR2C(O)O—, —OC(O)NR2—, —NR2C(O)NR2—, —NR2—, —NR2CR2R2a—, —CR2R2aNR2—, O, —CR2R2aO—, and —OCR2R2a—;
• Y is selected from:
• (CH2)rNR2R2a, provided that X—Y do not form a N—N, O—N, or S—N bond and that X is other than a group terminating with C(O),
• C3-10 carbocyclic residue substituted with 0-2 R4a, and
• pyridyl substituted with 0-2 R4a;
• R4, at each occurrence, is selected from ═O, (CH2)rOR2, halo, C1-4 alkyl, —CN, NO2, (CH2)rNR2R2a, (CH2)rC(O)R2b, NR2C(O)R2b, C(O)NR2R2a, NR2C(O)NR2R2a, C(═NR2)NR2R2a, NHC(═NR2)NR2R2a, SO2NR2R2a, NR2SO2NR2R2a, NR2SO2—C1-4 alkyl, NR2SO2R5, S(O)pR5, (CF2)rCF3, NCH2R1″, OCH2R1″, SCH2R1″, N(CH2)2(CH2)tR1′, O(CH2)2(CH2)tR1′, and S(CH2)2(CH2)tR1′;
• alternatively, one R4 is pyridyl;
• R4a, at each occurrence, is selected from ═O, (CH2)rOR2, halo, C1-4 alkyl, —CN, NO2, (CH2)rNR2R2a, NR2C(O)R2b, C(O)NR2R2a, NR2C(O)NR2R2a, C(═NR2)NR2R2a, NHC(═NR2)NR2R2a, SO2NR2R2a, NR2SO2NR2R2a, NR2SO2—C1-4 alkyl, NR2SO2R5, S(O)pR5, and (CF2)rCF3;
• alternatively, one R4a is pyridyl;
• R4b, at each occurrence, is selected from ═O, (CH2)rOR3, halo, C1-4 alkyl, —CN, NO2, (CH2)rNR3R3a, (CH2)rC(O)R3, NR3O(O)R3a, C(O)NR3R3a, NR3C(O)NR3R3a, C(═NR3)NR3R3a, NH3C(═NR3)NR3R3a, SO2NR3R3a, NR3SO2NR3R3a, NR3SO2-C1-4 alkyl, NR3SO2CF3, NR3SO2-phenyl, S(O)pCF3, S(O)p-C1-4 alkyl, S(O)p-phenyl, and (CF2)rCF3;
• R5, at each occurrence, is selected from CF3, C1-6 alkyl, phenyl substituted with 0-2 R6, and benzyl substituted with 0-2 R6;
• R6, at each occurrence, is selected from H, OH, (CH2)rOR2, halo, C1-4 alkyl, CN, NO2, (CH2)rNR2R2a, (CH2)rC(O)R2b, NR2C(O)R2b, NR2C(O)NR2R2a, C(═NH)NH2, NHC(═NR)NH2, SO2NR2R2a, NR2SO2NR2R2a, and NR2SO2C1-4 alkyl;
• R7, at each occurrence, is selected from H, OH, C1-6 alkyl, C1-6 alkylcarbonyl, C1-6 alkoxy, C1-4 alkoxycarbonyl, (CH2)n-phenyl, C6-10 aryloxy, C6-10 aryloxycarbonyl, C6-10 arylmethylcarbonyl, C1-4 alkylcarbonyloxy C1-4 alkoxycarbonyl, C6-10 arylcarbonyloxy C1-4 alkoxycarbonyl, C1-6 alkylaminocarbonyl, phenylaminocarbonyl, and phenyl C1-4 alkoxycarbonyl;
• R8, at each occurrence, is selected from H, C1-6 alkyl and (CH2)n-phenyl;
• R9, at each occurrence, is selected from H, C1-6 alkyl and (CH2)n-phenyl;
• n, at each occurrence, is selected from 0, 1, 2, and 3;
• p, at each occurrence, is selected from 0, 1, and 2;
• r, at each occurrence, is selected from 0, 1, 2, and 3;
• and,
• t, at each occurrence, is selected from 0 and 1;
• provided that D—E— and —Z—A—B are not both benzamidines and B is other than C(O)(CH2)rNR2R2a.