# US 9,518,064 B2 · Imidazothiadiazole and imidazopyridazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation

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- Number: US 9,518,064 B2
- Document ID: US9518064B2
- Status: Granted
- Kind: B2
- Application number: 14/396,831
- Filed: 2013-04-24
- Published: 2015-04-30
- Granted: 2016-12-13
- Earliest claimed: 2012-04-26
- Assignees: Bristol-Myers Squibb Company; Universite de Montreal
- Applicants: Bristol-Myers Squibb Company; Universite De Montreal
- Inventors: Alain Martel; François Tremblay; Anne Marinier; Eldon Scott Priestley; Shoshana L. Posy; R. Michael Lawrence; Michael M. Miller
- Web page: https://patentgrep.com/patent/US9518064B2

## CPC

- C07D 513/04: Ortho-condensed systems
- A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 487/04: Ortho-condensed systems
- A61K 31/433: Thidiazoles
- A61K 31/437: the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
- A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465)
- A61K 31/497: containing further heterocyclic rings
- A61K 31/506: not condensed and containing further heterocyclic rings
- A61K 31/513: having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- A61K 38/12: Cyclic peptides {, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C (A61K38/043 - A61K38/046 take precedence)}
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

The present invention provides imidazothiadiazole compounds of Formula (I); Wherein W, Y, R0, R2, R4, Ra, Rb, X1, X2, X3 and X4 are as defined herein, or a stereoisomer, tautomer, pharmaceutically acceptable salt, prodrug ester or solvate form thereof, wherein all of the variables are as defined herein. These compounds are inhibitors of platelet aggregation and thus can be used as medicaments for treating or preventing thromboembolic disorders.

## Claims

### Claim 1

A compound of Formula I:
or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate or prodrug thereof, wherein:
W is O or S;
R0 is R1 or R1a;
Y is S or —CR8═CR9—;
R1 is independently selected from the group consisting of:
halo,
C1-C4 alkyl,
C2-C3 alkenyl,
C2-C3 alkynyl,
C3-C4 cycloalkyl,
C1-C4 alkoxy,
C1-C2 alkoxy-C1-C2 alkyl,
tetrahydrofuran-2-yl;
C1-C4 alkylthio,
C1-C4 alkylNH—,
(C1-C4 alkyl)2N—,
halo-C1-C2-alkyl, which contains 1 to 5 halogens, where halo is F or Cl,
halo-C3-C4 cycloalkyl,
halo-C1-C2 alkoxy, and
halo-C1-C2 alkylthio;
R1a is independently selected from the group consisting of:
H,
halo,
C1-C4 alkyl,
C2-C3 alkenyl,
C2-C3 alkynyl,
C3-C4 cycloalkyl,
C1-C4 alkoxy,
C1-C2 alkoxy-C1-C2 alkyl,
tetrahydrofuran-2-yl;
C1-C4 alkylthio,
C1-C4 alkylNH—,
(C1-C4 alkyl)2N—,
halo-C1-C2-alkyl, which contains 1 to 5 halogens, where halo is F or Cl,
halo-C3-C4 cycloalkyl,
halo-C1-C2 alkoxy, and
halo-C1-C2 alkylthio;
R8 and R9 are independently selected from the group consisting of:
H,
halo,
C1-C4 alkyl,
C1-C4 alkoxy,
halo-C1-C2 alkyl,
halo-C1-C2 alkoxy,
CN, and
OH;
provided that at least one of R1a, R8 and R9 is other than H;
R2 is selected from the group consisting of:
H,
halo,
C1-C4 alkyl,
alkoxy, and
cyano;
X1 is selected from the group consisting of CH, N or CR10;
X2, X3 and X4 are independently selected from CR3 or N;
R3 is selected from the group consisting of H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 alkoxy, C1-C4 alkylthio, halo, OH, CN, OCF3, OCHF2, OCH2F, C1-C2-alkoxy-C1-C2-alkoxy, halo-C1-C3-alkyl, which contains 1 to 5 halogens, benzyloxy substituted by 0 to 3 groups independently selected from the group consisting of halo, C1-C4 alkoxy, C1-C4 alkyl, cyclopropyl, CF3, OCF3, 5- or 6-membered heteroaryl, OH, OCHF2, di-C1-C4-alkylamino, and cyano, and —(CH2)n1-phenyl substituted by 0 to 3 groups independently selected from the group consisting of halo, C1-C4 alkoxy, C1-C4 alkyl, cyclopropyl, CF3, OCF3, 5- or 6-membered heteroaryl, OH, OCHF2, di-C1-C4-alkylamino, and cyano;
R4 and R5 are independently selected from H, C1-C6 alkyl, halo-C1-C3 alkyl, hydroxy-C1-C3 alkyl, and C1-C3 alkoxy-C1-C3 alkyl; or R4 and R5 can be taken together with the carbon to which they are attached to form a C3-C7 cycloalkyl ring;
is phenyl or a 6-membered heteroaryl ring, at least one ring member of which is a nitrogen, which
ring is substituted with 0 to 2 Ra groups;
B is selected from the group consisting of a C6-C10 aryl, a 5- to 10-membered heteroaryl, a 4- to 10-membered heterocyclyl containing carbon atoms and 1 to 4 additional heteroatoms selected from N, O, and S, and a C3-C8 cycloalkyl which may contain unsaturation, all of which are substituted by 0 to 3 Rb groups;
Ra, at each occurrence, is independently selected from the group consisting of H, halo, halo-C1-C4 alkoxy, OH, CN, NO2, NR6R7, COOH, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkoxycarbonyl, (C═O)NR6R7, C1-C4 alkoxy-C1-C4 alkoxy, C1-C4 alkylsulfonyl, C1-C4 alkylsulfinyl, S(═O)2NR6R7, and C1-C5 alkyl substituted by 0 to 7 groups independently selected from halo, CF3, OCF3, OH, hydroxy-C1-C4-alkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkoxy, di-C1-C4-alkylaminophenyl-C1-C4-alkyl, (di-C1-C4-alkoxy-C1-C4-alkyl)-C1-C4-alkyl, di-C1-C4-alkylamino, C3-C6-cycloalkyl, phenyl, and C1-C4 alkylthio;
Rb, at each occurrence, is independently selected from the group consisting of H, halo, halo-C1-C4 alkoxy, OH, CN, NO2, NR6R7, COOH, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkoxycarbonyl, (C═O)NR6R7, C1-C4 alkoxy-C1-C4 alkoxy, C1-C4 alkylsulfonyl, C1-C4 alkyl sulfinyl, S(═O)2NR6R7, N(R13)(C═O)NR6R7, N(R13)(C═O)OR14, N(R13)(C═O)R14, NR13S(O)R14, NR13SO2R14, O(C═O)NR6R7, O(C═O)OR14, O(C═O)R14, (C═O)OR14, C6-C10 aryl, 5-6-membered heteroaryl, 4- to 10-membered heterocyclyloxy and C1-C5 alkyl substituted by 0 to 7 groups independently selected from halo, CF3, OCF3, OH, hydroxy-C1-C4-alkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkoxy, di-C1-C4-alkylaminophenyl-C1-C4-alkyl, (di-C1-C4-alkoxy-C1-C4-alkyl)-C1-C4-alkyl, di-C1-C4-alkylamino, C3-C6-cycloalkyl, phenyl, C1-C4-alkoxyphenyl-C1-C4-alkoxy, 4- to 10-membered heterocyclyloxy and C1-C4 alkylthio;
R6 and R7 are independently, at each occurrence, selected from the group consisting of:
H,
C1-C4 alkyl,
halo-C1-C4-alkyl,
C1-C4 alkyleneoxy-C1-C4-alkylene,
C2-C4 alkenyl,
C2-C4 alkynyl,
—(CR14R14)n1-phenyl substituted by 0 to 3 groups independently selected from the group consisting of halo, C1-C4 alkoxy, C1-C4 alkyl, cyclopropyl, CF3, OCF3, 5- or 6-membered heteroaryl, OH, OCHF2, di-C1-C4-alkylamino, and cyano,
—(CHR13)n1—C3-C6-cycloalkyl substituted by 0 to 3 groups independently selected from the group consisting of halo, CF3, OCF3, 5- or 6-membered heteroaryl, OH, hydroxy-C1-C4-alkyl, and C1-C4 alkyl,
—(CHR13)n1-4- to 10-membered-heterocyclyl substituted by 0 to 3 groups independently selected from the group consisting of halo, CF3, OCF3, 5- or 6-membered heteroaryl, OH, oxo, hydroxy-C1-C4-alkyl, and C1-C4 alkyl,
—(CHR13)n1-5- to 10-membered-heteroaryl substituted by 0 to 3 groups independently selected from the group consisting of halo, CF3, OCF3, 5- or 6-membered heteroaryl, OH, hydroxy-C1-C4-alkyl, and C1-C4 alkyl,
di-C1-C4-alkylamino-C1-C4-alkyl,
C1-C4-alkylcarbonylamino-C1-C4-alkyl,
di-C1-C4-alkoxy-C1-C4-alkyl,
di-C1-C4-alkylaminophenyl,
hydroxy-C1-C4-alkyl,
cyano-C1-C4-alkyl,
C1-C4-alkoxy-C1-C4-alkyl,
C1-C4-alkoxycarbonyl-C1-C4-alkyl,
C1-C4-alkoxycarbonyl,
C1-C4-alkylcarbonyl,
phenylcarbonyl;
C1-C4-alkoxycarbonylamino-C1-C4-alkylcarbonyl,
di-C1-C4-alkylamino-C1-C4-alkylcarbonyl,
amino-C1-C4-alkylcarbonyl,
4- to 10-membered-heterocyclyl-carbonyl, and
alternatively, R6 and R7, when attached to the same nitrogen, combine to form a 4- to 8-membered heterocyclic ring containing carbon atoms substituted by 0 to 3 groups independently selected from the group consisting of halo, CF3, CHF2, OCF3, OCHF2, OCH2F, 5- or 6-membered heteroaryl, OH, oxo, hydroxy-C1-C4-alkyl, C1-C4 alkyl and C1-C4 alkoxy, and 0 to 2 additional heteroatoms selected from N, NR13, O and S(O)p;
R13 is independently, at each occurrence, selected from the group consisting of H, C1-C6 alkyl and —(CH2)phenyl;
R14 is independently, at each occurrence, selected from the group consisting of H, C1-C6 alkyl, halo-C1-C4-alkyl, C1-C4-alkoxycarbonylamino, (C6-C10 arylcarbonylamino), (a 5- to 10-membered heteroarylcarbonylamino) and —(CH2)n1phenyl substituted by 0 to 3 groups independently selected from the group consisting of halo, C1-C4 alkoxy, C1-C4 alkyl, cyclopropyl, CF3, OCF3, 5- or 6-membered heteroaryl, OH, OCHF2, di-C1-C4-alkylamino, and cyano,
R10 is selected from the group consisting of C1-C4 alkyl, halo, C1-C4 alkoxy, and halo-C1-C2-alkyl, which contains 1 to 5 halogens, where halo is F or Cl;
n1, at each occurrence, is selected from 0, 1, 2, 3, 4 or 5; and
p, at each occurrence, is selected from 0, 1 and 2.

### Claim 2 (depends on 1)

The compound as defined in claim 1, wherein the compound is a compound of formula IAA:

### Claim 3 (depends on 2)

The compound of claim 2 wherein:
W is O;
R0 is R1 or R1a;
Y is S or —CR8═CR9—;
is phenyl or a 6-membered heteroaryl ring, at least one ring member of which is a nitrogen, which
ring is substituted with 0 to 2 Ra groups;
is attached at the meta position of
and is selected from the group consisting of C6-C10 aryl ring, a 5- to 10-membered heteroaryl ring, a 4- to 10-membered heterocyclyl ring or a C3-C6-membered cycloalkyl ring, wherein each rings is substituted with 0 to 3 Rb groups;
R1 is selected from the group consisting of:
halo,
C1-C4 alkyl,
C1-C4 alkoxy,
halo-C1-C2-alkyl, which contains 1 to 5 halogens, where halo is F or Cl, and C1-C4 alkylthio;
R1a is selected from the group consisting of:
H,
halo,
C1-C4 alkyl,
C1-C4 alkoxy,
halo-C1-C2-alkyl, which contains 1 to 5 halogens, and
C1-C4 alkylthio;
R8 and R9 are independently selected from the group consisting of:
H,
C1-C4 alkyl,
halo,
C1-C4 alkoxy,
CF3,
CF3O,
CHF2, and
OH;
provided that at least one of R1a, R8 and R9 is other than H;
R2 is selected from the group consisting of:
H,
halo,
C1-C4 alkyl,
C1-C4 alkoxy, and
cyano;
X1 is selected from the group consisting of CH, N or CR10;
X2, X3 and X4 are independently selected from CR3 or N;
R3 is selected from the group consisting of H, C1-C4 alkoxy, halo, CF3O, CHF2O, and halo-C1-C2-alkyl, which contains 1 to 5 halogens;
R4 and R5 are independently selected from H and C1-C6 alkyl, or R4 and R5 can be taken together with the carbon to which they are attached to form a C3-C6 cycloalkyl ring;
Ra is, at each occurrence, independently selected from the group consisting of:
H, halo, OCF3, NR6R7, OCHF2, halo-C1-C2-alkyl substituted with 1 to 5 fluorines, CF3,
C1-C4 alkyl,
C1-C4 alkoxy,
C1-C4 alkylthio,
OH,
CN,
NO2,
COOH,
C1-C4 alkoxycarbonyl,
C(═O)NR6R7,
C1-C4 alkylsulfonyl, and
S(═O)2NR6R7;
Rb is, at each occurrence, independently selected from the group consisting of:
H, halo, OCF3, NR6R7, OCHF2, halo-C1-C2-alkyl substituted with 1 to 5 fluorines, CF3,
C1-C4 alkyl,
C1-C4 alkoxy,
C1-C4 alkylthio,
OH,
CN,
NO2,
COOH,
C1-C4 alkoxycarbonyl,
C(═O)NR6R7,
C1-C4 alkylsulfonyl, and
S(═O)2NR6R7; or
R6 and R7 are, independently, at each occurrence, selected from the group consisting of:
H,
C1-C4 alkyl, and
—(CH2)n1 phenyl,
alternatively, R6 and R7, when attached to the same nitrogen, combine to form a 4- to 6-membered heterocyclic ring containing carbon atoms and 1 to 2 additional heteroatoms selected from N, NR13, O and S(O)p;
R13 is independently, at each occurrence, selected from the group consisting of H, alkyl and —(CH2)phenyl;
n1, at each occurrence, is selected from 0, 1, 2, 3, 4 and 5; and
p, at each occurrence, is selected from 0, 1 and 2.

### Claim 4 (depends on 3)

The compound of claim 3, wherein the compound is a compound of formula IA or IB:

### Claim 5 (depends on 1)

The compound of claim 1 wherein:
W is O or S;
R0 is R1 or R1a;
Y is S or —CR8═CR9—;
R1 is independently selected from the group consisting of:
halo,
C1-C4 alkyl,
C2-C3 alkenyl,
C2-C3 alkynyl,
C3-C4 cycloalkyl,
C1-C4 alkoxy,
C1-C2 alkoxy-C1-C2 alkyl,
tetrahydrofuran-2-yl;
halo-C1-C2-alkyl, which contains 1 to 5 halogens, where halo is F or Cl,
halo-C3-C4 cycloalkyl, and
halo-C1-C2 alkoxy;
R1a is independently selected from the group consisting of:
H,
halo,
C1-C4 alkyl,
C2-C3 alkenyl,
C2-C3 alkynyl,
C3-C4 cycloalkyl,
C1-C4 alkoxy,
C1-C2 alkoxy-C1-C2 alkyl,
tetrahydrofuran-2-yl;
halo-C1-C2-alkyl, which contains 1 to 5 halogens, where halo is F or Cl,
halo-C3-C4 cycloalkyl, and
halo-C1-C2 alkoxy;
R8 and R9 are independently selected from the group consisting of:
H,
halo,
C1-C4 alkyl,
C1-C4 alkoxy,
halo-C1-C2 alkyl,
halo-C1-C2 alkoxy, and
OH;
provided that at least one of R1a, R8 and R9 is other than H;
R2 is selected from the group consisting of:
H,
halo,
C1-C4 alkyl, and
C1-C4 alkoxy;
X1 is selected from the group consisting of CH, N or CR10;
X2, X3 and X4 are independently selected from CR3 or N;
R3 is selected from the group consisting of H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 alkoxy, C1-C4 alkylthio, halo, OH, CN, OCF3, OCHF2, OCH2F, C1-C2-alkoxy-C1-C2-alkoxy, halo-C1-C3-alkyl, which contains 1 to 5 halogens, and —(CH2)n1-phenyl substituted by 0 to 3 groups independently selected from the group consisting of halo, C1-C4 alkoxy, C1-C4 alkyl, cyclopropyl, CF3, OCF3, 5- or 6-membered heteroaryl, OH, OCHF2, di-C1-C4-alkylamino, and cyano;
R4 and R5 are independently selected from H, C1-C6 alkyl, halo-C1-C3 alkyl, hydroxy-C1-C3 alkyl, and C1-C3 alkoxy-C1-C3 alkyl, or R4 and R5 can be taken together with the carbon to which they are attached to form a C3-C7 cycloalkyl ring;
is phenyl or a 6-membered heteroaryl ring, at least one ring member of which is a nitrogen, which
ring is substituted with 0 to 2 Ra groups;
B is selected from the group consisting of a C6-C10 aryl, a 5- to 10-membered heteroaryl, a 4-to 10-membered heterocyclyl containing carbon atoms and 1 to 4 additional heteroatoms selected from N, O, and S, and a C3-C8 cycloalkyl which may contain unsaturation, all of which are substituted by 0 to 3 Rb groups;
Ra, at each occurrence, is independently selected from the group consisting of H, halo, halo-C1-C4 alkoxy, OH, CN, NO2, NR6R7, COOH, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkoxycarbonyl, (C═O)NR6R7, C1-C4 alkoxy-C1-C4 alkoxy, C1-C4 alkylsulfonyl, C1-C4 alkylsulfinyl, S(═O)2NR6R7, and C1-C5 alkyl substituted by 0 to 7 groups independently selected from halo, CF3, OCF3, OH, hydroxy-C1-C4-alkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkoxy, di-C1-C4-alkylaminophenyl-C1-C4-alkyl, (di-C1-C4-alkoxy-C1-C4-alkyl)-C1-C4-alkyl, di-C1-C4-alkylamino, C3-C6-cycloalkyl, phenyl, and C1-C4 alkylthio;
Rb, at each occurrence, is independently selected from the group consisting of H, halo, halo-C1-C4 alkoxy, OH, CN, NO2, NR6R7, COOH, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkoxycarbonyl, (C═O)NR6R7, C1-C4 alkoxy-C1-C4 alkoxy, C1-C4 alkylsulfonyl, C1-C4 alkylsulfinyl, S(═O)2NR6R7, N(R13)(C═O)NR6R7, N(R13)(C═O)OR14, N(R13)(C═O)R14, NR13S(O)R14, NR13SO2R14, O(C═O)NR6R7, O(C═O)OR14, O(C═O)R14, (C═O)OR14, 5-6-membered heteroaryl, and C1-C5 alkyl substituted by 0 to 7 groups independently selected from halo, CF3, OCF3, OH, hydroxy-C1-C4-alkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkoxy, di-C1-C4-alkylaminophenyl-C1-C4-alkyl, (di-C1-C4-alkoxy-C1-C4-alkyl)-C1-C4-alkyl, di-C1-C4-alkylamino, C3-C6-cycloalkyl, phenyl, and C1-C4 alkylthio;
R6 and R7 are independently, at each occurrence, selected from the group consisting of:
H,
C1-C4 alkyl,
halo-C1-C4-alkyl,
C1-C4 alkyleneoxy-C1-C4-alkylene,
C2-C4 alkenyl,
C2-C4 alkynyl,
—(CR14R14)n1-phenyl substituted by 0 to 3 groups independently selected from the group consisting of halo, C1-C4 alkoxy, C1-C4 alkyl, cyclopropyl, CF3, OCF3, 5- or 6-membered heteroaryl, OH, OCHF2, di-C1-C4-alkylamino, and cyano,
—(CHR13)n1—C3-C6-cycloalkyl substituted by 0 to 3 groups independently selected from the group consisting of halo, CF3, OCF3, 5- or 6-membered heteroaryl, OH, hydroxy-C1-C4-alkyl, and C1-C4 alkyl,
—(CHR13)n1-4- to 10-membered-heterocyclyl substituted by 0 to 3 groups independently selected from the group consisting of halo, CF3, OCF3, 5- or 6-membered heteroaryl, OH, oxo, hydroxy-C1-C4-alkyl, and C1-C4 alkyl,
—(CHR13)n1-5- to 10-membered-heteroaryl substituted by 0 to 3 groups independently selected from the group consisting of halo, CF3, OCF3, 5- or 6-membered heteroaryl, OH, hydroxy-C1-C4-alkyl, and C1-C4 alkyl,
di-C1-C4-alkylamino-C1-C4-alkyl,
C1-C4-alkylcarbonylamino-C1-C4-alkyl,
di-C1-C4-alkoxy-C1-C4-alkyl,
di-C1-C4-alkylaminophenyl,
hydroxy-C1-C4-alkyl,
cyano-C1-C4-alkyl,
C1-C4-alkoxy-C1-C4-alkyl,
C1-C4-alkoxycarbonyl-C1-C4-alkyl,
C1-C4-alkoxycarbonyl,
C1-C4-alkylcarbonyl,
phenylcarbonyl; and
alternatively, R6 and R7, when attached to the same nitrogen, combine to form a 4- to 6-membered heterocyclic ring containing carbon atoms substituted by 0 to 3 groups independently selected from the group consisting of halo, CF3, CHF2, OCF3, OCHF2, OCH2F, 5- or 6-membered heteroaryl, OH, oxo, hydroxy-C1-C4-alkyl, C1-C4 alkyl and C1-C4 alkoxy, and 0 to 2 additional heteroatoms selected from N, NR13, O and S(O)p;
R13 is independently, at each occurrence, selected from the group consisting of H, C1-C6 alkyl and —(CH2)phenyl;
R14 is independently, at each occurrence, selected from the group consisting of H, C1-C6 alkyl, halo-C1-C4-alkyl, C1-C4-alkoxycarbonylamino, (C6-C10 arylcarbonylamino), and —(CH2)n1-phenyl substituted by 0 to 3 groups independently selected from the group consisting of halo, C1-C4 alkoxy, C1-C4 alkyl, cyclopropyl, CF3, OCF3, 5- or 6-membered heteroaryl, OH, OCHF2, di-C1-C4-alkylamino, and cyano,
R10 is selected from the group consisting of C1-C4 alkyl, halo, C1-C4 alkoxy, and halo-C1-C2-alkyl, which contains 1 to 5 halogens, where halo is F or Cl;
n1, at each occurrence, is selected from 0, 1, 2, 3, 4 or 5; and
p, at each occurrence, is selected from 0, 1 and 2.

### Claim 6 (depends on 1)

The compound of claim 1 wherein:
W is O or S;
R0 is R1 or R1a;
Y is S or —CR8═CR9—;
R1 is independently selected from the group consisting of:
halo,
C1-C4 alkyl,
C2-C3 alkenyl,
C2-C3 alkynyl,
C3-C4 cycloalkyl,
C1-C4 alkoxy,
C1-C2 alkoxy-C1-C2 alkyl,
tetrahydrofuran-2-yl;
C1-C4 alkylthio,
halo-C1-C2-alkyl, which contains 1 to 5 halogens, where halo is F or Cl,
halo-C3-C4 cycloalkyl,
halo-C1-C2 alkoxy, and
halo-C1-C2 alkylthio;
R1a is independently selected from the group consisting of:
H,
halo,
C1-C4 alkyl,
C2-C3 alkenyl,
C2-C3 alkynyl,
C3-C4 cycloalkyl,
C1-C4 alkoxy,
C1-C2 alkoxy-C1-C2 alkyl,
tetrahydrofuran-2-yl;
C1-C4 alkylthio,
halo-C1-C2-alkyl, which contains 1 to 5 halogens, where halo is F or Cl,
halo-C3-C4 cycloalkyl,
halo-C1-C2 alkoxy, and
halo-C1-C2 alkylthio;
R8 and R9 are independently selected from the group consisting of:
H,
halo,
C1-C4 alkyl,
C1-C4 alkoxy,
halo-C1-C2 alkyl, and
halo-C1-C2 alkoxy;
provided that at least one of R1a, R8 and R9 is other than H;
R2 is selected from the group consisting of:
H,
halo,
C1-C3 alkyl, and
C1-C2 alkoxy;
X1 is selected from the group consisting of CH, N or CR10;
X2, X3 and X4 are independently selected from CR3 or N;
R3 is selected from the group consisting of H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 alkoxy, C1-C4 alkylthio, halo, OH, CN, OCF3, C1-C2-alkoxy-C1-C2-alkoxy, halo-C1-C3-alkyl, which contains 1 to 5 halogens, benzyloxy substituted by 0 to 3 groups independently selected from the group consisting of halo, C1-C4 alkoxy, C1-C4 alkyl, cyclopropyl, CF3, OCF3, 5- or 6-membered heteroaryl, OH, OCHF2, di-C1-C4-alkylamino, and cyano, and —(CH2)n1-phenyl substituted by 0 to 3 groups independently selected from the group consisting of halo, C1-C4 alkoxy, C1-C4 alkyl, cyclopropyl, CF3, OCF3, 5- or 6-membered heteroaryl, OH, OCHF2, di-C1-C4-alkylamino, and cyano;
R4 and R5 are independently selected from H, C1-C6 alkyl, halo-C1-C3 alkyl, hydroxy-C1-C3 alkyl, and C1-C3 alkoxy-C1-C3 alkyl, or R4 and R5 can be taken together with the carbon to which they are attached to form a C3-C7 cycloalkyl ring;
is phenyl or a 6-membered heteroaryl ring, at least one ring member of which is a nitrogen, which
ring is substituted with 0 to 2 Ra groups;
B is selected from the group consisting of a C6-C10 aryl, a 5- to 10-membered heteroaryl, a 4-to 10-membered heterocyclyl containing carbon atoms and 1 to 4 additional heteroatoms selected from N, O, and S, and a C3-C8 cycloalkyl which may contain unsaturation, all of which are substituted by 0 to 3 Rb groups;
Ra, at each occurrence, is independently selected from the group consisting of H, halo, halo-C1-C4 alkoxy, OH, CN, NO2, NR6R7, COOH, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkoxycarbonyl, (C═O)NR6R7, C1-C4 alkoxy-C1-C4 alkoxy, C1-C4 alkylsulfonyl, C1-C4 alkylsulfinyl, S(═O)2NR6R7, and C1-C5 alkyl substituted by 0 to 7 groups independently selected from halo, CF3, OCF3, OH, hydroxy-C1-C4-alkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkoxy, di-C1-C4-alkyl aminophenyl-C1-C4-alkyl, (di-C1-C4-alkoxy-C1-C4-alkyl)-C1-C4-alkyl, di-C1-C4-alkylamino, C3-C6-cycloalkyl, phenyl, and C1-C4 alkylthio;
Rb, at each occurrence, is independently selected from the group consisting of H, halo, halo-C1-C4 alkoxy, OH, CN, NO2, NR6R7, COOH, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkoxycarbonyl, (C═O)NR6R7, C1-C4 alkoxy-C1-C4 alkoxy, C1-C4 alkylsulfonyl, C1-C4 alkylsulfinyl, S(═O)2NR6R7, N(R13)(C═O)NR6R7, N(R13)(C═O)OR14, N(R13)(C═O)R14, NR13S(O)R14, NR13SO2R14, O(C═O)NR6R7, O(C═O)OR14, O(C═O)R14, (C═O)OR14, 5-6-membered heteroaryl, and C1-C5 alkyl substituted by 0 to 7 groups independently selected from halo, CF3, OCF3, OH, hydroxy-C1-C4-alkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkoxy, di-C1-C4-alkylaminophenyl-C1-C4-alkyl, (di-C1-C4-alkoxy-C1-C4-alkyl)-C1-C4-alkyl, di-C1-C4-alkylamino, C3-C6-cycloalkyl, phenyl, and C1-C4 alkylthio;
R6 and R7 are independently, at each occurrence, selected from the group consisting of:
H,
C1-C4 alkyl,
halo-C1-C4-alkyl,
C1-C4 alkyleneoxy-C1-C4-alkylene,
C2-C4 alkenyl,
C2-C4 alkynyl,
—(CR14R14)phenyl substituted by 0 to 3 groups independently selected from the group consisting of halo, C1-C4 alkoxy, C1-C4 alkyl, cyclopropyl, CF3, OCF3, 5- or 6-membered heteroaryl, OH, OCHF2, di-C1-C4-alkylamino, and cyano,
—(CHR13)n1—C3-C6-cycloalkyl substituted by 0 to 3 groups independently selected from the group consisting of halo, CF3, OCF3, 5- or 6-membered heteroaryl, OH, hydroxy-C1-C4-alkyl, and C1-C4 alkyl,
—(CHR13)n1-4- to 10-membered-heterocyclyl substituted by 0 to 3 groups independently selected from the group consisting of halo, CF3, OCF3, 5- or 6-membered heteroaryl, OH, oxo, hydroxy-C1-C4-alkyl, and C1-C4 alkyl,
—(CHR13)n1-5- to 10-membered-heteroaryl substituted by 0 to 3 groups independently selected from the group consisting of halo, CF3, OCF3, 5- or 6-membered heteroaryl, OH, hydroxy-C1-C4-alkyl, and C1-C4 alkyl,
di-C1-C4-alkylamino-C1-C4-alkyl,
di-C1-C4-alkoxy-C1-C4-alkyl,
hydroxy-C1-C4-alkyl,
cyano-C1-C4-alkyl,
C1-C4-alkoxy-C1-C4-alkyl,
C1-C4-alkoxycarbonyl-C1-C4-alkyl,
C1-C4-alkoxycarbonyl,
C1-C4-alkylcarbonyl,
phenylcarbonyl;
C1-C4-alkoxycarbonylamino-C1-C4-alkylcarbonyl,
di-C1-C4-alkylamino-C1-C4-alkylcarbonyl,
amino-C1-C4-alkylcarbonyl,
4- to 10-membered-heterocyclyl-carbonyl, and
alternatively, R6 and R7, when attached to the same nitrogen, combine to form a 4- to 8-membered heterocyclic ring containing carbon atoms substituted by 0 to 3 groups independently selected from the group consisting of halo, CF3, CHF2, OCF3, OCHF2, OCH2F, 5- or 6-membered heteroaryl, OH, oxo, hydroxy-C1-C4-alkyl, C1-C4 alkyl and C1-C4 alkoxy, and 0 to 2 additional heteroatoms selected from N, NR13, O and S(O)p;
R13 is independently, at each occurrence, selected from the group consisting of H, C1-C6 alkyl and —(CH2)phenyl;
R14 is independently, at each occurrence, selected from the group consisting of H, C1-C6 alkyl, halo-C1-C4-alkyl, C1-C4-alkoxycarbonylamino, (C6-C10 arylcarbonylamino), (a 5- to 10-membered heteroarylcarbonylamino) and —(CH2)n1-phenyl substituted by 0 to 3 groups independently selected from the group consisting of halo, C1-C4 alkoxy, C1-C4 alkyl, cyclopropyl, CF3, OCF3, 5- or 6-membered heteroaryl, OH, OCHF2, di-C1-C4-alkylamino, and cyano,
R10 is selected from the group consisting of C1-C4 alkyl, halo, C1-C4 alkoxy, and halo-C1-C2-alkyl, which contains 1 to 5 halogens, where halo is F or Cl;
n1, at each occurrence, is selected from 0, 1, 2, 3, 4 or 5; and
p, at each occurrence, is selected from 0, 1 and 2.

### Claim 7 (depends on 6)

The compound of claim 6 wherein:
W is O or S;
R0 is R1 or R1a;
Y is S or —CR8═CR9—;
R1 is independently selected from the group consisting of:
halo,
C1-C4 alkyl,
C2-C3 alkenyl,
C2-C3 alkynyl,
C3-C4 cycloalkyl,
C1-C4 alkoxy,
C1-C4 alkylthio,
halo-C1-C2-alkyl, which contains 1 to 5 halogens, where halo is F or Cl,
halo-C3-C4 cycloalkyl,
halo-C1-C2 alkoxy, and
halo-C1-C2 alkylthio;
R1a is independently selected from the group consisting of:
H,
halo,
C1-C4 alkyl,
C2-C3 alkenyl,
C2-C3 alkynyl,
C3-C4 cycloalkyl,
C1-C4 alkoxy,
C1-C4 alkylthio,
halo-C1-C2-alkyl, which contains 1 to 5 halogens, where halo is F or Cl,
halo-C3-C4 cycloalkyl,
halo-C1-C2 alkoxy, and
halo-C1-C2 alkylthio;
R8 and R9 are independently selected from the group consisting of:
H,
halo,
C1-C4 alkyl,
C1-C4 alkoxy,
halo-C1-C2 alkyl, and
halo-C1-C2 alkoxy;
provided that at least one of R1a, R8 and R9 is other than H;
R2 is selected from the group consisting of:
H,
fluoro,
chloro, and
CH3;
X1 is selected from the group consisting of CH, N or CR10;
X2, X3 and X4 are independently selected from CR3 or N;
R3 is selected from the group consisting of H, C1-C3 alkyl, C2-C3 alkenyl, C2-C3 alkynyl, C1-C3 alkoxy, C1-C3 alkylthio, halo, OH, CN, OCF3, and halo-C1-C3-alkyl, which contains 1 to 5 halogens;
R4 and R5 are independently selected from H, C1-C3 alkyl, halo-C1-C3 alkyl, hydroxy-C1-C3 alkyl, and C1-C3 alkoxy-C1-C3 alkyl, or R4 and R5 can be taken together with the carbon to which they are attached to form a C3-C7 cycloalkyl ring;
is phenyl or a 6-membered heteroaryl ring, at least one ring member of which is a nitrogen, which
ring is substituted with 0 to 2 Ra groups;
B is selected from the group consisting of a C6-C10 aryl, a 5- to 10-membered heteroaryl, a 4-to 10-membered heterocyclyl containing carbon atoms and 1 to 4 additional heteroatoms selected from N, O, and S, and a C3-C8 cycloalkyl which may contain unsaturation, all of which are substituted by 0 to 3 Rb groups;
Ra, at each occurrence, is independently selected from the group consisting of H, halo, halo-C1-C4 alkoxy, OH, CN, NO2, NR6R7, COOH, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkoxycarbonyl, (C═O)NR6R7, C1-C4 alkoxy-C1-C4 alkoxy, C1-C4 alkylsulfonyl, C1-C4 alkylsulfinyl, S(═O)2NR6R7, and C1-C5 alkyl substituted by 0 to 7 groups independently selected from halo, CF3, OCF3, OH, hydroxy-C1-C4-alkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkoxy, di-C1-C4-alkylaminophenyl-C1-C4-alkyl, (di-C1-C4-alkoxy-C1-C4-alkyl)-C1-C4-alkyl, C3-C6-cycloalkyl, phenyl, and C1-C4 alkylthio;
Rb, at each occurrence, is independently selected from the group consisting of H, halo, halo-C1-C4 alkoxy, OH, CN, NO2, NR6R7, COOH, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkoxycarbonyl, (C═O)NR6R7, C1-C4 alkoxy-C1-C4 alkoxy, C1-C4 alkylsulfonyl, C1-C4 alkylsulfinyl, S(═O)2NR6R7, N(R13)(C═O)NR6R7, N(R13)(C═O)OR14, N(R13)(C═O)R14, NR13S(O)R14, NR13SO2R14, O(C═O)NR6R7, O(C═O)OR14, O(C═O)R14, (C═O)OR14, 5-6-membered heteroaryl, and C1-C5 alkyl substituted by 0 to 7 groups independently selected from halo, CF3, OCF3, OH, hydroxy-C1-C4-alkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkoxy, di-C1-C4-alkylaminophenyl-C1-C4-alkyl, (di-C1-C4-alkoxy-C1-C4-alkyl)-C1-C4-alkyl, di-C1-C4-alkylamino, C3-C6-cycloalkyl, phenyl, and C1-C4 alkylthio;
R6 and R7 are independently, at each occurrence, selected from the group consisting of:
H,
C1-C4 alkyl,
halo-C1-C4-alkyl,
C1-C4 alkyleneoxy-C1-C4-alkylene,
C2-C4 alkenyl,
—(CR14R14)n1-phenyl substituted by 0 to 3 groups independently selected from the group consisting of halo, C1-C4 alkoxy, C1-C4 alkyl, cyclopropyl, CF3, OCF3, 5- or 6-membered heteroaryl, OH, OCHF2, di-C1-C4-alkylamino, and cyano,
—(CHR13)n1—C3-C6-cycloalkyl substituted by 0 to 3 groups independently selected from the group consisting of halo, CF3, OCF3, 5- or 6-membered heteroaryl, OH, hydroxy-C1-C4-alkyl, and C1-C4 alkyl,
—(CHR13)n1-4- to 10-membered-heterocyclyl substituted by 0 to 3 groups independently selected from the group consisting of halo, CF3, OCF3, 5- or 6-membered heteroaryl, OH, oxo, hydroxy-C1-C4-alkyl, and C1-C4 alkyl,
—(CHR13)n1-5- to 10-membered-heteroaryl substituted by 0 to 3 groups independently selected from the group consisting of halo, CF3, OCF3, 5- or 6-membered heteroaryl, OH, hydroxy-C1-C4-alkyl, and C1-C4 alkyl,
di-C1-C4-alkylamino-C1-C4-alkyl,
di-C1-C4-alkoxy-C1-C4-alkyl,
hydroxy-C1-C4-alkyl,
cyano-C1-C4-alkyl,
C1-C4-alkoxy-C1-C4-alkyl,
C1-C4-alkoxycarbonyl-C1-C4-alkyl,
C1-C4-alkoxycarbonyl,
C1-C4-alkylcarbonyl,
phenylcarbonyl;
C1-C4-alkoxycarbonylamino-C1-C4-alkylcarbonyl,
di-C1-C4-alkylamino-C1-C4-alkylcarbonyl,
amino-C1-C4-alkylcarbonyl,
4- to 10-membered-heterocyclyl-carbonyl, and
alternatively, R6 and R7, when attached to the same nitrogen, combine to form a 4- to 8-membered heterocyclic ring containing carbon atoms substituted by 0 to 3 groups independently selected from the group consisting of halo, CF3, CHF2, OCF3, OCHF2, OCH2F, 5- or 6-membered heteroaryl, OH, oxo, hydroxy-C1-C4-alkyl, C1-C4 alkyl and C1-C4 alkoxy, and 0 to 2 additional heteroatoms selected from N, NR13, O and S(O)p;
R13 is independently, at each occurrence, selected from the group consisting of H, C1-C6 alkyl and —(CH2)phenyl;
R14 is independently, at each occurrence, selected from the group consisting of H, C1-C6 alkyl, halo-C1-C4-alkyl, C1-C4-alkoxycarbonylamino, (C6-C10 arylcarbonylamino) and —(CH2)n1-phenyl substituted by 0 to 3 groups independently selected from the group consisting of halo, C1-C4 alkoxy, C1-C4 alkyl, cyclopropyl, CF3, OCF3, 5- or 6-membered heteroaryl, OH, OCHF2, di-C1-C4-alkylamino, and cyano,
R10 is selected from the group consisting of C1-C4 alkyl, halo, and halo-C1-C2-alkyl, which contains 1 to 5 halogens, where halo is F or Cl;
n1, at each occurrence, is selected from 0, 1, 2, 3 or 4; and
p, at each occurrence, is selected from 0, 1 and 2.

### Claim 8 (depends on 1)

The compound of claim 1 wherein:
W is O;
R0 is R1 or R1a;
Y is S or —CR8═CR9—;
R1 is independently selected from the group consisting of:
halo,
C1-C2 alkyl,
cyclopropyl,
C1-C2 alkoxy,
C1-C2 alkylthio,
halo-C1-C2-alkyl, which contains 1 to 5 halogens, where halo is F or Cl, and
halo-C3-C4 cycloalkyl;
R1a is independently selected from the group consisting of:
H,
halo,
C1-C2 alkyl,
cyclopropyl,
C1-C2 alkoxy,
C1-C2 alkylthio,
halo-C1-C2-alkyl, which contains 1 to 5 halogens, where halo is F or Cl, and
halo-C3-C4 cycloalkyl;
R8 and R9 are independently selected from the group consisting of:
H,
fluoro,
chloro,
C1-C3 alkyl,
C1-C2 alkoxy, and
halo-C1-C2 alkyl;
provided that at least one of R1a, R8 and R9 is other than H;
R2 is H;
X1 is selected from the group consisting of CH or N;
X2, X3 and X4 are independently selected from CR3;
R3 is selected from the group consisting of H, C1-C3 alkyl, C1-C3 alkoxy, fluoro, chloro, OCF3, and halo-C1-C2-alkyl, which contains 1 to 5 halogens;
R4 and R5 are independently selected from H, C1-C6 alkyl, halo-C1-C3 alkyl, hydroxy-C1-C3 alkyl and C1-C3 alkoxy-C1-C3 alkyl;
is selected from the group consisting of phenyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, and triazinyl;
B is selected from the group consisting of a C6-C10 aryl, a 5- to 10-membered heteroaryl, a 4-to 10-membered heterocyclyl containing carbon atoms and 1 to 2 additional heteroatoms selected from N, O, and S, and a C3-C6 cycloalkyl which may contain unsaturation, all of which are substituted by 0 to 3 Rb groups;
Ra, at each occurrence, is independently selected from the group consisting of H, halo, halo-C1-C4 alkoxy, OH, CN, NO2, NR6R7, COOH, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkoxycarbonyl, (C═O)NR6R7, C1-C4 alkoxy-C1-C4 alkoxy, C1-C4 alkylsulfonyl, C1-C4 alkylsulfinyl, S(═O)2NR6R7, and C1-C5 alkyl substituted by 0 to 7 groups independently selected from halo, CF3, OCF3, OH, hydroxy-C1-C4-alkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkoxy, di-C1-C4-alkylaminophenyl-C1-C4-alkyl, (di-C1-C4-alkoxy-C1-C4-alkyl)-C1-C4-alkyl, di-C1-C4-alkylamino, C3-C6-cycloalkyl, phenyl, and C1-C4 alkylthio;
Rb, at each occurrence, is independently selected from the group consisting of H, halo, halo-C1-C4 alkoxy, OH, CN, NO2, NR6R7, COOH, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkoxycarbonyl, (C═O)NR6R7, C1-C4 alkoxy-C1-C4 alkoxy, C1-C4 alkylsulfonyl, C1-C4 alkylsulfinyl, S(═O)2NR6R7, N(R13)(C═O)NR6R7, N(R13)(C═O)OR14, N(R13)(C═O)R14, NR13S(O)R14, NR13SO2R14, O(C═O)NR6R7, O(C═O)OR14, O(C═O)R14, (C═O)OR14, 5-6-membered heteroaryl, and C1-C5 alkyl substituted by 0 to 7 groups independently selected from halo, CF3, OCF3, OH, hydroxy-C1-C4-alkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkoxy, di-C1-C4-alkylaminophenyl-C1-C4-alkyl, (di-C1-C4-alkoxy-C1-C4-alkyl)-C1-C4-alkyl, di-C1-C4-alkylamino, C3-C6-cycloalkyl, phenyl, and C1-C4 alkylthio;
R6 and R7 are independently, at each occurrence, selected from the group consisting of:
H,
C1-C4 alkyl,
halo-C1-C4-alkyl,
C2-C4 alkenyl,
—(CR14R14)n1-phenyl substituted by 0 to 3 groups independently selected from the group consisting of halo, C1-C4 alkoxy, C1-C4 alkyl, cyclopropyl, CF3, OCF3, 5- or 6-membered heteroaryl, OH, OCHF2, di-C1-C4-alkylamino, and cyano,
—(CHR13)n1—C3-C6-cycloalkyl substituted by 0 to 3 groups independently selected from the group consisting of halo, CF3, OCF3, 5- or 6-membered heteroaryl, OH, hydroxy-C1-C4-alkyl, and C1-C4 alkyl,
—(CHR13)n1-4- to 10-membered-heterocyclyl substituted by 0 to 3 groups independently selected from the group consisting of halo, CF3, OCF3, 5- or 6-membered heteroaryl, OH, oxo, hydroxy-C1-C4-alkyl, and C1-C4 alkyl,
—(CHR13)n1-5- to 10-membered-heteroaryl substituted by 0 to 3 groups independently selected from the group consisting of halo, CF3, OCF3, 5- or 6-membered heteroaryl, OH, hydroxy-C1-C4-alkyl, and C1-C4 alkyl,
di-C1-C4-alkylamino-C1-C4-alkyl,
di-C1-C4-alkoxy-C1-C4-alkyl,
hydroxy-C1-C4-alkyl,
cyano-C1-C4-alkyl,
C1-C4-alkoxy-C1-C4-alkyl,
C1-C4-alkoxycarbonyl-C1-C4-alkyl,
C1-C4-alkoxycarbonyl,
C1-C4-alkylcarbonyl,
phenylcarbonyl;
C1-C4-alkoxycarbonylamino-C1-C4-alkylcarbonyl, and
di-C1-C4-alkylamino-C1-C4-alkylcarbonyl,
alternatively, R6 and R7, when attached to the same nitrogen, combine to form a 4- to 8-membered heterocyclic ring containing carbon atoms substituted by 0 to 3 groups independently selected from the group consisting of halo, CF3, CHF2, OCF3, OCHF2, OCH2F, 5- or 6-membered heteroaryl, OH, oxo, hydroxy-C1-C4-alkyl, C1-C4 alkyl and C1-C4 alkoxy, and 0 to 2 additional heteroatoms selected from N, NR13, O and S(O)p;
R13 is independently, at each occurrence, selected from the group consisting of H, C1-C6 alkyl and —(CH2)phenyl;
R14 is independently, at each occurrence, selected from the group consisting of H, C1-C6 alkyl, halo-C1-C4-alkyl, C1-C4-alkoxycarbonylamino and —(CH2)n1phenyl substituted by 0 to 3 groups independently selected from the group consisting of halo, C1-C4 alkoxy, C1-C4 alkyl, cyclopropyl, CF3, OCF3, 5- or 6-membered heteroaryl, OH, OCHF2, di-C1-C4-alkylamino, and cyano,
n1, at each occurrence, is selected from 0, 1, 2 or 3; and
p, at each occurrence, is selected from 0, 1 and 2.

### Claim 9 (depends on 8)

The compound of claim 8 wherein:
W is O;
R0 is R1 or R1a;
Y is S or —CR8═CR9—;
R1 is independently selected from the group consisting of:
C1-C2 alkyl,
C1-C2 alkoxy,
C1-C2 alkylthio, and
halo-C1-C2-alkyl, which contains 1 to 5 halogens, where halo is F or Cl;
R1a is independently selected from the group consisting of:
H,
fluoro,
chloro,
C1-C2 alkyl,
C1-C2 alkoxy,
C1-C2 alkylthio, and
halo-C1-C2-alkyl, which contains 1 to 5 halogens, where halo is F or Cl;
R8 and R9 are independently selected from the group consisting of:
H,
fluoro,
chloro,
CH3,
OCH3,
CF3, and
CHF2;
provided that at least one of R1a, R8 and R9 is other than H;
R2 is H;
X1 is selected from the group consisting of CH or N;
X2 and X4 are CH;
X3 is CR3;
R3 is selected from the group consisting of H, C1-C3 alkyl, C1-C3 alkoxy, fluoro, chloro, OCF3, and halo-C1-C2-alkyl, which contains 1 to 5 halogens;
R4 and R5 are independently selected from H and C1-C6 alkyl;
is selected from the group consisting of phenyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, and triazinyl;
is selected from the group consisting of phenyl, naphthyl pyridyl, pyrimidinyl, pyrrolyl, pyrazolyl, thienyl, thiazolyl,
Ra, at each occurrence, is independently selected from the group consisting of H, halo, halo-C1-C4 alkoxy, OH, CN, NO2, NR6R7, COOH, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkoxycarbonyl, (C═O)NR6R7, C1-C4 alkoxy-C1-C4 alkoxy, C1-C4 alkylsulfonyl, C1-C4 alkylsulfinyl, S(═O)2NR6R7, and C1-C5 alkyl substituted by 0 to 7 groups independently selected from halo, CF3, OCF3, OH, hydroxy-C1-C4-alkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkoxy, di-C1-C4-alkylaminophenyl-C1-C4-alkyl, (di-C1-C4-alkoxy-C1-C4-alkyl)-C1-C4-alkyl, di-C1-C4-alkylamino, C3-C6-cycloalkyl, phenyl, and C1-C4 alkylthio;
Rb, at each occurrence, is independently selected from the group consisting of H, halo, halo-C1-C4 alkoxy, OH, CN, NO2, NR6R7, COOH, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkoxycarbonyl, (C═O)NR6R7, alkoxy-C1-C4 alkoxy, C1-C4 alkylsulfonyl, C1-C4 alkylsulfinyl, S(═O)2NR6R7, N(R13)(C═O)NR6R7, N(R13)(C═O)OR14, N(R13)(C═O)R14, NR13S(O)R14, NR13SO2R14, O(C═O)NR6R7, O(C═O)OR14, O(C═O)R14, (C═O)OR14, 5-6-membered heteroaryl, and C1-C5 alkyl substituted by 0 to 7 groups independently selected from halo, CF3, OCF3, OH, hydroxy-C1-C4-alkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkoxy, di-C1-C4-alkylaminophenyl-C1-C4-alkyl, (di-C1-C4-alkoxy-C1-C4-alkyl)-C1-C4-alkyl, di-C1-C4-alkylamino, C3-C6-cyclo alkyl, phenyl, and C1-C4 alkylthio;
R6 and R7 are independently, at each occurrence, selected from the group consisting of:
H,
C1-C4 alkyl,
halo-C1-C4-alkyl,
C2-C4 alkenyl,
—(CR14R14)n1-phenyl substituted by 0 to 3 groups independently selected from the group consisting of halo, C1-C4 alkoxy, C1-C4 alkyl, cyclopropyl, CF3, OCF3, 5- or 6-membered heteroaryl, OH, OCHF2, di-C1-C4-alkylamino, and cyano,
—(CHR13)n1—C3-C6-cycloalkyl substituted by 0 to 3 groups independently selected from the group consisting of halo, CF3, OCF3, 5- or 6-membered heteroaryl, OH, hydroxy-C1-C4-alkyl, and C1-C4 alkyl,
—(CHR13)n1-4- to 10-membered-heterocyclyl substituted by 0 to 3 groups independently selected from the group consisting of halo, CF3, OCF3, 5- or 6-membered heteroaryl, OH, oxo, hydroxy-C1-C4-alkyl, and C1-C4 alkyl,
—(CHR13)n1-5- to 10-membered-heteroaryl substituted by 0 to 3 groups independently selected from the group consisting of halo, CF3, OCF3, 5- or 6-membered heteroaryl, OH, hydroxy-C1-C4-alkyl, and C1-C4 alkyl,
di-C1-C4-alkylamino-C1-C4-alkyl,
di-C1-C4-alkoxy-C1-C4-alkyl,
hydroxy-C1-C4-alkyl,
cyano-C1-C4-alkyl,
C1-C4-alkoxy-C1-C4-alkyl,
C1-C4-alkoxycarbonyl-C1-C4-alkyl,
C1-C4-alkoxycarbonyl,
C1-C4-alkylcarbonyl, and
phenylcarbonyl;
alternatively, R6 and R7, when attached to the same nitrogen, combine to form a 4- to 8-membered heterocyclic ring containing carbon atoms substituted by 0 to 3 groups independently selected from the group consisting of halo, CF3, CHF2, OCF3, OCHF2, OCH2F, 5- or 6-membered heteroaryl, OH, oxo, hydroxy-C1-C4-alkyl, C1-C4 alkyl and C1-C4 alkoxy, and 0 to 2 additional heteroatoms selected from N, NR13, O and S(O)p;
R13 is independently, at each occurrence, selected from the group consisting of H, and C1-C3 alkyl;
R14 is independently, at each occurrence, selected from the group consisting of H, C1-C3 alkyl, and halo-C1-C2-alkyl;
n1, at each occurrence, is selected from 0, 1, 2 or 3; and
p, at each occurrence, is selected from 0, 1 and 2.

### Claim 10 (depends on 9)

The compound of claim 9 wherein:
W is O;
R0 is R1 or R1a;
Y is S or —CH═CH—;
R1 is independently selected from the group consisting of:
CH3,
OCH3,
SCH3,
CHFCH3, and
CF2CH3;
R1a is independently selected from the group consisting of:
chloro,
CH3, and
OCH3,
R2 is H;
X1 is CH;
X2 and X4 are CH;
X3 is CR3;
R3 is selected from the group consisting of OCH3, fluoro, and chloro;
R4 and R5 are independently selected from H and CH3;
is selected from the group consisting of phenyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, and triazinyl;
is selected from the group consisting of phenyl, naphthyl pyridyl, pyrimidinyl, pyrrolyl, pyrazolyl, thienyl, thiazolyl,
Ra, at each occurrence, is independently selected from the group consisting of H, halo, halo-C1-C4 alkoxy, OH, CN, NO2, NR6R7, COOH, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkoxycarbonyl, (C═O)NR6R7, C1-C4 alkoxy-C1-C4 alkoxy, C1-C4 alkylsulfonyl, C1-C4 alkylsulfinyl, S(═O)2NR6R7, and C1-C5 alkyl substituted by 0 to 7 groups independently selected from halo, CF3, OCF3, OH, hydroxy-C1-C4-alkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkoxy, di-C1-C4-alkylaminophenyl-C1-C4-alkyl, (di-C1-C4-alkoxy-C1-C4-alkyl)-C1-C4-alkyl, di-C1-C4-alkylamino, C3-C6-cycloalkyl, phenyl, and C1-C4 alkylthio;
Rb, at each occurrence, is independently selected from the group consisting of H, halo, halo-C1-C4 alkoxy, OH, CN, NO2, NR6R7, COOH, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkoxycarbonyl, (C═O)NR6R7, C1-C4 alkoxy-C1-C4 alkoxy, C1-C4 alkylsulfonyl, C1-C4 alkylsulfinyl, S(═O)2NR6R7, N(R13)(C═O)NR6R7, N(R13)(C═O)OR14, N(R13)(C═O)R14, NR13S(O)R14, NR13SO2R14, O(C═O)NR6R7, O(C═O)OR14, O(C═O)R14, (C═O)OR14, 5-6-membered heteroaryl, and C1-C5 alkyl substituted by 0 to 7 groups independently selected from halo, CF3, OCF3, OH, hydroxy-C1-C4-alkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkoxy, di-C1-C4-alkylaminophenyl-C1-C4-alkyl, (di-C1-C4-alkoxy-C1-C4-alkyl)-C1-C4-alkyl, di-C1-C4-alkylamino, C3-C6-cycloalkyl, phenyl, and C1-C4 alkylthio;
R6 and R7 are independently, at each occurrence, selected from the group consisting of:
H,
C1-C4 alkyl,
halo-C1-C4-alkyl,
di-C1-C4-alkylamino-C1-C4-alkyl,
di-C1-C4-alkoxy-C1-C4-alkyl,
hydroxy-C1-C4-alkyl,
cyano-C1-C4-alkyl,
C1-C4-alkoxy-C1-C4-alkyl,
C1-C4-alkoxycarbonyl-C1-C4-alkyl, and
C1-C4-alkoxycarbonyl;
alternatively, R6 and R7, when attached to the same nitrogen, combine to form a 4- to 7-membered heterocyclic ring containing carbon atoms substituted by 0 to 2 groups independently selected from the group consisting of halo, CF3, CHF2, OCF3, OCHF2, OCH2F, OH, oxo, hydroxy-C1-C2-alkyl, C1-C3 alkyl and C1-C3 alkoxy, and 0 to 2 additional heteroatoms selected from N, NR13, O and S(O)p;
R13 is independently, at each occurrence, selected from the group consisting of H and C1-C3 alkyl;
R14 is independently, at each occurrence, selected from the group consisting of H and C1-C3 alkyl
n1, at each occurrence, is selected from 0, 1, 2 or 3; and
p, at each occurrence, is selected from 0, 1 and 2.

### Claim 11 (depends on 1)

The compound of claim 1, wherein:
X1 is CH or N;
R1 is C1-C3 alkoxy or halo-C1-C2-alkyl which contains 1 to 5 halogens;
R2 is H;
R3 is H, alkoxy or halogen;
is selected from the group consisting of phenyl, pyridyl and pyrimidinyl, all of which are substituted with 0 to 2 Ra groups;
is selected from the group consisting of:
a) phenyl;
b) phenyl substituted with 1 to 2 Rb substituents selected from halo, OH, halo-C1-C2-alkyl, which contains 1 to 5 halogens, CN, NO2,
N(C1-C4 alkyl)2, CF3, C1-C4 alkyl, and C1-C4 alkoxy;
c) phenyl fused to a heterocyclo group;
d) monocyclic heteroaryl containing 5 or 6 ring members which contain:
1 oxygen atom,
2 nitrogen atoms,
2 sulfur atoms,
1 nitrogen atom,
1 sulfur atom,
1 oxygen atom,
or combinations thereof, which monocyclic heteroaryl is substituted with 0 to 2 Rb substituents selected from halo, CN, NO2, OH, C1-C4 alkyl, halo-C1-C4 alkyl, C1-C4 alkoxy, halo-C1-C4 alkoxy,
N(C1-C4 alkyl)2, C1-C4 alkoxy-C1-C4 alkoxy, COOH, alkoxycarbonyl, heterocyclyl, or heterocyclylcarbonyl;
e) bicyclic heteroaryl containing 8 or 9 ring members and which contains a sulfur atom, nitrogen atoms or combinations thereof in the ring.

### Claim 12 (depends on 1)

The compound of claim 1, wherein the compound is selected from:

### Claim 13 (depends on 1)

A pharmaceutical composition, which comprises a pharmaceutically acceptable carrier and a compound of claim 1, or stereoisomers, tautomers, pharmaceutically acceptable salts, or solvates thereof, alone or in combination with another therapeutic agent.

### Claim 14 (depends on 1)

A method for the treatment of a thromboembolic disorder or the primary or secondary prophylaxis of a thromboembolic disorder, which comprises the steps of administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1, or stereoisomers, tautomers, pharmaceutically acceptable salts, or solvates thereof, wherein the thromboembolic disorder is selected from the group consisting of arterial cardiovascular thromboembolic disorders, venous cardiovascular thromboembolic disorders, cerebrovascular thromboembolic disorders, and thromboembolic disorders in the chambers of the heart or in the peripheral circulation.

### Claim 15 (depends on 1)

A method of inhibiting or preventing platelet aggregation, which comprises the step of administering to a subject in need thereof a therapeutically effective amount of a PAR4 antagonist, of claim 1.

### Claim 16 (depends on 12)

A pharmaceutical composition, which comprises a pharmaceutically acceptable carrier and a compound of claim 12, or stereoisomers, tautomers, pharmaceutically acceptable salts, or solvates thereof, alone or in combination with another therapeutic agent.

### Claim 17 (depends on 12)

A method for the treatment of a thromboembolic disorder or the primary or secondary prophylaxis of a thromboembolic disorder, which comprises the steps of administering to a patient in need thereof a therapeutically effective amount of a compound of claim 12, or stereoisomers, tautomers, pharmaceutically acceptable salts, or solvates thereof, wherein the thromboembolic disorder is selected from the group consisting of arterial cardiovascular thromboembolic disorders, venous cardiovascular thromboembolic disorders, cerebrovascular thromboembolic disorders, and thromboembolic disorders in the chambers of the heart or in the peripheral circulation.

### Claim 18 (depends on 12)

A method of inhibiting or preventing platelet aggregation, which comprises the step of administering to a subject in need thereof a therapeutically effective amount of a PAR4 antagonist, of claim 12.