Thrombin receptor antagonists

A compound represented by the structural formula

• or a pharmaceutically acceptable salt or solvate thereof, wherein:
• the single dotted line represents an optional single bond;
• represents an optional double bond;
• n is 0-2;
• Q is
• R1 is independently selected from the group consisting of H, (C1-C6)alkyl, fluoro(C1-C6)alkyl-, difluoro(C1-C6)alkyl-, trifluoro-(C1-C6)alkyl-, (C3-C6)cycloalkyl, (C2-C6)alkenyl, hydroxy-(C1-C6)alkyl-, and amino(C1-C6)alkyl-;
• R2 is independently selected from the group consisting of H, (C1-C6)alkyl, fluoro(C1-C6)alkyl-, difluoro(C1-C6)alkyl-, trifluoro-(C1-C6)alkyl-, (C3-C6)cycloalkyl, (C2-C6)alkenyl, hydroxy-(C1-C6)alkyl-, and amino(C1-C6)alkyl-;
• R3 is H, hydroxy, (C1-C6)alkoxy, —SOR16, —SO2R17, —C(O)OR17, —C(O)NR18R19, —(C1-C6)alkyl—C(O)NR18R19, (C1-C6)alkyl, halogen, fluoro(C1-C6)alkyl-, difluoro(C1-C6)alkyl-, trifluoro(C1-C6)alkyl-, (C3-C6)cycloalkyl, (C3-C6)-cycloalkyl-(C1-C6)alkyl-, (C2-C6)alkenyl, aryl(C1-C6)alkyl-, aryl(C2-C6)alkenyl-, heteroaryl(C1-C6)alkyl-, heteroaryl(C2-C6)alkenyl-, hydroxy(C1-C6)-alkyl-, —NR22R23, NR22R23-(C1—C6)alkyl-, aryl, thio(C1-C6)alkyl-, (C1-C6)alkyl-thio(C1-C6)alkyl-, (C1-C6)alkoxy(C1-C6)alkyl-, NR18R19—C(O)—(C1-C6)alkyl- or (C3-C6)cycloalkyl-(C1-C6)alkyl-;
• Het is a mono- or bi-cyclic heteroaryl group of 5 to 10 atoms comprised of 1 to 9 carbon atoms and 1 to 4 heteroatoms independently selected from the group consisting of N, O and S, wherein a ring nitrogen can form an N-oxide or a quaternary group with a (C1-C4)alkyl group, wherein Het is attached to B by a carbon atom ring member, and wherein the Het group is substituted by W;
• W is 1 to 4 substituents independently selected from the group consisting of H, (C1-C6)alkyl, fluoro(C1-C6)alkyl-, difluoro(C1-C6)alkyl-, trifluoro(C1-C6)alkyl-, (C3-C6)cycloalkyl, hydroxy(C1-C6)alkyl-, dihydroxy(C1-C6)alkyl-, NR25R26(C1-C6)alkyl-, thio(C1-C6)alkyl-, —OH, (C1-C6)alkoxy, halogen, —NR4R5, —C(O)OR17, —COR16, (C1-C6)alkylthio-, R21-aryl, R21-aryl(C1-C6)alkyl-, aryl wherein adjacent carbons form a ring comprising a methylenedioxy group, and R21-heteroaryl;
• R4 and R5 are independently selected from the group consisting of H, (C1-C6)alkyl, phenyl, benzyl and (C3-C6)cycloalkyl, or R4 and R5 taken together are —(CH2)4—, —(CH2)5— or —(CH2)2NR7—(CH2)2— and form a ring with the nitrogen to which they are attached;
• R6 is H, (C1-C6)alkyl or phenyl;
• R7 is H, (C1-C6)alkyl, —C(O)—R16, —C(O)OR17 or —SO2R17;
• R8, R10 and R11 are independently selected from the group consisting of R1 and —OR1, provided that when the optional double bond is present, R10 is absent;
• R9 is H, OH or (C1-C6)alkoxy;
• B is —(CH2)n3—, cis or trans —(CH2)n4CR12CR12a(CH2)n5— or —(CH2)n4C≡C(CH2)n5—, wherein n3 is 0-5, n4 and n5 are independently 0-2, and R12 and R12a are independently selected from the group consisting of H, (C1-C6)alkyl and halogen;
• X is —O— or —NR6— when the dotted line represents a single bond, or X is —OH or —NHR20 when the bond is absent;
• Y is ═O, ═S, (H, H), (H, OH) or (H, (C1-C6)alkoxy) when the dotted line represents a single bond, or when the bond is absent, Y is ═O, (H, H), (H, OH), (H, SH) or (H, (C1-C6)alkoxy);
• each R13 is independently selected from H, (C1-C6)alkyl, (C3-C8)cycloalkyl, —(CH2)n6NHC(O)OR16b, —(CH2)n6NHC(O)R16b, —(CH2)n6NHC(O)NR4R5, —(CH2)n6NHSO2R16, —(CH2)n6NHSO2NR4R5, and —(CH2)n6C(O)NR28R29 where n6 is 0-4, haloalkyl, and halogen;
• each R14 is independently selected from H, (C1-C6)alkyl, —OH, (C1-C6)alkoxy, R27-aryl(C1-C6)alkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, —(CH2)n6NHC(O)OR16b, —(CH2)n6NHC(O)R16b, —(CH2)n6NHC(O)NR4R5, —(CH2)n6NHSO2R16, —(CH2)n6NHSO2NR4R5, and —(CH2) n6C(O)NR28R29 where n6 is 0-4, halogen and haloalkyl;
• or
• R13 and R14 taken together form a spirocyclic or a heterospirocyclic ring of 3-6 atoms;
• wherein at least one of R13 or R14 is selected from the group consisting of —(CH2)n6NHC(O)OR16b, —(CH2)n6NHC(O)R16b, —(CH2)n6NHC(O)NR4R5, —(CH2)n6NHSO2R16, —(CH2)n6NHSO2NR4R5, and —(CH2) n6C(O)NR28R29 where n6 is 0-4;
• R15 is absent when the dotted line represents a single bond and is H, (C1-C6)alkyl, —NR18R19, or —OR17 when the bond is absent;
• R16 is independently selected from the group consisting of (C1-C6)alkyl, phenyl and benzyl;
• R16b is H, alkoxy, (C1-C6)alkyl, (C1-C6)alkoxy(C1-C6)alkyl-, R22—O—C(O)—(C1-C6)alkyl-, (C3-C6)cycloalkyl, R21-aryl, R21-aryl(C1-C6)alkyl, haloalkyl, alkenyl, halosubstituted alkenyl, alkynyl, halosubstituted alkynyl, R21-heteroaryl, R21—(C1-C6)alkyl heteroaryl, R21—(C1-C6)alkyl heterocycloalkyl, R28R29N—(C1-C6)alkyl, R28R29N—(CO)—(C1-C6)alkyl, R28R29N—(CO)O—(C1-C6)alkyl, R28O(CO)N(R29)—(C1-C6)alkyl, R28S(O)2N(R29)—(C1-C6)alkyl, R28R29N—(CO)—N(R29)—(C1-C6)alkyl, R28R29N—S(O)2N(R29)—(C1-C6)alkyl, R28—(CO)N(R29)—(C1-C6)alkyl, R28R29N—S(O)2—(C1-C6)alkyl, HOS(O)2—(C1-C6)alkyl, (OH)2P(O)2—(C1-C6)alkyl, R28—S—(C1-C6)alkyl, R28—S(O)2—(C1-C6)alkyl or hydroxy(C1-C6)alkyl);
• R17, R18 and R19 are independently selected from the group consisting of H, (C1-C6)alkyl, phenyl, and benzyl;
• R20 is H, (C1-C6)alkyl, phenyl, benzyl, —C(O)R6 or —SO2R6;
• R21 is 1 to 3 substituents independently selected from the group consisting of H, —CN, —CF3, —OCF3, halogen, —NO2, (C1-C6)alkyl, —OH, (C1-C6)alkoxy, (C1-C6)-alkylamino-, di-((C1-C6)alkyl)amino-, NR25R26(C1-C6)alkyl-, hydroxy-(C1-C6)alkyl-, —C(O)OR17, —C(O)R17, —NHCOR16, —NHSO2R16, —NHSO2CH2CF3, —C(O)NR25R26, —NR25—C(O)—NR25R26, —S(O)R13, —S(O)2R 13 and —SR13;
• R22 is H or (C1-C6)alkyl;
• R23 is H, (C1-C6)alkyl, —C(O)R24, —SO2R24, —C(O)NHR24 or —SO2NHR24;
• R24 is (C1-C6)alkyl, hydroxy (C1-C6)alkyl or NR25R26—((C1-C6)alkyl)—;
• R25 and R26 are independently selected from the group consisting of H and (C1-C6)alkyl;
• R27 is 1, 2 or 3 substituents selected from the group consisting of H, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy, halogen and —OH;
• and
• R28 and R29 are independently selected from the group consisting of H, (C1-C6)alkyl, (C1-C6)alkoxy, R27-aryl(C1-C6)alkyl, heteroaryl, heteroarylalkyl, hydroxy(C1-C6)alkyl, (C1-C6)alkoxy(C1-C6)alkyl, heterocyclyl, heterocyclylalkyl, and haloalkyl;
• or
• R28 and R29 taken together form a spirocyclic or a heterospirocyclic ring of 3-6 atoms.