Non-peptidyl inhibitors of VLA-4 dependent cell binding useful in treating inflammatory, autoimmune, and respiratory diseases

A compound of Formula (1.0.0)

• and pharmaceutically acceptable salts and other prodrug derivative thereof, wherein:
• A is (C1-C6) alkyl, cycloalkyl, aryl, heteroaryl or heterocyclyl as defined herein;
• where said alkyl, cycloalkyl, aryl, heteroaryl or heterocyclyl is optionally substituted with 0 to 3 R9;
• or is a member selected from the group consisiting of the following radicals:
• A1-NHC(═O)NH-A2-, A1-NHC(═O)O-A2-, A1-OC(═O)NH-A2-, A1-NHSO2NH-A2-, A1-NHC(═O)-A2-, A1-C(═O)NH-A2-, A1NHSO2-A2-, A1SO2NH-A2-, A1-(CH2)rO-A2-, A1-O(CH2)rA2-, A1-(CH2)rA2, where A1 is aryl and A2 is aryl or pyridyl:
• group is substituted with 0 to 3 R9;
• B is a member independently selected from the group consisting of the following:
• where the symbol “*” indicates the point of attachment of the moiety represented by each partial Formula (1.1.0) through (1.1.4), (1.1.6) and (1.1.8) to the moiety “CR2R3” in Formula (1.0.0);
• and the symbol “→” indicates the point of attachment of the moiety represented by each partial Formula (1.1.0) through (1.1.4), (1.1.6) and (1.1.8) to the moiety “E” in Formula (1.0.0);
• each of Formula (1.1.0) through (1.1.4), (1.1.6) and (1.1.8), may be optionally substituted with R9;
• E is a single bond
• X is —O—;
• Y is —C(═O);
• k is an integer independently selected from 0, 1 and 2;
• m is an integer independently selected from 0 and 1;
• n is an integer independently selected from 0, 1 and 2;
• p is 1;
• q is an integer independently selected from 0,1 and 2;
• r is an integer independently selected from 0, 1 and 2;
• R2 and R3 are each independently selected from the group consisting of hydrogen and (C1-C6) alkyl substituted with 0 to 3 R13;
• R4 is hydrogen;
• or (C1-C6) alkyl optionally substituted with R13;
• R5 and R6 are independently hydrogen;
• (C1-C6) alkyl;
• (C2-C6) alkenyl;
• (C2-C6) alkynyl;
• CF3;
• aryl;
• cycloalkyl;
• heteroaryl;
• or heterocyclyl;
• R7 is (C1-C6) alkyl;
• (CH2)kOR5;
• (CH2)kNR6C(═O)R5;
• (CH2)kNR6C(═O)OR5;
• (CH2)kNR6SO2R5;
• (CH2)kNR6R5;
• F;
• CF3;
• OCF3;
• aryl, substituted with to 3 R9;
• heterocyclyl, substituted with 0 to 3 R9;
• heteroaryl, substituted with 0 to 3 R9;
• cycloalkyl, substituted with 0 to 3 R7;
• or may be taken together with R8 to for a cycloalkyl or heterocyclyl ring;
• or R7 may be taken together with R11 to form a cycloalkyl or heterocyclyl ring;
• R8 is hydrogen;
• F;
• (C1-C6) alkyl or (C1-C6) alkoxy;
• R9 is halogen;
• (C1-C6) alkyl;
• (C1-C6) alkoxy;
• (C3-C6) cycloalkyl;
• (C3-C6) cycloalkoxy;
• cyano;
• (CH2)kOH;
• C(═O)R5;
• (CH2)kC(O)NR5R6;
• (CH2)kNR5R6;
• (CH2)kNR5SO2R6;
• CF3;
• OCF3;
• SO2NR5R6;
• (CH2)mC(═O)OR5;
• when R9 is attached to a saturated carbon atom R9 may be ═O or ═S;
• when R9 is attached to a sulphur atom R9 ma be ═O;
• R10 is hydrogen;
• C(═O)R5;
• C(═O)OR5;
• (C1-C6) alkyl;
• aryl;
• heterocyclyl;
• heteroaryl;
• cycloalkyl;
• or SO2R5;
• R11 and R12 are independently hydrogen;
• (C1-C6) alkyl;
• hydroxy;
• cyano;
• (C1-C6) alkoxy;
• NR6C(═O)R5;
• NR6SO2R5;
• NR6R5;
• CF3;
• F;
• aryl;
• heterocyclyl;
• heteroaryl;
• cycloalkyl;
• cycloalkoxy;
• or R11 may be taken together with R12 to for a cycloalkyl or heterocyclyl ring;
• and
• R13 is independently selected from the group consisting of halogen;
• CF3;
• (C1-C6) alkyl;
• aryl;
• heteroaryl;
• heterocyclyl;
• hydroxy;
• cyano;
• (C1-C6) alkoxy;
• (C3-C6) cycloalkyl;
• (C3-C6) cycloalkoxy;
• (C2-C6) alkynyl;
• (C2-C6) alkenyl;
• -NR6R5;
• —C(═O)NR5R6;
• SO2R5;
• C(═O)R5;
• NR5SO2R6;
• NR5C(═O)R6;
• C(═O)NR5SO2R6;
• NR5C(═O)OR6;
• and SO2NR6R5.