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

• Main Authors: DUPLANTIER, ALLEN, JACOB, MILICI, ANTHONY, JOHN, CHUPAK, LOUIS, STANLEY, LAU, WAN, FANG
• Format: Patent
• Language: English
• Published: 29.09.2003
• Edition: 7
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

There is disclosed a genus of non-peptidyl compounds, wherein said compounds are VLA-4 inhibitors useful in treating inflammatory, autoimmune, and respiratory diseases, and wherein said compounds comprise a compound of Formula (1.0.0): and pharmaceutically acceptable salts and other prodrug derivatives thereof, wherein: A is (C1-C6) alkyl, cycloalkyl, aryl, heteroaryl or heterocyclyl 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-, A1-NHSO2-A2-, A1-SO2NH-A2-, A1-(CH2)rO-A2-, A1-O(CH2)r-A2, A1-(CH2)r-A2-, where A1 and A2 are each independently selected from the group consisting of hydrogen, aryl, (C1-C6) alkyl, (C2-C6) alkenyl, (C2-C6) alkynyl, cycloalkyl, heteroaryl, and heterocyclyl substituted with 0 to 3 R9; B is a member independently selected from the group consisting of the following: E is a single bond; -O-; -NR10-; -CH-CH-; -CC-; S(-O)q; -CR11R12NR10-; or -CR11R12-; X is -O-; -C(-O)-; -S(-O)q-; or -NR10-; X1, X2 and X3 are each independently selected from the group consisting of CH, CR9 or N; Y is a single bond; -C(-O)-; -C(-S)-; or -S(-O)2-; 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 0 to 3 R9; heterocyclyl, substituted with 0 to 3 R9; heteroaryl, substituted with 0 to 3 R9; cycloalkyl, substituted with 0 to 3 R9; or R7 may be taken together with R8 to form a cycloalkyl or heterocyclyl ring; or R7 may be taken together with R11 to form a cycloalkyl or heterocyclyl ring; and R8 is hydrogen; F; (C1-C6) alkyl or (C1-C6) alkoxy.