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

摘要

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.