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

• Main Authors: MILICI, ANTHONY JOHN, LAU,WAN FANG, DUPLANTIER, ALLEN JACOB, CHUPAK, LOUIS STANLEY
• Format: Patent
• Language: English
• Published: 27.02.2004
• 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

A compound or pharmaceutically acceptable salts and prodrug thereof has the formula (1.0.0) wherein: A is optionally substituted alkyl, cycloalkyl, aryl, heteroaryl or heterocyclic or is 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-, A2NHSO2-A2-, A1-SO2NH-A2-, A1-(CH2)rO- A2-, A1-O-(CH2)rA2-or A1-(CH2)rA2-; A1 and A2 are independently H, alkenyl, alkynyl or optionally substituted alkyl, cycloalkyl, aryl, heteroaryl or heterocyclic; B is a group of formula (1.1.6) the symbol "*" indicates the point of attachment of the moiety represented by each partial Formula (1.1.0) and the symbol "à" indicates the point of attachment of the moiety to "E" in Formula (1.0.0) and the group of formula (1.1.6) may be optionally substituted; E is a -CR11R12; X is -O- and Y is -C(=O)- or S(O)2; k, n, and r are independently is 0 to 2; m is 0 or 1 and p is 1; R2 is hydrogen or alkyl; R3 and R4 re both H or taken together with the carbon and nitrogen atoms to which they are attached form an optionally substituted pyrrolidinyl group; R7 is alkyl, (CH2)kOR5, (CH2)kNR6C(=O)R5, (CH2)kNR6C(=O)OR5, (CH2)kNR6SO2R5, (CH2)kNR6R5, F, CF3, OCF3, or optionally substituted aryl, heterocyclyl, heteroaryl or cycloalkyl and R8 is hydrogen, F, CN, alkyl or alkoxy or taken together form a cycloalkyl or heterocyclic ring. R5, R6, R11 and R12 are as defined in the specification. The compounds are useful in treating an inflammatory, autoimmune or respiratory disease by inhibiting cell adhesion.