Benzyl compounds which inhibit leukocyte adhesion mediated by VLA-4

A compound of formula II:

• where
• R1 is selected from the group consisting of alkyl, substituted alkyl, phenyl, substituted phenyl, cycloalkyl, heterocyclic, substituted heterocyclic, and heteroaryl;
• R2 and R3, together with the nitrogen atom bound to R2 and the carbon atom bound to R3, form a saturated heterocyclic group or a saturated substituted heterocyclic group with the proviso that when monosubstituted, the substituent on said saturated heterocyclic group is not carboxyl;
• R5 is selected from the group consisting of —(CH2)n-aryl and —(CH2)n-heteroaryl, where n is an integer equal to 1 to 4;
• R6 is selected from the group consisting of amino, alkoxy, substituted alkoxy, cycloalkoxy, substituted cycloalkoxy, —O-(N-succinimidyl), —NH-adamantyl, —O-cholest-5-en-3-β-yl, —NHOY where Y is hydrogen, alkyl, substituted alkyl, aryl, and substituted aryl, —NH(CH2)pCOOY where p is an integer of from 1 to 8 and Y is as defined above, —OCH2NR9R10 where R9 is selected from the group consisting of —C(O)-aryl and —C(O)-substituted aryl and R10 is selected from the group consisting of hydrogen and —CH2COOR11 where R11 is alkyl, and —NHSO2Z where Z is alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic and substituted heterocyclic;
• Q is —C(X)NR7— wherein R7 is selected from the group consisting of hydrogen and alkyl, and X is selected from the group consisting of oxygen and sulfur;
• and pharmaceutically acceptable salts thereof,
• with the following provisos:
• A. when R1 is 4-methylphenyl, R2 and R3 together with the pendent nitrogen and carbon atoms form a pyrrolidin-2-yl ring, R5 is benzyl and Q is —C(O)NH—, then R6 is not —NH(CH2)2CO2Et or -(1R,2S,5R)-(−)-menthyl ester;
• B. when R1 is 4-methylphenyl, R2 and R3 together with the pendent nitrogen and carbon atoms form a 3-β-phenyl-D-pyrrolidin-2-yl ring, R5 is benzyl and Q is —C(O)NH—, then R6 is not —OCH2CH3;
• C. when R1 is 4-methylphenyl, R2 and R3 together with the pendent nitrogen and carbon atoms form a pyrrolidin-2-yl ring, R5 is D-benzyl and Q is —C(O)NH—, then R6 is not —OCH2CH3;
• and
• D. when R1 is 4-methylphenyl, R2 and R3 together with the pendent nitrogen and carbon atoms form a 5,5-dimethyl-1,1-dioxo-thiaprolyl ring, R5 is benzyl and Q is —C(O)NH—, then R6 is not —OC(CH3)3.