PHENYLALANINOL DERIVATIVES

摘要

New Phenylalaninol derivatives (I). Phenylalaninol derivatives of formula (I) are new: [Image] X : a benzamide group of formula (i), a heterocyclyl-amide group of formula (ii) or an imidazolin-3-yl-4-one group of formula (iii): [Image] R 15halo, NO 2, CN, lower alkylsulfonyl, lower alkyl, lower alkoxy, lower alkoxycarbonyl, carboxy, lower alkylaminosulfonyl, lower perfluoroalkyl, lower alkylthio, lower hydroxyalkyl, alkoxy-lower alkyl, alkylthio-lower alkyl, alkylsulfinyl-lower alkyl, alkylsulfonyl-lower alkyl, lower alkylsulfinyl, lower alkanoyl, aroyl, aryl or aryloxy; R 16H, halo, NO 2, CN, lower alkyl, OH lower perfluoroalkyl or lower alkylthio; Het : 5-6 membered heteroaryl containing 1-2 N, O or S; or 9-10 membered bicyclic heteroaryl containing 1-4 O, S or N; R 30H or lower alkyl; p : 0-1; R 18aryl or heteroaryl; R 19optionally substituted lower alkyl, aryl, heteroaryl, aralkyl or heteroaralkyl; R 20lower alkanoyl or aroyl; Y : a group of formula (iv) or (v) or a 5-6 membered heteroaryl, bonded via C and containing 1-3 O, N or S and optionally substituted by 1-2 lower alkyl, cycloalkyl, halo, CN, perfluoroalkyl or aryl, provided that at least one of the substituents is adjacent to the bonding C; [Image] a : an optional double bond; R 22, R 23H, lower alkyl, lower alkoxy, lower cycloalkyl, aryl aralkyl, NO 2, CN, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, lower alkanoyl, halo or perfluoro lower alkyl; provided that at least one is not H; R 24H, lower alkyl, lower alkoxy, aryl, NO 2, CN, lower alkylsulfony or halo; R 25lower alkyl, lower alkenyl (optionally fluorinated) or R 26(CH 2) e; R 26aryl, heteroaryl, N 3, CN, OH, lower alkoxy. lower alkoxycarbonyl, lower alkanoyl, lower alkylthio, lower alkylsulfonyl, lower alkylsulfinyl, perfluoro-lower alkanoyl, NO 2 or NR 28R 29; R 28H or lower alkyl; R 29H, lower alkyl, lower alkoxycarbonyl, lower alkanoyl, aroyl, perfluoro lower alkanoylamino, lower alkylsulfonyl, lower alkylaminocarbonyl or arylaminocarbonyl; or R 28 + R 294-6 membered carbocyclic ring optionally containing 1 O, N or S and optionally substituted on C by lower alkyl or halo; Q : (CH 2) fO, (CH 2) fS, (CH 2) fN(R 27), (CH 2) f or a bond; R 27H, lower alkyl, aryl, lower alkanoyl, aroyl or lower alkoxycarbonyl; e : 0-4; and f : 1-3. An independent claim is included for preparation of (I). ACTIVITY : Antirheumatic; antiarthritic; antiasthmatic; antiinflammatory; neuroprotective. MECHANISM OF ACTION : (I) inhibit the binding of vascular cell adhesion molecule-1 (VCAM1) and fibronectin to the integrin VLA-4 (not defined) on circulating lymphocytes, eosinophils, basophils and monocytes.