| abstract |
Halogenated amidino aminoacid derivatives (I) are new. Aminoacid derivatives of formula (I) and their salts are new. [Image] R1H, alkyl, alkenyl or alkynyl; R2as R1 or R- or S-alpha -aminoacid; R3, R4as R1 or NO2; R1-R4 are optionally substituted by T; T : lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, OH, lower alkoxy, aryloxy, SH, lower thioalkoxy, halo, CN, NO2, NH2, COOH, carboxyalkyl, carboxyaryl, amidino or guanidino; R11OH or R- or S-alpha -aminoacid; G : (i) 1-10C alkylene, 2-10C alkenylene or 2-10C alkynylene (all optionally substituted by one or more of halo, OH, CF3, NO2, CN, NH2, =CH2, alkyl, alkenyl, alkynyl or alkoxy (all optionally substituted by T or CF3)); (ii) (CH2)p(CX1X2)r(CH2)sQ(CH2)t(CX3X4)u(CH2)v; or (iii) (CH2)q(CX5X6)y(CH2)zA(CH2)k(CX7X8)j(CH2)h; p, r, s, t, u, v, w, y, z, k, j, h : 0-3; Q : Q = O, CO, S(O)a or NR12; a : 0-2, provided that if a = 1-2 then G must contain halo; R12H or alkyl (optionally substituted by alkyl, alkoxy, OH, CF3, NO2, CN, NH2 or halo); A : 3-6-membered carbocyclic or heterocyclic residue (optionally substituted by one or more of halo, alkyl, alkoxy, OH, CF3, NO2, CN or NH2); X1-X8H or halo; or alkyl, CH2, alkenyl or alkynyl (all optionally substituted by T or CF3); Y : heterocycle, mono-, di- or tri-haloalkyl, alkyl, cycloalkyl, alkenyl or alkynyl (all optionally substituted by one or more of halo, OH, CF3, NO2, CN, NH2, alkyl, alkenyl, alkynyl and alkoxy); or NR9R10; R9, R10H, alkyl, cycloalkyl, alkenyl, alkynyl, NO2, NH2, aryl or alkaryl; unless specified otherwise alkyl moieties have 1-10C, alkenyl or alkynyl moieties 2-10C and cycloalkyl moieties 3-10C; provided that at least one of G and Y contains a halogen; and that if G = (iii) then Y must contain halogen. ACTIVITY : Hypertensive; antiinflammatory; immunomodulatory; antidiabetic; cardiovascular; gastrointestinal; dermatological; bronchodilatory; anticancer; analgesic. MECHANISM OF ACTION : Inducible nitric oxide synthase (iNOS) inhibitor. |