Macrocyclic lactams and pharmaceutical use thereof

A compound of the formula

• in which
• R1 is CH(Re)C(═O)N(Ra)Rb or (CH2)kN(Rc)Rd, wherein
• k is 0, 1 or 2;
• Ra and Rb, independently, are hydrogen or an optionally substituted (C1-8)alkyl, (C3-7)cycloalkyl, (C3-7)cycloalkyl(C1-4)alkyl, aryl, aryl(C1-4)alkyl, heteroaryl or heteroaryl(C1-4)alkyl group,
• Rc and Rd, independently, are hydrogen or an optionally substituted (C1-8)alkyl, (C3-7)cycloalkyl, (C3-7)cycloalkyl(C1-4)alkyl, aryl, aryl(C1-4)alkyl, heteroaryl, heteroaryl(C1-4)alkyl, chroman-4-yl, isochroman-4-yl, thiochroman-4-yl, isothiochroman-4-yl, 1,1-dioxo-1lambda*6*-thiochroman-4-yl, 2,2-dioxo-2lambda*6*-isothiochroman-4-yl, 1,2,3,4-tetrahydro-quinolin-4-yl, 1,2,3,4-tetrahydro-isoquinolin-4-yl, 1,2,3,4-tetrahydro-naphthalen-1-yl, 1,1-dioxo-1,2,3,4-tetrahydro-1lambda*6*-benzo[e][1,2]thiazin-4-yl, 2,2-dioxo-1,2,3,4-tetrahydro-2lambda*6*-benzo[c][1,2]thiazin-4-yl, 1,1-dioxo-3,4-dihydro-1H-1lambda*6*-benzo[c][1,2]oxathiin-4-yl, 2,2-dioxo-3,4-dihydro-2H-2lambda*6*-benzo[e][1,2]oxathiin-4-yl, 2,3,4,5-tetrahydro-benzo[b]oxepin-5-yl or 1,3,4,5-tetrahydro-benzo[c]oxepin-5-yl group, or
• Ra and Rb, or Rc and Rd, together with the nitrogen to which they are attached, form an optionally substituted pyrrolidinyl, 1-piperidinyl, 4-morpholinyl or piperazinyl group;
• and
• Re is optionally substituted (C1-8)alkyl, (C1-4)alkoxy(C1-4)alkyl, (C3-7)cycloalkyl or (C3-7)cycloalkyl(C1-4)alkyl;
• R2 is hydrogen or (C1-4)alkyl;
• R3 is hydrogen, (C1-6)alkyl or an optionally substituted (C1-6)alkylOC(═O)NH, (C3-7)cycloalkylOC(═O)NH, (C3-7)cycloalkyl(C1-4)alkylOC(═O)NH, aryl(C1-4)alkylOC(═O)NH, heteroaryl(C1-4)alkylOC(═O)NH, (C1-4)alkylC(═O)NH, (C3-7)cycloalkylC(═O)NH, arylC(═O)NH, aryl(C1-4)alkylC(═O)NH, heteroarylC(═O)NH or heteroaryl(C1-4)alkylC(═O)NH group;
• U is a bond;
• V is CH═CH, CH2CH(OH), CH(OH)CH2 or CRhRhCRhRh, wherein each Rh, independently, is hydrogen, fluorine or (C1-4)alkyl;
• W is (C1-6)alkylene;
• X is an optionally substituted (C1-4)alkanylylidene or (C1-4)alkylene;
• Y is C(═O)NRg or N(Rg)C(═O), wherein
• Rg is hydrogen, (C1-8)alkyl or (C3-7)cycloalkyl;
• Z is a bond;
• and
• n is 0 to 5,
• the number of ring atoms included in the macrocyclic ring being 14, 15, 16 or 17, in free base form or in acid addition salt form.