Macrocyclic compounds and compositions useful as BACE inhibitors

A compound of the formula

• in which
• R1 is (CH2)kN(Ra)Rb, in which
• k is 0, 1 or 2;
• and either
• 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, 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-tetrahydroquinol-4-yl, 1,2,3,4-tetrahydroisoquinol-4-yl, 1,2,3,4-tetrahydronaphth-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-tetrahydrobenzo[b]oxepin-5-yl or 1,3,4,5-tetrahydrobenzo[c]oxepin-5-yl group or Ra and Rb, together with the nitrogen, to which they are attached, form an optionally substituted pyrrolidinyl, 1-piperidinyl, 4-morpholinyl or piperazinyl group;
• R3 is hydrogen or (C1-4)alkyl;
• either
• V1 is hydrogen and V2 is hydroxyl;
• or
• V1 and V2 together are oxo;
• X1 is (C1-8)alkylene;
• X2 is (C1-8)alkylene, O, S, C(═O), C(═O)O, OC(═O), C(═O)N(R2)—(C1-8)alkylenoxy attached via its carbonyl function to Y and attached via the oxygen atom of its alkylenoxy moiety to Ar, N(R2)C(═O), C(═O)N(R2) or N(R2), in which R2 is hydrogen or (C1-4)alkyl;
• Y is (C1-10)alkylene, (C1-8)alkylenoxy(C1-6)alkylene, (C1-10)alkenylene or (C1-8)alkenylenoxy-(C1-6)alkylene;
• Ar is phenylene to which X1 and X2 are attached in meta or para position to each other;
• and either
• Z is C(═O), AA is N[(C1-4)alkyl or (C3-7)cycloalkyl]CH(CH3)C(═O) and n is 1;
• or
• Z is S(═O)2, AA is CH2CH[(C1-4)alkyl]C(═O), and n is 1,
• the number of ring atoms included in the macrocyclic ring being 14, 15, 16, 17 or 18,
• in free base form or in acid addition salt form.