Human ADAM-10 inhibitors

A compound of structural formula I:

• and pharmaceutically acceptable salts thereof wherein L1 is —C(O)—, —S(O)2—, or —(CH2)n—;
• R1 is C1-C6-alkoxy-C1-C6-alkoxy;
• R2 is —R21-L2-R22;
• R21 is saturated or mono- or poly-unsaturated C5-C14-mono- or fused poly-cyclic ring, optionally containing one or two annular heteroatoms per ring and optionally substituted with one, two, or three R50 substituents;
• L2 is —O—, —C(O)—, —CH2—, —NH—, —S(O2)— or a direct bond;
• R22 is saturated or mono- or poly-unsaturated C5-C14-mono- or fused poly-cyclic ring, optionally containing one or two annular heteroatoms per ring and optionally substituted with one, two, or three R50 substituents;
• and
• R50 is R51-L3-(CH2)n—;
• L3 is —O—, —NH—, —S(O)0-2—, —C(O)—, —C(O)O—, —C(O)NH—, —OC(O)—, —NHC(O)—, —C6H4—, or a direct bond;
• R51 is —H, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, halo, —CF3, —OCF3, —OH, —NH2, mono-C1-C6alkyl amino, di-C1-C6alkyl amino, —SH, —CO2H, —CN, —NO2, —SO3H, or a saturated or mono- or poly-unsaturated C5-C14-mono- or fused poly-cyclic ring, optionally containing one or two annular heteroatoms per ring and optionally substituted with one, two, or three substituents;
• wherein n is 0, 1, 2, or 3;
• provided that an O or S is not singly bonded to another O or S.

A compound according to formula IV,

• and pharmaceutically acceptable salts thereof wherein,
• Z is —C(R15)═, —C(H)═, or —N═;
• Ar is aryl or heteroaryl, each optionally substituted;
• R15 is fluoro;
• p is 1, 2, or 3;
• L1 is —C(O)—, —S(O)2—, or —(CH2)n—;
• L4 is nothing or —O—;
• R1 is —H, —OR11, —(CH2)nR11, —C(O)R11, or —NR12R13;
• R11, R12, and R13 independently are
• j) R50;
• k) saturated or mono- or poly-unsaturated C5-C14-mono- or fused poly-cyclic ring, optionally containing one or two annular heteroatoms per ring and optionally substituted with one or two R50 substituents;
• l) C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, or —C(O)H, each of which is optionally substituted with one, two or three substituents independently selected from R50 and saturated or mono- or poly-unsaturated C5-C14-mono- or fused poly-cyclic ring, optionally containing one or two annular heteroatoms per ring and optionally substituted with one, two or three R50 substituents;
• or R12 and R13 together with the N to which they are covalently bound, a C5-C6 heterocycle optionally containing a second annular heteroatom and optionally substituted with one or two R50 substituents;
• and
• R50 is R51-L3-(CH2)n—;
• L3 is —O—, —NH—, —S(O)0-2—, —C(O)—, —C(O)O—, —C(O)NH—, —OC(O)—, —NHC(O)—, —C6H4—, or a direct bond;
• R51 is —H, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, halo, —CF3, —OCF3, —OH, —NH2, mono-C1-C6alkyl amino, di-C1-C6alkyl amino, —SH, —CO2H, —CN, —NO2, —SO3H, or a saturated or mono- or poly-unsaturated C5-C14-mono- or fused poly-cyclic ring, optionally containing one or two annular heteroatoms per ring and optionally substituted with one, two, or three substituents;
• wherein n is 0, 1, 2, or 3;
• provided that an O or S is not singly bonded to another O or S.