Sulfamides as gamma-secretase inhibitors

A compound of formula I(D):

• wherein:
• R2a represents H or C2-6acyl which is optionally substituted with a carboxylic acid group or with an amino group;
• R4 represents R9, halogen, CN, NO2, —OR9, —SR9, —S(O)tR10 where t is 1 or 2, —N(R9)2, —COR9, —CO2R9, —OCOR10, —CH═N—OR11, —CON(R9)2, —SO2N(R9)2, —NR9COR10, —NR9CO2R10, —NR9SO2R10, —CH═CHCH2N(R16)2, —CH2N(R16)2, —NHCOCH2OR10 or —NHCOCH2N(R16)2;
• R7 represents H or R8;
• or two R7 groups together with a nitrogen atom to which they are mutually attached may complete a pyrrolidine, piperidine, piperazine or morpholine ring;
• R8 represents C1-10alkyl, perfluoroC1-6alkyl, C3-10cycloalkyl, C3-6cycloalkylC1-6alkyl, C2-10alkenyl, C2-10alkynyl, Ar or —C1-6alkylAr;
• R9 H or R10;
• or two R9 groups together with a nitrogen atom to which they are mutually attached may complete a pyrrolidine, piperidine, piperazine or morpholine ring which is optionally substituted by R12, —COR12 or —SO2R12;
• R10 represents C1-10alkyl, perfluoroC1-6alkyl, C3-10cycloalkyl, C3-6cycloalkylC1-6alkyl, C2-10alkenyl, C2-10alkynyl, C6-10aryl, heteroaryl, heterocyclyl, C6-10arylC1-6alkyl, heteroarylC1-6 alkyl, heterocyclylC1-6alkyl, C1-6arylC2-6alkenyl, or heteroarylC2-6alkenyl, wherein the alkyl, cycloalkyl, alkenyl and alkynyl groups optionally bear one substituent selected from halogen, CF3, NO2, CN, —OR11, —SR11, —SO2R12, —COR11, —CO2R11, —CON(R11)2, —OCOR12, —N(R11)2 and —NR11COR12;
• and the aryl, heteroaryl and heterocyclic groups optionally bear up to 3 substituents independently selected from halogen, NO2, CN, R12, —OR11, —SR11, —SO2R12, —COR11, —CO2R11, —CON(R11)2, —OCOR12, —N(R11)2 and —NR11COR12;
• R11 represents H or R12;
• or two R11 groups together with a nitrogen atom to which they are mutually attached may complete a heterocyclic ring system of 3–10 atoms, 0–2 of which (in addition to said nitrogen atom) are selected from O, N and S, said ring system bearing 0–2 substituents selected from halogen, CN, NO2, oxo, R12, OH, OR12, NH2, NHR12, CHO, CO2H, COR12 and CO2R12;
• R12 represents C1-6alkyl which is optionally substituted with halogen, CN, OH, C1-4alkoxy or C1-4alkoxycarbonyl;
• perfluoroC1-6alkyl, C3-7cycloalkyl, C2-6alkenyl, C2-6alkynyl, Ar, —C1-6alkylAr, ArOC1-6alkyl or C-heterocyclyl which is optionally substituted with halogen, CN, C1-6alkyl, OH, perfluoroC1-6alkyl, C2-6acyl, C1-4alkoxy or C1-4alkoxycarbonyl;
• R14 represents H, C1-10alkyl, perfluoroC1-6alkyl, C3-10cycloalkyl, C3-6cycloalkylC1-6alkyl, C2-10 alkenyl, C2-10alkynyl, C1-6aryl, heteroaryl, C6-10arylC1-6alkyl, or heteroarylC1-6alkyl, wherein the alkyl, cycloalkyl, alkenyl and alkynyl groups optionally bear one substituent selected from halogen, CN, NO2, —OR7, —SR7, —S(O)tR8 where t is 1 or 2, —N(R7)2, —COR7, —CO2R7, —OCOR8, —CON(R7)2, —NR7COR8, —C1-6alkylNR7COR8, —NR7CO2R8 and —NR7SO2R8, and the aryl and heteroaryl groups optionally bear up to 3 substituents selected from R8, halogen, CN, NO2, —OR7, —SR7, —S(O)tR8 where t is 1 or 2, —(R7)2, —COR7, —CO2R7, —OCOR8, —CON(R7)2, —NR7COR8, —C1-6alkylNR7COR8, —NR7CO2R8 and —NR7SO2R8;
• each R16 independently represents H or R10, or two R16 groups together with the nitrogen to which they are mutually attached complete a mono- or bicyclic heterocyclic ring system of 5–10 ring atoms selected from C, N, O and S, said ring system optionally having an additional aryl or heteroaryl ring fused thereto, said heterocyclic system and optional fused ring bearing 0–3 substituents independently selected from halogen, oxo, NO2, CN, R12, —OR11, —SR11, —SO2R12, —COR11, —CO2R11, —CON(R11)2, —OCOR12, —N(R11)2 and —NR11COR12;
• Ar represents phenyl or heteroaryl either of which optionally bears up to 3 substituents independently selected from halogen, CF3, NO2, CN, OCF3, C1-6alkyl and C1-6alkoxy;
• “heterocycly” at every occurrence thereof means a cyclic or polycyclic system of up to 10 ring atoms selected from C, N, O and S, wherein none of the constituent rings is aromatic and wherein at least one ring atom is other than C;
• and
• “heteroaryl” at every occurrence thereof means a cyclic or polycyclic system of up to 10 ring atoms selected from C, N, O and S, wherein at least one of the constituent rings is aromatic and wherein at least one ring atom is other than C;
• w is 1 or 2;
• or a pharmaceutically acceptable salt thereof.