US 7,514,459 B2
Gamma-secretase inhibitors
Ian James Collins, Redhill (United Kingdom); Joanne Clare Hannam, Stansted (United Kingdom); Andrew Madin, Sawbridgeworth (United Kingdom); and Mark Peter Ridgill, Watton-at-Stone (United Kingdom)
Assigned to Merck Sharp & Dohme Ltd., Hoddesdon, Hertfordshire (United Kingdom)
Appl. No. 10/571,717
PCT Filed Sep. 16, 2004, PCT No. PCT/GB2004/003973
§ 371(c)(1), (2), (4) Date Mar. 09, 2006,
PCT Pub. No. WO2005/030731, PCT Pub. Date Apr. 07, 2005.
Claims priority of application No. 0322340.1 (GB), filed on Sep. 24, 2003; and application No. 0322341.9 (GB), filed on Sep. 24, 2003.
Prior Publication US 2006/0293373 A1, Dec. 28, 2006
Int. Cl. A61K 31/4164 (2006.01); A61K 31/4196 (2006.01); C07D 233/54 (2006.01); C07D 249/08 (2006.01)
U.S. Cl. 514—361  [548/125; 548/127; 548/267.2; 548/300.1; 548/312.4; 514/383; 514/385; 514/396; 514/399] 12 Claims
 
1. A compound of formula I:

OG Complex Work Unit Drawing
wherein Z represents CH or N and the resulting imidazole or triazole group is attached at one of the positions indicated by an asterisk and X is attached at a position adjacent thereto;
X represents H, OH, C1-4alkoxy, Cl or F;
Y represents a bond, O or NR3;
Ar represents phenyl or 6-membered heteroaryl, either of which bears 0-3 substituents independently selected from halogen, CF3, CHF2, CH2F, NO2, CN, OCF3, C1-6alkyl and C1-6alkoxy;
R1 represents H; or when Y represents NR3, R1 and R3 may together represent —CH2—;
R2 represents H or a hydrocarbon group of 1-10 carbon atoms which is optionally substituted with CN, C1-4alkoxy or up to 3 halogen atoms; or R2 represents heteroaryl of 5 or 6 ring atoms optionally bearing up to 3 substituents independently selected from halogen, CF3, CHF2, CH2F, NO2, CN, OCF3, C1-6alkyl and C1-6alkoxy; or when Y represents NR3, R2 and R3 together may complete a heterocyclic ring of up to 6 members which optionally bears up to 3 substituents independently selected from halogen, CF3, CHF2, CH2F, NO2, CN, OCF3, C1-6alkyl and C1-6alkoxy; and
R3 represents H or C1-4alkyl, or together with R2 completes a heterocyclic ring as defined above;
or together with R1 represents —CH2—;
provided that when X is H, and Y represents NR3 and R1 and R3 together represent —CH2—, R2 does not represent 2,2,2-trifluoroethyl; and provided that R1 and R2 are not both H;
or a pharmaceutically acceptable salt thereof.