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US 2006/0149092 A1Published application
Phenylcarboxylate beta-secretase inhibitors for the treatment of alzheimer's disease
AssigneeMerck & Co., Inc.
InventorsPhilippe Nantermet, Hemaka Rajapakse, Harold Selnick
Life of this patent
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Abstract
The present invention is directed to compounds which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the beta-secretase enzyme is involved.
Claims14
A compound of the formula I:
- wherein:
- R1 is selected from the group consisting of:
- (1) —C1-6alkyl,
- (2) —C2-6 alkenyl,
- (3) —C2-6 alkynyl,
- wherein said alkyl, alkenyl and alkynyl is unsubstituted or substituted with phenyl, which is unsubstituted or substituted with a group selected from:
- (i) halo,
- (ii) —C1-6alkyl,
- (iii) —C2-6 alkenyl,
- (iv) —C2-6 alkynyl,
- (v) —OH, and
- (vi) —O—C1-6alkyl,
- (4) hydrogen;
- R2 is selected from the group consisting of:
- (1) R4—S(O)2N(R7)—,
- wherein R4 is independently selected from the group consisting of:
- (a) —C1-6alkyl,
- (b) —C2-6 alkenyl,
- (c) —C2-6 alkynyl,
- wherein said alkyl, alkenyl and alkynyl is unsubstituted or substituted with 1-6 fluoro,
- (d) phenyl, and
- (e) benzyl,
- wherein R7 is independently selected from the group consisting of:
- (a) hydrogen,
- (b) —C1-6alkyl,
- (c) —C2-6 alkenyl,
- (d) —C2-6 alkynyl,
- wherein R8a and R8b are independently selected from the group consisting of:
- (a) hydrogen,
- (b) —CN,
- (c) halo,
- (d) —C1-6alkyl,
- (e) —C2-6 alkenyl, and
- (f) —C2-6 alkynyl
- R3 is selected from the group consisting of:
- R6a, R6b, and R6c are independently selected from the group consisting of:
- (1) hydrogen, and
- (2) halogen;
- R5 is selected from the group consisting of:
- (1) —C1-6alkyl,
- (2) —C2-6 alkenyl,
- (3) —C2-6 alkynyl,
- wherein said alkyl, alkenyl and alkynyl is unsubstituted or substituted with phenyl, and
- (4) hydrogen;
- R13 is selected from the group consisting of —CH═CH— and —O—;
- R9 and R10 are independently selected from the group consisting of:
- (1) hydrogen,
- (2) C1-6alkyl,
- (3) C2-6 alkenyl,
- (4) C2-6 alkynyl, wherein said alkyl, alkenyl and alkynyl is unsubstituted or substituted with phenyl,
- or R9 and R10 may be joined together to form a pyrrolidine or piperidine ring which is unsubstituted or substituted with —C1-6alkyl, —C2-6 alkenyl, —C2-6 alkynyl, —C1-6alkyl-O—C1-6alkyl, phenyl or pyridyl;
- R11 is selected from the group consisting of:
- (1) —OH,
- (2) —O—C1-6alkyl,
- (3) —O—C1-6alkyl-phenyl,
- (4) —O-phenyl, and
- (5) phenyl;
- R12 is selected from the group consisting of:
- (1) —NR9R10, and
- (2) —OH;
- m is independently 0, 1, or 2;
- and pharmaceutically acceptable salts thereof.
59 more elements
A compound which is selected from the group consisting of:
- and pharmaceutically acceptable salts thereof.
Dependencies are inferred from the claim text.