Oxime-containing acyl guanidines as beta-secretase inhibitors
AssigneeBristol-Myers Squibb Company
InventorsYong-Jin Wu, Samuel Gerritz, Shuhao Shi, Shirong Zhu
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Abstract
There is provided a series of substituted oxime-containing acyl guanidines of Formula (I) or a stereoisomer; or a nontoxic pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5, R6, and R7 are as defined herein, their pharmaceutical compositions and methods of use. These compounds inhibit the processing of amyloid precursor protein (APP) by β-secretase and, more specifically, inhibit the production of Aβ-peptide. The present disclosure is directed to compounds useful in the treatment of neurological disorders related to β-amyloid production, such as Alzheimer's disease and other conditions affected by anti-amyloid activity.
Claims9
A compound of Formula (I);
- or a stereoisomer thereof
- wherein
- R1 is phenyl optionally substituted with one or more groups selected from halogen, CN, CF3, OH, —NH2, C3-6cycloalkyl, C1-6alkoxy, C2-6alkenyl, C1-6alkyl optionally substituted with OH or —NH2, —(CH2)m—NHC(═O)OC1-6 alkyl, —(CH2)m—NHC(═O)Ophenyl optionally substituted with halogen;
- —(CH2)m—NHC(═O)R8 and —NHC(═O)R9;
- R2 and R3 are each independently hydrogen, methyl or trifluoromethyl;
- m is 0 or 1;
- R4 and R5 are each independently hydrogen or fluoro;
- R6 is hydrogen, C1-6alkyl, trifluoromethyl or C3-6cycloalkyl;
- R7 is phenyl or indol-3-yl optionally substituted with one or more groups selected from halogen, CN, CF3, OCH3, NO2, NH2, and NHC(═O)C1-6alkyl;
- R8 is C1-6alkyl or C3-6cycloalkyl in which each is optionally substituted with a group selected from halogen, CN, CF3 and C1-4alkoxy;
- R9 is —C1-6alkylNR10R11;
- R10 is hydrogen or C1-6alkyl;
- R11 is hydrogen, C1-6alkyl optionally substituted with OH, halogen, C1-4alkoxy or C1-4alkylcarboxyl;
- —(CH2)mC3-6cycloalkyl optionally substituted with phenyl or C1-4alkyl;
- —(CH2)mphenyl optionally substituted with halogen, hydroxyl or C1-4alkoxy;
- or R10 and R11 together with the nitrogen to which they are attached is azetidine, aziridine, pyrrolidine, piperidine or homopiperidine in which each is optionally substituted with a group selected from halogen, C1-6alkyl and C1-4alkoxy;
- or a nontoxic pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.