# US 7,745,470 B2 · Isophthalates as beta-secretase inhibitors

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- Number: US 7,745,470 B2
- Document ID: US7745470B2
- Status: Granted
- Kind: B2
- Application number: 11/370,728
- Filed: 2006-03-08
- Published: 2006-10-12
- Granted: 2010-06-29
- Earliest claimed: 2005-03-10
- Assignees: Bristol-Myers Squibb Company
- Inventors: Lorin A. Thompson, III; Kenneth M. Boy; Jianliang Shi; John E. Macor
- Web page: https://patentgrep.com/patent/US7745470B2

## CPC

- C07D 265/30: not condensed with other rings
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- C07D 207/09: Radicals substituted by nitrogen atoms, not forming part of a nitro radical
- C07D 207/12: Oxygen or sulfur atoms
- C07D 207/27: with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
- C07D 265/32: with oxygen atoms directly attached to ring carbon atoms
- C07D 403/12: linked by a chain containing hetero atoms as chain links
- C07D 413/12: linked by a chain containing hetero atoms as chain links
- C07D 413/14: containing three or more hetero rings
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

There is provided a series of substituted isophthalates of formula (I) or a stereoisomer thereof; or a pharmaceutically acceptable salt thereof, wherein W, R3, R5 and R6 as defined herein, their pharmaceutical compositions and methods of use. These novel 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.

## Claims

### Claim 1

The compound having formula (Id); or a stereoisomer thereof,
wherein
R1 is hydrogen or C1-6alkyl;
R2 is C1-6alkyl or phenyl(C1-4alkyl) in which said phenyl is optionally substituted with halogen; or R1 and R2 are joined together with the nitrogen to form a 5- or 6-membered ring optionally substituted by R4;
R3 is hydrogen, C1-6alkyl, oxazole, thiazole, or NR12—(CO)—R13 in which R12 and R13 are independently C1-6alkyl or are joined together with the nitrogen to form a 5- or 6-membered ring;
R4 is C1-4alkyl optionally substituted with C1-4alkoxy; and
R5 is C1-6alkyl or phenyl(C1-4alkyl) in which each group is optionally substituted with one or two halogen;
or a nontoxic pharmaceutically acceptable salt thereof.

### Claim 2

The compound, or a stereoisomer thereof, which is N-((1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((2R,4R)-4-propoxypyrrolidin-2-yl)propan-2-yl)-3-((R)-2-(methoxymethyl)pyrrolidine-1-carbonyl)-5-(oxazol-2-yl)benzamide.