# US 8,569,310 B2 · Pentafluorosulfur imino heterocyclic compounds as BACE-1 inhibitors, compositions and their use

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- Number: US 8,569,310 B2
- Document ID: US8569310B2
- Status: Granted
- Kind: B2
- Application number: 13/391,441
- Filed: 2010-10-06
- Published: 2012-08-02
- Granted: 2013-10-29
- Earliest claimed: 2009-10-08
- Assignees: Merck Sharp & Dohme Corp.
- Applicants: Ulrich Iserloh; Andrew W. Stamford; Jared N Cumming
- Inventors: Ulrich Iserloh; Andrew W. Stamford; Jared N Cumming
- Web page: https://patentgrep.com/patent/US8569310B2

## CPC

- C07D 239/22: with hetero atoms directly attached to ring carbon atoms
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/16: Anti-Parkinson drugs
- 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
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/04: Antibacterial agents
- C07D 405/04: directly linked by a ring-member-to-ring-member bond
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

In its many embodiments, the present invention provides certain pentafluorosulfur imino heterocyclic compounds, including compounds Formula (a) and pharmaceutically acceptable salts thereof. Compounds of Formula (a) have the general structure: (a) wherein each variable is selected independently and as defined herein. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (Aβ) protein, including Alzheimers Disease, are also disclosed.

## Claims

### Claim 1

A compound, or pharmaceutically acceptable salt thereof, said compound having the structural Formula (a):
wherein:
W is selected from the group consisting of —C(O)—, —C(S)—, and —C(═NR8A)—;
-L1- is present or absent and when present represents a divalent moiety selected from the group consisting of -alkyl-, -haloalkyl-, -heteroalkyl-, -alkenyl-, and -alkynyl-;
-L2- is present or absent and when present represents a divalent moiety selected from the group consisting of -alkyl-, -haloalkyl-, -heteroalkyl-, -alkenyl-, and -alkynyl-;
-L3- is present or absent and when present represents a divalent moiety selected from the group consisting of -alkyl-, -haloalkyl-, -heteroalkyl-, -alkenyl-, and -alkynyl-;
each -L4- (when present) independently is present or absent and when present represents a divalent moiety independently selected from the group consisting of -alkyl-, -haloalkyl-, -heteroalkyl-, -alkenyl-, -alkynyl-, —N(R8)—, —NHC(O)—, and —C(O)NH—;
m, n, p, q, r, s, and t are each independently selected integers, wherein:
m is 0 or more,
n is 0 or more,
p is 0 or more,
q is 0 or more,
r is 0, 1, or 2,
s is 0, 1, or 2,
t is 0, 1, or 2,
with the provisos that:
(i) the maximum value of the sum of m, q, and s is the maximum number of available substitutable hydrogen atoms on ring A,
(ii) the maximum value of the sum of n and r is the maximum number of available substitutable hydrogen atoms on ring B, and
(iii) the maximum value of the sum of p and t is the maximum number of available substitutable hydrogen atoms on ring C, and
(iv) the sum of r, s, and t is 1 or 2;
R1 is selected from the group consisting of: H, alkyl, haloalkyl, heteroalkyl, heterohaloalkyl, cycloalkyl, cycloalkylalkyl-, heterocycloalkyl, heterocycloalkylalkyl-, aryl, arylalkyl-, heteroaryl, and heteroarylalkyl-,
wherein each of said alkyl, haloalkyl, heteroalkyl, heterohaloalkyl, cycloalkyl, cycloalkylalkyl-, heterocycloalkyl, heterocycloalkylalkyl-, aryl, arylalkyl-, heteroaryl, and heteroarylalkyl- of R1 is unsubstituted or substituted with from 1 to 5 independently selected R10 groups;
R2 is selected from the group consisting of H, alkyl, halo, haloalkyl, aryl, arylalkyl-, heteroaryl, heteroarylalkyl-, cycloalkyl, cycloalkylalkyl-, cycloalkenyl, heterocycloalkyl, and heterocycloalkenyl,
wherein each of said alkyl, haloalkyl, aryl, arylalkyl-, heteroaryl, heteroarylalkyl-, cycloalkyl, cycloalkylalkyl-, cycloalkenyl, heterocycloalkyl, and heterocycloalkenyl of R2 is unsubstituted or substituted with from 1 to 5 independently selected R10 groups;
R3 is selected from the group consisting of alkyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, and heterocycloalkenyl,
wherein each of said alkyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, and heterocycloalkenyl of R3 is unsubstituted or substituted with from 1 to 5 independently selected R10 groups;
ring A is selected from the group consisting of monocyclic aryl, monocyclic heteroaryl,monocyclic cycloalkyl, monocyclic cycloalkenyl, monocyclic heterocycloalkyl, monocyclic heterocycloalkenyl, and a multicyclic group;
each R4 (when present) is independently selected from the group consisting of halo, —CN, —NO2, —Si(R6)3, —P(O)(OR7)2, —P(O)(OR7)(R7), —N(R8)2, —NR8C(O)R7, —NR8S(O)2R7, —NR8C(O)N(R8)2, —NR8C(O)OR7, —C(O)R7, —C(O)2R7, —C(O)N(R8)2, —S(O)R7, —S(O)2R7, —S(O)2N(R8)2, —OR7, —SR', alkyl, haloalkyl, haloalkoxy, heteroalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl-, heterocycloalkyl, aryl, and heteroaryl,
wherein each said alkyl, haloalkyl, haloalkoxy, heteroalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl-, heterocycloalkyl, aryl, and heteroaryl of R4 (when present) is optionally independently unsubstituted or further substituted with one or more independently selected groups selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, lower heteroalkyl, halo, —CN, —SF5, —OSF5, —NO2, —N(R8)2, —OR7, —C(O)N(R8)2, and cycloalkyl;
ring B is selected from the group consisting of monocyclic aryl, monocyclic heteroaryl, monocyclic cycloalkyl, monocyclic cycloalkenyl, monocyclic heterocycloalkyl, monocyclic heterocycloalkenyl, and a multicyclic group;
each R5 (when present) is independently selected from the group consisting of halo, —CN, —NO2, —Si(R6)3, —P(O)(OR7)2, —P(O)(OR7)(R7), —N(R8)2, —NR8C(O)R7, —NR8S(O)2R7, —NR8C(O)N(R8)2, —NR8C(O)OR7, —C(O)R7, —C(O)2R7, —C(O)N(R8)2, —S(O)R7, —S(O)2R7, —S(O)2N(R8)2, —OR7, —SR7, alkyl, haloalkyl, haloalkoxy, heteroalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl-, heterocycloalkyl, aryl, and heteroaryl,
wherein each said alkyl, haloalkyl, haloalkoxy, heteroalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl-, heterocycloalkyl, aryl, and heteroaryl of R5 (when present) is optionally independently unsubstituted or further substituted with one or more independently selected groups selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, lower heteroalkyl, halo, —CN, —SF5, —OSF5, —NO2, —N(R8)2, —OR7, —C(O)N(R8)2, and cycloalkyl;
each ring C (when present) is independently selected from the group consisting of monocyclic aryl, monocyclic heteroaryl, monocyclic cycloalkyl, monocyclic cycloalkenyl, monocyclic heterocycloalkyl, monocyclic heterocycloalkenyl, and a multicyclic group;
each R6 (when present) is independently selected from the group consisting of alkyl, aryl, arylalkyl-, haloalkyl, cycloalkyl, cycloalkylalkyl-, heteroaryl, and heteroarylalkyl-;
each R7 (when present) is independently selected from the group consisting of H, alkyl, alkenyl, heteroalkyl, haloalkyl, aryl, arylalkyl-, heteroaryl, heteroarylalkyl-, cycloalkyl, cycloalkylalkyl-, heterocycloalkyl, and heterocycloalkylalkyl-;
each R8 (when present) is independently selected from the group consisting of H, alkyl, alkenyl, heteroalkyl, haloalkyl, aryl, arylalkyl-, heteroaryl, heteroarylalkyl-, cycloalkyl, cycloalkylalkyl-, heterocycloalkyl, and heterocycloalkylalkyl-;
R8A is selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, arylcycloalkyl, OR7, —CN, —C(O)R7, —C(O)OR7, —S(O)2R7, —C(O)N(R8)2, —S(O)N(R8)2, —S(O)2N(R8)2, —NO2, and —N(R8)2;
each R9 (when present) is independently selected from the group consisting of: halogen, —CN, —NO2, —Si(R6)3, —P(O)(OR7)2, —P(O)(OR7)(R7), —N(R8)2, —NR8C(O)R7, —NR8S(O)2R7, —NR8C(O)N(R8)2, —NR8C(O)OR7, —C(O)R7, —C(O)2R7, —C(O)N(R8)2, —S(O)R7, —S(O)2R7, —S(O)2N(R8)2, —OR7, —SR7, alkyl, haloalkyl, heteroalkyl, alkenyl, alkynyl, aryl, arylalkyl-, cycloalkyl, heteroaryl, heteroarylalkyl-, and heterocycloalkyl;
each R10 (when present) is independently selected from the group consisting of halo, —CN, —NO2, —Si(R6)3, —P(O)(OR7)2, —P(O)(OR7)(R7), —N(R8)2, —NR8C(O)R7, —NR8S(O)2R7, —NR8C(O)N(R8)2, —NR8C(O)OR7, —C(O)R7, —C(O)2R7, —C(O)N(R8)2, —S(O)R7, —S(O)2R7, —S(O)2N(R8)2, —OR7, —SR7, alkyl, haloalkyl, haloalkoxy, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl,
wherein each said alkyl, haloalkyl, haloalkoxy, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl of R10 (when present) is optionally independently unsubstituted or further substituted with one or more independently selected groups selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, lower heteroalkyl, halo, —CN, —NO2, —N(R8)2, —OR7, —C(O)N(R8)2, and cycloalkyl; and
each R11 is independently selected from the group consisting of —SF5 and —OSF5.

### Claim 2

A compound, or pharmaceutically acceptable salt thereof, said compound having the structural Formula (I):
wherein:
W is selected from the group consisting of —C(O)—, —C(S)—, and —C(═NR8A)—;
-L1- is present or absent and when present represents a divalent moiety selected from the group consisting of -alkyl-, -haloalkyl-, -heteroalkyl-, -alkenyl-, and -alkynyl-;
-L2 - is present or absent and when present represents a divalent moiety selected from the group consisting of -alkyl-, -haloalkyl-, -heteroalkyl-, -alkenyl-, and -alkynyl-;
-L3- is present or absent and when present represents a divalent moiety selected from the group consisting of -alkyl-, -haloalkyl-, -heteroalkyl-, -alkenyl-, and -alkynyl-;
m, n, r, and s are each independently selected integers, wherein:
m is 0 or more,
n is 0 or more,
r is 0, 1, or 2,
s is 0, 1, or 2,
with the provisos that:
(i) the maximum value of the sum of m and s is the maximum number of available substitutable hydrogen atoms on ring A,
(ii) the maximum value of the sum of n and r is the maximum number of available substitutable hydrogen atoms on ring B, and
(iii) the sum of r and s is 1 or 2;
R1 is selected from the group consisting of: H, alkyl, haloalkyl, heteroalkyl, heterohaloalkyl, cycloalkyl, cycloalkylalkyl-, heterocycloalkyl, heterocycloalkylalkyl-, aryl, arylalkyl-, heteroaryl, and heteroarylalkyl-,
wherein each of said alkyl, haloalkyl, heteroalkyl, heterohaloalkyl, cycloalkyl, cycloalkylalkyl-, heterocycloalkyl, heterocycloalkylalkyl-, aryl, arylalkyl-, heteroaryl, and heteroarylalkyl- of R1 is unsubstituted or substituted with from 1 to 5 independently selected R10 groups;
R2 is selected from the group consisting of H, alkyl, halo, haloalkyl, aryl, arylalkyl-, heteroaryl, heteroarylalkyl-, cycloalkyl, cycloalkylalkyl-, cycloalkenyl, heterocycloalkyl, and heterocycloalkenyl,
wherein each of said alkyl, haloalkyl, aryl, arylalkyl-, heteroaryl, heteroarylalkyl-, cycloalkyl, cycloalkylalkyl-, cycloalkenyl, heterocycloalkyl, and heterocycloalkenyl of R2 is unsubstituted or substituted with from 1 to 5 independently selected R10 groups;
R3 is selected from the group consisting of alkyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, and heterocycloalkenyl,
wherein each of said alkyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, and heterocycloalkenyl of R3 is unsubstituted or substituted with from 1 to 5 independently selected R10 groups;
ring A is selected from the group consisting of monocyclic aryl, monocyclic heteroaryl, monocyclic cycloalkyl, monocyclic cycloalkenyl, monocyclic heterocycloalkyl, monocyclic heterocycloalkenyl, and a multicyclic group;
each R4 (when present) is independently selected from the group consisting of halo, —CN, —NO2, —Si(R6)3, —P(O)(OR7)2, —P(O)(OR7)(R7), —N(R8)2, —NR8C(O)R7, —NR8S(O)2R7, —NR8C(O)N(R8)2, —NR8C(O)OR7, —C(O)R7, —C(O)2R7, —C(O)N(R8)2, —S(O)R7, —S(O)2R7, —S(O)2N(R8)2, —OR7,—SR7, alkyl, haloalkyl, haloalkoxy, heteroalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl-, heterocycloalkyl, aryl, and heteroaryl,
wherein each said alkyl, haloalkyl, haloalkoxy, heteroalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl-, heterocycloalkyl, aryl, and heteroaryl of R4 (when present) is optionally independently unsubstituted or further substituted with one or more independently selected groups selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, lower heteroalkyl, halo, —CN, —SF5, —OSF5, —NO2, —N(R8)2, —OR7, —C(O)N(R8)2, and cycloalkyl;
ring B is selected from the group consisting of monocyclic aryl, monocyclic heteroaryl, monocyclic cycloalkyl, monocyclic cycloalkenyl, monocyclic heterocycloalkyl, monocyclic heterocycloalkenyl, and a multicyclic group;
each R5 (when present) is independently selected from the group consisting of halo, —CN, —NO2, —Si(R6)3, —P(O)(OR7)(R7), —N(R8)2, —NR8C(O)R7, —NR8S(O)2R7, —NR8C(O)N(R8)2, —NR8C(O)OR7, —C(O)R7, —C(O)2R7, —C(O)N(R8)2, —S(O)R7, —S(O)2R7, —S(O)2N(R8)2, —OR7, —SR7, alkyl, haloalkyl, haloalkoxy, heteroalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl-, heterocycloalkyl, aryl, and heteroaryl,
wherein each said alkyl, haloalkyl, haloalkoxy, heteroalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl-,heterocycloalkyl, aryl, and heteroaryl of R5 (when present) is optionally independently unsubstituted or further substituted with one or more independently selected groups selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, lower heteroalkyl, halo, —CN, —SF5, —OSF5, —NO2, —N(R8)2, —OR7, —C(O)N(R8)2, and cycloalkyl;
each R6 (when present) is independently selected from the group consisting of alkyl, aryl, arylalkyl-, haloalkyl, cycloalkyl, cycloalkylalkyl-, heteroaryl, and heteroarylalkyl-;
each R7 (when present) is independently selected from the group consisting of H, alkyl, alkenyl, heteroalkyl, haloalkyl, aryl, arylalkyl-, heteroaryl, heteroarylalkyl-, cycloalkyl, cycloalkylalkyl-, heterocycloalkyl, and heterocycloalkylalkyl-;
each R8 (when present) is independently selected from the group consisting of H, alkyl, alkenyl, heteroalkyl, haloalkyl, aryl, arylalkyl-, heteroaryl, heteroarylalkyl-, cycloalkyl, cycloalkylalkyl-, heterocycloalkyl, and heterocycloalkylalkyl-;
R8A is selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, arylcycloalkyl, OR7, —CN, —C(O)R7, —C(O)OR7, —S(O)2R7, —C(O)N(R8)2, —S(O)2N(R8)2, —S(O)2N(R8)2, —NO2, and —N(R8)2;
each R10 (when present) is independently selected from the group consisting of halo, —CN, —NO2, —Si(R6)3, —P(O)(OR7)2, —P(O)(OR7)(R7), —N(R8)2, —NR8C(O)R7, —NR8S(O)2R7, —NR8C(O)N(R8)2, —NR8C(O)OR7, —C(O)R7, —C(O)2R7, —C(O)N(R8)2, —S(O)R7, —S(O)2R7, —S(O)2N(R8)2, —OR7, —SR7, alkyl, haloalkyl, haloalkoxy, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl,
wherein each said alkyl, haloalkyl, haloalkoxy, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl of R10 (when present) is optionally independently unsubstituted or further substituted with one or more independently selected groups selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, lower heteroalkyl, halo, —CN, —NO2, —N(R8)2, —OR7, —C(O)N(R8)2, and cycloalkyl; and
each R11 is independently selected from the group consisting of —SF5 and —OSF5.

### Claim 3 (depends on 1)

A compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein:
R1 is selected from the group consisting of H, lower alkyl, and cyclopropyl.

### Claim 4 (depends on 1)

A compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein:
R2 is H.

### Claim 5 (depends on 1)

A compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein:
-L2- is a bond or a -alkyl- group; and
R3 is selected from the group consisting H, alkyl, haloalkyl, heteroalkyl, cycloalkyl, and cycloalkylalkyl-.

### Claim 6 (depends on 1)

A compound of claim 1, or a pharmaceutically acceptable salt thereof, said compound having a structural Formula (II):

### Claim 7 (depends on 6)

A compound of claim 6, or a pharmaceutically acceptable salt thereof, wherein:
-L1- is a bond or a divalent -alkyl- group;
m is 0 or more;
s is 0, 1, or 2;
ring A is selected from the group consisting of phenyl, pyridyl, pyrazinyl, pyrazolyl, furanyl, thienyl, pyrimidinyl, pyridazinyl, thiazolyl, and oxazolyl;
each R4 (when present) is independently selected from the group consisting of halo, —CN, —NO2, —N(R8)2, —NR8C(O)R7, —C(O)N(R8)2, —OR7, alkyl, haloalkyl, heteroalkyl, and alkynyl;
-L3- is a bond or a divalent —CH2— group;
n is 0 or more;
r is 0, 1, or 2;
ring B is selected from the group consisting of phenyl, benzoxazolyl, benzofuranyl, benzimidazolyl, benzisoxazolyl, pyridyl, pyrazinyl, furanyl, thienyl, pyrimidinyl, pyridazinyl, thiazolyl, oxazolyl, quinolinyl, isoquinolinyl, dihydroquinolinyl, naphthyl, benzothienyl, benzothiazolyl, indazolyl, and indolyl;
each R5 (when present) is independently selected from the group consisting of halo, —CN, —N(R8)2, —NR8C(O)R7, —NR8S(O)2R7, —C(O)R7, —S(O)R7, S(O)2R7, —OR7, —SR7, alkyl, haloalkyl, heteroalkyl, —O-heteroalkyl, alkenyl, cycloalkyl, heterocycloalkyl, aryl, and monocyclic heteroaryl,
wherein each said alkyl, said alkenyl, said alkenyl, said cycloalkyl, said heterocycloalkyl, said aryl, and said monocyclic heteroaryl of R5 (when present) is optionally and independently further substituted with one or more groups independently selected from the group consisting of halo, lower alkyl, lower alkenyl, lower alkynyl, lower heteroalkyl, —CN, —NO2, —N(R8)2, and —OH;
with the provisos that
(i) the sum of m and s is the maximum number of substitutable hydrogen atoms on ring A,
(ii) the sum of n and r is the maximum number of substitutable hydrogen atoms on ring B, and
(iii) the sum of r and s is 1 or 2.

### Claim 8 (depends on 6)

A compound of claim 6, or a pharmaceutically acceptable salt thereof, wherein:
-L1- is a bond or a divalent —CH2- group;
ring A is selected from the group consisting of phenyl and thienyl;
wherein, when ring. A is phenyl, the sum of m and s is 0 to 5, and
when ring A is thienyl, the sum of m and s is 0 to 3;
each R4 (when present) is independently selected from the group consisting of halo, —CN, —NO2, —N(R8)2, —NR8C(O)R7, —C(O)N(R8)2, OR7, alkyl, haloalkyl, heteroalkyl, and alkynyl;
-L3- is a bond or a diavalent -alkyl- group;
ring B is selected from the group consisting of phenyl, pyridyl, thienyl, naphthyl, quinolinyl, isoquinolinyl, and benzothienyl;
n is 0 or more;
r is 0, 1, or 2, with the provisos that (i) the sum of n and r is the maximum number of substitutable hydrogen atoms on ring B, and (ii) the sum of r and s is 1 or 2;
each R5 (when present) is independently selected from the group consisting of halo, —CN, —N(R8)2, —NR8C(O)R7, —NR8S(O)2R7 —C(O)R7, —S(O)R7, —S(O)2R7, —SR', alkyl, haloalkyl, heteroalkyl, —O-heteroalkyl, alkenyl, alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, pyridyl, furanyl, thienyl, pyridazinyl, oxazolyl, isoxazolyl, oxetanyl, and pyrrolyl,
wherein each said alkyl, -alkoxy, haloalkyl, heteroalkyl, —O-heteroalkyl, alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, pyridyl, furanyl, thienyl, pyridazinyl, oxazolyl, isoxazolyl, oxetanyl, and pyrrolyl of R5 (when present) is optionally and independently further substituted with one or more groups independently selected from the group consisting of halo, lower alkyl, lower alkenyl, lower alkynyl, lower heteroalkyl, —CN, —NO2, —N(R8)2, and —OH;
and each R7 and each R8 (when present) is independently selected from the group consisting of H and lower alkyl.

### Claim 9 (depends on 6)

A compound of claim 6, or a pharmaceutically acceptable salt thereof, wherein:
-L1- is a bond or a divalent —CH2- group;
the moiety,
is selected from the group consisting of
n is 0, 1, 2, or 3;
ring B is selected from the group consisting of phenyl, pyridyl, thienyl, naphthyl, quinolinyl, isoquinolinyl, and benzothienyl; and
each R5 (when present) is independently selected from the group consisting of halo, —CN, —SFS, lower alkyl, lower alkenyl, lower haloalkyl, —C(O)—Cyclopropyl, oxetanyl, lower alkyl—Substituted oxetanyl, cyclopropyl, lower heteroalkyl substituted cyclopropyl, lower alkyl—CN, lower heteroalkyl, and phenyl.

### Claim 10 (depends on 6)

A compound of claim 6, or a pharmaceutically acceptable salt thereof, wherein:
-L1- is a bond or a divalent —CH2- group;
s is 0;
the moiety,
is selected from the group consisting of
n is 0, 1, 2, or 3,
r is 1 or 2;
ring B is selected from the group consisting of phenyl, pyridyl, thienyl, naphthyl, quinolinyl, isoquinolinyl, and benzothienyl; and
each R5 (when present) is independently selected from the group consisting of halo, —CN, lower alkyl, lower alkenyl, lower haloalkyl, —C(O)-Cyclopropyl, oxetanyl, lower alkyl-Substituted oxetanyl, cyclopropyl, lower heteroalkyl substituted cyclopropyl, lower alkyl-CN, lower heteroalkyl, and phenyl.

### Claim 11 (depends on 6)

A compound of claim 6, or a pharmaceutically acceptable salt thereof, wherein:
-L1- is a bond or a divalent —CH2- group;
s is 0;
the moiety,
is selected from the group consisting of
-L3- is a bond or a divalent —CH2— group;
ring B is phenyl;
n is 0;
r is 1; and
and the moiety

### Claim 12 (depends on 11)

A compound of claim 11, or a pharmaceutically acceptable salt thereof, wherein:
R11 is —SF5.

### Claim 13 (depends on 11)

A compound of claim 11, or a pharmaceutically acceptable salt thereof, wherein:
R11 is —OSF5.

### Claim 14

A compound, or a pharmaceutically acceptable salt thereof, said compound being selected from the group consisting of:
Ex. #
Structure
1
2
3
4
5
6
7
8
9

### Claim 15 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)

A pharmaceutical composition comprising at least one compound of any one of claims 1-14, or a pharmaceutically acceptable salt thereoof, and a pharmaceutically acceptable carrier or diluent.

### Claim 16 (depends on 15)

A pharmaceutical composition of claim 15, wherein said at least one additional therapeutic agent is at least one agent selected from:
m1 agonists; m2 antagonists; cholinesterase inhibitors; galantamine;
rivastigimine; N-methyl-D-aspartate receptor antagonists; combinations of cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists; gamma secretase modulators; gamma secretase inhibitors; non—Steroidal anti-inflammatory agents; anti-inflammatory agents that can reduce neuroinflammation; anti-amyloid antibodies; vitamin E; nicotinic acetylcholine receptor agonists; CB1 receptor inverse agonists; CB1 receptor antagonists; antibiotics; growth hormone secretagogues; histamine H3 antagonists; AMPA agonists; PDE4 inhibitors; GABAA inverse agonists; inhibitors of amyloid aggregation; glycogen synthase kinase beta inhibitors; promoters of alpha secretase activity; PDE-10 inhibitors; Tau kinase inhibitors; Tau aggregation inhibitors; RAGE inhibitors; anti-Abeta vaccine; APP ligands; agents that upregulate insulin, cholesterol lowering agents; cholesterol absorption inhibitors; combinations of HMG-CoA reductase inhibitors and cholesterol absorption inhibitors; fibrates; combinations of fibrates and cholesterol lowering agents and/or cholesterol absorption inhibitors; nicotinic receptor agonists; niacin; combinations of niacin and cholesterol absorption inhibitors and/or cholesterol lowering agents; LXR agonists; LRP mimics; H3 receptor antagonists; histone deacetylase inhibitors; hsp90 inhibitors; 5-HT4 agonists; 5-HT6 receptor antagonists; mGluR1 receptor modulators or antagonists; mGluR5 receptor modulators or antagonists; mGluR2/3 antagonists; Prostaglandin EP2 receptor antagonists; PAI-1 inhibitors; agents that can induce Abeta efflux; Metal—Protein attenuating compound; GPR3 modulators; and antihistamines.