Methods of treatment of amyloidosis using bi-aryl aspartyl protease inhibitors

• US 20060014737A1
• Filed: 03/09/2005
• Published: 01/19/2006
• Est. Priority Date: 03/09/2004
• Status: Abandoned Application

• Current Assignee: Elan Pharmaceuticals Incorporated (Perrigo Company PLC)
• Original Assignee: Elan Pharmaceuticals Incorporated (Perrigo Company PLC)
• Inventors: Tucker, John, Sealy, Jennifer, John, Varghese, Hom, Roy
• Application Number:
  US11/075,445
• Publication Number:
  US 20060014737A1
• Time in Patent Office: Days
• US Class Current: 514/227.500
• CPC Class Codes: A61K 31/138 Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61K 31/54 having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame

Abstract

The invention relates to novel compounds and methods of treating diseases, disorders, and conditions associated with amyloidosis. Amyloidosis refers to a collection of diseases, disorders, and conditions associated with abnormal deposition of A-beta protein.

Claims

1. A method of preventing or treating at least one condition which benefits from inhibition of at least one aspartyl-protease, comprising:

administering to a host in need thereof a composition comprising a therapeutically effective amount of at least one compound of formula (I),

or a pharmaceutically acceptable salt thereof, wherein

R₁ is selected from

wherein;

X, Y, and Z are independently selected from

—

C(H)_0-2—

,

—

O—

,

—

C(O)—

,

—

NH—

, and

—

N—

,

wherein at least one bond of the (IIf) ring may optionally be a double bond;

R₅₀, R_50a, and R_50b are independently selected from

—

H,

-halogen,

—

OH,

—

SH,

—

CN,

—

C(O)-alkyl,

—

NR₇R₈,

—

S(O)_0-2-alkyl,

-alkyl,

-alkoxy,

—

O-benzyl optionally substituted with at least one substituent independently selected from —

H, —

OH, and alkyl,

—

C(O)—

NR₇R₈,

-alkyloxy,

-alkoxyalkoxyalkoxy, and

-cycloalkyl;

wherein the alkyl, alkoxy, and cycloalkyl groups within R₅₀, R_50a, and R_50b are optionally substituted with at least one substituent independently selected from alkyl, halogen, —

OH, —

NR₅R₆, —

NR₇R₈, —

CN, haloalkoxy, and alkoxy;

R₅ and R₆ are independently selected from —

H and alkyl;

or

R₅ and R₆, and the nitrogen to which they are attached, form a 5 or 6-membered heterocycloalkyl ring; and

R₇ and R₈ are independently selected from

—

H,

-alkyl optionally substituted with at least one group independently selected from —

OH, —

NH₂, and halogen,

-cycloalkyl, and

-alkyl-O-alkyl;

R₂ is selected from —

C(O)—

CH₃, —

C(O)—

CH₂(halogen), —

C(O)—

CH(halogen)₂,

U is selected from —

C(O)—

, —

C(═

S)—

, —

S(O)_0-2—

, —

C═

N—

R₂₁—

, —

C═

N—

OR₂₁—

, —

C(O)—

NR₂₀—

, —

C(O)—

O—

, —

S(O)₂—

NR₂₀—

, and —

S(O)₂—

O—

;

U′

is selected from —

C(O)—

, —

C═

N—

R₂₁—

, —

C═

N—

OR₂₁—

, —

C(O)—

NR₂₀—

, and —

C(O)—

O—

;

V is selected from aryl, heteroaryl, cycloalkyl, heterocycloalkyl, —

[C(R₄)(R₄)]₁1₃-D, and -(T)_0-1-R_N;

V′

is selected from -(T)_0-1-R_N′

;

wherein the aryl, heteroaryl, cycloalkyl, and heterocycloalkyl groups included within V and V′

are optionally substituted with 1 or 2 R_B groups;

wherein at least one carbon of the aryl, heteroaryl, cycloalkyl, and heterocycloalkyl groups included within V and V′

are optionally replaced with —

N—

, —

O—

, —

NH—

, —

C(O)—

, —

C(S)—

, —

C(═

N—

H)—

, —

C(═

N—

OH)—

, —

C(=N-alkyl)-, or —

C(═

N—

O-alkyl)-;

R_B at each occurrence is independently selected from halogen, —

OH, —

CF₃, —

OCF₃, —

O-aryl, —

CN, —

NR₁₀₁R′

₁₀₁, -alkyl, -alkoxy, —

(CH₂)_0-4—

(C(O))_0-1—

(O)_0-1-alkyl, —

C(O)—

OH, —

(CH₂)_0-3-cycloalkyl, -aryl, -heteroaryl, and -heterocycloalkyl;

wherein, the alkyl, alkoxy, cycloalkyl, aryl, heteroaryl, or heterocycloalkyl groups included within R_B are optionally substituted with 1 or 2 groups independently selected from —

C₁-C₄ alkyl, —

C₁-C₄ alkoxy-, —

C₁-C₄ haloalkyl, —

C₁-C₄ haloalkoxy, -halogen, —

OH, —

CN, and —

NR₁₀₁R′

₁₀₁;

R₁₀₁ and R′

₁₀₁ are independently selected from —

H, -alkyl, —

(C(O))_0-1—

(O)_0-1-alkyl, —

C(O)—

OH, and -aryl;

R₄ and R_4′

are independently selected from -hydrogen, -alkyl, —

(CH₂)_0-3-cycloalkyl, —

(CH₂)_0-3—

OH, -fluorine, —

CF₃, —

OCF₃, —

O-aryl, -alkoxy, —

C₃-C₇ cycloalkoxy, -aryl, and -heteroaryl, or

R₄ and R_4′

are taken together with the carbon to which they are attached to form a 3, 4, 5, 6, or 7 membered carbocyclic ring wherein 1, 2, or 3 carbons of the ring is optionally replaced with —

O—

, —

N(H)—

, —

N(alkyl)-, —

N(aryl)-, —

C(O)—

, or —

S(O)_0-2;

D is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, wherein the aryl, heteroaryl, cycloalkyl, and heterocycloalkyl are optionally substituted with 1 or 2 R_B groups;

T is selected from —

NR₂₀— and

—

O—

;

R₂₀ is selected from H, —

CN, -alkyl, -haloalkyl, and -cycloalkyl;

R₂₁-is selected from —

H, -alkyl, -haloalkyl, and -cycloalkyl;

R_N is selected from —

OH, —

NH₂, —

NH(alkyl), —

NH(cycloalkyl), —

N(alkyl)(alkyl), —

N(alkyl)(cycloalkyl), —

N(cycloalkyl)(cycloalkyl), —

R′

₁₀₀, alkyl-R₁₀₀, —

(CRR′

)_1-6R′

₁₀₀, —

(CRR′

)_0-6R₁₀₀, —

(CRR′

)_1-6—

O—

R′

₁₀₀, —

(CRR′

)_1-6—

S—

R′

₁₀₀, —

(CRR′

)_1-6—

C(O)—

R₁₀₀, —

(CRR′

)_1-6—

SO₂—

R₁₀₀, and —

(CRR′

)_1-6—

NR₁₀₀—

R′

₁₀₀, —

(CRR′

)_1-6—

P(O)(O-alkyl)₂, alkyl-O-alkyl-C(O)OH, and —

CH(R_E1)—

(CH₂)_0-3-E₁-E₂-E₃;

R_N′

is —

SO₂R′

₁₀₀;

R and R′

are independently selected from -hydrogen, —

C₁-C₁₀ alkyl (optionally substituted with at least one group independently selected from —

OH, —

C₁-C₁₀ alkylaryl, and —

C₁-C₁₀ alkylheteroaryl);

R₁₀₀ and R′

₁₀₀ are independently selected from

-cycloalkyl,

-heterocycloalkyl,

-aryl,

-heteroaryl,

-alkoxy,

-aryl-W-aryl,

-aryl-W-heteroaryl,

-aryl-W-heterocycloalkyl,

-heteroaryl-W-aryl,

-heteroaryl-W-heteroaryl,

-heteroaryl-W-heterocycloalkyl,

-heterocycloalkyl-W-aryl,

-heterocycloalkyl-W-heteroaryl,

-heterocycloalkyl-W-heterocycloalkyl,

—

W—

R₁₀₂,

—

CH[(CH₂)_0-2—

O—

R₁₅₀]—

(CH₂)_0-2-aryl,

—

CH[(CH₂)_0-2—

O—

R₁₅₀]—

(CH₂)_0-2-cycloalkyl,

—

CH[(CH₂)_0-2—

O—

R₁₅₀]—

(CH₂)_0-2-heterocycloalkyl,

—

CH[(CH₂)_0-2—

O—

R₁₅₀]—

(CH₂)_0-2-heteroaryl,

—

C₁-C₁₀ alkyl optionally substituted with 1, 2, or 3 R₁₁₅ groups, wherein 1, 2, or 3 carbons of the alkyl group are optionally replaced with a group independently selected from —

C(O)— and

—

NH—

,

-alkyl-O-alkyl optionally substituted with 1, 2, or 3 R₁₁₅ groups,

-alkyl-5-alkyl optionally substituted with 1, 2, or 3 R₁₁₅ groups, and

-cycloalkyl optionally substituted with 1, 2, or 3 R₁₁₅ groups;

wherein the ring portions of each group included within R₁₀₀ and R′

₁₀₀ are optionally substituted with 1, 2, or 3 groups independently selected from —

OR, —

NO₂, -halogen, —

CN, —

OCF₃, —

CF₃, —

(CH₂)_0-4—

O—

P(═

O)(OR)(OR′

), —

(CH₂)_0-4—

C(O)—

NR₁₀₅R′

₁₀₅, —

(CH₂)_0-4—

O—

(CH₂)_0-4—

C(O)NR₁₀₂R₁₀₂′

, —

(CH₂)_0-4—

C(O)—

(C₁-C₁₂ alkyl), —

(CH₂)_0-4—

C(O)—

(CH₂)_0-4—

cycloalkyl, —

(CH₂)_0-4—

R₁₁₀, —

(CH₂)_0-4-R₁₂₀, —

(CH₂)_0-4—

R₁₃₀, —

(CH₂)_0-4—

C(O)—

R₁₁₀, —

(CH₂)_0-4—

C(O)—

R₁₂₀, —

(CH₂)_0-4—

C(O)—

R₁₃₀, —

(CH₂)_0-4—

C(O)—

R₁₄₀, —

(CH₂)_0-4—

C(O)—

O—

R₁₅₀, —

(CH₂)_0-4—

SO₂—

NR₁₀₅R′

₁₀₅, —

(CH₂)_0-4—

SO—

(C₁-C₈ alkyl), —

(CH₂)_0-4—

SO₂—

(C₁-C₁₂ alkyl), —

(CH₂)_0-4—

SO₂—

(CH₂)_0-4-cycloalkyl, —

(CH₂)_0-4—

N(R₁₅₀)—

C(O)—

O—

R₁₅₀, —

(CH₂)_0-4—

N(R₁₅₀)—

C(O)—

N(R₁₅₀)₂, —

(CH₂)_0-4—

N(R₁₅₀)—

CS—

N(R₁₅₀)₂, —

(CH₂)_0-4—

N(R₁₅₀)—

C(O)—

R₁₀₅, —

(CH₂)_0-4—

NR₁₀₅R′

₁₀₅, —

(CH₂)_0-4—

R₁₄₀, —

(CH₂)_0-4—

O—

C(O)-(alkyl), —

(CH₂)_0-4—

O—

P(O)—

(O—

R₁₁₀)₂, —

(CH₂)_0-4—

O—

C(O)—

N(R₁₅₀)₂, —

(CH₂)_0-4—

O—

CS—

N(R₁₅₀)₂, —

(CH₂)_0-4—

O—

(R₁₅₀), —

(CH₂)_0-4—

O—

R_150′

—

C(O)OH, —

(CH₂)_0-4—

S—

(R₁₅₀), —

(CH₂)_0-4—

N(R₁₅₀)—

SO₂—

R₁₀₅, —

(CH₂)_0-4-cycloalkyl, and —

(C₁-C₁₀)-alkyl;

R_E1 is selected from —

H, —

OH, —

NH₂, —

NH—

(CH₂)_0-3—

R_E2, —

NHR_E8, —

NR_E350C(O)R_E5, —

C₁-C₄ alkyl-NHC(O)R_E5, —

(CH₂)_0-4R_E8, —

O—

(C₁-C₄ alkanoyl), —

C₆-C₁₀ (aryloxy optionally substituted with 1, 2, or 3 groups that are independently selected from halogen, —

C₁-C₄ alkyl, —

CO₂H, —

C(O)—

C₁-C₄ alkoxy, and —

C₁-C₄ alkoxy), alkoxy, -aryl-(C₁-C₄ alkoxy), —

NR_E350CO₂R_E351, —

C₁-C₄ alkyl-NR_E350CO₂R_E351, —

CN, —

CF₃, —

CF₂—

CF₃, —

C≡

CH, —

CH₂—

CH═

CH₂, —

(CH₂)_1-4—

R_E2, —

(CH₂)_1-4—

NH—

R_E2, —

O—

(CH₂)_0-3—

R_E2, —

S—

(CH₂)_0-3—

R_E2, —

(CH₂)_0-4—

NHC(O)—

(CH₂)_0-6—

R_E352, and —

(CH₂)_0-4—

(R_E353)_0-1—

(CH₂)_0-4—

R_E354;

R_E2 is selected from —

SO₂—

(C₁-C₈ alkyl), —

SO—

(C₁-C₈ alkyl), —

S—

(C₁-C₈ alkyl), —

S—

C(O)-alkyl, —

SO₂—

NR_E3R_E4, —

C(O)—

C₁-C₂ alkyl, and —

C(O)—

NR_E4R_E10;

R_E3 and R_E4 are independently selected from —

H, —

C₁-C₃ alkyl, and —

C₃-C₆ cycloalkyl;

R_E10 is selected from alkyl, arylalkyl, alkanoyl, and arylalkanoyl;

R_E5 is selected from cycloalkyl, alkyl (optionally substituted with 1, 2, or 3 groups that are independently selected from halogen, —

NR_E6R_E7, C₁-C₄ alkoxy, —

C₅-C₆ heterocycloalkyl, —

C₅-C₆ heteroaryl, —

C₆-C₁₀ aryl, —

C₃-C₇ cycloalkyl C₁-C₄ alkyl, —

S—

C₁-C₄ alkyl, —

SO₂—

C₁-C₄ alkyl, —

CO₂H, —

C(O)NR_E6R_E7, —

CO₂—

C₁-C₄ alkyl, and —

C₆-C₁₀ aryloxy), heteroaryl (optionally substituted with 1, 2, or 3 groups that are independently selected from —

C₁-C₄ alkyl, —

C₁-C₄ alkoxy, halogen, —

C₁-C₄ haloalkyl, and —

OH), heterocycloalkyl (optionally substituted with 1, 2, or 3 groups independently selected from —

C₁-C₄ alkyl, —

C₁-C₄ alkoxy, halogen, and —

C₂-C₄ alkanoyl), aryl (optionally substituted with 1, 2, 3, or 4 groups independently selected from halogen, —

OH, —

C₁-C₄ alkyl, —

C₁-C₄ alkoxy, and —

C₁-C₄ haloalkyl), and —

NR_E6R_E7;

R_E6 and R_E7 are independently selected from —

H, alkyl, alkanoyl, aryl, —

SO₂—

C₁-C₄ alkyl, and -aryl-C₁-C₄ alkyl;

R_E8 is selected from —

SO₂-heteroaryl, —

SO₂-aryl, —

SO₂-heterocycloalkyl, —

SO₂—

C₁-C₁₀ alkyl, —

C(O)NHR_E9, heterocycloalkyl, —

S—

alkyl, and —

S—

C₂-C₄ alkanoyl;

R_E9 is selected from H, alkyl, and -aryl C₁-C₄ alkyl;

R_E350 is selected from H and alkyl;

R_E351 is selected from alkyl, -aryl-(C₁-C₄ alkyl), alkyl (optionally substituted with 1, 2, or 3 groups independently selected from halogen, cyano, heteroaryl, —

NR_E6R_E7, —

C(O)NR_E6R_E7, —

C₃-C₇ cycloalkyl, and —

C₁-C₄ alkoxy), heterocycloalkyl (optionally substituted with 1 or 2 groups independently selected from —

C₁-C₄ alkyl, —

C₁-C₄ alkoxy, halogen, —

C₂-C₄ alkanoyl, -aryl-(C₁-C₄ alkyl), and —

SO₂—

(C₁-C₄ alkyl)), heteroaryl (optionally substituted with 1, 2, or 3 groups independently selected from —

OH, —

C₁-C₄ alkyl, —

C₁-C₄ alkoxy, halogen, —

NH₂, —

NH(alkyl), and —

N(alkyl)(alkyl)), heteroarylalkyl (optionally substituted with 1, 2, or 3 groups independently selected from —

C₁-C₄ alkyl, —

C₁-C₄ alkoxy, halogen, —

NH₂, —

NH(alkyl), and —

N(alkyl)(alkyl)), aryl, heterocycloalkyl, —

C₃-C₈ cycloalkyl, and cycloalkylalkyl;

wherein the aryl, heterocycloalkyl, —

C₃-C₈ cycloalkyl, and cycloalkylalkyl groups included within R_E351 are optionally substituted with 1, 2, 3, 4 or 5 groups independently selected from halogen, —

CN, —

NO₂, alkyl, alkoxy, alkanoyl, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, alkoxyalkyl, —

C₁-C₆ thioalkoxy, —

C₁-C₆ thioalkoxy-alkyl, and alkoxyalkoxy;

R_E352 is selected from heterocycloalkyl, heteroaryl, aryl, cycloalkyl, —

S(O)_0-2-alkyl, —

CO₂H, —

C(O)NH₂, —

C(O)NH(alkyl), —

C(O)N(alkyl)(alkyl), —

CO₂-alkyl, —

NHS(O)_0-2-alkyl, —

N(alkyl)S(O)_0-2-alkyl, —

S(O)_0-2-heteroaryl, —

S(O)_0-2-aryl, —

NH(arylalkyl), —

N(alkyl)(arylalkyl), thioalkoxy, and alkoxy;

.

wherein each group included within R₃₅₂ is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently selected from alkyl, alkoxy, thioalkoxy, halogen, haloalkyl, haloalkoxy, alkanoyl, —

NO₂, —

CN, alkoxycarbonyl, and aminocarbonyl;

R_E353 is selected from —

O—

, —

C(O)—

, —

NH—

, —

N(alkyl)-, —

NH—

S(O)_0-2—

, —

N(alkyl)-S(O)_0-2—

S(O)_0-2—

NH—

, —

S(O)_0-2—

N(alkyl)-, —

NH—

C(S)—

, and —

N(alkyl)-C(S)—

;

R_E354 is selected from heteroaryl, aryl, arylalkyl, -heterocycloalkyl, —

CO₂H, —

CO₂-alkyl, —

C(O)NH(alkyl), —

C(O)N(alkyl)(alkyl), —

C(O)NH₂, —

C₁-C₈ alkyl, —

OH, aryloxy, alkoxy, arylalkoxy, —

NH₂, —

NH(alkyl), —

N(alkyl)(alkyl), and -alkyl-CO₂-alkyl;

wherein each group included within R_E354 is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently selected from alkyl, alkoxy, —

CO₂H, —

CO₂-alkyl, thioalkoxy, halogen, haloalkyl, haloalkoxy, hydroxyalkyl, alkanoyl, —

NO₂, —

CN, alkoxycarbonyl, and aminocarbonyl;

E₁ is selected from —

NR_E11— and

—

C₁-C₆ alkyl- (optionally substituted with 1, 2, or 3 groups selected from —

C₁-C₄ alkyl), and R_E11 is selected from —

H and alkyl;

or R_E1 and R_E11 combine to form —

(CH₂)_1-4—

;

E₂ is selected from a bond, —

SO₂—

, —

SO—

, —

S—

, and —

C(O)—

; and

E₃ is selected from —

H, —

C₁-C₄ haloalkyl, —

C₅-C₆ heterocycloalkyl, —

C₆-C₁₀ aryl, —

OH, —

N(E₃a)(E₃b), —

C₁-C₁₀ alkyl (optionally substituted with 1, 2, or 3 groups independently selected from halogen, hydroxy, alkoxy, thioalkoxy, and haloalkoxy), —

C₃-C₈ cycloalkyl (optionally substituted with 1, 2, or 3 groups independently selected from —

C₁-C₃ alkyl and halogen), alkoxy, aryl (optionally substituted with at least one group selected from halogen, alkyl, alkoxy, —

CN and —

NO₂), arylalkyl (optionally substituted with a group selected from halogen, alkyl, alkoxy, —

CN, and —

NO₂);

E_3a and E_3b are independently selected from —

H, —

C₁-C₁₀ alkyl (optionally substituted with 1, 2, or 3 groups independently selected from halogen, —

C₁-C₄ alkoxy, —

C₃-C₈ cycloalkyl, and —

OH), —

C₂-C₆ alkyl, —

C₂-C₆ alkanoyl, aryl, —

SO₂—

C₁-C₄ alkyl, -aryl-C₁-C₄ alkyl, and —

C₃-C₈ cycloalkyl C₁-C₄ alkyl;

or

E_3a, E_3b, and the nitrogen to which they are attached may optionally form a ring selected from piperazinyl, piperidinyl, morpholinyl, and pyrrolidinyl;

wherein each ring is optionally substituted with 1, 2, 3, or 4 groups that are independently selected from alkyl, alkoxy, alkoxyalkyl, and halogen;

W is selected from —

(CH₂)_0-4—

, —

O—

, —

S(O)_0-2—

, —

N(R₁₃₅)—

, —

CR(OH)—

, and —

C(O)—

;

R₁₀₂ and R₁₀₂′

are independently selected from hydrogen, —

OH, and —

C₁-C₁₀ alkyl optionally substituted with 1, 2, or 3 groups independently selected from -halogen, -aryl, and —

R₁₁₀;

R₁₀₅ and R′

₁₀₅ are independently selected from

—

H,

—

R₁₁₀,

—

R₁₂₀,

-cycloalkyl,

—

(C₁-C₂ alkyl)-cycloalkyl,

-(alkyl)-O—

(C₁-C₃ alkyl), and

-alkyl optionally substituted with at least one group independently selected from —

OH, -amine, and -halogen;

or

R₁₀₅ and R′

₁₀₅ together with the atom to which they are attached form a 3, 4, 5, 6, or 7 membered carbocyclic ring, wherein one member is optionally a heteroatom selected from —

O—

, —

S(O)_0-2—

, and —

N(R₁₃₅)—

, wherein the carbocyclic ring is optionally substituted with 1, 2 or 3 R₁₄₀ groups; and

wherein the at least one carbon of the carbocyclic ring is optionally replaced with —

C(O)—

;

R₁₁₀ is aryl optionally substituted with 1 or 2 R₁₂₅ groups;

R₁₁₅ at each occurrence is independently selected from halogen, —

OH, —

C(O)—

O—

R₁₀₂, —

C₁-C₆ thioalkoxy, —

C(O)—

O-aryl, —

NR₁₀₅R′

₁₀₅, —

SO₂—

(C₁-C₈ alkyl), —

C(O)—

R₁₈₀, R₁₈₀, —

C(O)NR₁₀₅R′

₁₀₅, —

SO₂NR₁₀₅R′

₁₀₅, —

NH—

C(O)-(alkyl), —

NH—

C(O)—

OH, —

NH—

C(O)—

OR, —

NH—

C(O)—

O-aryl, —

O—

C(O)-(alkyl), —

O—

C(O)-amino, —

O—

C(O)-monoalkylamino, —

O—

C(O)-dialkylamino, —

O—

C(O)-aryl, —

O-(alkyl)-C(O)—

O—

H, —

NH—

SO₂—

(alkyl), -alkoxy, and -haloalkoxy;

R₁₂₀ is -heteroaryl, optionally substituted with 1 or 2 R₁₂₅ groups;

R₁₂₅ at each occurrence is independently selected from -halogen, -amino, -monoalkylamino, -dialkylamino, —

OH, —

CN, —

SO₂—

NH₂, —

SO₂—

NH-alkyl, —

SO₂—

N(alkyl)₂, —

SO₂—

(C₁-C₄ alkyl), —

C(O)—

NH₂, -Q(O)—

NH-alkyl, —

C(O)—

N(alkyl)₂, -alkyl optionally substituted with 1, 2, or 3 groups independently selected from C₁-C₃ alkyl, halogen, —

OH, —

SH, —

CN, —

CF₃, —

C₁-C₃ alkoxy, -amino, -monoalkylamino, and -dialkylamino, and -alkoxy optionally substituted with 1, 2, or 3-halogen;

R₁₃₀ is heterocycloalkyl optionally substituted with 1 or 2 R₁₂₅ groups;

R₁₃₅ is independently selected from alkyl, cycloalkyl, —

(CH₂)_0-2-(aryl), —

(CH₂)_0-2-(heteroaryl), and —

(CH₂)_0-2-(heterocycloalkyl);

R₁₄₀ at each occurrence is independently selected from heterocycloalkyl optionally substituted with 1, 2, 3, or 4 groups independently selected from -alkyl, -alkoxy, -halogen, -hydroxy, -cyano, -nitro, -amino, -monoalkylamino, -dialkylamino, -haloalkyl, -haloalkoxy, -amino-alkyl, -monoalkylamino-alkyl, and -dialkylaminoalkyl; and

wherein at least one carbon of the heterocycloalkyl is optionally replaced with —

C(O);

R₁₅₀ is independently selected from

-hydrogen,

-cycloalkyl,

—

(C₁-C₂ alkyl)-cycloalkyl,

—

R₁₁₀,

—

R₁₂₀, and

-alkyl optionally substituted with 1, 2, 3, or 4 groups independently selected from —

OH, —

NH₂, —

C₁-C₃ alkoxy, —

R₁₁₀, and -halogen;

R₁₅₀′

is independently selected from

-cycloalkyl,

—

(C₁-C₃ alkyl)-cycloalkyl,

—

R₁₂₀, and

-alkyl optionally substituted with 1, 2, 3, or 4 groups independently selected from —

OH, —

NH₂, —

C₁-C₃ alkoxy, —

R₁₁₀, and -halogen; and

R₁₈₀ is independently selected from

-morpholinyl,

-thiomorpholinyl,

-piperazinyl,

-piperidinyl,

-homomorpholinyl,

-homothiomorpholinyl,

-homothiomorpholinyl S-oxide,

-homothiomorpholinyl S,S-dioxide,

-pyrrolinyl, and

-pyrrolidinyl;

wherein each R₁₈₀ is optionally substituted with 1, 2, 3, or 4 groups independently selected from -alkyl, -alkoxy, -halogen, -hydroxy, -cyano, -nitro, -amino, -monoalkylamino, -dialkylamino, -haloalkyl, -haloalkoxy, -aminoalkyl, -monoalkylamino-alkyl, -dialkylamino-alkyl and —

C(O); and

wherein at least one carbon of R₁₈₀ is optionally replaced with —

C(O)—

;

R_C is

n is 0 or 1;

m is 0 or 1;

G is selected from —

C(O)— and

—

CO₂—

;

I is (CH₂)_0-4;

J is selected from —

(CR₂₄₅R₂₅₀)—

;

K is selected from aryl and heteroaryl;

L is selected from

-a bond,

-alkyl- optionally substituted with at least one group independently selected from R₂₀₅,

-(CH₂)_0-4—

(CO)_0-1—

N(R₂₂₀)—

,

—

(CH₂)_0-4—

(CO)_0-1—

,

—

(CH₂)_0-4—

CO₂—

,

—

(CH₂)_0-4—

SO₂—

N(R₂₂₀)—

,

—

(CH₂)_0-4—

N(H or R₂₁₅)—

CO₂—

,

—

(CH₂)_0-4—

N(H or R₂₁₅)—

SO₂—

,

—

(CH₂)_0-4—

N(H or R₂₁₅)—

C(O)—

N(R₂₁₅)—

,

—

(CH₂)_0-4—

N(H or R₂₁₅)—

C(O)—

,

—

(CH₂)_0-4—

N(R₂₂₀)—

,

—

(CH₂)_0-4—

O—

, and

—

(CH₂)_0-4—

S—

;

Q is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl;

wherein each cycloalkyl or heterocycloalkyl included within R_C is optionally substituted with at least one group independently selected from R₂₀₅;

wherein each aryl or heteroaryl group included within R_C is optionally substituted with at least one group independently selected from R₂₀₀;

wherein at least one heteroatom of the heteroaryl group included within R_C is optionally substituted with a group independently selected from

—

(CO)_0-1R₂₁₅,

—

(CO)_0-1R₂₂₀, and

—

S(O)_0-2R₂₀₀;

wherein the aryl or heteroaryl group included within R_C is optionally substituted with R₂₀₀;

R₂₀₀ at each occurrence is independently selected from;

-alkyl optionally substituted with at least one group independently selected from R₂₀₅,

—

OH,

—

NO₂,

-halogen,

—

CN,

—

(CH₂)_0-4—

C(O)H,

—

(CO)_0-1R₂₁₅,

—

(CO)_0-1R₂₂₀,

—

(CH₂)_0-4—

(CO)_0-1—

N R₂₂₀R₂₂₅,

—

(CH₂)_0-4—

C(O)-alkyl,

—

(CH₂)_0-4—

(CO)_0-1-cycloalkyl,

—

(CH₂)_0-4—

(CO)_0-1-heterocycloalkyl,

—

(CH₂)_0-4—

(CO)_0-1-aryl,

—

(CH₂)_0-4—

(CO)_0-1-heteroaryl,

—

(CH₂)_0-4—

CO₂R₂₁₅,

—

(CH₂)_0-4—

SO₂—

N R₂₂₀R₂₂₅,

—

(CH₂)_0-4—

S(O)_0-2-alkyl,

—

(CH₂)_0-4—

S(O)_0-2-cycloalkyl,

—

(CH₂)_0-4—

N(H or R₂₁₅)—

CO₂R₂₁₅,

—

(CH₂)_0-4—

N(H or R₂₁₅)—

SO₂—

R₂₂₀,

—

(CH₂)_0-4—

N(H or R₂₁₅)—

C(O)—

N(R₂₁₅)₂,

—

(CH₂)_0-4—

N(H or R₂₁₅)—

C(O)—

R₂₂₀,

—

(CH₂)_0-4—

NR₂₂₀R₂₂₅,

—

(CH₂)_0-4—

O—

C(O)-alkyl,

—

(CH₂)_0-4—

O—

(R₂₁₅),

—

(CH₂)_0-4—

S—

(R₂₁₅),

—

(CH₂)_0-4—

O-alkyl optionally substituted with at least one halogen, and -adamantane;

wherein each aryl and heteroaryl group included within R₂₀₀ is optionally substituted with at least one group independently selected from R₂₀₅, R₂₁₀, and alkyl optionally substituted with at least one group independently selected from R₂₀₅ and R₂₁₀;

wherein each cycloalkyl or heterocycloalkyl group included within R₂₀₀ is optionally substituted with at least one group independently selected from R₂₁₀;

R₂₀₅ at each occurrence is independently selected from

-alkyl,

-haloalkoxy,

—

(CH₂)_0-3-cycloalkyl,

-halogen,

—

(CH₂)_0-6—

OH,

—

O-aryl,

—

OH,

—

SH,

—

(CH₂)_0-4—

C(O)H,

—

(CH₂)_0-6—

CN,

—

(CH₂)_0-6—

C(O)—

NR₂₃₅R₂₄₀,

—

(CH₂)_0-6—

C(O)—

R₂₃₅,

—

(CH₂)_0-4—

N(H or R₂₁₅)—

SO₂—

R₂₃₅,

—

CF₃,

—

CN,

-alkoxy,

-alkoxycarbonyl, and

—

NR₂₃₅R₂₄₀;

R₂₁₀ at each occurrence is independently selected from

—

OH,

—

CN,

—

(CH₂)_0-4—

C(O)H,

-alkyl optionally substituted with at least one group independently selected from R₂₀₅,

—

S(O)₂-alkyl,

-halogen,

-alkoxy,

-haloalkoxy,

—

NR₂₂₀R₂₂₅,

-cycloalkyl optionally substituted with at least one group independently selected from R₂₀₅,

—

C(O)-alkyl,

—

S(O)₂—

N R₂₃₅R₂₄₀,

—

C(O)—

NR₂₃₅R₂₄₀, and

—

S-alkyl;

R₂₁₅ at each occurrence is independently selected from

-alkyl,

—

(CH₂)_0-2-cycloalkyl,

—

(CH₂)_0-2-aryl,

—

(CH₂)_0-2-heteroaryl,

—

(CH₂)_0-2-heterocycloalkyl, and

—

CO₂—

CH₂-aryl;

wherein the aryl groups included within R₂₁₅ are optionally substituted with at least one group independently selected from R₂₀₅ and R₂₁₀,

wherein the heterocycloalkyl and heteroaryl groups included within R₂₁₅ are optionally substituted with at least one group independently selected from R₂₁₀;

R₂₂₀ and R₂₂₅ at each occurrence are independently selected from

—

H,

-alkyl,

—

(CH₂)_0-4—

C(O)H,

—

(CH₂)_0-4—

C(O)-alkyl,

-hydroxyalkyl,

-alkoxycarbonyl,

-alkylamino,

—

S(O)₂-alkyl,

—

C(O)-alkyl optionally substituted with at least one halogen,

—

C(O)—

NH₂,

—

C(O)—

NH(alkyl),

—

C(O)—

N(alkyl)(alkyl),

-haloalkyl,

—

(CH₂)_0-2-cycloalkyl,

-(alkyl)-O-(alkyl),

-aryl,

-heteroaryl, and

-heterocycloalkyl;

wherein the aryl, heteroaryl and heterocycloalkyl groups included within R₂₂₀ and R₂₂₅ are each optionally substituted with at least one group independently selected from R₂₇₀;

R₂₃₅ and R₂₄₀ at each occurrence are independently selected from

—

H,

—

OH,

—

CF₃,

—

OCH₃,

—

NH—

CH₃,

—

N(CH₃)₂,

—

(CH₂)_0-4—

C(O)—

(H or alkyl),

-alkyl,

—

C(O)-alkyl,

—

SO₂-alkyl, and

-aryl;

R₂₄₅ and R₂₅₀ at each occurrence are independently selected from

—

H,

—

OH,

—

(CH₂)_0-4CO₂-alkyl,

—

(CH₂)_0-4C(O)-alkyl,

-alkyl,

-hydroxyalkyl,

-alkoxy,

-haloalkoxy,

—

(CH₂)_0-4-cycloalkyl,

—

(CH₂)_0-4-aryl,

—

(CH₂)_0-4-heteroaryl, and

—

(CH₂)_0-4-heterocycloalkyl;

or

R₂₄₅ and R₂₅₀ are taken together with the carbon to which they are attached to form a monocyclic or bicyclic ring system of 3, 4, 5, 7, or 8 carbon atoms;

wherein at least one carbon atom is optionally replaced by at least one group independently selected from —

O—

, —

S—

, —

SO₂—

, —

C(O)—

, —

NR₂₂₀—

, and —

N(alkyl)(alkyl); and

wherein the ring is optionally substituted with at least one group independently selected from

-alkyl,

-alkoxy,

—

OH,

—

NH₂,

—

NH(alkyl),

—

N(alkyl)(alkyl),

—

NH—

C(O)-alkyl,

—

NH—

SO₂-alkyl, and

-halogen;

wherein the aryl, heteroaryl, and heterocycloalkyl groups included within R₂₄₅ and R₂₅₀ are optionally substituted with at least one group independently selected from halogen, alkyl, —

CN, and —

OH;

R₂₇₀ at each occurrence is independently selected from

—

R₂₀₅,

-alkyl optionally substituted with at least one group independently selected from R₂₀₅,

-aryl,

-halogen,

-alkoxy,

-haloalkoxy,

—

NR₂₃₅R₂₄₀,

—

OH,

—

CN,

-cycloalkyl optionally substituted with at least one group independently selected from R₂₀₅,

—

C(O)-alkyl,

—

S(O)₂—

N R₂₃₅R₂₄₀,

—

CO—

N R₂₃₅R₂₄₀,

—

S(O)₂-alkyl, and

—

(CH₂)_0-4—

C(O)H.

2. The method according to claim 1, wherein R₁ is 3,5-difluorobenzyl.

3. The method according to claim 1, wherein R₂ is —

C(O)—

CH₃.

4. The method according to claim 1, wherein R_C is selected from 5-(2,2-dimethyl-propyl)-2-(2-propyl-imidazol-1-yl)-benzyl, 5-(2,2-dimethyl-propyl)-2-(1H-pyrrol-2-yl)-benzyl, 5-(2,2-dimethyl-propyl)-2-(imidazol-1-yl)-benzyl, 5-(2,2-dimethyl-propyl)-2-(1H-pyrazol-4-yl)-benzyl, 5-(2,2-dimethyl-propyl)-2-[1,2,3]thiadiazol-4-yl-benzyl, 5-(2,2-dimethyl-propyl)-2-thiazol-5-yl-benzyl, 5-(2,2-dimethyl-propyl)-2-(3-methyl-isothiazol-5-yl)-benzyl, 5-(2,2-dimethyl-propyl)-2-(2H-[1,2,3] triazol-4-yl)-benzyl, 5-(2,2-dimethyl-propyl)-2-pyridin-3-yl-benzyl, 5-(2,2-dimethyl-propyl)-2-(6-fluoro-pyridin-3-yl)-benzyl, 5-(2,2-dimethyl-propyl)-2-(2-fluoro-pyridin-3-yl)-benzyl, 5-(2,2-dimethyl-propyl)-2-pyridazin-3-yl-benzyl, 5-(2,2-dimethyl-propyl)-2-pyrimidin-5-yl-benzyl, 5-(2,2-dimethyl-propyl)-2-imidazol-1-yl-phenyl]-cyclopropyl, 5-(2,2-dimethyl-propyl)-2-pyrazin-2-yl-benzyl, 5-(2,2-dimethyl-propyl)-2-(5-ethyl-imidazol-1-yl)-benzyl, 3-Chloro-5-(2,2-dimethyl-propyl)-2-imidazol-1-yl-benzyl, 5-(2,2-dimethyl-propyl)-2-tetrazol-1-yl-benzyl, and 5-(2,2-dimethyl-propyl)-2-imidazol-1-yl-benzyl.

5. The method according to claim 1, wherein the at least one compound of formula (I) is chosen from N-{1-(3,5-difluoro-benzyl)-3-[5-(2,2-dimethyl-propyl)-2-(2-propyl-imidazol-1-yl)-benzylamino]-2-hydroxy-propyl}-acetamide, N-(1-(3,5-difluorophenyl)-3-hydroxy-4-(5-neopentyl-2-(1H-pyrrol-2-yl)benzylamino)butan-2-yl)acetamide, N-(4-(2-(1H-imidazol-1-yl)-5-neopentylbenzylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl)acetamide N-(4-(2-(1H-imidazol-1-yl)-5-neopentylbenzylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl)acetamide, N-{1-(3,5-difluoro-benzyl)-3-[5-(2,2-dimethyl-propyl)-2-(1H-pyrazol-4-yl)-benzylamino]-2-hydroxy-propyl}-acetamide, N-{1-(3,5-difluoro-benzyl)-3-[5-(2,2-dimethyl-propyl)-2-[1,2,3]thiadiazol-4-yl-benzylamino]-2-hydroxy-propyl}-acetamide, N-{1-(3,5-difluoro-benzyl)-3-[5-(2,2-dimethyl-propyl)-2-thiazol-5-yl-benzylamino]-2-hydroxy-propyl}-acetamide, N-{1-(3,5-difluoro-benzyl)-3-[5-(2,2-dimethyl-propyl)-2-(3-methyl-isothiazol-5-yl)-benzylamino]-2-hydroxy-propyl}-acetamide, N-{1-(3,5-difluoro-benzyl)-3-[5-(2,2-dimethyl-propyl)-2-(2H-[1,2,3]triazol-4-yl)-benzylamino]-2-hydroxy-propyl}-acetamide, N-(1-(3,5-difluorophenyl)-3-hydroxy-4-(5-neopentyl-2-(pyridin-3-yl)benzylamino)butan-2-yl)acetamide, N-(1-(3,5-difluorophenyl)-4-(2-(6-fluoropyridin-3-yl)-5-neopentylbenzylamino)-3-hydroxybutan-2-yl)acetamide, N-(4-(2-(3-acetylth iophen-2-yl)-5-neopentylbenzylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl)acetamide, N-{1-(3,5-difluoro-benzyl)-3-[5-(2,2-dimethyl-propyl)-2-(2-fluoro-pyridin-3-yl)-benzylamino]-2-hydroxy-propyl}-acetamide, N-{1-(3,5-difluoro-benzyl)-3-[5-(2,2-dimethyl-propyl)-2-pyridazin-3-yl-benzylamino]-2-hydroxy-propyl}-acetamide, N-{1-(3,5-difluoro-benzyl)-3-[5-(2,2-dimethyl-propyl)-2-pyrimidin-5-yl-benzylamino]-2-hydroxy-propyl}-acetamide, N-(1-(3,5-difluoro-benzyl)-3-{1-[5-(2,2-dimethyl-propyl)-2-imidazol-1-yl-phenyl]-cyclopropylamino}-2-hydroxy-propyl)-acetamide, N-{1-(3,5-difluoro-benzyl)-3-[5-(2,2-dimethyl-propyl)-2-pyrazin-2-yl-benzylamino]-2-hydroxy-propyl}-acetamide, N-{1-(3,5-difluoro-benzyl)-3-[5-(2,2-dimethyl-propyl)-2-(5-ethyl-imidazol-1-yl)-benzylamino]-2-hydroxy-propyl}-acetamide, N-[3-[3-chloro-5-(2,2-dimethyl-propyl)-2-imidazol-1-yl-benzylamino]-1-(3,5-difluoro-benzyl)-2-hydroxy-propyl]-acetamide, N-{1-(3,5-difluoro-benzyl)-3-[5-(2,2-dimethyl-propyl)-2-tetrazol-1-yl-benzylamino]-2-hydroxy-propyl}-acetamide, N-(1-(3,5-difluorophenyl)-4-(2-(3,5-dimethylisoxazol-4-yl)-5-neopentylbenzylamino)-3-hydroxybutan-2-yl)acetamide, N-{1-(3,5-Difluoro-benzyl)-2-hydroxy-3-[1-(3-th iazol-2-yl-phenyl)-cyclopropylamino]-propyl}-acetamide, N-{1-(3,5-Difluoro-benzyl)-3-[2-(2,2-dimethyl-propyl)-5-(4-hydroxymethyl-imidazol-1-yl)-benzylamino]-2-hydroxy-propyl}-acetamide, N-{1-(3,5-Difluoro-benzyl)-3-[2-(2,2-dimethylpropyl)-5-thiophen-2-yl-benzylamino]-2-hydroxy-propyl}-acetamide, N-[3-[5-(3-Acetyl-thiophen-2-yl)-2-(2,2-dimethyl-propyl)-benzylamino]-1-(3,5-difluoro-benzyl)-2-hydroxy-propyl]-acetamide, N-{1-(3,5-Difluoro-benzyl)-3-[2-(2,2-dimethyl-propyl)-5-fu ran-3-yl-benzylamino]-2-hydroxy-propyl}-acetamide, N-{1-(3,5-Difluoro-benzyl)-3-[2-(2,2-dimethyl-propyl)-5-furan-2-yl-benzylamino]-2-hydroxy-propyl}-acetamide, N-{1-(3,5-Difluoro-benzyl)-3-[2-(2,2-dimethyl-propyl)-5-(1H-pyrrol-2-yl)-benzylamino]-2-hydroxy-propyl}-acetamide, N-{1-(3,5-Difluoro-benzyl)-3-[2-(2,2-dimethyl-propyl)-5-(4-methyl-thiophen-2-yl)-benzylamino]-2-hydroxy-propyl}-acetamide, N-{1-(3,5-Difluoro-benzyl)-3-[2-(2,2-dimethyl-propyl)-5-thiophen-3-yl-benzylamino]-2-hydroxy-propyl}-acetamide, N-[3-[5-Benzofuran-2-yl-2-(2,2-dimethyl-propyl)-benzylamino]-1-(3,5-difluoro-benzyl)-2-hydroxy-propyl]-acetamide, N-[3-[5-Benzo[b]thiophen-2-yl-2-(2,2-dimethyl-propyl)-benzylamino]1-(3,5-difluoro-benzyl)-2-hydroxy-propyl-acetamide, N-{1-(3,5-Difluoro-benzyl)-3-[2-(2,2-dimethyl-propyl)-5-(1-propyl-1H-pyrazol-4-yl)-benzylamino]-2-hydroxy-propyl}-acetamide, N-{1-(3,5-Difluoro-benzyl)-3-[2-(2,2-dimethyl-propyl}-5-(2-formyl-thiophen-3-yl)-benzylamino]-2-hydroxy-propyl]-acetamide, N-{1-(3,5-Difluoro-benzyl)-3-[2-(2,2-dimethyl-propyl)-5-(5-formyl-thiophen-2-yl)-benzylamino]-2-hydroxy-propyl}-acetamide, N-(1-(3,5-difluorophenyl)-3-hydroxy-4-(1-(2-(thiazol-2-yl)phenyl)cyclopropylamino)butan-2-yl)acetamide, N-(1-(3,5-difluorophenyl)-3-hydroxy-4-(5-neopentyl-2-(thiophen-2-yl)benzylamino)butan-2-yl)acetamide, N-(4-(2-(5-acetylthiophen-2-yl)-5-neopentylbenzylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl)acetamide, N-(1-(3,5-difluorophenyl)-4-(2-(furan-3-yl)-5-neopentylbenzylamino)-3-hydroxybutan-2-yl)acetamide, N-(1-(3,5-difluorophenyl)-4-(2-(furan-2-yl)-5-neopentylbenzylamino)-3-hydroxybutan-2-yl)acetamide, N-(1-(3,5-difluorophenyl)-3-hydroxy-4-(5-neopentyl-2-(thiophen-3-yl)benzylamino)butan-2-yl)acetamide, N-(1-(3,5-difluorophenyl)-3-hydroxy-4-(2-(4-methylthiophen-2-yl)-5-neopentylbenzylamino)butan-2-yl)acetamide, N-(4-(2-(benzofuran-2-yl)-5-neopentylbenzylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl)acetamide, N-(1-(3,5-difluorophenyl)-3-hydroxy-4-(5-neopentyl-2-(1-propyl-1H-pyrazol-4-yl)benzylamino)butan-2-yl)acetamide, N-(4-(2-(1H-indol-2-yl)-5-neopentylbenzylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl)acetamide, N-(1-(3,5-difluorophenyl)-3-hydroxy-4-(2-(1-methyl-1H-pyrazol-4-yl)-5-neopentylbenzylamino)butan-2-yl)acetamide, N-(1-(3,5-difluorophenyl)-3-hydroxy-4-(5-neopentyl-2-(1H-pyrazol-4-yl)benzylamino)butan-2-yl)acetamide, N-(1-(3,5-difluorophenyl)-3-hydroxy-4-(2-(5-methylthiophen-2-yl)-5-neopentylbenzylamino)butan-2-yl)acetamide, N-(1-(3,5-difluorophenyl)-4-(2-(2-formylthiophen-3-yl)-5neopentylbenzylamino)-3-hydroxybutan-2-yl)acetamide, N-(1-(3,5-difluorophenyl)-4-(2-(5-formylthiophen-2-yl)-5-neopentylbenzylamino)-3-hydroxybutan-2-yl)acetamide, N-(4-(2-(benzo[b]thiophen-2-yl)-5-neopentylbenzylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl)acetamide, N-{1-(3,5-difluoro-benzyl)-3-[5-(2,2-dimethyl-propyl)-2-imidazol-1-yl-benzylamino]-2-hydroxy-propyl}-acetamide, N-(1-(3,5-difluorophenyl)-3-hydroxy-4-(2-(4-methyl-1H-imidazol-1-yl)-5-neopentylbenzylamino)butan-2-yl)acetamide, N-(1-(3,5-difluorophenyl)-3-hydroxy-4-(5-neopentyl-2-(4-phenyl-1H-imidazol-1-yl)benzylamino)butan-2-yl)acetamide, N-(4-(2-(1H-benzo[d]imidazol-1-yl)-5-neopentylbenzylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl)acetamide, N-(4-(2-(3-acetyl-1H-pyrrol-1-yl)-5-neopentylbenzylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl)acetamide, 1-(2-((3-acetamido-4-(3,5-difluorophenyl)-2-hydroxybutylamino)methyl)-4-neopentylphenyl)-1H-imidazole-4-carboxylic acid, N-{1-(3,5-Difluoro-benzyl)-3-[5-(2,2-dimethyl-propyl)-2-indol-1-yl-benzylamino]-2-hydroxy-propyl}-acetamide, N-(4-(2-(1H-indol-1-yl)-5-neopentylbenzylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl)acetamide, N-(1-(3,5-difluorophenyl)-3-hydroxy-4-(5-neopentyl-2-(1H-pyrazol-1-yl)benzylamino)butan-2-yl)acetamide, N-(4-(2-(3-acetyl-1H-pyrazol-1-yl)-5-neopentylbenzylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl)acetamide, N-(1-(3,5-difluorophenyl)-3-hydroxy-4-(2-(3-methyl-1H-pyrazol-1-yl)-5-neopentylbenzylamino)butan-2-yl)acetamide, N-{1-(3,5-Difluoro-benzyl)-3-[5-(2,2-dimethyl-propyl)-2-(4-methyl-pyrazol-1-yl)-benzylamino]-2-hydroxy-propyl}-acetamide, N-(4-(2-(1H-indazol-1-yl)-5-neopentylbenzylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl)acetamide, N-(1-(3,5-difluorophenyl)-3-hydroxy-4-(5-neopentyl-2-(1H-1,2,3-triazol-1-yl)benzylamino)butan-2-yl)acetamide, N-(1-(3,5-difluorophenyl)-3hydroxy-4-(5-neopentyl-2-(2H-1,2,3-triazol-2-yl)benzylamino)butan-2-yl)acetamide, N-(1-(3,5-difluorophenyl)-3-hydroxy-4-(5-neopentyl-2-(1H-1,2,4-triazol-1-yl)benzylamino)butan-2-yl)acetamide, N-(1-(3,5-difluorophenyl)-3-hydroxy-4-(5-neopentyl-2-(pyrrolidin-1-yl)benzylamino)butan-2-yl)acetamideN-(1-(3,5-difluorophenyl)-3-hydroxy-4-(2-(2-mercapto-1H-imidazol-1-yl)-5-neopentylbenzylamino)butan-2-yl)acetamide, methyl 3-(1-(2-((3-acetamido-4-(3,5-difluorophenyl)-2-hydroxybutylamino)methyl)-4-neopentylphenyl)-1H-imidazol-4-yl)acrylate, 3-(1-(2-((3-acetamido-4-(3,5-difluorophenyl)-2-hydroxybutylamino)methyl)-4-neopentylphenyl)-1H-imidazol-4-yl)-2-aminopropanoic acid, N-(1-(3,5-difluorophenyl)-3-hydroxy-4-(2-(3-hydroxypyrrolidin-1-yl)-5-neopentylbenzylamino)butan-2-yl)acetamide, and N-(1-(3,5-difluorophenyl)-3-hydroxy-4-(5-neopentyl-2-(piperidin-1-yl)benzylamino)butan-2-yl)acetamide, or a pharmaceutically acceptable salt thereof.

6. The method according to claim 1, wherein the aspartyl protease is beta-secretase and the condition is Alzheimer'"'"'s disease, Down'"'"'s syndrome or Trisomy 21, hereditary cerebral hemorrhage with amyloidosis of the Dutch type, chronic inflammation due to amyloidosis, prion diseases, Familial Amyloidotic Polyneuropathy, cerebral amyloid angiopathy, degenerative dementias, dementia associated with Parkinson'"'"'s disease, dementia associated with progressive supranuclear palsy and dementia associated with cortical basal degeneration, diffuse Lewy body type of Alzheimer'"'"'s disease, and frontotemporal dementias with parkinsonism.

7. The method according to claim 1 wherein the at least one compound of formula (I),

8. The method according to claim 7, wherein the at least one compound of formula (I) is N-{1-(3,5-Difluoro-benzyl)-3-[5-(2,2-dimethyl-propyl)-2-imidazol-1-yl-benzylamino]-2-hydroxy-propyl}-acetamide.

9. The method according to claim 7, wherein the condition is Alzheimer'"'"'s disease and the at least one aspartyl protease is beta-secretase.

10. The method according to claim 7, wherein the condition is dementia and the at least one aspartyl protease is beta-secretase.

11. A method according to claim 1 wherein the at least one compound of formula (I),

12. The method according to claim 11, wherein the at least one compound of formula (I) is chosen from N-(4-(2-(1H-imidazol-1-yl)-5-neopentylbenzylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl)acetamide, N-(1-(3,5-difluorophenyl)-3-hydroxy-4-(2-(4-(hydroxymethyl)-1H-imidazol-1-yl)-5-neopentylbenzylamino)butan-2-yl)acetamide, N-{1-(3,5-Difluoro-benzyl)-3-[5-(2,2-dimethyl-propyl)-2-(4-methyl-imidazol-1-yl)-benzylamino]-2-hydroxy-propyl}-acetamide, N-[3-[2-Benzoimidazol-1-yl-5-(2,2-dimethyl-propyl)-benzylamino]-1-(3,5-difluoro-benzyl)-2-hydroxy-propyl]-acetamide, 1-[2-{[3-Acetylamino-4-(3,5-difluoro-phenyl)-2-hydroxy-butylamino]-methyl}-4-(2,2-dimethyl-propyl)-phenyl]-1H-imidazole-4-carboxylic acid, N-(1-(3,5-difluorophenyl)-3-hydroxy-4-(5-neopentyl-2-(2H-1,2,3-triazol-2-yl)benzylamino)butan-2-yl)acetamide, and N-(1-(3,5-difluorophenyl)-3-hydroxy-4-(5-neopentyl-2-(1H-pyrazol-4-yl)benzylamino)butan-2-yl)acetamide .

13. The method according to claim 11, wherein the condition is Alzheimer'"'"'s disease and the at least one aspartyl protease is beta-secretase.

14. The method according to claim 11, wherein the condition is dementia and the at least one aspartyl protease is beta-secretase.

15. A method according to claim 1 wherein the at least one compound of formula (I),

16. The method according to claim 15, wherein the at least one compound of formula (I) is N-(4-(2-(1H-imidazol-1-yl)-5-neopentylbenzylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl)acetamide.

17. The method according to claim 15, wherein the condition is Alzheimer'"'"'s disease and the at least one aspartyl protease is beta-secretase.

18. The method according to claim 15, wherein the condition is dementia and the at least one aspartyl protease is beta-secretase.