Hydroxy alkyl amines

• US 7,144,897 B2
• Filed: 05/31/2002
• Issued: 12/05/2006
• Est. Priority Date: 06/01/2001
• Status: Expired due to Fees

• Current Assignee: Elan Pharmaceuticals Incorporated (Perrigo Company PLC), Pharmacia & Upjohn Company (Pfizer Inc.)
• Original Assignee: Elan Pharmaceuticals Incorporated (Perrigo Company PLC), Pharmacia & Upjohn Company (Pfizer Inc.)
• Inventors: Brown, David L., Romero, Arthur Glenn, Fobian, Yvette M., John, Varghese, Freskos, John, Fang, Larry
• Primary Examiner(s): NORTHINGTON DAVIS, ZINNA
• Application Number:
  US10/160,777
• Publication Number:
  US 20030166717A1
• Time in Patent Office: 1,649 Days
• Field of Search: 560/27, 514/315, 514/351, 514/423, 514/445, 514/461, 514/625, 546/242, 546/300, 548/530, 549/62, 549/475, 564/193
• US Class Current: 514/315
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: 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
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07C 2601/02 with a three-membered ring
• CPC Class Codes: C07C 2601/08 the ring being saturated
• CPC Class Codes: C07C 2601/14 The ring being saturated
• CPC Class Codes: C07C 317/46 the carbon skeleton being further substituted by singly-bound oxygen atoms
• CPC Class Codes: C07C 317/48 the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
• CPC Class Codes: C07C 317/50 at least one of the nitrogen atoms being part of any of the groups , X being a hetero atom, Y being any atom
• CPC Class Codes: C07C 323/60 with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms
• CPC Class Codes: C07C 327/32 having sulfur atoms of esterified thiocarboxyl groups bound to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
• CPC Class Codes: C07D 207/12 Oxygen or sulfur atoms
• CPC Class Codes: C07D 207/26 2-Pyrrolidones
• CPC Class Codes: C07D 207/28 2-Pyrrolidone-5- carboxylic acids; Functional derivatives thereof, e.g. esters, nitriles
• CPC Class Codes: C07D 209/08 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 211/46 having a hydrogen atom as the second substituent in position 4
• CPC Class Codes: C07D 211/96 Sulfur atom
• CPC Class Codes: C07D 213/30 Oxygen atoms
• CPC Class Codes: C07D 213/81 Amides; Imides
• CPC Class Codes: C07D 213/82 in position 3
• CPC Class Codes: C07D 231/12 : with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 231/14 : with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 233/56 : with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
• CPC Class Codes: C07D 233/64 : with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
• CPC Class Codes: C07D 233/74 : with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to other ring members
• CPC Class Codes: C07D 233/90 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 237/04 : having less than three double bonds between ring members or between ring members and non-ring members
• CPC Class Codes: C07D 241/24 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 249/08 : 1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
• CPC Class Codes: C07D 261/18 : Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen
• CPC Class Codes: C07D 277/36 : Sulfur atoms
• CPC Class Codes: C07D 277/56 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• CPC Class Codes: C07D 295/185 : from aliphatic carboxylic acids
• CPC Class Codes: C07D 307/20 : Oxygen atoms
• CPC Class Codes: C07D 309/12 : only hydrogen atoms and one oxygen atom directly attached to ring carbon atoms, e.g. tetrahydropyranyl ethers
• CPC Class Codes: C07D 317/30 : Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 319/06 : not condensed with other rings
• CPC Class Codes: C07D 333/32 : Oxygen atoms
• CPC Class Codes: C07D 333/34 : Sulfur atoms
• CPC Class Codes: C07D 333/48 : by oxygen atoms

Abstract

Disclosed are compounds of formula X,

which are useful in treating Alzheimer'"'"'s disease and other similar diseases. Pharmaceutical compositions comprising compounds of formula X and methods of preparing the compounds of formula X are also disclosed.

Claims

1. A compound of the formula:

2. A compound according to claim 1 wherein

R₁ is (CH₂)_n1—

(R_1-aryl) where n₁ is one and R_1-aryl is phenyl optionally substituted with 1, 2, 3, or 4 groups independently selected from C₁–

C₆ alkyl optionally substituted with 1, 2, or 3 substituents selected from the group consisting of C₁–

C₃ alkyl, halogen, —

OH, —

SH, —

NR_1-aR_1-b, —

C≡

N, —

CF₃, and C₁–

C₃ alkoxy;

halogen;

C₁–

C₆ alkoxy;

—

NR_N-2R_N-3; and

OH;

wherein

R_N-2 and R_N-3 at each occurrence are independently selected from the group consisting of —

C₁–

C₈ alkyl optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of —

OH, —

NH₂, phenyl and halogen;

—

C₃–

C₈ cycloalkyl;

—

(C₁–

C₂ alkyl)-(C₃–

C₈ cycloalkyl);

—

(C₁–

C₆ alkyl)-O—

(C₁–

C₃ alkyl);

—

C₂–

C₆ alkenyl;

—

C₂–

C₆ alkynyl;

—

C₁–

C₆ alkyl chain with one double bond and one triple bond;

aryl;

heteroaryl;

heterocycloalkyl;

or

R_N-2, R_N-3 and the nitrogen to which they are attached form a 5, 6, or 7 membered heterocycloalkyl or heteroaryl group, wherein said heterocycloalkyl or heteroaryl group is optionally fused to a benzene, pyridine, or pyrimidine ring, and said groups are unsubstituted or substituted with 1, 2, 3, 4, or 5 groups that at each occurrence are independently C₁–

C₆ alkyl, C₁–

C₆ alkoxy, halogen, halo C₁–

C₆ alkyl, halo C₁–

C₆ alkoxy, —

CN, —

NO₂, —

NH₂, NH(C₁–

C₆ alkyl), N(C₁–

C₆ alkyl)(C₁–

C₆ alkyl), —

OH, —

C(O)NH₂, —

C(O)NH(C₁–

C₆ alkyl), —

C(O)N(C₁–

C₆ alkyl)(C₁–

C₆ alkyl), C₁–

C₆ alkoxy C₁–

C₆ alkyl, C₁–

C₆ thioalkoxy, and C₁–

C₆ thioalkoxy C₁–

C₆ alkyl.

3. A compound according to claim 2, wherein

R_N is:

4. A compound according to claim 3, wherein

5. A compound according to claim 4, wherein

R₁ is benzyl which is optionally substituted with 1, 2, 3, or 4 groups independently selected from halogen, C₁–

C₄ alkoxy, hydroxy, and C₁–

C₄ alkyl optionally substituted with 1, 2, or 3 substituents halogen, OH, SH, NH₂, NH(C₁–

C₆ alkyl), N—

(C₁–

C₆ alkyl)(C₁–

C₆ alkyl), C≡

N, CF₃;

R₂ and R₃ are independently selected from H or C₁–

C₄ alkyl optionally substituted with 1 substituent selected from halogen, —

OH, —

SH, —

C≡

N, —

CF₃, C₁–

C₃ alkoxy, NH₂, NH(C₁–

C₆ alkyl), and NH (C₁–

C₆ alkyl)(C₁–

C₆ alkyl);

R_C is C₁–

C₈ alkyl optionally substituted with 1, 2, or 3 groups independently selected from R₂₀₅, —

SH, —

C═

ONR₂₃₅R₂₄₀, and —

S(═

O)₂NR₂₃₅R₂₄₀;

—

(CH₂)_0-3—

(C₃–

C₆) cycloalkyl wherein the cycloalkyl is optionally substituted with 1, 2, or 3 groups independently selected from R₂₀₅, —

CO₂H, and —

CO₂—

(C₁–

C₄ alkyl);

—

(CR₂₄₅R₂₅₀)_0-4-phenyl optionally substituted with 1, 2, or 3 R₂₀₀;

—

(CR₂₄₅R₂₅₀)_0-3-pyridyl;

—

(CR₂₄₅R₂₅₀)_0-3-pyridazinyl;

—

(CR₂₄₅R₂₅₀)_0-3-pyrimidinyl;

—

(CR₂₄₅R₂₅₀)_0-3-pyrazinyl;

—

(CR₂₄₅R₂₅₀)_0-3-furyl;

—

(CR₂₄₅R₂₅₀)_0-3-indolyl;

—

(CR₂₄₅R₂₅₀)_0-3-thienyl;

—

(CR₂₄₅R₂₅₀)_0-3-pyrrolyl;

—

(CR₂₄₅R₂₅₀)_0-3-pyrazolyl;

(CR₂₄₅R₂₅₀)_0-3-benzoxazolyl;

—

(CR₂₄₅R₂₅₀)_0-3-imidazolyl;

each of the above heteroaryl groups is optionally substituted with 1, 2, 3, or 4 R₂₀₀;

—

(CR₂₄₅R₂₅₀)_0-3-imidazolidinyl;

(CR₂₄₅R₂₅₀)_0-3-tetrahydrofuryl;

(CR₂₄₅R₂₅₀)_0-3-tetrahydropyranyl;

(CR₂₄₅R₂₅₀)_0-3-piperazinyl;

(CR₂₄₅R₂₅₀)_0-3-pyrrolidinyl;

(CR₂₄₅R₂₅₀)_0-3-piperidinyl;

(CR₂₄₅R₂₅₀)_0-3-indolinyl;

each of the above heterocycloalkyl groups is optionally substituted with 1, 2, 3, or 4 R₂₁₀;

(CH₂)_0-1—

CH((CH₂)_0-4—

OH)-(CH₂)_0-1-phenyl;

—

(CH₂)_0-1—

CH (C₁–

C₄ hydroxyalkyl)-(CH₂)_0-1-pyridyl;

R₂₀₀ at each occurrence is independently C₁–

C₆ alkyl optionally substituted with 1, 2, or 3 R₂₀₅ groups;

OH;

—

NO₂;

halogen;

—

CO₂H;

C≡

N;

—

(CH₂)_0-4—

CO—

NR₂₂₀R₂₂₅;

—

(CH₂)_0-4—

CO—

(C₁–

C₈ alkyl);

—

(CH₂)_0-4—

CO₂R₂₁₅; and

—

(CH₂)_0-4—

O'"'"'(C₁–

C₆ alkyl optionally substituted with 1, 2, 3, or 5 —

F);

R₂₀₅ at each occurrence is independently C₁–

C₆ alkyl, halogen, —

OH, —

O-phenyl, —

SH, —

C≡

N, —

CF₃, C₁–

C₆ alkoxy, NH₂, NH(C₁–

C₆ alkyl), and N—

(C₁–

C₆ alkyl)(C₁–

C₆ alkyl);

R₂₁₀ at each occurrence is independently C₁–

C₆ alkyl optionally substituted with 1 or 2 R₂₀₅ groups;

halogen;

C₁–

C₄ alkoxy;

C₁–

C₄ haloalkoxy;

—

NR₂₂₀R₂₂₅;

OH;

C≡

N;

C₃–

C₇ cycloalkyl optionally substituted with 1 or 2 R₂₀₅ groups;

—

CO—

(C₁–

C₄ alkyl);

—

SO_{2 —}

NR₂₃₅R₂₄₀;

—

CO—

NR₂₃₅R₂₄₀;

—

SO₂—

(C₁–

C₄ alkyl); and

═

O;

wherein

R₂₁₅ at each occurrence is independently C₁–

C₆ alkyl, —

(CH₂)_0-2-(phenyl), C_{3 —}

C₆ cycloalkyl, —

(CH₂)_0-2-(pyridyl), —

(CH₂)_0-2-(pyrrolyl), —

(CH₂)_0-2-(imidazolyl), —

(CH₂)_0-2-(pyrimidyl), —

(CH₂)_0-2-(pyrrolidinyl), —

(CH₂)_0-2-(imidazolidinyl) —

(CH₂)_0-2-(piperazinyl), —

(CH₂)_0-2-(piperidinyl), and —

(CH₂)_0-2-(morpholinyl);

wherein the phenyl group at each occurrence is optionally substituted with 1 or 2 groups that are independently R₂₀₅ or R₂₁₀;

wherein each heterocycloalkyl group at each occurrence is optionally substituted with 1 or 2 R₂₁₀;

wherein each heteroaryl group at each occurrence is optionally substituted with 1 or 2 R₂₁₀;

R₂₂₀ and R₂₂₅ at each occurrence are independently —

H, —

C₁–

C₄ alkyl, hydroxy C₁–

C₄ alkyl, halo C₁–

C₄ alkyl;

—

C₃–

C₆ cycloalkyl, and —

(C₁–

C₄ alkyl)-O—

(C₁–

C₂ alkyl);

R₂₃₅ and R₂₄₀ at each occurrence are independently H, or C₁–

C₆ alkyl;

R₂₄₅ and R₂₅₀ at each occurrence are independently H, C₁–

C₄ alkyl, C₁–

C₄ hydroxyalkyl, C₁–

C₄ alkoxy, C₁–

C₄ haloalkoxy, or

R₂₄₅ and R₂₅₀ are taken together with the carbon to which they are attached to form a carbocycle of 3, 5, or 6 carbon atoms.

6. A compound according to claim 5, wherein

X is —

C₁–

C₃ alkylidenyl optionally optionally substituted with 1 methyl group;

Z is SO₂;

SO;

or S;

Y is OH;

—

N(Y₁)(Y₂);

phenyl;

benzyl;

or C₁–

C₁₀ alkyl optionally substituted with 1 or 2 substituents which can be the same or different and are selected from halogen, hydroxy, methoxy, ethoxy, thiomethoxy, thioethoxy, and CF₃;

wherein

Y₁ and Y₂ are the same or different and are H;

C₁–

C₄ alkyl optionally substituted with 1 or 2 substituents selected from halogen, methoxy, ethoxy, cyclopropyl, and OH;

or

—

N(Y₁)(Y₂) forms a ring selected from piperazinyl, piperidinyl, morpholinyl, and pyrolidinyl, wherein each ring is optionally substituted with 1 or 2 groups that are independently C₁–

C₄ alkyl, C₁–

C₄ alkoxy, or halogen;

R₁ is benzyl which is optionally substituted with 1, 2, or 3 groups independently selected from methyl, ethyl, n-propyl, isopropyl, hydroxymethyl, monohalomethyl, dihalomethyl, trihalomethyl, —

CH₂CF₃, methoxymethyl, halogen, methoxy, ethoxy, n-propyloxy, isopropyloxy, and OH;

R₂ and R₃ are independently H or C₁–

C₄ alkyl;

R_C is C₁–

C₆ alkyl optionally substituted with 1, 2, or 3 R₂₀₅ groups;

cyclopropyl, cyclopropylmethyl, cyclopentyl, cyclopentylmethyl, cyclohexyl, cyclohexylmethyl;

—

(CR₂₄₅R₂₅₀)_0-3-phenyl optionally substituted with 1 or 2 R₂₀₀ groups;

—

(CR₂₄₅R₂₅₀)_0-3-pyridyl optionally substituted with 1 or 2 R₂₀₀;

—

(CR₂₄₅R₂₅₀)_0-3-piperazinyl;

or (CR₂₄₅R₂₅₀)_0-3-pyrrolidinyl;

—

(CR₂₄₅R₂₅₀)_0-3-piperidinyl;

each of the above heterocycloalkyl groups is optionally substituted with 1 or 2 R₂₁₀ groups;

R₂₀₀ at each occurrence is independently selected from C₁–

C₄ alkyl optionally substituted with 1 or 2 R₂₀₅ groups;

OH; and

halogen;

R₂₀₅ at each occurrence is independently selected from C₁–

C₄ alkyl, halogen, —

OH, —

SH, —

C≡

N, —

CF₃, and C₁–

C₄ alkoxy;

R₂₁₀ at each occurrence is independently selected from C₁–

C₄ alkyl optionally substituted with 1 or 2 R₂₀₅ groups;

halogen;

C₁–

C₄ alkoxy;

OCF₃;

NH₂, NH(C₁–

C₆ alkyl);

N(C₁–

C₆ alkyl)(C₁–

C₆ alkyl);

OH; and

—

CO—

(C₁–

C₄ alkyl);

wherein

R₂₄₅ and R₂₅₀ at each occurrence are independently selected from H, C₁–

C₄ hydroxyalkyl, C₁–

C₄ alkoxy, or

R₂₄₅ and R₂₅₀ are taken together with the carbon to which they are attached to form a carbocycle of 3, 5, or 6 carbon atoms.

7. A compound according to claim 4 that is selected from

S-butyl-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-D-cysteinamide;

3-(butylsulfinyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-D-alaninamide;

3-(butylsulfonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-D-alaninamide;

3-(butylsulfonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-L-alaninamide;

3-(butylsulfonyl)-N˜

1˜

-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-(isopentylamino)propyl]-D-alaninamide;

N˜

1˜

-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(3-ethylphenyl)cyclopropyl]amino}-2-hydroxypropyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-L-alaninamide;

N˜

1˜

-[(1S,2R)-3-(cyclopropylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

1˜

-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxypropyl-3-(isopentylamino)]-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

1˜

-{(1S,2S)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]alaninamide hydrochloride.

8. A compound according to claim 3 wherein

R_N is:

9. A compound according to claim 8, wherein

X is —

C₁–

C₃ alkylidenyl;

Z is SO₂;

SO;

or S;

Y is OH;

—

N(Y₁)(Y₂);

phenyl;

benzyl;

or C₁–

C₁₀ alkyl optionally substituted with 1 or 2 substituents which can be the same or different and are selected from halogen, hydroxy, methoxy, ethoxy, thiomethoxy, thioethoxy, and CF₃;

wherein

Y₁ and Y₂ are the same or different and are H;

C₁–

C₄ alkyl optionally substituted with 1 or 2 substituents selected from halogen, methoxy, ethoxy, cyclopropyl, and OH;

or

—

N(Y₁)(Y₂) forms a ring selected from piperazinyl, piperidinyl, morpholinyl, and pyrolidinyl, wherein each ring is optionally substituted with 1 or 2 groups that are independently C₁–

C₄ alkyl, C₁–

C₄ alkoxy, or halogen;

R₁ is benzyl which is optionally substituted with 1, 2, or 3 groups independently selected from methyl, ethyl, n-propyl, isopropyl, hydroxymethyl, monohalomethyl, dihalomethyl, trihalomethyl, —

CH₂CF₃, methoxymethyl, halogen, methoxy, ethoxy, n-propyloxy, isopropyloxy, and OH;

R₂ and R₃ are independently H or C₁–

C₄ alkyl;

R_C is C₁–

C₆ alkyl optionally substituted with 1, 2, or 3 R₂₀₅ groups;

cyclopropyl, cyclopropylmethyl, cyclopentyl, cyclopentylmethyl, cyclohexyl, cyclohexylmethyl;

—

(CR₂₄₅R₂₅₀)_0-3-phenyl optionally substituted with 1 or 2 R₂₀₀ groups;

or —

(CR₂₄₅R₂₅₀)_0-3-pyridyl optionally substituted with 1 or 2 R₂₀₀;

R₂₀₀ at each occurrence is independently C₁–

C₄ alkyl optionally substituted with 1 or 2 R₂₀₅ groups;

OH;

or halogen;

R₂₀₅ at each occurrence is independently C₁–

C₄ alkyl, halogen, —

OH, —

SH, —

C≡

N, —

CF₃, or C₁–

C₄ alkoxy;

R₂₄₅ and R₂₅₀ at each occurrence are independently H, C₁–

C₄ hydroxyalkyl, or C₁–

C₄ alkoxy, or

R₂₄₅ and R₂₅₀ are taken together with the carbon to which they are attached to form a carbocycle of 3 carbon atoms.

10. A compound according to claim 9, wherein

R₅₁ is benzyl;

phenethyl;

C₁–

C₆ alkyl optionally substituted with 1, 2, or 3 groups that are independently halogen, cyano, —

NR₆R₇, —

C(O)NR₆R₇, or —

C₁–

C₄ alkoxy;

pyrrolidinyl, tetrahydrofuryl, tetrahydro-thienyl 1,1-dioxide, tetrahydrothienyl, pyranyl, piperidinyl, pyrrolidinonyl, each of which is optionally substituted with 1 or 2 groups that are independently C₁–

C₄ alkyl, C₁–

C₄ alkoxy, halogen, C₂–

C₄ alkanoyl, benzyl, and —

SO₂ C₁–

C₄ alkyl;

pyrrolidinonyl C₁–

C₄ alkyl optionally substituted with 1 or 2 groups that are independently C₁–

C₄ alkyl, C₁–

C₄ alkoxy, halogen, C₂–

C₄ alkanoyl, C₁–

C₄ alkyl, and —

SO₂ C₁–

C₄ alkyl;

C₂–

C₄ alkenyl;

C₂–

C₄ alkynyl;

pyridinyl C₁–

C₄ alkyl optionally substituted with 1, or 2 groups that are independently C₁–

C₄ alkyl, C₁–

C₄ alkoxy, halogen, NH₂, NH(C₁–

C₆ alkyl) or N(C₁–

C₆ alkyl)(C₁–

C₆ alkyl);

cyclopentyl;

cyclohexyl;

or cyclopropylmethyl;

wherein the cycloalkyl, and cycloalkylalkyl groups are optionally substituted with 1, or 2 groups that are independently halogen, CN, NO₂, methyl, ethyl, methoxy, ethoxy, C₂–

C₄ alkanoyl, CF₃, OCF₃, or hydroxy;

R₆ and R₇ are independently H, C₁–

C₄ alkyl, C₂–

C₄ alkanoyl, or benzyl;

Y is OH;

—

N(Y₁)(Y₂);

phenyl;

benzyl;

or C₁–

C₁₀ alkyl optionally substituted with 1 or 2 substituents which can be the same or different and are selected from halogen, hydroxy, methoxy, ethoxy, thiomethoxy, thioethoxy, and CF₃;

wherein

Y₁ and Y₂ are the same or different and are H or C₁–

C₄ alkyl optionally substituted with 1 or 2 substituents selected from halogen, methoxy, ethoxy, cyclopropyl, and OH.

11. A compound according to claim 10 of the formula

12. A compound according to claim 8, wherein

R_C is C₃–

C₈ alkyl, cyclopropyl, cyclopentyl, cyclohexyl, or —

(C₁–

C₄) alkyl-cyclopropyl.

13. A compound according to claim 12 of the formula

14. A compound according to claim 8 that is selected from

3-(butylsulfinyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-[(methoxy)carbonyl]-D-alaninamide;

S-butyl-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-[(methoxy)carbonyl]-D-cysteinamide;

N˜

2˜

-[(benzyloxy)carbonyl]-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(4,4,4-trifluorobutyl)sulfonyl]-D-alaninamide;

N˜

2˜

-[(benzyloxy)carbonyl]-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(4,4,4-trifluorobutyl)sulfinyl]-D-alaninamide;

N˜

2˜

-[(benzyloxy)carbonyl]-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-S-(4,4,4-trifluorobutyl)-D-cysteinamide;

3-(butylsulfonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-[(methoxy)carbonyl]-D-alaninamide;

3-(butylsulfonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-[(2,2,2-trifluoroethoxy)carbonyl]-D-alaninamide;

N˜

2˜

-[(2-cyanoethoxy)carbonyl]-N-1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-(butylsulfonyl)-D-alaninamide;

3-(butylsulfonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-{[(3R)-pyrrolidin-3-yl]carbonyl}-D,L-alaninamide;

3-(butylsulfonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-{[(3S)-tetrahydrofuran-3-yloxy]carbonyl}-D-alaninamide;

N˜

2˜

-{[2-(acetylamino)ethoxy]carbonyl}-3-(butylsulfonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-D-alaninamide;

3-(butylsulfonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-{[[(pyridin-3-yl)methyl]oxy]carbonyl}-D-alaninamide;

3-(butylsulfonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-{[[(pyridin-4-yl)methyl]oxy]carbonyl}-D-alaninamide;

3-(butylsulfonyl)-N˜

2˜

-[(methoxy)carbonyl]-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-(cyclopropylamino)-2-hydroxypropyl}-D-alaninamide;

3-(butylsulfonyl)-N˜

2˜

-[(2-cyanoethoxy)carbonyl]-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-(cyclopropylamino)-2-hydroxypropyl}-D-alaninamide;

N˜

2˜

-[(benzyloxy)carbonyl]-3-(butylsulfonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-methylbutyl)amino]-2-hydroxypropyl}-D-alaninamide;

3-(butylsulfonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-methylbutyl)amino]-2-hydroxypropyl}-N˜

2˜

-[(methyloxy)carbonyl]-D-alaninamide;

N˜

2˜

-[(2-cyanoethoxy)carbonyl]-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-(cyclopropylamino)-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

2˜

-{[2-(acetylamino)ethoxy]carbonyl}-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-(cyclopropylamino)-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-methylbutyl)amino]-2-hydroxypropyl}-N˜

2˜

-[(methyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

2˜

-[(benzyloxy)carbonyl]-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-methylbutyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

2˜

-{[2-(diethylamino)-2-oxoethoxy]carbonyl}-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-[(methoxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-[(isopropoxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

2˜

-[(cyclopropylmethoxy)carbonyl]-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

2˜

-[(allyloxy)carbonyl]-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

2˜

-[(2-cyanoethoxy)carbonyl]-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

2˜

-{[2-(acetylamino)ethoxy]carbonyl}-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-N˜

2˜

-{[[(pyridin-3-yl)methyl]oxy]carbonyl}-D-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-N˜

2˜

-{[[(pyridin-4-yl)methyl]oxy]carbonyl}-D-alaninamide;

benzyl (1R)-1-[({(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}amino)carbonyl]-3-(methylsulfonyl)propylcarbamate;

N˜

2˜

-[(benzyloxy)carbonyl]-3-(butylsulfonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-D-alaninamide trifluroacetate;

N˜

2˜

-[(benzyloxy)carbonyl]-3-(butylsulfonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-L-alaninamide trifluroacetate;

N˜

2˜

-[(benzyloxy)carbonyl]-N˜

1˜

-((1S,2S)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1R)-2-hydroxy-1-phenylethyl]amino}propyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

2˜

-[(benzyloxy)carbonyl]-N˜

1˜

-((1S,2S)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1R)-2-methoxy-1-phenylethyl]amino}propyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

2˜

-[(benzyloxy)carbonyl]-N˜

1˜

-((1S,2S)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1S)-2-methoxy-1-phenylethyl]amino}propyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

2˜

-[(benzyloxy)carbonyl]-N˜

1˜

-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(3-ethylphenyl)cyclopropyl]amino}-2-hydroxypropyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-N˜

2˜

-{[(prop-2-ynyl)oxy]carbonyl}-D-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2-(2-methoxyethylcarbonyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

2˜

-{[(3R)-1-acetylpyrrolidin-3-yl]carbonyl}-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-{[(3S)-tetrahydrofuran-3-yloxy]carbonyl}-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-{[(3S)-tetrahydrofuran-3-yloxy]carbonyl}-3-[(1-propylbutyl)sulfonyl]-L-alaninamide;

N˜

2˜

-[(benzyloxy)carbonyl]-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

2˜

-[(benzyloxy)carbonyl]-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-L-alaninamide;

N˜

2˜

-[(benzyloxy)carbonyl]-N˜

1˜

-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(3-ethylphenyl)cyclopropyl]amino}-2-hydroxypropyl)-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

2˜

-[(benzyloxy)carbonyl]-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

2˜

-[(benzyloxy)carbonyl]-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-methylbutyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

2˜

-[(benzyloxy)carbonyl]-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-(cyclopropylamino)-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

2˜

-[(benzyloxy)carbonyl]-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(cyclopropylmethyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

2˜

-[(benzyloxy)carbonyl]-N˜

1˜

-{(1S,2S)-1-(3,5-difluorobenzyl)-3-[(3-ethylphenyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

2˜

-[(benzyloxy)carbonyl]-N˜

1˜

-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({2-[3-(trifluoromethyl)phenyl]ethyl}amino)propyl]-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-N˜

2˜

-{[[(pyridin-3-yl)methyl]oxy]carbonyl}-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-{[(3S)-tetrahydrofuran-3-yloxy]carbonyl}-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-{[(3R)-tetrahydrofuran-3-yloxy]carbonyl}-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-benzyl-3-[(3-methoxybenzyl)amino]-2-hydroxypropyl}-N˜

2-{[(3S)-tetrahydrofuran-3-yloxy]carbonyl}-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

2˜

-{[(3R)-1-acetylpyrrolidin-3-yl]carbonyl}-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-N˜

2˜

-{[(3R)-pyrrolidin-3-yl]carbonyl}-D,L-alaninamide;

N˜

2˜

-{[(3R)-1-benzylpyrrolidin-3-yl]carbonyl}-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5diflurobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-{[(3S)-1,1-dioxidotetrahydrothien-3-yloxy]carbonyl}-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-{[(3S)-tetrahydrothiophen-3-yloxy]carbonyl}-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

2˜

-(cyclopentylcarbonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

2˜

-(cyclohexylcarbonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

1˜

-[(1S,2R)-3-(cyclopropylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-3-[(1-propylbutyl)sulfonyl]-N˜

2˜

-{[tetrahydropyran-4-yloxy]carbonyl}-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-N˜

2˜

-{[tetrahydropyran-4-yloxy]carbonyl}-D,L-alaninamide;

3-(butylsulfonyl)-N˜

1˜

-{(1S,2R)-1(3,5-difluorobenzyl)-3-[(3-ethynylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

(methoxycarbonyl)-D-alaninamide;

3-(butylsulfonyl)-N˜

1˜

-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propyl)-N˜

2˜

(methoxycarbonyl)-D-alaninamide;

3-(butylsulfonyl)-N˜

1˜

-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(3-ethylphenyl)cyclopropyl]amino}-2-hydroxypropyl)-N˜

2˜

(methoxycarbonyl)-D-alaninamide;

3-(butylsulfonyl)-N˜

1˜

-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(3-ethynylphenyl)cyclopropyl]amino}-2-hydroxypropyl)-N˜

2˜

(methoxycarbonyl)-D-alaninamide; and

3-(butylsulfonyl)-N˜

1˜

-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)propyl]-N˜

2˜

(methoxycarbonyl)-D-alaninamide.

15. A compound according to claim 3, wherein

R_N is:

16. A compound according to claim 15, wherein

R₁ is benzyl which is optionally substituted with 1, 2, 3, or 4 groups independently selected from C₁–

C₄ alkyl optionally substituted with 1, or 2 substituents selected from halogen, —

OH, —

SH, NH₂, NH(C₁–

C₆ alkyl), N—

(C₁–

C₆ alkyl)(C₁–

C₆ alkyl), —

C≡

N, —

CF₃, and C₁–

C₃ alkoxy;

halogen;

C₁–

C₄ alkoxy; and

OH.

17. A compound according to claim 16, wherein

X is C₁–

C₃ alkylidenyl optionally optionally substituted with 1 or 2 methyl groups;

Z is SO₂;

SO;

or S;

Y is H;

C₁–

C₄ haloalkyl;

pyrrolidinyl;

piperidinyl;

imidazolidinyl;

piperazinyl;

OH;

—

N(Y₁)(Y₂);

C₁–

C₁₀ alkyl optionally substituted with 1 thru 3 substituents which can be the same or different and are selected from halogen, hydroxy, C₁–

C₄ alkoxy, C₁–

C₄ thioalkoxy, and C₁–

C₄ haloalkoxy;

C₃–

C₆ cycloalkyl optionally substituted with 1, 2, or 3 groups independently selected from C₁–

C₃ alkyl and halogen;

C₁–

C₄ alkoxy;

phenyl, benzyl or phenethyl each of which is optionally substituted with halogen, C₁–

C₄ alkyl, C₁–

C₄ alkoxy, CN or NO₂;

wherein

Y₁ and Y₂ are indepenently H;

C₁–

C₆ alkyl optionally substituted with 1, 2, or 3 substituents selected from halogen, C₁–

C₄ alkoxy, C₃–

C₆ cycloalkyl, and OH;

C₂–

C₆ alkanoyl;

phenyl;

—

SO₂—

C₁–

C₄ alkyl;

phenyl C₁–

C₄ alkyl;

or C₃–

C₆ cycloalkyl C₁–

C₄ alkyl;

or

—

N(Y₁)(Y₂) forms a ring selected from piperazinyl, piperidinyl, morpholinyl, and pyrolidinyl, wherein each ring is optionally substituted with 1, 2, or 3 groups that are independently C₁–

C₄ alkyl, C₁–

C₄ alkoxy, C₁–

C₄ alkoxy C₁–

C₄ alkyl, or halogen; and

R₂ and R₃ are independently H or C₁–

C₄ alkyl.

18. A compound according to claim 17 wherein

X is C, or C₂ alkylidenyl;

Z is SO₂;

SO;

or S; and

Y is phenyl;

C₁–

C₁₀ alkyl optionally substituted with 1, 2, or 3 halogen;

or OH;

or

Y is —

N(Y₁)(Y₂);

wherein

Y₁ and Y₂ are independently H or C₁–

C₄ alkyl.

19. A compound according to claim 18, of the formula:

20. A compound according to claim 18, wherein

21. A compound according to claim 15 selected from

3-(butylsulfonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-(3,3,3-trifluoropropanoyl)-D-alaninamide;

3-(butylsulfonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-(trifluoroacetyl)-D-alaninamide;

N˜

2˜

-acetyl-3-(butylsulfonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-D-alaninamide;

3-(butylsulfonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-(pyridin-4-ylcarbonyl)-D-alaninamide;

3-(butylsulfonyl)-N˜

2˜

-(cyclopropylcarbonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-D-alaninamide;

3-(butylsulfonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

(beta-alanyl)-D-alaninamide;

3-(butylsulfonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

glycyl-D-alaninamide;

3-(butylsulfonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

(N,N-dimethylglycyl)-D-alaninamide;

3-(butylsulfonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

(N,N-dimethyl-beta-alanyl)-D-alaninamide;

3-(butylsulfonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-(methoxyacetyl)-D-alaninamide;

3-(butylsulfonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-(pyridin-3-ylcarbonyl)-D-alaninamide;

3-(butylsulfonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-[(2,4-dimethyl-1,3-thiazol-5-yl)carbonyl]-D-alaninamide;

3-(butylsulfonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-[3-(trifluoromethyl)-1H-pyrazol-4-yl)carbonyl]-D-alaninamide;

3-(butylsulfonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-[(3-methyl-1H-pyrazol-5-yl)carbonyl]-D-alaninamide;

3-(butylsulfonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-(1H-imidazol-4-ylacetyl)-D-alaninamide;

3-(butylsulfonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-(pyrazin-2-ylcarbonyl)-D-alaninamide;

3-(butylsulfonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-[(6-hydroxypyridin-3-yl)carbonyl]-D-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-(cyclopropylamino)-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-N˜

2˜

-(pyridin-4-ylcarbonyl)-D-alaninamide;

N˜

2˜

-acetyl-3-(butylsulfonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-methylbutyl)amino]-2-hydroxypropyl}-D-alaninamide;

N˜

1˜

-[(1S,2R)-3-(cyclopropylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N˜

2˜

-(cyclopropylcarbonyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

2˜

-acetyl-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-methylbutyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-N˜

2˜

-(pyridin-4-ylcarbonyl)-D-alaninamide;

N˜

2˜

-[(5-bromoopyridin-3-yl)carbonyl]-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

2˜

-[(5-chloropyridin-3-yl)carbonyl]-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

(3-fluorobenzoyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-[(5-methylpyridin-3-yl)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

2˜

-phenylglycyl-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-N˜

2˜

-{[3-(trifluoromethyl)-1H-pyrazol-4-yl]carbonyl}-D-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-[(3-methyl-1H-pyrazol-5-yl)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-N˜

2-(1,3-thiazol-4-ylcarbonyl)-D-alaninamide;

N˜

2˜

-[(1-acetylpiperidin-4-yl)carbonyl]-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

2˜

-[4-(acetylamino)butanoyl]-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

2˜

-acetyl-beta-alanyl-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

2˜

-(chloroacetyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-(methoxyacetyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-(3-methoxypropanoyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-(2,2-dimethylpropanoyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-isobutyryl-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

2˜

-butyryl-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

2˜

-acetyl-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

1˜

-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(3-ethylphenyl)cyclopropyl]amino}-2-hydroxypropyl)-3-[(1-propylbutyl)sulfonyl]-N˜

2˜

-[(pyridin-3-yl)carbonyl]-D-alaninamide trifluoracetate;

N˜

1˜

-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(3-ethylphenyl)cyclopropyl]amino}-2-hydroxypropyl)-3-[(1-propylbutyl)sulfonyl]-N˜

2˜

-[(pyridin-4-yl)carbonyl]-D-alaninamide trifluoracetate;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(3-ethylphenyl)cyclopropyl]amino}-2-hydroxypropyl)-N˜

2-(3-hydroxybenzoyl}-3-[(1-propylbutyl)sulfonyl]-D-alaninamide trifluoracete;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-N˜

2˜

-[(pyridin-3-yl)carbonyl]-D-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl)-N˜

2˜

-(3-hydroxybenzoyl}-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

2˜

-(cyclopropylcarbonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-propionyl-3-[(1-propylbutyl)sulfonyl]-D-alaninamide;

3-[butylsulfonyl]-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-[(pyridin-3-yl)carbonyl]-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(3-ethylphenyl)cyclopropyl]amino}-2-hydroxypropyl)-N˜

2˜

-(3-hydroxybenzoyl}-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide trifluoracete;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(3-ethylphenyl)cyclopropyl]amino}-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-N˜

2˜

-[(pyridin-4-yl)carbonyl]-D-alaninamide trifluoracetate;

N˜

1˜

-{(1S,2S)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-[(6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)carbonyl]-3-[(1-propylbutyl)sulfonyl]alaninamide hydorchloride;

5-oxo-D-prolyl-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]alaninamide;

5-oxo-L-prolyl-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]alaninamide;

N˜

1˜

-{(1S,2S)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-[3-(4-oxo-2-thioxo-1,3-thiazolidin-3-yl)propanoyl]-3-[(1-propylbutyl)sulfonyl]alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-[(piperidin-4-yl)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-[(2,4-dimethyl-1,3-thiazol-5-yl)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-[(2-methyl-4-(trifluoromethyl)-1,3-thiazol-5-yl)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-[(3,5-dimethylisoxazol-4-yl)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-[(3-methyl-1H-pyrazol-5-yl)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide triflouroacetate;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-[(1H-pyrazol-4-yl)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-[(1H-imidazol-5-yl)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-(1H-imidazol-4-ylacetyl)-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-N˜

2˜

-[(pyrazin-2-yl)carbonyl]-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-[(3,5-dihydroxypyridin-4-yl)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-[(6-hydroxypyridin-3-yl)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

2˜

-[(6-chloropyridin-3-yl)carbonyl]-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-N˜

2˜

-[(pyridin-4-yl)carbonyl]-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-[(pyridin-3-yl)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-N˜

2˜

-[(pyridin-2-yl)carbonyl]-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-[1H-indole-6-carbonyl]-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-N˜

2-(2,3,4-trimethoxybenzoyl)-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-[(pyridin-2-yl)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-(3-hydroxybenzoyl)-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-(3-methylbenzoyl)-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-(3-ethylbenzyl)-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

2˜

-(3-chlorobenzoyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-(4-methylbenzoyl)-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-(4-methoxybenzoyl)-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-(4-triflluoromethylbenzoyl)-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

2˜

-(cyclohexylcarbonyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

2˜

(benzoyl)-N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

2˜

(benzoyl)-N˜

1˜

-[(1S,2R)-3-(cyclopropylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-3-[(1-propylbutyl)sulfonyl]alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-(phenylacetyl)-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N˜

2˜

-(3-phenylpropanoyl)-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N-(3-({(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}amino)-3-oxo-2-{[(1-propylbutyl)sulfonyl]methyl}propyl)benzamide;

N˜

1˜

-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N˜

2˜

-(cyclopropylacetyl)-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N˜

2˜

-[(methylsulfonyl)acetyl]-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N˜

2˜

-[(methylthio)acetyl]-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N˜

2˜

-(4-hydroxy-4-oxobutanoyl)-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N˜

2˜

-[4-(methylamino)-4-oxobutanoyl]-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N˜

1˜

-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N˜

2˜

-(4-methoxy-4-oxobutanoyl)-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide;

N-(methylsulfonyl)glycyl-N˜

1˜

-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide; and

N˜

2˜

-acetyl-N˜

1˜

-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-(phenylsulfonyl)-D,L-alaninamide.

22. A compound according to claim 3, wherein

R_N is of the formula:

23. A compound according to claim 3, of the formula:

24. A compound according to claim 1, wherein

R₄ is H;

C₁–

C₄ alkyl-NHC(O)R₅;

—

(CH₂)_0-4R₈;

—

O—

C₁–

C₄ alkanoyl;

OH;

C₆–

C₁₀ aryloxy optionally substituted with 1, 2, or 3 groups that are independently halogen, C₁–

C₄ alkyl, CO₂H, —

C(O)—

C₁–

C₄ alkoxy, or C₁–

C₄ alkoxy;

C₁–

C₆ alkoxy;

aryl C₁–

C₄ alkoxy;

—

C₁–

C₄ alkyl-NR₅₀CO₂R₅₁;

—

C≡

N;

—

CF₃;

—

CF₂—

CF₃;

—

C≡

CH;

—

CH₂—

CH═

CH₂;

—

(CH₂)_1-4—

R_4-1;

—

(CH₂)_1-4—

NH—

R_4-1;

—

O—

(CH₂)_n6—

R_4-1;

—

S—

(CH₂)_n6—

R_4-1;

(CH₂)_0-4—

NHC(O)—

(CH₂)_0-6—

R₅₂;

or —

(CH₂)_0-4—

R₅₃—

(CH₂)_0-4—

R₅₄.

25. A compound according to claim 24, wherein

R₁ is (CH₂)_n1—

(R₁-aryl) where n₁ is zero or one and R_1-aryl is phenyl optionally substituted with 1, 2, 3, or 4 groups independently selected from C₁–

C₆ alkyl optionally substituted with 1, 2, or 3 substituents selected from the group consisting of C₁–

C₃ alkyl, halogen, —

OH, —

SH, —

NR_1-aR_1-b, —

C≡

N, —

CF₃, and C₁–

C₃ alkoxy;

halogen;

C₁–

C₆ alkoxy;

—

NR_N-2R_N-3; and

OH;

wherein

R_N-2 and R_N-3 at each occurrence are independently selected from the group consisting of —

C₁–

C₈ alkyl optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of —

OH, —

NH₂, phenyl and halogen;

—

C₃–

C₈ cycloalkyl;

—

(C₁–

C₂ alkyl)-(C₃–

C₈ cycloalkyl);

—

(C₁–

C₆ alkyl)-O—

(C₁–

C₃ alkyl);

—

C₂–

C₆ alkenyl;

—

C₂–

C₆ alkynyl;

—

C₁–

C₆ alkyl chain with one double bond and one triple bond;

aryl;

heteroaryl;

heterocycloalkyl;

or

R_N-2, R_N-3 and the nitrogen to which they are attached form a 5, 6, or 7 membered heterocycloalkyl or heteroaryl group, wherein said heterocycloalkyl or heteroaryl group is optionally fused to a benzene, pyridine, or pyrimidine ring, and said groups are unsubstituted or substituted with 1, 2, 3, 4, or 5 groups that at each occurrence are independently C₁–

C₆ alkyl, C₁–

C₆ alkoxy, halogen, halo C₁–

C₆ alkyl, halo C₁–

C₆ alkoxy, —

CN, —

NO₂, —

NH₂, NH(C₁–

C₆ alkyl), N(C₁–

C₆ alkyl)(C₁–

C₆ alkyl), —

OH, —

C(O)NH₂, —

C(O)NH(C₁–

C₆ alkyl), —

C(O)N(C₁–

C₆ alkyl)(C₁–

C₆ alkyl), C₁–

C₆ alkoxy C₁–

C₆ alkyl, C₁–

C₆ thioalkoxy, and C₁–

C₆ thioalkoxy C₁–

C₆ alkyl.

26. A compound according to claim 25, wherein

R₄ is H;

C₁–

C₄ alkyl-NHC(O)R₅;

—

(CH₂)_0-4R₈;

—

C₁–

C₄ alkyl-NR₅₀CO₂R₅₁;

—

C≡

N;

—

CF₃;

—

CF₂—

CF₃;

—

C≡

CH;

—

CH₂—

CH═

CH₂;

—

(CH₂)_1-4—

R_4-1;

—

(CH₂)_1-4—

NH—

R_4-1;

(CH₂)_0-4—

NHC(O)—

(CH₂)_0-6—

R₅₂;

or —

(CH₂)_0-4—

R₅₃—

(CH₂)_0-4—

R₅₄.

27. A compound according to claim 26, wherein

X is C₁–

C₄ alkylidenyl optionally substituted with 1, 2, or 3 methyl groups;

or —

NR_4-6—

;

or

R₄ and R_4-6 combine to form —

(CH₂)_n10—

, wherein

n₁₀ is 1, 2, 3, or 4;

Z is selected from SO₂;

SO;

or S;

Y is selected from H;

C₁–

C₄ haloalkyl;

C₅–

C₆ heterocycloalkyl containing at least one N, O, or S;

phenyl;

OH;

—

N(Y₁)(Y₂);

C₁–

C₁₀ alkyl optionally substituted with 1 thru 3 substituents which can be the same or different and are 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;

phenyl optionally substituted with halogen, C₁–

C₄ alkyl, C₁–

C₄ alkoxy, CN or NO₂;

phenyl C₁–

C₄ alkyl optionally substituted with halogen, C₁–

C₄ alkyl, C₁–

C₄ alkoxy, CN or NO₂;

wherein

Y₁ and Y₂ are the same or different and are H;

C₁–

C₁₀ alkyl optionally substituted with 1, 2, or 3 substituents selected from the group consisting of halogen, C₁–

C₄ alkoxy, C₃–

C₈ cycloalkyl, and OH;

C₂–

C₆ alkenyl;

C₂–

C₆ alkanoyl;

phenyl;

—

SO₂—

C₁–

C₄ alkyl;

phenyl C₁–

C₄ alkyl; and

C₃–

C₈ cycloalkyl C₁–

C₄ alkyl;

or

—

N(Y₁)(Y₂) forms a ring selected from piperazinyl, piperidinyl, morpholinyl, and pyrolidinyl, wherein each ring is optionally substituted with 1, 2, 3, or 4 groups that are independently C₁–

C₆ alkyl, C₁–

C₆ alkoxy, C₁–

C₆ alkoxy C₁–

C₆ alkyl, or halogen.

28. A compound according to claim 27, wherein

R₁ is benzyl which is optionally substituted with 1, 2, 3, or 4 groups independently selected from halogen, C₁–

C₄ alkoxy, hydroxy, and C₁–

C₄ alkyl optionally substituted with 1, 2, or 3 substituents halogen, OH, SH, NH₂, NH(C₁–

C₆ alkyl), N—

(C₁–

C₆ alkyl)(C₁–

C₆ alkyl), C≡

N, CF₃;

R₂ and R₃ are independently selected from H or C₁–

C₄ alkyl optionally substituted with 1 substituent selected from halogen, —

OH, —

SH, —

C≡

N, —

CF₃, C₁–

C₃ alkoxy, NH₂, NH(C₁–

C₆ alkyl), and NH(C₁–

C₆ alkyl)(C₁–

C₆ alkyl);

R_C is C₁–

C₈ alkyl optionally substituted with 1, 2, or 3 groups independently selected from R₂₀₅, —

SH, —

C═

ONR₂₃₅R₂₄₀, and —

S(═

O)₂NR₂₃₅R₂₄₀;

—

(CH₂)_0-3—

(C₃–

C₆) cycloalkyl wherein the cycloalkyl is optionally substituted with 1, 2, or 3 groups independently selected from R₂₀₅, —

CO₂H, and —

CO₂—

(C₁–

C₄ alkyl);

—

(CR₂₄₅R₂₅₀)_0-4-phenyl optionally substituted with 1, 2, or 3 R₂₀₀;

—

(CR₂₄₅R₂₅₀)_0-3-pyridyl;

—

(CR₂₄₅R₂₅₀)_0-3-pyridazinyl;

—

(CR₂₄₅R₂₅₀)_0-3-pyrimidinyl;

—

(CR₂₄₅R₂₅₀)_0-3-pyrazinyl;

—

(CR₂₄₅R₂₅₀)_0-3-furyl;

—

(CR₂₄₅R₂₅₀)_0-3-indolyl;

—

(CR₂₄₅R₂₅₀)_0-3-thienyl;

—

(CR₂₄₅R₂₅₀)_0-3-pyrrolyl;

—

(CR₂₄₅R₂₅₀)_0-3-pyrazolyl;

(CR₂₄₅R₂₅₀)_0-3-benzoxazolyl;

—

(CR₂₄₅R₂₅₀)_0-3-imidazolyl;

each of the above heteroaryl groups is optionally substituted with 1, 2, 3, or 4 R₂₀₀;

—

(CR₂₄₅R₂₅₀)_0-3-imidazolidinyl;

(CR₂₄₅R₂₅₀)_0-3-tetrahydrofuryl;

(CR₂₄₅R₂₅₀)_0-3-tetrahydropyranyl;

(CR₂₄₅R₂₅₀)_0-3-piperazinyl;

(CR₂₄₅R₂₅₀)_0-3-pyrrolidinyl;

(CR₂₄₅R₂₅₀)_0-3-piperidinyl;

(CR₂₄₅R₂₅₀)_0-3-indolinyl;

each of the above heterocycloalkyl groups is optionally substituted with 1, 2, 3, or 4 R₂₁₀;

(CH₂)_0-1-CH((CH₂)_0-4—

OH)—

(CH₂)_0-1-phenyl;

—

(CH₂)_0-1 —

CH(C₁–

C₄ hydroxyalkyl)-(CH₂)_0-1-pyridyl;

R₂₀₀ at each occurrence is independently C₁–

C₆ alkyl optionally substituted with 1, 2, or 3 R₂₀₅ groups;

OH;

—

NO₂;

halogen;

—

CO₂H;

C≡

N;

—

(CH₂)_0-4—

CO—

NR₂₂₀R₂₂₅;

—

(CH₂)_0-4—

CO—

(C₁–

C₈ alkyl);

—

(CH₂)_0-4—

CO₂R₂₁₅; and

—

(CH₂)_0-4—

O—

(C₁–

C₆ alkyl optionally substituted with 1, 2, 3, or 5 —

F);

R₂₀₅ at each occurrence is independently C₁–

C₆ alkyl, halogen, —

OH, —

O-phenyl, —

SH, —

C≡

N, —

CF₃, C₁–

C₆ alkoxy, NH₂, NH(C₁–

C₆ alkyl), and N—

(C₁–

C₆ alkyl)(C₁–

C₆ alkyl);

R₂₁₀ at each occurrence is independently C₁–

C₆ alkyl optionally substituted with 1 or 2 R₂₀₅ groups;

halogen;

C₁–

C₄ alkoxy;

C₁–

C₄ haloalkoxy;

—

NR₂₂₀R₂₂₅;

OH;

C≡

N;

C₃–

C₇ cycloalkyl optionally substituted with 1 or 2 R₂₀₅ groups;

—

CO—

(C₁–

C₄ alkyl);

—

SO_{2 —}

NR₂₃₅R₂₄₀;

—

CO—

NR₂₃₅R₂₄₀;

—

SO₂—

(C₁–

C₄ alkyl); and

═

O;

wherein

R₂₁₅ at each occurrence is independently C₁–

C₆ alkyl, —

(CH₂)_0-2-(phenyl), C₃–

C₆ cycloalkyl, —

(CH₂)_0-2-(pyridyl), —

(CH₂)_0-2-(pyrrolyl), —

(CH₂)_0-2-(imidazolyl), —

(CH₂)_0-2-(pyrimidyl), —

(CH₂)_0-2-(pyrrolidinyl), —

(CH₂)_0-2-(imidazolidinyl) —

(CH₂)_0-2-(piperazinyl), —

(CH₂)_0-2-(piperidinyl), and —

(CH₂)_0-2-(morpholinyl);

wherein the phenyl group at each occurrence is optionally substituted with 1 or 2 groups that are independently R₂₀₅ or R₂₁₀;

wherein each heterocycloalkyl group at each occurrence is optionally substituted with 1 or 2 R₂₁₀;

wherein each heteroaryl group at each occurrence is optionally substituted with 1 or 2 R₂₁₀;

R₂₂₀ and R₂₂₅ at each occurrence are independently —

H, —

C₁–

C₄ alkyl, hydroxy C₁–

C₄ alkyl, halo C₁–

C₄ alkyl;

—

C₃–

C₆ cycloalkyl, and —

(C₁–

C₄ alkyl)-O—

(C₁–

C₂ alkyl);

R₂₃₅ and R₂₄₀ at each occurrence are independently H, or C₁–

C₆ alkyl;

R₂₄₅ and R₂₅₀ at each occurrence are independently H, C₁–

C₄ alkyl, C₁–

C₄ hydroxyalkyl, C₁–

C₄ alkoxy, C₁–

C₄ haloalkoxy, or

R₂₄₅ and R₂₅₀ are taken together with the carbon to which they are attached to form a carbocycle of 3, 5, or 6 carbon atoms.

29. A compound according to claim 28 wherein

R₄ is H;

C₁–

C₄ alkyl-NHC(O)R₅;

—

(CH₂)_0-4R₈;

—

C₁–

C₄ alkyl-NR₅₀CO₂R₅₁;

—

(CH₂)_1-4—

R_4-1;

—

(CH₂)_1-4-NH—

R_4-1;

(CH₂)_1-4—

NHC(O)—

(CH₂)_0-6—

R₅₂;

or —

(CH₂)_1-4—

R₅₃—

(CH₂)_0-4—

R₅₄;

wherein

R_4-1 is —

SO₂—

(C₁–

C₈ alkyl), —

SO₂—

NR_4-2R_4-3;

or —

CO—

NR_4-3R_4-4;

wherein

R_4-2 and R_4-3 are independently H, or C₁–

C₃ alkyl;

R_4-4 is C₁–

C₄ alkyl, phenyl C₁–

C₄ alkyl, C₂–

C₄ alkanoyl, or phenyl C₁–

C₄ alkanoyl;

R₅ is selected from the group consisting of cyclopropyl;

cyclopentyl;

cyclohexyl;

C₁–

C₆ alkyl optionally substituted with 1, 2, or 3 groups that are independently halogen, —

NR₆R₇, C₁–

C₄ alkoxy, C₅–

C₆ heterocycloalkyl, C₅–

C₆ heteroaryl, phenyl, C₃–

C₇ cycloalkyl, —

S—

C₁–

C₄ alkyl, —

SO₂—

C₁–

C₄ alkyl, —

CO₂H, —

CONR₆R₇, —

CO₂—

C₁–

C₄ alkyl, or phenyloxy;

pyridyl, thiazolyl, pyrazolyl, pyrazinyl, optionally substituted with 1, 2, or 3 groups that are independently C₁–

C₄ alkyl, C₁–

C₄ alkoxy, halogen, C₁–

C₄ haloalkyl, or OH;

piperidinyl, dihydropyridazinonyl, pyrrolidinonyl, thioxothiazolidinonyl, isoxazolyl, imidazolyl, indolyl, optionally substituted with 1, 2, or 3 groups that are independently C₁–

C₄ alkyl, C₁–

C₄ alkoxy, halogen, or C₂–

C₄ alkanoyl;

phenyl optionally substituted with 1, 2, 3, or 4 groups that are independently halogen, OH, C₁–

C₄ alkyl, C₁–

C₄ alkoxy, or C₁–

C₄ haloalkyl;

wherein

R₆ and R₇ are independently selected from the group consisting of H, C₁–

C₆ alkyl, C₂–

C₆ alkanoyl, phenyl, —

SO₂—

C₁–

C₄ alkyl, benzyl, and phenethyl;

R₈ is —

SO₂-thienyl optionally substituted with 1 or 2 groups that are independently C₁–

C₄ alkyl or halogen;

—

SO₂-phenyl, —

SO₂-piperidinyl, —

SO₂-pyrrolidinyl, imidazolidinyyl dione, —

C(O)NHR₉, —

S—

C₁–

C₆ alkyl, or —

S—

C₂–

C₄ alkanoyl, wherein

R₉ is phenyl C₁–

C₄ alkyl, C₁–

C₄ alkyl, or H;

R₅₀ is H or C₁–

C₄ alkyl;

R₅₁ is selected from benzyl;

phenethyl;

C₁–

C₆ alkyl optionally substituted with 1, 2, or 3 groups that are independently halogen, cyano, —

NR₆R₇, —

C(O)NR₆R₇, or —

C₁–

C₄ alkoxy;

heterocycloalkyl containing at least one N, O, or S and optionally substituted with 1 or 2 groups that are independently C₁–

C₄ alkyl, C₁–

C₄ alkoxy, halogen, C₂–

C₄ alkanoyl, phenyl C₁–

C₄ alkyl, and —

SO₂ C₁–

C₄ alkyl;

heterocycloalkylalkyl containing at least one N, O, or S and optionally substituted with 1 or 2 groups that are independently C₁–

C₄ alkyl, C₁–

C₄ alkoxy, halogen, C₂–

C₄ alkanoyl, phenyl C₁–

C₄ alkyl, and —

SO₂ C₁–

C₄ alkyl;

C₂–

C₆ alkenyl;

C₂–

C₆ alkynyl;

heteroaryl optionally substituted with 1, 2, or 3 groups that are independently OH, C₁–

C₄ alkyl, C₁–

C₄ alkoxy, halogen, NH₂, NH(C₁–

C₆ alkyl) or N(C₁–

C₆ alkyl)(C₁–

C₆ alkyl);

heteroarylalkyl containing at least one N, O, or S and optionally substituted with 1, 2, or 3 groups that are independently C₁–

C₄ alkyl, C₁–

C₄ alkoxy, halogen, NH₂, NH(C₁–

C₆ alkyl) or N(C₁–

C₆ alkyl)(C₁–

C₆ alkyl);

phenyl;

C₃–

C₆ cycloalkyl, and C₃–

C₆ cycloalkyl C₁–

C₄ alkyl, wherein the phenyl;

C₃–

C₆ cycloalkyl, and C₃–

C₆ cycloalkyl C₁–

C₄ alkyl groups are optionally substituted with 1, 2, or 3 groups that are independently halogen, CN, NO₂, C₁–

C₄ alkyl, C₁–

C₄ alkoxy, C₂–

C₆ alkanoyl, C₁–

C₄ haloalkyl, C₁–

C₄ haloalkoxy, hydroxy, C₁–

C₄ hydroxyalkyl, C₁–

C₄ thioalkoxy;

R₅₂ is heterocycloalkyl, heteroaryl, phenyl, C₃–

C₆ cycloalkyl, —

S(O)_0-2—

C₁–

C₆ alkyl, CO₂H, —

C(O)NH₂, —

C(O)NH(alkyl), —

C(O)N(alkyl)(alkyl), —

CO₂-alkyl, —

NHS(O)_0-2—

C₁–

C₆ alkyl, —

N(alkyl)S(O)_0-2—

C₁–

C₆ alkyl, —

S(O)_0-2-heteroaryl, —

S(O)_0-2-aryl, —

NH(arylalkyl), —

N(alkyl)(arylalkyl), thioalkoxy, or alkoxy, each of which is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently C₁–

C₄ alkyl, C₁–

C₄ alkoxy, C₁–

C₄ thioalkoxy, halogen, C₁–

C₄ haloalkyl, haloalkoxy, C₂–

C₆ alkanoyl, NO₂, CN, C₁–

C₄ alkoxycarbonyl, or aminocarbonyl;

R₅₃ is absent, —

O—

, —

C(O)—

, —

NH—

, —

N(alkyl)-, —

NH—

S(O)_0-2—

, —

N(alkyl)-S(O)_0-2—

, —

S(O)_0-2—

NH—

, or —

S(O)_0-2—

N(alkyl)-;

R₅₄ is pyridyl, thienyl, imidazolyl, phenyl, phenyl C₁–

C₄ alkyl, piperidyl, pyrrolidinyl, imidazolidinyl dione, CO₂H, —

CO₂-alkyl, —

C(O)NH(alkyl), —

C(O)N(alkyl) (alkyl), —

C(O)NH₂, C₁–

C₈ alkyl, OH, phenyloxy, alkoxy, phenylalkoxy, NH₂, NH(alkyl), N(alkyl)(alkyl), or —

C₁–

C₆ alkyl-CO₂—

C₁–

C₆ alkyl, each of which is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently alkyl, alkoxy, CO₂H, —

CO₂—

alkyl, thioalkoxy, halogen, haloalkyl, haloalkoxy, hydroxyalkyl, alkanoyl, NO₂, CN, alkoxycarbonyl, or aminocarbonyl.

30. A compound according to claim 29 of the formula:

31. A compound according to claim 29 of the formula:

32. A compound according to claim 1, wherein

R₄ is —

C₁–

C₄ alkyl-NR₅₀CO₂R₅₁;

—

(CH₂)_1-4—

NH—

R_4-1;

or (CH₂)_1-4—

NHC (O)—

(CH₂)_0-6—

R₅₂;

wherein

R₅₀ is H or C₁–

C₄ alkyl;

R₅₁ is selected from benzyl;

phenethyl;

C₁–

C₆ alkyl optionally substituted with 1, 2, or 3 groups that are independently halogen, cyano, —

NR₆R₇, —

C(O)NR₆R₇, or —

C₁–

C₄ alkoxy;

heterocycloalkyl containing at least one N, O, or S and optionally substituted with 1 or 2 groups that are independently C₁–

C₄ alkyl, C₁–

C₄ alkoxy, halogen, C₂–

C₄ alkanoyl, phenyl C₁–

C₄ alkyl, and —

SO₂ C₁–

C₄ alkyl;

heterocycloalkylalkyl containing at least one N, O, or S and optionally substituted with 1 or 2 groups that are independently C₁–

C₄ alkyl, C₁–

C₄ alkoxy, halogen, C₂–

C₄ alkanoyl, phenyl C₁–

C₄ alkyl, and —

SO₂ C₁–

C₄ alkyl;

C₂–

C₆ alkenyl;

C₂–

C₆ alkynyl;

heteroaryl optionally substituted with 1, 2, or 3 groups that are independently OH, C₁–

C₄ alkyl, C₁–

C₄ alkoxy, halogen, NH₂, NH(C₁–

C₆ alkyl) or N(C₁–

C₆ alkyl)(C₁–

C₆ alkyl);

heteroarylalkyl containing at least one N, O, or S and optionally substituted with 1, 2, or 3 groups that are independently C₁–

C₄ alkyl, C₁–

C₄ alkoxy, halogen, NH₂, NH(C₁–

C₆ alkyl) or N(C₁–

C₆ alkyl)(C₁–

C₆ alkyl);

phenyl;

C₃–

C₆ cycloalkyl, and C₃–

C₆ cycloalkyl C₁–

C₄ alkyl, wherein the phenyl;

C₃–

C₆ cycloalkyl, and C₃–

C₆ cycloalkyl C₁–

C₄ alkyl groups are optionally substituted with 1, 2, or 3 groups that are independently halogen, CN, NO₂, C₁–

C₄ alkyl, C₁–

C₄ alkoxy, C₂–

C₆ alkanoyl, C₁–

C₄ haloalkyl, C₁–

C₄ haloalkoxy, hydroxy, C₁–

C₄ hydroxyalkyl, C₁–

C₄ thioalkoxy;

R₆ and R₇ are independently selected from the group consisting of H, C₁–

C₆ alkyl, C₂–

C₆ alkanoyl, phenyl, —

SO₂—

C₁–

C₄ alkyl, benzyl, and phenethyl;

R₅₂ is heterocycloalkyl, heteroaryl, phenyl, C₃–

C₆ cycloalkyl, —

S(O)_0-2—

C₁–

C₆ alkyl, CO₂H, —

C(O)NH₂, —

C(O)NH(alkyl), —

C(O)N(alkyl)(alkyl), —

CO₂-alkyl, —

NHS(O)_0-2—

C₁–

C₆ alkyl, —

N(alkyl)S(O)_0-2—

C₁–

C₆ alkyl, —

S(O)_0-2-heteroaryl, —

S(O)_0-2-aryl, —

NH(arylalkyl), —

N(alkyl)(arylalkyl), thioalkoxy, or alkoxy, each of which is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently C₁–

C₄ alkyl, C₁–

C₄ alkoxy, C₁–

C₄ thioalkoxy, halogen, C₁–

C₄ haloalkyl, haloalkoxy, C₂–

C₆ alkanoyl, NO₂, CN, C₁–

C₄ alkoxycarbonyl, or aminocarbonyl.

33. A compound according to claim 32, wherein

R₄ is —

O—

C₁–

C₄ alkanoyl;

OH;

phenyloxy or napthyloxy, each of which is optionally substituted with 1, 2, or 3 groups that are independently halogen, C₁–

C₄ alkyl, CO₂H, —

C(O)—

C₁–

C₄ alkoxy, or C₁–

C₄ alkoxy;

C₁–

C₆ alkoxy;

phenyl C₁–

C₄ alkoxy;

—

O—

(CH₂)_n6—

R_4-1;

or —

S—

(CH₂)_n6—

R_4-1

R_4-1 is —

SO₂—

(C₁–

C₈ alkyl), —

SO₂—

NR_4-2R_4-3;

or —

CO—

NR_4-3R_4-4;

wherein

R_4-2 and R_4-3 are independently H, or C₁–

C₃ alkyl;

R_4-4 is C₁–

C₄ alkyl, phenyl C₁–

C₄ alkyl, C₂–

C₄ alkanoyl, or phenyl C₁–

C₄ alkanoyl.

34. A method for the treatment of Alzheimer'"'"'s disease, mild cognitive impairment Down'"'"'s syndrome, Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch-Type, cerebral amyloid angiopathy, other degenerative dementias, dementias of mixed vascular and degenerative origin, dementia associated with Parkinson'"'"'s disease, dementia associated with progressive supranuclear palsy, dementia associated with cortical basal degeneration, diffuse Lewy body type of Alzheimer'"'"'s disease compriseing administration of a therapeutically effective amount of a compound or salt according to claim 1, to a patient in need thereof.

35. A method of treatment as in claim 34, wherein the patient is a human.

36. A method of treatment according to claim 34, wherein the disease is dementia.

37. A method according to claim 34, wherein the treatment is of Alzheimer'"'"'s disease.