Hydroxypropyl amides for the treatment of Alzheimer's disease

• US 7,262,208 B2
• Filed: 04/30/2003
• Issued: 08/28/2007
• Est. Priority Date: 04/30/2002
• 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: John, Varghese, Beck, James P., Brogley, Louis, Pulley, Shon R., Tucker, John A., Jacobs, Jon S., Sherer, Brian A., Xu, Ying Zi
• Primary Examiner(s): AULAKH, CHARANJIT
• Application Number:
  US10/427,106
• Publication Number:
  US 20040039034A1
• Time in Patent Office: 1,581 Days
• Field of Search: 514/330, 514/378, 514/588, 514/616, 514/416, 546/226, 546/210, 546/316, 548/240, 548/250, 548/335.1, 548/470, 549/74, 564/152
• US Class Current: 514/330
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: C07C 233/78 with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
• CPC Class Codes: C07C 235/10 having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by nitrogen atoms not being part of nitro or nitroso groups
• CPC Class Codes: C07C 235/34 having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
• CPC Class Codes: C07C 235/74 of a saturated carbon skeleton
• CPC Class Codes: C07C 237/20 the carbon skeleton containing six-membered aromatic rings
• CPC Class Codes: C07C 2601/02 with a three-membered ring
• CPC Class Codes: C07C 2601/10 the ring being unsaturated
• CPC Class Codes: C07C 271/22 to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
• CPC Class Codes: C07C 275/24 containing six-membered aromatic rings
• CPC Class Codes: C07C 279/28 having nitrogen atoms of guanidine groups bound to cyano groups, e.g. cyanoguanidines, dicyandiamides
• CPC Class Codes: C07C 311/05 to acyclic carbon atoms of hydrocarbon radicals substituted by nitrogen atoms, not being part of nitro or nitroso groups
• CPC Class Codes: C07D 209/46 with an oxygen atom in position 1
• CPC Class Codes: C07D 211/62 attached in position 4
• CPC Class Codes: C07D 213/56 Amides
• CPC Class Codes: C07D 215/38 Nitrogen atoms nitro radicals C07D215/18
• CPC Class Codes: C07D 239/42 One nitrogen atom nitro radicals C07D239/30
• CPC Class Codes: C07D 261/08 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 307/33 in position 2, the oxygen atom being in its keto or unsubstituted enol form
• CPC Class Codes: C07D 333/22 Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom
• CPC Class Codes: C07D 333/24 : 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 401/06 : linked by a carbon chain containing only aliphatic carbon atoms

Abstract

The present invention relates to compounds of formula (I):

useful in treating Alzheimer'"'"'s disease and other similar diseases. These compounds include inhibitors of the beta-secretase enzyme that are useful in the treatment of Alzheimer'"'"'s disease and other diseases characterized by deposition of A beta peptide in a mammal. The compounds of the invention are useful in pharmaceutical compositions and methods of treatment to reduce A beta peptide formation.

Claims

1. A compound of formula I:

2. A compound according to claim 1 wherein

R₁ and Y together form —

C₁–

C₆ alkyl-aryl, —

C₁–

C₆ alkyl-heteroaryl, or —

C₁–

C₆ alkyl-heterocyclyl, where the ring portions of each are optionally substituted with 1, 2, 3, or 4 groups independently selected from halogen, —

OH, —

SH, —

C≡

N, —

NO₂, —

NR₁₀₅R′

₁₀₅, —

CO₂R, —

N(R)COR′

, or —

N(R)SO₂R′

, —

C(═

O)—

(C₁–

C₄)alkyl, —

SO₂-amino, —

SO₂-mono or dialkylamino, —

C(═

O)-amino, —

C(═

O)-mono or dialkylamino, —

SO₂—

(C₁–

C₄)alkyl, or

C₁–

C₆ alkoxy optionally substituted with 1, 2, or 3 groups which are independently selected from halogen, or

C₃–

C₇, cycloalkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, —

OH, —

SH, —

C≡

N, —

CF₃, C₁–

C₃ alkoxy, amino, —

C₁–

C₆ alkyl and mono- or dialkylamino, or

C₁–

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

OH, —

SH, —

C≡

N, —

CF₃, —

C₁–

C₃ alkoxy, amino, mono- or dialkylamino and —

C₁–

C₃ alkyl, or

C₂–

C₁₀ alkenyl or C₂–

C₁₀ alkynyl each of which is optionally substituted with 1, 2, or 3 groups independently selected from halogen, —

OH, —

SH, —

C≡

N, —

CF₃, C₁–

C₃ alkoxy, amino, C₁–

C₆ alkyl and mono- or dialkylamino; and

the heterocyclyl group is optionally further substituted with oxo.

3. A compound according to claim 1 wherein R₃, R₃′

, R₄ and R₅ are each hydrogen.

4. A compound according to claim 1 wherein

R₆ is —

(CR₂₄₅R₂₅₀)_0-4-aryl, —

(CR₂₄₅R₂₅₀)-_0-4-heteroaryl, —

(CR₂₄₅R₂₅₀)_0-4-heterocyclyl, —

(C₁–

C₆ alkyl)—

O—

(C₁–

C₆ alkyl)—

OH;

—

(C₁–

C₆ alkyl)—

O—

(C₁–

C₆ alkenyl);

—

(C₁–

C₆ alkyl)—

O—

(C₁–

C₆ alkyl)—

O—

(C₁–

C₆ alkyl);

—

(C₁–

C₆ alkyl)—

O—

(C₀-C₆ alkyl)-aryl;

—

(C₁–

C₆ alkyl)—

O—

(C₀–

C₆ alkyl)-cycloalkyl;

—

CH₂—

NH—

CH₂—

CH(—

O—

CH₂—

CH₃)₂, —

(CH₂)_0-6—

C(═

NR₂₃₅)(NR₂₃₅R₂₄₀), —

(C₂–

C₆ alkenyl)-heteroaryl, —

(CR₂₄₅R₂₅₀)_1-4—

N(R₂₃₅)—

C(═

O)—

O—

(C₁–

C₃ alkyl)-aryl, —

(CR₂₄₅R₂₅₀)_1-4—

N(R₂₃₅)—

C(═

O)—

(C₀–

C₃ alkyl)-aryl, —

(CR₂₄₅R₂₅₀)_1-4—

N(R₂₃₅)—

C(═

O)—

(C<sub>0–

C3</sub> alkyl)-heteroaryl, —

(CR₂₄₅R₂₅₀)_1-4—

C(═

O)—

aryl, —

(CR₂₄₅R₂₅₀)_1-4—

C(═

O)-heteroaryl, or

C₁–

C₁₀ alkyl optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R₂₀₅, cyclopentenyl, —

OC═

ONR₂₃₅R₂₄₀, —

S(═

O)_0-2(C₁–

C₆ alkyl), —

SH, —

NR₂₃₅C═

ONR₂₃₅R₂₄₀, —

C═

ONR₂₃₅R₂₄₀, —

NR₂₃₅—

C(═

O)—

O—

R₂₀₅, and —

S(═

O)₂NR₂₃₅R₂₄₀, —

NR₂₃₅C(═

O)—

(C₁–

C₆ alkyl), ═

O, or

—

(CH₂)_0-3—

(C₃–

C₈) cycloalkyl wherein the cycloalkyl is optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R₂₀₅, —

CO₂H, —

CO—

(C₁–

C₄ alkyl), —

CO—

NH₂, —

CO—

NH(C₁–

C₆ alkyl) and —

CO—

N—

(C₁–

C₆ alkyl)(C₁–

C₆ alkyl), or

C₂–

C₁₀ alkenyl or C₂–

C₁₀ alkynyl, each of which is optionally substituted with 1, 2, or 3 independently selected R₂₀₅ groups, wherein

each aryl and heteroaryl is optionally substituted with 1, 2, or 3 R₂₀₀, and wherein each heterocyclyl is optionally substituted with 1, 2, 3, or 4 independently selected R₂₁₀, and each cycloalkyl is optionally substituted with 1 or 2 R₂₀₅ groups.

5. A compound according to claim 1 selected from the group consisting of:

5-({5-[(tert-butoxycarbonyl)amino]pentanoyl}amino)-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(3E)-pent-3-enoylaminol]-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl }amino)-5-[(ethoxyacetyl)amino]-D-erythro-pentitol;

5-[(3-cyclopentylpropanoyl)amino]-1,2,4, 5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl }amino)-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-(pentanoylamino)-D-erythro-pentitol;

5-({6-[(tert-butoxycarbonyl)amino]hexanoyl}amino)-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

5-{[(benzyloxy)acetyl]amino}-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(4-phenylbutanoyl)amino]-D-erythro-pentitol;

5-({3-[1-(tert-butoxycarbonyl)piperidin-4-yl]propanoyl}amino)-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(methoxyacetyl)amino]-D-erythro-pentitol;

1,2,4,5-tetradeoxy-5-(3,5-difluorophenyl)-4-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-1-[(4-methylpentanoyl)amino]-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-5-{[4-(3,4-dimethoxyphenyl)butanoyl]amino}-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-{[4-(4-methoxyphenyl)butanoyl]amino}-D-erythro-pentitol;

5-{[3-(1-{6-[(tert-butoxycarbonyl)amino]hexanoyl}piperidin-4-yl)propanoyl]amino}-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

5-[(3-cyclohexylpropanoyl)amino]-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-({3-[1-(3-hydroxypropanoyl)piperidin-4-yl]propanoyl}amino)-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamnio)carbonyl]-5-methylbenzoyl}amino)-5-[(4-phenoxybutanoyl)amino]-D-erythro-pentitol;

1,2,4,5tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-{[(2E)-3-(2-thienyl)prop-2-enoyl]amino}-D-erythro-pentitol;

5-(butyrylamino)-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

5-[(butoxyacetyl)amino]-1,2,4,5-tetradeoxy-1-(3,5difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(4,4,4-trifluoro-3-methylbutanoyl)amino]-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(2-hydroxy-4-methylpentanoyl)amino]-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-{[4-(2-thienyl)butanoyl]amino}-D-erythro-pentitol;

5-[(cyclopropylacetyl)amino]-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl }amino)-D-erythro-pentitol;

5-({3-[1-(tert-butoxycarbonyl)piperidin-3-yl]propanoyl}amino)-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(3-hydroxybutanoyl)amino]-D-erythro-pentitol;

5-({3-[1-(6-aminohexanoyl)piperidin-4-yl]propanoyl}amino)-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

5-({4-[(tert-butoxycarbonyl)amino]butanoyl}amino)-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)5-[(5-methylhexanoyl)amino]-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-(hept-6-ynoylamino)-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-(pent-4enoylamino)-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-({3-[1-(1H-imidazol-5-ylacetyl)piperidin-4-yl]propanoyl}amino)-D-erythro-pentitol;

1-[(3-carboxypropanoyl)amino]-1,2,4,5-tetradeoxy-5-(3,5-difluorophenyl)-4-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-{[(2-methoxyethoxy)acetyl]amino}-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(3-{1-[3-(1H-imidazol-5-yl)propanoyl]piperidin-4-yl}propanoyl)amino]-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-(pent-4-ynoylamino)-D-erythro-pentitol;

5-[(cyclopent-2-en-1-ylacetyl)amino]-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(3methylpentanoyl)amino]-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(3-phenylpropanoyl)amino]-D-erythro-pentitol;

5-[(4-{[(benzyloxy)carbonyl]amino}-3-hydroxybutanoyl)amino]-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(3Z)-hex-3-enoylamino]-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(2-thienylacetyl)amino]-D-erythro-pentitol;

5-{[N-(cyclohexa-2,4-dien-1-ylacetyl)glycyl]amino}-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

5-({3-[1-(tert-butoxycarbonyl)piperidin-4-yl]butanoyl}amino)-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

5-{[4-(benzyloxy)butanoyl]amino}-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluoropheflyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(3-methoxypropanoyl)amino]-D-erythro-pentitol;

5-[(N-acetylglycyl)amino]-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluoropheflyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(6-oxoheptanoyl)amino]-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(5-oxohexanoyl)amino]-D-erythro-pentitol;

5-[(cycloheptylacetyl)amino]-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-5-[(3-{1-[4-(dimethylamino)butanoyl]piperidin-4-yl}propanoyl)amino]-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-{[(3R)-3-hydroxy-3 -phenylpropanoyl]amino}-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-{[N-(pyridin-3-ylcarbonyl)glycyl]amino}-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(5-oxo-5-phenylpentanoyl)amino]-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluoropheflyl)-5-({3-[1-(N,N-dimethylglycyl)piperidin-4-yl]propanoyl}amino)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

5-({N-[(benzyloxy)carbonyl]-β

-alanyl}amino)-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

5-[(N-benzoyl-N-methylglycyl)amino]-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

5-[(4-cyclohexylbutanoyl)amino]-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

5-{[(4R)-4-amino-5-phenylpentanoyl]amino}-1,2,4,5-tetradeoxy-1(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(3-pyridin-3-ylpropanoyl)amino]-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-{[3-(2-thienyl)propanoyl]amino}-D-erythro-pentitol;

5-{[N-(tert-butoxycarbonyl) -β

-alanyl]amino}-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

5-{[(2-butoxyethoxy)acetyl]amino}-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-5-{[4-(dimethylamino)butanoyl]amino}-2-({3-[(dipropylamino)carbonyl]-5 -methylbenzoyl}amino)-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluoropheflyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-{[(3S)-3-hydroxy-3-phenylpropanoyl]amino}-D-erythro-pentitol;

1,2,4,5-tetradeoxy-5-[(N,N-diethyl-β

-alanyl)amino]-1-(3,5-difluorophenyl) -2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

5-{[N-(tert-butoxycarbonyl)glycyl]amino}-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-{[3-(1H-imidazol-5-yl)propanoyl]amino}-D-erythro-pentitol;

5-{[3-(4-chlorophenoxy)propanoyl]amino}-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

1,2,4,5-tetradeoxy-5-({3-[1-(N,N-diethyl-β

-alanyl)piperidin-4-yl]propanoyl}amino)-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(3-piperidin-3-ylpropanoyl)amino]-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(3-piperidin-4-ylpropanoyl)amino]-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(1H-tetrazol-1-ylacetyl)amino]-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(1H-imidazol-5-ylacetyl)amino]-D-erythro-pentitol;

5-{[4-(acetylamino)butanoyl]amino}-1,2,4,5-tetradeoxy-1-(3,5 -difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(3-hydroxypropanoyl)amino]-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-{[(3-methylisoxazol-5-yl)acetyl]amino}-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-5-{[4-(dimethylamino)-4-oxobutanoyl]amino}-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-5-[(N,N-dimethylglycyl)amino]-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

5-[(4-aminobutanoyl)amino]-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

5-[(5-aminopentanoyl)amino]-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

5-[(6-aminohexanoyl)amino]-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-L-threo-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(N-methylglycyl)amino]-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(phenoxyacetyl)amino]-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-{[(1-oxo-1,3-dihydro-2H-isoindol-2-yl)acetyl]amino}-D-erythro-pentitol;

5-{[3-(allyloxy)propanoyl]amino}-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5- methylbenzoyl}amino)-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(2-hydroxyhexanoyl)amino]-D-erythro-pentitol;

5-β

-alanylamino)-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

5-{[N-(tert-butoxycarbonyl)-N-methylglycyl]amino}-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-{[(2S)-2-hydroxy-4-methylpentanoyl]amino}-D-erythro-pentitol;

5-({(4S) -4-[(tert-butoxycarbonyl)amino]-5-phenylpentanoyl}amino) -1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-(glycylamino)-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino) -5-[({[(1S,2R,5S)-2-isopropyl-5-methylcyclohexyl]oxy}acetyl)amino]-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[({[(1R, 2S, 5R) -2-isopropyl-5-methylcyclohexyl]oxy}acetyl)amino]-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino) -5-[(phenylacetyl)amino]-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(4-oxo-4-phenylbutanoyl)amino]-D-erythro-pentitol;

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(3-phenoxypropanoyl)amino]-D-erythro-pentitol; and

1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-{[4-oxo-4-(2-thienyl)butanoyl]amino}-D-erythro-pentitol. (S, S)—

N—

[4-Butyrylamino-1-(3,5-difluorobenzyl)-2- hudroxybutyl]-5-methyl-N′

, N′

-dipropyl-isophthalamide; and

3-[(3R, 4S)-6-([3-[1-(6-aminohexanoyl)piperidin-4- yl)propanoyl]amino)-3- (3,5-difluorobenzyl)-4-hydroxyhexanoyl]- 5-methyl-N,N-dipropylbenzamide.

6. A composition comprising a compound according to claim 1 and at least one pharmaceutically acceptable carrier, solvent, adjuvant or diluent.