Diaminediols for the treatment of Alzheimer's disease

• US 7,067,542 B2
• Filed: 07/10/2002
• Issued: 06/27/2006
• Est. Priority Date: 07/10/2001
• Status: Expired due to Fees

• Current Assignee: Pharmacia & Upjohn LLC (Pfizer Inc.)
• Original Assignee: Pharmacia & Upjohn Company (Pfizer Inc.)
• Inventors: Chrusciel, Robert A., Schostarez, Heinrich Josef
• Primary Examiner(s): Saeed, Kamal A.
• Assistant Examiner(s): Coppins, Janet L
• Application Number:
  US10/192,625
• Publication Number:
  US 20030083353A1
• Time in Patent Office: 1,448 Days
• Field of Search: 548/190, 548/200, 546/304, 546/314, 564/297, 564/300, 514/615, 514/649, 514/354, 514/423, 514/448, 514/471
• US Class Current: 514/354
• 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: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07C 235/84 with the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 255/44 at least one of the singly-bound nitrogen atoms being acylated
• CPC Class Codes: C07C 271/20 to carbon atoms of hydrocarbon radicals substituted by nitrogen atoms not being part of nitro or nitroso groups
• CPC Class Codes: C07C 323/42 Y being a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07D 213/82 in position 3
• CPC Class Codes: C07D 263/34 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 263/48 Nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 277/56 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen

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 the formula I:

2. A compound according to claim 1 with the proviso that neither R_N nor R_N′

is an alpha amino acid.

3. A compound according to claim 2 wherein

R₁ is C₁–

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

OH, ═

O, —

SH, —

C≡

N, —

CF₃, —

C₁–

C₃ alkoxy, —

S—

(C₁–

C₃)alkyl, amino, mono- or dialkylamino, —

N(R)C(O)R′

—

, —

OC(═

O)-amino and —

OC(═

O)-mono- or dialkylamino, or

R₁ is C₂–

C₆ alkenyl or C₂–

C₆ 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, and mono- or dialkylamino.

4. A compound according to claim 3 wherein

R₁′

is —

CH₂-phenyl where the phenyl ring is optionally substituted with 1, 2, 3, or 4 groups independently selected from halogen, C₁–

C₄ alkoxy, hydroxy, —

NO₂, and C₁–

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

C₆ alkyl), N—

(C₁–

C₆ alkyl)(C₁–

C₆ alkyl), C≡

N, CF₃.

5. A compound according to claim 4 wherein

R_N and R_N′

are independently —

C(═

O)—

(CRR′

)_0-6R₁₀₀; and

R′

₁₀₀ represents aryl, heteroaryl, heterocyclyl, where the ring portions of each are optionally substituted with 1, 2, or 3 groups independently selected from

—

OR, —

NO₂, C₁–

C₆ alkyl, halogen, —

C≡

N, —

OCF₃, —

CF₃, —

(CH₂)_0-4—

O—

P(═

O)(OR)(OR′

), —

(CH₂)_0-4—

CO—

NR₁₀₅R′

₁₀₅, —

(CH₂)_0-4—

O—

(CH₂)_0-4—

CONR₁₀₂R₁₀₂′

, —

(CH₂)_0-4—

CO—

(C₁–

C₁₂ alkyl), —

(CH₂)_0-4—

CO—

(C₂–

C₁₂ alkenyl), —

(CH₂)_0-4—

CO—

(C₂–

C₁₂ alkynyl), —

(CH₂)_0-4—

CO—

(CH₂)_0-4(C₃–

C₇ cycloalkyl), —

(CH₂)_0-4—

R₁₁₀, —

(CH₂)_0-4—

R₁₂₀, —

(CH₂)_0-4—

R₁₃₀, —

(CH₂)_0-4—

CO—

R₁₁₀, —

(CH₂)_0-4—

CO—

R₁₂₀, —

(CH₂)_0-4—

CO—

R₁₃₀, —

(CH₂)_0-4—

CO—

R₁₄₀, —

(CH₂)_0-4—

CO—

O—

R₁₅₀, —

(CH₂)_0-4—

SO₂—

NR₁₀₅R′

₁₀₅, —

(CH₂)_0-4—

SO—

(C₁–

C₈ alkyl), —

(CH₂)_0-4—

SO_2-(C₁–

C₁₂ alkyl), —

(CH₂)_0-4—

SO₂—

(CH₂)_0-4—

(C₃–

C₇ cycloalkyl), —

(CH₂)_0-4—

N(R₁₅₀)—

CO—

O—

R₁₅₀, —

(CH₂)_0-4—

N(R₁₅₀)—

CO—

N(R₁₅₀)₂, —

(CH₂)_0-4—

N(R₁₅₀)—

CS—

N(R₁₅₀)₂, —

(CH₂)_0-4—

N(R₁₅₀)—

CO—

R₁₀₅, —

(CH₂)_0-4—

NR₁₀₅R′

₁₀₅, —

(CH₂)_0-4—

R₁₄₀, —

(CH₂)_0-4—

O—

CO—

(C₁–

C₆ alkyl), —

(CH₂)_0-4—

O—

P(O)—

(O—

R₁₁₀)₂, —

(CH₂)_0-4—

O—

CO—

N(R₁₅₀)₂, —

(CH₂)_0-4—

O—

CS—

N(R₁₅₀)₂, —

(CH₂)_0-4—

O—

(R₁₅₀), —

(CH₂)_0-4—

O—

R₁₅₀′

—

COOH, —

(CH₂)_0-4—

S—

(R₁₅₀), —

(CH₂)_0-4—

N(R₁₅₀)—

SO₂—

R₁₀₅, —

(CH₂)_0-4—

C₃–

C₇ cycloalkyl, (C₂–

C₁₀)alkenyl, and (C₂–

C₁₀)alkynyl, or

R′

₁₀₀ is C₁–

C₁₀ alkyl optionally substituted with 1, 2, or 3 R₁₁₅ groups.

6. A compound according to claim 5 wherein

R_N′

is —

C(═

O)-aryl optionally substituted with 1, 2, or 3 groups independently selected from

—

OR, —

NO₂, C₁–

C₆ alkyl, halogen, —

C≡

N, —

OCF₃, —

CF₃, —

(CH₂)_0-4—

CO—

NR₁₀₅R′

₁₀₅, and —

(CH₂)_0-4—

N(R₁₅₀)—

SO₂—

R₁₀₅, or

R_N′

is —

C(═

O)—

C₁–

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

OH, —

CO₂R₁₀₂, —

C₁–

C₆ thioalkoxy, —

CO₂-phenyl, —

NR₁₀₅R′

₁₀₅, —

SO₂—

(C₁–

C₈ alkyl), —

C(═

O)R₁₈₀, R₁₈₀, —

CONR₁₀₅R′

₁₀₅, —

SO₂NR₁₀₅R′

₁₀₅, —

NH—

CO—

(C₁–

C₆ alkyl), —

NH—

CO—

R₁₁₀, —

NH—

CO—

R₁₂₀, —

NH—

C(═

O)—

OH, —

NH—

C(═

O)—

OR, —

NH—

C(═

O)—

O-phenyl, —

O—

C(═

O)—

(C₁–

C₆ alkyl), —

O—

C(═

O)-amino, —

O—

C(═

O)-mono- or dialkylamino, —

O—

C(═

O)-phenyl, —

O—

(C₁–

C₆ alkyl)-CO₂H, —

NH—

SO₂—

(C₁–

C₆ alkyl), C₁–

C₆ alkoxy and C₁–

C₆ haloalkoxy.

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

5-(acetylamino)-1,2,5,6-tetradeoxy-2-[({2-[methyl(methylsulfonyl)amino]-1,3-thiazol-4-yl}carbonyl)amino]-1-phenyl-D-glucitol,

5-(benzoylamino)-1,2,5,6-tetradeoxy-2-[({2-[methyl(methylsulfonyl)amino]-1,3-thiazol-4-yl}carbonyl)amino]-1-phenyl-D-glucitol,

N-[(1S,2R,3R,4R)-4-(acetylamino)-1-benzyl-2,3-dihydroxyoctyl]-2-[methyl(methylsulfonyl)amino]-1,3-thiazole-4-carboxamide,

N-[(1S,2R,3R,4R)-4-(benzoylamino)-1-benzyl-2,3-dihydroxyoctyl]-2-[methyl(methylsulfonyl)amino]-1,3-thiazole-4-carboxamide,

5-(acetylamino)-1,2,5,6-tetradeoxy-7-S-methyl-2-[({2-[methyl(methylsulfonyl)amino]-1,3-thiazol-4-yl}carbonyl)amino]-1-phenyl-7-thio-D-gluco-heptitol,

5-(benzoylamino)-1,2,5,6-tetradeoxy-7-S-methyl-2-[({2-[methyl(methylsulfonyl)amino]-1,3-thiazol-4-yl}carbonyl)amino]-1-phenyl-7-thio-D-gluco-heptitol,

5-(acetylamino)-1,2,5,6-tetradeoxy-7-O-methyl-2-[({2-[methyl(methylsulfonyl)amino]-1,3-thiazol-4-yl}carbonyl)amino]-1-phenyl-D-gluco-heptitol,

5-(benzoylamino)-1,2,5,6-tetradeoxy-7-O-methyl-2-[({2-[methyl(methylsulfonyl)amino]-1,3-thiazol-4-yl}carbonyl)amino]-1-phenyl-D-gluco-heptitol,

5-(acetylamino)-6-cyano-1,2,5,6-tetradeoxy-2-[({2-[methyl(methylsulfonyl)amino]-1,3-thiazol-4-yl}carbonyl)amino]-1-phenyl-D-glucitol,

5-(benzoylamino)-6-cyano-1,2,5,6-tetradeoxy-2-[({2-[methyl(methylsulfonyl)amino]-1,3-thiazol-4-yl}carbonyl)amino]-1-phenyl-D-glucitol,

5-(acetylamino)-1,2,5,6-tetradeoxy-2-[({2-[(methylsulfonyl)amino]-1,3-thiazol-4-yl}carbonyl)amino]-1-phenyl-D-glucitol,

5-(benzoylamino)-1,2,5,6-tetradeoxy-2-[({2-[(methylsulfonyl)amino]-1,3-thiazol-4-yl}carbonyl)amino]-1-phenyl-D-glucitol,

N-[(1S,2R,3R,4R)-4-(acetylamino)-1-benzyl-2,3-dihydroxyoctyl]-2-[(methylsulfonyl)amino]-1,3-thiazole-4-carboxamide,

N-[(1S,2R,3R,4R)-4-(benzoylamino)-1-benzyl-2,3-dihydroxyoctyl]-2-[(methylsulfonyl)amino]-1,3-thiazole-4-carboxamide,

5-(acetylamino)-1,2,5,6-tetradeoxy-7-S-methyl-2-[({2-[(methylsulfonyl)amino]-1,3-thiazol-4-yl}carbonyl)amino]-1-phenyl-7-thio-D-gluco-heptitol,

5-(benzoylamino)-1,2,5,6-tetradeoxy-7-S-methyl-2-[({2-[(methylsulfonyl)amino]-1,3-thiazol-4-yl}carbonyl)amino]-1-phenyl-7-thio-D-gluco-heptitol,

5-(acetylamino)-1,2,5,6-tetradeoxy-7-O-methyl-2-[({2-[(methylsulfonyl)amino]-1,3-thiazol-4-yl}carbonyl)amino]-1-phenyl-D-gluco-heptitol,

5-(benzoylamino)-1,2,5,6-tetradeoxy-7-O-methyl-2-[({2-[(methylsulfonyl)amino]-1,3-thiazol-4-yl}carbonyl)amino]-1-phenyl-D-gluco-heptitol,

5-(acetylamino)-6-cyano-1,2,5,6-tetradeoxy-2-[({2-[(methylsulfonyl)amino]-1,3-thiazol-4-yl}carbonyl)amino]-1-phenyl-D-glucitol,

5-(benzoylamino)-6-cyano-1,2,5,6-tetradeoxy-2-[({2-[(methylsulfonyl)amino]-1,3-thiazol-4-yl}carbonyl)amino]-1-phenyl-D-glucitol,

5-(acetylamino)-1,2,5,6-tetradeoxy-2-[({2-[methyl(methylsulfonyl)amino]-1,3-oxazol-4-yl}carbonyl)amino]-1-phenyl-D-glucitol,

5-(benzoylamino)-1,2,5,6-tetradeoxy-2-[({2-[methyl(methylsulfonyl)amino]-1,3-oxazol-4-yl}carbonyl)amino]-1-phenyl-D-glucitol,

N-[(1S,2R,3R,4R)-4-(acetylamino)-1-benzyl-2,3-dihydroxyoctyl]-2-[methyl(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide,

N-[(1S,2R,3R,4R)-4-(benzoylamino)-1-benzyl-2,3-dihydroxyoctyl]-2-[methyl(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide,

5-(acetylamino)-1,2,5,6-tetradeoxy-7-S-methyl-2-[({2-[methyl(methylsulfonyl)amino]-1,3-oxazol-4-yl}carbonyl)amino]-1-phenyl-7-thio-D-gluco-heptitol,

5-(benzoylamino)-1,2,5,6-tetradeoxy-7-S-methyl-2-[({2-[methyl(methylsulfonyl)amino]-1,3-oxazol-4-yl}carbonyl)amino]-1-phenyl-7-thio-D-gluco-heptitol,

5-(acetylamino)-1,2,5,6-tetradeoxy-7-O-methyl-2-[({2-[methyl(methylsulfonyl)amino]-1,3-oxazol-4-yl}carbonyl)amino]-1-phenyl-D-gluco-heptitol,

5-(benzoylamino)-1,2,5,6-tetradeoxy-7-O-methyl-2-[({2-[methyl(methylsulfonyl)amino]-1,3-oxazol-4-yl}carbonyl)amino]-1-phenyl-D-gluco-heptitol,

5-(acetylamino)-6-cyano-1,2,5,6-tetradeoxy-2-[({2-[methyl(methylsulfonyl)amino]-1,3-oxazol-4-yl}carbonyl)amino]-1-phenyl-D-glucitol,

5-(benzoylamino)-6-cyano-1,2,5,6-tetradeoxy-2-[({2-[methyl(methylsulfonyl)amino]-1,3-oxazol-4-yl}carbonyl)amino]-1-phenyl-D-glucitol,

5-(acetylamino)-1,2,5,6-tetradeoxy-2-[({2-[(methylsulfonyl)amino]-1,3-oxazol-4-yl}carbonyl)amino]-1-phenyl-D-glucitol,

5-(benzoylamino)-1,2,5,6-tetradeoxy-2-[({2-[(methylsulfonyl)amino]-1,3-oxazol-4-yl}carbonyl)amino]-1-phenyl-D-glucitol,

N-[(1S,2R,3R,4R)-4-(acetylamino)-1-benzyl-2,3-dihydroxyoctyl]-2-[(methylsulfonyl)amino]-1,3-oxazol-4-carboxamide,

N-[(1S,2R,3R,4R)-4-(benzoylamino)-1-benzyl-2,3-dihydroxyoctyl]-2-[(methylsulfonyl)amino]-1,3-oxazol-4-carboxamide,

5-(acetylamino)-1,2,5,6-tetradeoxy-7-S-methyl-2-[({2-[(methylsulfonyl)amino]-1,3-oxazol-4-yl}carbonyl)amino]-1-phenyl-7-thio-D-gluco-heptitol,

5-(benzoylamino)-1,2,5,6-tetradeoxy-7-S-methyl-2-[({2-[(methylsulfonyl)amino]-1,3-oxazol-4-yl}carbonyl)amino]-1-phenyl-7-thio-D-gluco-heptitol,

5-(acetylamino)-1,2,5,6-tetradeoxy-7-O-methyl-2-[({2-[(methylsulfonyl)amino]-1,3-oxazol-4-yl}carbonyl)amino]-1-phenyl-D-gluco-heptitol,

5-(benzoylamino)-1,2,5,6-tetradeoxy-7-O-methyl-2-[({2-[(methylsulfonyl)amino]-1,3-oxazol-4-yl}carbonyl)amino]-1-phenyl-D-gluco-heptitol,

5-(acetylamino)-6-cyano-1,2,5,6-tetradeoxy-2-[({2-[(methylsulfonyl)amino]-1,3-oxazol-4-yl}carbonyl)amino]-1-phenyl-D-glucitol,

5-(benzoylamino)-6-cyano-1,2,5,6-tetradeoxy-2-[({2-[(methylsulfonyl)amino]-1,3-oxazol-4-yl}carbonyl)amino]-1-phenyl-D-glucitol,

5-(acetylamino)-1,2,5,6-tetradeoxy-1-(3,5difluorophenyl)-2-[({2-[methyl(methylsulfonyl)amino]-1,3-thiazol-4-yl}carbonyl)amino]-D-glucitol,

5-(benzoylamino)-1,2,5,6-tetradeoxy-1-(3,5difluorophenyl)-2-[({2-[methyl(methylsulfonyl)amino]-1,3-thiazol-4-yl}carbonyl)amino]-D-glucitol,

N-[(1S,2R,3R,4R)-4-(acetylamino)-1-(3,5-difluorobenzyl)-2,3-dihydroxyoctyl]-2-[methyl(methylsulfonyl)amino]-1,3-thiazole-4-carboxamide,

N-[(1S,2R,3R,4R)-4-(benzoylamino)-1-(3,5-difluorobenzyl)-2,3-dihydroxyoctyl]-2-[methyl(methylsulfonyl)amino]-1,3-thiazole-4-carboxamide,

5-(acetylamino)-1,2,5,6-tetradeoxy-1-(3,5-difluorophenyl)-7-S-methyl-2-[({2-[methyl(methylsulfonyl)amino]-1,3-thiazol-4-yl}carbonyl)amino]-7-thio-D-gluco-heptitol,

5-(benzoylamino)-1,2,5,6-tetradeoxy-1-(3,5-difluorophenyl)-7-S-methyl-2-[({2-[methyl(methylsulfonyl)amino]-1,3-thiazol-4-yl}carbonyl)amino]-7-thio-D-gluco-heptitol,

5-(acetylamino)-1,2,5,6-tetradeoxy-1-(3,5-difluorophenyl)-7-O-methyl-2-[({2-[methyl(methylsulfonyl)amino]-1,3-thiazol-4-yl}carbonyl)amino]-D-gluco-heptitol,

5-(benzoylamino)-1,2,5,6-tetradeoxy-1-(3,5-difluorophenyl)-7-O-methyl-2-[({2-[methyl(methylsulfonyl)amino]-1,3-thiazol-4-yl}carbonyl)amino]-D-gluco-heptitol,

5-(acetylamino)-6-cyano-1,2,5,6-tetradeoxy-1-(3,5-difluorophenyl)-2-[({2-[methyl(methylsulfonyl)amino]-1,3-thiazol-4-yl}carbonyl)amino]-D-glucitol,

5-(benzoylamino)-6-cyano-1,2,5,6-tetradeoxy-1-(3,5-difluorophenyl)-2-[({2-[methyl(methylsulfonyl)amino]-1,3-thiazol-4-yl}carbonyl)amino]-D-glucitol,

5-(acetylamino)-1,2,5,6-tetradeoxy-1-(3,5-difluorophenyl)-2-[({2-[(methylsulfonyl)amino]-1,3-thiazol-4-yl}carbonyl)amino]-D-glucitol,

5-(benzoylamino)-1,2,5,6-tetradeoxy-1-(3,5-difluorophenyl)-2-[({2-[(methylsulfonyl)amino]-1,3-thiazol-4-yl}carbonyl)amino]-D-glucitol,

N-[(1S,2R,3R,4R)-4-(acetylamino)-1-(3,5-difluorobenzyl)-2,3-dihydroxyoctyl]-2-[(methylsulfonyl)amino]-1,3-thiazole-4-carboxamide,

N-[(1S,2R,3R,4R)-4-(benzoylamino)-1-(3,5-difluorobenzyl)-2,3-dihydroxyoctyl]-2-[(methylsulfonyl)amino]-1,3-thiazole-4-carboxamide,

5-(acetylamino)-1,2,5,6-tetradeoxy-1-(3,5-difluorophenyl)-7-S-methyl-2-[({2-[(methylsulfonyl)amino]-1,3-thiazol-4-yl}carbonyl)amino]-7-thio-D-gluco-heptitol,

5-(benzoylamino)-1,2,5,6-tetradeoxy-1-(3,5-difluorophenyl)-7-S-methyl-2-[({2-[(methylsulfonyl)amino]-1,3-thiazol-4-yl}carbonyl)amino]-7-thio-D-gluco-heptitol,

5-(acetylamino)-1,2,5,6-tetradeoxy-1-(3,5-difluorophenyl)-7-O-methyl-2-[({2-[(methylsulfonyl)amino]-1,3-thiazol-4-yl}carbonyl)amino]-D-gluco-heptitol,

5-(benzoylamino)-1,2,5,6-tetradeoxy-1-(3,5-difluorophenyl)-7-O-methyl-2-[({2-[(methylsulfonyl)amino]-1,3-thiazol-4-yl}carbonyl)amino]-D-gluco-heptitol,

5-(acetylamino)-6-cyano-1,2,5,6-tetradeoxy-1-(3,5-difluorophenyl)-2-[({2-[(methylsulfonyl)amino]-1,3-thiazol-4-yl}carbonyl)amino]-D-glucitol,

5-(benzoylamino)-6-cyano-1,2,5,6-tetradeoxy-1-(3,5-difluorophenyl)-2-[({2-[(methylsulfonyl)amino]-1,3-thiazol-4-yl}carbonyl)amino]-D-glucitol,

5-(acetylamino)-1,2,5,6-tetradeoxy-1-(3,5-difluorophenyl)-2-[({2-[methyl(methylsulfonyl)amino]-1,3-oxazol-4-yl}carbonyl)amino]-D-glucitol,

5-(benzoylamino)-1,2,5,6-tetradeoxy-1-(3,5-difluorophenyl)-2-[({2-[methyl(methylsulfonyl)amino]-1,3-oxazol-4-yl}carbonyl)amino]-D-glucitol,

N-[(1S,2R,3R,4R)-4-(acetylamino)-1-(3,5-difluorobenzyl)-2,3-dihydroxyoctyl]-2-[methyl(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide,

N-[(1S,2R,3R,4R)-4-(benzoylamino)-1-(3,5-difluorobenzyl)-2,3-dihydroxyoctyl]-2-[methyl(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide,

5-(acetylamino)-1,2,5,6-tetradeoxy-1-(3,5-difluorophenyl)-7-S-methyl-2-[({2-[methyl(methylsulfonyl)amino]-1,3-oxazol-4-yl}carbonyl)amino]-7-thio-D-gluco-heptitol,

5-(benzoylamino)-1,2,5,6-tetradeoxy-1-(3,5-difluorophenyl)-7-S-methyl-2-[({2-[methyl(methylsulfonyl)amino]-1,3-oxazol-4-yl}carbonyl)amino]-7-thio-D-gluco-heptitol,

5-(acetylamino)-1,2,5,6-tetradeoxy-1-(3,5-difluorophenyl)-7-O-methyl-2-[({2-[methyl(methylsulfonyl)amino]-1,3-oxazol-4-yl}carbonyl)amino]-D-gluco-heptitol,

5-(benzoylamino)-1,2,5,6-tetradeoxy-1-(3,5-difluorophenyl)-7-O-methyl-2-[({2-[methyl(methylsulfonyl)amino]-1,3-oxazol-4-yl}carbonyl)amino]-D-gluco-heptitol,

5-(acetylamino)-6-cyano-1,2,5,6-tetradeoxy-1-(3,5-difluorophenyl)-2-[({2-[methyl(methylsulfonyl)amino]-1,3-oxazol-4-yl}carbonyl)amino]-D-glucitol,

5-(benzoylamino)-6-cyano-1,2,5,6-tetradeoxy-1-(3,5-difluorophenyl)-2-[({2-[methyl(methylsulfonyl)amino]-1,3-oxazol-4-yl}carbonyl)amino]-D-glucitol,

5-(acetylamino)-1,2,5,6-tetradeoxy-1-(3,5-difluorophenyl)-2-[({2-[(methylsulfonyl)amino]-1,3-oxazol-4-yl}carbonyl)amino]-D-glucitol,

5-(benzoylamino)-1,2,5,6-tetradeoxy-1-(3,5-difluorophenyl)-2-[({2-[(methylsulfonyl)amino]-1,3-oxazol-4-yl}carbonyl)amino]-D-glucitol,

N-[(1S,2R,3R,4R)-4-(acetylamino)-1-(3,5-difluorobenzyl)-2,3-dihydroxyoctyl]-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide,

N-[(1S,2R,3R,4R)-4-(benzoylamino)-1-(3,5-difluorobenzyl)-2,3-dihydroxyoctyl]-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide,

5-(acetylamino)-1,2,5,6-tetradeoxy-1-(3,5-difluorophenyl)-7-S-methyl-2-[({2-[(methylsulfonyl)amino]-1,3-oxazol-4-yl}carbonyl)amino]-7-thio-D-gluco-heptitol,

5-(benzoylamino)-1,2,5,6-tetradeoxy-1-(3,5-difluorophenyl)-7-S-methyl-2-[({2-[(methylsulfonyl)amino]-1,3-oxazol-4-yl}carbonyl)amino]-7-thio-D-gluco-heptitol,

5-(acetylamino)-1,2,5,6-tetradeoxy-1-(3,5-difluorophenyl)-7-O-methyl-2-[({2-[(methylsulfonyl)amino]-1,3-oxazol-4-yl}carbonyl)amino]-D-gluco-heptitol,

5-(benzoylamino)-1,2,5,6-tetradeoxy-1-(3,5-difluorophenyl)-7-O-methyl-2-[({2-[(methylsulfonyl)amino]-1,3-oxazol-4-yl}carbonyl)amino]-D-gluco-heptitol,

5-(acetylamino)-6-cyano-1,2,5,6-tetradeoxy-1-(3,5-difluorophenyl)-2-[({2-[(methylsulfonyl)amino]-1,3-oxazol-4-yl}carbonyl)amino]-D-glucitol, and

5-(benzoylamino)-6-cyano-1,2,5,6-tetradeoxy-1-(3,5-difluorophenyl)-2-[({2-[(methylsulfonyl)amino]-1,3-oxazol-4-yl}carbonyl)amino]-D-glucitol.