JP3470692B2 - Aminobutanoic acid derivative - Google Patents

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an aminobutanoic acid derivative, a method for producing the same, and a drug containing the derivative as an active ingredient. More specifically, the general formula (1)

[Chemical 8] (In the formula, all symbols have the same meanings as described below.) Aminobutanoic acid derivative, a non-toxic salt thereof, a method for producing them, and a drug containing them.

[0002]

2. Description of the Related Art Matrix metalloproteinases (hereinafter abbreviated as MMPs) have zinc (hereinafter Z
Abbreviated as n ²⁺ . ) Is a neutral metalloproteinase, which acts under physiological conditions by degrading collagen, laminin, proteoglycan, fibronectin, elastin, gelatin, etc. to grow and remodel joint tissue, bone tissue, connective tissue, etc. is doing. To date, 10 or more types of molecular species having different primary structures have been identified for MMPs. Specifically, interstitial collagenase (MMP-1), leukocyte collagenase (MM
P-8), gelatinase A (MMP-2), gelatinase B (MMP-9), stromlysin 1 (MMP-
3), stromlysin 2 (MMP-10), matrilysin (MMP-7), metalloelastase (MMP-)
12) and the like.

The properties common to each of these enzymes are:
(1) having Zn ²⁺ in the active center and requiring calcium ion (Ca ²⁺ ) for enzymatic activity, (2) being secreted as a latent enzyme and being activated extracellularly, (3 )
It has a high homology to the amino acid sequence, (4) it has the ability to decompose various extracellular matrix components existing in vivo, and (5) its activity is inhibited by a common inhibitor, tissue metalloproteinase inhibitor (TIMP). Things are known.

[0004] MMP inhibitors prevent and / or prevent various diseases caused by abnormally increased MMP secretion and activity.
Or considered to be useful for treatment. For example, rheumatism,
Osteoarthritis, pathological bone resorption, osteoporosis, periodontal disease, interstitial nephritis, arteriosclerosis, emphysema, liver cirrhosis, corneal damage, metastatic infiltration and proliferation of cancer cells, autoimmune disease (Crohn's disease, Schgren's disease, etc.) , Diseases caused by transmigration or infiltration of leukocyte cells, angiogenesis, multiple sclerosis, aortic aneurysm, endometriosis and the like.

Several compounds having a matrix metalloproteinase inhibitory action are known. Above all,
Substrate near the cleavage point of collagen (Gly-Ile-Al
a-Gly or Gly-Leu-Ala-Gly)
Is known to have a high affinity for collagenase. A number of chemically modified substrate analog matrix metalloproteinase inhibitors that have a zinc-affinity group at the cleavage site of this substrate have been studied [Inhibitors
of matrix metalloproteinases (MMP's), NigelRA Bee
ley, Phillip RJ Ansell, Andrew JP Docherty et al Cur
r. Opin. Ther. Patents., 4 , 7-16 (1994), Current Drug
s Ltd ISSN 0962-2594]. However, these substrate analog inhibitors are expected to have various problems because they are peptide analogs. Therefore, it is desired to make these inhibitors non-peptidic, and some reports have been made.

For example, in the examples of the specification of EP 757037, the formula (W)

[Chemical 9] It is disclosed that the sulfonyl amino acid derivative represented by the formula (1) has a matrix metalloproteinase inhibitory action.

Examples of the specification of EP 757984 include the formula (X)

[Chemical 10] It is disclosed that the hydroxamic acid derivative represented by the formula (1) has a matrix metalloproteinase inhibitory action.

In the examples of the specification of WO 9723459, the formula (Y)

[Chemical 11] It has been disclosed that the aromatique keto-acid derivative represented by the formula (1) has a matrix metalloproteinase inhibitory action.

In the examples of the specification of WO9718188, the formula (Z)

[Chemical 12] It is disclosed that the hydroxamic acid derivative represented by the formula (1) has matrix metalloproteinase and TNFα secretion inhibitory effects.

[0010]

DISCLOSURE OF THE INVENTION The present inventors have found that matrix metalloproteinase, e.g. gelatinase, result of performing intensive studies to find compounds having an inhibitory effect against stromelysin or collagenase, etc., ^gamma - carboxylic acid amino derivatives of amino acids It has been found that a novel aminobutanoic acid derivative represented by the general formula (I) achieves the object.

The present invention is 1) General formula (I)

[Chemical 13] (Wherein all symbols have the same meanings as described below), R ¹ is —COOR ¹⁰ or —C.
Represents ONHOR ¹⁰ , wherein R ¹⁰ is a hydrogen atom or C1-8
Represents an alkyl group, one of R ² and R ³ represents a hydrogen atom, the other represents a methyl group, R ⁴ and R ⁵ represent a hydrogen atom, and one of R ⁶ and R ⁷ represents a hydrogen atom. Represents an atom, the remaining one represents a methyl group substituted by an —OR ¹¹ group, R ¹¹ represents (i) hydrogen atom, and (ii) C1.
8 alkyl group C substituted or (iii) -OR ^15,
1 to 8 represents an alkyl group, R ¹⁵ represents a hydrogen atom, and C 1 to 8
C1-8 substituted with an alkyl group (excluding ethyl group), a benzyl group, or a C1-8 alkoxy group.
Represents an alkyl group, R ⁸ represents a hydrogen atom, and R ⁹ represents General formula (1) (In the formula, R ¹ represents -COOR ¹⁰ or -CONHOR ¹⁰ , R ¹⁰ represents a hydrogen atom or a C1-8 alkyl group, R ¹¹ represents (i) a hydrogen atom, (ii) a C1-8 alkyl group,
Or (iii) represents a C1-8 alkyl group substituted with —OR ¹⁵ , wherein R ¹⁵ represents a hydrogen atom, a C1-8 alkyl group (excluding an ethyl group), a benzyl group, or a C1-8 group.
It represents a C1-8 alkyl group substituted with an 8 alkoxy group. ) Aminobutanoic acid derivative represented by the formula), or a non-toxic salt thereof, 2) A process for producing the aminobutanoic acid derivative represented by the general formula (1) and a non-toxic salt thereof, and 3) Aminobutane represented by the general formula (1) The present invention relates to a drug containing an acid derivative and a non-toxic salt thereof as an active ingredient.

In the general formula (I), R ¹ is --COOR ¹⁰ ,-
CONHOR ¹⁰ , -CONHHR ¹⁰ ,-(CH ₂ ) _n S
R ⁵⁰ or —Y—PO (OR ⁵¹ ) ₂ is represented, and R ¹⁰ is (i) hydrogen atom, (ii) C1-8 alkyl group, (iii) phenyl group, (iv) phenyl group or C1-8 alkoxy group. Represents a C1-8 alkyl group substituted with, or (v) a phenyl group, a benzyl group or an oxycarbonyl group substituted with a C1-8 alkyl group, n represents an integer of 0 to 3, and R ⁵⁰ represents (i) hydrogen. Atom, (ii) C1-8 alkyl group, (iii) -COR ⁵² (wherein R ⁵² represents a C1-8 alkyl group or a phenyl group), (iv) -SR
⁵³ (in the group, R ⁵³ represents a hydrogen atom, a C1-8 alkyl group or a phenyl group), and R ⁵¹ represents a hydrogen atom, C
Represents 1-8 alkyl group or a phenyl group, Y is a single bond, -CH ₂ - or -O- and ^{represents, R 2, R 3, R} 4,
R ^5, R ^6, R ⁷ are each independently 1) hydrogen atom, 2) C1-8 alkyl group, 3) C2-8 alkenyl ^{group, 4) -OR 11, 5)} -SR 11, 6) -NR ¹² R ¹³ , 7) —COR ¹⁴ , 8) Cyc1, 9) —OR ¹¹ , —SR ¹¹ , —NR ¹² R ¹³ , —COR ¹⁴ ,
C1~8 alkyl group selected from guanidino group or Cyc1 is substituted or ^{10) -OR 11, -SR 11,} , -NR 12 R 13, -CO
R ¹⁴ represents a C 2-8 alkenyl group substituted with a group selected from a guanidino group or Cyc 1, or R ³
Groups and R ⁴ groups together C1~8 alkylene group, R ⁵ groups and R ⁶ groups together form C1~8 alkylene, R ³ groups and R ⁶ groups together form C1~8 alkylene Group, R ² group and R
³ groups together C2~8 alkylene group, R ⁴ group and R ⁵
C2~8 alkylene group together, or R ⁶ groups and R ⁷ groups represents a C2~8 alkylene group together, or

R ² represents a 2-propynyl group, and R ³ , R
⁴ , R ⁵ , R ⁶ and R ⁷ are each independently 1) a hydrogen atom, 2) a C1-8 alkyl group, 3) a C2-8 alkenyl group, 4) -OR ¹¹ , 5) -SR ¹¹ , 6). —NR ¹² R ¹³ , 7) —COR ¹⁴ , 8) Cyc1, 9) —OR ¹¹ , —SR ¹¹ , —NR ¹² R ¹³ , —COR ¹⁴ ,
C1~8 alkyl group selected from guanidino group or Cyc1 is substituted or ^{10) -OR 11, -SR 11,} , -NR 12 R 13, -CO
R ¹⁴ represents a C 2-8 alkenyl group substituted with a group selected from a guanidino group or Cyc 1, or R ³
Groups and R ⁴ groups together C1~8 alkylene group, R ⁵ groups and R ⁶ groups together form C1~8 alkylene, R ³ groups and R ⁶ groups together form C1~8 alkylene Group, R ⁴ group and R
C2~8 alkylene group ⁵ groups together form or R ⁶ groups and R ⁷ groups together represent a C2~8 alkylene group,

In the group, Cyc1 represents a carbocycle or a heterocycle, and these carbocycles or heterocycles are one or more (i) C1-8 alkyl groups, (ii) C1-8.
Alkoxy group, (iii) nitro group, (iv) guanidino group, (v) amidino group, (vi) halogen atom, (vii) nitrile group, (viii) hydroxyl group, (ix) benzyloxy group,
(X) -NR ¹⁰¹ R ¹⁰² (R ¹⁰¹ and R ¹⁰² each independently represent a hydrogen atom or a C1-8 alkyl group), (xi) -COOR ¹⁰³ (R ¹⁰³ is a hydrogen atom or C 1-8). Represents an alkyl group), (xii) trifluoromethyl group, (xiii) trifluoromethyloxy group,
(Xiv) phenyl group, (xv) phenyl group substituted by C1-8 alkyl group or C1-8 alkoxy group, (xvi) phenyloxy group, (xvii) phenylsulfonyl group, (xviii) phenyl group or nitrile group A C1-8 alkyl group substituted by, a (xix) heterocycle or (xx) keto group, a C1-8 alkoxy group substituted by a (xxi) -CONR ¹⁰⁴ R ¹⁰⁵ group (in which R ¹⁰⁴ and R ¹⁰⁵
Are each independently a hydrogen atom, a C1-8 alkyl group or a phenyl group. ) May be substituted.

R¹¹Is (i) hydrogen atom, (ii) C1-8a
Rukyi group, (iii) Cyc1 group, (iv) -COR¹⁸Base,
(V) -OR¹⁵, -SR¹⁵, -NR¹⁶R¹⁷, -CO
R¹⁸A guanidino group or a group selected from Cyc1
Represents a substituted C1-8 alkyl group, R¹⁵Is a hydrogen atom,
C1-8 alkyl group, Cyc1, or Cyc1 or
Is a C1-8 alkyl group substituted with a C1-8 alkoxy group
And R¹⁶Is a hydrogen atom or a C1-8 alkyl group
Represent, R¹⁷Is a hydrogen atom, a C1-8 alkyl group or-
COR¹⁹(Motochu, R¹⁹Is a C1-8 alkyl group, Cyc1
Or represents a C1-8 alkyl group substituted by Cyc1
You ), And R¹⁸Is a hydroxyl group, a C1-8 alkyl group,
C1-8 alkoxy group or -NR²⁰R ^{twenty one}(Motochu, R²⁰
And R^{twenty one}Are each independently a hydrogen atom, C1-8
Rualkyl group, Cyc1 or C1-8 substituted by Cyc1
Represents an alkyl group. ), And R¹²Is a hydrogen atom, C
1-8 alkyl group, substituted with Cyc1 or Cyc1
Represents a C1-8 alkyl group, R¹³Is a hydrogen atom, C1
8 alkyl group, Cyc1, C1-8 substituted with Cyc1
Alkyl group or -COR^{twenty two}(Motochu, R^{twenty two}Is C1-8
Rualkyl group, Cyc1 or C1-8 substituted by Cyc1
Represents an alkyl group. ), And R¹⁴Is a hydroxyl group, C1
~ 8 alkyl group, C1-8 alkoxy group, Cyc1, C
yc1 substituted C1-8 alkyl group or -NR^{twenty three}R
^{twenty four}(Motochu, R^{twenty three}And R^{twenty four}Each independently (i)
Hydrogen atom, (ii) C1-8 alkyl group, (iii) Cyc
1 or (iv) Cyc1 or C1 substituted with a hydroxyl group
8 represents an alkyl group. ),

(1) R ⁸ is 1) hydrogen atom, 2) C1-8 alkyl group, 3) C1-8 alkoxycarbonyl group, 4) -OR ²⁶ , -SR ²⁶ , -NR ²⁷ R ²⁸ or -COR.
^When a group selected from ²⁹ represents a substituted C1-8 alkyl group, or 5) Cyc2 represents a substituted C1-8 alkoxycarbonyl group, R ⁹ represents

[Chemical 14] Represents,

(2) R ⁸ is

[Chemical 15] R ⁹ represents 1) a C1-8 alkyl group, 2) a C1-8 alkoxy group, 3) a C1-8 alkoxy group substituted by Cyc2, 4) —OR ²⁶ , —SR ²⁶ , —NR ²⁷ R ²⁸ , A C1-8 alkyl group substituted with a group selected from —COR ²⁹ or Cyc2, or

[Chemical 16] Represents,

In the group, Cyc2 represents a carbocycle or a heterocycle, and these carbocycles or heterocycles are one or more (i) C1-8 alkyl groups, (ii) C1-8.
Alkoxy group, (iii) nitro group, (iv) guanidino group, (v) amidino group, (vi) halogen atom, (vii) nitrile group, (viii) hydroxyl group, (ix) benzyloxy group,
^{(X) -NR 201 R 202 (} R 201 and R ²⁰² are each independently a hydrogen atom or a C1~8 alkyl ^{group.), (Xi) -COOR 203} (R 203 is a hydrogen atom or a C1~8 Represents an alkyl group), (xii) trifluoromethyl group, (xiii) trifluoromethyloxy group,
(Xiv) phenyl group, (xv) phenyl group substituted by C1-8 alkyl group or C1-8 alkoxy group, (xvi) phenyloxy group, (xvii) phenylsulfonyl group, (xviii) phenyl group or nitrile group C1~8 alkyl group substituted by, (xix) heterocyclic or (xx) keto group, (xxi) -CONR ²⁰⁴ in C1~8 alkoxy group (group substituted with R ²⁰⁵ groups, R ²⁰⁴ and R ²⁰⁵
Are each independently a hydrogen atom, a C1-8 alkyl group or a phenyl group. ) May be substituted.

R ²⁶ is a hydrogen atom, a C1-8 alkyl group, C
represents a C1-8 alkyl group substituted with yc2 or Cyc2, R ²⁷ represents a hydrogen atom, a C1-8 alkyl group, Cyc
2 or Cyc2 represents a substituted C1-8 alkyl group, R ²⁸ is a hydrogen atom, a C1-8 alkyl group, Cyc2,
Cyc2 substituted C1-8 alkyl group or -COR
³⁰ (R ³⁰ is a C1-8 alkyl group, Cyc2 or Cyc
2 represents a substituted C1-8 alkyl group. R ²⁹ represents a hydroxyl group, a C 1-8 alkyl group, Cyc 2, C
yc2 substituted C1-8 alkyl group or -NR ³¹ R
³² (R ³¹ and R ³² are each independently a hydrogen atom, C1
~ 8 alkyl group, Cyc2 or C substituted with Cyc2
1 to 8 represents an alkyl group. ),

[0020]

[Chemical 17] Represents a carbocycle or a heterocycle, R ²⁵ represents -E-G,

[0021] E is 1) a single ^{bond, 2) -CONR 33 -, 3} ) -NR 33 CO-, 4) -CO-O-, 5) -O-CO-, 6) -NR 33 -CO-NR ^{34 -, 7) -CO-CH} 2 -, 8) -CO-, 9) -O-CO-NR 33 -, 10) -NR 33 -CO-O-, 11) -O-CO-O-, ^{12) -CS-NR 33 -,} 13) -NR 33 -CS-, 14) -CS-O-, 15) -O-CS-, 16) -NR 33 -CS-NR 34 -, 17) -CS _{-CH 2 -, 18) -CS-,} 19) -O-CS-NR 33 -, 20) -NR 33 -CS-O-, 21) -O-CS-O-, 22) -CH 2 -CH _{2 -, 23) -HC = CH-} , 24) -C≡C-, 25) -SO 2 -NR 33 -, 26) -NR 33 -SO 2 -, 27) -SO 2 -CH 2 -, or Two 8) represents —CH ₂ —SO ₂ —,

In the group, R ³³ and R ³⁴ are each independently a hydrogen atom, a C1-8 alkyl group, Cyc3 or Cyc.
3 represents a substituted C1-8 alkyl group, Cyc3 represents a carbocycle or a heterocycle, and these carbocycles or heterocycles represent one or more (i) C1-8alkyl groups, (ii) C1 ~ 8 alkoxy group, (iii) nitro group, (iv) guanidino group, (v) amidino group, (vi) halogen atom, (vii) nitrile group, (viii) hydroxyl group, (i
x) benzyloxy group, (x) -NR ³⁰¹ R ³⁰² (R ³⁰¹ and R ³⁰² are each independently a hydrogen atom or C1 to
8 represents an alkyl group. ), (Xi) -COOR ³⁰³ (R
³⁰³ represents a hydrogen atom or a C1-8 alkyl group. ), (Xii) trifluoromethyl group, (xiii) trifluoromethyloxy group, (xiv) phenyl group, (xv)
Phenyl group substituted by C1-8 alkyl group or C1-8 alkoxy group, (xvi) phenyloxy group, (xvii) phenylsulfonyl group, (xviii) C1-8 alkyl group substituted by phenyl group or nitrile group , (Xix) heterocycle or (xx) keto group, (xxi) -C
C1-8 alkoxy group substituted with ONR ³⁰⁴ R ³⁰⁵ group (in the group, R ³⁰⁴ and R ³⁰⁵ each independently represent a hydrogen atom, a C1-8 alkyl group or a phenyl group)
May be replaced with.

G is 1) hydrogen atom, 2) C1-8 alkyl group, 3) Cyc4, 4) -OR ³⁵ , 5) -SR ³⁵ , 6) halogen atom, 7) nitro group, 8) nitrile group, 9 ) -NR ³⁶ R ³⁷ , 10) -COR ³⁸ , 11) Cyc 4, -OR ³⁵ , -SR ³⁵ , halogen atom,
Represents a C1-8 alkyl group substituted with a group selected from —NR ³⁶ R ³⁷ or —COR ³⁸ ,

In the group, Cyc4 represents a carbocycle or a heterocycle, and these carbocycles or heterocycles are one or more (i) C1-8 alkyl groups, (ii) C1-8.
Alkoxy group, (iii) nitro group, (iv) guanidino group, (v) amidino group, (vi) halogen atom, (vii) nitrile group, (viii) hydroxyl group, (ix) benzyloxy group,
(X) -NR ⁴⁰¹ R ⁴⁰² (R ⁴⁰¹ and R ⁴⁰² each independently represent a hydrogen atom or a C1-8 alkyl group), (xi) -COOR ⁴⁰³ (R ⁴⁰³ is a hydrogen atom or C1-8). Represents an alkyl group), (xii) trifluoromethyl group, (xiii) trifluoromethyloxy group,
(Xiv) phenyl group, (xv) phenyl group substituted by C1-8 alkyl group or C1-8 alkoxy group, (xvi) phenyloxy group, (xvii) phenylsulfonyl group, (xviii) phenyl group or nitrile group A C1-8 alkyl group substituted by, (xix) heterocycle, (x
x) a keto group or a C1-8 alkoxy group substituted with a (xxi) -CONR ⁴⁰⁴ R ⁴⁰⁵ group (in which R ⁴⁰⁴ and R ⁴⁰⁵
Are each independently a hydrogen atom, a C1-8 alkyl group or a phenyl group. ) May be substituted.

R ³⁵ is a hydrogen atom, a C1-8 alkyl group, C
1-8 alkoxy group, Cyc4 or a C1-8 alkyl group substituted with Cyc4, R ³⁶ is a hydrogen atom, C 1
~ 8 alkyl group, Cyc4 or C substituted with Cyc4
1 to 8 represents an alkyl group, R ³⁷ represents a hydrogen atom, C 1 to 8
An alkyl group, Cyc4, a C1-8 alkyl group substituted by Cyc4 or -COR ³⁹ (R ³⁹ represents a C1-8 alkyl group, Cyc4 or a C1-8 alkyl group substituted by Cyc4) and R ³⁸ represents a hydroxyl group. , C1-8 alkyl group, Cyc4, C1-8 alkyl group substituted with Cyc4, —NR ⁴⁰ R ⁴¹ (R ⁴⁰ and R ⁴¹ are each independently a hydrogen atom, C 1-8 alkyl group, Cyc 4 or C
yc4 represents a substituted C1-8 alkyl group. ) Or together with -EG represents a C1-4 alkylidene group,

P represents an integer of 1 to 5, M is C1 to 8
Represents an alkylene group, J represents a single bond, an oxygen atom, a sulfur atom or —NR ⁴² — (R ⁴² represents a hydrogen atom or a C1-8 alkyl group),

Embedded image is a single bond, or R ² , R ³ , R ⁴ , R ⁵ ,
When two adjacent groups of R ⁶ and R ⁷ which are not bonded to the same carbon are hydrogen, they are eliminated to represent a double bond (provided that the R ³ group and the R ⁴ group together form C 1 to C 1 When an 8 alkylene group, an R ⁵ group and an R ⁶ group together represent a C1-8 alkylene group, and an R ³ group and an R ⁶ group together represent a C1-8 alkylene group, they do not represent a double bond.

[0027]

[0028]

Detailed Description of the Invention In the present invention, isomers include all of them unless otherwise specified. For example, the alkyl group, the alkoxy group and the alkylene group include straight chain and branched chain groups. Double bonds in alkenylene groups include those that are E, Z and EZ mixtures.
Also included are isomers formed by the presence of asymmetric carbon atoms such as when a branched chain alkyl group, alkoxy group and alkylene group are present.

In the present invention, the C1-8 alkyl group means
Methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl groups and isomers thereof. C1-8 alkoxy group means methoxy, ethoxy,
Propoxy, butoxy, pentyloxy, hexyloxy, heptyloxy, octyloxy groups and isomers thereof.

A C1-8 alkyl group substituted by a phenyl group means methyl substituted by one phenyl group,
Ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl groups and isomers thereof. C1
The C1-8 alkyl group substituted with an 8 alkoxy group means methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, heptyloxy, octyloxy group and methyl, ethyl substituted by one of these isomer groups, Propyl, butyl, pentyl, hexyl, heptyl, octyl groups and isomers thereof.

A C1-8 alkyl group substituted by a nitrile group means methyl substituted by one nitrile group,
Ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl groups and isomers thereof. An oxycarbonyl group substituted with a phenyl group is a phenyloxycarbonyl group. An oxycarbonyl group substituted with a benzyl group is a benzyloxycarbonyl group.

The oxycarbonyl group substituted by a C1-8 alkyl group is a methyloxycarbonyl, ethyloxycarbonyl, propyloxycarbonyl, butyloxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl, heptyloxycarbonyl, octyloxycarbonyl group or the like. Is an isomer of.

The C2-8 alkenyl group means vinyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, butadienyl, pentadienyl, hexadienyl, heptadienyl, octadienyl, hexatrienyl, heptatrienyl, octatrienyl groups and isomers thereof. Is.

The C1-8 alkylene group is methylene, ethylene, trimethylene, tetramethylene, pentamethylene, hexamethylene, heptamethylene, octamethylene group and isomers thereof. The C2-8 alkylene group is an ethylene, trimethylene, tetramethylene, pentamethylene, hexamethylene, heptamethylene, octamethylene group or an isomer thereof.

The halogen atom means chlorine, bromine, fluorine or iodine atom. The C1-8 alkoxycarbonyl group is a methyloxycarbonyl, ethyloxycarbonyl, propyloxycarbonyl, butyloxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl, heptyloxycarbonyl, octyloxycarbonyl group and isomers thereof. C1-4 alkylidene group means methylidene, ethylidene, propylidene,
Butylidene and isomers thereof.

The carbocycle means a C3-15 monocyclic, bicyclic or tricyclic carbocyclic ring. As these rings, for example,
Cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclopentene, cyclohexene, cyclopentadiene, cyclohexadiene,
Benzene, pentalene, indene, naphthalene, azulene, fluorene, phenanthrene, anthracene, acenaphthylene, biphenylene, perhydropentalene, perhydroindene, perhydronaphthalene, perhydroazulene, perhydrofluorene, perhydrophenanthrene, perhydroanthracene , Perhydroacenaphthylene, perhydrobiphenylene, adamantyl ring and the like.

Heterocycle means 1 to 4 nitrogen atoms and 1 to 2 nitrogen atoms.
Represents a 5- to 18-membered monocyclic, bicyclic or tricyclic heterocycle containing 1 oxygen atom and / or 1 to 2 sulfur atom.
1 to 4 membered monocyclic, bicyclic or tricyclic heterocyclic ring containing 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms and / or 1 to 2 sulfur atoms is 1 to 4 Containing 5 nitrogen atoms, 1 to 2 oxygen atoms and / or 1 to 2 sulfur atoms
To 18-membered monocyclic, bicyclic or tricyclic heterocyclic aryl or partially or fully saturated thereof.

5 to 5 containing the above-mentioned 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms and / or 1 to 2 sulfur atoms.
The 18-membered monocyclic, bicyclic or tricyclic heterocyclic aryl includes pyrrole, imidazole, triazole, tetrazole, pyrazole, pyridine, pyrazine, pyrimidine,
Pyridazine, azepine, diazepine, furan, pyran,
Oxepin, oxazepine, thiophene, thiain (thiopyran), thiepine, oxazole, isoxazole, thiazole, isothiazole, oxadiazole,
Oxaazine, oxadiazine, oxaazepine, oxadiazepine, thiadiazole, thiaazine, thiadiazine, thiaazepine, thiadiazepine, indole, isoindole, benzofuran, isobenzofuran, benzothiophene, isobenzothiophene, indazole,
Quinoline, isoquinoline, phthalazine, naphthyridine,
Examples include quinoxaline, quinazoline, cinnoline, benzoxazole, benzothiazole, benzimidazole, carbazole and acridine ring.

5 to 5 containing the above-mentioned 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms and / or 1 to 2 sulfur atoms.
The 18-membered monocyclic or bicyclic heterocycle partially or wholly saturated includes pyrroline, pyrrolidine, imidazoline, imidazolidine, triazoline, triazolidine,
Tetrazoline, tetrazolidine, pyrazoline, pyrazolidine, piperidine, piperazine, tetrahydropyridine, tetrahydropyrimidine, tetrahydropyridazine, dihydrofuran, tetrahydrofuran, dihydropyran, tetrahydropyran, dihydrothiophene, tetrahydrothiophene, dihydrothiain (dihydrothiopyran), tetrahydrothiain (Tetrahydrothiopyran), dihydrooxazole, tetrahydrooxazole, dihydroisoxazole, tetrahydroisoxazole, dihydrothiazole, tetrahydrothiazole, dihydroisothiazole, tetrahydroisothiazole, morpholine, thiomorpholine, indoline, isoindoline, dihydrobenzofuran, perhydrobenzofuran , Dihydro Benzofuran, perhydroisobenzofuran, dihydrobenzothiophene, perhydrobenzothiophene, dihydroisobenzothiophene, perhydroisobenzothiophene, dihydroindazole, perhydroindazole, dihydroquinoline, tetrahydroquinoline, perhydroquinoline, dihydroisoquinoline, tetrahydroisoquinoline, Perhydroisoquinoline, dihydrophthalazine, tetrahydrophthalazine, perhydrophthalazine, dihydronaphthyridine, tetrahydronaphthyridine, perhydronaphthyridine, dihydroquinoxaline, tetrahydroquinoxaline, perhydroquinoxaline, dihydroquinazoline, tetrahydroquinazoline, perhydroquinazoline, dihydrocinnoline , Tetrahydrocinnoline, perhydr Cinnoline, dihydrobenzoxazole, perhydrobenzoxazole, dihydrobenzothiazole, perhydrobenzothiazole, dihydrobenzimidazole, perhydrobenzimidazole, benzoxazepine, benzooxadiazepine, benzothiazepine, benzothiadiazepine, benzazepine , Benzodiazepines, indolooxoazepines, indolotetrahydrooxazepines, indolooxadiazepines, indolotetrahydrooxadiazepines, indolothiaazepines, indolotetrahydrothiaazepines, indolothiadiazepines, indolotetrahydrothiadiazepines , Indoloazepine, indolotetrahydroazepine, indolodiazepine, indolotetrahydrodiazepine, benzofurazan, benzothia Diazole, benzotriazole, camphor, imidazothiazole, dihydrocarbazole,
Tetrahydrocarbazole, perhydrocarbazole,
Examples thereof include dihydroacridine, tetrahydroacridine, perhydroacridine, dioxolane, dioxane, dithiolane, dithiane, dioxazine and dithiazine ring.

[0041]

Salt: In the present invention, all non-toxic salts are included.
For example, common salts, acid addition salts, hydrate salts and the like can be mentioned. The compound of the present invention represented by the general formula (I) can be converted into the corresponding salt by a known method. The salt is preferably non-toxic and water-soluble. Suitable salts include salts of alkali metals (potassium, sodium, etc.), salts of alkaline earth metals (calcium, magnesium, etc.), ammonium salts, pharmaceutically acceptable organic amines (tetramethylammonium, triethylamine, methylamine). , Dimethylamine, cyclopentylamine, benzylamine, phenethylamine, piperidine, monoethanolamine, diethanolamine, tris (hydroxymethyl) amine, lysine, arginine, N-methyl-D-glucamine, etc.).

The compound of the present invention represented by the general formula (I) is
It is converted into the corresponding acid addition salt by a known method. The acid addition salt is preferably non-toxic and water-soluble. Suitable acid addition salts include inorganic acid salts such as hydrochlorides, hydrobromides, sulfates, phosphates, nitrates, or acetates, trifluoroacetates, lactates, tartrates, oxalates. Such as, fumarate, maleate, citrate, benzoate, methanesulfonate, ethanesulfonate, benzenesulfonate, toluenesulfonate, isethionate, glucuronate, gluconate. Organic acid salts.
Further, the compound of the present invention represented by the general formula (I) or a salt thereof can be converted into a hydrate by a known method.

Among the compounds of the present invention represented by the general formula (I), preferred compounds are the general formula (IA)

[Chemical 20] (In the formula, all symbols have the same meanings as described above.),

General formula (IB)

[Chemical 21] (In the formula, all symbols have the same meanings as described above.),

General formula (IC)

[Chemical formula 22] (In the formula, all symbols have the same meanings as described above.),

General formula (ID)

[Chemical formula 23] (In the formula, all symbols have the same meanings as described above.),

General formula (IE)

[Chemical formula 24] (In the formula, all symbols have the same meanings as described above.),

General formula (IF)

[Chemical 25] (In the formula, all symbols have the same meanings as described above.),

General formula (IG)

[Chemical formula 26] (In the formula, all symbols have the same meanings as described above.),

General formula (I-H)

[Chemical 27] (In the formula, all symbols have the same meanings as described above.),

General formula (I-J)

[Chemical 28] (In the formula, all symbols have the same meanings as described above.),

General formula (I-K)

[Chemical 29] (In the formula, all symbols have the same meanings as described above.),

General formula (IL)

[Chemical 30] (In the formula, all symbols have the same meanings as described above.),

General formula (IM)

[Chemical 31] (In the formula, all symbols have the same meanings as described above.),

General formula (IN)

[Chemical 32] (In the formula, all symbols have the same meanings as described above.),

General formula (I-O)

[Chemical 33] (In the formula, all symbols have the same meanings as described above.),

General formula (IP)

[Chemical 34] (In the formula, G ¹ represents a methyl group, a halogen atom, a nitro group or a nitrile group, and other symbols have the same meanings as described above),

General formula (I-Q)

[Chemical 35] (Wherein all symbols have the same meanings as described above).

More preferably, Tables 1 to 105 below.
And the nontoxic salts thereof and the compounds described in Examples. In the tables below, Phth is a phthalimido group, Ph is a phenyl group, MOM is a methoxymethyl group, EOM is an ethoxymethyl group, MEM is a (2-methoxyethoxy) methyl group, and BOM is a benzyloxymethyl group.

[0060]

[Table 1]

[0061]

[Table 2]

[0062]

[Table 3]

[0063]

[Table 4]

[0064]

[Table 5]

[0065]

[Table 6]

[0066]

[Table 7]

[0067]

[Table 8]

[0068]

[Table 9]

[0069]

[Table 10]

[0070]

[Table 11]

[0071]

[Table 12]

[0072]

[Table 13]

[0073]

[Table 14]

[0074]

[Table 15]

[0075]

[Table 16]

[0076]

[Table 17]

[0077]

[Table 18]

[0078]

[Table 19]

[0079]

[Table 20]

[0080]

[Table 21]

[0081]

[Table 22]

[0082]

[Table 23]

[0083]

[Table 24]

[0084]

[Table 25]

[0085]

[Table 26]

[0086]

[Table 27]

[0087]

[Table 28]

[0088]

[Table 29]

[0089]

[Table 30]

[0090]

[Table 31]

[0091]

[Table 32]

[0092]

[Table 33]

[0093]

[Table 34]

[0094]

[Table 35]

[0095]

[Table 36]

[0096]

[Table 37]

[0097]

[Table 38]

[0098]

[Table 39]

[0099]

[Table 40]

[0100]

[Table 41]

[0101]

[Table 42]

[0102]

[Table 43]

[0103]

[Table 44]

[0104]

[Table 45]

[0105]

[Table 46]

[0106]

[Table 47]

[0107]

[Table 48]

[0108]

[Table 49]

[0109]

[Table 50]

[0110]

[Table 51]

[0111]

[Table 52]

[0112]

[Table 53]

[0113]

[Table 54]

[0114]

[Table 55]

[0115]

[Table 56]

[0116]

[Table 57]

[0117]

[Table 58]

[0118]

[Table 59]

[0119]

[Table 60]

[0120]

[Table 61]

[0121]

[Table 62]

[0122]

[Table 63]

[0123]

[Table 64]

[0124]

[Table 65]

[0125]

[Table 66]

[0126]

[Table 67]

[0127]

[Table 68]

[0128]

[Table 69]

[0129]

[Table 70]

[0130]

[Table 71]

[0131]

[Table 72]

[0132]

[Table 73]

[0133]

[Table 74]

[0134]

[Table 75]

[0135]

[Table 76]

[0136]

[Table 77]

[0137]

[Table 78]

[0138]

[Table 79]

[0139]

[Table 80]

[0140]

[Table 81]

[0141]

[Table 82]

[0142]

[Table 83]

[0143]

[Table 84]

[0144]

[Table 85]

[0145]

[Table 86]

[0146]

[Table 87]

[0147]

[Table 88]

[0148]

[Table 89]

[0149]

[Table 90]

[0150]

[Table 91]

[0151]

[Table 92]

[0152]

[Table 93]

[0153]

[Table 94]

[0154]

[Table 95]

[0155]

[Table 96]

[0156]

[Table 97]

[0157]

[Table 98]

[0158]

[Table 99]

[0159]

[Table 100]

[0160]

[Table 101]

[0161]

[Table 102]

[0162]

[Table 103]

[0163]

[Table 104]

[0164]

[Table 105]

[0165]

Method for Producing Compound of the Present Invention The compound of the present invention represented by the general formula (I) can be produced by the following method or the method described in Examples. [1] Of the compounds of the present invention represented by the general formula (I), R
^The compound in which ¹ is -COOR ^10, that is, the compound of the general formula (I-
1)

[Chemical 36] (In the formula, all symbols have the same meanings as described above.) The compounds represented by the following (a) to (c) can be produced.

(A) --COOR ¹⁰ group in R ¹ group is --CO
Does not represent an OH group and is R ² , R ³ , R ⁴ , R ⁵ , R ⁶ ,
A compound in which none of R ⁷ , R ⁸ and R ^{9 represents a} —COOH group or a group containing it, a hydroxyl group or a group containing it, or an amino group or a group containing it, that is, a compound of the general formula (I- 1a)

[Chemical 37] (In the formula, R ^10-1a is a C 1-8 alkyl group substituted by a C 1-8 alkyl group, a phenyl group, a phenyl group or a C 1-8 alkoxy group, or an oxy group substituted by a phenyl, benzyl or C 1-8 alkyl group. ^Represents a carbonyl group, R ^2-1a , R ^3-1a , R ^4-1a , R ^5-1a , R ^6-1a , R
^7-1a , R ^8-1a and R ^9-1a are R ² , R ³ , R ⁴ and R ⁵ , respectively.
It has the same meaning as R ⁶ , R ⁷ , R ⁸ and R ⁹ . However, R
^2-1a , R ^3-1a , R ^4-1a , R ^5-1a , R ^6-1a , R ^7-1a , R
^{None of 8-1a} and R ^{9-1a represents} a -COOH group, a hydroxyl group, an amino group or a group containing them, and the other symbols have the same meanings as described above. ) Is a compound represented by the general formula (II)

[Chemical 38] (Wherein all symbols have the same meanings as described above) and a compound of the general formula (III)

[Chemical Formula 39] (In the formula, all symbols have the same meanings as described above.) The compound can be produced by subjecting it to an amidation reaction.

The amidation reaction between the compound represented by the general formula (II) and the compound represented by the general formula (III) is known, and for example, the method using (1) acid halide and (2) mixed acid anhydride The method of using, the method of using a condensing agent (3), etc. are mentioned.

These methods will be described in detail. (1) The method using an acid halide is, for example, carboxylic acid in an inert organic solvent (chloroform, methylene chloride, diethyl ether, tetrahydrofuran, etc.) or without solvent, An acid halide (oxaryl chloride, thionyl chloride, etc.) is reacted at −20 ° C. to a reflux temperature, and the obtained acid halide is treated with an amine in the presence of a tertiary amine (pyridine, triethylamine, dimethylaniline, dimethylaminopyridine, etc.). Inert organic solvent (chloroform, methylene chloride, diethyl ether, tetrahydrofuran, etc.)
The reaction is carried out at 0 to 40 ° C in the medium.

(2) The method using a mixed acid anhydride is carried out, for example, by using a carboxylic acid as an inert organic solvent (chloroform, methylene chloride, diethyl ether, tetrahydrofuran, etc.).
Acid halide (pivaloyl chloride, tosyl chloride, mesyl chloride, etc.) or acid derivative (ethyl chloroformate, in the presence of a tertiary amine (pyridine, triethylamine, dimethylaniline, dimethylaminopyridine, etc.) in a medium or without solvent. Isobutyl chloroformate, etc.),
The mixture is reacted at 0 to 40 ° C, and the obtained mixed acid anhydride is reacted with an amine at 0 to 40 ° C in an inert organic solvent (chloroform, methylene chloride, diethyl ether, tetrahydrofuran, etc.).
It is carried out by reacting with.

(3) The method using a condensing agent is, for example, a carboxylic acid and an amine in an organic solvent (chloroform, methylene chloride, dimethylformamide, diethyl ether, tetrahydrofuran, etc.) or without a solvent, and a tertiary amine (pyridine). , Triethylamine, dimethylaniline, dimethylaminopyridine, etc.) in the presence or absence of (1,3-dicyclohexylcarbodiimide (DC
C), 1-ethyl-3- [3- (dimethylamino) propyl] carbodiimide (EDC), 1,1′-carbonyldiimidazole (CDI), 2-chloro-1-methylpyridinium iodine, etc.) -With or without hydroxybenztriazole (HOBt)
It is carried out by reacting at 40 ° C. It is desirable that all of these reactions (1), (2) and (3) be carried out under an inert gas (argon, nitrogen, etc.) atmosphere under anhydrous conditions.

(B) The --COOR ¹⁰ group in the R ¹ group is --CO
Does not represent an OH group and is R ² , R ³ , R ⁴ , R ⁵ , R ⁶ ,
At least one of the R ⁷ , R ⁸ and R ⁹ groups is --CO
Compounds representing an OH group or a group containing it, a hydroxyl group or a group containing it, or an amino group or a group containing it, that is, general formula (I-1b)

[Chemical 40] ^{(Wherein, R 2-1b, R 3-1b, R} 4-1b, R 5-1b, R 6-1b, R
^7-1b , R ^8-1b and R ^9-1b are R ² , R ³ , R ⁴ and R ⁵ , respectively.
It has the same meaning as R ⁶ , R ⁷ , R ⁸ and R ⁹ . However, R
^{2-1b, R 3-1b, R 4-1b,} R 5-1b, R 6-1b, R 7-1b, R
^At least one of the ^8-1b and R ^9-1b groups is -COO.
It represents an H group, a hydroxyl group, an amino group or a group containing them, and other symbols have the same meanings as described above. ) Is a compound represented by the formula (I-1a)
A compound in which an H group, a hydroxyl group, an amino group or a group containing them is protected, that is, a compound represented by the general formula (I-1a1)

[Chemical 41] (In the formula, R ^2-1a1 , R ^3-1a1 , R ^4-1a1 , R ^5-1a1 , R
^6-1a1 , R ^7-1a1 , R ^8-1a1 and R ^9-1a1 are R ² , respectively.
It has the same meaning as R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ and R ⁹ . However, R ^2-1a1 , R ^3-1a1 , R ^4-1a1 , R ^5-1a1 , R
^6-1a1 , R ^7-1a1 , R ^{8-1a 1} and R ^9-1a 1 at least one of which is protected by a —COOH group (for example, methyl group, ethyl group, t-butyl group and benzyl group). Group), a protected hydroxyl group (eg, methoxymethyl group, tetrahydropyranyl group, t-butyldimethylsilyl group, acetyl group, benzyl group, etc.) or protected amino group (eg, benzyloxycarbonyl group, t- Butoxycarbonyl group, trifluoroacetyl group, etc.) or a group containing them, and other symbols have the same meanings as described above. ) Can be produced by subjecting the compound represented by the formula (1) to alkali hydrolysis, deprotection reaction under acidic conditions, silyl group deprotection reaction or hydrogenolysis deprotection reaction.

The deprotection reaction by alkali hydrolysis is known, and for example, in an organic solvent (methanol, tetrahydrofuran, dioxane, etc.), an alkali metal hydroxide (sodium hydroxide, potassium hydroxide, lithium hydroxide, etc.), Alkaline earth metal hydroxides (barium hydroxide,
Calcium hydroxide, etc.) or carbonates (sodium carbonate,
It is carried out at a temperature of 0 to 40 ° C. using potassium carbonate or the like) or an aqueous solution thereof or a mixture thereof.

Deprotection reactions under acidic conditions are known,
For example, in an organic solvent (methylene chloride, chloroform, dioxane, ethyl acetate, anisole, etc.), an organic acid (acetic acid,
Trifluoroacetic acid, methanesulfonic acid, trimethylsilyl iodide, etc.) or an inorganic acid (hydrochloric acid, sulfuric acid, etc.) or a mixture thereof (hydrobromic acid acetic acid, etc.) at a temperature of 0 to 100 ° C. The deprotection reaction of the silyl group is known, and is carried out, for example, in an organic solvent miscible with water (tetrahydrofuran, acetonitrile, etc.) using tetrabutylammonium fluoride at a temperature of 0 to 40 ° C.

The deprotection reaction by hydrogenolysis is known, and examples thereof include an inert solvent [ether system (eg, tetrahydrofuran, dioxane, diemethoxyethane, diethyl ether etc.), alcohol system (eg methanol,
Ethanol etc.), benzene series (eg benzene, toluene etc.), ketone series (eg acetone, methyl ethyl ketone etc.), nitrile series (eg acetonitrile etc.), amide series (eg dimethylformamide etc.),
Water, ethyl acetate, acetic acid or a mixed solvent of two or more thereof, etc.] in the presence of a hydrogenation catalyst (eg, palladium-carbon, palladium black, palladium, palladium hydroxide, platinum dioxide, nickel, Raney nickel, etc.) In the presence of an acid (eg, hydrochloric acid, sulfuric acid, hypochlorous acid, boric acid, tetrafluoroboric acid, etc.) or an organic acid (eg, acetic acid, p-toluenesulfonic acid, oxalic acid, trifluoroacetic acid, formic acid, etc.) or 0 to 200 ° C. in the absence of hydrogen atmosphere under normal pressure or pressure or in the presence of ammonium formate.
Performed at the temperature of. When an acid is used, its salt may be used.

(C) The —COOR ¹⁰ group in the R ¹ group is —CO
A compound having an OH group, that is, a compound represented by the general formula (I-1c)

[Chemical 42] (Wherein all symbols have the same meanings as described above), the compound represented by the general formula (I-1a) or (I-1b) is
A compound produced by the formula (I-1ab)

[Chemical 43] (In the formula, all symbols have the same meanings as described above.) The compound can be produced by subjecting it to alkali hydrolysis, deprotection reaction under acidic conditions or deprotection reaction by hydrogenolysis. The hydrolysis under alkaline conditions, the deprotection reaction under acid conditions, and the deprotection reaction by hydrogenolysis are known, and they are carried out by the methods described above.

[2] In the compounds of the present invention represented by the general formula (I), R ¹ is --CONHOR ¹⁰ or --CONHN.
A compound that is HR ^10, that is, a compound of general formula (I-2)

[Chemical 44] (In the formula, R ^1-2 is -CONHOR ¹⁰ or -CONHN
HR ¹⁰ and other symbols have the same meanings as described above. The compound represented by () can be produced by the following methods (a) and (b).

(A) R ¹ is -CONHOR ¹⁰ or -C
Represents ONNHHR ¹⁰ and R ² , R ³ , R ⁴ , R ⁵ , R
Compounds in which none of ⁶ , R ⁷ , R ⁸ and R ⁹ groups represent a —COOH group or a group containing it, that is, a compound represented by the general formula (I-2a)

[Chemical formula 45] (In the formula, R ^2-2a , R ^3-2a , R ^4-2a , R ^5-2a , R ^6-2a , R
^7-2a , R ^8-2a and R ^9-2a are R ² , R ³ , R ⁴ and R ⁵ , respectively.
It has the same meaning as R ⁶ , R ⁷ , R ⁸ and R ⁹ . However, R
^2-2a , R ^3-2a , R ^4-2a , R ^5-2a , R ^6-2a , R ^7-2a , R
^{Neither 8-2a nor} R ^9-2a represents a --COOH group or a group containing them, and the other symbols have the same meanings as described above. In the compound represented by the formula (I-1), the R ¹ group represents a COOH group, and R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ and R are compounds represented by the formula (I). ^A compound in which none of ⁸ and R ⁹ represents a --COOH group or a group containing it, that is, a compound of the general formula (I-1d)

[Chemical formula 46] (Wherein all symbols have the same meanings as described above) and the general formula (IV) H ₂ N-OR ¹⁰ (IV) (wherein R ¹⁰ has the same meaning as described above). Alternatively, the compound represented by the general formula (V) H ₂ N—NHR ¹⁰ (V) (wherein R ¹⁰ has the same meaning as described above) is subjected to an amidation reaction, and if necessary, subsequently alkali It can be produced by subjecting it to hydrolysis under conditions and / or deprotection reaction under acid conditions and / or deprotection reaction by hydrogenolysis. This amidation reaction, hydrolysis under alkaline conditions, deprotection reaction under acid conditions, and deprotection reaction by hydrogenolysis are known and are carried out by the above-mentioned methods.

(B) R ¹ is -CONHOR ¹⁰ or -C
Represents ONNHHR ¹⁰ and R ² , R ³ , R ⁴ , R ⁵ , R
^A compound in which at least one of the groups R ⁶ , R ⁷ , R ⁸ and R ⁹ represents a —COOH group or a group containing it.
That is, the general formula (I-2b)

[Chemical 47] (In the formula, R ^2-2b , R ^3-2b , R ^4-2b , R ^5-2b , R ^6-2b , R
^7-2b, R ^8-2b, each ^{R 9-2b R 2, R 3,} R 4, R 5,
It has the same meaning as R ⁶ , R ⁷ , R ⁸ and R ⁹ . However, R
^{2-2b, R 3-2b, R 4-2b,} R 5-2b, R 6-2b, R 7-2b, R
^{In the} groups ^8-2b and R ^9-2b , at least one group represents a -COOH group or a group containing them, and the other symbols have the same meanings as described above. The compound represented by the formula) is a compound of the above formula (I-2a) in which the —COOH group or the group containing them is protected, that is, the compound represented by the formula (I-
2a1)

[Chemical 48] (In the formula, R ^2-2a1 , R ^3-2a1 , R ^4-2a1 , R ^5-2a1 , R
^6-2a1 , R ^7-2a1 , R ^8-2a1 and R ^9-2a1 are R ² and
It has the same meaning as R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ and R ⁹ . However, R ^2-2a1 , R ^3-2a1 , R ^4-2a1 , R ^5-2a1 , R
^At least one of ^6-2a1 , R ^7-2a1 , R ^{8-2a 1} and R ^9-2a1 groups is protected by a —COOH group (eg, methyl group, ethyl group, t-butyl group and benzyl group); Group or the like) or a group containing them, and other symbols have the same meanings as described above. It can be produced by subjecting the compound represented by the formula (1) to an alkali hydrolysis, a deprotection reaction under acidic conditions or a deprotection reaction by hydrogenolysis. The hydrolysis under alkaline conditions, the deprotection reaction under acid conditions, and the deprotection reaction by hydrogenolysis are known, and they are carried out by the methods described above.

[3] Compounds of the present invention represented by the general formula (I), wherein R ¹ is-(CH ₂ ) _n SR ^50, that is, the general formula (I-3)

[Chemical 49] (Wherein, R ^1-3 is -. (CH ₂₎ represents an _n SR ^50, and the other symbols represent the same meanings as described above), a compound represented by the
It can be produced by the following methods (a) and (b).

(A) R¹Is-(CH₂)_nSR⁵⁰Represents
And R², R³, R^Four, R^Five, R⁶, R ⁷, R⁸And R⁹
Any of the groups is a -COOH group or a group containing it.
Compounds not represented, ie, general formula (I-3a)

[Chemical 50] (In the formula, R ^2-3a , R ^3-3a , R ^4-3a , R ^5-3a , R ^6-3a , R
^7-3a , R ^8-3a and R ^9-3a are R ² , R ³ , R ⁴ and R ⁵ , respectively.
It has the same meaning as R ⁶ , R ⁷ , R ⁸ and R ⁹ . However, R
^2-3a , R ^3-3a , R ^4-3a , R ^5-3a , R ^6-3a , R ^7-3a , R
^{None of 8-3a} and R ^9-3a groups represents a -COOH group or a group containing them, and other symbols have the same meanings as described above. ) Is a compound represented by the general formula (V
I)

[Chemical 51] (In the formula, X represents a halogen atom and other symbols have the same meanings as described above.), And a compound represented by the general formula (VII) R ⁵⁰¹ SK (VII) (wherein R ⁵⁰¹ is C1-8). Alkyl group, -COR ⁵² ,-
SR ⁵³¹ (in the group, R ⁵³¹ represents a C1-8 alkyl group or a phenyl group). It can be produced by reacting a compound represented by

When R ⁵⁰ represents a hydrogen atom or --SH, it can be produced by subjecting the compound obtained above to a deprotection reaction.
The above reaction is known and, for example, an organic solvent (acetone,
It is carried out by refluxing in tetrahydrofuran or the like). Further, the deprotection reaction that is subsequently performed is known, and for example, in an organic solvent (methanol, tetrahydrofuran, dioxane, etc.), an alkali metal hydroxide (sodium hydroxide, potassium hydroxide, lithium hydroxide, etc.),
It is carried out at a temperature of 0 to 40 ° C. using an alkaline earth metal hydroxide (barium hydroxide, calcium hydroxide, etc.) or carbonate (sodium carbonate, potassium carbonate, etc.) or an aqueous solution thereof, or a mixture thereof.

(B) R¹Is-(CH₂)_nSR⁵⁰Represents
And R², R³, R^Four, R^Five, R⁶, R ⁷, R⁸And R⁹
At least one of the groups is a -COOH group or
A compound representing a group containing it, that is, a compound represented by the general formula (I-
3b)

[Chemical 52] (In the formula, R ^2-3b , R ^3-3b , R ^4-3b , R ^5-3b , R ^6-3b , R
^7-3b , R ^8-3b and R ^9-3b are R ² , R ³ , R ⁴ and R ⁵ , respectively.
It has the same meaning as R ⁶ , R ⁷ , R ⁸ and R ⁹ . However, R
^2-3b , R ^3-3b , R ^4-3b , R ^5-3b , R ^6-3b , R ^7-3b , R
^{In the} groups ^8-3b and R ^9-3b , at least one group represents a -COOH group or a group containing them, and the other symbols have the same meanings as described above. ) Is a compound of the above formula (I-3a) in which a —COOH group or a group containing them is protected, that is, a compound of the formula (I-
3a1)

[Chemical 53] (In the formula, R ^2-3a1 , R ^3-3a1 , R ^4-3a1 , R ^5-3a1 , R 3
^6-3a1 , R ^7-3a1 , R ^8-3a1 and R ^9-3a1 are R ² , respectively.
It has the same meaning as R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ and R ⁹ . However, R ^2-3a1 , R ^3-3a1 , R ^4-3a1 , R ^5-3a1 , R
^At least one of the groups ^6-3a1 , R ^7-3a1 , R ^{8-3a 1} and R ^9-3a1 is protected by a —COOH group (for example, methyl group, ethyl group, t-butyl group and benzyl group); Group or the like) or a group containing them, and other symbols have the same meanings as described above. It can be produced by subjecting the compound represented by the formula (1) to an alkali hydrolysis, a deprotection reaction under acidic conditions or a deprotection reaction by hydrogenolysis. The hydrolysis under alkaline conditions, the deprotection reaction under acid conditions, and the deprotection reaction by hydrogenolysis are known, and they are carried out by the methods described above.

[4] A compound of the present invention represented by the general formula (I), wherein R ¹ is -Y-PO (OR ^{5 1} ) ₂ .
That is, the general formula (I-4)

[Chemical 54] (Wherein, R ^1-4 represents _{^{-Y-PO (OR 51) 2}} , and other symbols. Of the same meanings as defined above), a compound represented by the method of the following (a) ~ (d) Can be manufactured in.

(A) R ¹ represents —Y ¹ —PO (OR ⁵¹ ) ₂ (wherein Y ¹ represents —O— and other symbols have the same meanings as described above), and R ² , R ³ , R ⁴ ,
All of the groups R ⁵ , R ⁶ , R ⁷ , R ⁸ and R ⁹ are —COO.
A compound which does not represent an H group or a group containing it, that is, a compound of the general formula (I-4a)

[Chemical 55] (In the formula, R ^2-4a , R ^3-4a , R ^4-4a , R ^5-4a , R ^6-4a , R
^7-4a , R ^8-4a and R ^9-4a are R ² , R ³ , R ⁴ and R ⁵ , respectively.
It has the same meaning as R ⁶ , R ⁷ , R ⁸ and R ⁹ . However, R
^2-4a , R ^3-4a , R ^4-4a , R ^5-4a , R ^6-4a , R ^7-4a , R
^{None of the 8-4a} and R ^9-4a groups represents a -COOH group or a group containing them, and the other symbols have the same meanings as described above. ) Is a compound represented by the general formula (VI
II)

[Chemical 56] (Wherein all symbols have the same meanings as described above), and a compound of the general formula (IX)

[Chemical 57] (In the formula, R ⁵¹¹ represents a C1-8 alkyl group, a phenyl group or a known protecting group for phosphoric acid, and other symbols have the same meanings as described above.) When protected, it can be produced by subsequent deprotection reaction. The above reaction is known and, for example, in an organic solvent (pyridine or the like),
It is carried out by reacting at 0 to 40 ° C. The deprotection reaction of the protecting group of phosphoric acid is known, and for example, using zinc acetic acid in an organic solvent (pyridine or the like), 0 to 40 ° C.
It is carried out by reacting with.

(B) R ¹ represents --Y ¹ --PO (OR ⁵¹ ) ₂ and, among R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ and R ⁹ groups, Compounds in which at least one group represents a -COOH group or a group containing it, i.e. formula (I-4b)

[Chemical 58] (In the formula, R ^2-4b , R ^3-4b , R ^4-4b , R ^5-4b , R ^6-4b , R
^7-4b , R ^8-4b and R ^9-4b are R ² , R ³ , R ⁴ and R ⁵ , respectively.
It has the same meaning as R ⁶ , R ⁷ , R ⁸ and R ⁹ . However, R
^2-4b , R ^3-4b , R ^4-4b , R ^5-4b , R ^6-4b , R ^7-4b , R
^Among the groups ^8-4b and R ^9-4b , at least one group represents a -COOH group or a group containing them, and the other symbols have the same meanings as described above. ) Is a compound of the above formula (I-4a) in which a —COOH group or a group containing them is protected, that is, the compound of the formula (I-
4a1)

[Chemical 59] (In the formula, R ^2-4a1 , R ^3-4a1 , R ^4-4a1 , R ^5-4a1 , R
^6-4a1 , R ^7-4a1 , R ^8-4a1 and R ^9-4a1 are each R ² ,
It has the same meaning as R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ and R ⁹ . However, R ^2-4a1 , R ^3-4a1 , R ^4-4a1 , R ^5-4a1 , R
^At least one of the ^6-4a1 , R ^7-4a1 , R ^{8-4a 1} and R ^9-4a1 groups is protected by a —COOH group (for example, methyl group, ethyl group, t-butyl group and benzyl group); Group or the like) or a group containing them, and other symbols have the same meanings as described above. It can be produced by subjecting the compound represented by the formula (1) to an alkali hydrolysis, a deprotection reaction under acidic conditions or a deprotection reaction by hydrogenolysis. The hydrolysis under alkaline conditions, the deprotection reaction under acid conditions, and the deprotection reaction by hydrogenolysis are known, and they are carried out by the methods described above.

(C) R ¹ represents --Y ² --PO (OR ⁵¹ ) ₂ (wherein Y ² represents a single bond or --CH _2- , and other symbols have the same meanings as described above). And a compound in which none of the R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ and R ⁹ groups represents a —COOH group or a group containing it, that is, a compound represented by the general formula (I- 4c)

[Chemical 60] (In the formula, R ^2-4c , R ^3-4c , R ^4-4c , R ^5-4c , R ^6-4c , R
^7-4c , R ^8-4c and R ^9-4c are R ² , R ³ , R ⁴ and R ⁵ , respectively.
It has the same meaning as R ⁶ , R ⁷ , R ⁸ and R ⁹ . However, R
^2-4c , R ^3-4c , R ^4-4c , R ^5-4c , R ^6-4c , R ^7-4c , R
^{Neither 8-4c nor} R ^9-4c represents a --COOH group or a group containing them, and the other symbols have the same meanings as described above. ) Is a compound represented by the general formula (X):

[Chemical formula 61] (Wherein all symbols have the same meanings as described above), the compound of the general formula (XI) or (XII) (R ⁵¹¹ O) ₃ P (XI) (R ⁵¹¹ O) ₂ POK (XII ) (Wherein all symbols have the same meanings as described above), and when phosphoric acid is protected, it can be produced by subsequent deprotection reaction. . The above reaction is known, and is carried out, for example, by reacting in an organic solvent (tetrahydrofuran, dimethylformamide, etc.) at 0 to 120 ° C. The deprotection reaction of the phosphoric acid group is known and is carried out by the method described above.

(D) R ¹ represents —Y ² —PO (OR ⁵¹ ) ₂ and, among R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ and R ⁹ groups, A compound in which at least one group represents a -COOH group or a group containing the same, that is, the general formula (I-4d)

[Chemical formula 62] (In the formula, R ^2-4d , R ^3-4d , R ^4-4d , R ^5-4d , R ^6-4d , R
^7-4d , R ^8-4d and R ^9-4d are R ² , R ³ , R ⁴ and R ⁵ , respectively.
It has the same meaning as R ⁶ , R ⁷ , R ⁸ and R ⁹ . However, R
^2-4d , R ^3-4d , R ^4-4d , R ^5-4d , R ^6-4d , R ^7-4d , R
^Among the groups ^8-4d and R ^9-4d , at least one group represents a -COOH group or a group containing them, and the other symbols have the same meanings as described above. ) Is a compound of the above formula (I-4c) in which the —COOH group or a group containing them is protected, that is, the compound of the formula (I-
4c1)

[Chemical formula 63] (In the formula, R ^2-4c1 , R ^3-4c1 , R ^4-4c1 , R ^5-4c1 , R
^6-4c1 , R ^7-4c1 , R ^8-4c1 and R ^9-4c1 are R ² , respectively.
It has the same meaning as R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ and R ⁹ . However, R ^2-4c1 , R ^3-4c1 , R ^4-4c1 , R ^5-4c1 , R
^At least one of the groups ^6-4c1 , R ^7-4c1 , R ^{8-4c 1} and R ^9-4c1 is protected by a —COOH group (for example, methyl group, ethyl group, t-butyl group and benzyl group); Group or the like) or a group containing them, and other symbols have the same meanings as described above. It can be produced by subjecting the compound represented by the formula (1) to an alkali hydrolysis, a deprotection reaction under acidic conditions or a deprotection reaction by hydrogenolysis.

The hydrolysis under alkaline conditions, the deprotection reaction under acid conditions, and the deprotection reaction by hydrogenolysis are known and are carried out by the above-mentioned methods. In the present invention, the deprotection reaction means a general deprotection reaction that can be easily understood by those skilled in the art, such as alkaline hydrolysis, deprotection reaction under acidic conditions, and deprotection reaction by hydrogenolysis. The intended compound of the present invention can be easily produced by properly selecting the reaction.

As can be easily understood by those skilled in the art, the protecting group for the carboxyl group includes a methyl group, an ethyl group, a t-butyl group and a benzyl group. There is no particular limitation as long as it is a group capable of leaving. For example TWGreene, Protective Gro
The one described in ups in Organic Synthesis, Wiley, New York, 1991 is used.

Examples of the hydroxyl-protecting group include a methoxymethyl group, a tetrahydropyranyl group, a t-butyldimethylsilyl group, an acetyl group and a benzyl group. Other than these, it is a group which can be easily and selectively removed. There is no particular limitation as long as it exists. For example, TW Greene, Protective Groups
The one described in Organic Synthesis, Wiley, New York, 1991 is used.

Examples of the amino group-protecting group include a benzyloxycarbonyl group, a t-butoxycarbonyl group, and a trifluoroacetyl group. Other than these, it is particularly limited as long as it is a group that can be easily and selectively removed. Not done. For example TW Greene, Protective Groups in Organic Sy
The one described in nthesis, Wiley, New York, 1991 is used.

General formula (II), general formula (III), general formula (I
V), general formula (V), general formula (VI), general formula (VII), general formula (VIII), general formula (IX), general formula (X), general formula (XI), or general formula (XII The compound shown in () is known per se or can be easily produced by a known method.

In each reaction in the present specification, the reaction product is obtained by a conventional purification means such as distillation under normal pressure or reduced pressure, high performance liquid chromatography using silica gel or magnesium silicate, thin layer chromatography, or It can be purified by a method such as column chromatography, washing, or recrystallization. Purification may be carried out for each reaction or after completion of some reactions.

[0194]

[Pharmacological activity of the compound of the present invention] It was proved by the following experiment that the compound of the present invention represented by the general formula (I) has a matrix metalloproteinase inhibitory activity.

(1) Gelatinase A Inhibitory Activity [Experimental Method] 10 mM p-aminophenylmercuric acetate (40 μl) in a solution of progeratinase A (5 μl) purified from normal human dermal fibroblasts (HNDF) in assay buffer (40 μl). APMA) (5 μl)
The enzyme was activated by preincubating at 37 ° C. for 1 hour. Synthetic substrate (MOCAc-Pro-Leu-Gly-A2pr (Dnp) -Ala-
Arg-NH ₂ ) (130 μl; final concentration 13.5 μM) and various concentrations of the test compound solution or no test compound added solution (20 μl) were preincubated at 37 ° C. for 5 minutes. The activated enzyme (50 μl / well) prepared above was added thereto and incubated at 37 ° C. for 15 minutes to start the enzyme reaction. Enzyme activity is fluorescence intensity per minute [325 nm (Ex) / 393 nm
(Em)]. The inhibitory activity was represented by the inhibition rate (%) with respect to the enzyme activity when the test compound was not added. For example, the compound of Example 71 has an IC ₅₀ value of 0.
It was 50 nM.

(2) Collagenase Inhibitory Activity [Experimental Method] 1 mg / ml trypsin (45 μl) was added to an assay buffer (105 μl) solution of procollagenase (5 μl) purified from human normal skin fibroblasts (HNDF). The enzyme was activated by preincubation at 37 ° C for 1 minute. 5 mg / in the solution
ml soybean trypsin inhibitor
tor) (SBTI; 50 μl) was added to inactivate trypsin. Synthetic substrate (Ac-Pro-Leu-Gly- [2-mercapto
4-methyl-pentanoyl] -Leu-Gly-OEt) (105 μl; final concentration 1.33 mM) and various concentrations of test compound solutions or test compound-free solutions (20 μl)
Pre-incubated at 6 ° C for 5 minutes. Activated enzyme prepared above (75 μl / tube, 50 μl)
Was added and incubated at 26 ° C. for 10 minutes.
A total of 40 points of absorbance at 324 nm were measured during this 10 minutes, and Vmax at 30 points was taken as the measured value. For example, the compound of Example 71 has an IC ₅₀ value of 2.
It was 5 μM.

(3) Strommlysin Inhibitory Activity [Experimental Method] 9 volumes of human stromlysin (Yagai) were added to 10 mM p-aminophenylmercuric acetate (APM).
A) It was mixed with 1 volume and activated at 37 ° C. for 20 hours. Assay buffer (50mM Tris-HCl, 10mM CaCl ₂ , 0.05% B
rij35, 0.02% NaN ₃ (pH 7.5)) 10 μl of a test compound dissolved in 150 μl of dimethyl sulfoxide and synthetic substrate NFF-3 (Mca-Arg-Pro-Lys-Pro-Val-Glu-Nva-Trp-Ar)
g-Lys (DNP) -NH ₂ , Nva: norvaline, Peptide Research Institute)
10 mM dimethyl sulfoxide solution of 0.5 mM with water
After adding 10 μl of the reaction mixture to 30 μl of the assay buffer and incubating at 37 ° C. for 10 minutes, 50 μl of the activated stromlysin solution was added.
1 was added to start the enzymatic reaction. The enzyme activity was represented by the amount of increase in fluorescence intensity [325 nm (Ex) / 393 nm (Em)] per minute. The inhibitory activity was represented by the inhibition rate (%) with respect to the enzyme activity when the test compound was not added. For example, the compound of Example 71 had an IC ₅₀ value of 26 nM.

[0198]

[Toxicity] The toxicity of the compound of the present invention is extremely low,
It can be judged to be sufficiently safe for use as a medicine.

[0199]

[Application to pharmaceuticals] In animals including humans, particularly in humans, rheumatism, osteoarthritis, pathological bone resorption, osteoporosis, periodontal disease, by inhibiting matrix metalloproteinases such as gelatinase, stromlysin or collagenase. Interstitial nephritis, arteriosclerosis, emphysema, liver cirrhosis, corneal damage, cancer cell metastasis invasion and proliferation disease, autoimmune disease (Crohn's disease, Schgren's disease, etc.), leukocyte cell migration and infiltration It is useful for the prevention and / or treatment of angiogenesis, multiple sclerosis, aortic aneurysm, endometriosis and the like.

In order to use the compound of the present invention represented by the general formula (I), a non-toxic salt thereof, an acid addition salt or a hydrate thereof for the above-mentioned purpose, it is usually systemically or topically, orally or It is administered in parenteral form.

Dosage depends on age, body weight, symptoms, therapeutic effect,
Although it varies depending on the administration method, treatment time, etc., it is usually 1 dose per adult per dose in the range of 1 mg to 1000 mg.
Orally administered once to several times a day, or once per adult, in the range of 1 mg to 100 mg, parenterally administered once to several times a day (preferably intravenous administration), Alternatively, it is continuously administered intravenously within the range of 1 hour to 24 hours per day. Of course, as described above, since the dose varies depending on various conditions, a dose smaller than the above dose may be sufficient in some cases, or a dose exceeding the range may be necessary in some cases.

When the compound of the present invention is administered, it is used as a solid composition, a liquid composition and other compositions for oral administration and an injection, an external preparation, a suppository etc. for parenteral administration. Solid compositions for oral administration include tablets, pills, capsules, powders, granules and the like. Capsules include hard capsules and soft capsules.

In such solid compositions, the one or more active substances comprises at least one inert diluent such as lactose, mannitol, glucose, hydroxypropyl cellulose, microcrystalline cellulose, starch, polyvinylpyrrolidone, Mixed with magnesium aluminometasilicate. The composition comprises, according to a conventional method, additives other than an inert diluent, for example, a lubricant such as magnesium stearate, a disintegrant such as calcium fibrin glycolate, a stabilizer such as lactose, glutamic acid or asparagine. It may contain a solubilizing agent such as an acid. If necessary, the tablets or pills may be coated with a film of a gastric or enteric substance such as sucrose, gelatin, hydroxypropylcellulose, hydroxypropylmethylcellulose phthalate, or may be coated with two or more layers. . Also included are capsules of absorbable material such as gelatin.

Liquid compositions for oral administration include pharmaceutically acceptable emulsions, solutions, syrups, elixirs and the like. In such a liquid composition, one or more active substances are contained in a commonly used inert diluent (eg, purified water, ethanol). The composition may contain, in addition to an inert diluent, auxiliary agents such as a wetting agent and a suspending agent, a sweetening agent, a flavoring agent, an aromatic agent, and a preservative.

Other compositions for oral administration include spray formulations which contain one or more active substances and are formulated in a manner known per se. This composition contains, in addition to an inert diluent, a stabilizer such as sodium bisulfite and a buffer that provides isotonicity, for example, isotonic agents such as sodium chloride, sodium citrate or citric acid. May be. For example, US Pat. Nos. 2,868,691 and US Pat.
It is described in detail in No. 3,095,355.

The injections for parenteral administration according to the present invention include sterile aqueous or non-aqueous solutions, suspensions and emulsions. Examples of the aqueous solution and suspension include distilled water for injection and physiological saline. Examples of the water-insoluble solution and suspension include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, alcohols such as ethanol, Polysorbate 80 (registered trademark) and the like. Such compositions may further contain adjuvants such as preservatives, wetting agents, emulsifiers, dispersants, stabilizers (eg lactose), solubilizers (eg glutamic acid, aspartic acid). . These are sterilized by filtration through a bacteria-retaining filter, blending of a bactericide, or irradiation. They can also be used by producing a sterile solid composition, for example, by dissolving in sterilized or sterile distilled water for injection or other solvent before use of a lyophilized product.

Other compositions for parenteral administration include external solutions, ointments, coatings, suppositories for rectal administration, which contain one or more active substances and are formulated by a conventional method. Includes pessaries and the like for vaginal administration.

[0208]

The present invention will be described in detail below with reference to reference examples and examples, but the present invention is not limited thereto. Chromatographic separation points and TLC
The solvent in parentheses shown in () indicates the elution solvent or developing solvent used, and the ratio represents the volume ratio. The solvent in parentheses shown in the NMR part indicates the solvent used for the measurement.

Reference Example 1 2- (dihydroxyboronyl) benzofuran

[Chemical 64] Benzofuran (128 g) in tetrahydrofuran (54
0 ml) solution under cooling with dry ice-methanol bath,
1.6N n-butyllithium hexane solution (750m
l) was added dropwise. The reaction mixture was stirred at 0 ° C. for 30 minutes, and triisopropyl borate (275 ml) was added dropwise under cooling with a dry ice-methanol bath. The reaction mixture was stirred at 0 ° C. for 1 hour. The reaction mixture was concentrated to 1 residue.
An aqueous solution of N hydrochloric acid was added, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated. The obtained crystals were washed with hexane and dried to give the title compound (1
57 g) was obtained. TLC: Rf 0.28 (n-hexane: ethyl acetate = 1: 1
1).

Reference Example 2 4- (Benzofuran-2-yl) benzoic acid ethyl ester

[Chemical 65] In a solution of 4-iodobenzoic acid ethyl ester (5 g) in dimethylformamide (10 ml), the compound (2.64 g) prepared in Reference Example 1 and dichlorobis (triphenylphosphine) palladium (II) [PdCl ₂ (PPh ₃ ) ₂ ] ( 0.6
35 g) and triethylamine (10 ml) were added. The reaction mixture was stirred at 80 ° C. for 6 hours. A 1N aqueous hydrochloric acid solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated. The obtained crystals were washed with hexane / diethyl ether and dried to give the title compound (3.6 g) having the following physical data. TLC: Rf 0.61 (n-hexane: ethyl acetate = 9:
1).

Reference Example 3 4- (Benzofuran-2-yl) benzoic acid

[Chemical formula 66] The dioxane (1) of the compound (3.4 g) produced in Reference Example 2
5 ml) solution at room temperature with 1N aqueous sodium hydroxide solution (1
5.3 ml) was added. The reaction mixture was stirred at room temperature for 9 hours. A 1N aqueous hydrochloric acid solution was added to the reaction mixture until it became acidic, and the mixture was extracted with ethyl acetate: tetrahydrofuran (2: 1). The extract was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated. The obtained crystals were washed with ethyl acetate / diethyl ether and dried to give the title compound (2.1 g) having the following physical data. TLC: Rf 0.43 (chloroform: methanol: acetic acid = 100: 10: 1).

Reference Example 4 4- (Benzofuran-2-yl) benzoyl chloride

[Chemical formula 67] A mixture of the compound (13.4 g) produced in Reference Example 3 and thionyl chloride (80 ml) was stirred at 80 ° C. for 6 hours. The reaction mixture was cooled to room temperature and concentrated. The obtained residue was washed with hexane / diethyl ether to give the title compound (12.7 g) having the following physical data. NMR (CDCl ₃ ): δ 8.19 (2H, d, J = 8.8Hz), 7.98
(2H, d, J = 8.8Hz), 7.68-7.61 (1H, m), 7.59-7.53 (1
H, m), 7.42-7.23 (3H, m).

Example 1 4- (N- (4- (benzofuran-2-yl) phenylcarbonyl) amino) butanoic acid ethyl ester

[Chemical 68] A solution of 4-aminobutanoic acid ethyl ester (0.5 g) in dichloromethane (20 ml) was treated with triethylamine (1 m).
l) was added. A solution of the compound prepared in Reference Example 4 (0.72 g) in dichloromethane (10 ml) was added to the mixture at 0 ° C. The reaction mixture was stirred at room temperature for 30 minutes. A 1N aqueous hydrochloric acid solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated. The obtained residue was washed with ethyl acetate / diethyl ether and dried to give the title compound (0.732 g) having the following physical data. TLC: Rf 0.38 (n-hexane: ethyl acetate = 1: 1
1).

Example 2 4- (N- (4- (benzofuran-2-yl) phenylcarbonyl) amino) butanoic acid

[Chemical 69] To a solution of the compound (670 mg) prepared in Example 1 in tetrahydrofuran (5 ml) was added a 1N sodium hydroxide aqueous solution (4.4 ml). The reaction mixture was stirred at room temperature for 3 hours. A 1N aqueous hydrochloric acid solution was added to the reaction mixture until it became acidic, and the mixture was extracted with ethyl acetate / tetrahydrofuran. The extract was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated to give the title compound (0.617 g) having the following physical data. TLC: Rf 0.40 (chloroform: methanol: acetic acid = 100: 10: 1); NMR (CD ₃ OD): δ 8.58 (1H, t, J = 5.6Hz), 8.01
(2H, d, J = 8.8Hz), 7.96 (2H, d, J = 8.8Hz), 7.71-7.63
(2H, m), 7.57 (1H, d, J = 0.8Hz), 7.39-7.23 (2H, m),
3.32-3.25 (2H, m), 2.29 (2H, t, J = 7.6Hz), 1.84-1.
70 (2H, m).

Examples 2 (1) to 2 (24) Using the corresponding acid halide in place of the compound prepared in Reference Example 4, the same procedure as in Example 1 → Example 2 was repeated, and The compound shown in was obtained.

Example 2 (1) 4- (N- (4-methylphenylcarbonyl) amino)
Butanoic acid

[Chemical 70] TLC: Rf 0.50 (chloroform: methanol: acetic acid = 18: 2: 1); NMR (CD ₃ OD): δ 12.10 (1H, brs), 8.30 (1H, t,
J = 5.5Hz), 7.76 (2H, d, J = 8.0Hz), 7.28 (2H, d, J = 8.
0Hz), 3.30 (2H, m), 2.30 (2H, t, J = 7.2Hz), 1.75 (2
H, m).

Example 2 (2) 4- (N- (4-butyloxyphenylcarbonyl) amino) butanoic acid

[Chemical 71] TLC: Rf 0.48 (chloroform: methanol: acetic acid = 18: 2: 1); NMR (d ₆ -DMSO): δ 12.03 (1H, brs), 8.29 (1H,
t, J = 5.5Hz), 7.78 (2H, d, J = 8.8Hz), 6.95 (2H, d, J
= 8.8Hz), 3.99 (2H, t, J = 6.4Hz), 3.30-3.14 (2H, m),
2.24 (2H, t, J = 7.6Hz), 1.79-1.62 (4H, m), 1.51-1.3
2 (2H, m), 0.91 (3H, t, J = 7.4Hz).

Example 2 (3) 4- (N- (3-butyloxyphenylcarbonyl) amino) butanoic acid

[Chemical 72] TLC: Rf 0.58 (chloroform: methanol: acetic acid = 18: 2: 1); NMR (d ₆ -DMSO): δ 12.04 (1H, brs), 8.42 (1H,
t, J = 5.4Hz), 7.41-7.28 (3H, m), 7.07-7.00 (1H, m),
3.99 (2H, t, J = 6.4Hz), 3.24 (2H, m), 2.25 (2H, t,
J = 7.3Hz), 1.80-1.64 (4H, m), 1.42 (2H, m), 0.92 (3
H, t, J = 7.3 Hz).

Example 2 (4) 4- [N- [4- (2- (4-methylphenyl) ethynyl) furan-2-ylcarbonyl] amino] butanoic acid

[Chemical formula 73] TLC: Rf 0.54 (chloroform: methanol: acetic acid = 18: 2: 1); NMR (d ₆ -DMSO): δ 12.07 (1H, brs), 8.51 (1H,
t, J = 6.0Hz), 7.44 (2H, d, J = 8.1Hz), 7.25 (2H, d, J
= 8.1Hz), 7.12 (1H, d, J = 3.7Hz), 6.94 (1H, d, J = 3.7H)
z), 3.26-3.23 (2H, m), 2.33 (3H, s), 2.23 (2H, d,
J = 7.5Hz), 1.79-1.63 (2H, m).

Example 2 (5) 4- (N- (4- (pyrrol-1-yl) phenylcarbonyl) amino) butanoic acid

[Chemical 74] TLC: Rf 0.59 (chloroform: methanol: acetic acid = 18: 2: 1); NMR (d ₆ -DMSO): δ 12.04 (1H, brs), 7.94 (2H,
d, J = 8.8Hz), 7.66 (2H, d, J = 8.8Hz), 7.47-7.44 (2H,
m), 6.31-6.28 (2H, m), 3.32-3.25 (2H, m), 2.29 (2
H, t, J = 7.3Hz), 1.77 (2H, m).

Example 2 (6) 4- (N- (trans-4-methylcyclohexylcarbonyl) amino) butanoic acid

[Chemical 75] TLC: Rf 0.55 (chloroform: methanol: acetic acid = 18: 2: 1); NMR (d ₆ -DMSO): δ 12.01 (1H, brs), 7.67 (1H,
t, J = 6.0Hz), 3.02 (2H, m), 2.19 (2H, t, J = 7.5Hz),
2.06-1.91 (1H, m), 1.74-1.52 (6H, m), 1.46-1.18 (4
H, m), 0.98-0.76 (4H, m).

Example 2 (7) 4- (N- (4- (3-methoxy-1-propynyl) phenylcarbonyl) amino) butanoic acid

[Chemical 76] TLC: Rf 0.45 (chloroform: methanol: acetic acid = 18: 2: 1); NMR (d ₆ -DMSO): δ 12.03 (1H, brs), 8.54 (1H,
t, J = 5.3Hz), 7.85 (2H, d, J = 8.2Hz), 7.52 (2H, d, J
= 8.2Hz), 4.34 (2H, s), 3.35 (3H, s), 3.34-3.22 (2
H, m), 2.28 (2H, t, J = 7.0Hz), 1.76 (2H, m).

Example 2 (8) 4- (N- (4-butylphenylcarbonyl) amino)
Butanoic acid

[Chemical 77] TLC: Rf 0.54 (chloroform: methanol: acetic acid = 18: 2: 1); NMR (CD ₃ OD): δ 12.03 (1H, brs), 8.37 (1H, t,
J = 5.5Hz), 7.75 (2H, d, J = 8.2Hz), 7.25 (2H, d, J = 8.
2Hz), 3.33-3.22 (2H, m), 2.62 (2H, t, J = 7.5Hz), 2.
27 (2H, t, J = 7.4Hz), 1.83-1.67 (2H, m), 1.65-1.48
(2H, m), 1.40-1.22 (2H, m), 0.90 (3H, t, J = 7.1H
z).

Example 2 (9) 4- (N- (benzofuran-2-ylcarbonyl) amino) butanoic acid

[Chemical 78] TLC: Rf 0.32 (chloroform: methanol: acetic acid = 100: 10: 1); NMR (d ₆ -DMSO): δ 8.73 (1H, t, J = 5.4Hz), 7.78
-7.73 (1H, m), 7.66-7.61 (1H, m), 7.51 (1H, d, J =
0.8Hz), 7.49-7.41 (1H, m), 7.36-7.28 (1H, m), 3.28
(2H, m), 2.27 (2H, t, J = 7.4Hz), 1.83-1.68 (2H,
m).

Example 2 (10) 4- [N- [4- (2- (4-chlorophenyl) ethenyl) phenylcarbonyl] amino] butanoic acid

[Chemical 79] TLC: Rf 0.28 (chloroform: methanol = 1
0: 1); NMR (d ₆ -DMSO): δ 8.48 (1H, t, J = 5.6Hz), 7.85
(2H, d, J = 8.4Hz), 7.67 (2H, d, J = 8.4Hz), 7.65 (2
H, d, J = 8.8Hz), 7.44 (2H, d, J = 8.8Hz), 7.40 (1H, d,
J = 16.4Hz), 7.30 (1H, d, J = 16.4Hz), 3.27 (2H, m),
2.27 (2H, t, J = 7.4Hz), 1.82-1.68 (2H, m).

Example 2 (11) 4- [N- [4- (2- (4- (imidazol-1-yl) phenyl) ethynyl) phenylcarbonyl] amino] butanoic acid

[Chemical 80] TLC: Rf 0.29 (chloroform: methanol: acetic acid = 100: 10: 1); NMR (d ₆ -DMSO): δ 8.65 (1H, t, J = 5.4Hz), 8.36
(1H, brs), 7.90 (2H, d, J = 8.4Hz), 7.84 (1H, brs),
7.77 (2H, d, J = 9.2Hz), 7.71 (2H, d, J = 9.2Hz), 7.6
5 (2H, d, J = 8.4Hz), 7.13 (1H, brs), 3.28 (2H, m),
2.31 (2H, t, J = 7.2Hz), 1.82-1.68 (2H, m).

Example 2 (12) 4- (N- (trans-4-propylcyclohexylcarbonyl) amino) butanoic acid

[Chemical 81] TLC: Rf 0.65 (chloroform: methanol: acetic acid = 18: 2: 1); NMR (d ₆ -DMSO): δ 12.00 (1H, s), 7.74-7.61 (1
H, t, J = 6.0Hz), 3.02 (2H, m), 2.19 (2H, t, J = 7.2H
z), 2.11-1.92 (1H, m), 1.78-1.53 (6H, m), 1.43-1.0
8 (7H, m), 0.95-0.89 (5H, m).

Example 2 (13) 4- [N- [4- (2- (4-methylphenyl) ethynyl) phenylcarbonyl] amino] butanoic acid

[Chemical formula 82] TLC: Rf 0.57 (chloroform: methanol: acetic acid = 18: 2: 1); NMR (CD ₃ OD): δ 12.05 (1H, s), 8.57 (1H, t, J
= 5.5Hz), 7.88 (2H, d, J = 8.3Hz), 7.61 (2H, d, J = 8.3
Hz), 7.47 (2H, d, J = 8.3Hz), 7.25 (2H, d, J = 8.3Hz),
3.34-3.24 (2H, m), 2.35 (3H, s), 2.29 (2H, t, J =
7.2Hz), 1.77 (2H, m).

Example 2 (14) 4- [N- [4-((4-bromophenyl) aminosulfonyl) phenylcarbonyl] amino] butanoic acid

[Chemical 83] TLC: Rf 0.45 (chloroform: methanol: acetic acid = 18: 2: 1); NMR (d ₆ -DMSO): δ 12.03 (1H, brs), 10.53 (1H,
brs), 8.68-8.62 (1H, m), 7.95 (2H, d, J = 8.6Hz),
7.81 (2H, d, J = 8.6Hz), 7.42 (2H, d, J = 9.0Hz), 7.05
(2H, d, J = 9.0Hz), 3.33-3.21 (2H, m), 2.27 (2H, t,
J = 7.3Hz), 1.74 (2H, m).

Example 2 (15) 4- [N- (4-cyclohexylphenylcarbonyl)
Amino] butanoic acid

[Chemical 84] TLC: Rf 0.33 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 12.04 (1H, s), 8.45-8.27 (1
H, m), 7.75 (2H, d, J = 8.4Hz), 7.28 (2H, d, J = 8.4H
z), 3.34-3.21 (2H, m), 2.64-2.44 (1H, m), 2.26 (2
H, t, J = 7.3Hz), 1.85-1.61 (7H, m), 1.56-1.19 (5H,
m).

Example 2 (16) 4- [N- [4- (4-propylphenyl) phenylcarbonyl] amino] butanoic acid

[Chemical 85] TLC: Rf 0.32 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 12.05 (1H, s), 8.56-8.44 (1
H, m), 7.93 (2H, d, J = 8.4Hz), 7.73 (2H, d, J = 8.4H
z), 7.64 (2H, d, J = 8.4Hz), 7.30 (2H, d, J = 8.4Hz),
3.40-3.25 (2H, m), 2.61 (2H, t, J = 7.4Hz), 2.29 (2
H, t, J = 7.3Hz), 1.86-1.54 (4H, m), 0.92 (3H, t, J =
7.4 Hz).

Example 2 (17) 4- [N- [4- (4-hydroxyphenyl) phenylcarbonyl] amino] butanoic acid

[Chemical 86] TLC: Rf 0.17 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 12.05 (1H, s), 9.62 (1H,
s), 8.53-8.42 (1H, m), 7.89 (2H, d, J = 8.5Hz), 7.66
(2H, d, J = 8.2Hz), 7.56 (2H, d, J = 8.5Hz), 6.87 (2H,
d, J = 8.2Hz), 3.36-3.26 (2H, m), 2.29 (2H, t, J = 7.
2Hz), 1.77 (2H, m).

Example 2 (18) 4- [N- [4- (4-chlorophenyl) furan-2-
Ilcarbonyl] amino] butanoic acid

[Chemical 87] TLC: Rf 0.24 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 12.07 (1H, s), 8.62-8.51 (1
H, m), 7.94 (2H, d, J = 8.4Hz), 7.54 (2H, d, J = 8.4H
z), 7.17-7.11 (2H, m), 3.33-3.22 (2H, m), 2.29 (2
H, t, J = 7.2Hz), 1.77 (2H, m).

Example 2 (19) 4- [N- [4- (4-heptylphenyl) phenylcarbonyl] amino] butanoic acid

[Chemical 88] TLC: Rf 0.65 (chloroform: methanol: acetic acid = 18: 2: 1); NMR (d ₆ -DMSO): δ 12.04 (1H, s), 8.55-8.45 (1
H, m), 7.93 (2H, d, J = 8.4Hz), 7.73 (2H, d, J = 8.4H
z), 7.63 (2H, d, J = 8.4Hz), 7.29 (2H, d, J = 8.4Hz),
3.37-3.23 (2H, m), 2.62 (2H, t, J = 7.5Hz), 2.29 (2
H, t, J = 7.1Hz), 1.78 (2H, m), 1.68-1.48 (2H, m), 1.
39-1.15 (8H, m), 0.86 (3H, t, J = 6.6Hz).

Example 2 (20) 4- [N- [4- (4-methoxyphenyl) phenylcarbonyl] amino] butanoic acid

[Chemical 89] TLC: Rf 0.11 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 12.05 (1H, s), 8.55-8.45 (1
H, m), 7.91 (2H, d, J = 8.4Hz), 7.71 (2H, d, J = 8.4H
z), 7.68 (2H, d, J = 8.9Hz), 7.05 (2H, d, J = 8.9Hz),
3.81 (3H, s), 3.35-3.22 (2H, m), 2.29 (2H, t, J = 7.
3Hz), 1.76 (2H, m).

Example 2 (21) 4- [N- [4- (4-chlorophenyl) phenylcarbonyl] amino] butanoic acid

[Chemical 90] NMR (d ₆ -DMSO): δ 12.07 (1H, s), 8.59-8.50 (1
H, m), 7.95 (2H, d, J = 8.4Hz), 7.81-7.71 (4H, m), 7.
54 (2H, d, J = 8.8Hz), 3.33-3.24 (2H, m), 2.29 (2H,
t, J = 7.3Hz), 1.82-1.71 (2H, m).

Example 2 (22) 4- [N- (5-benzyloxyindol-2-ylcarbonyl) amino] butanoic acid

[Chemical Formula 91] TLC: Rf 0.13 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 11.39 (1H, s), 8.42 (1H, t,
J = 5.6Hz), 7.50-7.20 (6H, m), 7.15 (1H, d, J = 2.2H
z), 6.99 (1H, d, J = 1.8Hz), 6.89 (1H, dd, J = 8.6, 2.
2Hz), 5.07 (2H, s), 3.27 (2H, m), 2.27 (2H, t, J =
7.4Hz), 1.73 (2H, m).

Example 2 (23) 4- [N- [5- (2- (4-chlorophenyl) ethenyl) furan-2-ylcarbonyl] amino] butanoic acid

[Chemical Formula 92] TLC: Rf 0.52 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1); NMR (d ₆ -DMSO): δ 12.06 (1H, brs), 8.43 (1H,
t, J = 5.8Hz), 7.59 (2H, d, J = 8.8Hz), 7.42 (2H, d, J
= 8.8Hz), 7.26 (1H, d, J = 16.6Hz), 7.14 (1H, d, J = 16.
6Hz), 7.09 (1H, d, J = 3.2Hz), 6.63 (1H, d, J = 3.2H
z), 3.25 (2H, m), 2.26 (2H, t, J = 7.2Hz), 1.73 (2H,
m).

Example 2 (24) 4- [N- (4-phenoxyphenylcarbonyl) amino] butanoic acid

[Chemical formula 93] TLC: Rf 0.47 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1); NMR (d ₆ -DMSO): δ 8.41 (1H, t, J = 5.4Hz), 7.85
(2H, d, J = 8.4Hz), 7.42 (2H, t, J = 8.0Hz), 7.18 (1
H, t, J = 7.2Hz), 6.97-7.08 (4H, m), 3.24 (2H, m),
2.25 (2H, t, J = 7.4Hz), 1.72 (2H, m).

Example 3 N- (1-methoxy-1,1-dimethylmethyl) oxy-4- (N- (4- (benzofuran-2-yl) phenylcarbonyl) amino) butyramide

[Chemical 94] N- (1-methoxy-1,1) was added to a solution of the compound (0.55 g) prepared in Example 2 in dimethylformamide (10 ml).
-Dimethylmethyloxy) amine (0.455g), 1-hydroxybenzotriazole hydrate (0.391g), 1
-Ethyl-3- (3-dimethylaminopropyl) carbodiimide / hydrochloride (0.489 g) was added under ice cooling, and the mixture was stirred at room temperature for 3 hours.
Stir for hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogen carbonate solution and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated to give the title compound (0.23
0 g) was obtained. TLC: Rf 0.13 (chloroform: methanol = 1)
0: 1).

Example 4 N-Hydroxy-4- (N- (4- (benzofuran-2
-Yl) phenylcarbonyl) amino) butyramide

[Chemical 95] To a solution of the compound (0.230 g) produced in Example 3 in methanol (10 ml) was added a 1N aqueous hydrochloric acid solution (100 ml). The reaction mixture was stirred at room temperature for 10 minutes. The reaction mixture was concentrated, and the obtained residue was washed with diethyl ether to give the title compound (0.218 g) having the following physical data. TLC: Rf 0.22 (chloroform: methanol: acetic acid = 100: 10: 1); NMR (d ₆ -DMSO): δ 10.39 (1H, brs), 8.59 (1H,
t, J = 5.8Hz), 8.01 (2H, d, J = 9.0Hz), 7.96 (2H, d, J
= 9.0Hz), 7.67 (2H, m), 7.57 (1H, d, J = 0.5Hz), 7.39
-7.23 (2H, m), 3.27 (2H, q, J = 5.8Hz), 2.03 (2H, t,
J = 7.6Hz), 1.76 (2H, m).

Examples 4 (1) -4 (36) Instead of the compounds prepared in Example 2, Examples 2 (1) -4
2 (24), or a compound obtained by operating in a similar manner to the method shown in Example 1 → Example 2 using the corresponding compound, and shown in Example 3 → Example 4 The compound shown below was obtained by the same procedure as described above.

Example 4 (1) N-hydroxy-4- (N- (4-methylphenylcarbonyl) amino) butyramide

[Chemical 96] TLC: Rf 0.23 (chloroform: methanol = 1
0: 1); NMR (d ₆ -DMSO): δ 10.39 (1H, s), 8.70 (1H,
s), 8.40 (1H, t, J = 5.2Hz), 7.74 (2H, d, J = 8.1Hz),
7.25 (2H, d, J = 8.1Hz), 3.24 (2H, td, J = 6.6,5.2Hz),
2.35 (3H, s), 2.02 (2H, t, J = 7.7Hz), 1.74 (2H,
m).

Example 4 (2) N-hydroxy-4- (N- (4-butyloxyphenylcarbonyl) amino) butyramide

[Chemical 97] TLC: Rf 0.29 (chloroform: methanol: acetic acid = 18: 2: 1); NMR (d ₆ -DMSO): δ 10.39 (1H, s), 8.70 (1H, br)
s), 8.32 (1H, t, J = 5.8Hz), 7.80 (2H, d, J = 9.0Hz),
6.96 (2H, d, J = 9.0Hz), 4.01 (2H, t, J = 6.4Hz), 3.35
-3.15 (2H, m), 2.01 (2H, t, J = 7.3Hz), 1.81-1.64 (4
H, m), 1.44 (2H, m), 0.94 (3H, t, J = 7.4Hz).

Example 4 (3) N-hydroxy-4- (N- (3-butyloxyphenylcarbonyl) amino) butyramide

[Chemical 98] TLC: Rf 0.31 (chloroform: methanol: acetic acid = 18: 2: 1); NMR (d ₆ -DMSO): δ 10.39 (1H, s), 8.45 (1H, t,
J = 5.2Hz), 7.43-7.29 (3H, m), 7.19-7.01 (1H, m), 4.
01 (2H, t, J = 6.3Hz), 3.30-3.18 (2H, m), 2.02 (2H,
t, J = 7.5Hz), 1.83-1.64 (4H, m), 1.49 (2H, m), 0.95
(3H, t, J = 7.3Hz).

Example 4 (4) N-Hydroxy-4- [N- [4-((4-methylphenyl) ethynyl) furan-2-ylcarbonyl] amino] butyramide

[Chemical 99] TLC: Rf 0.32 (chloroform: methanol: acetic acid = 18: 2: 1); NMR (d ₆ -DMSO): δ 10.40 (1H, brs), 10.22 (1H,
s), 8.56 (1H, t, J = 5.7Hz), 7.47 (2H, d, J = 8.3Hz),
7.28 (2H, d, J = 8.3Hz), 7.16 (1H, d, J = 3.6Hz), 6.9
6 (1H, d, J = 3.6Hz), 3.28-3.14 (2H, m), 2.36 (3H,
s), 2.00 (2H, t, J = 7.5Hz), 1.83-1.64 (2H, m).

Example 4 (5) N-Hydroxy-4- (N- (4- (pyrrol-1-yl) phenylcarbonyl) amino) butyramide

[Chemical 100] TLC: Rf 0.31 (chloroform: methanol: acetic acid = 18: 2: 1); NMR (d ₆ -DMSO): δ 10.40 (1H, s), 9.00-8.24 (1
H, brs), 8.52 (1H, t, J = 5.6Hz), 7.94 (2H, d, J = 8.5
Hz), 7.68 (2H, d, J = 8.5Hz), 7.50-7.44 (2H, m), 6.34
-6.29 (2H, m), 3.38-3.31 (2H, m), 2.04 (2H, t, J =
7.5Hz), 1.76 (2H, m).

Example 4 (6) N-hydroxy-4- (N- (trans-4-methylcyclohexylcarbonyl) amino) butyramide

[Chemical 101] TLC: Rf 0.29 (chloroform: methanol: acetic acid = 18: 2: 1); NMR (d ₆ -DMSO): δ 10.37 (1H, s), 10.20 (1H,
s), 7.69 (1H, t, J = 5.3Hz), 3.07-2.92 (2H, m), 2.31
-1.88 (3H, m), 1.74-1.52 (6H, m), 1.46-1.18 (3H,
m), 0.98-0.76 (2H, m), 0.85 (3H, d, J = 6.6Hz).

Example 4 (7) N-hydroxy-4- (N- (4- (3-methoxy-1)
-Propynyl) phenylcarbonyl) amino) butyramide

[Chemical 102] TLC: Rf 0.32 (chloroform: methanol: acetic acid = 18: 2: 1); NMR (d ₆ -DMSO): δ 10.39 (1H, s), 8.57 (1H, t,
J = 5.5Hz), 7.85 (2H, d, J = 8.6Hz), 7.53 (2H, d, J = 8.
6Hz), 4.35 (2H, s), 3.35 (3H, s), 3.25 (2H, dt, J =
5.5, 7.2Hz), 2.02 (2H, t, J = 7.2Hz), 1.74 (2H, quin
t, J = 7.2 Hz).

Example 4 (8) N-hydroxy-4- (N- (4-butylphenylcarbonyl) amino) butyramide

[Chemical 103] TLC: Rf 0.37 (chloroform: methanol: acetic acid = 18: 2: 1); NMR (d ₆ -DMSO): δ 10.40 (1H, brs), 10.20 (1H,
s), 8.41 (1H, t, J = 5.4Hz), 7.76 (2H, d, J = 8.0Hz),
7.25 (2H, d, J = 8.0Hz), 3.23 (2H, dt, J = 5.4Hz, J =
7.0Hz), 2.62 (2H, t, J = 8.2Hz), 2.02 (2H, t, J = 7.0H
z), 1.83-1.66 (2H, m), 1.64-1.48 (2H, m), 1.30 (2
H, m), 0.90 (3H, t, J = 7.2Hz).

Example 4 (9) N-hydroxy-4- (N- (benzofuran-2-ylcarbonyl) amino) butyramide

[Chemical 104] TLC: Rf 0.16 (chloroform: methanol: acetic acid = 100: 10: 1); NMR (d ₆ -DMSO): δ 10.38 (1H, brs), 9.30-8.10
(1H, br), 8.75 (1H, t, J = 6.2Hz), 7.76 (1H, m), 7.64
(1H, m), 7.51 (1H, d, J = 0.6Hz), 7.45 (1H, dt, J =
1.6, 7.0Hz), 7.32 (1H, dt, J = 1.0, 7.6Hz), 3.25 (2
H, q, J = 6.2Hz), 2.01 (2H, t, J = 7.0Hz), 1.74 (2H ,.
m).

Example 4 (10) N-hydroxy-4- [N- [4- (2- (4-chlorophenyl) ethenyl) phenylcarbonyl] amino] butyramide

[Chemical 105] TLC: Rf 0.17 (chloroform: methanol: acetic acid = 100: 10: 1); NMR (d ₆ -DMSO): δ 10.39 (1H, brs), 8.50 (1H,
t, J = 5.8Hz), 7.86 (2H, d, J = 8.4Hz), 7.67 (2H, d, J
= 8.4Hz), 7.65 (2H, d, J = 8.4Hz), 7.44 (2H, d, J = 8.4H)
z), 7.39 (1H, d, J = 16.2Hz), 7.30 (1H, d, J = 16.2H)
z), 3.25 (2H, m), 2.02 (2H, t, J = 7.6Hz), 1.74 (2H,
m).

Example 4 (11) N-Hydroxy-4- [N- [4-((4- (imidazol-1-yl) phenyl) ethynyl) phenylcarbonyl] amino] butyramide

[Chemical formula 106] TLC: Rf 0.14 (chloroform: methanol: acetic acid = 100: 10: 1); NMR (d ₆ -DMSO): δ 10.43 (1H, brs), 9.71 (1H,
s), 8.67 (1H, t, J = 5.6Hz), 8.33 (1H, brs), 7.95-7.
82 (8H, m), 7.67 (2H, d, J = 8.4Hz), 3.25 (2H, m),
2.02 (2H, t, J = 7.4Hz), 1.74 (2H, m).

Example 4 (12) N-Hydroxy-4- (N- (trans-4-propylcyclohexylcarbonyl) amino) butyramide

[Chemical formula 107] TLC: Rf 0.34 (chloroform: methanol: acetic acid = 18: 2: 1); NMR (d ₆ -DMSO): δ 10.35 (1H, s), 7.67 (1H, t,
J = 5.3Hz), 2.99 (2H, m), 2.39-1.88 (3H, m), 1.78-1.
61 (6H, m), 1.45-1.07 (7H, m), 0.95-0.76 (5H, m).

Example 4 (13) N-Hydroxy-4- [N- [4-((4-methylphenyl) ethynyl) phenylcarbonyl] amino] butyramide

[Chemical 108] TLC: Rf 0.38 (chloroform: methanol: acetic acid = 18: 2: 1); NMR (d ₆ -DMSO): δ 10.39 (1H, s), 8.62-8.53 (1
H, t, J = 5.3Hz), 7.89 (2H, d, J = 8.6Hz), 7.61 (2H, d,
J = 8.6Hz), 7.47 (2H, d, J = 8.0Hz), 7.25 (2H, d, J =
8.0Hz), 3.27 (2H, m), 2.35 (3H, s), 2.03 (2H, t, J
= 6.8Hz), 1.76 (2H, m).

Example 4 (14) N-Hydroxy-4- [N- [4-((4-bromophenyl) aminosulfonyl) phenylcarbonyl] amino] butyramide

[Chemical 109] TLC: Rf 0.16 (chloroform: methanol: acetic acid = 18: 2: 1); NMR (d ₆ -DMSO): δ 10.55 (1H, s), 10.38 (1H, b
rs), 8.67 (1H, m), 7.96 (2H, d, J = 8.4Hz), 7.82 (2
H, d, J = 8.4Hz), 7.43 (2H, d, J = 9.0Hz), 7.06 (2H, d,
J = 9.0Hz), 3.32-3.16 (2H, m), 2.01 (2H, t, J = 7.4H
z), 1.82-1.66 (2H, m).

Example 4 (15) N-hydroxy-4- [N- (4-cyclohexylphenylcarbonyl) amino] butyramide

[Chemical 110] TLC: Rf 0.40 (chloroform: methanol: acetic acid = 18: 2: 1); NMR (d ₆ -DMSO): δ 10.39 (1H, s), 8.43-8.36 (1
H, m), 7.76 (2H, d, J = 8.4Hz), 7.34 (2H, d, J = 8.4H
z), 3.30-3.13 (2H, m), 2.63-2.54 (1H, m), 2.01 (2
H, t, J = 7.6Hz), 1.86-1.65 (6H, m), 1.48-1.24 (6H,
m).

Example 4 (16) N-Hydroxy-4- [N- [4- (4-propylphenyl) phenylcarbonyl] amino] butyramide

[Chemical 111] TLC: Rf 0.40 (chloroform: methanol: acetic acid = 18: 2: 1); NMR (d ₆ -DMSO): δ 10.40 (1H, s), 8.70 (1H, br)
s), 8.57-8.49 (1H, m), 7.93 (2H, d, J = 8.5Hz), 7.74
(2H, d, J = 8.5Hz), 7.64 (2H, d, J = 8.5Hz), 7.31 (2H,
d, J = 8.5Hz), 3.31-3.20 (2H, m), 2.61 (2H, t, J = 7.
4Hz), 2.04 (2H, t, J = 7.2Hz), 1.76 (2H, m), 1.62 (2
H, m), 0.92 (3H, t, J = 7.4Hz).

Example 4 (17) N-Hydroxy-4- [N- [4- (4-hydroxyphenyl) phenylcarbonyl] amino] butyramide

[Chemical 112] TLC: Rf 0.23 (chloroform: methanol: acetic acid = 18: 2: 1); NMR (d ₆ -DMSO): δ 10.40 (1H, s), 9.80-9.45 (1
H, brs), 8.53-8.44 (1H, m), 7.89 (2H, d, J = 8.5Hz),
7.67 (2H, d, J = 8.5Hz), 7.56 (2H, d, J = 8.8Hz), 6.8
7 (2H, d, J = 8.8Hz), 3.31-3.20 (2H, m), 2.03 (2H,
t, J = 7.4Hz), 1.83-1.68 (2H, m).

Example 4 (18) N-Hydroxy-4- [N- [4- (4-chlorophenyl) furan-2-ylcarbonyl] amino] butyramide

[Chemical 113] TLC: Rf 0.38 (chloroform: methanol: acetic acid = 18: 2: 1); NMR (d ₆ -DMSO): δ 10.40 (1H, s), 8.64-8.51 (1
H, m), 7.95 (2H, d, J = 8.4Hz), 7.54 (2H, d, J = 8.4H
z), 7.16-7.11 (2H, m), 3.31-3.18 (2H, m), 2.08-1.9
5 (2H, m), 1.76 (2H, m).

Example 4 (19) N-Hydroxy-4- [N- [4- (4-heptylphenyl) phenylcarbonyl] amino] butyramide

[Chemical 114] TLC: Rf 0.34 (chloroform: methanol: acetic acid = 18: 2: 1); NMR (d ₆ -DMSO): δ 10.40 (1H, brs), 8.57-8.50
(1H, m), 7.93 (2H, d, J = 8.4Hz), 7.74 (2H, d, J = 8.4
Hz), 7.64 (2H, d, J = 8.4Hz), 7.30 (2H, d, J = 8.4Hz),
3.32-3.22 (2H, m), 2.62 (2H, t, J = 7.7Hz), 2.04 (2
H, t, J = 7.3Hz), 1.76 (2H, m), 1.69-1.52 (2H, m),
1.38-1.17 (8H, m), 0.86 (3H, t, J = 6.6Hz).

Example 4 (20) N-hydroxy-4- [N- [4- (4-methoxyphenyl) phenylcarbonyl] amino] butyramide

[Chemical 115] TLC: Rf 0.26 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.40 (1H, s), 8.57-8.47 (1
H, m), 7.91 (2H, d, J = 8.5Hz), 7.71 (2H, d, J = 8.5H
z), 7.68 (2H, d, J = 8.8Hz), 7.05 (2H, d, J = 8.8Hz),
3.81 (3H, s), 3.26 (2H, m), 2.03 (2H, t, J = 7.5Hz),
1.83-1.69 (2H, m).

Example 4 (21) N-hydroxy-4- [N- [4- (4-chlorophenyl) phenylcarbonyl] amino] butyramide

[Chemical formula 116] TLC: Rf 0.34 (chloroform: methanol: acetic acid = 18: 2: 1); NMR (d ₆ -DMSO): δ 10.41 (1H, s), 8.62-8.52 (1
H, m), 7.95 (2H, d, J = 8.4Hz), 7.82-7.72 (4H, m), 7.
55 (2H, d, J = 8.4Hz), 3.35-3.20 (2H, m), 2.04 (2H,
t, J = 7.5Hz), 1.83-1.69 (2H, m).

Example 4 (22) N-Hydroxy-4- [N- (5-benzyloxyindol-2-ylcarbonyl) amino] butyramide

[Chemical 117] TLC: Rf 0.26 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1); NMR (d ₆ -DMSO): δ 11.38 (1H, brs), 10.38 (1H,
brs), 8.70 (1H, brs), 8.43 (1H, t, J = 5.8Hz), 7.28
-7.48 (6H, m), 7.16 (1H, d, J = 2.2Hz), 6.99 (1H, d,
J = 1.4Hz), 6.89 (1H, dd, J = 8.7Hz, 2.4Hz), 5.07 (2H,
s), 3.25 (2H, m), 2.02 (2H, t, J = 6.8Hz), 1.70-1.8
1 (2H, m).

Example 4 (23) N-Hydroxy-4- [N- [5- (2- (4-chlorophenyl) ethenyl) furan-2-ylcarbonyl] amino] butyramide

[Chemical 118] TLC: Rf 0.27 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1); NMR (d ₆ -DMSO): δ 10.38 (1H, brs), 8.71 (1H,
brs), 8.46 (1H, t, J = 5.8Hz), 7.60 (2H, d, J = 8.8H)
z), 7.43 (2H, d, J = 8.8Hz), 7.23 (1H, d, J = 16.6Hz),
7.15 (1H, d, J = 16.6Hz), 7.09 (1H, d, J = 3.4Hz), 6.
63 (1H, d, J = 3.4Hz), 3.22 (2H, m), 2.00 (2H, t, J =
7.4Hz), 1.73 (2H, m).

Example 4 (24) N-Hydroxy-4- [N- (4-phenoxyphenylcarbonyl) amino] butyramide

[Chemical formula 119] TLC: Rf 0.25 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1); NMR (d ₆ -DMSO): δ 10.36 (1H, brs), 8.69 (1H,
brs), 8.41 (1H, t, J = 5.6Hz), 7.85 (2H, d, J = 8.8H
z), 7.41 (2H, t, J = 7.4Hz), 7.19 (1H, t, J = 7.4Hz),
6.97-7.09 (4H, m), 3.22 (2H, m), 1.99 (2H, t, J = 7.
6Hz), 1.71 (2H, m).

Example 4 (25) N-hydroxy-5- [N- [4- (benzofuran-2)
-Yl) phenylcarbonyl] amino] pentanamide

[Chemical 120] TLC: Rf 0.26 (chloroform: methanol = 1
0: 1); NMR (d ₆ -DMSO): δ 10.36 (1H, s), 8.67 (1H, br.
s), 8.57 (1H, t, J = 5.6Hz), 8.01 (2H, d, J = 8.8Hz),
7.96 (2H, d, J = 8.8Hz), 7.71-7.63 (2H, m), 7.57 (1H,
br.s), 7.39-7.23 (2H, m), 3.30-3.23 (2H, m), 2.02
-1.94 (2H, m), 1.60-1.44 (4H, m).

Example 4 (26) N-hydroxy-6- [N- [4- (benzofuran-2
-Yl) phenylcarbonyl] amino] hexanamide

[Chemical 121] TLC: Rf 0.28 (chloroform: methanol = 1
0: 1); NMR (d ₆ -DMSO): δ 10.33 (1H, s), 8.80-8.50 (1
H, br.s), 8.54 (1H, t, J = 5.6Hz), 8.01 (2H, d, J = 8.
8Hz), 7.95 (2H, d, J = 8.8H), 7.71-7.62 (2H, m), 7.56
(1H, s), 7.39-7.23 (2H, m), 3.30-3.21 (2H, m), 1.
95 (2H, t, J = 7.2Hz), 1.59-1.46 (4H, m), 1.36-1.20
(2H, m).

Example 4 (27) N-Hydroxy-4- [N-[[(4'-carbamoylmethoxy) biphenyl-4-yl] carbonyl] amino] butyramide

[Chemical formula 122] TLC: Rf 0.22 (chloroform: methanol: acetic acid: water = 50: 10: 1: 1); NMR (d ₆ -DMSO): δ 10.37 (1H, brs), 8.70 (1H, br
s), 8.49 (1H, t, J = 5.4Hz), 7.89 (2H, d, J = 8.8Hz), 7.
70 (2H, d, J = 8.2Hz), 7.67 (2H, d, J = 8.2Hz), 7.54 (1H,
brs), 7.39 (1H, brs), 7.04 (2H, d, J = 8.8Hz), 4.46 (2
H, s), 3.20-3.31 (2H, m), 2.01 (2H, t, J = 7.2Hz), 1.6
6-1.80 (2H, m).

Example 4 (28) N-Hydroxy-4- [N- [4- (4-phenylpiperidin-1-yl) phenylcarbonyl] amino] butyramide

[Chemical 123] TLC: Rf 0.32 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.39 (1H, s), 8.69 (1H, s),
8.20 (1H, t, J = 5.8Hz), 7.73 (2H, d, J = 8.6Hz), 7.4
0-7.12 (5H, m), 6.98 (2H, d, J = 8.6Hz), 4.06-3.90
(2H, m), 3.30-3.16 (2H, m), 2.96-2.60 (3H, m), 2.0
0 (2H, t, J = 7.6Hz), 1.95-1.59 (6H, m).

Example 4 (29) N-hydroxy-4- [N- [4- [3- (4-chlorophenoxy) -1-propynyl] phenylcarbonyl]
Amino] butyramide

[Chemical formula 124] TLC: Rf 0.26 (chloroform: methanol = 8:
1); NMR (d ₆ -DMSO): δ 10.38 (1H, s), 8.71 (1H, s),
8.57 (1H, t, J = 5.4Hz), 7.85 (2H, d, J = 8.4Hz), 7.5
3 (2H, d, J = 8.4Hz), 7.38 (2H, d, J = 9.2Hz), 7.08 (2
H, d, J = 9.2Hz), 5.08 (2H, s), 3.40-3.15 (2H, m, ov
erlap with H2Oin dmso), 2.02 (2H, t, J = 7.2Hz), 1.7
4 (2H, m).

Example 4 (30) N-hydroxy-4- [N- [4- (3-phenoxy-
1-propynyl) phenylcarbonyl] amino] butyramide

[Chemical 125] TLC: Rf 0.38 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.38 (1H, s), 8.70 (1H, s),
8.57 (1H, t, J = 5.4Hz), 7.85 (2H, d, J = 8.3Hz), 7.5
2 (2H, d, J = 8.3Hz), 7.34 (2H, dd, J = 7.0 and 8.6H
z), 7.10-6.90 (3H, m), 5.06 (2H, s), 3.25 (2H, dt,
J = 5.4 and 7.2Hz), 2.02 (2H, t, J = 7.2Hz), 1.74 (2
H, m).

Example 4 (31) N-hydroxy-4- [N- [4- (4-methoxyphenoxy) phenylcarbonyl] amino] butyramide

[Chemical formula 126] TLC: Rf 0.40 (chloroform: methanol: acetic acid: water = 50: 10: 1: 1); NMR (d ₆ -DMSO): δ 10.37 (1H, brs), 8.70 (1H, b)
rs), 8.40 (1H, t, J = 5.5Hz), 7.82 (2H, d, J = 9.1Hz),
7.06-6.91 (6H, m), 3.79 (3H, s), 3.21 (2H, m), 1.
96 (2H, m), 1.72 (2H, m).

Example 4 (32) N-hydroxy-4- [N- [4- (4-hydroxyphenoxy) phenylcarbonyl] amino] butyramide

[Chemical 127] TLC: Rf 0.25 (chloroform: methanol: acetic acid: water = 50: 10: 1: 1); NMR (d ₆ -DMSO): δ 8.37 (1H, t, J = 5.5Hz), 7.81
(2H, d, J = 8.8Hz), 6.92 (2H, d, J = 9.1Hz), 6.90 (2H,
d, J = 8.8Hz), 6.80 (2H, d, J = 9.1Hz), 3.21 (2H, m),
1.99 (2H, m), 1.71 (2H, m).

Example 4 (33) N-Hydroxy-4- [N- [4- (4-phenoxypiperazin-1-yl) phenylcarbonyl] amino] butyramide

[Chemical 128] TLC: Rf 0.31 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.38 (1H, s), 8.69 (1H, s),
8.19 (1H, t, J = 5.2Hz), 7.73 (2H, d, J = 8.8Hz), 7.2
8 (2H, dd, J = 8.8, 7.4Hz), 7.02-6.87 (5H, m), 4.68-
4.52 (1H, m), 3.73-3.56 (2H, m), 3.32-3.10 (4H,
m), 2.11-1.92 (4H, m), 1.82-1.59 (4H, m).

Example 4 (34) N-hydroxy-4- [N- [4- (4-phenyl-
1,2,5,6-Tetrahydropyridin-1-yl) phenylcarbonyl] amino] butyramide

[Chemical formula 129] TLC: Rf 0.42 (chloroform: methanol: acetic acid: water = 50: 10: 1: 1); NMR (d ₆ -DMSO): δ 10.38 and 9.78 (total 1H, bo
th brs), 9.02 and 8.69 (total 1H, both brs), 8.20
(1H, t, J = 5.5Hz), 7.75 (2H, d, J = 9.1Hz), 7.48 (2H,
m), 7.36 (2H, m), 7.26 (1H, m), 6.98 (2H, d, J = 9.
1Hz), 6.29 (1H, brs), 3.94 (2H, m), 3.58 (2H, m),
3.20 (2H, m), 2.62 (2H, m), 1.99 (2H, m), 1.71 (2
H, m).

Example 4 (35) N-hydroxy-4- [N- [4- (1-heptinyl)
Phenylcarbonyl] amino] butyramide

[Chemical 130] TLC: Rf 0.24 (chloroform: methanol = 1
0: 1); NMR (d ₆ -DMSO): δ 10.37 (1H, s), 8.52 (1H, t,
J = 5.6Hz), 7.80 (2H, d, J = 8.4Hz), 7.44 (2H, d, J = 8.4
Hz), 3.23 (2H, br.q, J = 5.8Hz), 2.43 (2H, t, J = 6.6H
z), 2.00 (2H, t, J = 7.4Hz), 1.79-1.65 (2H, m), 1.62
-1.48 (2H, m), 1.44-1.22 (4H, m), 0.88 (3H, t, J =
6.6 Hz).

Example 4 (36) N-hydroxy-4- [N- (4-benzyloxyphenylcarbonyl) amino] butyramide

[Chemical 131] TLC: Rf 0.11 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1); NMR (d ₆ -DMSO): δ 10.36 and 9.78 (total 1H, ea
ch br), 8.99 and 8.68 (total 1H, each br), 8.31 (1
H, m), 7.80 (2H, d, J = 8.8Hz), 7.45-7.3 (5H, m), 7.
05 (2H, d, J = 8.8Hz), 5.15 (2H, s), 3.21 (2H, m),
1.99 (2H, t, J = 7.4Hz), 1.72 (2H, m).

Example 5 4- (N-methyl-N- (4- (benzofuran-2-yl) phenylcarbonyl) amino) butanoic acid ethyl ester

[Chemical 132] Methyl iodide (0.35 ml) was added to a dimethylformamide (3 ml) solution of the compound (0.1 g) produced in Example 1. The mixture was added with 60% sodium hydride (13m at 0 ° C).
g) was added. The reaction mixture was stirred at room temperature for 1 hour. A 1N aqueous hydrochloric acid solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated to give the title compound (113 mg) having the following physical data. TLC: Rf 0.33 (n-hexane: ethyl acetate = 1: 1
1).

Example 6 4- (N-methyl-N- (4- (benzofuran-2-yl) phenylcarbonyl) amino) butanoic acid

[Chemical 133] The title compound having the following physical data was obtained by substituting the compound prepared in Example 5 for the compound prepared in Example 1 and operating in the same manner as in Example 2. TLC:
Rf 0.51 (chloroform: methanol = 9: 1); NMR (CD ₃ OD): δ 7.98 (2H, d, J = 8.4Hz), 7.66-
7.59 (1H, m), 7.57-7.46 (3H, m), 7.37-7.19 (3H,
m), 3.62 and 3.40 (2H, t, J = 7.5Hz), 3.10 and 3.03
(3H, s), 2.45 and 2.20 (2H, t, J = 7.5Hz), 2.10-1.75
(2H, m).

Example 7 N-Hydroxy-4- (N-methyl-N- (4- (benzofuran-2-yl) phenylcarbonyl) amino) butyramide

[Chemical 134] The title compound having the following physical data was obtained by substituting the compound prepared in Example 6 for the compound prepared in Example 2 and operating in the same manner as in Example 3 → Example 4. TLC: Rf 0.31 (chloroform: methanol = 9:
1); NMR (CD ₃ OD): δ 7.99 (2H, d, J = 8.4Hz), 7.66-
7.59 (1H, m), 7.58-7.45 (3H, m), 7.37-7.20 (3H,
m), 3.70-3.54 and 3.42-3.30 (2H, m), 3.16-2.95 (3
H, m), 2.30-1.80 (4H, m).

Example 8 4- (N- (4- (benzofuran-2-yl) phenylcarbonyl) amino) -2 (S) -hydroxybutanoic acid methyl ester

[Chemical 135] 4-Amino-2 (S) -hydroxybutanoic acid methyl ester (E
It was produced in the same manner as the method described in P393441. Was used in the same manner as in Example 1 to obtain the title compound having the following physical data. TLC: Rf 0.11 (n-hexane: ethyl acetate = 1: 1
1); NMR (d ₆ -DMSO): δ 8.58 (1H, t, J = 6.0Hz), 8.01
(2H, d, J = 8.8Hz), 7.96 (2H, d, J = 8.8Hz), 7.71-7.6
3 (2H, m), 7.57 (1H, brs), 7.39-7.24 (2H, m), 4.19-
4.10 (1H, m), 3.62 (3H, s), 3.38 (2H, q, J = 6.0Hz),
2.06-1.68 (2H, m).

Example 9 4- (N- (4- (benzofuran-2-yl) phenylcarbonyl) amino) -2 (S) -hydroxybutanoic acid

[Chemical 136] The title compound having the following physical data was obtained by substituting the compound prepared in Example 8 for the compound prepared in Example 1 and operating in the same manner as in Example 2. TLC: Rf 0.10 (chloroform: methanol: acetic acid = 100: 10: 1); NMR (d ₆ -DMSO): δ 8.49 (1H, t, J = 5.6Hz), 7.92
(2H, d, J = 8.8Hz), 7.87 (2H, d, J = 8.8Hz), 7.62-7.5
3 (2H, m), 7.48 (1H, d, J = 0.6Hz), 7.30-7.14 (2H,
m), 3.95 (1H, dd, J = 4.4, 8.4Hz), 3.29 (2H, m), 1.9
8-1.58 (2H, m).

Example 9 (1) 4- (N- (4- (benzofuran-2-yl) phenylcarbonyl) amino) -2 (R) -hydroxybutanoic acid

[Chemical 137] Operation similar to the method shown in Example 8 → Example 9 using 4-amino-2 (R) -hydroxybutanoic acid methyl ester instead of 4-amino-2 (S) -hydroxybutanoic acid methyl ester. Then, the title compound having the following physical properties was obtained. TLC: Rf 0.10 (chloroform: methanol: acetic acid = 100: 10: 1); NMR (d ₆ -DMSO): δ 8.49 (1H, t, J = 5.6Hz), 7.92
(2H, d, J = 8.8Hz), 7.87 (2H, d, J = 8.8Hz), 7.62-7.5
3 (2H, m), 7.48 (1H, d, J = 0.6Hz), 7.30-7.14 (2H,
m), 3.95 (1H, dd, J = 4.4, 8.4Hz), 3.29 (2H, m), 1.9
8-1.58 (2H, m).

Example 10 4- (N- (4- (benzofuran-2-yl) phenylcarbonyl) amino) -2 (S) -benzyloxymethoxybutanoic acid methyl ester

[Chemical 138] A solution of the compound (0.2 g) prepared in Example 8 in dichloromethane (1 ml) was added with diisopropylethylamine (2 m).
l) was added. Benzyloxymethyl chloride (0.79 ml) was added to the mixture. The reaction mixture was stirred at 50 ° C. for 30 minutes. A 1N aqueous hydrochloric acid solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel column chromatography (n-hexane: ethyl acetate = 3: 2) to give the title compound (0.176 g) having the following physical data. TLC: Rf 0.47 (n-hexane: ethyl acetate = 1: 1
1).

Example 11 4- (N- (4- (benzofuran-2-yl) phenylcarbonyl) amino) -2 (S) -benzyloxymethoxybutanoic acid

[Chemical 139] The title compound having the following physical data was obtained by substituting the compound prepared in Example 10 for the compound prepared in Example 1 and operating in the same manner as in Example 2. TLC: Rf 0.45 (chloroform: methanol: acetic acid = 100: 20: 1); NMR (d ₆ -DMSO): δ 8.61 (1H, t, J = 5.4Hz), 8.01
(2H, d, J = 8.8Hz), 7.95 (2H, d, J = 8.8Hz), 7.709-7.
63 (2H, m), 7.57 (1H, brs), 4.80 (1H, d, J = 8.8Hz),
4.79 (1H, d, J = 8.8Hz), 4.64 (1H, d, J = 11.8Hz), 4.
54 (1H, d, J = 11.8Hz), 4.13 (1H, dd, J = 4.2, 8.2Hz),
3.52-3.28 (2H, m), 2.12-1.82 (2H, m).

Examples 11 (1) to 11 (3) Using the corresponding amine compound and acid halide, Example 8
-> Example 10-> It operated similarly to the method shown by Example 11, and obtained the compound shown below.

Example 11 (1) 4- (N- (4- (benzofuran-2-yl) phenylcarbonyl) amino) -2 (R) -benzyloxymethoxybutanoic acid

[Chemical 140] TLC: Rf 0.45 (chloroform: methanol: acetic acid = 100: 20: 1); NMR (d ₆ -DMSO): δ 8.61 (1H, t, J = 5.4Hz), 8.01
(2H, d, J = 8.8Hz), 7.95 (2H, d, J = 8.8Hz), 7.709-7.
63 (2H, m), 7.57 (1H, brs), 4.80 (1H, d, J = 8.8Hz),
4.79 (1H, d, J = 8.8Hz), 4.64 (1H, d, J = 11.8Hz), 4.
54 (1H, d, J = 11.8Hz), 4.13 (1H, dd, J = 4.2, 8.2Hz),
3.52-3.28 (2H, m), 2.12-1.82 (2H, m).

Example 11 (2) 4- (N- (4- (2- (4-chlorophenyl) ethenyl) phenylcarbonyl) amino) -2 (S) -benzyloxymethoxybutanoic acid

[Chemical 141] TLC: Rf 0.18 (chloroform: methanol = 1
0: 1); NMR (d ₆ -DMSO): δ 8.52 (1H, t, J = 5.4Hz), 7.84
(2H, d, J = 8.4Hz), 7.67 (2H, d, J = 8.4Hz), 7.65 (2
H, d, J = 8.8Hz), 7.44 (2H, d, J = 8.8Hz), 7.35-7.28
(7H, m), 4.80 (1H, d, J = 8.8Hz), 4.77 (1H, d, J = 8.8Hz
Hz), 4.63 (1H, d, J = 11.8Hz), 4.54 (1H, d, J = 11.8H
z), 4.12 (1H, dd, J = 4.4, 8.0Hz), 3.50-3.26 (2H,
m), 2.10-1.78 (2H, m).

Example 11 (3) 4- (N- (4-chlorophenylcarbonyl) amino)
-2-benzyloxymethoxybutanoic acid

[Chemical 142] TLC: Rf 0.32 (chloroform: methanol: acetic acid = 100: 10: 1); NMR (d ₆ -DMSO): δ 8.57 (1H, t, J = 5.6Hz), 7.84
(2H, d, J = 8.8Hz), 7.52 (2H, d, J = 8.8Hz), 7.30 (5
H, s), 4.80 (1H, d, J = 8.8Hz), 4.76 (1H, d, J = 8.8H)
z), 4.63 (1H, d, J = 11.8Hz), 4.53 (1H, d, J = 11.8H
z), 4.11 (1H, dd, J = 4.4, 8.2Hz), 3.49-3.24 (2H, m),
2.08-1.77 (2H, m).

Example 12 N-hydroxy-4- (N- (4- (benzofuran-2
-Yl) phenylcarbonyl) amino) -2 (S) -hydroxybutyramide

[Chemical 143] The title compound having the following physical data was obtained by substituting the compound prepared in Example 9 for the compound prepared in Example 2 and operating in the same manner as in Example 3 → Example 4. TLC: Rf 0.42 (chloroform: methanol: water =
100: 20: 1); NMR (d ₆ -DMSO): δ 10.49.
(1H, brs), 8.55 (1H, t, J = 5.4Hz), 8.01 (2H, d, J =
9.0Hz), 7.96 (2H, d, J = 9.0Hz), 7.71-7.62 (2H, m),
7.57 (1H, brs), 7.39-7.23 (2H, m), 3.94 (1H, dd, J
= 4.2, 8.2Hz), 3.41-3.31 (2H, m), 2.02-1.64 (2H,
m).

Examples 12 (1) -12 (5) Instead of the compound prepared in Example 9, Example 9 (1),
Using the compounds produced in Example 11 and Examples 11 (1) to 11 (3), the same procedure as in Example 12 was carried out to obtain the compounds shown below.

Example 12 (1) N-hydroxy-4- (N- (4- (benzofuran-2)
-Yl) phenylcarbonyl) amino) -2 (R) -hydroxybutyramide

[Chemical 144] TLC: Rf 0.42 (chloroform: methanol: water =
100: 20: 1); NMR (d ₆ -DMSO): δ 10.49 (1H, brs), 8.55 (1H,
t, J = 5.4Hz), 8.01 (2H, d, J = 9.0Hz), 7.96 (2H, d, J
= 9.0Hz), 7.71-7.63 (2H, m), 7.57 (1H, brs), 7.39-
7.23 (2H, m), 3.94 (1H, dd, J = 4.2, 8.2Hz), 3.41-3.
31 (2H, m), 2.02-1.62 (2H, m).

Example 12 (2) N-hydroxy-4- (N- (4- (benzofuran-2
-Yl) phenylcarbonyl) amino) -2 (S) -benzyloxymethoxybutyramide

[Chemical 145] TLC: Rf 0.24 (chloroform: methanol = 1
0: 1); NMR (d ₆ -DMSO): δ 10.75 (1H, brs), 8.90 (1H,
brs), 8.55 (1H, t, J = 5.6Hz), 8.01 (2H, d, J = 8.8H
z), 7.96 (2H, d, J = 8.8Hz), 7.71-7.63 (2H, m), 7.58
(1H, brs), 7.39-7.24 (7H, m), 4.77 (1H, d, J = 8.8H
z), 4.68 (1H, d, J = 8.8Hz), 4.58 (2H, s), 4.04 (1H,
t, J = 5.8Hz), 3.49-3.25 (2H, m), 1.93 (2H, m).

Example 12 (3) N-hydroxy-4- (N- (4- (benzofuran-2)
-Yl) phenylcarbonyl) amino) -2 (R) -benzyloxymethoxybutyramide

[Chemical 146] TLC: Rf 0.24 (chloroform: methanol = 1
0: 1); NMR (d ₆ -DMSO): δ 10.75 (1H, brs), 8.90 (1H,
brs), 8.55 (1H, t, J = 5.6Hz), 8.01 (2H, d, J = 8.8H
z), 7.96 (2H, d, J = 8.8Hz), 7.71-7.63 (2H, m), 7.58
(1H, brs), 7.39-7.24 (7H, m), 4.77 (1H, d, J = 8.8H
z), 4.68 (1H, d, J = 8.8Hz), 4.58 (2H, s), 4.04 (1H,
t, J = 5.8Hz), 3.49-3.25 (2H, m), 1.93 (2H, m).

Example 12 (4) N-hydroxy-4- (N- (4- (2- (4-chlorophenyl) ethenyl) phenylcarbonyl) amino)-
2 (S) -benzyloxymethoxybutyramide

[Chemical 147] TLC: Rf 0.22 (chloroform: methanol = 1)
0: 1); NMR (d ₆ -DMSO): δ 10.74 (1H, brs), 8.89 (1H,
brs), 8.45 (1H, t, J = 5.6Hz), 7.85 (2H, d, J = 8.4H
z), 7.67 (2H, d, J = 8.4Hz), 7.65 (2H, d, J = 8.6Hz),
7.45 (2H, d, J = 8.6Hz), 7.35-7.26 (7H, m), 4.76 (1
H, d, J = 8.8Hz), 4.67 (1H, d, J = 8.8Hz), 4.57 (2H,
s), 4.02 (1H, t, J = 5.8Hz), 3.48-3.28 (2H, m), 1.91
(2H, m).

Example 12 (5) N-hydroxy-4- (N- (4-chlorophenylcarbonyl) amino) -2-benzyloxymethoxybutyramide

[Chemical 148] TLC: Rf 0.34 (chloroform: methanol = 1)
0: 1); NMR (d ₆ -DMSO): δ 10.73 (1H, brs), 8.89 (1H,
brs), 8.52 (1H, m), 7.84 (2H, d, J = 8.4Hz), 7.52 (2
H, d, J = 8.4Hz), 7.30 (5H, brs), 4.75 (1H, d, J = 8.8H)
z), 4.66 (1H, d, J = 8.8Hz), 4.56 (2H, s), 4.01 (1H,
t, J = 6.6Hz), 3.45-3.25 (2H, m), 1.89 (2H, m).

Example 13 4- (N- (4-chlorophenylcarbonyl) amino)
-2- (t-butyloxycarbonylmethoxy) butanoic acid methyl ester

[Chemical 149] A solution of 4- (N- (4-chlorophenylcarbonyl) amino) -2-hydroxybutanoic acid methyl ester (3g) in tetrahydrofuran (15ml) at -78 ° C in a mixture of 60% sodium hydride (2.38g) in tetrahydrofuran (10ml). Was dripped. Reaction mixture at 0 ° C. for 30
After stirring for a minute, t-butyl bromoacetate (0.975
g) was added dropwise at -78 ° C. The reaction mixture was stirred at 0 ° C. for 1.5 hours. A 1N aqueous hydrochloric acid solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogen carbonate solution and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated. The residue was subjected to silica gel column chromatography (n-hexane: ethyl acetate = 1: 1).
Purification by 1) gave the title compound (3.194 g) having the following physical data. TLC: Rf 0.63 (n-hexane: ethyl acetate = 1: 1
1).

Example 14 4- (N- (4-chlorophenylcarbonyl) amino)
-2- (carboxymethoxy) butanoic acid methyl ester

[Chemical 150] A solution of the compound (3.194 g) produced in Example 13 in trifluoroacetic acid (50 ml) was stirred at room temperature for 1 hour. The reaction mixture was concentrated, diethyl ether was added to crystallize,
The crystals were washed with diethyl ether and dried to give the title compound (2.275 g) having the following physical data. TLC: Rf 0.28 (chloroform: methanol: acetic acid = 100: 10: 1).

Example 15 4- (N- (4-chlorophenylcarbonyl) amino)
-2-((N-benzyl-N-methylamino) carbonylmethoxy) butanoic acid methyl ester

[Chemical 151] A solution of the compound (0.5 g) prepared in Example 14 in dimethylformamide (5 ml) was added to N-benzyl-N-methylamine (0.213 g), 1-hydroxybenzotriazole hydrate (0.27 g), 1-ethyl-. 3- (3-Dimethylaminopropyl) carbodiimide / hydrochloride (0.337g)
Was added under ice cooling, and the mixture was stirred at room temperature for 1 hour. 1 in the reaction mixture
An aqueous solution of N hydrochloric acid was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogen carbonate solution and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated,
The title compound (0.664 g) having the following physical data was obtained. TLC: Rf 0.60 (n-hexane: ethyl acetate = 1: 1
1).

Example 16 4- (N- (4-chlorophenylcarbonyl) amino)
-2-((N-benzyl-N-methylamino) carbonylmethoxy) butanoic acid

[Chemical 152] The title compound having the following physical data was obtained by substituting the compound prepared in Example 15 for the compound prepared in Example 1 and operating in the same manner as in Example 2. TLC: Rf 0.21 (chloroform: methanol: acetic acid = 100: 10: 1); NMR (d ₆ -DMSO): δ 8.83 and 8.72 (total 1H,
m), 7.87 and 7.86 (total 2H, d, J = 8.8Hz), 7.53-7.2
3 (7H, m), 4.53 and 4.49 (total 2H, s), 4.38 (1H,
d, J = 15.0Hz), 4.24 (1H, d, J = 15.0Hz), 3.52-3.37 (1
H, m), 2.86 and2.80 (total 3H, s), 2.08-1.72 (2H,
m).

Examples 16 (1) and 16 (2) Using the corresponding amine compound instead of N-benzyl-N-methylamine, the procedure of Example 15 → Example 16 was repeated, The compound shown below was obtained.

Example 16 (1) 4- (N- (4-chlorophenylcarbonyl) amino)
-2-((N-phenyl-N-methylamino) carbonylmethoxy) butanoic acid

[Chemical 153] TLC: Rf 0.29 (chloroform: methanol: acetic acid = 100: 10: 1); NMR (d ₆ -DMSO): δ 8.72 (1H, t, J = 5.8Hz), 7.88
(2H, d, J = 8.4Hz), 7.53 (2H, d, J = 8.4Hz), 7.49-7.3
4 (5H, m), 4.05-3.82 (3H, m), 3.44-3.33 (2H, m),
3.19 (3H, s), 2.04-1.64 (2H, m).

Example 16 (2) 4- (N- (4-chlorophenylcarbonyl) amino)
-2-((N-phenylethyl-N-methylamino) carbonylmethoxy) butanoic acid

[Chemical 154] TLC: Rf 0.32 (chloroform: methanol: acetic acid = 100: 10: 1); NMR (d ₆ -DMSO): δ 8.83 (0.5H, t, J = 5.5Hz), 8.
75 (0.5H, t, J = 5.5Hz), 7.89 (1H, d, J = 8.4Hz), 7.86
(1H, d, J = 8.4Hz), 7.53 (1H, d, J = 8.4Hz), 7.49 (1H,
d, J = 8.4Hz), 7.30 (5H, s), 4.39 (0.5H, d, J = 15.4H
z), 4.17 (0.5H, d, J = 15.4Hz), 4.13 (0.5H, d, J = 14.
6Hz), 3.95 (0.5H, dd, J = 8.8, 3.0Hz), 3.90 (0.5H,
d, J = 14.6Hz), 3.79 (0.5H, dd, J = 9.0, 3.6Hz), 3.60-
3.30 (4H, m), 2.90-2.70 (2H, m), 2.10-1.60 (2H,
m).

Example 17 N-Hydroxy-4- (N- (4-chlorophenylcarbonyl) amino) -2-((N-benzyl-N-methylamino) carbonylmethoxy) butyramide

[Chemical 155] The title compound having the following physical data was obtained by substituting the compound prepared in Example 16 for the compound prepared in Example 2 and operating in the same manner as in Example 3 → Example 4. TLC: Rf 0.39 (chloroform: methanol = 1)
0: 1); NMR (d ₆ -DMSO): δ 10.93 and 10.90 (total 1H,
brs, and brs), 9.05-8.65 (2H, m), 7.87 and 7.86 (t
otal 2H, d and d, J = 8.8Hz and J = 8.8Hz), 7.52 and
7.45 (total 2H, d and d, J = 8.8Hz and J = 8.8Hz), 7.3
7-7.19 (5H, m), 4.54 and 4.50 (total 2H, s and s),
4.44 and 4.36 (total 1H, d and d, J = 14.2Hz and J = 1
5.0Hz), 4.24 and 4.20 (total 1H, d and d, J = 14.2Hz
and J = 15.0Hz), 3.94-3.88 (1H, m), 2.84 and 2.80
(total 3H, s and s), 2.00-1.68 (2H, m).

Examples 17 (1) and 17 (2) Example 16 in place of the compound prepared in Example 16
Using the compounds produced in (1) and 16 (2), the same procedure as in Example 17 was carried out to obtain the compounds shown below.

Example 17 (1) N-hydroxy-4- (N- (4-chlorophenylcarbonyl) amino) -2-((N-phenyl-N-methylamino) carbonylmethoxy) butyramide

[Chemical 156] TLC: Rf 0.48 (chloroform: methanol = 1
0: 1); NMR (d ₆ -DMSO): δ 10.79 (1H, brs), 9.20-8.40
(1H, br), 8.68 (1H, m), 7.87 (2H, d, J = 8.8Hz), 7.53
(2H, d, J = 8.8Hz), 7.46-7.34 (5H, m), 4.14-3.67 (3
H, m), 3.55-3.25 (2H, m), 3.19 (3H, s), 1.95-1.60
(2H, m).

Example 17 (2) N-hydroxy-4- (N- (4-chlorophenylcarbonyl) amino) -2-((N-phenylethyl-N-
Methylamino) carbonylmethoxy) butyramide

[Chemical 157] TLC: Rf 0.40 (chloroform: methanol = 1)
0: 1); NMR (d ₆ -DMSO): δ 10.90 (1H, brs), 8.87 (1H,
brs), 8.83-8.67 (1H, m), 7.89 and 7.87 (total 2H, d
and d, J = 8.4Hz and J = 8.4Hz), 7.53 and 7.49 (total
2H, d and d, J = 8.4Hz and J = 8.4Hz), 7.33-7.17 (5H,
m), 4.31 and 4.10 and 3.99 (total 2H, d and d and
s, J = 15.4Hz and J = 15.4Hz), 3.85 and 3.69 (total 1
H, dd and dd, J = 4.4, 8.8Hz and J = 4.0, 8.4Hz), 3.56
-3.32 (2H, m), 2.84-2.72 (2H, m), 1.97-1.68 (2H, m
m).

Example 18 3 (S) -Hydroxy-4- (N- (4- (benzofuran-2-yl) phenylcarbonyl) amino) butanoic acid methyl ester

[Chemical 158] 3 (S) instead of 4-aminobutanoic acid ethyl ester
-Hydroxy-4-aminobutanoic acid methyl ester (Ac
ta Chem. Scand., Ser. B, 37 , 341 (1983)) was carried out in the same manner as in Example 1 to obtain the title compound having the following physical properties. TLC: Rf 0.31 (n-hexane: ethyl acetate = 1: 1
1); NMR (d ₆ -DMSO): δ 8.57 (1H, t, J = 6.0Hz), 8.00
(4H, s), 7.71-7.63 (2H, m), 7.57 (1H, brs), 7.40-
7.24 (2H, m), 5.13 (1H, d, J = 5.6Hz), 4.18-4.00 (1
H, m), 3.57 (3H, s), 3.30 (2H, t, J = 6.0Hz), 2.55
(1H, dd, J = 4.0,15.0Hz), 2.31 (1H, dd, J = 4.0, 15.0H)
z).

Example 19 3 (S) -Hydroxy-4- (N- (4- (benzofuran-2-yl) phenylcarbonyl) amino) butanoic acid

[Chemical 159] The title compound having the following physical data was obtained by substituting the compound prepared in Example 18 for the compound prepared in Example 1 and operating in the same manner as in Example 2. TLC: Rf 0.24 (chloroform: methanol: acetic acid = 100: 10: 1); NMR (d ₆ -DMSO): δ 8.55 (1H, t, J = 5.8Hz), 8.00
(4H, s), 7.71-7.63 (2H, m), 7.58 (1H, brs), 7.39-
7.23 (2H, m), 5.16-4.92 (1H, brs), 4.14-4.00 (1H,
m), 3.30 (2H, t, J = 5.8Hz), 2.46 (1H, dd, J = 4.2, 1
5.0Hz), 2.23 (1H, dd, J = 8.4, 15.0Hz).

Example 19 (1) 3 (R) -hydroxy-4- (N- (4- (benzofuran-2-yl) phenylcarbonyl) amino) butanoic acid

[Chemical 160] Using 3 (R) -hydroxy-4-aminobutanoic acid ethyl ester in place of 3 (S) -hydroxy-4-aminobutanoic acid methyl ester, operate in the same manner as in Example 18 → Example 19, and then: The title compound having the following physical properties was obtained. TLC: Rf 0.24 (chloroform: methanol: acetic acid = 100: 10: 1); NMR (d ₆ -DMSO): δ 8.55 (1H, t, J = 5.8Hz), 8.00
(4H, s), 7.71-7.63 (2H, m), 7.58 (1H, brs), 7.39-
7.23 (2H, m), 5.16-4.92 (1H, brs), 4.14-4.00 (1H,
m), 3.30 (2H, t, J = 5.8Hz), 2.46 (1H, dd, J = 4.2, 1
5.0Hz), 2.23 (1H, dd, J = 8.4, 15.0Hz).

Example 20 3 (S) -methoxymethyloxy-4- (N- (4-
(Benzofuran-2-yl) phenylcarbonyl) amino) butanoic acid and 4- (N- (4- (benzofuran-
2-yl) phenylcarbonyl) amino) -2-butenoic acid

[Chemical 161]

[Chemical 162] Example 10 using the compound prepared in Example 18 (using methoxymethyl chloride in place of benzyloxymethyl chloride) → The same operation as in Example 11 was conducted to give the title compound having the following physical data. Respectively obtained.

Example 20 (1) TLC: Rf 0.21 (chloroform: methanol = 1)
NMR (d ₆ -DMSO): δ 8.72 (1H, t, J = 5.6Hz), 8.00
(4H, s), 7.72-7.64 (2H, m), 7.60 (1H, brs), 7.40-
7.20 (2H, m), 4.63 (2H, s), 4.08 (1H, m), 3.40 (2H,
m), 2.40-2.20 (2H, m).

Example 20 (2) TLC: Rf 0.12 (chloroform: methanol = 1)
0: 1); NMR (d ₆ -DMSO): δ 8.88 (1H, t, J = 5.6Hz), 8.02
(4H, s), 7.71-7.62 (2H, m), 7.59 (1H, brs), 7.40-
7.20 (2H, m), 6.80 (1H, dt, J = 15.0, 5.0Hz), 5.85
(1H, d, J = 15.0Hz), 4.09-4.01 (2H, m).

Example 20 (3) 3 (R) -methoxymethyloxy-4- (N- (4-
(Benzofuran-2-yl) phenylcarbonyl) amino) butanoic acid

[Chemical formula 163] Using 3 (R) -hydroxy-4-aminobutanoic acid ethyl ester in place of 3 (S) -hydroxy-4-aminobutanoic acid methyl ester, the same procedure as in Example 18 → Example 20 was repeated. The title compound having the following physical properties was obtained. TLC: Rf 0.21 (chloroform: methanol = 1
NMR (d ₆ -DMSO): δ 8.72 (1H, t, J = 5.6Hz), 8.01
(4H, s), 7.70-7.65 (2H, m), 7.61 (1H, brs), 7.40-
7.20 (2H, m), 4.62 (2H, s), 4.08 (1H, m), 3.42 (2H,
m), 2.40-2.20 (2H, m).

Example 21 3 (S) -Acetyloxy-4- (N- (4- (benzofuran-2-yl) phenylcarbonyl) amino) butanoic acid methyl ester

[Chemical 164] The compound (0.3 g) prepared in Example 18, pyridine (5
ml) solution was added acetic anhydride (0.6 ml) at 0 ° C. The reaction mixture was stirred at room temperature for 2 hours. A 1N aqueous hydrochloric acid solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. Extract the water,
The extract was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and concentrated to give the title compound (0.325 g) having the following physical data. TLC: Rf 0.52 (n-hexane: ethyl acetate = 1:
2).

Example 22 4- (N- (4- (benzofuran-2-yl) phenylcarbonyl) amino) -3-butenoic acid methyl ester

[Chemical 165] A solution of the compound (0.15 g) prepared in Example 21 in tetrahydrofuran (1 ml) was added with 1,8-diazabicyclo [5.
4.0] Undec-7-ene [DBU] (0.13 ml) was added. The reaction mixture was stirred at 50 ° C. for 3 hours. A 1N aqueous hydrochloric acid solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate.
The extract was washed with water and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and concentrated to give the title compound (0.096 g) having the following physical data. TLC: Rf 0.70 (n-hexane: ethyl acetate = 1: 1
2).

Example 23 4- (N- (4- (benzofuran-2-yl) phenylcarbonyl) amino) -3-butenoic acid

[Chemical 166] The title compound having the following physical data was obtained by substituting the compound prepared in Example 22 for the compound prepared in Example 1 and operating in the same manner as in Example 2. TLC: Rf 0.22 (chloroform: methanol: acetic acid = 100: 10: 1); NMR (d ₆ -DMSO): δ 10.39 (1H, d, J = 9.8Hz), 8.0
5 (4H, s), 7.72-7.64 (2H, m), 7.61 (1H, d, J = 0.6H
z), 7.41-7.24 (2H, m), 6.95 (1H, dd, J = 9.8,14.4H
z), 5.54 (1H, dt, J = 14.4, 7.2Hz), 3.05 (2H, d, J =
7.2Hz).

Example 24 N-Hydroxy-3 (S) -hydroxy-4- (N-)
(4- (benzofuran-2-yl) phenylcarbonyl) amino) butyramide

[Chemical 167] The title compound having the following physical properties values was obtained by the same procedure as in Example 3 → Example 4 using the compound produced in Example 19 instead of the compound produced in Example 2. TLC: Rf 0.41 (chloroform: methanol: water =
100: 20: 1); NMR (d ₆ -DMSO): δ 10.39 (1H, brs), 8.55 (1H,
m), 8.00 (4H, s), 7.71-7.63 (2H, m), 7.57 (1H, br
s), 7.39-7.23 (2H, m), 5.50-4.30 (1H, br), 4.12-3.9
8 (1H, m), 3.40-3.18 (2H, m), 2.16 (1H, dd, J = 4.8,
14.0Hz), 2.03 (1H, dd, J = 8.2, 14.0Hz).

Examples 24 (1) -24 (6) Example 19 instead of the compound prepared in Example 19.
(1), Examples 20 (1) to 20 (3), using the compound prepared in Example 23, or the same procedure as in Example 24, or using the compound prepared in Example 18 The procedure was carried out in the same manner as in Example 10 → Example 11 → Example 24 to obtain the title compound having the following physical data.

Example 24 (1) N-hydroxy-3 (R) -hydroxy-4- (N-)
(4- (benzofuran-2-yl) phenylcarbonyl) amino) butyramide

[Chemical 168] TLC: Rf 0.41 (chloroform: methanol: water =
100: 20: 1); NMR (d ₆ -DMSO): δ 10.39 (1H, brs), 8.55 (1H,
m), 8.00 (4H, s), 7.71-7.63 (2H, m), 7.58 (1H, br
s), 7.39-7.24 (2H, m), 5.20-3.80 (1H, br), 4.12-3.9
8 (1H, m), 3.40-3.18 (2H, m), 2.16 (1H, dd, J = 4.8,
14.0Hz), 2.03 (1H, dd, J = 8.2, 14.0Hz).

Example 24 (2) N-hydroxy-3 (S) -methoxymethyloxy-4
-(N- (4- (benzofuran-2-yl) phenylcarbonyl) amino) butyramide

[Chemical 169] TLC: Rf 0.19 (chloroform: methanol = 1)
0: 1); NMR (d ₆ -DMSO): δ 10.47 (1H, brs), 8.80 (1H,
brs), 8.64 (1H, t, J = 5.8Hz), 8.02 (2H, d, J = 9.2H
z), 7.97 (2H, d, J = 9.2Hz), 7.71-7.63 (2H, m), 7.57
(1H, brs), 7.40-7.24 (2H, m), 4.60 (2H, s), 4.16-
4.04 (1H, m), 3.41 (2H, t, J = 5.8Hz), 3.21 (3H, s),
2.22-2.18 (2H, m).

Example 24 (3) N-hydroxy-4- (N- (4- (benzofuran-2)
-Yl) phenylcarbonyl) amino) -2-butenamide

[Chemical 170] TLC: Rf 0.20 (chloroform: methanol: acetic acid = 100: 10: 1); NMR (d ₆ -DMSO): δ 10.60 (1H, brs), 8.89 (1H,
t, J = 5.8Hz), 8.02 (4H, s), 7.71-7.63 (2H, m), 7.59
(1H, brs), 7.40 (2H, m), 6.69 (1H, dt, J = 15.4, 4.
8Hz), 5.86 (1H, d, J = 15.4Hz), 4.08-4.02 (2H, m).

Example 24 (4) N-hydroxy-3 (R) -methoxymethyloxy-4
-(N- (4- (benzofuran-2-yl) phenylcarbonyl) amino) butyramide

[Chemical 171] TLC: Rf 0.19 (chloroform: methanol = 1)
NMR (d ₆ -DMSO): δ 10.46 (1H, brs), 8.77 (1H, 0: 1);
brs), 8.64 (1H, t, J = 5.8Hz), 8.02 (2H, d, J = 9.2H
z), 7.97 (2H, d, J = 9.2Hz), 7.71-7.63 (2H, m), 7.58
(1H, brs), 7.40-7.24 (2H, m), 4.60 (2H, s), 4.16-
4.05 (1H, m), 3.42 (2H, t, J = 5.8Hz), 3.22 (3H, s),
2.22-2.19 (2H, m).

Example 24 (5) N-hydroxy-4- (N- (4- (benzofuran-2)
-Yl) phenylcarbonyl) amino) -3-butenamide

[Chemical 172] TLC: Rf 0.21 (chloroform: methanol: acetic acid = 100: 10: 1); NMR (d ₆ -DMSO): δ 10.45 (1H, brs), 10.37 (1H,
d, J = 9.6Hz), 8.98-8.52 (1H, brs), 8.04 (4H, s),
7.72-7.63 (2H, m), 7.61 (1H, brs), 7.41-7.24 (2H,
m), 6.94 (1H, dd, J = 9.6, 14.2Hz), 5.53 (1H, dt, J =
14.2, 7.8Hz), 2.76 (2H, d, J = 7.8Hz).

Example 24 (6) N-hydroxy-4- [N- [4- (benzofuran-2)
-Yl) phenylcarbonyl] amino] -3 (S) -benzyloxymethoxybutyramide

[Chemical 173] TLC: Rf 0.31 (chloroform: methanol = 1
0: 1); NMR (d ₆ -DMSO): δ 10.51 (1H, s), 8.67 (1H, t,
J = 5.6Hz), 7.98 (4H, m), 7.71-7.60 (2H, m), 7.57 (1
H, br.s), 7.39-7.20 (7H, m), 4.77 (1H, d, J = 6.8Hz),
4.73 (1H, d, J = 6.8Hz), 4.51 (2H, s), 4.20 (1H,
m), 3.49-3.43 (2H, m), 2.25 (2H, d, J = 6.2Hz).

Example 25 2-Benzyloxymethyl-4- (N- (4-methylphenylcarbonyl) amino) butanoic acid

[Chemical 174] Diisopropylamine (0.925 ml) in tetrahydrofuran (5 ml) and hexamethylphosphoramide (HMP
A) (3 ml) solution under argon atmosphere at -78 ° C 1.
63M n-butyllithium hexane solution (4.05 ml)
Was added. The mixture was stirred at -78 ° C for 15 minutes. A solution of the compound (0.442 g) produced in Example 2 (1) in tetrahydrofuran (3 ml) was added to this solution at -78 ° C. The reaction mixture was stirred at room temperature for 30 minutes. The reaction mixture was added to benzyloxymethyl chloride (0.31
3 g) was added. The reaction mixture was stirred at -78 ° C for 2 hours. A 1N aqueous hydrochloric acid solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated to give the title compound (0.22 g) having the following physical data. TLC: Rf 0.67 (chloroform: methanol: acetic acid = 18: 2: 1).

Example 26 N-Hydroxy-2-benzyloxymethyl-4- (N
-(4-Methylphenylcarbonyl) amino) butyramide

[Chemical 175] The title compound having the following physical data was obtained by the same procedure as in Example 3 → Example 4 using the compound produced in Example 25 instead of the compound produced in Example 2. TLC: Rf 0.36 (chloroform: methanol = 1)
0: 1); NMR (d ₆ -DMSO): δ 10.52 (1H, s), 8.86 (1H,
s), 8.32 (1H, t, J = 8.4Hz), 7.74 (2H, d, J = 8.4Hz),
7.31 (5H, m), 7.24 (2H, d, J = 8.4Hz), 4.46 (1H, d,
J = 12.5Hz), 4.44 (1H, d, J = 12.5Hz), 3.59 (1H, dd, J
= 8.8, 8.8Hz), 3.41 (1H, dd, J = 8.8, 5.5Hz), 3.21 (2
H, m), 2.44 (1H, m), 2.35 (3H, s), 1.66 (2H, m).

Example 27 N-Hydroxy-2-hydroxymethyl-4- (N-
(4-Methylphenylcarbonyl) amino) butyramide

[Chemical 176] To a solution of the compound (0.24 g) produced in Example 26 in methanol (10 ml) was added 10% palladium-carbon (0.024 g) under an argon atmosphere. The reaction mixture was stirred under a hydrogen atmosphere at room temperature for 2 hours. The reaction mixture was filtered through Celite (trade name), and the filtrate was concentrated. The residue was purified by silica gel column chromatography (chloroform: methanol = 10: 1) to give the title compound (0.158 g) having the following physical data. TLC: Rf 0.39 (ethyl acetate: acetic acid: water = 16:
3: 2); NMR (d ₆ -DMSO): δ 8.41 (1H, m), 7.76 (2H, d,
J = 8.0Hz), 7.24 (2H, d, J = 8.0Hz), 3.52 (1H, m), 3.37
(1H, m), 3.20 (2H, m), 2.35 (3H, s), 2.23 (1H,
m), 1.64 (2H, m).

Examples 27 (1) and 27 (2) Using the compound obtained by separating the compound prepared in Example 25 by liquid chromatography, the same procedure as in Example 3 → Example 4 → Example 27 is repeated. Then, the compound shown below was obtained.

Example 27 (1) N-hydroxy-2-hydroxymethyl-4- (N-
(4-Methylphenylcarbonyl) amino) butyramide

[Chemical 177] (In the formula, * represents an R or S form. The stereo structure has not been determined so far. However, it represents the opposite stereo structure of Example 27 (2).) TLC: Rf 0.17 (chloroform) : Methanol = 4:
1); NMR (CD ₃ OD): δ 7.70 (2H, d, J = 8.2Hz), 7.26
(2H, d, J = 8.2Hz), 3.79-3.52 (2H, m), 3.50-3.25 (2
H, m), 2.38 (3H, s), 2.38-2.25 (1H, m), 1.80 (2H, q
-like).

Example 27 (2) N-hydroxy-2-hydroxymethyl-4- (N-
(4-Methylphenylcarbonyl) amino) butyramide

[Chemical 178] (In the formula, * represents the R or S form. The stereostructure has not been determined so far. However, it represents the opposite stereostructure of Example 27 (1).) TLC: Rf 0.17 (chloroform) : Methanol = 4:
1); NMR (CD ₃ OD): δ 7.70 (2H, d, J = 8.2Hz), 7.26
(2H, d, J = 8.2Hz), 3.79-3.52 (2H, m), 3.50-3.25 (2
H, m), 2.38 (3H, s), 2.38-2.25 (1H, m), 1.80 (2H, q
-like).

Reference Example 5 4 (S) -Methylaminocarbonyl-4- (N-benzyloxycarbonylamino) butanoic acid t-butyl ester

[Chemical 179] The title compound having the following physical properties was obtained by the same procedure as in Example 15 using 4 (S) -carboxy-4- (N-benzyloxycarbonylamino) butanoic acid t-butyl ester and methylamine. Got TLC: Rf 0.73 (chloroform: methanol = 9:
1); NMR (CDCl ₃ ): δ 7.38-7.31 (5H, m), 6.24 (1H,
m), 5.65 (1H, m), 5.10 (2H, s), 4.20-4.12 (1H, m),
2.81 (3H, d, J = 5.0Hz), 2.49-2.24 (2H, m), 2.17-1.8
5 (2H, m), 1.44 (9H, s).

Reference Example 6 4 (S) -Methylaminocarbonyl-4-aminobutanoic acid t-butyl ester

[Chemical 180] The title compound having the following physical data was obtained by substituting the compound prepared in Reference Example 5 for the compound prepared in Example 26 and carrying out the same procedure as in Example 27. TLC: Rf 0.28 (chloroform: methanol = 9:
1).

Example 28 4 (S) -Methylaminocarbonyl-4- (N- (4-
Methylphenylcarbonyl) amino) butanoic acid t-butyl ester

[Chemical 181] Using the compound prepared in Reference Example 6 instead of the compound prepared in Reference Example 4, the procedure of Example 1 was repeated to give the title compound having the following physical data. TLC: Rf 0.46 (chloroform: methanol = 9:
1).

Example 29 4 (S) -Methylaminocarbonyl-4- (N- (4-
Methylphenylcarbonyl) amino) butanoic acid

[Chemical 182] The title compound having the following physical data was obtained by substituting the compound prepared in Example 28 for the compound prepared in Example 13 and operating in the same manner as in Example 14. TLC: Rf 0.40 (chloroform: methanol = 9:
1). NMR (d ₆ -DMSO): δ 12.13 (1H, brs), 8.33 (1H,
d, J = 7.8Hz), 7.86-7.78 (3H, m), 7.26 (2H, d, J = 8.1
Hz), 4.40-4.25 (1H, m), 2.59 (3H, d, J = 4.8Hz), 2.3
6 (3H, s), 2.30-2.23 (2H, m), 2.05-1.82 (2H, m).

Examples 29 (1) to 29 (3) Using the corresponding amine compound instead of the methylamine compound, the same procedure as in Reference Example 5 → Reference Example 6 → Example 28 → Example 29 was performed. Then, the compound shown below was obtained.

Example 29 (1) 4 (R) -methylaminocarbonyl-4- (N- (4-
Methylphenylcarbonyl) amino) butanoic acid

[Chemical 183] TLC: Rf 0.20 (chloroform: methanol = 5:
1); NMR (CDCl ₃ + CD ₃ OD): δ 7.60-7.33 (2H, m), 7.1
4-7.22 (2H, m), 4.52-4.66 (1H, m), 2.76 (3H, s),
2.30-2.56 (2H, m), 2.34 (3H, s), 1.84-2.22 (2H,
m).

Example 29 (2) 4 (S) -benzylaminocarbonyl-4- (N- (4
-Methylphenylcarbonyl) amino) butanoic acid

[Chemical 184] TLC: Rf 0.51 (chloroform: methanol = 4:
1); NMR (d ₆ -DMSO): δ 12.10 (1H, brs), 8.44 (2H,
d, J = 8.0Hz), 7.82 (2H, d, J = 8.0Hz), 7.27-7.21 (5H,
m), 4.49-4.40 (1H, m), 3.60 (1H, brs), 3.17 (2H,
s), 2.36 (3H, s), 2.40-2.25 (2H, m), 2.20-1.95 (2
H, m).

Example 29 (3) 4 (S)-(4-hydroxybutyl) aminocarbonyl-4- (N- (4-methylphenylcarbonyl) amino) butanoic acid

[Chemical 185] TLC: Rf 0.33 (chloroform: methanol = 4:
1).

Example 30 N-Hydroxy-4 (S) -methylaminocarbonyl-
4- (N- (4-methylphenylcarbonyl) amino)
Butyramide

[Chemical 186] The title compound having the following physical properties was obtained by the same procedure as in Example 3 → Example 4 using the compound produced in Example 29 instead of the compound produced in Example 2. TLC: Rf 0.69 (chloroform: methanol = 4:
1); NMR (d ₆ -DMSO): δ 10.37 (1H, brs), 8.69 (1H,
m), 8.43 (1H, d, J = 7.6Hz), 7.85-7.79 (3H, m), 7.25
(2H, d, J = 8.0Hz), 4.40-4.25 (1H, m), 2.59 (3H, d,
J = 4.6Hz), 2.06 (3H, s), 2.10-1.85 (4H, m).

Examples 30 (1) -30 (3) Example 29 instead of the compound prepared in Example 29
Example 3 using the compounds produced in (1) to 29 (3)
By operating in the same manner as the method indicated by 0, the following compounds were obtained.

Example 30 (1) N-hydroxy-4 (R) -methylaminocarbonyl-
4- (N- (4-methylphenylcarbonyl) amino)
Butyramide

[Chemical 187] TLC: Rf 0.30 (chloroform: methanol = 1)
0: 1); NMR (CD ₃ OD): δ 7.72 (2H, d, J = 8Hz), 7.20 (2
H, d, J = 8Hz), 4.44-4.50 (1H, m), 2.67 (3H, s), 2.3
1 (3H, s), 2.22-1.85 (4H, m).

Example 30 (2) N-hydroxy-4 (S) -benzylaminocarbonyl-4- (N- (4-methylphenylcarbonyl) amino) butyramide

[Chemical 188] TLC: Rf 0.42 (chloroform: methanol = 4:
1).

Example 30 (3) N-hydroxy-4 (S)-(4-hydroxybutyl)
Aminocarbonyl-4- (N- (4-methylphenylcarbonyl) amino) butyramide

[Chemical 189] TLC: Rf 0.23 (chloroform: methanol: acetic acid = 18: 2: 1); NMR (CDCl ₃ ): δ 7.74 (2H, d, J = 7.5Hz), 7.39
(1H, s), 7.25 (2H, d, J = 7.5Hz), 4.60-4.43 (1H, m),
3.61-3.56 (2H, m), 3.31-3.15 (2H, m), 2.40 (3H, s),
2.30-2.04 (4H, m), 1.62-1.48 (4H, m).

Example 31 4 (S) -methoxycarbonyl-4- [N- [4- (4
-(Tetrahydropyran-2-yloxy) -1-butynyl) phenylcarbonyl] amino] butanoic acid t-butyl ester

[Chemical 190] 4 (S) -methoxycarbonyl-4-aminobutanoic acid t
The title compound having the following physical data was obtained by operating in the same manner as in Example 1 using -butyl ester and the corresponding acid halide. TLC: Rf 0.35 (n-hexane: ethyl acetate = 1: 1
2); NMR (CDCl ₃ ): δ 7.78 (2H, d, J = 8.4Hz), 7.44
(2H, d, J = 8.4Hz), 7.21 (3H, s), 3.70-3.50 (2H, m),
2.75 (2H, t, J = 6.9Hz), 2.42 (2H, m), 2.30-2.00 (2
H, m), 2.00-1.50 (6H, m), 1.42 (9H, s).

Example 32 4 (S) -methoxycarbonyl-4- [N- [4- (4
-Hydroxy-1-butynyl) phenylcarbonyl] amino] butanoic acid

[Chemical 191] The title compound having the following physical data was obtained by substituting the compound prepared in Example 31 for the compound prepared in Example 13 and operating in the same manner as in Example 14. TLC: Rf 0.11 (n-hexane: ethyl acetate = 1: 1
1); NMR (CDCl ₃ + CD ₃ OD): δ 8.02 (1H, d, J = 7.6Hz),
7.77 (2H, d, J = 8.6Hz), 7.44 (2H, d, J = 8.6Hz), 4.8
2-4.70 (1H, m), 3.83-3.69 (5H, m), 2.68 (2H, t, J =
6.6Hz), 2.41 (2H, t, J = 6.6Hz), 2.26-1.99 (2H, m).

Example 33 N-Hydroxy-4 (S) -methoxycarbonyl-4-
[N- [4- (4-hydroxy-1-butynyl) phenylcarbonyl] amino] butyramide

[Chemical 192] The title compound having the following physical properties was obtained by the same procedure as in Example 3 → Example 4 using the compound produced in Example 32 instead of the compound produced in Example 2. TLC: Rf 0.30 (chloroform: methanol: acetic acid = 18: 2: 1); NMR (d ₆ -DMSO): δ 10.44 (1H, s), 10.20 (1H,
s), 8.89 (1H, d, J = 6.6Hz), 7.87 (2H, d, J = 7.8Hz),
7.47 (2H, d, J = 7.8Hz), 4.41 (1H, m), 3.66 (3H, s),
3.65-3.59 (2H, m), 2.58 (2H, t, J = 6.6Hz), 2.18-1.
95 (2H, m), 1.28-1.21 (2H, m).

Example 33 (1) N-hydroxy-4 (R) -carbonyl-4- [N-
[4- (3-Methoxy-1-propynyl) phenylcarbonyl] amino] butyramide

[Chemical formula 193] Using 4 (R) -t-butoxycarbonyl-4-aminobutanoic acid methyl ester and the corresponding acid halide, the same procedure as in Example 31 → Example 2 → Example 33 → Example 14 was repeated. The title compound having the following physical properties was obtained. TLC: Rf 0.18 (chloroform: methanol: acetic acid: water = 85: 15: 1: 1); NMR (d ₆ -DMSO): δ 7.86 (2H, d, J = 8.8Hz), 7.53 (2
H, d, J = 8.8Hz), 4.54-4.59 (1H, m), 4.34 (2H, s), 3.4
3 (3H, s), 2.05-2.36 (4H, m).

Example 34 4 (S) -t-butoxycarbonyl-4- (N- (4-
Methylphenylcarbonyl) amino) butanoic acid benzyl ester

[Chemical 194] Using 4 (S) -t-butoxycarbonyl-4-aminobutanoic acid benzyl ester and the corresponding acid halide, the same procedure as in Example 1 was carried out to obtain the title compound having the following physical properties. TLC: Rf 0.19 (n-hexane: ethyl acetate = 4:
1).

Example 35 4 (S) -t-butoxycarbonyl-4- (N- (4-
Methylphenylcarbonyl) amino) butanoic acid

[Chemical 195] The title compound having the following physical data was obtained by substituting the compound prepared in Example 34 for the compound prepared in Example 26 and operating in the same manner as in Example 27. TLC: Rf 0.38 (chloroform: methanol = 5:
1); NMR (CDCl ₃ ): δ 7.70 (2H, d, J = 8.2Hz), 7.22
(2H, d, J = 8.2Hz), 6.97 (1H, d, J = 7.5Hz), 4.71 (1H,
m), 2.47 (2H, m), 2.38 (3H, s), 2.28 (1H, m), 2.05
(1H, m), 1.49 (9H, s).

Example 36 N-Hydroxy-4 (S) -carboxy-4- (N-)
(4-Methylphenylcarbonyl) amino) butyramide

[Chemical 196] The title compound having the following physical properties was obtained by the same procedure as in Example 3 → Example 14 using the compound produced in Example 35 instead of the compound produced in Example 2. TLC: Rf 0.43 (ethyl acetate: acetic acid: water = 8: 1:
1); NMR (CD ₃ OD): δ 7.78 (2H, d, J = 8.0Hz), 7.28
(2H, d, J = 8.0Hz), 4.56 (1H, m), 2.40 (3H, s), 2.00
-2.38 (4H, m).

Example 37 4 (S) -Carboxy-4- (N- (4- (benzofuran-2-yl) phenylcarbonyl) amino) butanoic acid methyl ester

[Chemical 197] Using 4 (S) -carboxy-4-aminobutanoic acid methyl ester and the compound prepared in Reference Example 4 and in the same manner as in Example 1, the title compound having the following physical data was obtained. TLC: Rf 0.64 (chloroform: methanol: acetic acid = 18: 2: 1); NMR (CD ₃ OD): δ 12.74 (1H, brs), 8.74 (1H, d,
J = 7.8Hz), 8.04 (4H, s), 7.71-7.58 (3H, m), 7.42-7.
26 (2H, m), 4.45 (1H, m), 3.60 (3H, s), 2.51-2.44
(2H, m), 2.26-1.96 (2H, m).

Example 38 4 (S)-(morpholin-1-yl) carbonyl-4-
(N- (4- (benzofuran-2-yl) phenylcarbonyl) amino) butanoic acid

[Chemical 198] The title compound having the following physical properties was obtained by the same procedure as in Example 15 → Example 16 using the compound produced in Example 37 instead of the compound produced in Example 14. TLC: Rf 0.48 (chloroform: methanol = 4:
1); NMR (d ₆ -DMSO): δ 12.23 (1H, brs), 8.72 (1H,
d, J = 8.0Hz), 8.05-8.01 (4H, m), 7.74-7.58 (3H, m),
7.42-7.24 (2H, m), 5.03-4.86 (1H, m), 3.63-3.45
(8H, m), 2.37 (2H, t, J = 7.0Hz), 2.04-1.84 (2H,
m).

Example 39 4 (S) -Hydroxymethyl-4- (N- (4- (benzofuran-2-yl) phenylcarbonyl) amino) butanoic acid methyl ester

[Chemical formula 199] A solution of the compound (5.7 g) prepared in Example 37 in tetrahydrofuran (30 ml) was stirred at 0 ° C. with N-hydroxysuccinimide (2.2 g) and dichlorohexylcarbodiimide (4.0 g).
1 g) was added. The reaction mixture was stirred at 0 ° C. for 5 hours.
The reaction mixture was filtered, and sodium borohydride (1.19 g) and water (5 ml) were added to the filtrate at 0 ° C. The reaction mixture was stirred at room temperature for 30 minutes. A saturated ammonium chloride aqueous solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated to give the title compound (4.89 g) having the following physical data. TLC: Rf 0.21 (n-hexane: ethyl acetate = 3:
7); NMR (d ₆ -DMSO): δ 8.14 (1H, d, J = 8.4Hz), 7.99
(4H, s), 7.72-7.60 (2H, m), 7.55 (1H, d, J = 0.8Hz),
7.40-7.24 (2H, m), 4.75 (1H, t, J = 5.8Hz), 4.10-3.
90 (1H, m), 3.56 (3H, s), 3.55-3.39 (2H, m), 2.36
(2H, t, J = 7.4Hz), 2.06-1.62 (2H, m).

Example 40 4 (S) -Hydroxymethyl-4- (N- (4- (benzofuran-2-yl) phenylcarbonyl) amino) butanoic acid

[Chemical 200] The title compound having the following physical data was obtained by substituting the compound prepared in Example 39 for the compound prepared in Example 1 and operating in the same manner as in Example 2. TLC: Rf 0.33 (chloroform: methanol: acetic acid = 190: 10: 1); NMR (d ₆ -DMSO): δ 12.10-11.90 (1H, br), 8.14
(1H, d, J = 8.8Hz), 8.00 (4H, s), 7.73-7.60 (2H, m),
7.55 (1H, s), 7.41-7.22 (2H, m), 4.80-4.64 (1H,
m), 4.10-3.90 (1H, m), 3.54-3.35 (2H, m), 2.28 (2
H, t, J = 6.8Hz), 2.02-1.60 (2H, m).

Example 41 4 (S) -Methoxymethyloxymethyl-4- (N-)
(4- (benzofuran-2-yl) phenylcarbonyl) amino) butanoic acid methyl ester

[Chemical 201] Using the compound prepared in Example 39 in place of the compound prepared in Example 8 and operating in the same manner as in Example 10 (using methoxymethyl chloride in place of benzyloxymethyl chloride), A title compound having physical properties was obtained. TLC: Rf 0.65 (n-hexane: ethyl acetate = 3:
7); NMR (CDCl ₃ ): δ 7.94 (2H, d, J = 8.8Hz), 7.87
(2H, d, J = 8.8Hz) 7.64-7.50 (2H, m), 7.38-7.21 (2H,
m), 7.13 (1H, d, J = 0.8Hz), 6.78 (1H, d, J = 7.8Hz),
4.67 (2H, s), 4.46-4.28 (1H, m), 3.78 (1H, dd, J = 1
0.2, 3.4Hz), 3.65 (1H, dd, J = 10.2, 4.4Hz), 3.64 (3
H, s), 3.39 (3H, s), 2.62-2.38 (2H, m), 2.16-2.00
(2H, m).

Example 42 4 (S) -Methoxymethyloxymethyl-4- (N-
(4- (benzofuran-2-yl) phenylcarbonyl) amino) butanoic acid

[Chemical 202] The title compound having the following physical data was obtained by substituting the compound prepared in Example 41 for the compound prepared in Example 1 and operating in the same manner as in Example 2. TLC: Rf 0.19 (chloroform: methanol = 1)
9: 1); NMR (d ₆ -DMSO): δ 12.02 (1H, s), 8.30 (1H, d,
J = 8.2Hz), 8.00 (4H, s), 7.73-7.60 (2H, m), 7.56 (1
H, s), 7.41-7.22 (2H, m), 4.58 (2H, s), 4.26-4.08
(1H, m), 3.62-3.42 (2H, m), 3.32 (3H, s), 3.26 (3
H, s), 2.29 (2H, t, J = 6.8Hz), 2.02-1.62 (2H, m).

Example 43 2 (S) -benzyl-4 (S) -methoxymethyloxymethyl-4- (N- (4- (benzofuran-2-yl))
Phenylcarbonyl) amino) butanoic acid methyl ester

[Chemical 203] To a tetrahydrofuran (5 ml) solution of a 1.0 M solution of lithium bis (trimethylsilyl) amide in tetrahydrofuran (0.695 ml) was added a solution of the compound (0.474 g) prepared in Example 41 in tetrahydrofuran (5 ml) at -78 ° C. The mixture was stirred at −78 ° C. for 1 hour then benzyl bromide (0.113 ml) was added. The reaction mixture is -78
The mixture was stirred at 0 ° C for 3 hours. A saturated ammonium chloride aqueous solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography (n-hexane: ethyl acetate = 3: 2) to give the title compound (0.429 g) having the following physical data.
Got TLC: Rf 0.51 (n-hexane: ethyl acetate = 1: 1
1); NMR (CDCl ₃ ): δ 7.96 (2H, d, J = 8.8Hz), 7.84
(2H, d, J = 8.8Hz), 7.63-7.50 (2H, m), 7.38-7.10 (8
H, m), 6.57 (1H, d, J = 8.8Hz), 4.64 (1H, d, J = 8.8H)
z), 4.60 (1H, d, J = 8.8Hz), 4.50-4.30 (1H, m), 3.70
(1H, dd, J = 10.2, 3.2Hz), 3.59 (1H, dd, J = 10.2, 3.8
Hz), 3.40 (3H, s), 3.35 (3H, s), 3.04-2.72 (3H,
m), 2.19 (1H, ddd, J = 14.2, 10.4, 8.4Hz), 1.82 (1H,
dt, J = 14.2, 4.4Hz).

Example 44 2 (S) -Benzyl-4 (S) -methoxymethyloxymethyl-4- (N- (4- (benzofuran-2-yl))
Phenylcarbonyl) amino) butanoic acid

[Chemical 204] The title compound having the following physical data was obtained by substituting the compound prepared in Example 43 for the compound prepared in Example 1 and operating in the same manner as in Example 2. TLC: Rf 0.31 (chloroform: methanol = 1)
9: 1); NMR (CDCl ₃ ): δ 7.85 (2H, d, J = 8.8Hz), 7.79
(2H, d, J = 8.8Hz), 7.58-7.45 (2H, m), 7.36-7.10 (7
H, m), 7.04 (1H, d, J = 0.8Hz), 6.73 (1H, d, J = 8.8H
z), 4.60 (1H, d, J = 8.8Hz), 4.56 (1H, d, J = 8.8Hz),
4.50-4.30 (1H, m), 3.70 (1H, dd, J = 10.6, 3.2Hz),
3.57 (1H, dd, J = 10.6, 3.8Hz), 3.29 (3H, s), 3.11-2.
95 (1H, m), 2.90-2.75 (2H, m), 2.24-2.01 (1H, m),
1.90-1.72 (1H, m).

Examples 44 (1) to 44 (27) By using the compounds corresponding to the compounds produced in Reference Example 4, Example 37 → Example 39 → Example 41 (corresponding to methoxymethyl chloride instead). A compound may be used.) → Example 43 (A corresponding compound is used instead of benzyl bromide.) → The same operation as in Example 44 was carried out to obtain a compound shown below.

Example 44 (1) 2 (S) -Methyl-4 (S) -methoxymethyloxymethyl-4- (N- (4- (benzofuran-2-yl) phenylcarbonyl) amino) butanoic acid

[Chemical 205] TLC: Rf 0.25 (chloroform: methanol = 1)
9: 1); NMR (CDCl ₃ ): δ 7.89 (2H, d, J = 8.8Hz), 7.83
(2H, d, J = 8.8Hz), 7.62-7.50 (2H, m), 7.37-7.20 (2
H, m), 7.09 (1H, d, J = 1.0Hz), 6.63 (1H, d, J = 8.8H
z), 4.65 (2H, s), 4.55-4.36 (1H, m), 3.75 (1H, dd,
J = 10.2, 3.2Hz), 3.62 (1H, dd, J = 10.2, 4.0Hz), 3.38
(3H, s), 2.70-2.50 (1H, m), 2.23 (1H, ddd, J = 14.0,
11.0, 8.2Hz), 1.72 (1H, ddd, J = 14.0, 6.0, 4.4Hz),
1.30 (3H, d, J = 6.8Hz).

Example 44 (2) 2 (S)-(3-phenyl-2-propenyl) -4
(S) -Methoxymethyloxymethyl-4- (N- (4
-(Benzofuran-2-yl) phenylcarbonyl) amino) butanoic acid

[Chemical 206] TLC: Rf 0.44 (n-hexane: ethyl acetate = 3:
7); NMR (d ₆ -DMSO): δ 12.23 (1H, s), 8.34 (1H, d,
J = 8.4Hz), 8.00 (4H, s), 7.74-7.61 (2H, m), 7.57 (1
H, s), 7.41-7.18 (7H, m), 6.43 (1H, d, J = 15.6Hz),
6.20 (1H, dt, J = 15.6, 6.4Hz), 4.57 (2H, s), 4.40-
4.20 (1H, m), 3.62-3.48 (2H, m), 3.23 (3H, s), 2.60
-2.40 (3H, m), 1.92-1.80 (2H, m).

Example 44 (3) 2 (S)-(3-phenylpropyl) -4 (S) -methoxymethyloxymethyl-4- (N- (4- (benzofuran-2-yl) phenylcarbonyl) amino ) Butanoic acid

[Chemical formula 207] TLC: Rf 0.44 (n-hexane: ethyl acetate = 3:
7); NMR (CDCl ₃ ): δ 7.85 (2H, d, J = 8.8Hz), 7.79
(2H, d, J = 8.8Hz), 7.60-7.44 (2H, m), 7.34-7.06 (7
H, m), 7.03 (1H, d, J = 0.8Hz), 6.69 (1H, d, J = 8.8H
z), 4.62 (1H, d, J = 8.8Hz), 4.60 (1H, d, J = 8.8Hz),
4.48-4.28 (1H, m), 3.73 (1H, dd, J = 10.2, 3.4Hz),
3.59 (1H, dd, J = 10.2, 4.0Hz), 3.34 (3H, s), 2.68-2.
42 (3H, m), 2.21-2.00 (1H, m), 1.86-1.52 (5H, m).

Example 44 (4) 2 (S) -methyl-5-ethoxymethoxy-4 (S)-
[N- (4-chlorophenylcarbonyl) amino] pentanoic acid

[Chemical 208] TLC: Rf 0.46 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 12.06 (1H, s), 8.24 (1H, d,
J = 8.7Hz), 7.83 (2H, d, J = 8.4Hz), 7.51 (2H, d,
J = 8.4Hz), 4.57 (2H, s), 4.24-4.13 (1H, m), 3.52-
3.42 (4H, m), 2.37-2.25 (1H, m), 1.92-1.80 (1H,
m), 1.63-1.52 (1H, m), 1.06 (3H, t, J = 6.9Hz), 1.
05 (3H, d, J = 6.9Hz).

Example 44 (5) 2 (S) -methyl-5-ethoxymethoxy-4 (S)-
[N- (4-nitrophenylcarbonyl) amino] pentanoic acid

[Chemical 209] TLC: Rf 0.45 (methylene chloride: methanol = 9:
1); NMR (CDCl ₃ ): δ 8.27 (d, J = 9.0Hz, 2H), 7.96
(d, J = 9.0Hz, 2H), 6.89 (brd, J = 9.0Hz, 1H), 4.73
(d, J = 7.0Hz, 1H), 4.68 (d, J = 7.0Hz, 1H), 4.40
(m, 1H), 3.78 (dd, J = 10.6, 3.2Hz, 1H), 3.68-3.55
(m, 3H), 2.55 (m, 1H), 2.16 (ddd, J = 14.4, 10.2,
7.6Hz, 1H), 1.70 (ddd, J = 14.4,5.8, 5.0Hz, 1H),
1.28 (d, J = 7.0Hz, 3H), 1.20 (t, J = 7.0Hz, 3H).

Example 44 (6) 2 (S) -methyl-5-ethoxymethoxy-4 (S)-
[N- (4-bromophenylcarbonyl) amino] pentanoic acid

[Chemical 210] TLC: Rf 0.47 (methylene chloride: methanol = 9:
1); NMR (CDCl ₃ ): δ 7.65 (d, J = 8.8Hz, 2H), 7.54
(d, J = 8.8Hz, 2H), 6.67 (brd, J = 9.2Hz, 1H), 4.72
(d, J = 7.0Hz, 1H), 4.67 (d, J = 7.0Hz, 1H), 4.40
(m, 1H), 3.75 (dd, J = 10.4, 3.2Hz, 1H), 3.66-3.55
(m, 3H), 2.55 (m, 1H), 2.16 (ddd, J = 14.4, 10.2,
7.6Hz, 1H), 1.70 (ddd, J = 14.4,6.6, 4.8Hz, 1H),
1.27 (d, J = 7.0Hz, 3H), 1.20 (t, J = 7.0Hz, 3H).

Example 44 (7) 2 (S) -allyl-5-ethoxymethoxy-4 (S)-
[N- (4-nitrophenylcarbonyl) amino] pentanoic acid

[Chemical 211] TLC: Rf 0.31 (chloroform: methanol = 9:
1); NMR (CDCl ₃ ): δ 8.25 (d, J = 8.7Hz, 2H), 7.94
(d, J = 8.7Hz, 2H), 6.92 (d, J = 8.7Hz, 1H), 5.82-
5.68 (m, 1H), 5.14-5.06 (m, 2H), 4.73 (d, J = 6.9H
z, 1H), 4.68 (d, J = 6.9Hz, 1H), 4.45-4.32 (m, 1
H), 3.79 (dd, J = 10.2, 3.3Hz, 1H), 3.66-3.56 (m, 3
H), 2.63-2.31 (m, 3H), 2.14-2.03 (m, 1H), 1.82 (dt,
J = 14.1, 5.4Hz, 1H), 1.20 (t, J = 7.2Hz, 3H).

Example 44 (8) 2 (R) -methoxymethyl-5-ethoxymethoxy-4
(S)-[N- (4-nitrophenylcarbonyl) amino] pentanoic acid

[Chemical 212] TLC: Rf 0.24 (chloroform: methanol = 1
9: 1); NMR (CDCl ₃ ): δ 8.25 (d, J = 8.7Hz, 2H), 7.95
(d, J = 8.7Hz, 2H), 7.11 (d, J = 8.4Hz, 1H), 4.73
(d, J = 5.7Hz, 1H), 4.67 (d, J = 5.7Hz, 1H), 4.42-
4.31 (m, 1H), 3.80 (dd, J = 10.2, 3.3Hz, 1H), 3.69
-3.57 (m, 5H), 3.39 (s, 3H), 2.82-2.70 (m, 1H), 2.1
7 (ddd, J = 14.4, 10.2, 8.1Hz, 1H), 1.88 (dt, J = 1
4.4, 5.1Hz, 1H), 1.20 (t, J = 7.2Hz, 3H).

Example 44 (9) 2 (R) -benzyloxymethyl-5-ethoxymethoxy-4 (S)-[N- (4-nitrophenylcarbonyl) amino] pentanoic acid

[Chemical 213] TLC: Rf 0.41 (chloroform: methanol = 1
9: 1); NMR (CDCl ₃ ): δ 8.24 (d, J = 8.8Hz, 2H), 7.93
(d, J = 8.8Hz, 2H), 7.41-7.20 (m, 5H), 7.01 (d, J =
8.8Hz, 1H), 4.72 (d, J = 7.4Hz, 1H), 4.67 (d, J =
7.4Hz, 1H), 4.57 (s, 2H), 4.43-4.25 (m, 1H), 3.82
-3.52 (m, 6H), 2.89-2.70 (m, 1H), 2.19 (ddd, J = 1
4.8, 10.2, 8.0Hz, 1H), 1.70 (dt, J = 14.8, 5.0Hz, 1
H), 1.19 (t, J = 7.0Hz, 3H).

Example 44 (10) 2 (S) -methyl-5- (2-methoxyethoxy) methoxy-4 (S)-[N- (4-cyanophenylcarbonyl) amino] pentanoic acid

[Chemical 214] TLC: Rf 0.40 (chloroform: methanol = 1
9: 1); NMR (CDCl ₃ ): δ 7.91 (d, J = 8.4Hz, 2H), 7.70
(d, J = 8.4Hz, 2H), 7.07 (d, J = 9.0Hz, 1H), 4.75
(d, J = 6.9Hz, 1H), 4.70 (d, J = 6.9Hz, 1H), 4.45-
4.34 (m, 1H), 3.84 (dd, J = 10.5, 3.3Hz, 1H), 3.78
-3.60 (m, 3H), 3.54-3.51 (m, 2H), 3.29 (s, 3H), 2.61
-2.49 (m, 1H), 2.15 (ddd, J = 14.1,10.2, 7.5Hz, 1
H), 1.70 (ddd, J = 14.1,6.6, 5.1Hz, 1H), 1.20 (d,
J = 6.9Hz, 3H).

Example 44 (11) 2 (R)-(2-methoxyethoxy) methyl-5-ethoxymethoxy-4 (S)-[N- (4-nitrophenylcarbonyl) amino] pentanoic acid

[Chemical 215] TLC: Rf 0.17 (chloroform: methanol = 1
9: 1); NMR (CDCl ₃ ): δ 8.26 (d, J = 8.8Hz, 2H), 7.97
(d, J = 8.8Hz, 2H), 7.08 (d, J = 8.8Hz, 1H), 4.75-
4.62 (m, 2H), 4.44-4.28 (m, 1H), 3.82-3.48 (m, 10
H), 3.37 (s, 3H), 2.90-2.66 (m, 1H), 2.21 (ddd, J
= 14.4, 10.0, 8.6Hz, 1H), 1.92 (dt, J = 14.4, 4.8H
z, 1H), 1.20 (t, J = 7.0Hz, 3H).

Example 44 (12) 2 (S)-(2-propynyl) -5-ethoxymethoxy-4 (S)-[N- (4-nitrophenylcarbonyl)
Amino] pentanoic acid

[Chemical 216] TLC: Rf 0.30 (chloroform: methanol = 9:
1); NMR (CDCl ₃ ): δ 8.28 (d, J = 9.0Hz, 2H), 7.96
(d, J = 9.0Hz, 2H), 6.98 (d, J = 8.7Hz, 1H), 4.75
(d, J = 6.9Hz, 1H), 4.70 (d, J = 6.9Hz, 1H), 4.50-
4.38 (m, 1H), 3.84 (dd, J = 10.5, 3.0Hz, 1H), 3.70
-3.55 (m, 3H), 2.80-2.40 (m, 3H), 2.28-2.10 (m, 1
H), 2.10-1.95 (m, 2H), 1.21 (t, J = 7.2Hz, 3H).

Example 44 (13) 2 (S) -allyl-5- (2-methoxyethoxy) methoxy-4 (S)-[N- (4-cyanophenylcarbonyl) amino] pentanoic acid

[Chemical 217] TLC: Rf 0.26 (chloroform: methanol = 1
9: 1); NMR (CDCl ₃ ): δ 7.90 (d, J = 8.4Hz, 2H), 7.71
(d, J = 8.4Hz, 2H), 7.10 (d, J = 9.0Hz, 1H), 5.82-
5.66 (m, 1H), 5.16-5.03 (m, 2H), 4.75 (d, J = 6.9H
z, 1H), 4.70 (d, J = 6.9Hz, 1H), 4.38 (m, 1H), 3.8
5 (dd, J = 10.5, 3.6Hz, 1H), 3.80-3.58 (m, 3H), 3.
54 (t, J = 4.5Hz, 2H), 3.31 (s, 3H), 2.62-2.50 (m,
1H), 2.49-2.30 (m, 2H), 2.07 (dt, J = 14.4, 9.0Hz,
1H), 1.83 (dt, J = 14.4, 5.4Hz, 1H).

Example 44 (14) 2 (S) -methoxymethyl-5- (2-methoxyethoxy) methoxy-4 (S)-[N- (4-cyanophenylcarbonyl) amino] pentanoic acid

[Chemical 218] TLC: Rf 0.35 (chloroform: methanol = 9:
1); NMR (CD ₃ OD): δ 7.94 (d, J = 8.7Hz, 2H), 7.82
(d, J = 8.7Hz, 2H), 4.71 (d, J = 6.6Hz, 1H), 4.68
(d, J = 6.6Hz, 1H), 4.39-4.31 (m, 1H), 3.68-3.49
(m, 8H), 3.32 (s, 3H), 3.31 (s, 3H), 2.76-2.66 (m,
1H), 2.08-1.86 (m, 2H).

Example 44 (15) 2 (S)-(2-propynyl) -5-ethoxymethoxy-4 (S)-[N- (4-bromophenylcarbonyl)
Amino] pentanoic acid

[Chemical 219] TLC: Rf 0.36 (chloroform: methanol = 9:
1); NMR (CDCl ₃ ): δ 7.64 (d, J = 8.6Hz, 2H), 7.54
(d, J = 8.6Hz, 2H), 6.82 (d, J = 9.0Hz, 1H), 4.72
(d, J = 6.9Hz, 1H), 4.69 (d, J = 6.9Hz, 1H), 4.50-
4.35 (m, 1H), 3.80 (dd, J = 10.4, 3.2Hz, 1H), 3.70
-3.55 (m, 3H), 2.78-2.45 (m, 3H), 2.25-2.10 (m, 1
H), 2.10-1.95 (m, 2H), 1.20 (t, J = 7.2Hz, 3H).

Example 44 (16) 2 (S)-(2-propynyl) -5-ethoxymethoxy-4 (S)-[N- (4-chlorophenylcarbonyl)
Amino] pentanoic acid

[Chemical 220] TLC: Rf 0.36 (chloroform: methanol = 9:
1); NMR (CDCl ₃ ): δ 7.71 (d, J = 8.7Hz, 2H), 7.38
(d, J = 8.7Hz, 2H), 6.81 (d, J = 8.7Hz, 1H), 4.73
(d, J = 6.8Hz, 1H), 4.69 (d, J = 6.8Hz, 1H), 4.50-
4.35 (m, 1H), 3.80 (dd, J = 10.2, 3.0Hz, 1H), 3.70
-3.55 (m, 3H), 2.78-2.45 (m, 3H), 2.25-2.10 (m, 1
H), 2.10-1.95 (m, 2H), 1.20 (t, J = 7.2Hz, 3H).

Example 44 (17) 2 (R) -methoxymethyl-5-ethoxymethoxy-4
(S)-[N- (4-Bromophenylcarbonyl) amino] pentanoic acid

[Chemical 221] TLC: Rf 0.39 (chloroform: methanol = 9:
1); NMR (CD ₃ OD): δ 7.73-7.69 (m, 2H), 7.65-7.59
(m, 2H), 4.67 (s, 2H), 4.37-4.28 (m, 1H), 3.63-3.5
3 (m, 6H), 3.32 (s, 3H), 2.75-2.64 (m, 1H), 1.96-
1.89 (m, 2H), 1.15 (t, J = 7.2Hz, 3H).

Example 44 (18) 2 (R) -methoxymethyl-5-ethoxymethoxy-4
(S)-[N- (4-chlorophenylcarbonyl) amino] pentanoic acid

[Chemical 222] TLC: Rf 0.32 (chloroform: methanol = 9:
1); NMR (CD ₃ OD): δ 7.78 (d, J = 8.7Hz, 2H), 7.45
(d, J = 8.7Hz, 2H), 4.66 (s, 2H), 4.37-4.27 (m, 1
H), 3.63-3.54 (m, 6H), 3.32 (s, 3H), 2.74-2.62 (m,
1H), 1.97-1.88 (m, 2H), 1.15 (t, J = 7.2Hz, 3H).

Example 44 (19) 2 (R) -benzyloxymethyl-5- (2-methoxyethoxy) methoxy-4 (S)-[N- (4-cyanophenylcarbonyl) amino] pentanoic acid

[Chemical formula 223] TLC: Rf 0.48 (methylene chloride: methanol = 9:
1); NMR (CDCl ₃ ): δ 7.87 (d, J = 8.4Hz, 2H), 7.67
(d, J = 8.4Hz, 2H), 7.31 (m, 5H), 7.16 (brd, J = 9.
0Hz, 1H), 4.74 (d, J = 7.2Hz, 1H), 4.69 (d, J = 7.
2Hz, 1H), 4.55 (s, 2H), 4.34 (m, 1H), 3.83 (dd, J
= 10.2, 3.6Hz, 1H), 3.77-3.66 (m, 4H), 3.62 (dd, J
= 10.2, 4.2Hz, 1H), 3.51 (t, J = 4.5Hz, 2H), 3.29
(s, 3H), 2.79 (m, 1H), 2.15 (ddd, J = 14.1, 9.6,
7.5Hz, 1H), 1.91 (ddd, J = 14.1, 5.4, 5.4Hz, 1H).

Example 44 (20) 2 (R) -Benzyloxymethyl-5-ethoxymethoxy-4 (S)-[N- (4-chlorophenylcarbonyl) amino] pentanoic acid

[Chemical formula 224] TLC: Rf 0.50 (methylene chloride: methanol = 9:
1); NMR (CDCl ₃ ): δ 7.69 (d, J = 8.8Hz, 2H), 7.35
(d, J = 8.8Hz, 2H), 7.31 (m, 5H), 6.81 (brd, J = 8.
8Hz, 1H), 4.70 (d, J = 7.5Hz, 1H), 4.66 (d, J = 7.
5Hz, 1H), 4.55 (s, 2H), 4.33 (m, 1H), 3.80-3.50
(m, 6H), 2.80 (m, 1H), 2.15 (ddd, J = 14.2, 9.8,
7.6Hz, 1H), 1.89 (ddd, J = 14.2, 5.2,5.2Hz, 1H),
1.17 (t, J = 7.4Hz, 3H).

Example 44 (21) 2 (R) -benzyloxymethyl-5-ethoxymethoxy-4 (S)-[N- (4-bromophenylcarbonyl) amino] pentanoic acid

[Chemical formula 225] TLC: Rf 0.50 (methylene chloride: methanol = 9:
1); NMR (CDCl ₃ ): δ 7.62 (d, J = 8.8Hz, 2H), 7.51
(d, J = 8.8Hz, 2H), 7.31 (m, 5H), 6.81 (brd, J = 8.
8Hz, 1H), 4.70 (d, J = 7.0Hz, 1H), 4.65 (d, J = 7.
0Hz, 1H), 4.54 (s, 2H), 4.33 (m, 1H), 3.80-3.50
(m, 6H), 2.79 (m, 1H), 2.15 (ddd, J = 14.2, 9.8,
7.6Hz, 1H), 1.89 (ddd, J = 14.2, 5.2,5.2Hz, 1H),
1.18 (t, J = 7.4Hz, 3H).

Example 44 (22) 2 (S) -allyl-5-ethoxymethoxy-4 (S)-
[N- (4-bromophenylcarbonyl) amino] pentanoic acid

[Chemical formula 226] TLC: Rf 0.43 (chloroform: methanol = 9:
1); NMR (CDCl ₃ ): δ 7.63 (d, J = 8.7Hz, 2H), 7.53
(d, J = 8.7Hz, 2H), 6.72 (d, J = 9.0Hz, 1H), 5.83-
5.65 (m, 1H), 5.18-5.02 (m, 2H), 4.71 (d, J = 6.8H
z, 1H), 4.67 (d, J = 6.8Hz, 1H), 4.45-4.30 (m, 1
H), 3.76 (dd, J = 10.4, 3.2Hz, 1H), 3.70-3.50 (m, 3
H), 2.62-2.50 (m, 1H), 2.50-2.25 (m, 2H), 2.18-2.00
(m, 1H), 1.81 (td, J = 14.1, 5.1Hz, 1H), 1.20 (t,
J = 7.1Hz, 3H).

Example 44 (23) 2 (S) -allyl-5-ethoxymethoxy-4 (S)-
[N- (4-chlorophenylcarbonyl) amino] pentanoic acid

[Chemical 227] TLC: Rf 0.45 (chloroform: methanol = 9:
1); NMR (CDCl ₃ ): δ 7.70 (d, J = 8.7Hz, 2H), 7.38
(d, J = 8.7Hz, 2H), 6.73 (d, J = 9.0Hz, 1H), 5.82-
5.65 (m, 1H), 5.18-5.02 (m, 2H), 4.71 (d, J = 6.8H
z, 1H), 4.67 (d, J = 6.8Hz, 1H), 4.45-4.30 (m, 1
H), 3.76 (dd, J = 10.5, 3.3Hz, 1H), 3.70-3.50 (m, 3
H), 2.62-2.50 (m, 1H), 2.50-2.25 (m, 2H), 2.18-2.00
(m, 1H), 1.81 (td, J = 14.1, 5.3Hz, 1H), 1.20 (t,
J = 6.9Hz, 3H).

Example 44 (24) 2 (R)-(2-methoxyethoxy) methyl-5-ethoxymethoxy-4 (S)-[N- (4-bromophenylcarbonyl) amino] pentanoic acid

[Chemical 228] TLC: Rf 0.41 (chloroform: methanol = 9:
1); NMR (CDCl ₃ ): δ 7.65 (d, J = 8.8Hz, 2H), 7.54
(d, J = 8.8Hz, 2H), 6.85 (d, J = 8.8Hz, 1H), 4.70
(d, J = 7.0Hz, 1H), 4.66 (d, J = 7.0Hz, 1H), 4.42-
4.27 (m, 1H), 3.78-3.50 (m, 10H), 3.35 (s, 3H), 2.
83-2.70 (m, 1H), 2.18 (ddd, J = 14.0, 9.8, 7.0Hz,
1H), 1.82 (ddd, J = 14.0, 5.6, 4.4Hz, 1H), 1.18
(t, J = 7.4Hz, 3H).

Example 44 (25) 2 (R)-(2-methoxyethoxy) methyl-5- (2
-Methoxyethoxy) methoxy-4 (S)-[N- (4
-Cyanophenylcarbonyl) amino] pentanoic acid

[Chemical formula 229] TLC: Rf 0.16 (chloroform: methanol = 1
9: 1); NMR (CDCl ₃ ): δ 7.91 (d, J = 8.4Hz, 2H), 7.71
(d, J = 8.4Hz, 2H), 7.20 (d, J = 8.7Hz, 1H), 4.75
(d, J = 6.9Hz, 1H), 4.70 (d, J = 6.9Hz, 1H), 4.42-
4.31 (m, 1H), 3.84 (dd, J = 10.5, 3.9Hz, 1H), 3.78
-3.60 (m, 7H), 3.57-3.50 (m, 4H), 3.36 (s, 3H), 3.3
2 (s, 3H), 2.82-2.72 (m, 1H), 2.18 (ddd, J = 14.4,
10.2, 7.2Hz, 1H), 1.85 (dt, J = 14.4, 5.7Hz, 1H).

Example 44 (26) 2 (R)-(2-methoxyethoxy) methyl-5-ethoxymethoxy-4 (S)-[N- (4-chlorophenylcarbonyl) amino] pentanoic acid

[Chemical 230] TLC: Rf 0.31 (chloroform: methanol = 9:
1); NMR (CDCl ₃ ): δ 7.72 (d, J = 8.8Hz, 2H), 7.39
(d, J = 8.8Hz, 2H), 6.84 (d, J = 9.0Hz, 1H), 4.70
(d, J = 7.0Hz, 1H), 4.66 (d, J = 7.0Hz, 1H), 4.43-
4.27 (m, 1H), 3.78-3.50 (m, 10H), 3.35 (s, 3H), 2.
82-2.69 (m, 1H), 2.19 (ddd, J = 14.4, 10.6, 7.4Hz,
1H), 1.82 (ddd, J = 14.4, 5.6, 4.4Hz, 1H), 1.19
(t, J = 7.2Hz, 3H).

Example 44 (27) 2 (S)-(2-propynyl) -5- (2-methoxyethoxy) methoxy-4 (S)-[N- (4-cyanophenylcarbonyl) amino] pentanoic acid

[Chemical formula 231] TLC: Rf 0.37 (chloroform: methanol = 9:
1); NMR (CDCl ₃ ): δ 7.92 (d, J = 8.7 Hz, 2H), 7.69
(d, J = 8.7 Hz, 2H), 7.17 (d, J = 9.0 Hz, 1H), 4.
77 (d, J = 7.1 Hz, 1H), 4.71 (d, J = 7.1 Hz, 1H),
4.48-4.32 (m, 1H), 3.89 (dd, J = 10.5, 3.6 Hz, 1
H), 3.82-3.60 (m, 3H), 3.55 (t, J = 4.5 Hz, 2H),
3.31 (s, 3H), 2.78-2.50 (m, 3H), 2.25-2.10 (m, 1H),
2.10-1.95 (m, 2H).

Examples 44 (28) to 44 (29) By using the compounds corresponding to the compounds produced in Reference Example 4, Example 37 → Example 39 → Example 41 (corresponding to methoxymethyl chloride instead). A compound is used) → Example 43 (A corresponding compound is used instead of benzyl bromide) → Example 5 → The same operation as in the method of Example 44 is carried out to obtain a compound shown below.

Example 44 (28) 2 (S) -methyl-5-ethoxymethoxy-4 (S)-
[N-methyl-N- (4-bromophenylcarbonyl)
Amino] pentanoic acid

[Chemical 232] TLC: Rf 0.23 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 12.15 (1H, brs), 7.63-7.56
(2H, m), 7.34-7.25 (2H, m), 4.82-4.72 & 3.79-3.69 (1
H, m), 4.59 & 4.55 (2H, s), 3.61-3.37 (4H, m), 2.76 &
2.64 (3H, s), 2.08 (1H, sxt, J = 6.9Hz), 2.01-1.91
& 1.51-1.41 & 1.37-1.27 (2H, m), 1.14-1.04 (3H, m),
0.82 (3H, d, J = 6.9Hz).

Example 44 (29) 2 (S) -methyl-5-ethoxymethoxy-4 (S)-
[N-methyl-N- (4-nitrophenylcarbonyl)
Amino] pentanoic acid

[Chemical formula 233] TLC: Rf 0.42 (chloroform: methanol = 9:
1); NMR (CDCl ₃ ): δ 8.27 and 8.25 (d and d, J = 8.
7Hz and J = 8.7Hz, 2H), 7.68 and 7.58 (d and d, J
= 8.7Hz and J = 8.7Hz, 2H), 5.10-4.98 and 3.92-3.80
(m and m, 1H), 4.76-4.63 (m, 2H), 3.72-3.42 (m, 4
H), 2.96 and2.80 (s and s, 3H), 2.62-2.50 and 2.27
-2.21 (m and m, 1H), 2.12 and 1.59 (ddd and ddd, J
= 14.4, 10.5, 6.3Hz and 14.4, 7.5, 4.2Hz, 1H), 2.0
2 and1.41 (dt and dt, J = 14.4, 9.0Hz and 14.4, 5.
4Hz, 1H), 1.32 and 1.08 (dand d, J = 7.2Hz and 6.9
Hz, 3H), 1.23 and 1.22 (t and t, J = 7.2 and 7.2H
z, 3H).

Example 45 4 (S) -t-butyldimethylsilyloxymethyl-4
-(N- (4- (benzofuran-2-yl) phenylcarbonyl) amino) butanoic acid methyl ester

[Chemical formula 234] A solution of the compound (0.294 g) prepared in Example 39 in dimethylformamide (5 ml) was added with imidazole (0.107 g).
And t-butyldimethylsilyl chloride (0.241 g) were added. The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate, washed with water and saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography (n-hexane: ethyl acetate = 3: 1) to give the title compound (0.361 g) having the following physical data. TLC: Rf 0.83 (n-hexane: ethyl acetate = 1: 1
1); NMR (CDCl ₃ ): δ 7.94 (2H, d, J = 8.8Hz), 7.84
(2H, d, J = 8.8Hz), 7.63-7.52 (2H, m), 7.37-7.20 (3
H, m), 7.13 (1H, d, J = 0.8Hz), 6.62 (1H, d, J = 8.8H
z), 4.30-4.16 (1H, m), 3.74 (2H, d, J = 3.6Hz), 3.64
(3H, s), 2.59-2.38 (2H, m), 2.10-1.92 (2H, m), 0.
92 (9H, s), 0.086 (3H, s), 0.066 (3H, s).

Example 46 2 (S) -benzyl-4 (S) -t-butyldimethylsilyloxymethyl-4- (N- (4- (benzofuran-
2-yl) phenylcarbonyl) amino) butanoic acid methyl ester

[Chemical formula 235] The title compound having the following physical data was obtained by substituting the compound prepared in Example 45 for the compound prepared in Example 41 and operating in the same manner as in Example 42. TLC: Rf 0.43 (n-hexane: ethyl acetate = 7:
3); NMR (CDCl ₃ ): δ 7.93 (2H, d, J = 8.4Hz), 7.83
(2H, d, J = 8.4Hz), 7.63-7.50 (2H, m), 7.38-7.10 (8
H, m), 6.35 (1H, d, J = 8.8Hz), 4.36-4.17 (1H, m), 3.
74-3.60 (2H, m), 3.43 (3H, s), 3.02-2.68 (3H, m),
2.20-2.00 (1H, m), 1.90-1.74 (1H, m), 0.88 (9H, s),
0.038 (3H, s), 0.026 (3H, s).

Example 47 2 (S) -benzyl-4 (S) -t-butyldimethylsilyloxymethyl-4- (N- (4- (benzofuran-
2-yl) phenylcarbonyl) amino) butanoic acid

[Chemical 236] The title compound having the following physical data was obtained by substituting the compound prepared in Example 46 for the compound prepared in Example 1 and operating in the same manner as in Example 2. TLC: Rf 0.44 (chloroform: methanol = 1
9: 1); NMR (CD ₃ OD): δ 7.97 (2H, d, J = 8.4Hz), 7.90
(2H, d, J = 8.4Hz), 7.63-7.49 (2H, m), 7.37-7.10 (8
H, m), 4.35-4.18 (1H, m), 3.74-3.60 (2H, m), 3.05-
2.82 (2H, m), 2.80-2.64 (1H, m), 1.93 (2H, m), 0.8
7 (9H, s), 0.048 (6H, s).

Example 48 2 (R) -Benzyl-4 (S) -hydroxymethyl-4
-(N- (4- (benzofuran-2-yl) phenylcarbonyl) amino) butanoic acid

[Chemical 237] A solution of the compound (0.162 g) prepared in Example 47 in tetrahydrofuran (5 ml) was added at room temperature to a solution of 1 M tetrabutylammonium fluoride in tetrahydrofuran (0.4
ml) was added. The reaction mixture was stirred at room temperature for 2 hours.
Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated. The residue is subjected to silica gel column chromatography (n-hexane: ethyl acetate = 9: 1 to 1: 1).
Purification by 1: 9) gave the title compound (0.088 g) having the following physical data. TLC: Rf 0.22 (chloroform: methanol = 1)
9: 1); NMR (CD ₃ OD): δ 7.92 (4H, s), 7.60-7.42 (2H,
m), 7.38-7.06 (8H, m), 4.40-4.20 (1H, m), 3.64 (2
H, d, J = 5.4Hz), 3.02-2.82 (2H, m), 2.80-2.62 (1H,
m), 2.10-1.75 (2H, m).

Example 48 (1) 2 (S) -benzyl-4 (S) -hydroxymethyl-4
-(N- (4- (3-methoxy-1-propynyl) phenylcarbonyl) amino) butanoic acid

[Chemical 238] Using the corresponding acid halide in place of the compound prepared in Reference Example 4, the same procedure as in Example 37 → Example 39 → Example 45 → Example 46 → Example 47 → Example 48 was repeated, The title compound was obtained having the following physical data. TLC: Rf 0.21 (chloroform: methanol = 1
9: 1).

Example 49 N-Hydroxy-4 (S)-(morpholin-1-yl)
Carbonyl-4- (N- (4- (benzofuran-2-yl) phenylcarbonyl) amino) butyramide

[Chemical 239] The title compound having the following physical properties was obtained by the same procedure as in Example 3 → Example 4 using the compound prepared in Example 38 instead of the compound prepared in Example 2. TLC: Rf 0.39 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.42 (1H, s), 8.75 (1H, d,
J = 7.6Hz), 8.04 (4H, s), 7.74-7.57 (3H, m), 7.42-7.
25 (2H, m), 5.00-4.82 (1H, m), 3.71-3.40 (8H, m),
2.19-1.82 (4H, m).

Examples 49 (1) -49 (8) Instead of the compound prepared in Example 38, Examples 40, 42, 44, 44 (1) -44.
(3) Using the compounds produced in Example 48 and Example 48 (1), the same operation as in Example 49 was conducted,
The compound shown below was obtained.

Example 49 (1) N-hydroxy-4 (S) -hydroxymethyl-4-
(N- (4- (benzofuran-2-yl) phenylcarbonyl) amino) butyramide

[Chemical 240] TLC: Rf 0.22 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.36 (1H, d, J = 1.5Hz), 8.6
7 (1H, d, J = 1.5Hz), 8.19 (1H, d, J = 8.4Hz), 8.00 (4
H, s), 7.73-7.61 (2H, m), 7.57 (1H, d, J = 0.8Hz),
7.42-7.23 (2H, m), 4.73 (1H, t, J = 5.8Hz), 4.08-3.8
5 (1H, m), 3.58-3.38 (2H, m), 2.12-1.60 (4H, m).

Example 49 (2) N-Hydroxy-4 (S) -methoxymethyloxymethyl-4- (N- (4- (benzofuran-2-yl) phenylcarbonyl) amino) butyramide

[Chemical 241] TLC: Rf 0.47 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.37 (1H, s), 8.34 (1H, d,
J = 8.4Hz), 8.00 (4H, s), 7.73-7.61 (2H, m), 7.56 (1
H, s), 7.41-7.24 (2H, m), 4.58 (2H, s), 4.23-4.04
(1H, m), 3.62-3.44 (2H, m), 3.26 (3H, s), 2.12-1.6
2 (4H, m).

Example 49 (3) N-hydroxy-2 (S) -benzyl-4 (S) -methoxymethyloxymethyl-4- (N- (4- (benzofuran-2-yl) phenylcarbonyl) amino) Butyramide

[Chemical 242] TLC: Rf 0.35 (chloroform: methanol = 1)
9: 1); NMR (d ₆ -DMSO): δ 10.37 (1H, s), 8.69 (1H,
s), 8.25 (1H, d, J = 8.6Hz), 8.01 (4H, s), 7.72-7.61
(2H, m), 7.57 (1H, s), 7.41-7.09 (7H, m), 4.55 (2
H, s), 4.40-4.20 (1H, m), 3.53 (2H, d, J = 5.6Hz),
3.22 (3H, s), 2.79 (2H, d, J = 7.4Hz), 2.50-2.34 (1
H, m), 1.90-1.60 (2H, m).

Example 49 (4) N-hydroxy-2 (S) -methyl-4 (S) -methoxymethyloxymethyl-4- (N- (4- (benzofuran-2-yl) phenylcarbonyl) amino) Butyramide

[Chemical formula 243] TLC: Rf 0.23 (chloroform: methanol = 1
9: 1); NMR (d ₆ -DMSO): δ 10.41 (1H, d, J = 1.6Hz), 8.6
8 (1H, d, J = 1.6Hz), 8.20 (1H, d, J = 8.4Hz), 8.00 (4
H, s), 7.74-7.60 (2H, m), 7.56 (1H, d, J = 0.8Hz),
7.41-7.22 (2H, m), 4.58 (2H, s), 4.32-4.10 (1H,
m), 3.62-3.41 (2H, m), 3.25 (3H, s), 2.30-2.14 (1
H, m), 1.82-1.58 (2H, m), 1.05 (3H, d, J = 6.6Hz).

Example 49 (5) N-hydroxy-2 (S)-(3-phenyl-2-propenyl) -4 (S) -methoxymethyloxymethyl-4
-(N- (4- (benzofuran-2-yl) phenylcarbonyl) amino) butyramide

[Chemical formula 244] TLC: Rf 0.36 (chloroform: methanol = 1)
9: 1); NMR (d ₆ -DMSO): δ 10.50 (1H, s), 8.78 (1H,
s), 8.25 (1H, d, J = 8.4Hz), 8.00 (4H, s), 7.67 (2H,
t, J = 8.6Hz), 7.56 (1H, s), 7.40-7.14 (7H, m), 6.4
1 (1H, d, J = 16.0Hz), 6.15 (1H, dt, J = 16.0, 5.8Hz),
4.57 (2H, s), 4.32-4.14 (1H, m), 3.62-3.45 (2H,
m), 3.24 (3H, s), 2.46-2.22 (3H, m), 1.96-1.78 (2
H, m).

Example 49 (6) N-hydroxy-2 (S)-(3-phenylpropyl)
-4 (S) -methoxymethyloxymethyl-4- (N-
(4- (benzofuran-2-yl) phenylcarbonyl) amino) butyramide

[Chemical 245] TLC: Rf 0.35 (chloroform: methanol = 1)
9: 1); NMR (d ₆ -DMSO): δ 10.47 (1H, s), 8.82-8.66 (1
H, brs), 8.20 (1H, d, J = 8.4Hz), 7.99 (4H, s), 7.72
-7.61 (2H, m), 7.57 (1H, d, J = 0.6Hz), 7.41-7.10 (7
H, m), 4.57 (2H, s), 4.23-4.02 (1H, m), 3.60-3.42
(2H, m), 3.24 (3H, s), 2.62-2.40 (2H, m), 2.22-2.06
(1H, m), 1.84-1.64 (2H, m), 1.60-1.38 (4H, m).

Example 49 (7) N-hydroxy-2 (R) -benzyl-4 (S) -hydroxymethyl-4- (N- (4- (benzofuran-2-
Ill) phenylcarbonyl) amino) butyramide

[Chemical formula 246] TLC: Rf 0.37 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.32 (1H, s), 8.68 (1H,
s), 8.08 (1H, d, J = 8.4Hz), 8.02 (4H, s), 7.72-7.62
(2H, m), 7.59 (1H, s), 7.41-7.06 (7H, m), 4.82-4.
66 (1H, m), 4.24-4.04 (1H, m), 3.60-3.36 (2H, m),
2.92-2.66 (2H, m), 2.50-2.30 (1H, m), 1.92-1.52 (2
H, m).

Example 49 (8) N-hydroxy-2 (S) -benzyl-4 (S) -hydroxymethyl-4- (N- (4- (3-methoxy-1-)
Propynyl) phenylcarbonyl) amino) butyramide

[Chemical 247] TLC: Rf 0.23 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.28 (1H, brs), 8.62 (1H,
brs), 8.04 (1H, d, J = 8.4Hz), 7.87 (2H, d, J = 8.2H
z), 7.53 (2H, d, J = 8.2Hz), 7.24-7.05 (5H, m), 4.69
(1H, t, J = 5.7Hz), 4.33 (2H, s), 4.18-4.02 (1H,
m), 3.46-3.34 (2H, m), 3.31 (3H, s), 2.75 (2H, d, J
= 7.0Hz), 2.42-2.26 (1H, m), 1.89-1.52 (2H, m).

Example 49 (9) N-hydroxy-5-hydroxy-4 (S)-[N-
[4- (3-Methoxy-1-propynyl) phenylcarbonyl] amino] pentanamide

[Chemical 248] Example 37 → Example 39 → Example 40 → Example 4 using the corresponding compound instead of the compound prepared in Reference Example 4.
The title compound having the following physical properties values was obtained by operating in the same manner as in the method indicated by 9. TLC: Rf 0.36 (chloroform: methanol = 4:
1); NMR (d ₆ -DMSO): δ 10.35 (1H, s), 10.18 (1H,
s), 8.18 (1H, d, J = 8.4Hz), 7.88 (2H, d, J = 8.4Hz),
7.55 (2H, d, J = 8.4Hz), 4.53 (2H, s), 4.02-3.84 (1
H, m), 3.73-3.34 (2H, m), 3.35 (3H, s), 2.07-1.59
(4H, m).

Example 49 (10) N-hydroxy-5-hydroxy-4 (R)-[N-
[4- (3-Methoxy-1-propynyl) phenylcarbonyl] amino] pentanamide

Embedded image Carried out using 4 (R) -carboxy-4-aminobutanoic acid methyl ester instead of 4 (S) -carboxy-4-aminobutanoic acid methyl ester, and the corresponding compound instead of the compound prepared in Reference Example 4. The procedure of Example 37 → Example 39 → Example 40 → Example 49 was repeated to give the title compound having the following physical data. TLC: Rf 0.28 (chloroform: methanol: acetic acid: water = 85: 15: 1: 1); NMR (CD ₃ OD): δ 7.83 (2H, d, J = 8.4Hz), 7.51 (2H,
d, J = 8.4Hz), 4.34 (2H, s), 4.03-4.15 (1H, m), 3.62
(2H, d, J = 5.6Hz), 3.43 (3H, s), 2.19 (2H, t, J = 7.4H
z), 1.77-2.10 (2H, m).

Examples 49 (11) to 49 (21) Example 37 using the corresponding compound instead of Reference Example 4.
-> Example 38 (using a corresponding amine compound)-> It operated similarly to the method shown in Example 49, and the compound shown below was obtained.

Example 49 (11 ) N-hydroxy-4 (S)-(4-hydroxybutylcarbamoyl) -4- [N- [4- (3-methoxy-1-)
Propynyl) phenylcarbonyl] amino] butyramide

[Chemical 250] TLC: Rf 0.40 (chloroform: methanol = 4:
1); NMR (d ₆ -DMSO): δ 10.41 (1H, s), 8.61 (1H, d,
J = 7.8Hz), 7.98-7.88 (3H, m), 7.55 (2H, d, J = 8.4Hz),
4.44-4.27 (3H, m), 3.38 (2H, t, J = 6.2Hz), 3.35 (3
H, s), 3.13- 3.00 (2H, m), 2.09-1.83 (4H, m), 1.48
-1.34 (4H, m).

Example 49 (12) N-hydroxy-4 (S)-(3-phenylpropylcarbamoyl) -4- [N- [4- (3-methoxy-1-)
Propynyl) phenylcarbonyl] amino] butyramide

[Chemical 251] TLC: Rf 0.38 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.41 (1H, s), 8.72 (1H, s),
8.64 (1H, d, J = 7.6Hz), 8.04-7.94 (1H, m), 7.92 (2
H, d, J = 8.5Hz), 7.55 (2H, d, J = 8.5Hz), 7.32-7.14
(5H, m), 4.43-4.35 (3H, m), 3.33 (3H, s), 3.16-3.0
2 (2H, m), 2.62-2.49 (2H, m), 2.14-1.84 (4H, m),
1.80-1.62 (2H, m).

Example 49 (13) N-hydroxy-4 (S) -propylcarbamoyl-4
-[N- [4- (3-Methoxy-1-propynyl) phenylcarbonyl] amino] butyramide

[Chemical 252] TLC: Rf 0.23 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.40 (1H, s), 8.71 (1H, s),
8.61 (1H, d, J = 7.8Hz), 7.96-7.88 (3H, m), 7.55 (2
H, d, J = 8.3Hz), 4.43-4.26 (3H, m), 3.32 (3H, s),
3.09-2.95 (2H, m), 2.07-1.79 (4H, m), 1.41 (2H, se
xtet, J = 7.3Hz), 0.83 (3H, t, J = 7.3Hz).

Example 49 (14) N-hydroxy-4 (S)-(2-hydroxyethylcarbamoyl) -4- [N- [4- (3-methoxy-1-)
Propynyl) phenylcarbonyl] amino] butyramide

[Chemical 253] TLC: Rf 0.09 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.39 (1H, s), 8.71 (1H, s),
8.63 (1H, d, J = 7.6Hz), 7.97-7.87 (3H, m), 7.56 (2
H, d, J = 8.2Hz), 4.66 (1H, t, J = 5.4Hz), 4.43-4.35
(3H, m), 3.40 (2H, m), 3.33 (3H, s), 3.19-3.08 (2
H, m), 2.09-1.83 (4H, m).

Example 49 (15 ) N-hydroxy-4 (S)-(6-hydroxyhexylcarbamoyl) -4- [N- [4- (3-methoxy-1)
-Propinyl) phenylcarbonyl] amino] butyramide

[Chemical formula 254] TLC: Rf 0.42 (chloroform: methanol = 4:
1); NMR (d ₆ -DMSO): δ 10.37 (1H, s), 8.68 (1H, s),
8.57 (1H, d, J = 7.6Hz), 7.93-7.83 (3H, m), 7.53 (2
H, d, J = 8.4Hz), 4.37-4.25 (4H, m), 3.38-3.29 (5H,
m), 3.09-2.93 (2H, m), 2.12-1.78 (4H, m), 1.43-1.1
5 (8H, m).

Example 49 (16) N-hydroxy-4 (S)-[2- (4-methoxyphenyl) ethylcarbamoyl] -4- [N- [4- (3-
Methoxy-1-propynyl) phenylcarbonyl] amino] butyramide

[Chemical 255] TLC: Rf 0.25 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.40 (1H, s), 8.72 (1H, s),
8.62 (1H, d, J = 8.4Hz), 8.00-7.86 (3H, m), 7.60-7.
52 (2H, m), 7.10-7.08 (2H, d, J = 8.4Hz), 6.82-6.79
(2H, d, J = 8.4Hz), 4.40-4.25 (3H, m), 3.70-3.69 (3
H, s), 3.35 (3H, s), 3.36-3.15 (2H, m), 2.63 (2H,
t, J = 7.3Hz), 2.19-1.82 (4H, m).

Example 49 (17) N-hydroxy-4 (S)-(2-morpholinoethylcarbamoyl) -4- [N- [4- (3-methoxy-1-)
Propynyl) phenylcarbonyl] amino] butyramide

[Chemical 256] TLC: Rf 0.70 (chloroform: methanol = 4:
1); NMR (d ₆ -DMSO): δ 10.32 (1H, s), 8.60 (1H, d,
J = 7.6Hz), 8.32 (1H, s), 7.92 (2H, d, J = 8.4Hz), 7.83
(1H, t, J = 5.5Hz), 7.56 (2H, d, J = 8.4Hz), 4.42-4.30
(3H, m), 3.55-3.48 (4H, m), 3.35 (3H, s), 3.23-3.
20 (4H, m), 2.39-2.29 (4H, m), 2.21-1.83 (4H, m).

Example 49 (18) N-hydroxy-4 (S)-[2- (indole-3-
Ill) ethylcarbamoyl) -4- [N- [4- (3-
Methoxy-1-propynyl) phenylcarbonyl] amino] butyramide

[Chemical 257] TLC: Rf 0.33 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.79 (1H, s), 10.41 (1H,
s), 8.64 (1H, d, J = 7.6Hz), 8.12-8.04 (1H, m), 7.92
(2H, d, J = 8.5Hz), 7.61-7.52 (3H, m), 7.32 (1H, d,
J = 7.6Hz), 7.17-6.92 (3H, m), 4.45-4.35 (3H, m),
3.42-3.33 (4H, m), 2.82 (2H, t, J = 7.4Hz), 2.17-1.8
4 (4H, m).

Example 49 (19) N-Hydroxy-4 (S)-(4-phenylbutylcarbamoyl) -4- [N- [4- (3-methoxy-1-propynyl) phenylcarbonyl] amino] butyramide

[Chemical 258] TLC: Rf 0.16 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.40 (1H, s), 8.70 (1H, br)
s), 8.62 (1H, d, J = 7.8Hz), 7.98-7.87 (3H, m), 7.55
(2H, d, J = 8.5Hz), 7.30-7.14 (5H, m), 4.40-4.34 (3
H, m), 3.35 (3H, s), 3.09 (2H, q, J = 6.0Hz), 2.56
(2H, t, J = 7.0Hz), 2.12-1.83 (4H, m), 1.64-1.34 (4
H, m).

Example 49 (20) N-Hydroxy-4 (S)-(2-phenylethylcarbamoyl) -4- [N- [4- (3-methoxy-1-propynyl) phenylcarbonyl] amino] butyramide

[Chemical 259] TLC: Rf 0.36 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.39 (1H, s), 8.72 (1H, s),
8.63 (1H, d, J = 8.0Hz), 8.01 (1H, t, J = 5.7Hz), 7.9
2 (2H, d, J = 8.4Hz), 7.57 (2H, d, J = 8.4Hz), 7.29-7.1
4 (5H, m), 4.39-4.28 (3H, m), 3.35-3.23 (5H, m),
2.71 (2H, t, J = 7.5Hz), 2.09-1.82 (4H, m).

Example 49 (21) N-hydroxy-4 (S)-[3- (pyrazole-1-
) Propylcarbamoyl] -4- [N- [4- (3
-Methoxy-1-propynyl) phenylcarbonyl] amino] butyramide

[Chemical 260] TLC: Rf 0.23 (chloroform: methanol: acetic acid = 9: 1: 0.5); NMR (d ₆ -DMSO): δ 10.43 (1H, s), 8.69 (1H, d,
J = 7.5Hz), 8.06 (1H, t, J = 5.6Hz), 7.93 (2H, d, J = 8.4
Hz), 7.71 (1H, d, J = 2.0Hz), 7.56 (2H, d, J = 8.4Hz),
7.42 (1H, d, J = 2.0Hz), 6.21 (1H, t, J = 2.0Hz), 4.3
7-4.27 (3H, m), 4.11 (2H, t, J = 6.8Hz), 3.35 (3H,
s), 3.09-2.99 (2H, m), 2.12-1.86 (6H, m).

Example 49 (22) N-hydroxy-4 (R)-(3-phenylpropylcarbamoyl) -4- [N- [4- (3-methoxy-1-)
Propynyl) phenylcarbonyl] amino] butyramide

[Chemical 261] Example 37 → Example using 4 (R) -carboxy-4-aminobutanoic acid methyl ester and the corresponding compound instead of 4 (S) -carboxy-4-aminobutanoic acid methyl ester 38 (using corresponding amine compound) → The same operation as in Example 49 gave the title compound having the following physical data. TLC: Rf 0.44 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.39 (1H, brs), 8.70 (1H, br
s), 8.63 (1H, d, J = 7.8Hz), 7.98 (1H, t, J = 5.6Hz), 7.
90 (2H, d, J = 8.4Hz), 7.54 (2H, d, J = 8.4Hz), 7.10-7.2
8 (5H, m), 4.42-4.35 (3H, m), 3.32 (3H, s), 3.11-3.01
(2H, m), 2.57-2.47 (2H, m), 2.13-1.82 (4H, m), 1.74-
1.60 (2H, m).

Example 49 (23) N-hydroxy-2- (pyridin-3-yl) methyl-
4- (2-phenylethylcarbamoyl) -4- [N-
(4-phenoxyphenylcarbonyl) amino] butyramide

[Chemical 262] Instead of 4 (S) -carboxy-4-aminobutanoic acid methyl ester, 4 (S) -t-butoxycarbonyl-
Example 43 → Example 27 → Example 37 using 4- (N-benzyloxycarbonylamino) butanoic acid methyl ester and the corresponding compound instead of benzyl bromide.
(A corresponding compound is used instead of Reference Example 4) → Example 14 → Example 38 (using a corresponding amine compound) → The same operation as in Example 49 is carried out, and the following physical properties are obtained. The title compound was obtained. TLC: Rf 0.30, 0.36 (chloroform: methanol: acetic acid = 9: 1: 0.5); NMR (d ₆ -DMSO / MeOH): δ 8.33-8.26 (2H, m), 7.89
-7.82 (2H, m), 7.48 (1H, t, J = 8.1Hz), 7.39-7.31 (2
H, m), 7.24-7.06 (5H, m), 7.02-6.90 (6H, m), 4.48
(1H of 2 isomers, dd, J = 5.0Hz, 10.1Hz), 4.29 (1H o
f 2 isomers, dd, J = 4.2Hz, 10.5Hz), 3.20-3.02 (2H,
m), 2.95-2.84 (1H of 2 isomers, m), 2. 79-2.57 (1H
of 2 isomers + 2H, m), 2.51-2.27 (2H, m), 2.04-1.9
2 (2H of 2 isomers, m), 1.88-1.77 (2H of 2 isomers, m)
s, m).

Examples 49 (24) to 49 (35) Example 37 using the corresponding compound instead of Reference Example 4.
→ Example 39 → Example 41 (corresponding compound may be used instead of methoxymethyl chloride) → Example 42 → The same operation as in the method shown in Example 49,
The compound shown below was obtained.

Example 49 (24) N-hydroxy-5-methoxymethoxy-4 (S)-
[N- [4- (3-methoxy-1-propynyl) phenylcarbonyl] amino] pentanamide

[Chemical 263] TLC: Rf 0.22 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.35 (1H, s), 8.32 (1H, d,
J = 8.6Hz), 7.87 (2H, d, J = 8.4Hz), 7.55 (2H, d, J = 8.4
Hz), 4.57 (2H, s), 4.36 (2H, s), 4.20-4.01 (1H,
m), 3.55-3.44 (2H, m), 3.35 (3H, s), 3.24 (3H, s),
2.09-1.64 (4H, m).

Example 49 (25) N-hydroxy-5-benzyloxymethoxy-4
(S)-[N- [4- (3-Methoxy-1-propynyl) phenylcarbonyl] amino] pentanamide

[Chemical 264] TLC: Rf 0.24 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.37 (1H, s), 8.36 (1H, d,
J = 8.8Hz), 7.88 (2H, d, J = 8.5Hz), 7.55 (2H, d, J = 8.5
Hz), 7.37-7.26 (5H, m), 4.72 (2H, s), 4.53 (2H,
s), 4.35 (2H, s), 4.22-4.07 (1H, m), 3 .63-3.55 (2
H, m), 3.35 (3H, s), 2.09-1.68 (4H, m).

Example 49 (26) N-Hydroxy-5- (2-methoxyethoxy) methoxy-4 (S)-[N- [4- (3-phenoxy-1-propynyl) phenylcarbonyl] amino] pentanamide

[Chemical 265] TLC: Rf 0.41 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1); NMR (d ₆ -DMSO): δ 10.32 (1H, s), 8.65 (1H, s),
8.30 (1H, d, J = 8.6Hz), 7.84 (2H, d, J = 8.4Hz), 7.52 (2
H, d, J = 8.4Hz), 7.28-7.36 (2H, m), 6.93-7.06 (3H,
m), 5.04 (2H, s), 4.60 (2H, s), 3.95-4.16 (1H, m), 3.
38-3 .56 (6H, m), 3.19 (3H, s), 1.57-2.08 (4H, m).

Example 49 (27) N-hydroxy-5-methoxymethoxy-4 (S)-
[N- [4- (3-phenoxy-1-propynyl) phenylcarbonyl] amino] pentanamide

[Chemical 266] TLC: Rf 0.27 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1); NMR (d ₆ -DMSO): δ 10.31 (1H, brs), 8.69 (1H, br
s), 8.29 (1H, brs), 7.83 (2H, d, J = 8.7Hz), 7.51 (2H,
d, J = 8.4Hz), 7.16 (2H, t, J = 8.0Hz), 7.03 (2H, d, J = 8.
7Hz), 6.97 (1H, t, J = 7.5Hz), 5.05 (2H, s), 4.54 (2H,
s), 3.98-4.13 (1H, m), 3.42-3.52 (2H, m), 3.21 (3H,
s), 1.62-2.02 (4H, m).

Example 49 (28) N-hydroxy-5-benzyloxymethoxy-4
(S)-[N- [4- (3-phenoxy-1-propynyl) phenylcarbonyl] amino] pentanamide

[Chemical 267] TLC: Rf 0.47 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.34 (1H, s), 8.67 (1H, s),
8.35 (1H, d, J = 8.0Hz), 7.85 (2H, d, J = 8.4Hz), 7.52 (2
H, d, J = 8.4Hz), 7.37-7.25 (7H, m), 7.07-6.94 (3H,
m), 5.06 (2H, s), 4.70 (2H, s), 4.51 (2H, s), 4.01-3.
98 (1H, m), 3.56 (2H, d, J = 6.0Hz), 2.09-1.58 (4H,
m).

Example 49 (29) N-hydroxy-5-methoxymethoxy-4 (S)-
[N- (4-phenoxyphenylcarbonyl) amino]
Pentanamide

[Chemical 268] TLC: Rf 0.36 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1); NMR (d ₆ -DMSO): δ 10.33 (1H, s), 8.66 (1H, s),
8.16 (1H, d, J = 8.4Hz), 7.87 (2H, d, J = 8.8Hz), 7.46-7.
38 (2H, m), 7.22-7.15 (2H, m), 7.07-6.99 (3H, m), 4.54
(2H, s), 4.19-3.94 (1H, m), 3.49-3.45 (2H, m), 3.22
(3H, s), 2.07-1.57 (4H, m).

Example 49 (30) N-hydroxy-5-methoxymethoxy-4 (S)-
[N- [4- (4-chlorophenyl) phenylcarbonyl] amino] pentanamide

[Chemical 269] TLC: Rf 0.28 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.37 (1H, s), 8.31 (1H, d,
J = 8.2Hz), 7.97 (2H, d, J = 8.6Hz), 7.81-7.75 (4H, m),
7.55 (2H, d, J = 8.6Hz), 4.58 (2H, s), 4.19-4.03 (1
H, m), 3.56-3.49 (2H, m), 3.25 (3H, s), 2.09-1 .77
(4H, m).

Example 49 (31) N-hydroxy-5-methoxymethoxy-4 (S)-
[N- [4- [2- (4-methylphenyl) ethynyl]]
Phenylcarbonyl] amino] pentanamide

[Chemical 270] TLC: Rf 0.37 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1); NMR (d ₆ -DMSO): δ 10.35 (1H, brs.), 8.67 (1H, br
s.), 8.33 (1H, d, J = 8.6Hz), 7.89 (2H, d, J = 8.4Hz),
7.62 (2H, d, J = 8.4Hz), 7.47 (2H, d, J = 8.2Hz), 7.25 (2
H, d, J = 8.2Hz), 4.56 (2H, s), 4.19-3.98 (1H, m), 3.5
6-3.42 (2H, m), 3.23 (3H, s), 2.34 (3H, s), 2.09-1.58
(4H, m).

Example 49 (32) N-hydroxy-5-methoxymethoxy-4 (S)-
[N- [4- [2E- (4-chlorophenyl) ethenyl] phenylcarbonyl] amino] pentanamide

[Chemical 271] TLC: Rf 0.38 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.35 (1H, brs.), 8.67 (1H, br
s.), 8.23 (1H, d, J = 8.6Hz), 7.87 (2H, d, J = 8.2Hz),
7.68 (2H, d, J = 8.4Hz), 7.66 (2H, d, J = 8.4Hz), 7.41 (2
H, d, J = 8.2Hz), 7.40 (1H, d, J = 17.8Hz), 7.31 (1H, d,
J = 17.8Hz), 4.56 (2H, s), 4.19-3.98 (1H, m), 3.58-3.
41 (2H, m), 3.23 (3H, s), 2.11-1.56 (4H, m).

Example 49 (33) N-hydroxy-5-methoxymethoxy-4 (S)-
[N- [4- (1-heptynyl) phenylcarbonyl]
Amino] pentanamide

[Chemical 272] TLC: Rf 0.46 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.34 (1H, s), 8.67 (1H, s),
8.27 (1H, d, J = 8.4Hz), 7.82 (2H, d, J = 8.2Hz), 7.45 (2
H, d, J = 8.2Hz), 4.55 (2H, s), 4.18-3.97 (1H, m), 3.57
-3.41 (2H, m), 3.22 (3H, s), 2.49-2.40 (2H, m), 2.04-
1.22 (10H, m), 0.88 (3H, t, J = 6.8Hz).

Example 49 (34) N-hydroxy-5-ethoxymethoxy-4 (S)-
[N- (4-phenoxyphenylcarbonyl) amino]
Pentanamide

[Chemical 273] TLC: Rf 0.34 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.36 (s, 1H), 8.68 (s, 1H),
8.17 (d, J = 8.4Hz, 1H), 7.89 (d, J = 8.9Hz, 2H), 7.
43 (dd, J = 8.5, 7.5Hz, 2H), 7.20 (t, J = 7.5Hz, 1
H), 7.07 (dd, J = 1.1, 8.5Hz, 2H), 7.03 (d, J = 8.9H
z, 2H), 4.61 (s, 2H), 4.15-4.00 (m, 1H), 3.60-3.40
(m, 4H), 2.10-1.95 (m, 2H), 1.95-1.80 (m, 1H), 1.
80-1.60 (m, 1H), 1.11 (t, J = 7.1Hz, 3H).

Example 49 (35) N-hydroxy-5-ethoxymethoxy-4 (S)-
[N- (4-methylphenylcarbonyl) amino] pentanamide

[Chemical 274] TLC: Rf 0.30 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.32 (s, 1H), 8.65 (s, 1H),
8.10 (d, J = 8.4Hz, 1H), 7.73 (d, J = 8.3Hz, 2H), 7.
22 (d, J = 8.3Hz, 2H), 4.57 (s, 2H), 4.10-3.98 (m, 1
H), 3.52-3.40 (m, 4H), 2.32 (s, 3H), 2.01-1.94 (m,
2H), 1.91-1.78 (m, 1H), 1.73-1.61 (m, 1H), 1.05
(t, J = 7.1Hz, 3H).

Example 49 (36) N-hydroxy-5-methoxymethoxy-4 (R)-
[N- [4- (3-methoxy-1-propynyl) phenylcarbonyl] amino] pentanamide

[Chemical 275] Example 37 → Example using 4 (R) -carboxy-4-aminobutanoic acid methyl ester and the corresponding compound instead of 4 (S) -carboxy-4-aminobutanoic acid methyl ester 39 → Example 4
1 → Example 42 → The same procedure as in Example 49 was conducted to obtain the title compound having the following physical properties. TLC: Rf 0.25 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1); NMR (CD ₃ OD): δ 8.32 (1H, d, J = 8.8Hz), 7.82 (2
H, d, J = 8.8Hz), 7.52 (2H, d, J = 8.8Hz), 4.62 (2H,
s), 4.34 (2H, s), 4.16-4.31 (1H, m), 3.62 (2H, d,
J = 5.6Hz), 3.43 (3H, s), 3.33 (3H, s), 2.20 (2H, t,
J = 7.0Hz), 1.17-2.11 (2H, m).

Examples 49 (37) to 49 (67) Using the corresponding compounds instead of the compounds prepared in Reference Example 4, Example 37 → Example 39 → Example 41 → Example 4
3 (use methyl iodide instead of benzyl bromide)
-> Example 44-> It carried out similarly to the method shown in Example 49, and obtained the compound shown below.

Example 49 (37) N-hydroxy-2 (S) -methyl-5-methoxymethoxy-4 (S)-[N- [4- [2- (4-imidazolylphenyl) ethynyl] phenylcarbonyl] amino]
Pentanamide

[Chemical 276] TLC: Rf 0.33 (chloroform: methanol = 1)
0: 1); NMR (d ₆ -DMSO): δ 10.40 (1H, brs), 8.68 (1H, b
rs), 8.36 (1H, s), 8.24 (1H, d, J = 9.0Hz), 7.91 (2
H, d, J = 8.4Hz), 7.84 (1H, brs), 7.77 (2H, d, J = 9.0
Hz), 7.72 (2H, d, J = 9.0Hz), 7.66 (2H, d, J = 8.4Hz),
7.13 (1H, brs), 4.56 (2H, s), 4.22-4.11 (1H, m),
3.54-3.44 (2H, m), 3.23 (3H, s), 2.25-2.14 (1H,
m), 1.76-1.61 (2H, m), 1.03 (3H, d, J = 6.6Hz).

Example 49 (38) N-hydroxy-2 (S) -methyl-5-methoxymethoxy-4 (S)-[N- [4- (4-phenyl-1,
2,5,6-Tetrahydropyridin-1-yl) phenylcarbonyl] amino] pentanamide

[Chemical 277] TLC: Rf 0.32 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.39 (1H, brs), 8.67 (1H, b
rs), 7.90-7.70 (3H, m), 7.49 (2H, d, J = 7.5Hz), 7.37
(2H, t, J = 7.5Hz), 7.27 (1H, t, J = 7.5Hz), 6.99 (2H,
d, J = 9.0Hz), 6.35-6.25 (1H, brs), 4.56 (2H, s),
4.25-4.05 (1H, m), 4.00-3.90 (2H, m), 3.59 (2H, t,
J = 5.4Hz), 3.55-3.40 (2H, m), 3.24 (3H, s), 2.70-2.
55 (2H, m), 2.30-2.10 (1H, m), 1.80-1.60 (2H, m),
1.03 (3H, d, J = 6.9Hz).

Example 49 (39) N-Hydroxy-2 (S) -methyl-5-methoxymethoxy-4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide

[Chemical 278] TLC: Rf 0.49 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1); NMR (d ₆ -DMSO): δ 10.38 (1H, d, J = 1.5Hz), 8.66
(1H, d, J = 1.5Hz), 8.05 (1H, d, J = 8.4Hz), 7.88 (2H,
d, J = 8.7Hz), 7.45-7.40 (2H, m), 7.22-7.17 (1H, m), 7.
08-7.01 (4H, m), 4.55 (2H, s), 4.21-4.08 (1H, m), 3.5
2-3.44 (2H, m), 3.22 (3H, s), 2.25-2.09 (1H, m), 1.67
(2H, t, J = 7.2Hz), 1.01 (3H, d, J = 6.6Hz).

Example 49 (40) N-hydroxy-2 (S) -methyl-5-methoxymethoxy-4 (S)-[N- [4- [2- (4-chlorophenyl) ethenyl] phenylcarbonyl] amino ] Pentanamide

[Chemical formula 279] TLC: Rf 0.41 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1); NMR (d ₆ -DMSO): δ 10.39 (1H, s), 8.67 (1H, s),
8.10 (1H, d, J = 8.6Hz), 7.86 (2H, d, J = 8.4Hz), 7.70-7.
63 (4H, m), 7.45 (2H, d, J = 8.6Hz), 7.40 (1H, d, J = 16.6
Hz), 7.31 (1H, d, J = 16.6Hz), 4.56 (2H, s), 4.25-4.08
(1H, m), 3.57-3.41 (2H, m), 3.23 (3H, s), 2.25-2.15
(1H, m), 1.68 (2H, t, J = 6.6Hz), 1.02 (3H, d, J = 7.0H
z).

Example 49 (41) N-Hydroxy-2 (S) -methyl-5-methoxymethoxy-4 (S)-[N- [4- (4-propylphenyl) phenylcarbonyl] amino] pentanamide

[Chemical 280] TLC: Rf 0.31 (chloroform: methanol = 1)
0: 1); NMR (d ₆ -DMSO): δ 10.39 (1H, brs), 8.67 (1H, b
rs), 8.14 (1H, d, J = 8.7Hz), 7.93 (2H, d, J = 8.4Hz),
7.73 (2H, d, J = 8.4Hz), 7.63 (2H, d, J = 8.1Hz), 7.3
0 (2H, d, J = 8.1Hz), 4.56 (2H, s), 4.24-4.12 (1H,
m), 3.55-3.44 (2H, m), 3.23 (3H, s), 2.59 (2H, t,
J = 7.2Hz), 2.26-2.35 (1H, m), 1.73-1.65 (2H, m), 1.
61 (2H, m), 1.03 (3H, d, J = 6.9Hz), 0.91 (3H, t, J =
7.2Hz).

Example 49 (42) N-hydroxy-2 (S) -methyl-5-methoxymethoxy-4 (S)-[N- [4- (benzothiophene-2
-Yl) phenylcarbonyl] amino] pentanamide

[Chemical 281] TLC: Rf 0.33 (chloroform: methanol = 1)
0: 1); NMR (d ₆ -DMSO): δ 10.40 (1H, brs), 8.68 (1H, b
rs), 8.19 (1H, d, J = 9.0Hz), 8.01-7.94 (4H, m), 7.8
8-7.85 (3H, m), 7.44-7.35 (2H, m), 4.57 (2H, s),
4.24-4.12 (1H, m), 3.55-3.45 (2H, m), 3.24 (3H,
s), 2.26-2.15 (1H, m), 1.77-1.62 (2H, m), 1.04 (3
H, d, J = 6.6 Hz).

Example 49 (43) N-Hydroxy-2 (S) -methyl-5-methoxymethoxy-4 (S)-[N- [4- (3-methoxyphenoxy) phenylcarbonyl] amino] pentanamide

[Chemical 282] TLC: Rf 0.38 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1); NMR (d ₆ -DMSO): δ 10.36 (s, 1H), 8.67 (s, 1H),
7.87 (d, J = 8.8Hz, 2H), 7.32 (m, 1H), 7.05 (d, J =
8.8Hz, 2H), 6.77 (m, 1H), 6.63 (m, 1H), 6.60 (m, 1
H), 4.55 (s, 2H), 4.15 (m, 1H), 3.74 (s, 3H), 3.22
(s, 3H), 2.18 (m, 1H), 1.66 (m, 2H), 1.02 (d, J = 6.
6Hz, 3H).

Example 49 (44) N-Hydroxy-2 (S) -methyl-5-methoxymethoxy-4 (S)-[N- [4- (4-methoxyphenoxy) phenylcarbonyl] amino] pentanamide

[Chemical 283] TLC: Rf 0.45 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.50-10.20 (br, 1H), 8.80-
8.50 (br, 1H), 8.01 (d, J = 8.4Hz, 1H), 7.85 (d, J =
8.7Hz, 2H), 7.05 (d, J = 9.2Hz, 2H), 6.99 (d, J = 9.2H
z, 2H), 6.94 (d, J = 8.7Hz, 2H), 4.56 (s, 2H), 4.25-
4.05 (m, 1H), 3.77 (s, 3H), 3.55-3.40 (m, 2H), 3.2
3 (s, 3H), 2.30-2.10 (m, 1H), 1.80-1.60 (m, 2H),
1.02 (d, J = 6.9Hz, 3H).

Example 49 (45) N-Hydroxy-2 (S) -methyl-5-methoxymethoxy-4 (S)-[N- (4-benzoylphenylcarbonyl) amino] pentanamide

[Chemical 284] TLC: Rf 0.36 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.38 (1H, s), 8.66 (1H, s),
8.31 (1H, d, J = 8.1Hz), 7.98 (2H, d, J = 8.7Hz), 7.7
9-7.65 (5H, m), 7.55 (2H, t, J = 7.5Hz), 4.55 (2H,
s), 4.24-4.12 (1H, m), 3.52-3.42 (2H, m), 3.21 (3
H, s), 2.25-2.13 (1H, m), 1.71-1.63 (2H, m), 1.01
(3H, d, J = 6.9Hz).

Example 49 (46) N-Hydroxy-2 (S) -methyl-5-methoxymethoxy-4 (S)-[N- [4- (naphthalen-2-yl) phenylcarbonyl] amino] pentanamide

[Chemical 285] TLC: Rf 0.31 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1); NMR (d ₆ -DMSO): δ 10.41 (br, 1H), 8.68 (br, 1)
H), 8.30 (s, 1H), 8.05-7.9 (m, 8H), 7.6-7.5 (m, 2
H), 4.58 (s, 2H), 4.20 (m, 1H), 3.51 (m, 2H), 3.24
(s, 3H), 2.01 (m, 1H), 1.72 (m, 2H), 1.04 (d, J =
6.6Hz, 3H).

Example 49 (47) N-hydroxy-2 (S) -methyl-5-methoxymethoxy-4 (S)-[N- [4-[(4-methoxybiphenyl-4'-yl) oxy]] Phenylcarbonyl] amino] pentanamide

[Chemical 286] TLC: Rf 0.34 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.60-10.35 (br, 1H), 8.80-
8.60 (br, 1H), 8.11 (d, J = 8.4Hz, 1H), 7.94 (d, J
= 8.4Hz, 2H), 7.66 (d, J = 8.8Hz, 2H), 7.59 (d, J
= 8.8Hz, 2H), 7.20-6.95 (m, 6H), 4.57 (s, 2H), 4.
30-4.10 (m, 1H), 3.81 (s, 3H), 3.60-3.40 (m, 2H),
3.25 (s, 3H), 2.40-2.10 (m, 1H), 1.90-1.60 (m, 2
H), 1.04 (d, J = 6.6Hz, 3H).

Example 49 (48) N-Hydroxy-2 (S) -methyl-5-methoxymethoxy-4 (S)-[N- [4- (4-ethoxyphenyl) phenylcarbonyl] amino] pentanamide

[Chemical 287] TLC: Rf 0.41 (chloroform: methanol = 1
0: 1); NMR (d ₆ -DMSO): δ 10.39 (1H, brs), 8.67 (1H, b
rs), 8.11 (1H, d, J = 8.7Hz), 7.91 (2H, d, J = 8.1Hz),
7.70 (2H, d, J = 8.1Hz), 7.66 (2H, d, J = 8.7Hz), 7.0
2 (2H, d, J = 8.7Hz), 4.56 (2H, s), 4.24-4.12 (1H,
m), 4.07 (2H, q, J = 6.9Hz), 3.54-3.44 (2H, m), 3.23
(3H, s), 2.26-2.34 (1H, m), 1.73-1.65 (2H, m), 1.
34 (3H, t, J = 6.9Hz), 1.03 (3H, d, J = 6.9Hz).

Example 49 (49) N-hydroxy-2 (S) -methyl-5-methoxymethoxy-4 (S)-[N- [4- (4-phenoxyphenyl) phenylcarbonyl] amino] pentanamide

[Chemical 288] TLC: Rf 0.43 (chloroform: methanol = 1
0: 1); NMR (d ₆ -DMSO): δ 10.40 (1H, brs), 8.67 (1H, b
rs), 8.14 (1H, d, J = 8.6Hz), 7.94 (2H, d, J = 8.4Hz),
7.75 (2H, d, J = 8.8Hz), 7.74 (2H, d, J = 8.4Hz), 7.4
6-7.38 (2H, m), 7.21-7.05 (3H, m), 7.10 (2H, d, J =
8.8Hz), 4.57 (2H, s), 4.27-4.10 (1H, m), 3.58-3.42
(2H, m), 3.23 (3H, s), 2.29-2.12 (1H, m), 1.73-1.
66 (2H, m), 1.03 (3H, d, J = 6.6Hz).

Example 49 (50) N-Hydroxy-2 (S) -methyl-5-methoxymethoxy-4 (S)-[N- [4- (3-cyanomethylphenyl) phenylcarbonyl] amino] pentanamide

[Chemical formula 289] TLC: Rf 0.40 (chloroform: methanol = 1)
0: 1); NMR (d ₆ -DMSO): δ 10.40 (1H, brs), 8.67 (1H, b
rs), 8.18 (1H, d, J = 8.7Hz), 7.96 (2H, d, J = 8.4Hz),
7.76 (2H, d, J = 8.4Hz), 7.70 (1H, s), 7.69 (1H, d,
J = 7.8Hz), 7.52 (1H, t, J = 7.8Hz), 7.39 (1H, d, J = 7.
8Hz), 4.57 (2H, s), 4.24-4.13 (1H, m), 4.11 (2H,
s), 3.52 (1H, dd, J = 5.3, 9.9Hz), 3.47 (1H, dd, J =
6.0, 9.9Hz), 3.23 (3H, s), 2.27-2.34 (1H, m), 1.77
-1.62 (2H, m), 1.03 (3H, d, J = 6.6Hz).

Example 49 (51 ) N-hydroxy-2 (S) -methyl-5-methoxymethoxy-4 (S)-[N- [4- (biphenyl-4-yl) phenylcarbonyl] amino] pentanamide

[Chemical 290] TLC: Rf 0.26 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1); NMR (d ₆ -DMSO): δ 10.40 (br, 1H), 8.67 (br, 1)
H), 8.18 (d, J = 8.8Hz, 1H), 7.96 (d, J = 8.5Hz, 2
H), 7.85-7.75 (m, 6H), 7.73 (m, 2H), 7.49 (m, 2H),
7.39 (m, 1H), 4.57 (s, 2H), 4.19 (m, 1H), 3.50
(m, 2H), 3.24 (s, 3H), 2.21 (m, 1H), 1.70 (m, 2H),
1.03 (d, J = 6.6Hz, 3H).

Example 49 (52) N-Hydroxy-2 (S) -methyl-5-methoxymethoxy-4 (S)-[N- [4- (3-hydroxyphenoxy) phenylcarbonyl] amino] pentanamide

[Chemical formula 291] TLC: Rf 0.17 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1); NMR (d ₆ -DMSO): δ 10.32 (br, 1H), 8.67 (br, 1)
H), 8.04 (d, J = 8.8Hz, 1H), 7.87 (d, J = 8.8Hz, 2
H), 7.18 (t, J = 8.2Hz, 1H), 7.02 (d, J = 8.8Hz, 2
H), 6.58 (m, 1H), 6.45 (m, 1H), 6.40 (m, 1H), 4.55
(s, 2H), 4.15 (m, 1H), 3.47 (m, 2H), 3.22 (s, 3H),
2.07 (m, 1H), 1.66 (m, 2H), 1.01 (d, J = 6.9Hz, 3
H).

Example 49 (53) N-hydroxy-2 (S) -methyl-5-methoxymethoxy-4 (S)-[N- [4- [2- (4-methylphenyl) ethynyl] phenylcarbonyl] Amino] pentanamide

[Chemical 292] TLC: Rf 0.23 (chloroform: methanol = 1
9: 1); NMR (d ₆ -DMSO): δ 10.40 (1H, s), 8.21 (1H, d,
J = 8.4Hz), 7.90 (2H, d, J = 8.4Hz), 7.61 (2H, d, J = 8.4
Hz), 7.47 (2H, d, J = 8.0Hz), 7.25 (2H, d, J = 8.0Hz),
4.57 (2H, s), 4.30- 4.10 (1H, m), 3.60-3.40 (2H,
m), 3.24 (3H, s), 2.35 (3H, s), 2.28-2.10 (1H, m),
1.78-1.60 (2H, m), 1.04 (3H, d, J = 7.0Hz).

Example 49 (54) N-hydroxy-2 (S) -methyl-5-methoxymethoxy-4 (S)-[N- [4- (4-hydroxyphenoxy) phenylcarbonyl] amino] pentanamide

[Chemical formula 293] TLC: Rf 0.23 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.38 (s, 1H), 9.41 (s, 1H),
8.67 (s, 1H), 7.98 (d, J = 8.7Hz, 1H), 7.84 (d, J
= 8.9Hz, 2H), 6.95-6.85 (m, 4H), 6.81 (d, J = 8.9H
z, 2H), 4.56 (s, 2H), 4.25-4.10 (m, 1H), 3.55-3.40
(m, 2H), 3.24 (s, 3H), 2.25-2.10 (m, 1H), 1.70-1.
60 (m, 2H), 1.03 (d, J = 6.9Hz, 3H).

Example 49 (55) N-Hydroxy-2 (S) -methyl-5-methoxymethoxy-4 (S)-[N- [4- (4-chlorophenyl)
Phenylcarbonyl] amino] pentanamide

[Chemical formula 294] TLC: Rf 0.39 (chloroform: methanol = 1)
0: 1); NMR (d ₆ -DMSO): δ 10.40 (1H, d, J = 1.8Hz), 8.67
(1H, d, J = 1.8Hz), 8.18 (1H, d, J = 8.4Hz), 7.95 (2
H, d, J = 8.4Hz), 7.76 (2H, d, J = 8.4Hz), 7.76 (2H, d,
J = 8.7Hz), 7.54 (2H, d, J = 8.7Hz), 4.56 (2H, s), 4.
24-4.12 (1H, m), 3.55-3.44 (2H, m), 3.23 (3H, s),
2.26-2.14 (1H, m), 1.77-1.62 (2H, m), 1.03 (3H, d,
J = 6.9Hz).

Example 49 (56) N-hydroxy-2 (S) -methyl-5-methoxymethoxy-4 (S)-[N-[[5- (4-methoxyphenyl) -2-thienyl] carbonyl] Amino] pentanamide

[Chemical formula 295] TLC: Rf 0.29 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.41 (s, 1H), 8.69 (s, 1H),
8.14 (d, J = 8.7Hz, 1H), 7.75 (d, J = 3.9Hz, 1H), 7.6
3 (d, J = 8.7Hz, 2H), 7.39 (d, J = 3.9Hz, 1H), 7.00 (d,
J = 8.7Hz, 2H), 4.57 (s, 2H), 4.20-4.00 (m, 1H), 3.
80 (s, 3H), 3.55-3.45 (m, 2H), 3.25 (s, 3H), 2.30-
2.15 (m, 1H), 1.68 (t, J = 7.2Hz, 2H), 1.04 (d, J = 6.
9Hz, 3H).

Example 49 (57) N-Hydroxy-2 (S) -methyl-5-methoxymethoxy-4 (S)-[N- [4-[(biphenyl-3-yl) oxy] phenylcarbonyl] amino ] Pentanamide

[Chemical 296] TLC: Rf 0.42 (chloroform: methanol: acetic acid = 100: 10: 1); NMR (d ₆ -DMSO): δ 10.38 (1H, s), 8.66 (1H, s),
8.06 (1H, d, J = 8.4Hz), 7.90 (2H, d, J = 8.4Hz), 7.68-7.
63 (2H, m), 7.52-7.33 (6H, m), 7.12-7.00 (3H, m), 4.55
(2H, s), 4.24-4.05 (1H, m), 3.54-3.40 (2H, m), 3.32
(3H, s), 2.15-2.25 (1H, m), 1.67 (2H, t, J = 7.0Hz),
1.01 (3H, d, J = 7.0Hz).

Example 49 (58) N-Hydroxy-2 (S) -methyl-5-methoxymethoxy-4 (S)-[N- [4- (1-heptinyl) phenylcarbonyl] amino] pentanamide

[Chemical 297] TLC: Rf 0.49 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.38 (1H, s), 8.66 (1H, s),
8.13 (1H, d, J = 8.8Hz), 7.82 (2H, d, J = 8.4Hz), 7.4
4 (2H, d, J = 8.4Hz), 4.56 (2H, s), 4.28-4.06 (1H,
m), 3.60-3.40 (2H, m), 3.23 (3H, s), 2.43 (2H, t,
J = 6.8Hz), 2.27-2.10 (1H, m), 1.74-1.46 (4H, m), 1.
45-1.20 (4H, m), 1.03 (3H, t, J = 6.6Hz), 0.90 (3H,
t, J = 7.0 Hz).

Example 49 (59) N-hydroxy-2 (S) -methyl-5-methoxymethoxy-4 (S)-[N- [4- (3-phenoxy-1-
Propynyl) phenylcarbonyl] amino] pentanamide

[Chemical 298] TLC: Rf 0.49 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.38 (1H, s), 8.66 (1H, s),
8.20 (1H, d, J = 8.7Hz), 7.85 (2H, d, J = 8.4Hz), 7.5
2 (2H, d, J = 8.4Hz), 7.37- 7.29 (2H, m), 7.08-6.96
(3H, m), 5.06 (2H, s), 4.55 (2H, s), 4.22-4.10 (1
H, m), 3.55-3.40 (2H, m), 3.22 (3H, s), 2.24-2.12
(1H, m), 1.67-1.58 (2H, m), 1.02 (3H, d, J = 6.9Hz).

Example 49 (60) N-hydroxy-2 (S) -methyl-5-methoxymethoxy-4 (S)-[N- [4- (4-cyanophenyl)
Phenylcarbonyl] amino] pentanamide

[Chemical 299] TLC: Rf 0.34 (chloroform: methanol = 1)
NMR (d ₆ -DMSO): δ 10.40 (1H, d, J = 1.5Hz), 8.67
(1H, d, J = 1.5Hz), 8.22 (1H, d, J = 8.7Hz), 7.98 (2
H, d, J = 8.4Hz), 7.95 (4H, s), 7.85 (2H, d, J = 8.4H)
z), 4.56 (2H, s), 4.24-4.32 (1H, m), 3.55-3.45 (2
H, m), 3.23 (3H, s), 2.26-2.15 (1H, m), 1.77-1.62
(2H, m), 1.03 (3H, d, J = 6.9Hz).

Example 49 (61) N-hydroxy-2 (S) -methyl-5-methoxymethoxy-4 (S)-[N- [4- (3-cyanophenyl)
Phenylcarbonyl] amino] pentanamide

[Chemical 300] TLC: Rf 0.35 (chloroform: methanol = 1)
NMR (d ₆ -DMSO): δ 10.40 (1H, d, J = 1.5Hz), 8.67
(1H, d, J = 1.5Hz), 8.24 (1H, t, J = 1.5Hz), 8.21 (1
H, d, J = 8.7Hz), 8.10-8.07 (1H, m), 7.97 (2H, d, J =
8.4Hz), 7.88-7.84 (1H, m), 7.85 (2H, d, J = 8.4Hz),
7.69 (1H, t, J = 7.8Hz), 4.57 (2H, s), 4.24-4.13 (1
H, m), 3.55-3.45 (2H, m), 3.23 (3H, s), 2.26-2.15
(1H, m), 1.77-1.62 (2H, m), 1.03 (3H, d, J = 6.9H
z).

Example 49 (62) N-hydroxy-2 (S) -methyl-5-methoxymethoxy-4 (S)-[N- (4-benzylphenylcarbonyl) amino] pentanamide

[Chemical 301] TLC: Rf 0.43 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.34 (1H, s), 8.64 (1H, s),
7.98 (1H, d, J = 8.4Hz), 7.74 (2H, d, J = 8.1Hz), 7.3
0-7.12 (7H, m), 4.52 (2H, s), 4.16-4.07 (1H, m),
3.96 (2H, s), 3.50-3.38 (2H, m), 3.19 (3H, s), 2.
19-2.09 (1H, m), 1.64 (2H, t, J = 7.4Hz), 0.98 (3H,
d, J = 6.6 Hz).

Example 49 (63) N-hydroxy-2 (S) -methyl-5-methoxymethoxy-4 (S)-[N- [4- [2E- (pyridine-4
-Yl) ethenyl] phenylcarbonyl] amino] pentanamide

[Chemical 302] TLC: Rf 0.18 (chloroform: methanol: acetic acid = 100: 10: 1); NMR (d ₆ -DMSO): δ 10.42 (1H, s), 8.67 (1H, d, J =
1.5Hz), 8.56 (2H, d, J = 6.0Hz), 8.16 (1H, d, J = 8.4Hz),
7.89 (2H, d, J = 8.4Hz), 7.73 (2H, d, J = 8.4Hz), 7.59
(1H, d, J = 16.5Hz), 7.57 (2H, d, J = 6.0Hz), 7.36 (1H,
d, J = 16.5Hz), 4.56 (2H, s), 4.23-4.08 (1H, m), 3.54-
3.44 (2H, m), 3.22 (3H, s), 2.28-2.15 (1H, m), 1.72-
1.66 (2H, m), 1.02 (3H, d, J = 6.6Hz).

Example 49 (64) N-hydroxy-2 (S) -methyl-5-methoxymethoxy-4 (S)-[N- [4- (benzoxazole-
2-yl) phenylcarbonyl] amino] pentanamide

[Chemical 303] TLC: Rf 0.28 (chloroform: methanol = 1
0: 1); NMR (d ₆ -DMSO): δ 10.41 (1H, brs), 8.68 (1H, b
rs), 8.35 (1H, d, J = 8.8Hz), 8.28 (2H, d, J = 8.4Hz),
8.07 (2H, d, J = 8.4Hz), 7.86-7.80 (2H, m), 7.51-7.3
8 (2H, m), 4.57 (2H, s), 4.28-4.11 (1H, m), 3.59-
3.42 (2H, m), 3.24 (3H, s), 2.30-2.13 (1H, m), 1.81
-1.59 (2H, m), 1.04 (3H, d, J = 6.6Hz).

Example 49 (65) N-hydroxy-2 (S) -methyl-5-methoxymethoxy-4 (S)-[N- [4- (3-ethoxyphenyl) phenylcarbonyl] amino] pentanamide

[Chemical 304] TLC: Rf 0.35 (chloroform: methanol = 1)
0: 1); NMR (d ₆ -DMSO): δ 10.39 (brs, 1H), 8.67 (brs,
1H), 8.16 (d, J = 8.4Hz, 1H), 7.93 (d, J = 8.12Hz,
2H), 7.75 (d, J = 8.1Hz, 2H), 7.38 (t, J = 8.1Hz,
1H), 7.26 (br.d, J = 8.1Hz, 1H), 7.22 (brs, 1H),
6.96 (dd, J = 8.1, 2.1Hz, 1H), 4.57 (s, 2H), 4.24-
4.13 (m, 1H), 4.10 (q, J = 7.2Hz, 2H), 3.55-3.45
(m, 2H), 3.23 (s, 3H), 2.26-2.14 (m, 1H), 1.77-1.6
2 (m, 2H), 1.35 (t, J = 7.2Hz, 3H), 1.03 (d, J =
6.6Hz, 3H).

Example 49 (66) N-Hydroxy-2 (S) -methyl-5-methoxymethoxy-4 (S)-[N- [4- (4-methylphenylcarbonylamino) phenylcarbonyl] amino] pentane Amide

[Chemical 305] TLC: Rf 0.22 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.38 (brs, 1H), 8.05 (d, J =
8.4Hz, 1H), 7.96-7.84 (m, 6H), 7.34 (d, J = 8.1Hz, 2
H), 4.57 (s, 2H), 4.25-4.10 (m, 1H), 3.60-3.40 (m,
2H), 3.25 (s, 3H), 2.40 (s, 3H), 2.30-2.15 (m, 1
H), 1.85-1.60 (m, 2H), 1.04 (d, J = 6.9Hz, 3H).

Example 49 (67) N-hydroxy-2 (S) -methyl-5-methoxymethoxy-4 (S)-[N-[[5- [2- (4-methylphenyl) ethynyl] -2 -Thienyl] carbonyl] amino] pentanamide

[Chemical 306] TLC: Rf 0.27 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.41 (s, 1H), 8.69 (s, 1H),
8.31 (d, J = 8.7Hz, 1H), 7.77 (d, J = 4.1Hz, 1H), 7.
46 (d, J = 7.8Hz, 2H), 7.39 (d, J = 4.1Hz, 1H), 7.26
(d, J = 7.8Hz, 2H), 4.57 (s, 2H), 4.20-4.00 (m, 1H),
3.60-3.40 (m, 2H), 3.24 (s, 3H), 2.35 (s, 2H), 2.
20 (m, 1H), 1.68 (t, J = 7.2Hz, 2H), 1.03 (d, J = 6.9H
z, 3H).

Examples 49 (68) -49 (92) Compounds prepared in Examples 44 (4) -44 (6), 44 (10), or compounds equivalent to the compounds prepared in Reference Example 4 were prepared. Using Example 37-> Example 39-> Example 41 (use the corresponding compound instead of methoxymethyl chloride)-> Example 43 (use methyl iodide instead of benzyl bromide)-> Example 44. The compound obtained by the same operation as in the method shown was operated in the same manner as in Example 49 to give the compound shown below.

Example 49 (68) N-Hydroxy-2 (S) -methyl-5- (2-methoxyethoxy) methoxy-4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide

[Chemical 307] TLC: Rf 0.43 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.35 (1H, s), 8.64 (1H, s),
8.01 (1H, d, J = 8.7Hz), 7.85 (2H, d, J = 8.7Hz), 7.4
1 (2H, t, J = 7.7Hz), 7.17 (1H, t, J = 7.7Hz), 7.04 (2
H, d, J = 7.7Hz), 7.00 (2H, d, J = 8.7Hz), 4.59 (2H,
s), 4.18-4.06 (1H, m), 3.55-3.37 (6H, m), 3.19 (3
H, s), 2.15 (1H, m), 1.68-1.60 (2H, m), 0.99 (3H,
d, J = 6.6 Hz).

Example 49 (69 ) N-hydroxy-2 (S) -methyl-5-t-butylcarbonyloxy-4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide

[Chemical 308] TLC: Rf 0.52 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.38 (1H, s), 8.07 (1H, d,
J = 9.0Hz), 7.82 (2H, d, J = 8.7Hz), 7.41 (2H, t, J = 7.7
Hz), 7.18 (1H, t, J = 7.7Hz), 7.07-6.99 (4H, m), 4.3
0-4.18 (1H, m), 4.07-3.94 (2H, m), 2.20-2.1 1 (1H,
m), 1.73-1.49 (2H, m), 1.06 (9H, s), 0.99 (3H, d,
J = 6.6Hz).

Example 49 (70) N-Hydroxy-2 (S) -methyl-5-benzyloxymethoxy-4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide

[Chemical formula 309] TLC: Rf 0.40 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1); NMR (d ₆ -DMSO): δ 10.38 (s, 1H), 8.64 (s, 1H),
8.07 (d, J = 8.5Hz, 1H), 7.88 (d, J = 8.8Hz, 2H),
7.45-7.4 (m, 2H), 7.35-7.25 (m, 5H), 7.19 (t, J =
7.4Hz, 1H), 7.05 (d, J = 8.8Hz, 2H), 7.01 (d, J =
8.5Hz, 2H), 4.70 (s, 2H), 4.50 (s, 2H), 4.18 (m, 1
H), 3.58 (d, J = 11.3Hz, 1H), 3.53 (d, J = 11.3Hz,
1H), 2.19 (m, 1H), 1.30 (m, 2H), 1.01 (d, J = 6.9H
z, 3H).

Example 49 (71) N-hydroxy-2 (S) -methyl-5-ethoxymethoxy-4 (S)-[N- (trans-4-methylcyclohexylcarbonyl) amino] pentanamide

[Chemical 310] TLC: Rf 0.39 (chloroform: methanol = 1)
0: 1); NMR (d ₆ -DMSO): δ 10.37 (brs, 1H), 8.66 (brs,
1H), 7.39 (d, J = 8.4Hz, 1H), 4.56 (s, 2H), 3.89-3.7
7 (m, 1H), 3.47 (q, J = 7.2Hz, 2H), 3.38-3.28 (m, 2
H), 2.14-1.92 (m, 2H), 1.74-1.59 (m, 4H), 1.56-1.4
6 (m, 2H), 1.40-1.21 (m, 3H), 1.10 (t, J = 7.2Hz, 3
H), 0.95 (d, J = 6.9Hz, 3H), 0.93-0.78 (m, 2H), 0.84
(d, J = 6.6Hz, 3H).

Example 49 (72) N-hydroxy-2 (S) -methyl-5-ethoxymethoxy-4 (S)-[N- (4-methylphenylcarbonyl) amino] pentanamide

[Chemical 311] TLC: Rf 0.29 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.35 (s, 1H), 8.63 (brs, 1
H), 7.95 (d, J = 8.8Hz, 1H), 7.72 (d, J = 8.0Hz, 2H),
7.22 (d, J = 8.0Hz, 2H), 4.58 (s, 2H), 4.18-4.04 (m,
1H), 3.53-3.39 (m, 4H), 2.32 (s, 3H), 2.15 (m, 1
H), 1.64 (t, J = 7.4Hz, 2H), 1.06 (t, J = 7.1Hz, 3H),
0.99 (d, J = 7.0Hz, 3H).

Example 49 (73) N-Hydroxy-2 (S) -methyl-5-ethoxymethoxy-4 (S)-[N- (4-chlorophenylcarbonyl) amino] pentanamide

[Chemical 312] TLC: Rf 0.44 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.36 (s, 1H), 8.15 (d, J =
8.4Hz, 1H), 7.83 (d, J = 8.8Hz, 2H), 7.50 (d, J =
8.8Hz, 2H), 4.57 (s, 2H), 4.21-4.06 (m, 1H), 3.53-
3.38 (m, 4H), 2.22-2.10 (m, 1H), 1.64 (t, J = 7.0H
z, 2H), 1.06 (t, J = 6.9Hz, 3H), 0.99 (d, J = 6.6H
z, 3H).

Example 49 (74) N-Hydroxy-2 (S) -methyl-5-ethoxymethoxy-4 (S)-[N- (adamantylcarbonyl) amino] pentanamide

[Chemical 313] TLC: Rf 0.46 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.35 (s, 1H), 8.63 (s, 1H),
6.80 (d, J = 9.0Hz, 1H), 4.54 (s, 2H), 3.94-3.83
(m, 1H), 3.43 (q, J = 7.2Hz, 2H), 3.36-3.24 (m, 2
H), 2.14-2.02 (m, 1H), 1.96-1.88 (m, 3H), 1.76-1.4
5 (m, 14H), 1.09 (t, J = 7.2Hz, 3H), 0.92 (d, J =
6.6Hz, 3H).

Example 49 (75 ) N-hydroxy-2 (S) -methyl-5-ethoxymethoxy-4 (S)-[N- (2-furylcarbonyl) amino] pentanamide

[Chemical 314] TLC: Rf 0.24 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.34 (s, 1H), 8.63 (s, 1H),
7.96 (d, J = 8.4Hz, 1H), 7.80-7.79 (m, 1H), 7.06
(d, J = 3.4Hz, 1H), 6.58 (dd, J = 3.4Hz, 1.7Hz, 1
H), 4.56 (s, 2H), 4.15-4.02 (m, 1H), 3.51-3.38 (m,
4H), 2.18-2.04 (m, 1H), 1.61 (t, J = 6.2Hz, 2H), 1.0
6 (t, J = 7.1Hz, 3H), 0.97 (d, J = 6.8Hz, 3H).

Example 49 (76) N-Hydroxy-2 (S) -methyl-5-ethoxymethoxy-4 (S)-[N-[(benzothiazol-6-yl) carbonyl] amino] pentanamide

[Chemical 315] TLC: Rf 0.34 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.37 (s, 1H), 9.50 (s, 1H),
8.62 (d, J = 1.5 Hz, 1H), 8.23 (d, J = 8.4Hz, 1
H), 8.12 (d, J = 8.7Hz, 1H), 7.97 (dd, J = 8.7Hz,
1.9Hz, 1H), 4.59 (s, 2H), 4.21-4.11 (m, 1H), 3.5 3
-3.42 (m, 4H), 2.25-2.14 (m, 1H), 1.72-1.61 (m, 2
H), 1.06 (t, J = 7.2Hz, 3H), 1.00 (d, J = 6.6Hz, 3
H).

Example 49 (77) N-hydroxy-2 (S) -methyl-5-ethoxymethoxy-4 (S)-[N- (4-fluorophenylcarbonyl) amino] pentanamide

[Chemical 316] TLC: Rf 0.34 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.36 (s, 1H), 8.09 (d, J =
8.7Hz, 1H), 7.88 (dd, J = 5.7Hz, 9.0Hz, 2H), 7.26
(t, J = 9.0 Hz, 2H), 4.57 (s, 2H), 4.16-4.05 (m, 1
H), 3.50-3.41 (m, 4H), 2.15 (m, 1H), 1.68-1.61 (m,
2H), 1.06 (t, J = 7.0Hz, 3H), 0.98 (d, J = 6.8Hz, 3
H).

Example 49 (78) N-hydroxy-2 (S) -methyl-5-ethoxymethoxy-4 (S)-[N-[(2-bromofuryl-5-yl) carbonyl] amino] pentanamide

[Chemical 317] TLC: Rf 0.28 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.35 (s, 1H), 9.64 (s, 1H),
8.07 (d, J = 8.7Hz, 1H), 7.10 (d, J = 3.6Hz, 1H),
6.72 (d, J = 3.6Hz, 1H), 4.56 (s, 2H), 4.11-4.00
(m, 1H), 3.49-3.40 (m, 4H), 2.16-2.05 (m, 1H), 1.6
7-1.53 (m, 2H), 1.06 (t, J = 7.2Hz, 3H), 0.97 (d, J
= 6.3Hz, 3H).

Example 49 (79) N-Hydroxy-2 (S) -methyl-5-ethoxymethoxy-4 (S)-[N- (4-nitrophenylcarbonyl) amino] pentanamide

[Chemical 318] TLC: Rf 0.35 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.39 (brs, 1H), 8.66 (brs,
1H), 8.46 (brd, J = 8.8Hz, 1H), 8.30 (d, J = 8.8Hz,
1H), 8.06 (d, J = 8.8Hz, 2H), 4.59 (s, 2H), 4.15
(m, 1H), 3.50 (d, J = 5.8Hz, 1H), 3.47 (q, J = 6.8
Hz, 2H), 2.17 (m, 1H), 1.67 (m, 2H), 1.07 (t, J =
6.8Hz, 3H), 1.02 (d, J = 6.8Hz, 3H).

Example 49 (80) N-Hydroxy-2 (S) -methyl-5-ethoxymethoxy-4 (S)-[N- (4-bromophenylcarbonyl) amino] pentanamide

[Chemical 319] TLC: Rf 0.35 (methylene chloride: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.37 (brs, 1H), 8.65 (brs,
1H), 8.17 (brd, J = 8.4Hz, 1H), 7.79 (d, J = 8.8Hz,
2H), 7.66 (d, J = 8.8Hz, 2H), 4.58 (s, 2H), 4.13
(m, 1H), 3.47 (d, J = 7.0Hz, 2H), 3.47 (q, J = 7.0
Hz, 2H), 2.16 (m, 1H), 1.65 (m, 2H), 1.07 (t, J =
7.0Hz, 3H), 1.01 (d, J = 6.6Hz, 3H).

Example 49 (81) N-hydroxy-2 (S) -methyl-5-ethoxymethoxy-4 (S)-[N- (4-cyanophenylcarbonyl) amino] pentanamide

[Chemical 320] TLC: Rf 0.24 (chloroform: methanol = 1
9: 1); NMR (d ₆ -DMSO): δ 10.39 (s, 1H), 8.67 (s, 1H),
8.36 (d, J = 8.7Hz, 1H), 8.00 (d, J = 8.4Hz, 2H),
7.95 (d, J = 8.4Hz, 2H), 4.60 (s, 2H), 4.22-4.08
(m, 1H), 3.58-3.40 (m, 4H), 2.23-2.12 (m, 1H), 1.78
-1.58 (m, 2H), 1.09 (t, J = 6.9Hz, 3H), 1.03 (d, J
= 6.9Hz, 3H).

Example 49 (82) N-hydroxy-2 (S) -methyl-5-ethoxymethoxy-4 (S)-[N- [4- (4-pyridyloxy)
Phenylcarbonyl] amino] pentanamide

[Chemical 321] TLC: Rf 0.30 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.40 (s, 1H), 8.69 (s, 1H),
8.50 (dd, J = 4.7,1.5Hz, 2H), 8.15 (d, J = 8.4Hz,
1H), 7.98 (d, J = 8.7Hz, 2H), 7.25 (d, J = 8.7Hz,
2H), 6.97 (dd, J = 4.7, 1.5Hz, 2H), 4.62 (s, 2H),
4.30-4.10 (m, 1H), 3.60-3.40 (m, 4H), 2.30-2.10
(m, 1H), 1.80-1.60 (m, 2H), 1.11 (t, J = 7.1Hz, 3
H), 1.04 (d, J = 6.9Hz, 3H).

Example 49 (83) N-Hydroxy-2 (S) -methyl-5- (2-methoxyethoxy) methoxy-4 (S)-[N- (4-cyanophenylcarbonyl) amino] pentanamide

[Chemical 322] TLC: Rf 0.26 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.37 (s, 1H), 8.65 (s, 1H),
8.36 (d, J = 8.7Hz, 1H), 8.00-7.93 (m, 4H), 4.61
(s, 2H), 4.20-4.06 (m, 1H), 3.56-3.52 (m, 2H), 3.49
(d, J = 6.0Hz, 2H), 3.42-3.39 (m, 2H), 3.20 (s, 3
H), 2.20-2.12 (m, 1H), 1.75-1.58 (m, 2H), 1.01 (t,
J = 6.9Hz, 3H).

Example 49 (84) N-Hydroxy-2 (S) -methyl-5-methoxymethoxy-4 (S)-[N- (4-chlorophenylcarbonyl) amino] pentanamide

[Chemical Formula 323] TLC: Rf 0.50 (methylene chloride: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.36 (d, J = 1.8Hz, 1H), 8.
64 (d, J = 1.8Hz, 1H), 8.17 (d, J = 8.4Hz, 1H), 7.
85 (d, J = 8.4Hz, 2H), 7.51 (d, J = 8.4Hz, 2H), 4.5
3 (s, 2H), 4.11 (m, 1H), 3.46 (m, 2H), 3.20 (s, 3
H), 2.16 (m, 1H), 1.65 (m, 2H), 1.00 (d, J = 6.6H
z, 3H).

Example 49 (85) N-Hydroxy-2 (S) -methyl-5-benzyloxymethoxy-4 (S)-[N- (4-chlorophenylcarbonyl) amino] pentanamide

[Chemical 324] TLC: Rf 0.50 (methylene chloride: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.36 (s, 1H), 8.64 (s, 1H),
8.19 (d, J = 8.4Hz, 1H), 7.86 (d, J = 9.0Hz, 2H),
7.51 (d, J = 9.0Hz, 2H), 7.28 (m, 5H), 4.69 (s, 2
H), 4.49 (s, 2H), 4.15 (m, 1H), 3.54 (d, J = 6.0H
z, 2H), 2.17 (m, 1H), 1.68 (m, 2H), 1.00 (d, J =
6.9Hz, 3H).

Example 49 (86) N-Hydroxy-2 (S) -methyl-5- (2-methoxyethoxy) methoxy-4 (S)-[N- (4-chlorophenylcarbonyl) amino] pentanamide

[Chemical 325] TLC: Rf 0.45 (methylene chloride: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.36 (s, 1H), 8.64 (s, 1H),
8.16 (d, J = 8.4Hz, 1H), 7.85 (d, J = 9.0Hz, 2H),
7.51 (d, J = 9.0Hz, 2H), 4.60 (s, 2H), 4.13 (m, 1
H), 3.55-3.38 (m, 6H), 3.19 (s, 3H), 2.14 (m, 1H),
1.65 (m, 2H), 1.00 (d, J = 6.9Hz, 3H).

Example 49 (87) N-hydroxy-2 (S) -methyl-5-ethoxymethoxy-4 (S)-[N- (2-nitrophenylcarbonyl) amino] pentanamide

[Chemical formula 326] TLC: Rf 0.22 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.39 (d, J = 1.2Hz, 1H), 8.70
(d, J = 1.2Hz, 1H), 8.45 (d, J = 8.4Hz, 1H), 8.01 (d
d, J = 7.8Hz, 1.2Hz, 1H), 7.80-7.60 (m, 3H), 4.62 (s,
2H), 4.08-3.95 (m, 1H), 3.55-3.36 (m, 4H), 2.31-
2.19 (m, 1H), 1.65 (t, J = 7.2Hz, 2H), 1.12 (t, J = 7.
2Hz, 3H), 1.03 (d, J = 7.2Hz, 3H).

Example 49 (88) N-Hydroxy-2 (S) -methyl-5-ethoxymethoxy-4 (S)-[N- (3-nitrophenylcarbonyl) amino] pentanamide

[Chemical 327] TLC: Rf 0.31 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.38 (s, 1H), 8.69-8.68 (m,
1H), 8.64 (brs, 1H), 8.52 (d, J = 8.7Hz, 1H), 8.3
9-8.35 (m, 1H), 8.30-8.27 (m, 1H), 7.77 (t, J = 8.
1Hz, 1H), 4.60 (s, 2H), 4.24-4.11 (m, 1H), 3.52-3.
44 (m, 4H), 2.22-2.11 (m, 1H), 1.78-1.60 (m, 2H),
1.08 (t, J = 7.2Hz, 3H), 1.02 (d, J = 6.9Hz, 3H).

Example 49 (89) N-hydroxy-2 (S) -methyl-5-ethoxymethoxy-4 (S)-[N- (2-methoxy-4-nitrophenylcarbonyl) amino] pentanamide

[Chemical 328] TLC: Rf 0.26 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.38 (s, 1H), 8.66 (brs, 1)
H), 8.09 (d, J = 8.4Hz, 1H), 7.87-7.77 (m, 3H), 4.
61, (s, 2H), 4.14-4.02 (m, 1H), 3.95 (s, 3H), 3.53
-3.43 (m, 4H), 2.25-2 .13 (m, 1H), 1.75-1.55 (m, 2
H), 1.09 (t, J = 6.9Hz, 3H), 1.02 (d, J = 6.9Hz, 3
H).

Example 49 (90) N-hydroxy-2 (S) -methyl-5-ethoxymethoxy-4 (S)-[N- (3-methoxy-4-nitrophenylcarbonyl) amino] pentanamide

[Chemical 329] TLC: Rf 0.26 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.39 (s, 1H), 8.67 (s, 1H),
8.34 (d, J = 8.4Hz, 1H), 7.94 (d, J = 8.7Hz, 1H),
7.70 (d, J = 1.2Hz, 1H), 7.53 (dd, J = 8.7Hz, 1.2H
z, 1H), 4.60 (s, 2H), 4.21-4.09 (m, 1H), 3.99 (s,
3H), 3.54-3.45 (m, 4H), 2.22-2.10 (m, 1H), 1.78-1.
62 (m, 2H), 1.08 (t, J = 6.9Hz, 3H), 1.02 (d, J =
6.9Hz, 3H).

Example 49 (91) N-Hydroxy-2 (S) -methyl-5-ethoxymethoxy-4 (S)-[N- (3-hydroxy-4-nitrophenylcarbonyl) amino] pentanamide

[Chemical 330] TLC: Rf 0.22 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 11.08 (s, 1H), 10.28 (s, 1
H), 8.56 (s, 1H), 8.21 (d, J = 8.7Hz, 1H), 7.84 (d,
J = 8.4Hz, 1H), 7.43 (d, J = 1.8Hz, 1H), 7.28 (d
d, J = 8.4Hz, 1.8Hz, 1H), 4.49 (s, 2H), 4.08-3.95
(m, 1H), 3.41-3.34 (m, 4H), 2.12-2.01 (m, 1H), 1.5
8-1.53 (m, 2H), 0.99 (t, J = 6.9Hz, 3H), 0.91 (d,
J = 6.9Hz, 3H).

Example 49 (92) N-Hydroxy-2 (S) -methyl-5-ethoxymethoxy-4 (S)-[N- (4-dihydroxyboronylphenylcarbonyl) amino] pentanamide

[Chemical 331] TLC: Rf 0.19 (methylene chloride: methanol: acetic acid = 18: 1: 1); NMR (d ₆ -DMSO): δ 10.37 (s, 1H), 8.65 (s, 1H),
8.16 (s, 2H), 8.05 (d, J = 8.4Hz, 1H), 7.83 (d, J
= 8.4Hz, 2H), 7.77 (d, J = 8.4Hz, 2H), 4.58 (s, 2
H), 4.14 (m, 1H), 3.47 (m, 4H), 2.16 (m, 1H), 1.66
(m, 2H), 1.07 (t, J = 6.9Hz, 3H), 1.01 (d, J = 6.9
Hz, 3H).

Examples 49 (93) to 49 (111) Examples 44 (7), 44 (12), 44 (13), 44
(15), 44 (16), 44 (22), 44 (2
3), 44 (27) or the corresponding compound instead of the compound prepared in Reference Example 4, Example 37 → Example 3
9 → Example 41 (A corresponding compound may be used instead of methoxymethyl chloride) → Example 43
(The corresponding compound is used instead of benzyl bromide.)
→ A compound obtained by the same operation as in the method shown in Example 44 was operated in the same manner as in the method shown in Example 49,
The compound shown below was obtained.

Example 49 (93) N-hydroxy-2 (S) -isobutyl-5-methoxymethoxy-4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide

[Chemical 332] TLC: Rf 0.36 (chloroform: methanol = 1)
9: 1); NMR (d ₆ -DMSO): δ 10.46 (1H, s), 8.72 (1H, s),
8.00 (1H, d, J = 8.4Hz), 7.88 (2H, d, J = 8.8Hz), 7.4
8-7.38 (2H, m), 7.23-7.16 (1H, m), 7.10-7.03 (2H,
m), 7.01 (2H, d, J = 8.8Hz), 4.56 (2H, s), 4.22-4.0
1 (1H, m), 3.60-3.40 (2H, m), 3.24 (3H, s), 2.25-
2.08 (1H, m), 1.78-1.60 (2H, m), 1.58-1.32 (2H, m
m), 1.28-1.07 (1H, m), 0.82 (3H, d, J = 6.0Hz), 0.80
(3H, d, J = 6.0Hz).

Example 49 (94) N-hydroxy-2 (S) -ethyl-5-methoxymethoxy-4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide

[Chemical 333] TLC: Rf 0.60 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1); NMR (d ₆ -DMSO): δ 10.40 (1H, s), 8.71 (1H, s),
8.04 (1H, d, J = 8.1Hz), 7.87 (2H, d, J = 9.0Hz), 7.45-7.
40 (2H, m), 7.22-7.17 (1H, m), 7.08-7.00 (4H, m), 4.55
(2H, s), 4.04-4.18 (1H, m), 3.52-3.23 (2H, m), 3.22
(3H, s), 2.04-1.92 (1H, m), 1.78-1.57 (2H, m), 1.52-
1.34 (2H, m), 0.77 (3H, t, J = 7.2Hz).

Example 49 (95) N-Hydroxy-2 (S) -propyl-5-methoxymethoxy-4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide

[Chemical 334] TLC: Rf 0.60 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1); NMR (d ₆ -DMSO): δ 10.40 (1H, s), 8.69 (1H, s),
8.02 (1H, d, J = 8.4Hz), 7.86 (2H, d, J = 8.8Hz), 7.46-7.
37 (2H, m), 7.23-7.15 (1H, m), 7.08-6.98 (4H, m), 4.54
(2H, s), 4.16-4.00 (1H, m), 3.48-3.44 (2H, m), 3.21
(3H, s), 2.14-1.99 (1H, m), 1.78-1.58 (2H, m), 1.45-
1.28 (2H, m), 1.27-1.07 (2H, m), 0.80 (3H, t, J = 7.2H
z).

Example 49 (96) N-hydroxy-2 (R) -t-butoxycarbonylmethyl-5-methoxymethoxy-4 (S)-[N- (4-
Phenoxyphenylcarbonyl) amino] pentanamide

[Chemical 335] TLC: Rf 0.54 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.47 (1H, s), 8.75 (1H, s),
8.05 (1H, d, J = 8.4Hz), 7.88 (2H, d, J = 8.7Hz), 7.4
7-7.40 (2H, m), 7.23-7.17 (1H, m), 7.10-7.04 (2H, m
m), 7.03 (2H, d, J = 8.7Hz), 4.55 (2H, s), 4.20-4.03
(1H, m), 3.57-3.43 (2H, m), 3.23 (3H, s), 2.55-2.
34 (3H, m), 1.74-1.66 (2H, m), 1.36 (9H, s).

Example 49 (97) N-hydroxy-2 (S) -allyl-5-methoxymethoxy-4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide

[Chemical 336] TLC: Rf 0.62 (chloroform: methanol: acetic acid = 100: 5: 1); NMR (d ₆ -DMSO): δ 10.43 (1H, s), 8.66 (1H, brs),
8.06 (1H, d, J = 8.4Hz), 7.89-7.85 (2H, m), 7.47-7.38
(2H, m), 7.23-7.15 (1H, m), 7.09-6.99 (4H, m), 5.73-
5.60 (1H, m), 5.05-4.92 (2H, m), 4.54 (2H, s), 4.19-
4.05 (1H, m), 3.52 (1H, dd, J = 10.1Hz, 5.2Hz), 3.44 (1
H, dd, J = 10.1Hz, 5.2Hz), 3.22 (3H, s), 2.20-2.17 (3H,
m), 1.82-1.59 (2H, m).

Example 49 (98 ) N-Hydroxy-2 (S) -ethyl-5-ethoxymethoxy-4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide

[Chemical 337] TLC: Rf 0.33 (chloroform: methanol: acetic acid = 100: 5: 1); NMR (d ₆ -DMSO): δ 10.40 (1H, s), 8.70 (1H, s),
8.02 (1H, d, J = 8.4Hz), 7.86 (2H, d, J = 8.8Hz), 7.46-7.
38 (2H, m), 7.23-7.15 (1H, m), 7.08-6.99 (4H, m), 4.59
(2H, s), 4.19-4.01 (1H, m), 3.52-3.42 (2H, m), 3.47
(2H, q, J = 7.0Hz), 2.05-1.92 (1H, m), 1.79-1.32 (4H,
m), 1.07 (3H, t, J = 7.2Hz), 0.76 (3H, t, J = 7.0Hz).

Example 49 (99) N-hydroxy-2 (S) -ethyl-5- (2-methoxyethoxy) methoxy-4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide

[Chemical 338] TLC: Rf 0.31 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.40 (1H, s), 8.71 (1H, s),
8.02 (1H, d, J = 8.4Hz), 7.88 (2H, d, J = 8.8Hz), 7.4
8-7.38 (2H, m), 7.23-7.15 (1H, m), 7.10-7.05 (2H, m
m), 7.02 (2H, d, J = 8.8Hz), 4.62 (2H, m), 4.22-4.00
(1H, m), 3.61-3.38 (6H, m), 3.22 (3H, s), 2.09-1.
91 (1H, m), 1.82-1.60 (2H, m), 1.58-1.35 (2H, m),
0.78 (3H, t, J = 7.0Hz).

Example 49 (100 ) N-Hydroxy-2 (S) -ethyl-5-t-butylcarbonyloxy-4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide

[Chemical 339] TLC: Rf 0.69 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.41 (1H, s), 8.71 (1H, s),
8.07 (1H, d, J = 8.7Hz), 7.81 (2H, d, J = 8.6Hz), 7.4
1 (2H, t, J = 7.6Hz), 7.17 (1H, t, J = 7.6Hz), 7.04 (2
H, d, J = 7.6Hz), 7.00 (2H, d, J = 8.6Hz), 4.25-4.13
(1H, m), 4.08-3.94 (2H, m), 2.03-1.91 (1H, m), 1.6
3 (2H, t, J = 6.9Hz), 1.48-1.36 (2H, m), 1.06 (9H,
s), 0.75 (3H, t, J = 7.5Hz).

Example 49 (101) N-Hydroxy-2 (S) -allyl-5-ethoxymethoxy-4 (S)-[N- (4-methylphenylcarbonyl) amino] pentanamide

[Chemical 340] TLC: Rf 0.49 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.42 (s, 1H), 8.71 (s, 1H),
7.99 (d, J = 8.8Hz, 1H), 7.73 (d, J = 8.0Hz, 2H),
7.24 (d, J = 8.0Hz, 2H), 5.72-5.55 (m, 1H), 5.02-
4.91 (m, 2H), 4.58 (s, 2H), 4.19-4.01 (m, 1H), 3.5
2-3.41 (m, 4H), 2.33 (s, 3H), 2.12 (m, 3H), 1.79-
1.58 (m, 2H), 1.07 (t, J = 7.0Hz, 3H).

Example 49 (102) N-hydroxy-2 (S) -allyl-5-ethoxymethoxy-4 (S)-[N- (4-nitrophenylcarbonyl) amino] pentanamide

[Chemical 341] TLC: Rf 0.32 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.43 (d, J = 1.5Hz, 1H), 8.
71 (d, J = 1.5Hz, 1H), 8.47 (d, J = 8.4Hz, 1H), 8.
30-8.27 (m, 2H), 8.07-8.03 (m, 2H), 5.75-5.59 (m,
1H), 5.03-4.93 (m, 2H), 4.59 (s, 2H), 4.19-4.08
(m, 1H), 3.50 (d, J = 5.1Hz, 2H), 3.47 (q, J = 7.2
Hz, 2H), 2.23-2.12 (m, 3H), 1.80-1.60 (m, 2H), 1.07
(t, J = 7.2Hz, 3H).

Example 49 (103) N-Hydroxy-2-methylidene-5-ethoxymethoxy-4 (S)-[N- (4-nitrophenylcarbonyl) amino] pentanamide

[Chemical 342] TLC: Rf 0.50 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.77 (s, 1H), 8.84 (s, 1H),
8.61 (d, J = 8.4Hz, 1H), 8.32-8.27 (m, 2H), 8.05-
8.02 (m, 2H), 5.57 (s, 1H), 5.36 (s, 1H), 4.60 (s,
2H), 4.30-4.18 (m, 1H), 3.53-3.45 (m, 4H), 2.61 (d
d, J = 14.1Hz, 4.5Hz, 1H), 2.47-2.40 (m, 1H), 1.0
7 (t, J = 6.9Hz, 3H).

Example 49 (104) N-hydroxy-2 (S)-(2-propynyl) -5-
Ethoxymethoxy-4 (S)-[N- (4-nitrophenylcarbonyl) amino] pentanamide

[Chemical 343] TLC: Rf 0.39 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.54 (s, 1H), 8.81 (s, 1H),
8.49 (d, J = 8.4Hz, 1H), 8.29 (d, J = 8.7Hz, 2H),
8.07 (d, J = 8.7Hz, 2H), 4.59 (s, 2H), 4.20-4.03
(m, 1H), 3.60-3.40 (m, 4H), 2.78 (s, 1H), 2.40-2.2
0 (m, 3H), 1.95-1.80 (m, 1H), 1.80-1.60 (m, 1H),
1.08 (t, J = 7.1Hz, 3H).

Example 49 (105) N-Hydroxy-2 (S) -allyl-5- (2-methoxyethoxy) methoxy-4 (S)-[N- (4-cyanophenylcarbonyl) amino] pentanamide

[Chemical 344] TLC: Rf 0.22 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.42 (s, 1H), 8.71 (s, 1H),
8.36 (d, J = 8.7Hz, 1H), 7.98 (d, J = 8.4Hz, 2H),
7.94 (d, J = 8.4Hz, 2H), 5.74-5.58 (m, 1H), 5.05-
4.92 (m, 2H), 4.61 (s, 2H), 4.20-4.04 (m, 1H), 3.5
8-3.43 (m, 4H), 3.44- 3.37 (m, 2H), 3.19 (s, 3H),
2.22-2.10 (m, 3H), 1.81-1.58 (m, 2H).

Example 49 (106) N-hydroxy-2 (S)-(2-propynyl) -5-
Ethoxymethoxy-4 (S)-[N- (4-bromophenylcarbonyl) amino] pentanamide

[Chemical 345] TLC: Rf 0.36 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.52 (s, 1H), 8.80 (s, 1H),
8.20 (d, J = 8.7Hz, 1H), 7.79 (d, J = 8.4Hz, 2H), 7.6
4 (d, J = 8.4Hz, 2H), 4.58 (s, 2H), 4.18-4.02 (m, 1
H), 3.58-3.42 (m, 4H), 2.78-2.73 (brs, 1H), 2.38-
2.20 (m, 3H), 1.95-1.75 (m, 1H), 1.75-1.60 (m, 1
H), 1.08 (t, J = 6.9Hz, 3H).

Example 49 (107) N-hydroxy-2 (S)-(2-propynyl) -5-
Ethoxymethoxy-4 (S)-[N- (4-chlorophenylcarbonyl) amino] pentanamide

[Chemical 346] TLC: Rf 0.35 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.52 (s, 1H), 8.80 (s, 1H),
8.20 (d, J = 8.7Hz, 1H), 7.86 (d, J = 8.6Hz, 2H), 7.5
1 (d, J = 8.6Hz, 2H), 4.58 (s, 2H), 4.20-4.02 (m, 1
H), 3.60-3.40 (m, 4H), 2.80-2.75 (brs, 1H), 2.40-
2.20 (m, 3H), 1.95-1.78 (m, 1H), 1.78-1.60 (m, 1
H), 1.08 (t, J = 6.9Hz, 3H).

Example 49 (108) N-hydroxy-2 (S) -allyl-5-ethoxymethoxy-4 (S)-[N- (4-bromophenylcarbonyl) amino] pentanamide

[Chemical 347] TLC: Rf 0.35 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.42 (s, 1H), 8.71 (s, 1H),
8.19 (d, J = 8.7Hz, 1H), 7.78 (d, J = 8.6Hz, 2H), 7.6
5 (d, J = 8.6Hz, 2H), 5.75-5.58 (m, 1H), 5.05-4.90
(m, 2H), 4.58 (s, 2H), 4.20-4.05 (m, 1H), 3.58-3.4
0 (m, 4H), 2.25-2.08 (m, 3H), 1.80-1.60 (m, 2H),
1.07 (t, J = 7.1Hz, 3H).

Example 49 (109) N-Hydroxy-2 (S) -allyl-5-ethoxymethoxy-4 (S)-[N- (4-chlorophenylcarbonyl) amino] pentanamide

[Chemical 348] TLC: Rf 0.36 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.42 (s, 1H), 8.70 (s, 1H),
8.18 (d, J = 8.7Hz, 1H), 7.85 (d, J = 8.6Hz, 2H), 7.5
2 (d, J = 8.6Hz, 2H), 5.75-5.58 (m, 1H), 5.05-4.90
(m, 2H), 4.58 (s, 2H), 4.20-4.05 (m, 1H), 3.58-3.4
0 (m, 4H), 2.25-2.08 (m, 3H), 1.80-1.60 (m, 2H),
1.07 (t, J = 7.1Hz, 3H).

Example 49 (110) N-hydroxy-2 (R) -dimethylaminomethyl-5
-Ethoxymethoxy-4 (S)-[N- (4-nitrophenylcarbonyl) amino] pentanamide

[Chemical 349] TLC: Rf 0.30 (chloroform: methanol: acetic acid = 10: 2: 1); NMR (d ₆ -DMSO): δ 10.44 (brs, 1H), 8.73 (brs,
1H), 8.48 (d, J = 8.4Hz, 1H), 8.29 (d, J = 8.9Hz, 2H),
8.05 (d, J = 8.9Hz, 2H), 4.59 (s, 2H), 4.20-4.05
(m, 1H), 3.60-3.40 (m, 4H), 2.55-2.38 (m, 1H), 2.3
8-2.20 (m, 1H), 2.20-2.00 (m, 7H), 1.85-1.70 (m, 1
H), 1.70-1.58 (m, 1H), 1.08 (t, J = 6.9Hz, 3H).

Example 49 (111) N-hydroxy-2 (S)-(2-propynyl) -5-
(2-Methoxyethoxy) methoxy-4 (S)-[N-
(4-Cyanophenylcarbonyl) amino] pentanamide

[Chemical 350] TLC: Rf 0.35 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.53 (s, 1H), 8.81 (s, 1H),
8.41 (d, J = 8.7Hz, 1H), 7.99 (d, J = 8.7Hz, 2H), 7.9
4 (d, J = 8.7Hz, 2H), 4.61 (s, 2H), 4.20-4.05 (m, 1
H), 3.60-3.45 (m, 4H), 3.45-3.35 (m, 2H), 3.20 (s,
3H), 2.79 (s, 1H), 2.35-2.00 (m, 3H), 1.92-1.75
(m, 1H), 1.75-1.60 (m, 1H).

Examples 49 (112) to 49 (116) In place of 4 (S) -carboxy-4-aminobutanoic acid methyl ester, 4 (R) -carboxy-4-aminobutanoic acid methyl ester, and in Reference Example 4 Using the corresponding compound instead of the produced compound Example 37-> Example 39-> Example 41 (A corresponding compound may be used instead of methoxymethyl chloride.)-> Example 4
3 (Use the corresponding compound instead of benzyl bromide) → Example 44 → The same operation as in the method of Example 49 was carried out to obtain the compound shown below.

Example 49 (112) N-Hydroxy-2 (R) -benzyl-5-methoxymethoxy-4 (R)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide

[Chemical 351] TLC: Rf 0.39 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1); NMR (d ₆ -DMSO): δ 10.34 (1H, s), 8.66 (1H, s),
8.08 (1H, d, J = 8.8Hz), 7.89 (2H, d, J = 8.4Hz), 7.43 (2
H, t, J = 8.0Hz), 7.00-7.46 (10H, m), 4.53 (2H, s), 4.1
3-4.32 (1H, m), 3.48 (2H, d, J = 5.6Hz), 3.19 (3H, s),
2.76 (2H, d, J = 7.0Hz), 2.29-2.44 (1H, m), 1.58-1.84
(2H, m).

Example 49 (113) N-hydroxy-2 (R) -benzyl-5-methoxymethoxy-4 (R)-[N- [4- (3-phenoxy-1)
-Propinyl) phenylcarbonyl] amino] pentanamide

[Chemical 352] TLC: Rf 0.39 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1); NMR (d ₆ -DMSO): δ 10.33 (1H, s), 8.65 (1H, s),
8.22 (1H, d, J = 8.7Hz), 7.84 (2H, d, J = 8.4Hz), 7.51 (2
H, d, J = 8.4Hz), 7.32 (2H, t, J = 7.8Hz), 7.20 (2H, t,
J = 6.9Hz), 6.97-7.14 (6H, m), 5.05 (2H, s), 4.50 (2H,
s), 4.14-4.28 (1H, m), 3.46 (2H, d, J = 5.7Hz), 3.17 (3
H, s), 2.74 (2H, d, J = 7.2Hz), 2.29-2.39 (1H, m), 1.6
0-1.79 (2H, m).

Example 49 (114) N-hydroxy-2 (R) -methyl-5-ethoxymethoxy-4 (R)-[N- [4- (4-cyanophenyl)
Phenylcarbonyl] amino] pentanamide

[Chemical 353] TLC: Rf 0.35 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.37 (s, 1H), 8.65 (s, 1H),
8.18 (d, J = 8.4Hz, 1H), 7.95 (d, J = 8.6Hz, 2H), 7.8
3 (d, J = 8.6Hz, 2H), 4.59 (s, 2H), 4.16 (m, 1H), 3.6
0-3.40 (m, 4H), 2.17 (m, 1H), 1.67 (t, J = 6.9Hz, 2
H), 1.07 (t, J = 7.1Hz, 3H), 1.01 (d, J = 6.9Hz, 3H).

Example 49 (115) N-hydroxy-2 (R) -allyl-5-ethoxymethoxy-4 (R)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide

[Chemical 354] TLC: Rf 0.34 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.41 (s, 1H), 8.70 (s, 1H),
8.02 (d, J = 8.4Hz, 1H), 7.85 (d, J = 9.0Hz, 2H), 7.4
1 (t, J = 7.9Hz, 2H), 7.17 (t, J = 7.9Hz, 1H), 7.04 (d,
J = 7.9Hz, 2H), 6.99 (d, J = 9.0Hz, 2H), 5.74- 5.55
(m, 1H), 5.03-4.88 (m, 2H), 4.56 (s, 2H), 4.17-4.0
3 (m, 1H), 3.53-3.40 (m, 4H), 2.24-2.10 (m, 3H),
1.79-1.58 (m, 2H), 1.06 (t, J = 7.0Hz, 3H).

Example 49 (116) N-hydroxy-2 (R) -methyl-5-ethoxymethoxy-4 (R)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide

[Chemical 355] TLC: Rf 0.38 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.36 (s, 1H), 8.64 (s, 1H),
8.01 (d, J = 8.7Hz, 1H), 7.85 (d, J = 8.7Hz, 2H), 7.4
1 (t, J = 7.6Hz, 2H), 7.17 (t, J = 7.6Hz, 1H), 7.04 (d,
J = 7.6Hz, 2H), 7.00 (d, J = 8.7Hz, 2H), 4.57 (s, 2
H), 4.18-4.06 (m, 1H), 3.51-3.42 (m, 4H), 2.15 (m,
1H), 1.64 (t, J = 7.1Hz, 2H), 1.06 (t, J = 7.2Hz, 3H),
0.99 (d, J = 7.1Hz, 3H).

Examples 49 (117) to 49 (124) Using the corresponding compounds instead of the compounds prepared in Reference Example 4, Example 37 → Example 39 → Example 41 → Example 4
3 (Use the corresponding compound instead of benzyl bromide) → Example 44 → The same operation as in the method of Example 49 was carried out to obtain the compound shown below.

Example 49 (117) N-hydroxy-2 (S) -benzyl-5-methoxymethoxy-4 (S)-[N- [4- [2E- (4-chlorophenyl) ethenyl] phenylcarbonyl] amino ] Pentanamide

[Chemical 356] TLC: Rf 0.21 (chloroform: methanol = 1
9: 1); NMR (d ₆ -DMSO): δ 10.37 (1H, s), 8.15 (1H, d,
J = 8.4Hz), 7.89 (2H, d, J = 8.4Hz), 7.68 (2H, d, J = 8.4
Hz), 7.66 (2H, d, J = 8.8Hz), 7.45 (2H, d, J = 8.8Hz),
7.40-7.30 (2H, m), 7.29-7.08 (5H, m), 4.54 (2H,
s), 4.38-4.18 (1H, m), 3.60-3.40 (2H, m), 3.21 (3H,
s), 2.78 (2H, d, J = 6.6Hz), 2.55-2.30 (1H, m), 1.
92-1.60 (2H, m).

Example 49 (118) N-hydroxy-2 (S)-(indol-3-yl)
-5-Methoxymethoxy-4 (S)-[N- [4- (benzofuran-2-yl) phenylcarbonyl] amino]
Pentanamide

[Chemical 357] TLC: Rf 0.28 (chloroform: methanol = 1
9: 1); NMR (d ₆ -DMSO): δ 10.73 (1H, s), 10.37 (1H,
s), 8.67 (1H, d, J = 8.6Hz), 8.01 (4H, s), 7.78-7.4
8 (4H, m), 7.44-7.20 (3H, m), 7.10-6.80 (3H, m), 4.
53 (2H, s), 4.42-4.22 (1H, m), 3.62-3.40 (2H, m),
3.18 (3H, s), 3.00-2.78 (2H, m), 2.62-2.38 (1H,
m), 2.00-1.65 (2H, m).

Example 49 (119) N-hydroxy-2 (S) -benzyl-5-methoxymethoxy-4 (S)-[N- [4- [3- (4-chlorophenoxy-1-propynyl) phenyl] Carbonyl] amino] pentanamide

[Chemical 358] TLC: Rf 0.26 (chloroform: methanol = 1)
9: 1); NMR (d ₆ -DMSO): δ 10.35 (1H, s), 8.67 (1H, s),
8.24 (1H, d, J = 8.4Hz), 7.87 (2H, d, J = 8.4Hz), 7.5
3 (2H, d, J = 8.4Hz), 7.38 (2H, d, J = 9.2Hz), 7.30-7.0
0 (7H, m), 5.08 (2H, s), 4.53 (2H, s), 4.25 (1H,
m), 3.49 (2H, d, J = 5.4Hz), 3.20 (3H, s), 2.77 (2H,
d, J = 7.0Hz), 2.38 (1H, m), 1.90-1.60 (2H, m).

Example 49 (120) N-Hydroxy-2 (S) -benzyl-5-methoxymethoxy-4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide

[Chemical 359] TLC: Rf 0.39 (chloroform: methanol = 1)
9: 1); NMR (d ₆ -DMSO): δ 10.36 (1H, s), 8.09 (1H, d,
J = 8.6Hz), 7.91 (2H, d, J = 8.8Hz), 7.50-7.38 (2H, m),
7.30-7.08 (8H, m), 7.03 (2H, d, J = 8.8Hz), 4.54 (2H,
s), 4.36-4.18 (1H, m), 3.58-3.40 (2H, m), 3.20 (3
H, s), 2.84-2.65 (2H, m), 2.45-2.30 (1H, m), 1.88-
1.58 (2H, m).

Example 49 (121) N-Hydroxy-2 (S) -benzyl-5-methoxymethoxy-4 (S)-[N- [4- (4-phenylpiperidin-1-yl) phenylcarbonyl] amino ] Pentanamide

[Chemical 360] TLC: Rf 0.26 (chloroform: methanol = 1)
9: 1); NMR (d ₆ -DMSO): δ 10.33 (1H, s), 8.66 (1H, s),
7.82 (1H, d, J = 8.8Hz), 7.77 (2H, d, J = 8.8Hz), 7.3
8-7.06 (10H, m), 6.99 (2H, d, J = 8.8Hz), 4.54 (2H,
s), 4.38-4.16 (1H, m), 4.04-3.90 (2H, m), 3.58-3.4
0 (2H, m), 3.21 (3H, s), 2.96-2.60 (5H, m), 2.44-
2.28 (1H, m), 1.95-1.60 (6H, m).

Example 49 (122) N-hydroxy-2 (S) -benzyl-5-methoxymethoxy-4 (S)-[N- [4- (6-imidazolyl-
1-hexynyl) phenylcarbonyl] amino] pentanamide

[Chemical 361] TLC: Rf 0.46 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.35 (1H, s), 8.67 (1H, s),
8.18 (1H, d, J = 8.4Hz), 7.83 (2H, d, J = 8.4Hz), 7.6
3 (1H, t, J = 1.2Hz), 7.44 (2H, d, J = 8.4Hz), 7.28-7.0
7 (6H, m), 6.89 (1H, t, J = 1.2Hz), 4.53 (2H, s), 4.
36-4.17 (1H, m), 4.01 (2H, t, J = 7.0Hz), 3,60-3.40
(2H, m), 3.20 (3H, s), 2.84-2.70 (2H, m), 2.47 (2
H, t, J = 7.0Hz), 2.46-2.30 (1H, m), 1.96-1.62 (4H,
m), 1.58-1.40 (2H, m).

Example 49 (123) N-hydroxy-2 (S)-(naphthalen-1-yl)
-5-methoxymethoxy-4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide

[Chemical 362] TLC: Rf 0.36 (chloroform: methanol = 1)
9: 1); NMR (d ₆ -DMSO): δ 10.26 (1H, s), 8.63 (1H, s),
8.16 (1H, d, J = 8.4Hz), 8.04-7.82 (4H, m), 7.80-7.
70 (1H, m), 7.52-7.16 (7H, m), 7.14-6.96 (4H, m),
4.52 (2H, s), 4.50-4.28 (1H, m), 3.61-3.40 (2H,
m), 3.25-3.02 (5H, m), 2.69-2.52 (1H, m), 2.00-1.7
8 (2H, m).

Example 49 (124) N-hydroxy-2 (S)-[4- (benzofuran-2)
-Yl) benzyl] -5-methoxymethoxy-4 (S)
-[N- (4-iodophenylcarbonyl) amino] pentanamide

[Chemical Formula 363] TLC: Rf 0.49 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.38 (1H, s), 8.70 (1H, s),
8.25 (1H, d, J = 8.7Hz), 7.85 (2H, d, J = 8.4Hz), 7.79
(2H, d, J = 8.1Hz), 7.70-7.56 (4H, m), 7.36 (1H, s),
7.34-7.20 (4H, m), 4.55 (2H, s), 4.35-4.20 (1H,
m), 3.60-3.45 (2H, m), 3.21 (3H, s), 2.83 (2H, d, J
= 6.9Hz), 2.45-2.30 (1H, m), 1.90-1.60 (2H, m).

Examples 49 (125) -49 (233) Using the compounds corresponding to the compounds prepared in Reference Example 4 Example 37 → Example 39 → Example 41 (corresponding to methoxymethyl chloride instead) A compound is used.) → Example 43 (A corresponding compound is used in place of benzyl bromide) → Example 44 → The same operation as in the method of Example 49 is carried out to obtain a compound shown below.

Example 49 (125) N-Hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N- (trans-4-methylcyclohexylcarbonyl) amino] pentanamide

[Chemical 364] TLC: Rf 0.36 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.32 (s, 1H), 8.80-8.60 (br
s, 1H), 7.43 (d, J = 8.7Hz, 1H), 7.28-7.19 (m, 2H),
7.19-7.07 (m, 3H), 4.54 (s, 2H), 4.05-3.85 (m, 1
H), 3.60-3.20 (m, 4H), 2.80-2.60 (m, 2H), 2.38-2.2
0 (m, 1H), 2.10-1.90 (m, 1H), 1.80-1.60 (m, 5H),
1.60-1.45 (m, 1H), 1.45-1.20 (m, 3H), 1.11 (t, J =
6.9Hz, 3H), 1.00-0.80 (m, 5H).

Example 49 (126) N-hydroxy-2 (S)-(4-nitrobenzyl)-
5-ethoxymethoxy-4 (S)-[N- (trans-
4-Methylcyclohexylcarbonyl) amino] pentanamide

[Chemical 365] TLC: Rf 0.40 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.34 (s, 1H), 8.80-8.60 (br
s, 1H), 8.12 (d, J = 8.7Hz, 2H), 7.48 (d, J = 8.7H
z, 1H), 7.37 (d, J = 8.7Hz, 2H), 4.57 (s, 2H), 4.10
-3.90 (m, 1H), 3.55-3.25 (m, 4H), 3.00-2.70 (m, 2
H), 2.40-2.25 (m, 1H), 2.10-1.95 (m, 1H), 1.85-1.60
(m, 5H), 1.60-1.20 (m, 4H), 1.11 (t, J = 7.2Hz, 3
H), 1.00-0.80 (m, 5H).

Example 49 (127) N-hydroxy-2 (S)-(indol-3-yl)
-5-Ethoxymethoxy-4 (S)-[N- (trans-4-methylcyclohexylcarbonyl) amino] pentanamide

[Chemical 366] TLC: Rf 0.32 (chloroform: methanol = 1)
0: 1); NMR (d ₆ -DMSO): δ 10.73 (brs, 1H), 10.32 (brs,
1H), 8.66 (d, J = 1.5Hz, 1H), 7.49 (d, J = 7.8Hz,
1H), 7.41 (d, J = 8.7Hz, 1H), 7.28 (d, J = 8.1Hz,
1H), 7.05-6.99 (m, 2H), 6.94-6.88 (m, 1H), 4.50
(d, J = 6.9Hz, 1H), 4.47 (d, J = 6.9Hz, 1H), 4.02-
3.902 (m, 1H), 3.40 (q, J = 7.2Hz, 2H), 3.37-3.28
(m, 2H), 2.89-2.71 (m, 2H), 2.48-2.34 (m, 1H), 2.0
5-1.93 (m, 1H), 1.77-1.50 (m, 6H), 1.45-1.20 (m, 3
H), 1.06 (t, J = 7.2Hz, 3H), 0.95-0.80 (m, 2H), 0.
84 (d, J = 6.6Hz, 3H).

Example 49 (128) N-Hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N-[(pyridin-4-yl) carbonyl] amino] pentanamide

[Chemical 367] TLC: Rf 0.30 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.37 (s, 1H), 8.76-8.63 (m,
3H), 8.43 (d, J = 8.6Hz, 1H), 7.80-7.72 (m, 2H),
7.29-7.08 (m, 5H), 4.58 (s, 2H), 4.34-4.14 (m, 1H),
3.60-3.39 (m, 4H), 2.83-2.65 (m, 2H), 2.42-2.28
(m, 1H), 1.88-1.59 (m, 2H), 1.09 (t, J = 7.0Hz, 3
H).

Example 49 (129) N-hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N- (4-hydroxyphenylcarbonyl) amino] pentanamide

[Chemical 368] TLC: Rf 0.57 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.34 (s, 1H), 9.96-9.80 (b
r, 1H), 7.83 (d, J = 8.4Hz, 1H), 7.74 (d, J = 9.0H
z, 2H), 7.26-7.08 (m, 5H), 6.79 (d, J = 9.0Hz, 2
H), 4.57 (s, 2H), 4.30-4.17 (m, 1H), 3.58-3.40 (m,
4H), 2.76 (d, J = 6.6Hz, 2H), 2.42-2.32 (m, 1H),
1.82-1.60 (m, 2H), 1.09 (t, J = 7.2Hz, 3H).

Example 49 (130) N-hydroxy-2 (S)-(2-nitrobenzyl)-
5-ethoxymethoxy-4 (S)-[N- (trans-
4-Methylcyclohexylcarbonyl) amino] pentanamide

[Chemical formula 369] TLC: Rf 0.23 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.35 (s, 1H), 8.71 (s, 1H),
7.92 (dd, J = 8.4,1.2Hz, 1H), 7.61 (td, J = 7.4,
1.2Hz, 1H), 7.50-7.40 (m, 2H), 7.36 (d, J = 7.4Hz,
1H), 4.55 (s, 2H), 3.90-3.75 (m, 1H), 3.55-3.25
(m, 4H, overlap with H2O in DMSO), 3.10-2.90 (m, 2
H), 2.55-2.40 (m, 1H, overlap with DMSO), 2.10-1.9
0 (m, 1H), 1.80-1.55 (m, 6H), 1.50-1.20 (m, 3H),
1.10 (t, J = 7.1Hz, 3H), 1.00-0.75 (m, 5H).

Example 49 (131) N-hydroxy-2 (S)-(3-nitrobenzyl)-
5-ethoxymethoxy-4 (S)-[N- (trans-
4-Methylcyclohexylcarbonyl) amino] pentanamide

[Chemical 370] TLC: Rf 0.38 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.30 (s, 1H), 8.67 (s, 1H),
8.10-8.00 (m, 1H), 7.98 (s, 1H), 7.60-7.46 (m, 3
H), 4.56 (s, 2H), 4.10-3.95 (m, 1H), 3.55-3.30 (m,
4H, overlap with H2O in DMSO), 2.94 (dd, J = 13.
0, 4.7Hz, 1H), 2.80 (dd, J = 13.0, 9.9Hz, 1H), 2.3
0-2.20 (m, 1H), 2.10-1.95 (m, 1H), 1.85-1.60 (m, 5
H), 1.60-1.20 (m, 4H), 1.11 (t, J = 7.1Hz, 3H), 1.
00-0.80 (m, 5H).

Example 49 (132) N-hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N-[(1-methylpyrrole-2
-Yl) carbonyl] amino] pentanamide

[Chemical 371] TLC: Rf 0.31 (chloroform: methanol = 1)
9: 1); NMR (d ₆ -DMSO): δ 10.31 (s, 1H), 8.65 (d, J =
1.2Hz, 1H), 7.59 (d, J = 8.8Hz, 1H), 7.25-7.10 (m,
5H), 6.85-6.90 (m, 1H), 6.78-6.76 (m, 1H), 5.98
(t, J = 3.2Hz, 1H), 4.57 (s, 2H), 4.25-4.08 (m, 1
H), 3.83 (s, 3H), 3.50-3.39 (m, 4H), 2.75 (d, J =
7.0Hz, 2H), 2.45-2.29 (m, 1H), 1.82-1.52 (m, 2H),
1.08 (t, J = 7.0Hz, 3H).

Example 49 (133) N-hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N- (phenylcarbonyl) amino] pentanamide

[Chemical 372] TLC: Rf 0.34 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.34 (s, 1H), 8.60 (d, J =
1.6Hz, 1H), 8.12 (d, J = 8.8Hz, 1H), 7.85 (dd, J =
8.0Hz, 1.8Hz, 2H), 7.52-7.40 (m, 3H), 7.26-7.09
(m, 5H), 4.57 (s, 2H), 4.33-4.15 (m, 1H), 3.49 (d,
J = 5.4Hz, 2H), 3.45 (q, J = 7.0Hz, 2H), 2.76 (d,
J = 7.0Hz, 2H), 2.44-2.28 (m, 1H), 1.85-1.59 (m,
2H), 1.07 (t, J = 7.0Hz, 3H).

Example 49 (134) N-Hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N- (4-ethylphenylcarbonyl) amino] pentanamide

[Chemical 373] TLC: Rf 0.50 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.33 (d, J = 1.2Hz, 1H), 8.
65 (s, 1H), 8.02 (d, J = 8.4Hz, 1H), 7.78 (d, J =
8.2Hz, 2H), 7.30-7.09 (m, 7H), 4.57 (s, 2H), 4.15-
4.32 (m, 1H), 3.50-3.39 (m, 4H), 2.76 (d, J = 7.4H
z, 2H), 2.64 (q, J = 7.4Hz, 2H), 2.42-2.25 (m, 1
H), 1.58-1.82 (m, 2H), 1.17 (t, J = 7.6Hz, 3H), 1.
07 (t, J = 7.4Hz, 3H).

Example 49 (135) N-Hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N- (4-methylphenylcarbonyl) amino] pentanamide

[Chemical 374] TLC: Rf 0.56 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.32 (s, 1H), 8.64 (s, 1H),
8.00 (d, J = 8.7Hz, 1H), 7.73 (d, J = 8.1Hz, 2H),
7.26-7.05 (m, 7H), 4.54 (s, 2H), 4.26-4.15 (m, 1
H), 3.51-3.37 (m, 4H), 2.73 (d, J = 7.2Hz, 2H), 2.
32 (s, 3H), 2.39-2.25 (m, 1H), 1.80-1.58 (m, 2H),
1.05 (t, J = 7.1Hz, 3H).

Example 49 (136) N-Hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N- (4-nitrophenylcarbonyl) amino] pentanamide

[Chemical 375] TLC: Rf 0.25 (methylene chloride: methanol = 1
9: 1); NMR (d ₆ -DMSO): δ 10.36 (d, J = 1.5Hz, 1H), 8.
67 (d, J = 1.5Hz, 1H), 8.50 (d, J = 8.4Hz, 1H), 8.
30 (d, J = 9.0Hz, 2H), 8.08 (d, J = 9.0Hz, 2H), 7.2
5-7.11 (m, 5H), 4.56 (s, 2H), 4.23 (m, 1H), 3.50
(d, J = 5.7Hz, 2H), 3.43 (q, J = 7.2Hz, 2H), 2.75
(m, 2H), 2.36 (m, 1H), 1.72 (m, 2H), 1.07 (t, J =
7.2Hz, 3H).

Example 49 (137) N-hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N- (2,2,3,3-tetramethylcyclopropylcarbonyl) amino] Pentanamide

[Chemical 376] TLC: Rf 0.53 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.32 (d, J = 1.2Hz, 1H), 8.
69 (d, J = 1.2Hz, 1H), 7.49 (d, J = 8.4Hz, 1H), 7.
24-7.09 (m, 5H), 4.53 (s, 2H), 3.98-3.88 (m, 1H),
3.45 (q, J = 7.2Hz, 2H), 3.37-3.35 (m, 2H), 2.73-
2.66 (m, 3H), 2.35-2.25 (m, 1H), 1.70-1.43 (m, 2
H), 1.18-1.04 (m, 15H).

Example 49 (138) N-hydroxy-2 (S)-(3-methoxybenzyl)
-5-Ethoxymethoxy-4 (S)-[N- (4-methylphenylcarbonyl) amino] pentanamide

[Chemical 377] TLC: Rf 0.53 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.33 (d, J = 1.8Hz, 1H), 8.
67 (d, J = 1.8Hz, 1H), 8.06 (d, J = 9.0Hz, 1H), 7.
76 (d, J = 8.4Hz, 2H), 7.24 (d, J = 8.4Hz, 2H), 7.1
3-7.08 (m, 1H), 6.71-6.66 (m, 3H), 4.56 (s, 2H),
4.17-4.30 (m, 1H), 3.65 (s, 3H), 3.53-3.41 (m, 4H),
2.72 (d, J = 7.2Hz, 2H), 2.40-2.30 (m, 1H), 2.34
(s, 3H), 1.81-1.59 (m, 2H), 1.07 (t, J = 7.2Hz, 3
H).

Example 49 (139) N-hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N- (1-cyclohexenylcarbonyl) amino] pentanamide

[Chemical 378] TLC: Rf 0.25 (methylene chloride: methanol = 1
9: 1); NMR (d ₆ -DMSO): δ 10.31 (brs, 1H), 8.65 (brs,
1H), 7.28-7.08 (m, 6H), 6.49 (brs, 1H), 4.53 (s, 2
H), 4.05 (m, 1H), 3.43 (q, J = 7.2Hz, 2H), 3.47-3.3
5 (m, 2H), 2.69 (m, 2H), 2.28 (m, 1H), 2.20-2.04
(m, 4H), 1.74-1.46 (m, 6H), 1.09 (t, J = 7.2Hz, 3
H).

Example 49 (140) N-hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N [(1-cyclohexene-4-
Ile) carbonyl] amino] pentanamide

[Chemical 379] TLC: Rf 0.25 (methylene chloride: methanol = 1
9: 1); NMR (d ₆ -DMSO): δ 10.31 (brs, 1H), 8.67 (brs,
1H), 7.54 (d, J = 8.4Hz, 1H), 7.24-7.08 (m, 5H),
5.64 (m, 2H), 4.53 (s, 2H), 3.95 (m, 1H), 3.43 (q,
J = 7.2Hz, 2H), 3.47-3.28 (m, 2H), 2.75-2.63 (m,
2H), 2.33-1.44 (m, 10H), 1.09 (t, J = 7.2Hz, 3H).

Example 49 (141) N-Hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N- (4-dimethylaminophenylcarbonyl) amino] pentanamide

[Chemical 380] TLC: Rf 0.63 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.33 (s, 1H), 8.65 (s, 1H),
7.78-7.69 (m, 3H), 7.25-7.08 (m, 5H), 6.69 (d, J =
9.0Hz, 2H), 4.58 (s, 2H), 4.29-4.18 (m, 1H), 3.56-
3.41 (m, 4H), 2.97 (s, 6H), 2.77 (d, J = 7.2Hz, 2
H), 2.42-2.32 (m, 1H), 1.82-1.62 (m, 2H), 1.10 (t,
J = 6.9Hz, 3H).

Example 49 (142) N-Hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N- (4-carbamoylphenylcarbonyl) amino] pentanamide

[Chemical 381] TLC: Rf 0.37 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.37 (s, 1H), 8.68 (s, 1H),
8.24 (d, J = 8.7Hz, 1H), 8.08 (s, 1H), 7.98-7.87
(m, 4H), 7.48 (s, 1H), 7.28-7.10 (m, 5H), 4.58 (s,
2H), 4.32-4.19 (m, 1H), 3.58-3.40 (m, 4H), 2.77
(d, J = 6.9Hz, 2H), 2.42-2.32 (m, 1H), 1.83-1.61
(m, 2H), 1.09 (t, J = 7.2Hz, 3H).

Example 49 (143) N-hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N- (4-methoxycarbonylphenylcarbonyl) amino] pentanamide

[Chemical 382] TLC: Rf 0.31 (chloroform: methanol = 1)
9: 1); NMR (d ₆ -DMSO): δ 10.38 (s, 1H), 8.69 (s, 1H),
8.35 (d, J = 8.4Hz, 1H), 8.04 (d, J = 8.8Hz, 2H),
7.98 (d, J = 8.8Hz, 2H), 7.28-7.06 (m, 5H), 4.58
(s, 2H), 4.35-4.18 (m, 1H), 3.89 (s, 3H), 3.60-3.3
9 (m, 4H), 2.77 (d, J = 7.0Hz, 2H), 2.42-2.28 (m,
1H), 1.88-1.59 (m, 2H), 1.09 (t, J = 7.0Hz, 3H).

Example 49 (144) N-hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N- (cyclopentylcarbonyl) amino] pentanamide

[Chemical 383] TLC: Rf 0.51 (methylene chloride: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.32 (brs, 1H), 8.68 (brs,
1H), 7.49 (d, J = 8.7Hz, 1H), 7.25-7.08 (m, 5H),
4.53 (s, 2H), 3.92 (m, 1H), 3.43 (q, J = 7.2Hz, 2
H), 3.40-3.35 (m, 2H), 2.72 (dd, J = 13.5, 8.7Hz,
1H), 2.65 (dd, J = 13.5, 5.6Hz, 1H), 2.49 (m, 1H),
2.29 (m, 1H), 1.80-1.40 (m, 10H), 1.09 (t, J = 7.2
Hz, 3H).

Example 49 (145) N-hydroxy-2 (S)-(naphthalen-2-yl)
-5-Ethoxymethoxy-4 (S)-[N- (trans-4-methylcyclohexylcarbonyl) amino] pentanamide

[Chemical 384] TLC: Rf 0.31 (chloroform: methanol = 1)
9: 1); NMR (d ₆ -DMSO): δ 10.33 (s, 1H), 7.90-7.73 (m,
3H), 7.60 (s, 1H), 7.54-7.37 (m, 3H), 7.34-7.22
(m, 1H), 4.60-4.46 (m, 2H), 4.12-3.90 (m, 1H), 3.5
2-3.22 (m, 4H), 2.87 (d, J = 6.6Hz, 2H), 2.45-2.28
(m, 1H), 2.17-1.94 (m, 1H), 1.88-1.18 (m, 10H),
1.09 (t, J = 7.0Hz, 3H), 1.00-0.72 (m, 4H).

Example 49 (146) N-hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N- (4-trifluoromethylphenylcarbonyl) amino] pentanamide

[Chemical 385] TLC: Rf 0.58 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.34 (s, 1H), 8.67 (d, J =
2.1Hz, 1H), 8.38 (d, J = 8.7Hz, 1H), 8.04 (d, J =
8.4Hz, 2H), 7.83 (d, J = 8.4Hz, 2H), 7.25-7.10 (m,
5H), 4.56 (s, 2H), 4.30-4.18 (m, 1H), 3.50-3.36 (m
, 4H), 2.76-2.74 (m, 2H), 2.41-2.30 (m, 1H), 1.81
-1.62 (m, 2H), 1.07 (t, J = 7.2Hz, 3H).

Example 49 (147 ) N-Hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N- (4-iodophenylcarbonyl) amino] pentanamide

[Chemical 386] TLC: Rf 0.45 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.33 (s, 1H), 8.65 (brs, 1
H), 8.19 (d, J = 8.4Hz, 1H), 7.83 (d, J = 8.4Hz, 2
H), 7.63 (d, J = 8.4Hz, 2H), 7.24-7.09 (m, 5H), 4.5
5 (s, 2H), 4.28-4.15 (m, 1H), 3.48-3.39 (m, 4H),
2.74 (d, J = 7.2Hz, 2H), 2.38-2.29 (m, 1H), 1.79-
1.59 (m, 2H), 1.06 (t, J = 7.2Hz, 3H).

Example 49 (148) N-hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N- [4- (2-iodoethynyl) phenylcarbonyl] amino] pentanamide

[Chemical 387] TLC: Rf 0.37 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.35 (s, 1H), 8.66 (d, J =
1.5Hz, 1H), 8.28 (d, J = 8.4Hz, 1H), 7.90 (d, J =
8.4Hz, 2H), 7.71 (d, J = 8.4Hz, 2H), 7.24-7.10 (m,
5H), 4.56 (s, 2H), 4.29-4.18 (m, 1H), 3.50-3.35
(m, 4H), 2.75 (d, J = 6.9Hz, 2H), 2.40-2.31 (m, 1
H), 1.81-1.61 (m, 2H), 1.07 (t, J = 6.9Hz, 3H).

Example 49 (149) N-Hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N- (cycloheptylcarbonyl) amino] pentanamide

[Chemical 388] TLC: Rf 0.26 (methylene chloride: methanol = 1
9: 1); NMR (d ₆ -DMSO): δ 10.32 (brs, 1H), 8.68 (brs,
1H), 7.41 (d, J = 8.7Hz, 1H), 7.25-7.08 (m, 5H),
4.53 (s, 2H), 3.90 (m, 1H), 3.43 (q, J = 7.2Hz, 2
H), 3.40-3.30 (m, 2H), 2.68 (m, 2H), 2.33-2.20 (m,
2H), 1.80-1.30 (m, 14H), 1.09 (t, J = 7.2Hz, 3H).

Example 49 (150) N-hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N- (2-thienylcarbonyl)
Amino] pentanamide

[Chemical 389] TLC: Rf 0.48 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.35 (s, 1H), 8.17 (d, J =
9.0Hz, 1H), 7.79-7.76 (m, 1H), 7.72-7.69 (m, 1H),
7.23-7.06 (m, 6H), 4.54 (s, 2H), 4.19-4.08 (m, 1H),
3.50-3.38 (m, 4H), 2.76-2.67 (m, 2H), 2.40-2.30
(m, 1H), 1.79-1.57 (m, 2H), 1.05 (t, J = 7.2Hz, 3
H).

Example 49 (151) N-hydroxy-2 (R)-(3,4,4-trimethyl-2,5-dioxoimidazolidin-1-yl) methyl-5-ethoxymethoxy-4 (S )-[N- (4-Methylphenylcarbonyl) amino] pentanamide

[Chemical 390] TLC: Rf 0.41 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.63 (s, 1H), 8.78 (s, 1H),
7.99 (d, J = 7.8Hz, 1H), 7.73 (d, J = 8.1Hz, 2H),
7.24 (d, J = 8.1Hz, 2H), 4.57 (s, 2H), 4.10-3.95
(m, 1H), 3.60-3.30 (m, 6H, overlap with H2O in DMS
O), 2.78 (s, 3H), 2.70-2.50 (m, 1H), 2.35 (s, 3H),
1.72 (t, J = 6.9Hz, 2H), 1.30 (s, 3H), 1.28 (s, 3
H), 1.08 (t, J = 6.9Hz, 3H).

Example 49 (152) N-Hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N-[(2-bromo-5-thienyl) carbonyl] amino] pentanamide

[Chemical 391] TLC: Rf 0.38 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.35 (s, 1H), 8.27 (d, J =
8.7Hz, 1H), 7.60 (d, J = 3.9Hz, 1H), 7.27-7.17 (m,
3H), 7.17-7.06 (m, 3H), 4.53 (s, 2H), 4.14-4.03
(m, 1H), 3.49-3.36 (m, 4H), 2.78-2.63 (m, 2H), 2.3
8-2.27 (m, 1H), 1.77-1.56 (m, 2H), 1.05 (t, J = 6.9
Hz, 3H).

Example 49 (153) N-hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N- (4-bromophenylcarbonyl) amino] pentanamide

[Chemical 392] TLC: Rf 0.46 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.32 (s, 1H), 8.19 (d, J =
8.4Hz, 1H), 7.78 (d, J = 8.5Hz, 2H), 7.64 (d, J =
8.5Hz, 2H), 7.23-7.06 (m, 5H), 4.54 (s, 2H), 4.24-
4.13 (m, 1H), 3.50-3.36 (m, 4H), 2.76-2.69 (m, 2
H), 2.38- 2.27 (m, 1H), 1.79-1.58 (m, 2H), 1.05
(t, J = 7.0Hz, 3H).

Example 49 (154) N-hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N- (4-hydroxymethylphenylcarbonyl) amino] pentanamide

[Chemical 393] TLC: Rf 0.25 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.32 (s, 1H), 8.65 (s, 1H),
8.04 (d, J = 8.4Hz, 1H), 7.79 (d, J = 7.8Hz, 2H),
7.35 (d, J = 7.8Hz, 2H), 7.23-7.06 (m, 5H), 5.26
(t, J = 5.7Hz, 1H), 4.55 (s, 2H), 4.52 (d, J = 5.7H
z, 2H), 4.27-4.15 (m, 1H), 3.55-3.37 (m, 4H), 2.76
-2.70 (m, 2H), 2.34 (m, 1H), 1.81-1.59 (m, 2H), 1.
06 (t, J = 7.2Hz, 3H).

Example 49 (155) N-hydroxy-2 (S)-(benzothiophene-3-
Yl) -5-ethoxymethoxy-4 (S)-[N- (trans-4-methylcyclohexylcarbonyl) amino] pentanamide

[Chemical 394] TLC: Rf 0.37 (chloroform: methanol = 1)
9: 1); NMR (d ₆ -DMSO): δ 10.39 (s, 1H), 8.72 (s, 1H),
7.95-7.90 (m, 1H), 7.83-7.76 (m, 1H), 7.48 (d, J =
8.7Hz, 1H), 7.40-7.30 (m, 2H), 7.29 (s, 1H), 4.56-
4.48 (m, 2H), 4.12-3.97 (m, 1H), 3.47-3.28 (m, 4
H), 3.01 (dd, J = 14.4, 9.3Hz, 1H), 2.93 (dd, J = 1
4.4, 5.1Hz, 1H), 2.56-2.41 (m, 1H), 2.09-1.96 (m, 1
H), 1.82-1.53 (m, 6H), 1.48-1.20 (m, 3H), 1.09 (t,
J = 6.9Hz, 3H), 0.98-0.78 (m, 5H).

Example 49 (156) N-hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N- (4-cyanophenylcarbonyl) amino] pentanamide

[Chemical 395] TLC: Rf 0.32 (chloroform: methanol = 1)
9: 1); NMR (d ₆ -DMSO): δ 10.38 (s, 1H), 8.69 (s, 1H),
8.42 (d, J = 8.7Hz, 1H), 8.02 (d, J = 8.4Hz, 2H),
7.94 (d, J = 8.4Hz, 2H), 7.30-7.09 (m, 5H), 4.58
(s, 2H), 4.31-3.97 (m, 1H), 3.57-3.39 (m, 4H), 2.
83-2.68 (m, 2H), 2.42- 2.30 (m, 1H), 1.83-1.61 (m,
2H), 1.09 (t, J = 7.2Hz, 3H).

Example 49 (157) N-hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N-[(1-acetylpiperidin-4-yl) carbonyl] amino] pentanamide

Embedded image TLC: Rf 0.64 (chloroform: methanol = 5:
1); NMR (d ₆ -DMSO): δ 10.32 (brs, 1H), 7.58 (brd,
J = 9.0Hz, 1H), 7.25-7.08 (m, 5H), 4.53 (s, 2H),
4.32 (brd, J = 9.6Hz, 1H), 3.93 (m, 1H), 3.79 (br
d, J = 12.6Hz, 1H), 3.43 (q, J = 6.9Hz, 2H), 3.35
(m, 2H), 2.98 (brt, J = 12.0Hz, 1H), 2.68 (m, 2H),
2.49 (m, 1H), 2.40-2.20 (m, 2H), 1.98 (s, 3H), 1.7
5-1.30 (m, 6H), 1.09 (t, J = 6.9Hz, 3H).

Example 49 (158) N-hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N-[(1-methylpiperidine-
4-yl) carbonyl] amino] pentanamide

[Chemical 397] TLC: Rf 0.39 (chloroform: methanol: acetic acid = 7: 2: 1); NMR (d ₆ -DMSO): δ 10.30 (brs, 1H), 8.67 (brs,
1H), 7.48 (brd, J = 9.0Hz, 1H), 7.24-7.07 (m, 5H),
4.52 (s, 2H), 3.93 (m, 1H), 3.42 (q, J = 7.2Hz, 2
H), 3.34 (m, 2H), 2.70 (m, 4H), 2.26 (m, 1H), 2.00
(m, 1H), 2.10 (s, 3H), 1.81-1.45 (m, 8H), 1.08 (t,
J = 7.2Hz, 3H).

Example 49 (159) N-hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N- (4-formylphenylcarbonyl) amino] pentanamide

[Chemical 398] TLC: Rf 0.36 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.38 (s, 1H), 10.09 (s, 1
H), 8.69 (s, 1H), 8.38 (d, J = 8.4Hz, 1H), 8.05 (d,
J = 8.4Hz, 2H), 7.99 (d, J = 8.4Hz, 2H), 7.30-7.2
0 (m, 2H), 7.20-7.10 (m, 3H), 4.58 (s, 2H), 4.32-
4.20 (m, 1H), 3.60-3.40 (m, 4H), 2.83-2.70 (m, 2
H), 2.45-2.32 (m, 1H), 1.85-1.62 (m, 2H), 1.09 (t,
J = 6.9Hz, 3H).

Example 49 (160) N-hydroxy-2 (S)-(3-methoxybenzyl)
-5-Ethoxymethoxy-4 (S)-[N- (4-nitrophenylcarbonyl) amino] pentanamide

[Chemical 399] TLC: Rf 0.40 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.38 (d, J = 1.8Hz, 1H), 8.
70 (d, J = 1.8Hz, 1H), 8.51 (d, J = 8.4Hz, 1H), 8.
31 (d, J = 8.9Hz, 2H), 8.09 (d, J = 8.9Hz, 2H), 7.1
8-7.10 (m, 1H), 6.75-6.65 (m, 3H), 4.58 (s, 2H),
4.30-4.20 (m, 1H), 3.69 (s, 3H), 3.60-3.40 (m, 4H),
2.80-2.65 (m, 2H), 2.45-2.30 (m, 1H), 1.85-1.60
(m, 2H), 1.09 (t, J = 7.1Hz, 3H).

Example 49 (161) N-hydroxy-2 (S)-(3-methoxybenzyl)
-5-Ethoxymethoxy-4 (S)-[N- (4-chlorophenylcarbonyl) amino] pentanamide

[Chemical 400] TLC: Rf 0.47 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.36 (s, 1H), 8.23 (d, J =
8.4Hz, 1H), 7.89 (d, J = 8.6Hz, 2H), 7.53 (d, J =
8.6Hz, 2H), 7.17-7.08 (m, 1H), 6.80-6.65 (m, 3H),
4.58 (s, 2H), 4.30-4.18 (m, 1H), 3.68 (s, 3H), 3.6
0-3.35 (m, 4H, overlap with H2O in DMSO), 2.80-2.65
(m, 2H), 2.42-2.30 (m, 1H), 1.85-1.60 (m, 2H), 1.
09 (t, J = 6.9Hz, 3H).

Example 49 (162) N-hydroxy-2 (S)-(4-methoxybenzyl)
-5-Ethoxymethoxy-4 (S)-[N- (4-methylphenylcarbonyl) amino] pentanamide

[Chemical 401] TLC: Rf 0.49 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.30 (s, 1H), 8.64 (s, 1H),
8.02 (d, J = 8.8Hz, 1H), 7.75 (d, J = 8.4Hz, 2H),
7.24 (d, J = 8.4Hz, 2H), 7.02 (d, J = 8.4Hz, 2H),
6.76 (d, J = 8.4Hz, 2H), 4.56 (s, 2H), 4.12-4. 30
(m, 1H), 3.68 (s, 3H), 3.49-3.38 (m, 4H), 2.68 (d,
J = 7.4Hz, 2H), 2.39-2.22 (m, 1H), 2.34 (s, 3H), 1.
82-1.58 (m, 2H), 1.07 (t, J = 7.2Hz, 3H).

Example 49 (163) N-hydroxy-2 (S)-(2-methoxybenzyl)
-5-Ethoxymethoxy-4 (S)-[N- (4-methylphenylcarbonyl) amino] pentanamide

[Chemical 402] TLC: Rf 0.51 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.30 (s, 1H), 8.63 (d, J =
1.5Hz, 1H), 7.93 (d, J = 8.4Hz, 1H), 7.74 (d, J =
8.4Hz, 2H), 7.23 (d, J = 8.4Hz, 2H), 7.16-6.76 (m,
4H), 4.55 (s, 2H), 4.19-4.08 (m, 1H), 3.62 (s, 3
H), 3.48-3.38 (m, 4H), 2.71-2.62 (m, 2H), 2.51-2.4
0 (m, 1H), 2.33 (s, 3H), 1.75-1.70 (m, 2H), 1.06
(t, J = 7.2Hz, 3H).

Example 49 (164 ) N-hydroxy-2 (S)-(naphthalen-1-yl)
Methyl-5-ethoxymethoxy-4 (S)-[N- (4
-Methylphenylcarbonyl) amino] pentanamide

[Chemical 403] TLC: Rf 0.44 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.24 (s, 1H), 8.61 (s, 1H),
8.11 (d, J = 8.4Hz, 1H), 7.98 (d, J = 8.4Hz, 1H),
7.86-7.79 (m, 4H), 7.74-7.71 (d, J = 8.4Hz, 1H),
7.44-7.23 (m, 5H), 4.54 (s, 2H), 4.30-4.20 (m, 1
H), 3.50-3.47 (m, 2H), 3.95 (q, J = 7.2Hz, 2H), 3.
29-3.10 (m, 2H), 2.62-2.51 (m, 1H), 1.95-1.75 (m,
2H), 1.04 (t, J = 7.2Hz, 3H).

Example 49 (165) N-hydroxy-2 (S)-(3-methoxybenzyl)
-5-Ethoxymethoxy-4 (S)-[N- (trans-4-methylcyclohexylcarbonyl) amino] pentanamide

[Chemical 404] TLC: Rf 0.56 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.31 (s, 1H), 9.00-8.30 (br
s, 1H), 7.44 (d, J = 8.7Hz, 1H), 7.13 (t, J = 8.0H
z, 1H), 6.80-6.65 (m, 3H), 4.55 (d, J = 6.6Hz, 1
H), 4.51 (d, J = 6.6Hz, 1H), 4.00-3.85 (m, 1H), 3.
70 (s, 3H), 3.44 (q, J = 7.1Hz, 2H), 3.50-3.20 (m,
2H), 2.75-2.50 (m, 2H), 2.30-2.20 (m, 1H), 2.10-1.9
0 (m, 1H), 1.80-1.20 (m, 9H), 1.09 (t, J = 7.1Hz,
3H), 0.84 (d, J = 6.6Hz, 3H), 1.00-0.80 (m, 2H).

Example 49 (166) N-hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N- (4-methoxycyclohexylcarbonyl) amino] pentanamide

[Chemical 405] TLC: Rf 0.40 (methylene chloride: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.30 (brs, 1H), 8.67 (brs,
1H), 7.48 (brd, J = 8.4Hz, 0.4H), 7.41 (brd, J = 8.
4Hz, 0.6H), 7.24-7.08 (m, 5H), 4.53 (s, 2H), 3.93
(m, 1H), 3.43 (q, J = 7.2Hz, 2H), 3.34 (m, 3H), 3.
21 (s, 1.2H), 3.18 (s, 1.8H), 2.67 (m, 2H), 2.30-1.
30 (m, 12H), 1.09 (t, J = 7.2Hz, 3H).

Example 49 (167) N-hydroxy-2 (S)-(benzothiophene-3-
Iyl) methyl-5-ethoxymethoxy-4 (S)-[N
-(4-Bromophenylcarbonyl) amino] pentanamide

[Chemical 406] TLC: Rf 0.43 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.38 (d, J = 1.2Hz, 1H), 8.
68 (d, J = 1.2Hz, 1H), 8.27 (d, J = 8.4Hz, 1H), 7.
91 (d, J = 7.5Hz, 1H), 7.83-7.76 (m, 3H), 7.69-7.66
(m, 2H), 7.34-7.22 (m, 3H), 4.55 (s, 2H), 4.38-4.
25 (m, 1H), 3.49 (d, J = 5.1Hz, 2H), 3.41 (q, J =
7.2Hz, 2H), 3.02-2.98 (m, 2H), 2.56-2.48 (m, 1H),
1.91-1.70 (m, 2H), 1.04 (t, J = 7.2Hz, 3H).

Example 49 (168) N-hydroxy-2 (S)-(benzothiophene-3-
Iyl) methyl-5-ethoxymethoxy-4 (S)-[N
-(4-Chlorophenylcarbonyl) amino] pentanamide

[Chemical 407] TLC: Rf 0.44 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.38 (d, J = 1.5Hz, 1H), 8.
68 (d, J = 1.5Hz, 1H), 8.27 (d, J = 8.4Hz, 1H), 7.
93-7.87 (m, 3H), 7.78 (d, J = 7.5Hz, 1H), 7.55-7.52
(m, 2H), 7.34-7.22 (m, 3H), 4.55 (s, 2H), 4.38-4.
24 (m, 1H), 3.49 (d, J = 5.4Hz, 2H), 3.41 (q, J =
7.2Hz, 2H), 3.04-2.92 (m, 2H), 2.58-2.42 (m, 1H),
1.90-1.70 (m, 2H), 1.05 (t, J = 7.2Hz, 3H).

Example 49 (169) N-hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N-[(2-chloropyridine-5
-Yl) carbonyl] amino] pentanamide

[Chemical 408] TLC: Rf 0.36 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.35 (s, 1H), 8.81 (d, J =
2.4Hz, 1H), 8.65 (s, 1H), 8.43 (d, J = 9.0Hz, 1H),
8.21 (dd, J = 2.4Hz, 8.5Hz, 1H), 7.61 (d, J = 8.5H
z, 1H), 7.24- 7.07 (m, 5H), 4.54 (s, 2H), 4.24-4.
14 (m, 1H), 3.50-3.37 (m, 4H), 2.79-2.66 (m, 2H),
2.39-2.28 (m, 1H), 1.79-1.60 (m, 2H), 1.05 (t, J =
7.1Hz, 3H).

Example 49 (170) N-Hydroxy-2 (S)-(3,5-dimethoxybenzyl) -5-ethoxymethoxy-4 (S)-[N- (4
-Methylphenylcarbonyl) amino] pentanamide

[Chemical 409] TLC: Rf 0.33 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.33 (brs, 1H), 8.67 (brs,
1H), 8.02 (brd, J = 8.7Hz, 1H), 7.76 (d, J = 8.1Hz,
2H), 7.25 (d, J = 8.1Hz, 2H), 6.26 (s, 3H), 4.57
(s, 2H), 4.24 (m, 1H), 3.63 (s, 6H), 3.49 (m, 2H),
3.45 (q, J = 7.2Hz, 2H), 2.68 (brd, J = 7.2Hz, 2
H), 2.34 (s, 3H), 2.34 (m, 1H), 1.80-1.59 (m, 2H),
1.07 (t, J = 7.2Hz, 3H).

Example 49 (171) N-hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N- (4-methylcyclohexylcarbonyl) amino] pentanamide

[Chemical 410] TLC: Rf 0.38 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.29 (d, J = 1.5Hz, 1H), 8.
65 (d, J = 1.5Hz, 1H), 7.42 (brd, J = 8.4Hz, 0.16
H), 7.34 (brd, J = 8.4Hz, 0.84H), 7.23-7.08 (m, 5
H), 4.52 (s, 2H), 3.95 (m, 1H), 3.43 (q, J = 7.2H
z, 2H), 3.35 (m, 2H), 2.68 (m, 2H), 2.30-2.10 (m, 2
H), 1.80-1.30 (m, 11H), 1.08 (t, J = 7.2Hz, 3H),
0.88 (d, J = 6.6Hz, 2.5H), 0.83 (d, J = 6.6Hz, 0.5
H).

Example 49 (172) N-hydroxy-2 (S)-(3-methoxybenzyl)
-5-Ethoxymethoxy-4 (S)-[N- (4-cyanophenylcarbonyl) amino] pentanamide

[Chemical 411] TLC: Rf 0.32 (chloroform: methanol = 1)
9: 1); NMR (d ₆ -DMSO): δ 10.37 (s, 1H), 8.68 (s, 1H),
8.42 (d, J = 8.4Hz, 1H), 8.02 (d, J = 8.4Hz, 2H),
7.95 (d, J = 8.4Hz, 2H), 7.20-7.08 (m, 1H), 6.76-
6.65 (m, 3H), 4.58 (s, 2H), 4.33-4.15 (m, 1H), 3.
68 (s, 3H), 3.55-3.39 (m, 4H), 2.80-2.56 (m, 2H),
2.43-2.28 (m, 1H), 1.88-1.58 (m, 2H), 1.09 (t, J =
7.2Hz, 3H).

Example 49 (173) N-Hydroxy-2 (R)-(3,4,4-trimethyl-2,5-dioxoimidazolidin-1-yl) methyl-5-ethoxymethoxy-4 (S )-[N- (trans-4-methylcyclohexylcarbonyl) amino] pentanamide

[Chemical 412] TLC: Rf 0.47 (chloroform: methanol = 1
9: 1); NMR (d ₆ -DMSO): δ 10.59 (s, 1H), 8.78 (s, 1H),
7.43 (d, J = 8.4Hz, 1H), 4.52 (d, J = 6.9Hz, 1H),
4.50 (d, J = 6.9Hz, 1H), 3.77-3.65 (m, 1H), 3.48-
3.33 (m, 4H), 2.76 (s, 3H), 2.52-2.41 (m, 1H), 2.0
3-1.92 (m, 1H), 1.45-1.71 (m, 6H), 1.37-1.20 (m,
1H), 1.27 (s, 3H), 1.26 (s, 3H), 1.08 (t, J = 7.2H
z, 3H), 0.89-0.78 (m, 2H), 0.83 (d, J = 6.3Hz, 3
H).

Example 49 (174) N-hydroxy-2 (R)-(benzofuran-2-yl) methyl-5-ethoxymethoxy-4 (S)-[N-
(Trans-4-methylcyclohexylcarbonyl) amino] pentanamide

[Chemical 413] TLC: Rf 0.42 (chloroform: methanol = 1)
9: 1); NMR (d ₆ -DMSO): δ 10.52 (s, 1H), 8.78 (s, 1H),
7.52-7.42 (m, 3H), 7.23-7.13 (m, 2H), 6.53 (s, 1
H), 4.54 (d, J = 6.6Hz, 1H), 4.51 (d, J = 6.6Hz, 1
H), 3.95-3.82 (m, 1H), 3.46-3.33 (m, 4H), 2.97-2.8
1 (m, 2H), 2.55-2.42 (m, 1H), 2.04-1.95 (m, 1H),
1.74-1.56 (m, 7H), 1.39-1.26 (m, 4H), 1.07 (t, J =
7.2Hz, 3H), 0.84 (d, J = 6.6Hz, 3H).

Example 49 (175) N-hydroxy-2 (S)-(benzothiophene-3-
Iyl) methyl-5-ethoxymethoxy-4 (S)-[N
-(4-Nitrophenylcarbonyl) amino] pentanamide

[Chemical 414] TLC: Rf 0.36 (chloroform: methanol = 1)
9: 1); NMR (d ₆ -DMSO): δ 10.42 (s, 1H), 8.70 (brs, 1
H), 8.55 (d, J = 8.4Hz, 1H), 8.32-8.29 (m, 2H), 8.
11-8.08 (m, 2H), 7.93-7.90 (m, 1H), 7.81-7.78 (m,
1H), 7.34-7.25 (m, 3H), 4.55 (s, 2H), 4.38-4.25
(m, 1H), 3.51 (d, J = 5.7Hz, 2H), 3.41 (q, J = 7.2H
z, 2H), 3.05-2.94 (m, 2H), 2.57-2.53 (m, 1H), 1.91
-1.72 (m, 2H), 1.04 (t, J = 7.2Hz, 3H).

Example 49 (176) N-hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N- (4-cyanophenylcarbonyl) amino] pentanamide

[Chemical 415] TLC: Rf 0.47 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.34 (s, 1H), 8.66 (s, 1H),
8.22 (d, J = 8.4Hz, 1H), 7.85 (d, J = 8.4Hz, 2H), 7.5
5 (d, J = 8.4Hz, 2H), 7.24-7.09 (m, 5H), 4.56 (s, 2
H), 4.35 (s, 1H), 4.28-4.16 (m, 1H), 3.48 (d, J = 6.
0Hz, 2H), 3.43 (q, J = 6.9Hz, 2H), 2.75 (d, J = 7.2Hz,
2H), 2.40-2.29 (m, 1H), 1.81-1.61 (m, 2H), 1.07
(t, J = 6.9Hz, 3H).

Example 49 (177) N-hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N- (4-methylidenecyclohexylcarbonyl) amino] pentanamide

[Chemical 416] TLC: Rf 0.40 (methylene chloride: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.31 (s, 1H), 8.67 (s, 1H),
7.50 (brd, J = 8.7Hz, 1H), 7.25-7.08 (m, 5H), 4.61
(s, 2H), 4.53 (s, 2H), 3.93 (m, 1H), 3.43 (q, J = 6.9
Hz, 2H), 3.35 (m, 2H), 2.68 (m, 2H), 2.25 (m, 4H),
2.05-1.30 (m, 8H), 1.09 (t, J = 6.9Hz, 3H).

Example 49 (178) N-hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N-[(1-formylpiperidin-4-yl) carbonyl] amino] pentanamide

[Chemical 417] TLC: Rf 0.38 (methylene chloride: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.32 (s, 1H), 8.68 (s, 1H),
7.96 (s, 1H), 7.58 (brd, J = 8.7Hz, 1H), 7.25-7.08
(m, 5H), 4.53 (s, 2H), 4.13 (brd, J = 12.3Hz, 1H),
3.93 (m, 1H), 3.67 (brd, J = 10.5Hz, 1H), 3.43 (q, J
= 6.9Hz, 2H), 3.35 (m, 2H), 3.00 (brt, J = 12.3Hz, 1
H), 2.75-2.20 (m, 5H), 1.80-1.30 (m, 6H), 1.09 (t,
J = 6.9Hz, 3H).

Example 49 (179) N-hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N-[(1-methyl-1-cyclohexen-4-yl) carbonyl] amino ] Pentanamide

[Chemical 418] TLC: Rf 0.30 (chloroform: methanol = 1)
NMR (d ₆ -DMSO): δ 10.33 (brs, 1H), 7.53 (d, J =
8.4Hz, 1H), 7.30-7.05 (m, 5H), 5.35 (brs, 1H), 4.5
4 (s, 2H), 4.00-3.85 (m, 1H), 3.60-3.20 (m, 4H),
2.80-2.60 (m, 2H), 2.40-1.40 (m, 10H), 1.60 (s, 3
H), 1.10 (t, J = 7.2Hz, 3H).

Example 49 (180) N-Hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N-[(4-methyl-1-cyclohexenyl) carbonyl] amino] pentanamide

[Chemical 419] TLC: Rf 0.35 (chloroform: methanol = 1)
0: 1); NMR (d ₆ -DMSO): δ 10.32 (s, 1H), 8.65 (s, 1H),
7.35-7.00 (m, 6H), 6.46 (brs, 1H), 4.54 (s, 2H),
4.20-3.90 (m, 1H), 3.50-3.20 (m, 4H), 2.80-2.60
(m, 2H), 2.40-2.20 (m, 4H), 1.80-1.50 (m, 5H), 1.2
0-1.00 (m, 1H), 1.09 (t, J = 7.1Hz, 3H), 0.93 (d, J =
6.3Hz, 3H).

Example 49 (181) N-hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N- (4-fluorophenylcarbonyl) amino] pentanamide

[Chemical 420] TLC: Rf 0.45 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.36 (s, 1H), 8.60-8.55 (b
r, 1H), 8.16 (d, J = 8.7Hz, 1H), 7.94 (dd, J = 9.0, 5.
4Hz, 2H), 7.35-7.20 (m, 4H), 7.20-7.08 (m, 3H), 4.5
8 (s, 2H), 4.30-4.18 (m, 1H), 3.60-3.40 (m, 4H),
2.82-2.70 (m, 2H), 2.42-2.30 (m, 1H), 1.82-1.60 (m,
2H), 1.09 (t, J = 6.9Hz, 3H).

Example 49 (182) N-Hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N- (4-chlorophenylcarbonyl) amino] pentanamide

[Chemical 421] TLC: Rf 0.38 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.36 (s, 1H), 8.80-8.55 (b
r, 1H), 8.22 (d, J = 8.4Hz, 1H), 7.89 (d, J = 8.7Hz, 2
H), 7.53 (d, J = 8.7Hz, 2H), 7.30-7.10 (m, 5H), 4.57
(s, 2H), 4.30-4.15 (m, 1H), 3.60-3.40 (m, 4H), 2.
82-2.70 (m, 2H), 2.42-2.30 (m, 1H), 1.82-1.60 (m,
2H), 1.09 (t, J = 7.1Hz, 3H).

Example 49 (183) N-hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N- (4-hydroxycyclohexylcarbonyl) amino] pentanamide

[Chemical 422] TLC: Rf 0.38 (chloroform: methanol: acetic acid = 9: 1: 0.5); NMR (d ₆ -DMSO): δ 10.29 (s, 1H), 7.44 (d, J = 8.
8Hz, 0.4H), 7.35 (d, J = 8.8Hz, 0.6H), 7.26-7.03 (m,
5H), 4.51 (s, 2H), 4.02-3.82 (m, 1H), 3.76-3.67
(m, 1H), 3.41 (q, J = 7.1Hz, 2H), 3.39-3.26 (m, 2H),
2.72-2.62 (m, 2H), 2.33-2.19 (m, 1H), 2.15-1.90
(m, 1H), 1.87-1.24 (m, 10H), 1.07 (t, J = 7.1Hz, 3
H).

Example 49 (184) N-Hydroxy-2 (S)-(benzofuran-3-yl) methyl-5-ethoxymethoxy-4 (S)-[N-
(Trans-4-methylcyclohexylcarbonyl) amino] pentanamide

[Chemical 423] TLC: Rf 0.33 (chloroform: methanol = 1)
9: 1); NMR (d ₆ -DMSO): δ 10.41 (s, 1H), 8.74 (s, 1H),
7.76-7.56 (m, 2H), 7.55-7.38 (m, 2H), 7.37-7.15
(m, 2H), 4.58-4.46 (m, 2H), 4.13-3.90 (m, 1H), 3.5
8-3.30 (m, 4H), 2.92-2.62 (m, 2H), 2.50-2.34 (m, 1
H), 2.12-1.92 (m, 1H), 1.82-1.50 (m, 6H), 1.48-1.1
8 (m, 3H), 1.09 (t, J = 7.0Hz, 3H), 1.00-0.70 (m, 5
H).

Example 49 (185) N-hydroxy-2 (S)-(3-methoxybenzyl)
-5-Ethoxymethoxy-4 (S)-[N- (4-trifluoromethylphenylcarbonyl) amino] pentanamide

[Chemical formula 424] TLC: Rf 0.41 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.34 (s, 1H), 8.67 (s, 1H),
8.39 (d, J = 8.7Hz, 1H), 8.05 (d, J = 8.0Hz, 2H), 7.8
3 (d, J = 8.0Hz, 2H), 7.12 (t, J = 8.4Hz, 1H), 6.72-6.6
8 (m, 3H), 4.57 (s, 2H), 4.32-4.15 (m, 1H), 3.66
(s, 3H), 3.51-3.39 (m, 4H), 2.73 (d, J = 7.0Hz, 2H),
2.41-2.27 (m, 1H), 1.82-1.59 (m, 2H), 1.07 (t, J =
7.0Hz, 3H).

Example 49 (186) N-hydroxy-2 (S)-(1-methylindole-
3-yl) methyl-5- (2-methoxyethoxy) methoxy-4 (S)-[N- (trans-4-methylcyclohexylcarbonyl) amino] pentanamide

[Chemical 425] TLC: Rf 0.33 (chloroform: methanol = 1)
9: 1); NMR (d ₆ -DMSO): δ 10.30 (s, 1H), 8.64 (s, 1H),
7.52 (d, J = 7.8Hz, 1H), 7.42 (d, J = 8.4Hz, 1H), 7.3
2 (d, J = 7.8Hz, 1H), 7.11 (t, J = 7.8Hz, 1H), 6.98 (s,
1H), 6.96 (t, J = 7.8Hz, 1H), 4.58-4.48 (m, 2H), 4.
03-3.92 (m, 1H), 3.70 (s, 3H), 3.51-3.25 (m, 6H),
3.23 (s, 3H), 2.89-2.70 (m, 2H), 2.43-2.34 (m, 1
H), 2.08-1.95 (m, 1H), 1.80-1.48 (m, 6H), 1.47-1.2
0 (m, 3H), 0.96-0.78 (m, 5H).

Example 49 (187) N-hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N-[(1,3-dithian-2-
Ile) carbonyl] amino] pentanamide

[Chemical 426] TLC: Rf 0.39 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.33 (s, 1H), 8.71 (brs, 1)
H), 7.81 (d, J = 8.1Hz, 1H), 7.25-7.08 (m, 5H), 4.51
(s, 2H), 4.41 (s, 1H), 3.47-3.17 (m, 6H), 2.78-2.56
(m, 4H), 2.38-2.27 (m, 1H), 1.98-1.82 (m, 2H),
1.67-1.49 (m, 2H), 1.08 (t, J = 7.0Hz, 3H).

Example 49 (188) N-hydroxy-2 (S)-(3-methoxybenzyl)
-5-Ethoxymethoxy-4 (S)-[N- (4-bromophenylcarbonyl) amino] pentanamide

[Chemical 427] TLC: Rf 0.47 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.34 (s, 1H), 8.68 (brs, 1
H), 8.22 (d, J = 8.7Hz, 1H), 7.81-7.68 (m, 2H), 7.68-
7.64 (m, 2H), 7.12 (t, J = 8.1Hz, 1H), 6.71-6.66 (m,
3H), 4.56 (s, 2H), 4.16-4.27 (m, 1H), 3.66 (s, 3
H), 3.48 (d, J = 5.7Hz, 2H), 3.43 (q, J = 6.9Hz, 2H),
2.71 (d, J = 6.0Hz, 2H), 2.39-2.28 (m, 1H), 1.79-1.59
(m, 2H), 1.07 (t, J = 6.9Hz, 3H).

Example 49 (189) N-hydroxy-2 (S)-(3-methoxybenzyl)
-5-Ethoxymethoxy-4 (S)-[N-[(2-bromothiophen-5-yl) carbonyl] amino] pentanamide

[Chemical 428] TLC: Rf 0.46 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.35 (s, 1H), 8.68 (s, 1H),
8.28 (d, J = 8.7Hz, 1H), 7.62 (d, J = 4.2Hz, 1H), 7.2
6 (d, J = 4.2Hz, 1H), 7.12 (t, J = 7.8Hz, 1H), 6.72-6.6
6 (m, 3H), 4.55 (s, 2H), 4.18-4.05 (m, 1H), 3.68
(s, 3H), 3.49-3.38 (m, 4H), 2.75-2.62 (m, 2H), 2.3
8-2.26 (m, 1H), 1.78-1.58 (m, 2H), 1.07 (t, J = 7.2H
z, 1H).

Example 49 (190) N-hydroxy-2 (S)-(2-methoxybenzyl)
-5-Ethoxymethoxy-4 (S)-[N- (trans-4-methylcyclohexylcarbonyl) amino] pentanamide

[Chemical 429] TLC: Rf 0.30 (chloroform: methanol = 1)
9: 1); NMR (d ₆ -DMSO): δ 10.31 (s, 1H), 8.67 (s, 1H),
7.36 (d, J = 8.0Hz, 1H), 7.21-7.09 (m, 1H), 7.08-7.
00 (m, 1H), 6.89 (d, J = 7.4Hz, 1H), 6.81 (t, J = 7.4H
z, 1H), 4.56-4.48 (m, 2H), 3.90-3.75 (m, 1H), 3.74
(s, 3H), 3.43 (q, J = 7.0Hz, 2H), 3.40-3.24 (m, 2H),
2.80- 2.56 (m, 2H), 2.44-2.28 (m, 1H), 2.09-1.89
(m, 1H), 1.78-1.48 (m, 6H), 1.44-1.17 (m, 3H), 1.1
0 (t, J = 7.0Hz, 3H), 1.00-0.70 (m, 5H).

Example 49 (191) N-hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N-[(2-methylpyridine-5
-Yl) carbonyl] amino] pentanamide

[Chemical 430] TLC: Rf 0.22 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.33 (s, 1H), 8.86 (d, J = 2.
0Hz, 1H), 8.64 (s, 1H), 8.24 (d, J = 8.8Hz, 1H), 8.
06 (dd, J = 8.0Hz, 2.0Hz, 1H), 7.31 (d, J = 8.0Hz, 1
H), 7.26- 7.06 (m, 5H), 4.55 (s, 2H), 4.30-4.12
(m, 1H), 3.50-3.43 (m, 2H), 3.42 (q, J = 7.0Hz, 2H),
2.78- 2.66 (m, 2H), 2.49 (s, 3H), 2.44-2.27 (m, 1
H), 1.83-1.56 (m, 2H), 1.05 (t, J = 7.0Hz, 3H).

Example 49 (192) N-hydroxy-2 (S)-(benzofuran-3-yl) methyl-5-ethoxymethoxy-4 (S)-[N-
(4-Nitrophenylcarbonyl) amino] pentanamide

[Chemical 431] TLC: Rf 0.45 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.43 (s, 1H), 8.71 (brs, 1
H), 8.54 (d, J = 8.4Hz, 1H), 8.31 (d, J = 8.8Hz, 2H),
8.09 (d, J = 8.8Hz, 2H), 7.63-7.60 (m, 1H), 7.49 (d,
J = 7.6Hz, 1H), 7.29-7.13 (m, 2H), 4.55 (s, 2H), 4.
38-4.21 (m, 1H), 3.51 (d, J = 5.6Hz, 2H), 3.42 (q, J
= 7.0Hz, 2H), 2.84 (d, J = 7.4Hz, 2H), 2.40-2.20 (m,
1H), 1.91-1.63 (m, 2H), 1.05 (t, J = 7.0Hz, 3H).

Example 49 (193) N-hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N- (trans-4-hydroxycyclohexylcarbonyl) amino] pentanamide

[Chemical 432] TLC: Rf 0.41 (chloroform: methanol: acetic acid = 9: 1: 0.5); NMR (d ₆ -DMSO): δ 10.29 (s, 1H), 8.62 (brs, 1)
H), 7.42 (d, J = 8.7Hz, 1H), 7.24-7.05 (m, 5H), 4.51
(s, 2H), 3.96- 3.85 (m, 1H), 3.51-3.25 (m, 5H), 2.7
3-2.50 (m, 2H), 2.30-2.19 (m, 1H), 2.03-1.91 (m,
1H), 1.85-1.56 (m, 5H), 1.53-1.24 (m, 3H), 1.13-1.
03 (m, 5H).

Example 49 (194) N-hydroxy-2 (S)-(3-chlorobenzyl)-
5-Ethoxymethoxy-4 (S)-[N- (4-methylphenylcarbonyl) amino] pentanamide

[Chemical 433] TLC: Rf 0.50 (methylene chloride: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.34 (s, 1H), 8.06 (brd, J =
8.8Hz, 1H), 7.77 (d, J = 8.4Hz, 2H), 7.27-7.03 (m, 6
H), 4.57 (s, 2H), 4.23 (m, 1H), 3.50 (m, 2H), 3.44
(q, J = 7.0Hz, 2H), 2.90 (m, 2H), 2.34 (s, 3H), 2.3
4 (m, 1H), 1.80-1.60 (m, 2H), 1.08 (t, J = 7.0Hz, 3
H).

Example 49 (195) N-Hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N-[(2-hydroxypyridin-5-yl) carbonyl] amino] pentanamide

[Chemical 434] TLC: Rf 0.42 (chloroform: methanol: acetic acid = 9: 1: 0.5); NMR (d ₆ -DMSO): δ 11.93 (brs, 1H), 10.32 (s, 1)
H), 7.98 (d, J = 2.4Hz, 1H), 7.90 (d, J = 8.4Hz, 1H),
7.84 (dd, J = 2.4Hz, 8.4Hz, 1H), 7.24-7.06 (m, 5H),
6.31 (d, J = 9.6Hz, 1H), 4.53 (s, 2H), 4.18-4.02 (m,
1H), 3.45-3.33 (m, 4H), 2.75-2.64 (m, 2H), 2.36-
2.25 (m, 1H), 1.73-1.53 (m, 2H), 1.06 (t, J = 7.0Hz,
3H).

Example 49 (196) N-Hydroxy-2 (R)-(3,4,4-trimethyl-2,5-dioxoimidazolidin-1-yl) methyl-5-ethoxymethoxy-4 (S )-[N- (4-Bromophenylcarbonyl) amino] pentanamide

[Chemical 435] TLC: Rf 0.53 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.60 (s, 1H), 8.75 (brs, 1
H), 8.19 (d, J = 7.8Hz, 1H), 7.77-7.74 (m, 2H), 7.66-
7.62 (m, 2H), 4.54 (s, 2H), 4.06-3.96 (m, 1H), 3.50
-3.37 (m, 6H), 2.75 (s, 3H), 2.64-2.51 (m, 1H), 1.
69 (t, J = 7.2Hz, 2H), 1.27 (s, 3H), 1.26 (s, 3H),
1.05 (t, J = 6.9Hz, 3H).

Example 49 (197) N-Hydroxy-2 (S)-(3-methoxybenzyl)
-5-Ethoxymethoxy-4 (S)-[N- (4-dimethoxymethylphenylcarbonyl) amino] pentanamide

[Chemical Formula 436] TLC: Rf 0.50 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.36 (s, 1H), 8.68 (s, 1H),
8.16 (d, J = 8.4Hz, 1H), 7.89 (d, J = 8.2Hz, 2H), 7.4
6 (d, J = 8.2Hz, 2H), 7.13 (t, J = 8.0Hz, 1H), 6.80-6.6
5 (m, 3H), 5.44 (s, 1H), 4.58 (s, 2H), 4.35-4.20
(m, 1H), 3.66 (s, 3H), 3.60-3.35 (m, 4H), 3.25 (s,
6H), 2.74 (d, J = 6.9Hz, 2H), 2.45-2.30 (m, 1H), 1.8
5-1.60 (m, 2H), 1.09 (t, J = 6.9Hz, 3H).

Example 49 (198) N-Hydroxy-2 (S)-(3-trifluoromethyloxybenzyl) -5-ethoxymethoxy-4 (S)-
[N- (4-chlorophenylcarbonyl) amino] pentanamide

[Chemical 437] TLC: Rf 0.38 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.38 (s, 1H), 8.70 (s, 1H),
8.24 (d, J = 8.7Hz, 1H), 7.89 (d, J = 8.7Hz, 2H), 7.5
3 (d, J = 8.7Hz, 2H), 7.36 (t, J = 7.8Hz, 1H), 7.20-7.0
6 (m, 3H), 4.58 (s, 2H), 4.32-4.18 (m, 1H), 3.60-
3.40 (m, 4H), 2.90-2.75 (m, 2H), 2.42-2.30 (m, 1H),
1.85-1.60 (m, 2H), 1.09 (t, J = 7.1Hz, 3H).

Example 49 (199) N-hydroxy-2 (S)-(3-methoxybenzyl)
-5-Ethoxymethoxy-4 (S)-[N- [2-nitrothiophen-5-yl) carbonyl] amino] pentanamide

[Chemical 438] TLC: Rf 0.46 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.38 (s, 1H), 8.73-8.69 (m,
2H), 8.13 (d, J = 4.5Hz, 1H), 7.83 (d, J = 4.5Hz, 1
H), 7.16-7.11 (m, 1H), 6.73-6.67 (m, 3H), 4.56 (s,
2H), 4.18-4.09 (m, 1H), 3.69 (s, 3H), 3.49 (d, J =
8.1Hz, 2H), 3.43 (q, J = 7.2Hz, 2H), 2.79-2.63 (m, 2
H), 2.29-2.40 (m, 1H), 1.80-1.59 (m, 2H), 1.07 (t,
J = 7.2Hz, 3H).

Example 49 (200) N-hydroxy-2 (R)-(benzotriazole-1)
-Yl) methyl-5-ethoxymethoxy-4 (S)-
[N- (4-nitrophenylcarbonyl) amino] pentanamide

[Chemical formula 439] TLC: Rf 0.29 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.52 (s, 1H), 8.62 (d, J = 8.
4Hz, 1H), 8.32 (d, J = 9.0Hz, 2H), 8.08 (d, J = 9.0Hz,
2H), 8.00 (d, J = 8.1Hz, 1H), 7.80 (d, J = 8.1Hz, 1
H), 7.51 (t, J = 8.1Hz, 1H), 7.34 (t, J = 8.1Hz, 1H),
4.88 (dd, J = 14.1Hz, 9.0Hz, 1H), 4.75 (dd, J = 14.1H
z, 5.7Hz, 1H), 4.54 (s, 2H), 4.35-4.24 (m, 1H), 3.5
1 (d, J = 5.1Hz, 2H), 3.41 (q, J = 7.2Hz, 2H), 2.95-2.
86 (m, 1H), 1.86-1.81 (m, 2H), 1.05 (t, J = 7.2Hz, 3
H).

Example 49 (201) N-Hydroxy-2 (R)-(3,4,4-trimethyl-2,5-dioxoimidazolidin-1-yl) methyl-5-ethoxymethoxy-4 (S )-[N- (4-Nitrophenylcarbonyl) amino] pentanamide

[Chemical formula 440] TLC: Rf 0.40 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.63 (s, 1H), 8.76 (s, 1H),
8.47 (d, J = 8.1Hz, 1H), 8.28 (d, J = 8.9Hz, 2H), 8.0
3 (d, J = 8.9Hz, 2H), 4.56 (s, 2H), 4.10-3.98 (m, 1
H), 3.60-3.32 (m, 6H), 2.76 (s, 3H), 2.65-2.50 (m,
1H), 1.80-1.65 (m, 2H), 1.28 (s, 3H), 1.27 (s, 3
H), 1.06 (t, J = 7.2Hz, 3H).

Example 49 (202) N-Hydroxy-2 (R)-(3,4,4-trimethyl-2,5-dioxoimidazolidin-1-yl) methyl-5-ethoxymethoxy-4 (S )-[N- (4-Chlorophenylcarbonyl) amino] pentanamide

[Chemical 441] TLC: Rf 0.40 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.61 (s, 1H), 8.75 (s, 1H),
8.18 (d, J = 8.1Hz, 1H), 7.82 (d, J = 8.6Hz, 2H), 7.5
0 (d, J = 8.6Hz, 2H), 4.55 (s, 2H), 4.10-3.95 (m, 1
H), 3.60-3.35 (m, 6H), 2.76 (s, 3H), 2.65-2.45 (m,
1H), 1.80-1.62 (m, 2H), 1.28 (s, 3H), 1.26 (s, 3
H), 1.06 (t, J = 6.9Hz, 3H).

Example 49 (203) N-hydroxy-2 (S)-(3-phenylpropyl)
-5-methoxymethoxy-4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide

[Chemical 442] TLC: Rf 0.57 (chloroform: methanol = 1)
0: 1); NMR (d ₆ -DMSO): δ 10.44 (1H, brs), 8.72 (1H, b
rs), 8.04 (1H, d, J = 8.1Hz), 7.87 (2H, d, J = 8.8Hz),
7.45-7.40 (2H, m), 7.27-7.12 (6H, m), 7.08-7.04
(2H, m), 7.01 (2H, d, J = 8.8Hz), 4.54 (2H, s), 4.14
-4.03 (1H, m), 3.53-3.42 (2H, m), 3.21 (3H, s), 2.6
0-2.40 (2H, m), 2.16-2.06 (1H, m), 1.78-1.60 (2H,
m), 1.52-1.38 (4H, m).

Example 49 (204) N-hydroxy-2 (S)-(3-phenylpropyl)
-5-methoxymethoxy-4 (S)-[N- [4- [2
E- (4-chlorophenyl) ethenyl] phenylcarbonyl] amino] pentanamide

[Chemical 443] TLC: Rf 0.58 (chloroform: methanol = 1
0: 1); NMR (d ₆ -DMSO): δ 10.46 (1H, brs), 8.74 (1H, b
rs), 8.10 (1H, d, J = 8.7Hz), 7.86 (2H, d, J = 8.3Hz),
7.67 (2H, d, J = 8.3Hz), 7.65 (2H, d, J = 8.8Hz), 7.4
4 (2H, d, J = 8.8Hz), 7.38 (1H, d, J = 16.5Hz), 7.32
(1H, d, J = 16.5Hz), 7.27-7.22 (2H, m), 7.16-7.12 (3
H, m), 4.55 (2H, s), 4.16-4.05 (1H, m), 3.55-3.46
(2H, m), 3.22 (3H, s), 2.59-2.42 (2H, m), 2.17-2.0
7 (1H, m), 1.79-1.62 (2H, m), 1.53-1.41 (4H, m).

Example 49 (205) N-Hydroxy-2 (S)-(3-phenylpropyl)
-5-methoxymethoxy-4 (S)-[N- [4- (4
-Phenyl-1,2,5,6-tetrahydropyridine-
1-yl) phenylcarbonyl] amino] pentanamide

[Chemical 444] TLC: Rf 0.31 (chloroform: methanol = 2
0: 1); NMR (d ₆ -DMSO): δ 10.45 (1H, brs), 8.73 (1H, b
rs), 7.80 (1H, d, J = 8.3Hz), 7.77 (2H, d, J = 9.0Hz),
7.48 (2H, d, J = 7.2Hz), 7.36 (2H, t, J = 7.2Hz), 7.2
8-7.22 (3H, m), 7.16-7.12 (3H, m), 6.98 (2H, d, J =
9.0Hz), 6.29 (1H, brs), 4.54 (2H, s), 4.13-4.02 (1
H, m), 3.94 (2H, s), 3.58 (2H, t, J = 5.7Hz), 3.53-
3.42 (2H, m), 3.21 (3H, s), 2.66-2.58 (2H, m), 2.5
8-2.43 (2H, m), 2.18-2.07 (1H, m), 1.78-1.60 (2H,
m), 1.52-1.40 (4H, m).

Example 49 (206) N-hydroxy-2 (S)-(3-phenyl-2-propenyl) -5-ethoxymethoxy-4 (S)-[N-
(Trans-4-methylcyclohexylcarbonyl) amino] pentanamide

[Chemical formula 445] TLC: Rf 0.41 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.43 (s, 1H), 8.73 (brs, 1)
H), 7.43 (d, J = 8.4Hz, 1H), 7.33-7.24 (m, 4H), 7.20-
7.14 (m, 1H), 6.33 (d, J = 15.9Hz, 1H), 6.08 (dt, J = 1
5.9, 6.9Hz, 1H), 4.53 (s, 2H), 3.90-3.78 (m, 1H),
3.44 (q, J = 7.1Hz, 2H), 3.40-3.31 (m, 2H), 2.31-2.2
2 (m, 2H), 2.19-2.08 (m, 1H), 2.03-1.92 (m, 1H),
1.74-1.58 (m, 5H), 1.56-1.43 (m, 1H), 1.40-1.18
(m, 3H), 1.06 (t, J = 7.1Hz, 3H), 0.91-0.81 (m, 5
H).

Example 49 (207) N-hydroxy-2 (S)-(3-phenylpropyl)
-5-Ethoxymethoxy-4 (S)-[N- (trans-4-methylcyclohexylcarbonyl) amino] pentanamide

[Chemical formula 446] TLC: Rf 0.51 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.40 (s, 1H), 8.65 (brs, 1
H), 7.38 (d, J = 8.4Hz, 1H), 7.26-7.20 (m, 2H), 7.16-
7.08 (m, 3H), 4.53 (s, 2H), 3.83-3.72 (m, 1H), 3.49
-3.27 (m, 4H), 2.58-2.38 (m, 2H), 2.04-1.89 (m, 2
H), 1.77-1.52 (m, 5H), 1.50-1.21 (m, 8H), 1.07 (t,
J = 6.9Hz, 3H), 0.91-0.77 (m, 5H).

Example 49 (208) N-hydroxy-2 (S)-(2-phenylethyl)-
5- (2-methoxyethoxy) methoxy-4 (S)-
[N- (trans-4-methylcyclohexylcarbonyl) amino] pentanamide

[Chemical 447] TLC: Rf 0.34 (chloroform: methanol = 1)
NMR (d ₆ -DMSO): δ 10.45 (s, 1H), 9.20-8.40 (br)
s, 1H), 7.39 (d, J = 8.4Hz, 1H), 7.28-7.23 (m, 2H),
7.20-7.10 (m, 3H), 4.57 (s, 2H). 3.90-3.80 (m, 1H),
3.60-3.20 (m, 6H), 3.22 (s, 3H), 2.60-2.30 (m, 2
H), 2.10-2.00 (m, 1H), 2.05-1.90 (m, 1H), 1.80-1.4
0 (m, 9H), 1.40-1.20 (m, 2H), 0.95-0.75 (m, 2H),
0.84 (d, J = 6.6Hz, 3H).

Example 49 (209) N-hydroxy-2 (S)-(4-phenylbutyl)-
5- (2-methoxyethoxy) methoxy-4 (S)-
[N- (trans-4-methylcyclohexylcarbonyl) amino] pentanamide

[Chemical 448] TLC: Rf 0.36 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.38 (s, 1H), 7.39 (d, J = 8.
4Hz, 1H), 7.30-7.20 (m, 2H), 7.20-7.10 (m, 3H), 4.5
7 (s, 2H), 3.90-3.75 (m, 1H), 3.65-3.15 (m, 6H),
3.22 (s, 3H), 2.60-2.40 (m, 2H), 2.05-1.90 (m, 2
H), 1.85-1.05 (m, 15H), 0.95-0.75 (m, 2H), 0.84
(d, J = 6.3Hz, 3H).

Example 49 (210) N-hydroxy-2 (S)-(3-phenylpropyl)
-5-Ethoxymethoxy-4 (S)-[N- (4-bromophenylcarbonyl) amino] pentanamide

[Chemical 449] TLC: Rf 0.33 (chloroform: methanol = 1)
9: 1); NMR (d ₆ -DMSO): δ 10.44 (s, 1H), 8.72 (s, 1H),
8.16 (d, J = 8.2Hz, 1H), 7.79 (d, J = 8.4Hz, 2H), 7.6
5 (d, J = 8.4Hz, 2H), 7.32-7.08 (m, 5H), 4.59 (s, 2
H), 4.20-3.98 (m, 1H), 3.63-3.40 (m, 4H), 2.68-2.3
8 (m, 2H), 2.20- 2.01 (m, 1H), 1.82-1.61 (m, 2H),
1.60-1.30 (m, 4H), 1.08 (t, J = 7.0Hz, 3H).

Example 49 (211) N-hydroxy-2 (S)-(3-phenylpropyl)
-5-Ethoxymethoxy-4 (S)-[N- (4-nitrophenylcarbonyl) amino] pentanamide

[Chemical 450] TLC: Rf 0.29 (chloroform: methanol = 1
9: 1); NMR (d ₆ -DMSO): δ 10.45 (s, 1H), 8.72 (s, 1H),
8.45 (d, J = 8.4Hz, 1H), 8.29 (d, J = 9.0Hz, 2H),
8.06 (d, J = 9.0Hz, 2H), 7.29-7.20 (m, 2H), 7.19-
7.09 (m, 3H), 4.59 (s, 2H), 4.17-4.01 (m, 1H), 3.5
6-3.40 (m, 4H), 2.61-2.40 (m, 2H), 2.16-2.03 (m, 1
H), 1.80-1.60 (m, 2H), 1.58-1.32 (m, 4H), 1.07 (t,
J = 7.2Hz, 3H).

Example 49 (212) N-hydroxy-2 (R)-(2-phenoxyethyl)
-5-Ethoxymethoxy-4 (S)-[N- (4-nitrophenylcarbonyl) amino] pentanamide

[Chemical 451] TLC: Rf 0.35 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.51 (s, 1H), 8.76 (s, 1H),
8.47 (d, J = 8.4Hz, 1H), 8.29 (d, J = 8.9Hz, 2H), 8.0
7 (d, J = 8.9Hz, 2H), 7.30-7.20 (m, 2H), 6.95-6.80
(m, 3H), 4.59 (s, 2H), 4.25-4.12 (m, 1H), 3.95-3.7
8 (m, 2H), 3.60-3.40 (m, 4H), 2.40-2.25 (m, 1H),
2.00-1.65 (m, 4H), 1.07 (t, J = 7.1Hz, 3H).

Example 49 (213) N-hydroxy-2 (R)-(2-pyridyl) methyl-
5-Methoxymethoxy-4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide

[Chemical 452] TLC: Rf 0.20 (chloroform: methanol = 1)
9: 1); NMR (d ₆ -DMSO): δ 10.44 (1H, s), 8.69 (1H, s),
8.48-8.40 (1H, m), 8.06 (1H, d, J = 8.4Hz), 7.88 (2
H, d, J = 8.8Hz), 7.65 (1H, td, J = 7.8, 1.8Hz), 7.50-
7.38 (2H, m), 7.24- 7.12 (3H, m), 7.11-7.04 (2H,
m), 7.02 (2H, d, J = 8.8Hz), 4.52 (2H, s), 4.23-4.02
(1H, m), 3.49 (2H, d, J = 5.6Hz), 3.19 (3H, s), 2.96
(1H, dd, J = 13.8, 8.4Hz), 2.85 (1H, dd, J = 13.8, 6.
6Hz), 2.75-2.60 (1H, m), 1.77 (2H, t, J = 7.0Hz).

Example 49 (214) N-hydroxy-2 (R)-(2-pyridyl) methyl-
5-Methoxymethoxy-4 (S)-[N- [4- (benzofuran-2-yl) phenylcarbonyl] amino] pentanamide

[Chemical 453] TLC: Rf 0.45 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.70-10.40 (1H, brs), 9.00-
8.60 (1H, brs), 8.50-8.25 (2H, m), 7.99 (4H, s),
7.80-7.44 (4H, m), 7.41-7.06 (4H, m), 4.52 (2H, s),
4.31-4.10 (1H, m), 3.64-3.46 (2H, m), 3.19 (3H,
s), 3.06-2.82 (2H, m), 2.80-2.63 (1H, m), 2.00-1.7
0 (2H, m).

Example 49 (215) N-hydroxy-2 (S)-(3-pyridyl) methyl-
5-Methoxymethoxy-4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide

[Chemical 454] TLC: Rf 0.43 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.36 (1H, s), 8.69 (1H, s),
8.40-8.32 (2H, m), 8.12 (1H, d, J = 9.4Hz), 7.91 (2
H, d, J = 8.8Hz), 7.54-7.38 (3H, m), 7.29-7.17 (2H,
m), 7.12-7.06 (2H, m), 7.03 (2H, d, J = 8.8Hz), 4.56
(2H, s), 4.40-4.20 (1H, m), 3.60-3.42 (2H, m), 3.
22 (3H, s), 2.87 (1H, dd, J = 13.6, 4.8Hz), 2.75 (1
H, dd, J = 13.6, 9.6Hz), 2.43-2.28 (1H, m), 1.90-1.5
9 (2H, m).

Example 49 (216) N-hydroxy-2 (S)-(3-pyridyl) methyl-
5-methoxymethoxy-4 (S)-[N- [4- [2-
(4-Methylphenyl) ethynyl] phenylcarbonyl] amino] pentanamide

[Chemical 455] TLC: Rf 0.40 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.37 (1H, s), 8.70 (1H, s),
8.40-8.33 (2H, m), 8.29 (1H, d, J = 8.0Hz), 7.92 (2
H, d, J = 8.4Hz), 7.63 (2H, d, J = 8.4Hz), 7.57-7.42
(3H, m), 7.31- 7.20 (3H, m), 4.56 (2H, s), 4.40-4.
20 (1H, m), 3.62-3.44 (2H, m), 3.22 (3H, s), 2.87
(1H, dd, J = 13.6, 4.8Hz), 2.76 (1H, dd, J = 13.6, 9.2
Hz), 2.42-2.26 (4H, m), 1.91-1.59 (2H, m).

Example 49 (217) N-hydroxy-2 (S)-(3-pyridyl) methyl-
5-methoxymethoxy-4 (S)-[N- [4- (1-
Heptinyl) phenylcarbonyl] amino] pentanamide

[Chemical 456] TLC: Rf 0.34 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1); NMR (d ₆ -DMSO): δ 10.35 (1H, brs), 8.69 (1H, br
s), 8.37-8.33 (2H, m), 8.23 (1H, d, J = 8.4Hz), 7.83 (2
H, d, J = 8.0Hz), 7.51-7.43 (3H, m), 7.25 (1H, dd, J = 7.
8Hz, 4.8Hz), 4.54 (2H, s), 4.38-4.15 (1H, m), 3.50 (2
H, d, J = 5.4Hz), 3.20 (3H, s), 2.92-2.68 (2H, m), 2.
49-2.39 (1H, m), 1.91-1.20 (10H, m), 0.88 (3H, t, J =
7.0Hz).

Example 49 (218) N-hydroxy-2 (S)-(3-pyridyl) methyl-
5-methoxymethoxy-4 (S)-[N- [4- [2E
-(4-Chlorophenyl) ethenyl] phenylcarbonyl] amino] pentanamide

[Chemical 457] TLC: Rf 0.26 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1); NMR (d ₆ -DMSO): δ 10.40 (1H, brs), 8.72 (1H, br
s), 8.35 (2H, s), 8.21 (1H, d, J = 8.7Hz), 7.89 (2H, d,
J = 8.4Hz), 7.68 (2H, d, 8.4Hz), 7.65 (2H, d, J = 8.7H
z), 7.51 (1H, d, J = 7.2Hz), 7.44 (2H, d, J = 8.7Hz), 7.
39 (1H, d, J = 16.8Hz), 7.32 (1H, d, J = 16.8Hz), 7.27-
7.23 (1H, m), 4.55 (2H, s), 4.39-4.21 (1H, m), 3.61-
3.42 (2H, m), 3.21 (3H, s), 2.91-2.69 (2H, m), 2.45-
2.31 (1H, m), 1.91-1.60 (2H, m).

Example 49 (219) N-hydroxy-2 (S)-(3-pyridyl) methyl-
5-methoxymethoxy-4 (S)-[N- (trans-
4-Methylcyclohexylcarbonyl) amino] pentanamide

[Chemical formula 458] TLC: Rf 0.34 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.34 (1H, brs), 8.72 (1H, b
rs), 8.36 (1H, dd, J = 4.8, 1.5Hz), 8.32-8.30 (1H,
m), 7.52-7.45 (2H, m), 7.29-7.22 (1H, m), 4.51 (2
H, s), 4.05-3.93 (1H, m), 3.44-3.35 (2H, m), 3.22
(3H, s), 2.77 (1H, dd, J = 13.2, 4.8Hz), 2.69 (1H, d
d, J = 13.2, 9.6Hz), 2.35-2.22 (1H, m), 2.10-1.97 (1
H, m), 1.82-1.61 (5H, m), 1.60-1.44 (1H, m), 1.43-
1.20 (3H, m), 0.97-0.79 (5H, m).

Example 49 (220) N-hydroxy-2 (S)-(4-pyridyl) methyl-
5-Methoxymethoxy-4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide

[Chemical 459] TLC: Rf 0.27 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.44-10.30 (1H, brs), 8.75-
8.62 (1H, brs), 8.40 (2H, d, J = 6.0Hz), 8.13 (1H, d,
J = 8.4Hz), 7.91 (2H, d, J = 8.7Hz), 7.48-7.38 (2H,
m), 7.22-7.18 (1H, m), 7.13 (2H, d, J = 6.0Hz), 7.06
(2H, d, J = 7.8Hz), 7.02 (2H, d, J = 8.7Hz), 4.55 (2
H, s), 4.34-4.21 (1H, m), 3.58-3.42 (2H, m), 3.22
(3H, s), 2.91-2.71 (2H, m), 2.46-2.32 (1H, m), 1.8
5-1.61 (2H, m).

Example 49 (221) N-hydroxy-2 (R)-(2-pyridyl) methyl-
5- (2-methoxyethoxy) methoxy-4 (S)-
[N- (4-phenoxyphenylcarbonyl) amino]
Pentanamide

[Chemical 460] TLC: Rf 0.38 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1); NMR (d ₆ -DMSO): δ 10.43 (1H, s), 8.69 (1H, s),
8.45 (1H, d, J = 4.5Hz), 8.60 (1H, d, J = 8.4Hz), 7.87 (2
H, d, J = 8.4Hz), 7.65 (1H, t, J = 7.5Hz), 7.42 (2H, t,
J = 8.1Hz), 7.21-7.15 (3H, m), 7.08-7.00 (4H, m), 4.58
(2H, s), 4.06-4.22 (1H, m), 3.43-3.60 (4H, m), 3.42
-3.38 (2H, m), 3.20 (3H, s), 2.98-2.81 (2H, m), 2.61-
2.78 (1H, m), 1.75 (2H, t, J = 7.2Hz).

Example 49 (222) N-hydroxy-2 (S)-(3-pyridyl) methyl-
5-Ethoxymethoxy-4 (S)-[N- (2-methylphenylcarbonyl) amino] pentanamide

[Chemical 461] TLC: Rf 0.38 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO + CD ₃ OD (5 drops)): δ 8.36-8.32 (m,
2H), 7.50 (d, J = 7.5Hz, 1H), 7.34 (d, J = 7.5Hz, 1
H), 7.31-7.14 (m, 4H), 4.59 (2H, s), 4.26-4.16 (m,
1H), 3.52-3.43 (m, 4H), 2.87- 2.69 (m, 2H), 2.43
-2.34 (m, 1H), 2.31 (s, 3H), 1.77-1.57 (m, 2H), 1.
09 (t, J = 6.9Hz, 3H).

Example 49 (223) N-hydroxy-2 (S)-(3-pyridyl) methyl-
5-Ethoxymethoxy-4 (S)-[N- (3-methylphenylcarbonyl) amino] pentanamide

[Chemical 462] TLC: Rf 0.38 (chloroform: methanol = 9:
1); NMR (CD ₃ OD): δ 8.44-8.37 (m, 2H), 7.75-7.66
(m, 3H), 7.42-7.34 (m, 3H), 4.73 (s, 2H), 4.52-4.4
1 (m, 1H), 3.71- 3.57 (m, 4H), 3.13-2.88 (m, 2H),
2.55-2.42 (m, 4H), 2.06-1.90 (m, 2H), 1.21 (t, J = 7
.2Hz, 3H).

Example 49 (224 ) N-hydroxy-2 (S)-(3-pyridyl) methyl-
5-Ethoxymethoxy-4 (S)-[N- (4-methylphenylcarbonyl) amino] pentanamide

[Chemical 463] TLC: Rf 0.38 (chloroform: methanol = 9:
1); NMR (CD ₃ OD + d ₆ -DMSO (5 drops)): δ 8.46-8.42 (m,
2H), 7.84 (d, J = 8.4Hz, 2H), 7.72 (d, J = 7.8Hz, 1
H), 7.42-7.33 (m, 3H), 4.75 (s, 2H), 4.53-4.44 (m,
1H), 3.71-3.59 (m, 4H), 3.13- 2.88 (m, 2H), 2.57-
2.45 (m, 4H), 2.09-1.88 (m, 2H), 1.23 (t, J = 7.2Hz,
3H).

Example 49 (225) N-hydroxy-2 (S)-(3-pyridyl) methyl-
5-Ethoxymethoxy-4 (S)-[N- (4-methoxyphenylcarbonyl) amino] pentanamide

[Chemical 464] TLC: Rf 0.30 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.35 (s, 1H), 8.68 (s, 1H),
8.40-8.30 (m, 2H), 8.00 (d, J = 8.8Hz, 1H), 7.86 (d,
J = 8.8Hz, 2H), 7.53-7.44 (m, 1H), 7.28-7.20 (m, 1
H), 6.99 (d, J = 8.8Hz, 2H), 4.59 (s, 2H), 4.38-4.17
(m, 1H), 3.81 (s, 3H), 3.60-3.40 (m, 4H), 2.86 (d
d, J = 13.2, 5.2Hz, 1H), 2.74 (dd, J = 13.2, 9.2Hz, 1
H), 2.44-2.28 (m, 1H), 1.90-1.58 (m, 2H), 1.09 (t,
J = 6.8Hz, 3H).

Example 49 (226) N-hydroxy-2 (S)-(3-pyridyl) methyl-
5-ethoxymethoxy-4 (S)-(N-cyclohexylcarbonylamino) pentanamide

[Chemical 465] TLC: Rf 0.21 (chloroform: methanol = 1
0: 1); NMR (d ₆ -DMSO): δ 10.33 (brs, 1H), 8.70 (brs,
1H), 8.36 (dd, J = 1.8, 4.5Hz, 1H), 8.30 (d, J = 1.8H
z, 1H), 7.48-7.45 (m, 2H), 7.26 (dd, J = 4.5,7.6Hz,
1H), 4.55 (s, 2H), 4.40-3.51 (m, 1H), 3.45 (q, J =
7.2Hz, 2H), 3.83-3.32 (m, 2H), 2.80-2.63 (m, 2H),
2.32-2.21 (m, 1H), 2.14-2.03 (m, 1H), 1.78-1.45 (m,
7H), 1.40-1.06 (m, 5H), 1.10 (t, J = 6.9Hz, 3H).

Example 49 (227) N-hydroxy-2 (S)-(3-pyridyl) methyl-
5-Ethoxymethoxy-4 (S)-[N- (4-nitrophenylcarbonyl) amino] pentanamide

[Chemical 466] TLC: Rf 0.22 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.36 (s, 1H), 8.69 (s, 1H),
8.53 (d, J = 8.7Hz, 1H), 8.37-8.29 (m, 3H), 8.10-8.
06 (m, 2H), 7.52-7.48 (m, 1H), 7.28-7.23 (m, 1H),
4.58 (s, 2H), 4.21-4.32, (m, 1H), 3.52 (d, J = 5.7H
z, 2H), 3.45 (q, J = 7.2Hz, 2H), 2.86-2.69 (m, 2H),
2.42-2.23 (m, 1H), 1.85-1.62 (m 2H), 1.08 (t, J =
7.2Hz, 3H).

Example 49 (228) N-hydroxy-2 (S)-(3-pyridyl) methyl-
5-Ethoxymethoxy-4 (S)-[N- (4-bromophenylcarbonyl) amino] pentanamide

Embedded image TLC: Rf 0.32 (chloroform: methanol: acetic acid = 90: 10: 1); NMR (d ₆ -DMSO): δ 10.34 (s, 1H), 8.68 (s, 1H),
8.37-8.24 (m, 3H), 7.80 (d, J = 8.7Hz, 2H), 7.67 (d,
J = 8.7Hz, 2H), 7.49 (dt, J = 8.1Hz, 1.8Hz, 1H), 4.57
(s, 2H), 4.31-4.18 (m, 1H), 3.50 (d, J = 6.0Hz, 2H),
3.45 (q, J = 7.2Hz, 2H), 2.87-2.68 (m, 2H), 2.40-2.
24 (m, 1H), 1.82-1.59 (m, 2H), 1.07 (t, J = 7.2Hz, 3
H).

Example 49 (229) N-hydroxy-2 (S)-(3-quinolyl) methyl-
5-ethoxymethoxy-4 (S)-[N- (trans-
4-Methylcyclohexylcarbonyl) amino] pentanamide

[Chemical 468] TLC: Rf 0.37 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.31 (s, 1H), 8.67-8.65 (m,
2H), 7.98-7.83 (m, 3H), 7.73-7.49 (m, 3H), 4.55
(s, 2H), 4.13-3.97 (m, 1H), 3.43 (q, J = 7.0Hz, 2H),
3.42-3.36 (m, 2H), 3.06-2.80 (m, 2H), 2.48-2.30
(m, 1H), 2.15-1.98 (m, 1H), 1.81-1.26 (m 9H), 1.08
(t, J = 7.0Hz, 3H), 0.99-0.79 (m, 2H), 0.85 (d, J = 7.
0Hz, 3H).

Example 49 (230) N-Hydroxy-2 (S) -phenylthio-5-methoxymethoxy-4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide

Embedded image TLC: Rf 0.27 (chloroform: methanol: acetic acid = 100: 5: 1); NMR (d ₆ -DMSO): δ 10.69 (1H, s), 8.97 (1H, s),
8.17 (1H, d, J = 8.0Hz), 7.86 (2H, d, J = 8.8Hz), 7.47-7.
39 (4H, m), 7.34-7.16 (4H, m), 7.08-6.99 (4H, m), 4.53
(2H, s), 4.38-4.25 (1H, m), 3.62-3.35 (3H, m), 3.19
(3H, s), 2.02 (2H, t, J = 6.8Hz).

Example 49 (231) N-hydroxy-2 (S) -phenylthio-5-ethoxymethoxy-4 (S)-[N- (trans-4-methylcyclohexylcarbonyl) amino] pentanamide

[Chemical 470] TLC: Rf 0.37 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.67 (s, 1H), 8.94 (brs, 1
H), 7.52 (d, J = 8.1Hz, 1H), 7.38-7.22 (m, 5H), 4.52
(s, 2H), 4.04-3.93 (m, 1H), 3.52-3.24 (m, 5H), 2.01
-1.78 (m, 3H), 1.69-1.55 (m, 4H), 1.36-1.19 (m, 3
H), 1.07 (t, J = 7.0Hz, 3H), 0.91-0.75 (m, 5H).

Example 49 (232) N-hydroxy-2 (S) -methylthio-5-ethoxymethoxy-4 (S)-[N- (trans-4-methylcyclohexylcarbonyl) amino] pentanamide

[Chemical 471] TLC: Rf 0.38 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.56 (s, 1H), 8.88 (s, 1H),
7.48 (d, J = 8.4Hz, 1H), 4.55 (s, 2H), 4.04-3.90
(m, 1H), 3.46 (q, J = 7.1Hz, 2H), 3.39-3.25 (m, 2H),
2.96-2.87 (m, 1H), 2.04-1.91 (m, 4H), 1.90-1.77
(m, 1H), 1.76-1.55 (m, 5H), 1.40-1.18 (m, 3H), 1.0
8 (t, J = 7.1Hz, 3H), 0.92-0.74 (m, 5H).

Example 49 (233) N-hydroxy-2 (S)-(4-pyridyl) thio-5
-Ethoxymethoxy-4 (S)-[N- (trans-4
-Methylcyclohexylcarbonyl) amino] pentanamide

[Chemical 472] TLC: Rf 0.29 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.87 (s, 1H), 9.08 (s, 1H),
8.35 (d, J = 6.0Hz, 2H), 7.58 (d, J = 8.1Hz, 1H), 7.2
7 (d, J = 6.0Hz, 2H), 4.56 (s, 2H), 3.99-3.88 (m, 1
H), 3.78 (t, J = 7.4Hz, 1H), 3.45 (q, J = 7.2Hz, 2H),
3.42-3.31 (m, 2H), 2.02-1.87 (m, 3H), 1.71-1.56
(m, 4H), 1.35-1.17 (m, 3H), 1.07 (t, J = 7.2Hz, 3H),
0.91-0.76 (m, 5H).

Examples 49 (234) to 49 (253) Examples 44 (8), 44 (9), 44 (11), 44
(14), 44 (17) to 44 (21), 44 (24)
~ 44 (26) or the corresponding compound in place of the compound prepared in Reference Example 4, using Example 37 → Example 39 → Example 41 → Example 43 (instead of benzyl bromide , The corresponding compound is used.) → The compound obtained by the same operation as in the method shown in Example 44 was operated in the same manner as in the method shown in Example 49 to obtain the compound shown below. .

Example 49 (234) N-hydroxy-2 (S) -hydroxy-5-methoxymethoxy-4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide

[Chemical 473] TLC: Rf 0.57 (chloroform: methanol: acetic acid = 85: 15: 1); NMR (d ₆ -DMSO): δ 10.44 (1H, s), 8.69 (1H, brs),
8.19 (1H, d, J = 8.4Hz), 8.89 (2H, d, J = 8.8Hz), 7.48-
7.38 (2H, m), 7.22-7.16 (1H, m), 7.09-7.01 (4H, m),
5.36 (1H, brs), 4.55 (2H, s), 4.41-4.24 (1H, m), 3.87
(1H, dd, J = 9.8Hz, 2.6Hz), 3.56-3.42 (2H, m), 3.22 (3
H, s), 1.96-1.66 (2H, m).

Example 49 (235) N-hydroxy-2 (R) -hydroxymethyl-5-ethoxymethoxy-4 (S)-[N- (4-chlorophenylcarbonyl) amino] pentanamide

[Chemical 474] TLC: Rf 0.23 (chloroform: methanol: acetic acid = 90: 10: 1); NMR (d ₆ -DMSO): δ 10.55-10.10 (brs, 1H), 8.90-
8.50 (brs, 1H), 8.21 (d, J = 8.4Hz, 1H), 7.86 (d, J =
8.7Hz, 2H), 7.52 (d, J = 8.7Hz, 2H), 4.59 (s, 2H),
4.20-4.00 (m, 1H), 3.60-3.38 (m, 6H), 2.30-2.18
(m, 1H), 1.85-1.70 (m, 1H), 1.70-1.55 (m, 1H), 1.0
9 (t, J = 7.1Hz, 3H).

Example 49 (236) N-hydroxy-2 (R) -methoxymethyl-5-ethoxymethoxy-4 (S)-[N- (4-nitrophenylcarbonyl) amino] pentanamide

[Chemical 475] TLC: Rf 0.22 (chloroform: methanol = 1)
9: 1); NMR (d ₆ -DMSO): δ 10.46 (s, 1H), 8.75 (s, 1H),
8.48 (d, J = 8.4Hz, 1H), 8.29 (d, J = 8.8Hz, 2H), 8.0
6 (d, J = 8.8Hz, 2H), 4.59 (s, 2H), 4.22-4.00 (m, 1
H), 3.58-3.25 (m, 6H), 3.18 (s, 3H), 2.43-2.31 (m,
1H), 1.83-1.54 (m, 2H), 1.08 (t, J = 7.0Hz, 3H).

Example 49 (237) N-hydroxy-2 (R) -benzyloxymethyl-5
-Ethoxymethoxy-4 (S)-[N- (4-nitrophenylcarbonyl) amino] pentanamide

[Chemical 476] TLC: Rf 0.35 (chloroform: methanol = 1)
9: 1); NMR (d ₆ -DMSO): δ 10.52 (s, 1H), 8.79 (s, 1H),
8.50 (d, J = 8.7Hz, 1H), 8.30 (d, J = 8.7Hz, 2H), 8.0
7 (d, J = 8.7Hz, 2H), 7.40-7.22 (m, 5H), 4.60 (s, 2
H), 4.47 (d, J = 12.0Hz, 1H), 4.41 (d, J = 12.0Hz, 1
H), 4.20-4.07 (m, 1H), 3.61-3.42 (m, 6H), 2.53-2.40
(m, 1H), 1.89-1.78 (m, 1H), 1.77-1.62 (m, 1H), 1.0
8 (t, J = 7.2Hz, 3H).

Example 49 (238) N-hydroxy-2 (R)-(2-methoxyethoxy)
Methyl-5-ethoxymethoxy-4 (S)-[N- (4
-Nitrophenylcarbonyl) amino] pentanamide

[Chemical formula 477] TLC: Rf 0.24 (chloroform: methanol = 1
9: 1); NMR (d ₆ -DMSO): δ 10.47 (s, 1H), 8.77 (s, 1H),
8.49 (d, J = 8.1Hz, 1H), 8.30 (d, J = 8.7Hz, 2H),
8.08 (d, J = 8.7Hz, 2H), 4.61 (s, 2H), 4.20-4.07
(m, 1H), 3.58-3.38 (m, 10H), 3.23 (s, 3H), 2.47-2.
36 (m, 1H), 1.83-1.58 (m, 2H), 1.10 (t, J = 7.2Hz,
3H).

Example 49 (239) N-hydroxy-2 (R) -methoxymethyl-5- (2
-Methoxyethoxy) methoxy-4 (S)-[N- (4
-Cyanophenylcarbonyl) amino] pentanamide

[Chemical 478] TLC: Rf 0.26 (chloroform: methanol = 1)
9: 1); NMR (d ₆ -DMSO): δ 10.45 (s, 1H), 8.74 (s, 1H),
8.40 (d, J = 8.4Hz, 1H), 7.98 (d, J = 8.8Hz, 2H),
7.93 (d, J = 8.8Hz, 2H), 4.61 (s, 2H), 4.20-4.00
(m, 1H), 3.60-3.24 (m, 8H), 3.20 (s, 3H), 3.17 (s,
3H), 2.43-2.29 (m, 1H), 1.82-1.50 (m, 2H).

Example 49 (240) N-Hydroxy-2 (R) -methoxymethyl-5-ethoxymethoxy-4 (S)-[N- (trans-4-methylcyclohexylcarbonyl) amino] pentanamide

[Chemical 479] TLC: Rf 0.27 (chloroform: methanol = 1
9: 1); NMR (d ₆ -DMSO): δ 10.41 (s, 1H), 8.75 (s, 1H),
7.43 (d, J = 8.7Hz, 1H), 4.56 (s, 2H), 3.86-3.72
(m, 1H), 3.47 (q, J = 7.2Hz, 2H), 3.41-3.20 (m, 4H),
3.15 (s, 3H), 2.36- 2.24 (m, 1H), 2.05-1.93 (m, 1
H), 1.77-1.56 (m, 5H), 1.49-1.18 (m, 4H), 1.10 (t,
J = 7.2Hz, 3H), 0.95- 0.77 (m, 5H).

Example 49 (241) N-hydroxy-2 (R) -methoxymethyl-5-ethoxymethoxy-4 (S)-[N- (4-bromophenylcarbonyl) amino] pentanamide

[Chemical 480] TLC: Rf 0.31 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.43 (s, 1H), 8.74 (brs, 1
H), 8.21 (d, J = 8.4Hz, 1H), 7.78 (d, J = 8.7Hz, 2H),
7.66 (d, J = 8.7Hz, 2H), 4.58 (s, 2H), 4.13-4.01 (m,
1H), 3.50-3.31 (m, 6H), 3.16 (s, 3H), 2.42-2.12
(m, 1H), 1.79-1.53 (m, 2H), 1.07 (t, J = 7.2Hz, 3
H).

Example 49 (242) N-hydroxy-2 (R) -methoxymethyl-5-ethoxymethoxy-4 (S)-[N- (4-chlorophenylcarbonyl) amino] pentanamide

[Chemical 481] TLC: Rf 0.31 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.44 (s, 1H), 8.74 (s, 1H),
8.21 (d, J = 8.4Hz, 1H), 7.76 (d, J = 8.7Hz, 2H), 7.5
2 (d, J = 8.7Hz, 2H), 4.58 (s, 2H), 4.16-4.02 (m, 1
H), 3.50-3.33 (m, 6H), 3.16 (s, 3H), 2.42-2.32 (m,
1H), 1.79-1.55 (m, 2H), 1.07 (t, J = 7.2Hz, 3H).

Example 49 (243) N-hydroxy-2 (R) -benzyloxymethyl-5
-(2-Methoxyethoxy) methoxy-4 (S)-[N
-(4-Cyanophenylcarbonyl) amino] pentanamide

[Chemical 482] TLC: Rf 0.30 (methylene chloride: methanol = 1
9: 1); NMR (d ₆ -DMSO): δ 10.49 (d, J = 1.5Hz, 1H), 8.
77 (d, J = 1.5Hz, 1H), 8.41 (d, J = 8.4Hz, 1H), 7.
98 (d, J = 8.7Hz, 2H), 7.94 (d, J = 8.7Hz, 2H), 7.2
9 (m, 5H), 4.60 (s, 2H), 4.45 (d, J = 12.0Hz, 1H),
4.39 (d, J = 12.0Hz, 1H), 4.10 (m, 1H), 3.60-3.36
(m, 8H), 3.18 (s, 3H), 2.45 (m, 1H), 1.78 (m, 1H),
1.63 (m, 1H).

Example 49 (244) N-hydroxy-2 (R) -benzyloxymethyl-5
-Ethoxymethoxy-4 (S)-[N- (4-chlorophenylcarbonyl) amino] pentanamide

[Chemical 483] TLC: Rf 0.32 (methylene chloride: methanol = 1
9: 1); NMR (d ₆ -DMSO): δ 10.48 (s, 1H), 8.76 (s, 1H),
8.22 (d, J = 8.4Hz, 1H), 7.85 (d, J = 8.7Hz, 2H),
7.52 (d, J = 8.7Hz, 2H), 7.29 (m, 5H), 4.57 (s, 2
H), 4.44 (d, J = 12.0Hz, 1H), 4.39 (d, J = 12.0Hz,
1H), 4.08 (m, 1H), 3.55-3.40 (m, 6H), 2.45 (m, 1
H), 1.78 (m, 1H), 1.62 (m, 1H), 1.05 (t, J = 7.2Hz,
3H).

Example 49 (245) N-hydroxy-2 (R) -benzyloxymethyl-5
-Ethoxymethoxy-4 (S)-[N- (4-bromophenylcarbonyl) amino] pentanamide

[Chemical 484] TLC: Rf 0.32 (methylene chloride: methanol = 1
9: 1); NMR (d ₆ -DMSO): δ 10.49 (d, J = 1.8Hz, 1H), 8.
77 (d, J = 1.8Hz, 1H), 8.22 (d, J = 8.4Hz, 1H), 7.
78 (d, J = 8.7Hz, 2H), 7.66 (d, J = 8.7Hz, 2H), 7.2
9 (m, 5H), 4.57 (s, 2H), 4.44 (d, J = 12.0Hz, 1H),
4.39 (d, J = 12.0Hz, 1H), 4.08 (m, 1H), 3.55-3.40
(m, 6H), 2.45 (m, 1H), 1.78 (m, 1H), 1.62 (m, 1H),
1.05 (t, J = 7.2Hz, 3H).

Example 49 (246) N-hydroxy-2 (R)-[2- (3-methoxyphenoxy) ethyl] -5-ethoxymethoxy-4 (S)-
[N- (4-nitrophenylcarbonyl) amino] pentanamide

[Chemical 485] TLC: Rf 0.40 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.50 (s, 1H), 8.76 (s, 1H),
8.48 (d, J = 8.4Hz, 1H), 8.30 (d, J = 8.6Hz, 2H), 8.0
6 (d, J = 8.6Hz, 2H), 7.13 (t, J = 8.3Hz, 1H), 6.52-6.3
5 (m, 3H), 4.59 (s, 2H), 4.25-4.12 (m, 1H), 3.95-
3.75 (m, 2H), 3.68 (s, 3H), 3.60-3.40 (m, 4H), 2.40
-2.25 (m, 1H), 2.00-1.65 (m, 4H), 1.07 (t, J = 7.1H
z, 3H).

Example 49 (247) N-hydroxy-2 (R) -methoxymethyl-5-ethoxymethoxy-4 (S)-[N-[(2-nitrothiophen-5-yl) carbonyl] amino] pentane Amide

[Chemical 486] TLC: Rf 0.37 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.46 (s, 1H), 8.75 (brs, 1
H), 8.71 (d, J = 8.4Hz, 1H), 8.13 (d, J = 4.2Hz, 1H),
7.82 (d, J = 4.2Hz, 1H), 4.58 (s, 2H), 3.97-4.09 (m,
1H), 3.50-3.38 (m, 6H), 3.17 (s, 3H), 2.41-2.32
(m, 1H), 1.79-1.55 (m, 2H), 1.07 (t, J = 7.2Hz, 3
H).

Example 49 (248) N-Hydroxy-2 (R) -methoxymethyl-5-ethoxymethoxy-4 (S)-[N-[(2-bromothiophen-5-yl) carbonyl] amino] pentane Amide

[Chemical 487] TLC: Rf 0.34 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.44 (s, 1H), 8.75 (s, 1H),
8.27 (d, J = 8.1Hz, 1H), 7.61 (d, J = 4.2Hz, 1H), 7.2
7 (d, J = 4.2Hz, 1H), 4.57 (s, 2H), 4.05-3.91 (m, 1
H), 3.50-3.37 (m, 6H), 3.16 (s, 3H), 2.41-2.31 (m,
1H), 1.78-1.51 (m, 2H), 1.07 (t, J = 7.2Hz, 3H).

Example 49 (249) N-hydroxy-2 (R)-(2-methoxyethoxy)
Methyl-5-ethoxymethoxy-4 (S)-[N- (4
-Bromophenylcarbonyl) amino] pentanamide

[Chemical 488] TLC: Rf 0.31 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.43 (s, 1H), 8.74 (s, 1H),
8.20 (d, J = 8.6Hz, 1H), 7.78 (d, J = 8.6Hz, 2H), 7.6
5 (d, J = 8.6Hz, 2H), 4.58 (s, 2H), 4.18-4.01 (m, 1
H), 3.50-3.36 (m, 10H), 3.20 (s, 3H), 2.44-2.39
(m, 1H), 1.81-1.52 (m, 2H), 1.07 (t, J = 7.0Hz, 3
H).

Example 49 (250) N-hydroxy-2 (R)-(2-methoxyethoxy)
Methyl-5- (2-methoxyethoxy) methoxy-4
(S)-[N- (4-cyanophenylcarbonyl) amino] pentanamide

Embedded image TLC: Rf 0.24 (chloroform: methanol = 1
9: 1); NMR (d ₆ -DMSO): δ 10.45 (brs, 1H), 8.78 (brs,
1H), 8.43 (d, J = 8.1Hz, 1H), 7.99 (d, J = 8.4Hz, 2H),
7.94 (d, J = 8.4Hz, 2H), 4.61 (s, 2H), 4.16-4.02
(m, 1H), 3.57-3.35 (m, 12H), 3.21 (s, 3H), 3.20
(s, 3H), 2.42-2.32 (m, 1H), 1.80-1.56 (m, 2H).

Example 49 (251) N-hydroxy-2 (R)-(2-methoxyethoxy)
Methyl-5-ethoxymethoxy-4 (S)-[N- (4
-Chlorophenylcarbonyl) amino] pentanamide

[Chemical 490] TLC: Rf 0.34 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.43 (s, 1H), 8.74 (brs, 1
H), 8.20 (d, J = 8.4Hz, 1H), 7.87-7.83 (m, 2H), 7.54-
7.49 (m, 2H) 4.58 (s, 2H), 4.18-4.10 (m, 1H), 3.52
-3.36 (m, 10H), 3.20 (s, 3H), 2.42-2.29 (m, 1H),
1.81-1.53 (m, 2H), 1.07 (t, J = 7.0Hz, 3H).

Example 49 (252) N-hydroxy-2 (R) -benzyloxymethyl-5
-Ethoxymethoxy-4 (S)-[N- (trans-4
-Methylcyclohexylcarbonyl) amino] pentanamide

[Chemical formula 491] TLC: Rf 0.34 (chloroform: methanol = 1)
9: 1); NMR (d ₆ -DMSO): δ 10.46 (s, 1H), 8.78 (s, 1H),
7.44 (d, J = 8.4Hz, 1H), 7.38-7.21 (m, 5H), 4.59-4.
52 (m, 2H), 4.43 (d, J = 12.0Hz, 1H), 4.37 (d, J = 12.
0Hz, 1H), 3.85-3.72 (m, 1H), 3.54-3.28 (m, 6H), 2.
43-2.30 (m, 1H), 2.06-1.92 (m, 1H), 1.76-1.59 (m, 5
H), 1.52-1.20 (m, 4H), 1.09 (t, J = 6.9Hz, 3H), 0.93-
0.75 (m, 5H).

Example 49 (253) N-hydroxy-2 (R)-(3-thienyl) methoxymethyl-5-ethoxymethoxy-4 (S)-[N- (4
-Nitrophenylcarbonyl) amino] pentanamide

[Chemical 492] TLC: Rf 0.34 (chloroform: methanol = 1)
9: 1); NMR (d ₆ -DMSO): δ 10.49 (s, 1H), 8.76 (s, 1H),
8.49 (d, J = 8.4Hz, 1H), 8.30 (d, J = 8.8Hz, 2H), 8.0
6 (d, J = 8.8Hz, 2H), 7.49 (dd, J = 5.2, 2.8Hz, 1H),
7.40-7.36 (m, 1H), 7.03 (dd, J = 5.2, 1.6Hz, 1H), 4.
59 (s, 2H), 4.50-4.36 (m, 2H), 4.21-4.00 (m, 1H),
3.60-3.36 (m, 6H), 2.52-2.38 (m, 1H), 1.88-1.56 (m,
2H), 1.07 (t, J = 7.0Hz, 3H).

Examples 49 (254) to 49 (263) Using the corresponding compounds in place of the compounds prepared in Reference Example 4, Example 37 → Example 39 → Example 45 → Example 46 (benzyl bromide) The corresponding compound is used instead of.) → Example 47 → Example 48 → The same operation as the method shown in Example 49 is carried out to obtain the compound shown below.

Example 49 (254) N-Hydroxy-2 (R)-(2-pyridinyl) methyl-5-hydroxy-4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide

[Chemical 493] TLC: Rf 0.17 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1); NMR (d ₆ -DMSO): δ 10.35 (1H, brs), 8.63 (1H, br
s), 8.42-8.40 (1H, m), 7.91-7.86 (3H, m), 7.64 (1H, d
t, J = 7.8Hz, 1.8Hz), 7.45-7.39 (2H, m), 7.25-7.14 (3
H, m), 7.07-7.00 (4H, m), 4.67 (1H, brs), 4.15-3.94
(1H, m), 3.50-3.34 (2H, m), 2.97-2.81 (2H, m), 2.71-
2.62 (1H, m), 1.82-1.65 (2H, m).

Example 49 (255) N-Hydroxy-2 (S) -methyl-5-hydroxy-
4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide

Embedded image TLC: Rf 0.14 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.33 (1H, s), 8.62 (1H, s),
7.89-7.83 (3H, m), 7.41 (2H, t, J = 7.6Hz), 7.17 (1H
, t, J = 7.6Hz), 7.04 (2H, d, J = 7.6Hz), 7.00 (2H,
d, J = 8.7Hz), 4.68 (1H, t, J = 5.7Hz), 4.02-3.91 (1H,
m), 3.45-3.28 (2H, m), 2.21-2.08 (1H, m), 1.72-
1.55 (2H, m), 0.98 (3H, d, J = 6.6Hz).

Example 49 (256) N-hydroxy-2 (S) -methyl-5-hydroxy-
4 (S)-[N- (4-bromophenylcarbonyl) amino] pentanamide

[Chemical formula 495] TLC: Rf 0.25 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.37 (s, 1H), 8.64 (s, 1H),
8.02 (d, J = 8.6Hz, 1H), 7.81 (d, J = 8.4Hz, 2H), 7.6
5 (d, J = 8.4Hz, 2H), 4.80-4.64 (m, 1H), 4.10-3.88
(m, 1H), 3.60- 3.10 (m, 2H), 2.26-2.06 (m, 1H), 1.
80-1.56 (m, 2H), 1.02 (d, J = 6.8Hz, 3H).

Example 49 (257) N-hydroxy-2 (S)-(3-methoxybenzyl)
-5-hydroxy-4 (S)-[N- (4-bromophenylcarbonyl) amino] pentanamide

[Chemical 496] TLC: Rf 0.45 (methylene chloride: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.28 (s, 1H), 8.63 (s, 1H),
8.04 (brd, J = 8.4Hz, 1H), 7.82 (d, J = 8.4Hz, 2H), 7.
66 (d, J = 8.4Hz, 2H), 7.11 (t, J = 8.0Hz, 1H), 6.67
(m, 3H), 4.69 (brt, J = 5.8Hz, 1H), 4.09 (m, 1H), 3.
65 (s, 3H), 3.44 (m, 2H), 2.75 (brd, J = 7.2Hz, 2H),
2.33 (m, 1H), 1.85-1.50 (m, 2H).

Example 49 (258) N-hydroxy-2 (S)-(3-methoxybenzyl)
-5-hydroxy-4 (S)-[N- (4-nitrophenylcarbonyl) amino] pentanamide

[Chemical 497] TLC: Rf 0.52 (methylene chloride: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.31 (s, 1H), 8.64 (s, 1H),
8.34 (brd, J = 8.4Hz, 1H), 8.30 (d, J = 9.2Hz, 2H), 8.
09 (d, J = 9.2Hz, 2H), 7.11 (t, J = 8.8Hz, 1H), 6.70
(m, 3H), 4.73 (brt, J = 5.8Hz, 1H), 4.10 (m, 1H), 3.
67 (s, 3H), 3.43 (m, 2H), 2.73 (brd, J = 7.0Hz, 2H),
2.35 (m, 1H), 1.85-1.55 (m, 2H).

Example 49 (259) N-hydroxy-2 (S)-(3-methoxybenzyl)
-5-hydroxy-4 (S)-[N- (4-chlorophenylcarbonyl) amino] pentanamide

[Chemical 498] TLC: Rf 0.52 (methylene chloride: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.28 (s, 1H), 8.63 (s, 1H),
8.06 (brd, J = 8.4Hz, 1H), 7.89 (d, J = 8.7Hz, 2H), 7.
52 (d, J = 8.7Hz, 2H), 7.11 (t, J = 8.4Hz, 1H), 6.67
(m, 3H), 4.70 (brt, J = 5.7Hz, 1H), 4.10 (m, 1H), 3.
65 (s, 3H), 3.41 (m, 2H), 2.72 (brd, J = 7.2Hz, 2H),
2.33 (m, 1H), 1.82-1.55 (m, 2H).

Example 49 (260) N-hydroxy-2 (S)-(3-methoxybenzyl)
-5-Hydroxy-4 (S)-[N-[(2-bromothiophen-5-yl) carbonyl] amino] pentanamide

[Chemical 499] TLC: Rf 0.52 (methylene chloride: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.30 (s, 1H), 8.64 (s, 1H),
8.13 (brd, J = 8.8Hz, 1H), 7.63 (d, J = 4.0Hz, 1H), 7.
27 (d, J = 4.0Hz, 1H), 7.12 (t, J = 8.4Hz, 1H), 6.69
(m, 3H), 4.72 (brs, 1H), 4.00 (m, 1H), 3.68 (s, 3
H), 3.39 (m, 2H), 2.71 (brd, J = 7.2Hz, 2H), 2.32
(m, 1H), 1.83-1.49 (m, 2H).

Example 49 (261) N-hydroxy-2 (S)-(3-methoxybenzyl)
-5-Hydroxy-4 (S)-[N-[(2-nitrothiophen-5-yl) carbonyl] amino] pentanamide

[Chemical 500] TLC: Rf 0.47 (methylene chloride: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.32 (s, 1H), 8.65 (s, 1H),
8.57 (brd, J = 9.0Hz, 1H), 8.14 (d, J = 4.5Hz, 1H), 7.
84 (d, J = 4.5Hz, 1H), 7.12 (t, J = 8.4Hz, 1H), 6.69
(m, 3H), 4.78 (brs, 1H), 4.01 (m, 1H), 3.69 (s, 3
H), 3.42 (m, 2H), 2.71 (m, 2H), 2.33 (m, 1H), 1.81
-1.54 (m, 2H).

Example 49 (262) N-hydroxy-2 (S)-(3-methoxybenzyl)
-5-hydroxy-4 (S)-[N- (4-cyanophenylcarbonyl) amino] pentanamide

[Chemical 501] TLC: Rf 0.39 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.31 (s, 1H), 8.64 (s, 1H),
8.23 (d, J = 8.8Hz, 1H), 8.03 (d, J = 8.4Hz, 2H), 7.9
3 (d, J = 8.4Hz, 2H), 7.18-7.06 (m, 1H), 6.75-6.64
(m, 3H), 4.71 (t, J = 5.8Hz, 1H), 4.21-4.00 (m, 1H),
3.67 (s, 3H), 3.57-3.37 (m, 2H), 2.74 (d, J = 7.0Hz,
2H), 2.42- 2.25 (m, 1H), 1.90-1.52 (m, 2H).

Example 49 (263) N-hydroxy-2 (R) -benzyloxymethyl-5
-Hydroxy-4 (S)-[N- (4-nitrophenylcarbonyl) amino] pentanamide

[Chemical 502] TLC: Rf 0.62 (methylene chloride: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.47 (s, 1H), 8.74 (s, 1H),
8.33 (d, J = 8.8Hz, 1H), 8.29 (d, J = 8.6Hz, 2H),
8.06 (d, J = 8.6Hz, 2H), 7.29 (m, 5H), 4.72 (t, J
= 5.6Hz, 1H), 4.45 (d, J = 12.4Hz, 1H), 4.38 (d, J
= 12.0Hz, 1H), 3.95 (m, 1H), 3.60-3.35 (m, 4H),
2.45 (m, 1H), 1.78 (m, 1H), 1.62 (m, 1H).

Examples 49 (264) to 49 (269) Using the corresponding compounds, Example 37 → Example 39 → Example 41 (the corresponding compound may be used instead of methoxymethyl chloride) → Example 43 (Use the corresponding compound in place of benzyl bromide.) → Example 5 → Example 44 → The same procedure as in Example 49 was carried out to obtain the compound shown below.

Example 49 (264) N-hydroxy-5-methoxymethoxy-4 (S)-
[N-methyl-N- [4- (4-chlorophenyl) phenylcarbonyl] amino] pentanamide

[Chemical 503] TLC: Rf 0.22 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.36 (1H, s), 7.75-7.65 (4
H, m), 7.54-7.37 (4H, m), 4.66-3.68 (3H, m), 3.64-
3.35 (2H, m), 3.25, 3.21 (3H, s), 2.81, 2.74 (3H,
s), 2.07-1.55 (4H, m).

Example 49 (265) N-hydroxy-2 (S)-(3-pyridyl) methyl-
5-methoxymethoxy-4 (S)-[N-methyl-N-
[4- (4-chlorophenyl) phenylcarbonyl] amino] pentanamide

[Chemical 504] TLC: Rf 0.42 (chloroform: methanol: acetic acid = 9: 1: 0.5); NMR (d ₆ -DMSO): δ 10.43 (1H, s), 8.72 (1H, s),
8.45-8.29 (2H, m), 7.78-7.60 (5H, m), 7.58-7.40 (4
H, m), 7.33- 7.22 (1H, m), 4.97-4.84 (0.6H, m), 4.
56-4.44 (2H, m), 3.94-3.84 (0.4H, m), 3.64-3.30 (2
H, m), 3.25, 3.20 (3H, s), 2.82, 2.73 (3H, s), 2.85
-2.21 (3H, m), 1.88-1.49 (2H, m).

Example 49 (266) N-hydroxy-2 (S) -methyl-5-ethoxymethoxy-4 (S)-[N-methyl-N- (4-bromophenylcarbonyl) amino] pentanamide

[Chemical formula 505] TLC: Rf 0.36 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.47 & 10.45 (s, 1H), 8.72 & 8.
69 (s, 1H), 7.63 & 7.60 (d, J = 8.4Hz, 2H), 7.32 & 7.30
(d, J = 8.4Hz, 2H), 4.79-4.67 & 3.77-3.64 (m, 1H), 4.6
1 & 4.56 (s, 2H), 3.60-3.36 (m, 4H), 2.78 & 2.65 (s,
3H), 2.18-2.06 & 2.03-1.92 (m, 1H), 1.85-1.67 (m, 1
H), 1.54-1.43 & 1.38-1.27 (m, 1H), 1.10 (q, J = 6.6Hz,
3H), 1.03 & 0.73 (d, J = 6.9Hz, 3H).

Example 49 (267) N-hydroxy-2 (S)-(3-methoxybenzyl)
-5-Ethoxymethoxy-4 (S)-[N-methyl-N
-(4-Bromophenylcarbonyl) amino] pentanamide

[Chemical formula 506] TLC: Rf 0.47 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.44 & 10.42 (s, 1H), 8.71
(s, 1H), 7.66 & 7.53 (d, J = 8.1Hz, 2H), 7.36 & 7.29 (d,
J = 8.1Hz, 2H), 7.14 (t, J = 8.0Hz, 1H), 6.80-6.58 (m,
3H), 4.89-4.79 & 3.75-3.63 (m, 1H), 4.60 & 4.5 2 (s,
2H), 3.71 & 3.67 (s, 3H), 3.58-3.36 (m, 4H), 2.78 & 2.6
8 (s, 3H), 2.77-2.56 (m, 2H), 2.33-2.15 (m, 1H),
1.85-1.72 (m, 1H), 1.66-1.57 & 1.54-1.43 (m, 1H), 1.
15-1.04 (m, 3H).

Example 49 (268) N-Hydroxy-2 (S) -methyl-5-ethoxymethoxy-4 (S)-[N-methyl-N- (4-nitrophenylcarbonyl) amino] pentanamide

[Chemical 507] TLC: Rf 0.27 (chloroform: methanol = 1
9: 1); NMR (d ₆ -DMSO): δ 10.51 and 10.45 (s, 1H), 8.7
6 and 8.70 (s, 1H), 8.29 and 8.26 (d, J = 8.8Hz, 2H),
7.64 and 7.60 (d, J = 8.8Hz, 2H), 4.86-4.51 (m, 3
H), 3.70-3.36 (m, 4H), 2.84 and 2.65 (s, 3H), 2.22
-1.65 (m, 2H), 1.60-1.20 (m, 1H), 1.15 and 1.12 (t,
J = 7.0Hz, 3H), 1.07 and 0.79 (d, J = 7.0Hz, 3H).

Example 49 (269) N-hydroxy-2 (S) -methyl-5-benzyloxymethoxy-4 (S)-[N-methyl-N- (4-nitrophenylcarbonyl) amino] pentanamide

[Chemical 508] TLC: Rf 0.43 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.50 & 10.43 (s, 1H), 8.75 & 8.
69 (d, J = 1.5Hz, 1H), 8.27 & 8.25 (d, J = 8.9Hz, 2H), 7.
63 & 7.60 (d, J = 8.9Hz, 2H), 7.37-7.26 (m, 5H), 4.83-
4.67 (m, 2.5H), 4.58-4.46 (m, 2H), 3.69-3 .56 & 3.48
-3.37 (m, 2.5H), 2.83 & 2.63 (s, 3H), 2.20-2.10 & 2.
06-1.95 (m, 1H), 1.90-1.72 (m, 1H), 1.55-1.44 & 1.39
-1.29 (m, 1H), 1.05 & 0.76 (d, J = 6.8Hz, 3H).

Examples 49 (270) to 49 (277) Example 3 using the corresponding compound instead of Reference Example 4.
7-> Example 39-> Example 45-> Example 46 (using the corresponding compound instead of benzyl bromide)-> Example 5->
The procedure of Example 47 → Example 48 → Example 49 was repeated to give the compounds shown below.

Example 49 (270) N-hydroxy-2 (S)-(3-methoxybenzyl)
-5-hydroxy-4 (S)-[N-methyl-N- (4
-Chlorophenylcarbonyl) amino] pentanamide

[Chemical formula 509] TLC: Rf 0.51 (methylene chloride: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.40 (s, 0.45H), 10.38 (s,
0.55H), 8.67 (s, 1H), 7.53-7.35 (m, 3.45H), 7.24-
7.10 (m, 1.55H), 6.73-6.56 (m, 3H), 4.94 (brt, J =
5.2Hz, 0.45H), 4.79 (brt, J = 5.2Hz, 0.55H), 4.72
(m, 0.55H), 3.70 (s, 1.65H), 3.67 (s, 1.35H), 3.70
-3.30 (m, 2.45H), 2.78 (s, 1.35H), 2.66 (s, 1.65H),
2.80-2.10 (m, 4H), 1.80-1.35 (m, 2H).

Example 49 (271) N-hydroxy-2 (S)-(3-methoxybenzyl)
-5-hydroxy-4 (S)-[N-methyl-N- (4
-Nitrophenylcarbonyl) amino] pentanamide

[Chemical 510] TLC: Rf 0.56 (methylene chloride: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.39 (s, 0.5H), 10.37 (s,
0.5H), 8.69 (s, 0.5H), 8.64 (s, 0.5H), 8.28 (d, J =
8.8Hz, 1H), 8.17 (d, J = 8.8Hz, 1H), 7.68 (d, J = 8.8H
z, 1H), 7.59 (d, J = 8.8Hz, 1H), 7.11 (m, 1H), 6.72
(m, 2H), 6.57 (m, 1H), 4.95 (brt, J = 5.2Hz, 0.5H),
4.82 (brt, J = 5.2Hz, 0.5H), 4.69 (m, 0.5H), 3.68
(s, 3H), 3.60-3.30 (m, 2.5H), 3.55-3.25 (m, 2H),
2.80 (s, 1.5H), 2.63 (s, 1.5H), 2.80-2.10 (m, 4H),
1.80-1.35 (m, 2H).

Example 49 (272) N-hydroxy-2 (S)-(3-methoxybenzyl)
-5-hydroxy-4 (S)-[N-methyl-N- (4
-Bromophenylcarbonyl) amino] pentanamide

[Chemical 511] TLC: Rf 0.45 (methylene chloride: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.41 (s, 0.45H), 10.38 (s,
0.55H), 8.67 (s, 1H), 7.64 (d, J = 8.4Hz, 1.1H), 7.5
3 (d, J = 8.4Hz, 0.9H), 7.39 (d, J = 8.4Hz, 1.1H), 7.3
5 (d, J = 8.4Hz, 0.9H), 7.13 (t, J = 7.8Hz, 1H), 6.70
(m, 2.1H), 6.57 (m, 0.9H), 4.94 (brt, J = 5.1Hz, 0.4
5H), 4.79 (brt, J = 5.7Hz, 0.55H), 4.70 (m, 0.55H),
3.70 (s, 1.65H), 3.67 (s, 1.35H), 3.70-3.60 (m, 0.
45H), 3.55-3.25 (m, 2H), 2.78 (s, 1.35H), 2.66 (s,
1.65H), 2.80-2.10 (m, 4H), 1.80-1.35 (m, 2H).

Example 49 (273) N-hydroxy-2 (S) -methyl-5-hydroxy-
4 (S)-[N-methyl-N- (4-nitrophenylcarbonyl) amino] pentanamide

[Chemical 512] TLC: Rf 0.16 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.49 & 10.42 (s, 1H), 8.72 & 8.
67 (d, J = 1.5Hz, 1H), 8.27 & 8.25 (d, J = 8.8Hz, 2H), 7.
65 & 7.62 (d, J = 8.8Hz, 2H), 5.01 & 4.83 (t, J = 5.4Hz, 1
H), 4.65-4.54 & 3.51-3.40 (m, 1H), 3.53-3 .27 (m, 2
H), 2.81 & 2.62 (s, 3H), 2.17-2.09 & 2.03-1.91 (m, 1
H), 1.80-1.63 (m, 1H), 1.52-1.42 & 1.33-1.22 (m, 1
H), 1.05 & 0.72 (d, J = 6.9Hz, 3H).

Example 49 (274) N-Hydroxy-2 (S) -benzyl-5-hydroxy-4 (S)-[N-methyl-N- (4-nitrophenylcarbonyl) amino] pentanamide

[Chemical 513] TLC: Rf 0.25 (chloroform: methanol: water =
9: 1: 0.1); NMR (d ₆ -DMSO): δ 10.40 and 10.37 (s, 1H), 8.7
0 and 8.65 (brs, 1H), 8.29 and 8.19 (d, J = 8.7Hz, 2
H), 7.69 and 7.60 (d, J = 8.7Hz, 2H), 7.30-7.01 (m,
5H), 4.91 and 4.84 (t, J = 5.4Hz, 1H), 4.75-4.64 and
3.54-3.44 (m, 1H), 3.49-3.25 (m, 2H), 2.81 and 2.6
5 (s, 3H), 2.84-2.51 (m, 2H), 2.35-2.12 (m, 1H),
1.84-1.56 and 1.47-1.36 (m, 2H).

Example 49 (275) N-hydroxy-2 (S) -methyl-5-hydroxy-
4 (S)-[N-methyl-N- (4-bromophenylcarbonyl) amino] pentanamide

[Chemical 514] TLC: Rf 0.17 (chloroform: methanol: water =
9: 1: 0.1); NMR (d ₆ -DMSO): δ 10.43 (s, 1H), 8.66 (s, 1H),
7.62 and 7.59 (d, J = 8.1Hz, 2H), 7.35 (d, J = 8.1Hz,
2H), 4.98-4.92 and 4.81-4.73 (m, 1H), 4.63-4.52 a
nd 3.64-3.52 (m, 1H), 3.52-3.39 (m, 2H), 2.77 and
2.64 (s, 3H), 2.15-2.05 and 2.00-1.89 (m, 1H), 1.77
-1.58 and 1.53-1.43 and 1.32-1.21 (m, 2H), 1.04 an
d 0.68 (d, J = 6.7Hz, 3H).

Example 49 (276) N-Hydroxy-2 (S) -benzyl-5-hydroxy-4 (S)-[N-methyl-N- (4-bromophenylcarbonyl) amino] pentanamide

[Chemical 515] TLC: Rf 0.25 (chloroform: methanol: water =
9: 1: 0.1); NMR (d ₆ -DMSO): δ 10.40 and 10.37 (s, 1H), 8.6
6 (s, 1H), 7.64 and 7.54 (d, J = 8.6Hz, 2H), 7.39 and
7.36 (d, J = 8.6Hz, 2H), 7.28-6.97 (m, 5H), 4.95 an
d 4.79 (t, J = 5.4Hz, 1H), 4.75-4.65 and 3.69-3.60
(m, 1H), 3.52-3.26 (m, 2H), 2.78 and 2.66 (s, 3H),
2.82-2.55 (m, 2H), 2.31-2.12 (m, 1H), 1.80-1.56 a
nd 1.67-1.35 (m, 2H).

Example 49 (277) N-hydroxy-2 (S) -methyl-5-hydroxy-
4 (S)-[N-methyl-N- (4-chlorophenylcarbonyl) amino] pentanamide

[Chemical 516] TLC: Rf 0.17 (chloroform: methanol: water =
9: 1: 0.1); NMR (d ₆ -DMSO): δ 10.45 and 10.43 (s, 1H), 8.6
9 and 8.66 (s, 1H), 7.53-7.38 (m, 4H), 4.96 and 4.7
7 (t, J = 5.3Hz, 1H), 4.63-4.52 and 3.65-3.51 (m, 1
H), 3.51-3.40 (m, 2H), 2.78 and 2.64 (s, 3H), 2.15
-2.05 and 1.98-1.88 (m, 1H), 1.77-1.54 (m, 1H), 1.
54-1.43 and 1.32-1.21 (m, 1H), 1.03and 0.67 (d, J =
6.8Hz, 3H).

Example 50 2 (S) -benzyloxy-3 (S) -hydroxy-4
-(N- (4- (3-Methoxy-1-propynyl) phenylcarbonyl) amino) butanoic acid ethyl ester

[Chemical 517] 2 (S) instead of 4-aminobutanoic acid ethyl ester
-Benzyloxy-3 (S) -hydroxy-4-aminobutanoic acid ethyl ester (Bioorg. Med. Chem. Lett.,
It was produced in the same manner as described in 2 , 515 (1992). )
Was used in the same manner as in Example 1 except that the corresponding acid halide was used instead of the compound prepared in Reference Example 4 to obtain the title compound having the following physical data. TLC: Rf 0.20 (n-hexane: ethyl acetate = 3:
2).

Example 51 2 (S) -benzyloxy-3 (S) -hydroxy-4
-(N- (4- (3-methoxy-1-propynyl) phenylcarbonyl) amino) butanoic acid

[Chemical 518] The title compound having the following physical data was obtained by substituting the compound prepared in Example 50 for the compound prepared in Example 1 and operating in the same manner as in Example 2. TLC: Rf 0.22 (chloroform: methanol = 9:
1).

Example 52 2 (S) -benzyloxy-3 (S) -t-butylcarbonyloxy-4- (N- (4- (3-methoxy-1-
Propynyl) phenylcarbonyl) amino) butanoic acid ethyl ester

[Chemical 519] Example 5 in place of 4-aminobutanoic acid ethyl ester
The title compound having the following physical data was obtained by operating in the same manner as in Example 1 (using pivaloyl chloride in place of the compound prepared in Reference Example 4) using the compound prepared in 0. Obtained. TLC: Rf 0.44 (n-hexane: ethyl acetate = 7:
3); NMR (CDCl ₃ ): δ 7.49 (2H, d, J = 8.8Hz), 7.43-
7.30 (7H, m), 6.80-6.68 (1H, m), 5.36 (1H, td, J =
5.6, 3.8Hz), 4.87 (1H, d, J = 11.4Hz), 4.43 (1H, d,
J = 11.4Hz), 4.34 (2H, s), 4.25 (1H, d, J = 3.8Hz), 4.
22 (2H, q, J = 7.0Hz), 3.90 (1H, dt, J = 14.2, 5.6Hz),
3.66 (1H, dt, J = 14.2, 5.6Hz), 3.46 (3H, s), 1.29
(3H, t, J = 7.0Hz), 1.14 (9H, s).

Example 53 2-Benzyloxy-4- (N- (4- (3-methoxy-1-propynyl) phenylcarbonyl) amino) -2
-Butenoic acid

[Chemical 520] The title compound having the following physical data was obtained by substituting the compound prepared in Example 52 for the compound prepared in Example 1 and operating in the same manner as in Example 2. TLC: Rf 0.36 (chloroform: methanol = 9:
1).

Example 54 N-Hydroxy-2 (S) -benzyloxy-3 (S)
-Hydroxy-4- (N- (4- (3-methoxy-1-
Propynyl) phenylcarbonyl) amino) butyramide

[Chemical 521] The title compound having the following physical data was obtained by substituting the compound prepared in Example 51 for the compound prepared in Example 2 and carrying out the same procedure as in Example 3 → Example 4. TLC: Rf 0.25 (chloroform: methanol = 9:
1); NMR (CD ₃ OD): δ 7.74 (2H, d, J = 8.4Hz), 7.49
(2H, d, J = 8.4Hz), 7.45-7.20 (5H, m), 4.73 (1H, d,
J = 11.4Hz), 4.49 (1H, d, J = 11.4Hz), 4.34 (2H, s),
4.14-3.95 (1H, m), 3.91 (1H, d, J = 3.4Hz), 3.60 (1
H, dd, J = 13.6, 5.4Hz), 3.44 (3H, s), 3.42 (1H, dd,
J = 13.6, 7.2Hz).

Example 54 (1) N-hydroxy-2-benzyloxy-4- (N- (4
-(3-Methoxy-1-propynyl) phenylcarbonyl) amino) -2-butenamide

[Chemical 522] Substituting the compound prepared in Example 53 for the compound prepared in Example 51 and operating in the same manner as in Example 54, the title compound having the following physical data was obtained. TLC: Rf 0.37 (chloroform: methanol = 9:
1); NMR (CD ₃ OD): δ 8.52-8.40 (1H, m), 7.74 (2H,
d, J = 8.4Hz), 7.49 (2H, d, J = 8.4Hz), 7.45-7.20 (5H,
m), 5.89 (1H, t, J = 6.6Hz), 4.88 (2H, s), 4.33 (2H,
s), 4.02-3.90 (2H, m), 3.43 (3H, s).

Example 55 cis-1-carboxymethyl-2- (N- (4- (3-
Methoxy-1-propynyl) phenylcarbonyl) amino) cyclopentane

[Chemical 523] Cis-1 instead of 4-aminobutanoic acid ethyl ester
-Carboxymethyl-2-aminocyclopentane (J. C
hem. Soc., PerkinTrans. 1, 11 , 2553 (1982)) using the corresponding acid halide in place of the compound prepared in Reference Example 4 and the method shown in Example 1. The same operation was performed to obtain the title compound having the following physical properties. TLC: Rf 0.80 (chloroform: methanol: acetic acid = 18: 2: 1).

Examples 55 (1) to 55 (4) trans-1-carboxymethyl-2-aminocyclopentane, cis-3-aminocyclopentanoic acid instead of cis-1-carboxymethyl-2-aminocyclopentane. , Trans-3-aminocyclopentanoic acid (Chem. Be
r., 101 , 1525 (1968)) and 2-
Using aminomethylcyclopentanoic acid, the same procedure as in Example 55 was carried out to obtain the compound shown below.

Example 55 (1) trans-1-carboxymethyl-2- (N- (4-
(3-Methoxy-1-propynyl) phenylcarbonyl) amino) cyclopentane

[Chemical 524] TLC: Rf 0.36 (chloroform: methanol = 1)
NMR (CDCl ₃ ): δ 7.72 (2H, d, J = 8.4Hz), 7.49
(2H, d, J = 8.4Hz), 6.49 (1H, d, J = 7.4Hz), 4.34 (2H,
s), 4.04 (1H, m), 3.46 (3H, s), 2.56 (2H, m), 2.25
(2H, m), 1.99 (1H, m), 1.75 (2H, m), 1.50 (2H,
m).

Example 55 (2) trans-3- (N- (4- (3-methoxy-1-propynyl) phenylcarbonyl) amino) cyclopentanoic acid

[Chemical 525] TLC: Rf 0.21 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 12.09 (1H, s), 8.40 (1H, d,
J = 6.8Hz), 7.85 (2H, d, J = 8.4Hz), 7.53 (2H, d, J = 8.
4Hz), 4.42-4.22 (3H, m), 3.34 (3H, s), 3.30-2.82
(1H, m), 2.20-1.48 (6H, m).

Example 55 (3) cis-3- (N- (4- (3-methoxy-1-propynyl) phenylcarbonyl) amino) cyclopentanoic acid

[Chemical Formula 526] TLC: Rf 0.32 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 12.11 (1H, s), 8.45 (1H, d,
J = 7.4Hz), 7.85 (2H, d, J = 8.8Hz), 7.52 (2H, d, J = 8.
8Hz), 4.34 (2H, s), 4.33-4.18 (1H, m), 3.34 (3H,
s), 2.84-2.66 (1H, m), 2.18 (1H, m), 2.00-1.50 (5
H, m).

Example 55 (4) trans-2- (N- (4- (3-methoxy-1-propynyl) phenylcarbonyl) aminomethyl) cyclopentanoic acid

[Chemical 527] TLC: Rf 0.26 (chloroform: methanol = 1)
9: 1); NMR (CDCl ₃ ): δ 7.72 (2H, d, J = 8.2Hz), 7.46
(2H, d, J = 8.2Hz), 7.08-6.98 (1H, m), 4.33 (2H, s),
3.69 (1H, dt, J = 13.8, 5.4Hz), 3.45 (3H, s), 3.34
(1H, ddd, J = 13.8, 8.8, 5.4Hz), 2.62-2.30 (2H, m),
2.06-1.84 (3H, m), 1.80-1.62 (2H, m), 1.52-1.32 (1
H, m).

Example 56 cis-1- (N-hydroxyaminocarbonylmethyl)
-2- (N- (4- (3-methoxy-1-propynyl))
Phenylcarbonyl) amino) cyclopentane

[Chemical 528] The title compound having the following physical data was obtained by substituting the compound prepared in Example 55 for the compound prepared in Example 2 and operating in the same manner as in Example 3 → Example 4. TLC: Rf 0.33 (chloroform: methanol = 1)
0: 1); NMR (d ₆ -DMSO): δ 10.40 (1H, s), 8.37 (1H, d,
J = 7.8Hz), 7.86 (2H, d, J = 8.4Hz), 7.54 (2H, d, J = 8.
4Hz), 4.38 (1H, m), 4.35 (2H, s), 3.35 (3H, s), 2.
35 (1H, m), 2.09 (1H, dd, J = 14.6, 4.6Hz), 1.91 (1
H, m), 1.83 (1H, m), 1.80-1.50 (4H, m), 1.44 (1H,
m).

Examples 56 (1) -56 (4) Example 55 instead of the compound prepared in Example 55.
Example 56 using the compounds produced in (1) to (4)
The following compounds were obtained by operating in the same manner as the method shown in.

Example 56 (1) trans-1- (N-hydroxyaminocarbonylmethyl) -2- (N- (4- (3-methoxy-1-propynyl) phenylcarbonyl) amino) cyclopentane

[Chemical 529] TLC: Rf 0.43 (chloroform: methanol = 1
0: 1); NMR (d ₆ -DMSO): δ 10.37 (1H, s), 8.41 (1H, d,
J = 8.0Hz), 7.87 (2H, d, J = 8.4Hz), 7.53 (2H, d, J = 8.
4Hz), 4.35 (2H, s), 3.90 (1H, m), 3.35 (3H, s), 2.
19 (2H, m), 1.87 (3H, m), 1.58 (3H, m,), 1.24 (1
H, m).

Example 56 (2) trans-1- (N-hydroxyaminocarbonyl)-
3- (N- (4- (3-methoxy-1-propynyl) phenylcarbonyl) amino) cyclopentane

[Chemical 530] TLC: Rf 0.26 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.42 (1H, s), 8.80-8.60 (1
H, br), 8.37 (1H, d, J = 7.0Hz), 7.85 (2H, d, J = 8.4H
z), 7.53 (2H, d, J = 8.4Hz), 4.44-4.24 (3H, m), 3.35
(3H, s), 2.78-2.68 (1H, m), 2.10-1.50 (6H, m).

Example 56 (3) cis-1- (N-hydroxyaminocarbonyl) -3-
(N- (4- (3-methoxy-1-propynyl) phenylcarbonyl) amino) cyclopentane

[Chemical 531] TLC: Rf 0.38 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.62 (1H, s), 8.94-8.76 (1
H, br), 8.82 (1H, d, J = 7.8Hz), 7.87 (2H, d, J = 8.4H
z), 7.53 (2H, d, J = 8.4Hz), 4.34 (2H, s), 4.42-4.22
(1H, m), 3.35 (3H, s), 2.70-2.55 (1H, m), 2.14-1.
95 (1H, m), 1.92-1.62 (5H, m).

Example 56 (4) trans-1- (N-hydroxyaminocarbonyl)-
2- (N- (4- (3-methoxy-1-propynyl) phenylcarbonyl) aminomethyl) cyclopentane

[Chemical 532] TLC: Rf 0.31 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.39 (1H, s), 8.50 (1H, t,
J = 5.6Hz), 7.83 (2H, d, J = 8.2Hz), 7.52 (2H, d, J = 8.
2Hz), 4.34 (2H, s), 3.35 (3H, s), 3.32-3.14 (2H,
m), 2.40-2.22 (1H, m), 2.20-2.04 (1H, m), 1.90-1.5
0 (5H, m), 1.48-1.24 (1H, m).

Example 57 2 (R) -allyl-5-ethoxymethoxy-4 (S)-
[N- (4-phenoxyphenylcarbonyl) amino]
Pentanoic acid

[Chemical 533] Using a compound corresponding to the compound prepared in Reference Example 4 in a solution of lithium diisopropylamide (3.6 ml) in tetrahydrofuran (20 ml) at −20 ° C., Example 37 → Example 39 → Example 41 (methoxy) Ethoxymethyl chloride is used instead of methyl chloride.) → 2 (S) -2 obtained by the same procedure as in Example 43 (using allyl bromide instead of benzyl bromide). -Propenyl-4 (S) -ethoxymethoxymethyl-4- (N- (4-phenoxyphenylcarbonyl) aminobutanoic acid methyl ester (1.06
A solution of g) in tetrahydrofuran (4 ml) was added dropwise.
The mixture was stirred at -15 ° C for 30 minutes. A saturated ammonium chloride solution and water were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel chromatography (toluene: ethyl acetate = 87: 13). Purified compound (200m
The procedure described in Example 2 was repeated using g) to give the title compound (193 mg) having the following physical data.
Got TLC: Rf 0.19 (chloroform: methanol = 9:
1).

Example 58 N-Hydroxy-2 (R) -allyl-5-ethoxymethoxy-4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide

[Chemical 534] The title compound having the following physical properties values was obtained by the same procedure as in Example 3 → Example 4 using the compound prepared in Example 57. TLC: Rf 0.23 (chloroform: methanol = 1
0: 1); NMR (d ₆ -DMSO): δ 10.37 (s, 1H), 8.74 (brs, 1
H), 8.13 (d, J = 8.1Hz, 1H), 7.90-7.85 (m, 2H), 7.45-
7.39 (m, 2H), 7.19 (t, J = 7.2Hz, 1H), 7.07-6.99 (m,
4H), 5.69-5.60 (m, 1H), 5.02-4.93 (m, 2H), 4.56
(s, 2H), 3.99-3.89 (m, 1H), 3.80-3.39 (m, 4H), 2.2
6-2.01 (m, 3H), 1.85-1.79 (m, 1H), 1.61-1.54 (m, 1
H), 1.07 (t, J = 7.2Hz, 3H).

Examples 58 (1) to 58 (3) The compounds shown below were obtained in the same manner as in the process of Example 57 → Example 58 using the corresponding compounds.

Example 58 (1) N-hydroxy-2 (R) -benzyl-5-methoxymethoxy-4 (S)-[N- [4- (benzofuran-2-
Iyl) phenylcarbonyl] amino] pentanamide

[Chemical Formula 535] TLC: Rf 0.35 (chloroform: methanol = 1)
9: 1); NMR (d ₆ -DMSO): δ 10.37 (1H, s), 8.72 (1H, s),
8.28 (1H, d, J = 7.2Hz), 8.02 (2H, d, J = 8.8Hz), 7.9
7 (2H, d, J = 8.8Hz), 7.74- 7.62 (2H, m), 7.57 (1H,
d, J = 0.6Hz), 7.41-7.10 (7H, m), 4.56 (2H, s), 4.18
-3.98 (1H, m), 3.57-3.39 (2H, m), 3.23 (3H, s), 2.8
5 (1H, dd, J = 13.6, 8.4Hz), 2.64 (1H, dd, J = 13.6,
6.0Hz), 2.54-2.40 (1H, m), 2.03-1.80 (1H, m), 1.72
-1.52 (1H, m).

Example 58 (2) N-hydroxy-2 (R) -methyl-5-ethoxymethoxy-4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide

[Chemical Formula 536] TLC: Rf 0.29 (chloroform: methanol: acetic acid = 100: 10: 1); NMR (d ₆ -DMSO): δ 10.35 (s, 1H), 8.70 (s, 1H),
8.13 (d, J = 8.1Hz, 1H), 7.88 (d, J = 8.4Hz, 2H), 7.4
5-7.39 (m, 2H), 7.19 (t, J = 7.2Hz, 1H), 7.07-7.01
(m, 4H), 4.57 (s, 2H), 4.01-3.88 (m, 1H), 3.47 (q,
J = 7.2Hz, 2H), 3.44-3.38 (m, 2H), 2.30-2.18 (m, 1
H), 1.91-1.82 (m, 1H), 1.55-1.46 (m, 1H), 1.07 (t,
J = 7.2Hz, 3H), 0.99 (d, J = 6.9Hz, 3H).

Example 58 (3) N-hydroxy-2 (R) -methyl-5-ethoxymethoxy-4 (S)-[N- [4- (4-cyanophenyl)
Phenylcarbonyl] amino] pentanamide

[Chemical 537] TLC: Rf 0.49 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.36 (s, 1H), 8.69 (s, 1H),
8.28 (d, J = 8.2Hz, 1H), 8.00-7.94 (m, 6H), 7.84
(d, J = 8.4Hz, 2H), 4.57 (s, 2H), 4.06-3.88 (m, 1H),
3.52-3.42 (m, 4H), 2.34-2.18 (m, 1H), 1.95-1 .81
(m, 1H), 1.60-1.45 (m, 1H), 1.07 (t, J = 7.2Hz, 3H),
1.00 (d, J = 6.6Hz).

Examples 59 (1) to 59 (2) Prepared in 4 (R) -carboxy-4-aminobutanoic acid methyl ester instead of 4 (S) -carboxy-4-aminobutanoic acid methyl ester, and Reference Example 4. Example 37 → Example 39 → Example 41 (Comparative compound may be used instead of methoxymethyl chloride) → Example 43 using the corresponding compound instead of the above compound.
(The corresponding compound is used instead of benzyl bromide.)
Using the compound obtained by operating in the same manner as in
The same procedure as in Example 57 → Example 2 → Example 3 → Example 4 was repeated to obtain the compound shown below.

Example 59 (1) N-hydroxy-2 (S) -benzyl-5-methoxymethoxy-4 (R)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide

[Chemical 538] TLC: Rf 0.41 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1); NMR (d ₆ -DMSO): δ 10.33 (1H, s), 8.69 (1H, s),
8.12 (1H, d, J = 8.0Hz), 7.85 (2H, d, J = 8.8Hz), 7.37-7.
46 (2H, m), 6.99-7.27 (10H, m), 4.52 (2H, s), 3.90-4.1
3 (1H, m), 3.38-3.44 (2H, m), 3.20 (3H, s), 2.81 (1H,
dd, J = 13.2Hz, 6.2Hz), 2.59 (1H, dd, J = 13.2Hz, 6.2H
z), 2.38-2.52 (1H, m), 1.79-1.93 (1H, m), 1.50-1.63 (1
H, m).

Example 59 (2) N-hydroxy-2 (S) -benzyl-5-methoxymethoxy-4 (R)-[N- [4- (3-phenoxy-1)
-Propinyl) phenylcarbonyl] amino] pentanamide

[Chemical 539] TLC: Rf 0.41 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1); NMR (d ₆ -DMSO): δ 10.31 (1H, s), 8.68 (1H, s),
8.24 (1H, d, J = 8.1Hz), 7.81 (2H, d, J = 7.8Hz), 7.51 (2
H, d, J = 7.8Hz), 7.32 (2H, t, J = 7.8Hz), 6.95-7.24 (8
H, m), 5.05 (2H, s), 4.50 (2H, s), 3.90-4.07 (1H, m),
3.37-3.42 (2H, m), 3.18 (3H, s), 2.79 (1H, dd, J = 13.
5Hz, 6.2Hz), 2.58 (1H, dd, J = 13.5Hz, 6.2Hz), 2.43-
2.52 (1H, m), 1.82-1.89 (1H, m), 1.54-1.62 (1H, m).

Examples 60 (1) -60 (5) Using the compounds corresponding to the compounds prepared in Reference Example 4, Example 37 → Example 39 → Example 41 (corresponding to the methoxymethyl chloride instead. Compounds are used.) → Example 43 (Use the corresponding compound instead of benzyl bromide) → Example 2 → Example 3 → Example 4 →
The title compound having the following physical data was obtained by the same procedure as in Example 27.

Example 60 (1) N-hydroxy-2 (S)-(3-aminobenzyl)-
5-ethoxymethoxy-4 (S)-[N- (trans-
4-Methylcyclohexylcarbonyl) amino] pentanamide

[Chemical 540] TLC: Rf 0.27 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.45-10.10 (brs, 1H), 8.80-
8.45 (brs, 1H), 7.40 (d, J = 8.1Hz, 1H), 6.86 (t, J =
7.7Hz, 1H), 6.35 (d, J = 7.7Hz, 1H), 6.32 (s, 1H),
6.28 (d, J = 7.7Hz, 1H), 4.85 (s, 2H), 4.54 (s, 2H),
3.95-3.80 (m, 1H), 3.55-3.20 (m, 4H, overlap with
H2O in DMSO), 2.59 (dd, J = 13.2, 8.4Hz, 1H), 2.45
(dd, J = 13.2, 5.7Hz, 1H), 2.32-2.20 (m, 1H), 2.08-
1.92 (m, 1H), 1.80-1.57 (m, 5H), 1.57-1.44 (m, 1
H), 1.44-1.20 (m, 3H), 1.11 (t, J = 7.1Hz, 3H), 0.96
-0.76 (m, 5H).

Example 60 (2) N-Hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N- (4-carboxyphenylcarbonyl) amino] pentanamide

[Chemical 541] TLC: Rf 0.22 (chloroform: methanol: acetic acid = 90: 10: 1); NMR (d ₆ -DMSO): δ 13.50-12.70 (br, 1H), 10.37.
(s, 1H), 8.82-8.58 (br, 1H), 8.31 (d, J = 8.7Hz, 1
H), 8.01 (d, J = 8.7Hz, 2H), 7.95 (d, J = 8.7Hz, 2H),
7.27-7.08 (m, 5H), 4.58 (s, 2H), 4.34-4.19 (m, 1
H), 3.60-3.40 (m, 4H), 2.77 (d, J = 7.2, 2H), 2.42-2.
32 (m, 1H), 1.85-1.62 (m, 2H), 1.09 (t, J = 6.9Hz, 3
H).

Example 60 (3) N-hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N- (4-aminophenylcarbonyl) amino] pentanamide

[Chemical 542] TLC: Rf 0.36 (methylene chloride: methanol = 1
9: 1); NMR (d ₆ -DMSO): δ 10.34 (brs, 1H), 8.65 (brs,
1H), 7.61 (brd, J = 9.0Hz, 1H), 7.58 (d, J = 8.4Hz, 2
H), 7.22-7.08 (m, 5H), 6.52 (d, J = 8.4Hz, 2H), 5.57
(brs, 2H), 4.55 (s, 2H), 4.20 (m, 1H), 3.50-3.40
(m, 4H), 2.74 (d, J = 7.2Hz, 2H), 2.35 (m, 1H), 1.80
-1.59 (m, 2H), 1.07 (t, J = 7.2Hz, 3H).

Example 60 (4) N-hydroxy-2 (S) -benzyl-5-ethoxymethoxy-4 (S)-[N- (4-piperidylcarbonyl) amino] pentanamide

[Chemical Formula 543] TLC: Rf 0.50 (chloroform: methanol: acetic acid = 7: 2: 1); NMR (d ₆ -DMSO): δ 10.30 (brs, 1H), 7.47 (brd,
J = 9.0Hz, 1H), 7.25-7.08 (m, 5H), 4.53 (s, 2H), 3.9
3 (m, 1H), 3.43 (q, J = 6.9Hz, 2H), 3.35 (m, 2H), 2.9
4 (brd, J = 12.0Hz, 2H), 2.68 (m, 2H), 2.49 (m, 2H),
2.35-2.10 (m, 2H), 1.70-1.40 (m, 6H), 1.09 (t, J =
6.9Hz, 3H).

Example 60 (5) N-hydroxy-2 (S)-(3-hydroxybenzyl) -5-ethoxymethoxy-4 (S)-[N- (4-
Methylphenylcarbonyl) amino] pentanamide

[Chemical 544] TLC: Rf 0.45 (methylene chloride: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.33 (s, 1H), 9.16 (s, 1H),
8.64 (s, 1H), 7.99 (brd, J = 8.4Hz, 1H), 7.75 (d, J =
8.4Hz, 2H), 7.23 (d, J = 8.4Hz, 2H), 6.97 (t, J = 7.2H
z, 1H), 6.51 (m, 3H), 4.55 (s, 2H), 4.17 (m, 1H),
3.50 (m, 2H), 3.44 (q, J = 7.2Hz, 2H), 2.62 (m, 2H),
2.33 (s, 3H), 2.33 (m, 1H), 1.80-1.60 (m, 2H), 1.0
6 (t, J = 7.2Hz, 3H).

Examples 61 (1) to 61 (13) Compounds prepared in Example 1, or compounds obtained by operating in the same manner as in Example 1 using the corresponding compounds and benzyl bromide. Alternatively, the corresponding compound was used and operated in the same manner as in the method of Example 43 → Example 2 → Example 3 → Example 4 to give the title compound having the following physical properties.

Example 61 (1) N-hydroxy-2-benzyl-4- [N- [4- (benzofuran-2-yl) phenylcarbonyl] amino]
Butyramide

[Chemical Formula 545] TLC: Rf 0.39 (chloroform: methanol = 1)
0: 1); NMR (d ₆ -DMSO): δ 10.43 (1H, s), 8.52 (1H, t,
J = 5.6Hz), 8.00 (2H, d, J = 8.8Hz), 7.94 (2H, d, J = 8.8
Hz), 7.71-7.63 (2H, m), 7.57 (1H, s), 7.39-7.16 (7
H, m), 3.30-3.15 (2H, m), 2.83 (1H, dd, J = 8.6, 13.
6Hz), 2.66 (1H, dd, J = 6.2, 13.6Hz), 2.44-2.31 (1H,
m), 1.88-1.53 (2H, m).

Example 61 (2) N-hydroxy-2- (3-phenylpropyl) -4-
[N- [4- (benzofuran-2-yl) phenylcarbonyl] amino] butyramide

[Chemical 546] TLC: Rf 0.41 (chloroform: methanol = 1
0: 1); NMR (d ₆ -DMSO): δ 10.48 (1H, s), 8.50 (1H, t,
J = 5.6Hz), 8.01 (2H, d, J = 8.8Hz), 7.95 (2H, d, J = 8.8
Hz), 7.71-7.63 (2H, m), 7.57 (1H, s), 7.39-7.11 (7
H, m), 3.25-3.15 (2H, m), 2.59-2.47 (2H, m), 2.18-
2.02 (1H, m), 1.82-1.36 (6H, m).

Example 61 (3) N-hydroxy-2- (2-phenylethyl) -4-
[N- [4- (benzofuran-2-yl) phenylcarbonyl] amino] butyramide

[Chemical 547] TLC: Rf 0.47 (chloroform: methanol = 1
0: 1); NMR (CD ₃ OD): δ 7.98 (2H, d, J = 8.4Hz), 7.89 (2
H, d, J = 8.4Hz), 7.64-7.60 (1H, m), 7.56-7.52 (1H,
m), 7.36-7.09 (7H, m), 7.32 (1H, brs), 3.51-3.24
(2H, m), 2.68-2.50 (2H, m), 2.28-2.14 (1H, m), 2.0
4-1.69 (4H, m).

Example 61 (4) N-hydroxy-2-benzyl-4- [N- [4- [2
E- (4-chlorophenyl) ethenyl] phenylcarbonyl] amino] butyramide

[Chemical 548] TLC: Rf 0.46 (chloroform: methanol = 1
0: 1); NMR (d ₆ -DMSO): δ 10.41 (1H, brs), 8.76 (1H, b
rs), 8.41 (1H, t, J = 5.4Hz), 7.83 (2H, d, J = 8.4Hz),
7.66 (2H, d, J = 8.4Hz), 7.65 (2H, d, J = 8.8Hz), 7.4
4 (2H, d, J = 8.8Hz), 7.35-7.12 (7H, m), 3.28-3.15
(2H, m), 2.83 (1H, dd, J = 8.4, 13.2Hz), 2.65 (1H, d
d. J = 5.8, 13.2Hz), 2.46-2.30 (1H, m), 1.86-1.51 (2
H, m).

Example 61 (5) N-hydroxy-2-benzyl-4- [N- (4-phenoxyphenylcarbonyl) amino] butyramide

[Chemical formula 549] TLC: Rf 0.45 (chloroform: methanol = 1
0: 1); NMR (d ₆ -DMSO): δ 10.40 (1H, s), 8.75 (1H, br)
s), 8.35 (1H, t, J = 5.6Hz), 7.84 (2H, d, J = 8.8Hz),
7.47-7.38 (2H, m), 7.30-6.99 (10H, m), 3.26-3.14
(2H, m), 2.82 (1H, dd, J = 8.4, 13.6Hz), 2.64 (1H, d
d, J = 6.2, 13.6Hz), 2.43-2.28 (1H, m), 1.84-1.49 (2
H, m).

Example 61 (6) N-hydroxy-2- (naphthalen-1-yl) methyl-4- [N- (4-phenoxyphenylcarbonyl) amino] butyramide

[Chemical 550] TLC: Rf 0.45 (chloroform: methanol = 1
0: 1); NMR (d ₆ -DMSO): δ 10.39 (1H, brs), 8.74 (1H, b
rs), 8.33 (1H, t, J = 5.4Hz), 8.08-8.03 (1H, m), 7.9
2-7.75 (2H, m), 7.81 (2H, d, J = 8.8Hz), 7.54-7.40
(9H, m), 7.00 (2H, d, J = 8.8Hz), 3.33-3.07 (4H, m),
2.63-2.45 (1H, m), 1.96-1.56 (2H, m).

Example 61 (7) N-hydroxy-2-isopropyl-4- [N- (4-
Phenoxyphenylcarbonyl) amino] butyramide

[Chemical 551] TLC: Rf 0.35 (chloroform: methanol = 1)
0: 1); NMR (d ₆ -DMSO): δ 10.39 (1H, brs), 8.34 (1H,
t, J = 5.6Hz), 7.90 (2H, d, J = 8.8Hz), 7.43 (2H, t, J
= 7.4Hz), 7.19 (1H, t, J = 7.4Hz), 7.09-7.04 (2H, m),
7.01 (2H, d, J = 8.8Hz), 3.22-3.06 (2H, m), 1.78-1.
61 (4H, m), 0.87 (3H, d, J = 6.8Hz), 0.83 (3H, d, J =
6.0Hz).

Example 61 (8) N-hydroxy-2- (quinolin-4-yl) methyl-
4- [N- (4-phenoxyphenylcarbonyl) amino] butyramide

[Chemical 552] TLC: Rf 0.38 (chloroform: methanol = 1
0: 1); NMR (d ₆ -DMSO): δ 10.41 (1H, brs), 8.76 (1H, b
rs), 8.76 (1H, d, J = 4.4Hz), 8.37 (1H, t, J = 5.6Hz),
8.15 (1H, br.d, 7.6Hz), 8.00 (1H, d, J = 7.4Hz), 7.
83 (2H, d, J = 8.8Hz), 7.77-7.69 (1H, m), 7.62-7.54
(1H, m), 7.47-7.38 (2H, m), 7.30 (1H, d, J = 4.4Hz),
7.23-7.16 (1H, m), 7.08-7.05 (2H, m), 7.01 (2H,
d, J = 8.8Hz), 3.33-3.14 (4H, m), 2.64-2.50 (1H, m),
1.98-1.58 (2H, m).

Example 61 (9) N-hydroxy-2- (2-pyridyl) methyl-4-
[N- (4-phenoxyphenylcarbonyl) amino]
Butyramide

[Chemical 553] TLC: Rf 0.34 (chloroform: methanol = 1)
0: 1); NMR (d ₆ -DMSO): δ 10.47 (1H, brs), 8.76 (1H,
s), 8.47-8.43 (1H, m), 8.34 (1H, t, J = 5.6Hz), 7.83
(2H, d, J = 8.8Hz), 7.66 (1H, dt, J = 1.8, 7.6Hz), 7.
46-7.39 (2H, m), 7.23-7.15 (3H, m), 7.09-7.03 (2H,
m), 7.01 (2H, d, J = 8.8Hz), 3.25-3.12 (2H, m), 2.97
(1H, dd, J = 7.6, 13.6Hz), 2.78 (1H, dd, J = 6.6, 13.6
Hz), 2.76-2.56 (1H, m), 1.85-1.46 (2H, m).

Example 61 (10) N-hydroxy-2- (3-pyridyl) methyl-4-
[N- (4-phenoxyphenylcarbonyl) amino]
Butyramide

[Chemical formula 554] TLC: Rf 0.20 (chloroform: methanol = 1)
0: 1); NMR (d ₆ -DMSO): δ 10.41 (1H, brs), 8.76 (1H,
s), 8.40-8.37 (3H, m), 7.85 (2H, d, J = 8.8Hz), 7.56
(1H, dt, J = 7.6, 2.2Hz), 7.47-7.38 (2H, m), 7.30-7.
16 (2H, m), 7.10-7.04 (2H, m), 7.02 (2H, d, J = 8.8H
z), 3.30-3.13 (2H, m), 2.87-2.66 (2H, m), 2.44-2.30
(1H, m), 1.86-1.52 (2H, m).

Example 61 (11) N-hydroxy-2- (naphthalen-2-yl) methyl-4- [N- (4-phenoxyphenylcarbonyl) amino] butyramide

[Chemical 555] TLC: Rf 0.45 (chloroform: methanol = 1
0: 1); NMR (d ₆ -DMSO): δ 10.40 (1H, d, J = 1.4Hz), 8.74
(1H, d, J = 1.4Hz), 8.36 (1H, t, J = 5.6Hz), 7.84 (2
H, d, J = 8.8Hz), 7.83-7.79 (3H, m), 7.65 (1H, brs),
7.50-7.33 (5H, m), 7.19 (1H, tt, J = 1.8, 7.4Hz),
7.09-7.04 (2H, m), 7.01 (2H, d, J = 8.8Hz), 3.30-3.1
2 (2H, m), 2.98 (1H, dd, J = 8.8, 13.6Hz), 2.83 (1H,
dd, J = 6.0, 13.6Hz), 2.50-2.40 (1H, m), 1.90-1.54
(2H, m).

Example 61 (12) N-hydroxy-2- (4-pyridyl) methyl-4-
[N- (4-phenoxyphenylcarbonyl) amino]
Butyramide

[Chemical 556] TLC: Rf 0.17 (chloroform: methanol = 1)
0: 1); NMR (d ₆ -DMSO): δ 10.44 (1H, brs), 8.78 (1H, b
rs), 8.42 (2H, d, J = 5.8Hz), 8.38 (1H, t, J = 5.6Hz),
7.85 (2H, d, J = 8.8Hz), 7.47-7.38 (2H, m), 7.23-7.1
5 (3H, m), 7.10-7.05 (2H, m), 7.02 (2H, d, J = 8.8H
z), 3.30-3.13 (2H, m), 2.87-2.66 (2H, m), 2.48-2.33
(1H, m), 1.85-1.52 (2H, m).

Example 61 (13) N-hydroxy-2- (3-methoxybenzyl) -4-
[N- (4-phenoxyphenylcarbonyl) amino]
Butyramide

[Chemical 557] TLC: Rf 0.41 (chloroform: methanol = 1
0: 1); NMR (d ₆ -DMSO): δ 10.40 (1H, s), 8.76 (1H, br)
s), 8.35 (1H, t, J = 5.6Hz), 7.84 (2H, d, J = 8.8Hz),
7.47-7.39 (2H, m), 7.24-7.04 (4H, m), 7.01 (2H, d,
J = 8.8Hz), 6.75-6.70 (3H, m), 3.70 (3H, s), 3.30-3.
10 (2H, m), 2.79 (1H, dd, J = 8.8, 13.4Hz), 2.61 (1
H, dd, J = 6.2, 13.4Hz), 2.43-2.29 (1H, m), 1.83-1.48
(2H, m).

Example 62 N-Hydroxy-2-isobutyl-4- [N- (4-phenoxyphenylcarbonyl) amino] butyramide

[Choice 558] Using the compound obtained by operating in the same manner as in Example 1 using the corresponding compound and 3-bromo-2-methylpropene, Example 43 → Example 27 → Example 2 →
The procedure of Example 3 → Example 4 was repeated to give the title compound having the following physical data. TLC: Rf 0.33 (chloroform: methanol = 1)
0: 1); NMR (d ₆ -DMSO): δ 10.47 (1H, s), 9.10-8.41 (1
H, brs), 8.33 (1H, t, J = 5.2Hz), 7.85 (2H, d, J = 8.8H
z), 7.23 (2H, t, J = 7.4Hz), 7.19 (1H, t, J = 7.4Hz),
7.09-7.04 (2H, m), 7.01 (2H, d, J = 8.8Hz), 3.21-3.1
1 (2H, m), 2.22-2.04 (1H, m), 1.76-1.34 (4H, m),
1.16-1.02 (1H, m), 0.84 (3H, d, J = 5.4Hz), 0.81 (3
H, d, J = 5.8 Hz).

Example 63 5-Methoxy-4 (S)-[N- [4- (4-chlorophenyl) phenylcarbonyl] amino] pentanoic acid

[Chemical 559] 5-Hydroxy-4 obtained by the same procedure as in Example 37 → Example 38 using the corresponding compound.
(S)-[N- (4'-chlorobiphenyl-4-yl)
Carbonyl] aminopentanoic acid methyl ester (1.7
g) in tetrahydrofuran (5 ml), silica gel (500 mg) and diazomethane ether (4 m).
l) The solution was added. The mixture was stirred at room temperature for 10 minutes.
The reaction solution was concentrated. Tetrahydrofuran residue (5m
l) A solution of diazomethane in ether (4 ml) was added to the solution and stirred for 10 minutes. This operation was repeated 10 times. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 9: 1 → 3: 1) to obtain the methyl ester form of the title compound (1.42 g). The methyl ester compound (1.4 g) was used and operated in the same manner as in Example 2 to obtain the title compound (1.2 g) having the following physical data. TLC: Rf 0.50 (methylene chloride: methanol = 9:
1).

Example 64 N-hydroxy-5-methoxy-4 (S)-[N- [4
-(4-Chlorophenyl) phenylcarbonyl] amino] pentanamide

[Chemical 560] The title compound having the following physical data was obtained by operating in the same manner as in the method of Example 3 → Example 4 using the compound prepared in Example 63. TLC: Rf 0.38 (chloroform: methanol = 1
0: 1); NMR (d ₆ -DMSO): δ 10.35 (1H, brs), 8.27 (1H,
d, J = 8.4Hz), 7.95 (2H, d, J = 8.4Hz), 7.77 (2H, d, J
= 8.4Hz), 7.76 (2H, d, J = 8.8Hz), 7.54 (2H, d, J = 8.8
Hz), 4.20-4.03 (1H, m), 3.42 (1H, dd, J = 6.2, 9.6H
z), 3.33 (1H, dd, J = 6.2, 9.6Hz), 3.26 (3H, s), 2.0
8-1.95 (2H, m), 1.94-1.58 (2H, m).

Reference Example 7 2 (S) -Methyl-5-hydroxy-4 (S)-(N-
Benzyloxycarbonyl) aminopentanoic acid t-butyl ester

[Chemical 561] Example 39 → Example 45 → Example 46 using 4 (S) -carboxy-4- (N-benzyloxycarbonylamino) butanoic acid t-butyl ester (using methyl iodide instead of benzyl bromide) ) → The same operation as in Example 48 was carried out to give the title compound having the following physical data. TLC: Rf 0.36 (hexane: ethyl acetate = 3:
1).

Example 65 2 (S) -Methyl-5-succinimide-4 (S)-
[N- (4-chlorophenylcarbonyl) amino] pentanoic acid

[Chemical 562] The compound prepared in Reference Example 7 (1.42 g), succinimide (521 mg) and triphenylphosphine (1.38 g).
g) was dissolved in anhydrous tetrahydrofuran (20 ml),
Cooled to 0 ° C. Diethyl azodicarboxylate (2.3 ml; 40% toluene solution) was added dropwise to the mixture, and the mixture was stirred at 0 ° C for 2
Stir for hours. The reaction mixture was concentrated. The residue is subjected to silica gel or column chromatography (hexane: acetone =
9: 1, hexane: ethyl acetate = 3: 1 → 2: 1) 2
After purification twice, a mixture (2.09 g) of the desired product and triphenylphosphine oxide was obtained. This mixture of methanol (2
0 ml) solution to 10% palladium on carbon (400 mg)
Was added, and the mixture was stirred under a hydrogen atmosphere at room temperature for 1 hour. The reaction mixture was filtered through Celite (trade name), and the filtrate was concentrated. Dissolve the residue in dichloromethane (20 ml) and 0 ° C.
Cooled to. Triethylamine (2 ml) and p-chlorobenzoyl chloride (1.10 g) were added to this solution,
Stirred at 0 ° C. for 2 hours. The reaction mixture was diluted with ethyl acetate, washed successively with 1N hydrochloric acid, water, saturated aqueous sodium carbonate solution, water and saturated brine, dried over anhydrous sodium sulfate, and concentrated. The residue was subjected to silica gel or column chromatography (hexane: ethyl acetate = 3: 1 → 2: 1 → 3:
Purification in 2) gave the t-butyl ester form of the title compound (1.29 g). The title compound (845 mg) having the following physical properties was obtained by performing the same procedure as in Example 29 using t-butyl ester (1.07 g).
Got TLC: Rf 0.40 (methylene chloride: methanol = 9:
1); NMR (CDCl ₃ ): δ 7.64 (d, J = 9.0Hz, 2H), 7.35
(d, J = 9.0Hz, 2H), 6.55 (d, J = 8.7Hz, 1H), 4.51
(m, 1H), 3.69 (dd, J = 13.8, 9.3Hz, 1H), 3.62 (dd,
J = 13.8, 4.2Hz, 1H), 2.75-2.51 (m, 5H), 1.97 (dd
d, J = 14.4, 10.8, 7.2Hz, 1H), 1.65 (ddd, J = 14.
4, 6.3, 4.2Hz, 1H), 1.26 (d, J = 7.2Hz, 3H).

Example 66 N-Hydroxy-2 (S) -methyl-5-succinimide-4 (S)-[N- (4-chlorophenylcarbonyl) amino] pentanamide

[Chemical 563] The title compound having the following physical data was obtained by operating in the same manner as in the method of Example 3 → Example 4 using the compound prepared in Example 65. TLC: Rf 0.42 (methylene chloride: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.35 (d, J = 1.5Hz, 1H), 8.65
(d, J = 1.5Hz, 1H), 8.12 (d, J = 9.0Hz, 1H), 7.75 (d,
J = 8.4Hz, 2H), 7.51 (d, J = 8.4Hz, 2H), 4.22 (m, 1H),
3.49 (m, 2H), 2.53 (m, 4H), 2.17 (m, 1H), 1.70 (d
dd, J = 13.8, 10.5, 5.4Hz, 1H), 1.50 (ddd, J = 13.8,
9.0, 4.5Hz, 1H), 0.96 (d, J = 6.9Hz, 3H).

Example 66 (1) N-Hydroxy-2 (S) -methyl-5-succinimidooxy-4 (S)-[N-methyl-N- (4-nitrophenylcarbonyl) amino] pentanamide

[Chemical 564] Using the compound prepared in Reference Example 7, Example 65 (N-hydroxysuccinimide was used in place of succinimide, and p-chlorobenzoyl chloride was used in place of p-chlorobenzoyl chloride.
-Nitrobenzoyl chloride is used, and the t-butyl ester form is used in the next reaction. ) → Example 5 → Example 29 → The procedure was the same as in Example 66 to obtain the title compound having the following physical data. TLC: Rf 0.45 (methylene chloride: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.50 (s, 0.7H), 10.45 (s,
0.3H), 8.28 (d, J = 9.0Hz, 1.4H), 8.24 (d, J = 9.0Hz,
0.6H), 7.69 (d, J = 9.0Hz, 1.4H), 7.61 (d, J = 9.0Hz,
0.6H), 4.86 (m, 0.7H), 4.20-4.00 (m, 2H), 3.72 (m,
0.3H), 2.89 (s, 0.9H), 2.71 (s, 2.1H), 2.60 (m, 4
H), 2.20-1.70 (m, 2H), 1.60-1.30 (m, 1H), 1.05 (d,
J = 6.9Hz, 2.1H), 0.74 (d, J = 6.9Hz, 0.9H).

Reference Example 8 5-Ethoxymethoxy-4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanol

[Chemical 565] Example 37 using the corresponding compound instead of Reference Example 4
→ Example 39 → Example 41 → 5-ethoxymethoxy-4 obtained by operating in the same manner as in the method shown in Example 42
(S)-(N- (4-phenoxyphenylcarbonyl)
Aminopentanoic acid (3.62 g) in tetrahydrofuran (1
(00 ml) solution was cooled to 0 ° C. and then triethylamine (1.
69 ml) and ethyl chloroformate (1.2 ml) were added dropwise. The mixture was stirred at 0 ° C. for 1.5 hours. Sodium borohydride (0.5 eq) was added to the reaction mixture and added
After stirring for 0 minutes, acetic acid (5 ml) was added dropwise and the mixture was stirred for 30 minutes. The reaction solution was concentrated. Ethyl acetate and water were added to the residue, and the organic layer was separated. The organic layer was washed with water and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel column chromatography (ethyl acetate: hexane = 2: 1 (containing 1% triethylamine) → 4: 1) to obtain the title compound (1.84 g) having the following physical properties. TLC: Rf 0.52 (ethyl acetate: hexane = 4:
1).

Reference Example 9 1-Bromo-5-ethoxymethoxy-4 (S)-[N-
(4-phenoxyphenylcarbonyl) amino] pentane

[Chemical 566] A solution of the compound (490 mg) produced in Reference Example 8 in methylene chloride (10 ml) was added with triphenylphosphine (40
9 mg) and sodium hydrogen carbonate (328 mg) were added, and the mixture was cooled to 0 ° C. Carbon tetrabromide (647 m
A solution of g) in methylene chloride (5 ml) was added dropwise, and the mixture was stirred at 0 ° C for 1
Stir for 5 minutes. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with water and saturated sodium chloride, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 3: 1) to give the title compound (293 g) having the following physical data. TLC: Rf 0.41 (hexane: ethyl acetate = 2:
1).

Example 67 1-Acetylthio-5-ethoxymethoxy-4 (S)-
[N- (4-phenoxyphenylcarbonyl) amino]
Pentane

[Chemical 567] Potassium thioacetate (113 mg) was added to a solution of the compound (290 mg) produced in Reference Example 9 in acetone (8 ml), and the mixture was refluxed for 2 hours. After cooling, pour the reaction solution into water,
It was extracted with ethyl acetate. The extract was washed with water and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate,
Concentrated. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 3: 1) to give the title compound (268 mg) having the following physical data. TLC: Rf 0.28 (hexane: ethyl acetate = 2:
1). NMR (CDCl ₃ ): δ 7.77 (d, J = 8.7Hz, 2H), 7.38
(t, J = 7.5Hz, 2H), 7.17 (t, J = 7.5Hz, 1H), 7.05 (d, J
= 7.5Hz) and 7.01 (d, J = 8.7Hz) total 4H, 6.54 (d, J
= 8.7Hz, 1H), 4.72 (d, J = 6.9Hz, 1H), 4.68 (d, J = 6.9
Hz, 1H), 4.35-4.25 (m, 1H), 3.74 (dd, J = 10, 3Hz, 1
H), 3.63-3.58 (m, 3H), 2.92 (t, J = 6.9Hz, 2H), 2.32
(s, 3H), 1.80-1.65 (m, 4H), 1.21 (t, J = 7.2Hz, 3
H).

Example 68 5-Ethoxymethoxy-4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanethiol

[Chemical 568] A solution of the compound (230 mg) produced in Example 67 in methanol (5 ml) was added with potassium carbonate (146 m) at room temperature.
g) was added and stirred for 2 hours. The reaction solution was poured into ice / 1N hydrochloric acid and extracted with ethyl acetate. The extract was washed with water and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 3: 1),
The title compound (170 mg) having the following physical data was obtained. TLC: Rf 0.27 (hexane: ethyl acetate = 2:
1), NMR (CDCl ₃ ): δ 7.77 (d, J = 9Hz, 2H), 7.40-7.34
(m, 2H), 7.17 (t, J = 7.5Hz, 1H), 7.08-6.96 (m, 4
H), 6.54 (d, J = 9Hz, 1H), 4.73 (d, J = 6.9Hz, 1H), 4.
69 (d, J = 6.9Hz, 1H), 4.34-4.24 (m, 1H), 3.77 (dd,
J = 10.2, 3Hz, 1H), 3.66-3.56 (m, 3H), 2.63- 2.53
(m, 2H), 1.83-1.65 (m, 4H), 1.37 (t, J = 7.5Hz, 1H),
1.22 (t, J = 7.2Hz, 3H).

Example 69 5-Ethoxymethoxy-4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanoic acid methyl ester

[Chemical 569] Using 4 (S) -carboxy-4- (N-benzyloxycarbonylamino) butanoic acid methyl ester, the method shown in Example 39 → Example 41 (using ethoxymethyl chloride instead of methoxymethyl chloride). Methanol (150 g) of 5 (S) -ethoxymethoxy-4 (S)-(benzyloxycarbonyl) aminopentanoic acid methyl ester (10 g) obtained by the same operation was used.
ml) solution, 10% palladium on carbon (1 g) was added,
The mixture was heated under reflux for 2 hours under a hydrogen atmosphere. The reaction mixture was cooled, the insoluble material was filtered through Celite, and the filtrate was concentrated. A solution of the residue in dimethylformamide (DMF) (150 ml) was added with 1-hydroxybenzotriazole monohydrate (4.
8 g) and 4-phenoxybenzoic acid (6 g),
The mixture was ice-cooled, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (6.5 g) was added, and then triethylamine (4.7 ml) was added dropwise, followed by stirring at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with 1N hydrochloric acid, saturated aqueous sodium carbonate solution, and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated. The residue was washed with n-hexane to give the title compound (8.1 g) having the following physical data.
Got TLC: Rf 0.22 (n-hexane: ethyl acetate = 1: 1
1).

Example 70 2 (S) -Methyl-5-ethoxymethoxy-4 (S)-
[N- (4-phenoxyphenylcarbonyl) amino]
Pentanoic acid

[Chemical 570] Using the compound prepared in Example 69, Example 43 (using methyl iodide in place of benzyl bromide) → The same operation as in Example 2 is carried out to give the following physical properties. The compound was obtained. TLC: Rf 0.45 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1), NMR (DMSO-d ₆ ): d 7.75 (2H, d, J = 8.8Hz), 7.37 (2
H, m), 7.17 (1H, t, J = 7.4Hz), 7.03 (2H, m), 6.97 (2H,
d, J = 8.8Hz), 6.58 (1H, d, J = 9.1Hz), 4.71 (1H, d, J =
6.9Hz), 4.68 (1H, d, J = 6.9Hz), 4.43 (1H, m), 3.74 (1
H, dd, J = 3.0, 10.2Hz), 3.65-3.55 (3H, m), 2.56 (1H,
m), 2.16 (1H, m), 1.68 (1H, m), 1.27 (3H, d, J = 6.9Hz),
1.18 (3H, t, J = 7.1Hz).

Examples 70 (1) to 70 (2) Using the corresponding compounds and operating in the same manner as in Example 69 → Example 70, the following compounds were obtained.

Example 70 (1) 2 (S) -allyl-5-ethoxymethoxy-4 (S)-
[N- (4-phenoxyphenylcarbonyl) amino]
Pentanoic acid

[Chemical 571] TLC: Rf 0.49 (chloroform: methanol: acetic acid = 100: 10: 1).

Example 70 (2) 2 (S) -methyl-5-ethoxymethoxy-4 (S)-
[N- [4- (4-cyanophenyl) phenylcarbonyl] amino] pentanoic acid

[Chemical 572] NMR (DMSO-d ₆ ): d 12.7 (1H, s), 8.29-8.25 (2H,
m), 7.97-7.92 (6H, m), 7.83 (2H, d, J = 8.4Hz), 4.59 (2
H, s), 4.28-4.16 (1H, m), 3.53-3.42 (4H, m), 2.39-2.
30 (1H, m), 1.95-1.84 (1H, m), 1.64-1.54 (1H, m), 1.1
2-1.04 (6H, m).

Example 71 N-Hydroxy-2 (S) -methyl-5-ethoxymethoxy-4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide

[Chemical 573] The title compound having the following physical properties values was obtained by the same procedure as in Example 3 → Example 4 using the compound prepared in Example 70. TLC: Rf 0.40 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1); NMR (DMSO-d ₆ ): d 10.37 (1H, brs), 8.66 (1H, br
s), 8.03 (1H, d, J = 8.8Hz), 7.87 (2H, d, J = 8.8Hz), 7.
43 (2H, dd, J = 7.4, 8.5Hz), 7.20 (1H, t, J = 7.4Hz), 7.
06 (2H, d, J = 8.5Hz), 7.02 (2H, d, J = 8.8Hz), 4.59 (2H,
s), 4.14 (1H, m), 3.50-3.45 (4H, m), 2.17 (1H, m),
1.66 (2H, m), 1.09 (3H, t, J = 7.1Hz), 1.01 (3H, d, J =
6.9 Hz).

Examples 71 (1) to 71 (2) Using the compounds prepared in Examples 70 (1) or 70 (2), the same operation as in Example 71 was carried out,
The compound shown below was obtained.

Example 71 (1) N-Hydroxy-2 (S) -allyl-5-ethoxymethoxy-4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide

[Chemical 574] TLC: Rf 0.26 (chloroform: methanol: acetic acid = 100: 10: 1); NMR (d ₆ -DMSO): δ 10.42 (1H, s), 8.70 (1H, s),
8.03 (1H, d, J = 8.8Hz), 7.89-7.85 (2H, m), 7.47-7.37 (2
H, m), 7.23-7.15 (1H, m), 7.09-6.99 (4H, m), 5.77-5.5
5 (1H, m), 5.03-4.92 (2H, m), 4.58 (2H, s), 4.19-4.05
(1H, m), 3.53-3.42 (2H, m), 3.47 (2H, q, J = 7.0Hz),
2.19-2.17 (3H, m), 1.38-1.82 (2H, m), 1.08 (3H, t, J =
7.0Hz).

Example 71 (2) N-hydroxy-2 (S) -methyl-5-ethoxymethoxy-4 (S)-[N- [4- (4-cyanophenyl)
Phenylcarbonyl] amino] pentanamide

[Chemical 575] TLC: Rf 0.48 (chloroform: methanol = 9:
1); NMR (d ₆ -DMSO): δ 10.37 (1H, s), 8.18 (1H, d,
J = 8.4Hz), 7.99-7.91 (6H, m), 7.83 (2H, d, J = 8.2H
z), 4.58 (2H, s), 4.24-4.07 (1H, m), 3.54-3.41 (4
H, m), 2.26-2.10 (1H, m), 1.74-1.62 (2H, m), 1.12-
0.97 (6H, m).

[Formulation Example] Formulation Example 1 The following components were admixed in a conventional method and punched out to obtain 100 tablets each containing 50 mg of the active ingredient. -N-hydroxy-2 (S) -methyl-5-ethoxymethoxy-4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide ... 5.0 g-Carboxymethyl cellulose calcium (disintegrant) ... 0.2g ・ Magnesium stearate (lubricant) …… 0.1g ・ Microcrystalline cellulose …… 4.7g

Formulation Example 2 The following components were admixed in a conventional manner, the solution was sterilized in a conventional manner, 5 ml each was filled in an ampoule, and lyophilized in a conventional manner to contain 20 mg of the active ingredient in one ampoule. I got 100 ampoules. -N-hydroxy-2 (S) -methyl-5-ethoxymethoxy-4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide ...... 2.0 g-mannitol ...... 20 g-distilled water ...... 500 ml steam

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI A61P 1/16 A61P 1/16 7/00 7/00 9/00 9/00 9/10 101 9/10 101 11/00 11 / 00 13/12 13/12 15/00 15/00 19/02 19/02 19/10 19/10 27/02 27/02 29/00 101 29/00 101 35/00 35/00 35/02 35 / 02 35/04 35/04 37/00 37/00 43/00 111 43/00 111 C07C 259/06 C07C 259/06 (56) Reference JP-A 63-165352 (JP, A) JP-A 62 -10052 (JP, A) Japanese Patent Publication No. 9-505038 (JP, A) International Publication 89/02431 (WO, A1) US Patent 2745875 (US, A) (58) Fields investigated (Int. Cl. ⁷ , DB) Name) C07C 235/00 A61K 31/00 C07C 259/00 CA (STN) REGISTRY (STN)

Claims (4)

(57) [Claims] 1. A compound represented by the general formula (1): (In the formula, R ¹ represents —COOR ¹⁰ or —CONHOR ¹⁰ , R ¹⁰ represents a hydrogen atom or a C 1-8 alkyl group, and R ¹¹ represents (i) a hydrogen atom, (ii) a C 1-8 alkyl group, or
(iii) represents a C1-8 alkyl group substituted by -OR ^15, R ¹⁵ is a hydrogen atom, C1-8 alkyl group (provided that. excluding ethyl group), a benzyl group or C1-8 alkoxy group, Represents a substituted C1-8 alkyl group. ) The aminobutanoic acid derivative shown by these, or those nontoxic salts. 2. The compound is N-hydroxy-2 (S) -methyl-5-methoxymethoxy-4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide, N-hydroxy-2 (S). ) -Methyl-5- (2-methoxyethoxy) methoxy-4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide, N-hydroxy-2 (S) -methyl-5-benzyloxymethoxy -4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide, N-hydroxy-2 (S) -methyl-5-hydroxy-
The compound according to claim 1, which is 4 (S)-[N- (4-phenoxyphenylcarbonyl) amino] pentanamide or a non-toxic salt thereof. 3. A metalloproteinase inhibitor containing the aminobutanoic acid derivative represented by the general formula (1) according to claim 1 or a non-toxic salt thereof as an active ingredient. 4. Rheumatoid arthritis, osteoarthritis, which occurs when secretion of MMP containing the aminobutanoic acid derivative represented by the general formula (1) according to claim 1 or a non-toxic salt thereof as an active ingredient is abnormally enhanced, Pathological bone resorption, osteoporosis, periodontal disease, interstitial nephritis, arteriosclerosis, emphysema, cirrhosis,
Prevention of corneal damage, cancer cell metastasis invasion or proliferation, autoimmune disease, disease caused by leukocyte cell migration or invasion, angiogenesis, multiple sclerosis, aortic aneurysm, endometriosis and / or Therapeutic agent.