JPH09309875A - Sulfonylamino acid derivative and matrix metalloprotease inhibitor containing solfonyl amino acid derivative as active ingredient - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a new compound useful as a matrix metalloprotease inhibitor. SOLUTION: This compound is represented by formula I [R<1> is H or a 1-4C alkyl; R<2> is H, a 1-8C alkyl, phenyl, etc.; J is a single bond, a 2-4C alkylene, a group of formula II (R<4> and R<5> are each H, a 1-4C alkyl, etc.), etc.; G is (CH2 )m , etc.; (m) is 2-4; E is CONR<3> , NR<3> CO, COO, OCO, etc., (R<3> is H, a 1-4C alkyl, etc.); A is H, a 1-8C alkyl or a 3-7C cycloalkyl or Ar; Ar is a carbon ring, a heterocyclic aryl, etc.], e.g. N-[[4-(benzoylamino)phenyl]sulfonyl]glycine. The compound of formula I is obtained by subjecting a compound of formula III (J<1> is same as J; R<2-1> is a 1-8C alkyl, phenyl, etc.) to amidation reaction with a compound of the formula A<1> -J<1> -COOH (A<1> is same as A) and as necessary deprotecting the reaction product. The compound is useful for preventing and treating rheumatics, arthrosteitis, osteoporosis, periodontal diseases, interstitial nephritis, arteriosclerosis, liver emphysema, cirrhosis, corneal injury, autoimmune disease, etc.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a sulfonylamino acid derivative and a matrix metalloproteinase inhibitor containing the sulfonylamino acid derivative as an active ingredient.

More specifically, general formula (I)

Embedded image (Wherein all symbols have the same meanings as described below) and a matrix metalloproteinase inhibitor containing a non-toxic salt thereof as an active ingredient, and a general formula (I). The present invention relates to novel sulfonylamino acid derivatives, non-toxic salts thereof and methods for producing them.

[0003]

BACKGROUND OF THE INVENTION Matrix metalloproteinases (hereinafter abbreviated as MMPs) have zinc (hereinafter, Z) as an active center.
Abbreviated as n ²⁺ . ) Is a neutral metalloproteinase, and acts under physiological conditions by degrading collagen, laminin, proteoglycan, fibronectin, elastin, gelatin, etc. to grow and remodel joint tissue, bone tissue, connective tissue, etc. are doing. As of MMP, ten or more molecular species having different primary structures have been identified so far. The properties common to each of these enzymes are (1) having Zn ²⁺ in the active center and requiring calcium (Ca ²⁺ ) for enzyme activity, (2) being secreted as a latent enzyme, and extracellularly Receive activation,
(3) The amino acid sequence has high homology, (4)
It is known that it has the ability to decompose various extracellular matrix components existing in the body, and (5) its activity is inhibited by a common inhibitor, a tissue metalloproteinase inhibitor (TIMP).

Inhibitors of MMP are considered to be useful for the prevention and / or treatment of various diseases caused by abnormally enhanced secretion and activity of MMP. Such diseases include, for example, rheumatism, osteoarthritis, pathological bone resorption, osteoporosis, periodontal disease, interstitial nephritis, arteriosclerosis, emphysema, cirrhosis, corneal damage, cancer cell metastasis infiltration and proliferation diseases, Examples thereof include autoimmune diseases (Crohn's disease, Sjogren's disease, etc.), diseases caused by transmigration and infiltration of leukocyte cells, and angiogenesis.

[0005]

2. Description of the Related Art Several compounds having a matrix metalloproteinase inhibitory action are known. Among them, the substrate near the cleavage point of collagen (Gly-Ile-
Ala-Gly or Gly-Leu-Ala-Gl
It is known that y) has a high affinity for collagenase. Numerous studies have been conducted on matrix analog metalloproteinase inhibitors that are chemically modified with a zinc-affinity group at the cleavage site of this substrate [Inhibito
rs of matrix metalloproteinases (MMP's), Nigel
RA Beeley, Phillip RJ Ansell, Andrew JP Docherty
Curr. Opin. Ther. Patents., 4 , 7-16 (1994), Curr
ent Drugs Ltd ISSN 0962-2594]. However, these substrate analog inhibitors are expected to have various problems because they are peptide analogs. For this reason,
It is desired to non-peptize these inhibitors, and some reports have been made.

[0006] For example, in the specification of EP 606046, the general formula (X)

Embedded image

[Wherein Ar ^X is carbocyclic or heterocyclic aryl; R ^X is hydrogen, lower alkyl, carbocyclic aryl-lower alkyl, etc .; R ^1X is hydrogen, lower alkyl, Carbocyclic aryl-lower alkyl and the like; R ^2X is
Hydrogen or lower alkyl; or

In the formula (b), R ^X and R ^1X together with the chain to which they are attached form 1,2,3,4-tetrahydro-isoquinoline, piperidine ring, etc .; Ar ^X
And R ^2X has the meaning defined in (a); or

(C) R ^1X and R ^2X are taken together with the carbon atom to which they are attached, a C3-C7 cycloalkane, oxa-cyclohexane, thia, which is unsubstituted or substituted by lower alkyl. - cyclohexane; and Ar ^X and R ^2X has the meaning defined (a). ] It is disclosed that the aryl sulfonamide derivative represented by the formula [3] has a matrix metalloproteinase inhibitory action.

The general formula (Y)

Embedded image

[Wherein R ^1Y is a hydrogen atom, R ^2Y is a hydrogen atom; R ^1Y is a 4-methoxy group, R ^2Y is a hydrogen atom; R ^1Y is 4;
A fluoro group, R ^2Y is a hydrogen atom; R ^1Y is a 4-nitro group,
R ^2Y is hydrogen atom; R ^1Y is 3-nitro group, R ^2Y is hydrogen atom; R ^1Y is 2-nitro group, R ^2Y is hydrogen atom; R ^1Y is 4-
Formyl group, R ^2Y is hydrogen atom; R ^1Y is hydrogen atom, R ^2Y is (S) -phenyl group; R ^1Y is hydrogen atom, R ^2Y is (R)-
Phenyl group; R ^1Y is 4-methyl group, R ^2Y is (S) -phenyl group; R ^1Y is 4-methyl group, R ^2Y is (R) -phenyl group; R ^1Y is 4-methoxy group, R ^2Y is (S) -phenyl group; R ^1Y is 4-methoxy group, R ^2Y is (R) -phenyl group; R ^1Y is 4-fluoro group, R ^2Y is (S) -phenyl group; R ^1Y is 4-fluoro group R ^2Y is a (R) -phenyl group; R ^1Y is a 4-nitro group, R ^2Y is a (S) -phenyl group;
^{Alternatively,} R ^1Y represents a 4-nitro group and R ^2Y represents a (R) -phenyl group. ] It is disclosed that the phenylsulfonyl amino acid derivative represented by the formula [4] has an aldose reductase inhibitory action (Biochemical Pharmacology, 40 , 2219).
-2226 (1990)).

Further, in EP 347168, the general formula (Z)

[Chemical 12]

(In the formula, Y ^Z represents a sulfonyl (—SO ₂ —) group or a carbonyl (—CO—) group, R ^1Z and R ^2Z may be the same or different, and a hydrogen atom,
C1 optionally substituted with a carboxy (—COOH) group
To 16 alkyl groups and the like, R ^3Z is a hydrogen atom, a hydroxy group, a C1-6 alkyl group, a halogen atom, C1-4.
Represents an alkoxy group or a C2-5 acyloxy group,
mZ represents an integer of 1 to 4. (However, the symbols in the group are extracted only for the necessary parts.)
It is disclosed that the pivalic acid / p-substituted phenyl ester derivative represented by the above has an elastase inhibitory action.

Further, the following compounds are Antimicrobial ac
It has been disclosed to have tivity [J. Serb. Chem.
Soc. 56 (6), 311-318 (1991)]. N-[[4- (2,4
-Dichlorobenzoylamino) phenyl] sulfonyl]
Glycine, N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] -D, L-alanine,
N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] -β-alanine, N-[[4-
(2,4-Dichlorobenzoylamino) phenyl] sulfonyl] -L-valine, N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] -D, L
-Valine, N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] -L-leucine, N-
[[4- (2,4-Dichlorobenzoylamino) phenyl] sulfonyl] -D, L-leucine, N-[[4-
(2,4-Dichlorobenzoylamino) phenyl] sulfonyl] -D, L-serine, N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] -L
-Phenylalanine, N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] -L-tyrosine, N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] -D, L -Alanine methyl ester, N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] -L-valine methyl ester, N-[[4- (2,4-dichlorobenzoylamino) phenyl] Sulfonyl] -D, L-valine
Methyl ester, N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] -L-leucine methyl ester, N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl]- D, L-serine methyl ester, N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] -L-tyrosine methyl ester.

Further, the following compounds are Antifilarial act
disclosed to have ivity [Indian J. Chem.
30B , 182-187 (1991)]. N-[[4- (3-nitrobenzoylamino) phenyl] sulfonyl] -L-aspartic acid, N-[[3- (3-nitrobenzoylamino)
Phenyl] sulfonyl] -L-aspartic acid, N-
[[4- (3-Aminobenzoylamino) phenyl] sulfonyl] -L-aspartic acid, N-[[3- (3-
Aminobenzoylamino) phenyl] sulfonyl] -L
-Aspartic acid.

Further, the following compounds are Antineoplastic a
It is disclosed to have ctivity [Indian J. Che
m. 28B , 843-847 (1989)]. N-[[4- (benzoylamino) phenyl] sulfonyl] -L-glutamic acid,
N-[[4-[[(4-chlorobenzoylamino) phenyl] sulfonyl] -L-glutamic acid, N-[[4-
[[(4-Nitrobenzoylamino) phenyl] sulfonyl] -L-glutamic acid.

[0017]

OBJECTS OF THE INVENTION The present inventors have conducted extensive studies to find compounds having a matrix metalloproteinase inhibitory action, and as a result, found that the sulfonylamino acid derivative represented by the general formula (I) achieves the object. The sulfonylamino acid derivative represented by the general formula (I) of the present invention is a compound that has never been known as a matrix metalloproteinase inhibitor. Further, most of the sulfonylamino acid derivatives represented by the general formula (I) are novel compounds that have hitherto been unknown.
Further, it was also found that the compound of the present invention has a specific inhibitory effect on gelatinases among matrix metalloproteinases.

[0018]

DISCLOSURE OF THE INVENTION The present invention provides (i) general formula (I)

Embedded image [In the formula, R ¹ represents a hydrogen atom or a C1~4 alkyl group,, R ² is 1) hydrogen atom, 2) C1-8 alkyl group, 3) a phenyl group or a 4) a phenyl group,, -OCOR ¹⁶ groups (wherein R ¹⁶ is C1 to
Represents a 4-alkyl group. ), Or a CNR ¹⁷ R ¹⁸ group (in which R ¹⁷ and R ¹⁸ each independently represent a hydrogen atom or a C1-4 alkyl group).
Represents 1 to 4 alkyl groups,

E is 1) --CO--NR ³ --group (wherein R ³ is a hydrogen atom, C1 to
4 alkyl group, a phenyl group, or a C1-4 alkyl group substituted with a phenyl group. ), 2) -NR ³ -CO- group (wherein R ³ has the same meaning as described above), 3) -CO-O- group, 4) -O-CO- group, 5) -NR ³ —CO—NR ³ — group (wherein R ³ has the same meaning as described above), 6) —CO—CH ₂ — group, 7) —CO— group, 8) —O—CO—NR ³ —. Group (in the group, R ³ has the same meaning as described above), 9) —NR ³ —CO—O— group (in the group, R ³ has the same meaning as described above), 10) —O—CO—. O-group, 11) -CS-NR ³ -group (in the group, R ³ represents the same meaning as described above), 12) -NR ³ -CS- group (in the group, R ³ represents the same meaning as described above). , 13) —NR ³ —CS—NR ³ — group (in the group, R ³ has the same meaning as described above), 14) —O—CS—NR ³ — group (in the group, R ³ Represents the same meaning as described above.), 15 (Wherein, R ³ are as defined above.) -NR ³ -CS-O- group, 16) -CS-O- group, 17) -O-CS- group or 18,) -O-CS Represents an —O— group,

A is 1) a hydrogen atom, 2) a C1-8 alkyl group, 3) a C3-7 cycloalkyl group, or 4) an Ar group (wherein the Ar group represents a carbocyclic or heterocyclic aryl, and 1 From 3 C1-15 alkyl groups, C1
To 15 alkoxy group, halogen atom, nitro group, cyano group, guanidino group, amidino group, hydroxyl group, benzyloxy group, NR ⁹ R ¹⁰ group (wherein R ⁹ and R ¹⁰ are independently a hydrogen atom or represents a C1~4 alkyl group), -.. COOR ¹¹ group (wherein, R ¹¹ is represents a hydrogen atom or a C1~4 alkyl group), a trifluoromethyl group, a phenyl group or a substituted heterocyclic group May be. )

J is 1) a single bond, 2) a C2-4 alkylene group, 3) a C2-4 alkenylene group, or

Embedded image (In the group, R ⁴ and R ⁵ are each independently (i)
Hydrogen atom, (ii) C1-4 alkyl group, (iii) C1
4 alkoxy group, or together with the carbon atom to which R ⁴ and R ⁵ are bonded, represents a C3-7 cycloalkyl group. )

G is

Embedded image 1) — (CH ₂ ) _m — group (wherein m represents 2, 3 or 4) or

[0023]

Embedded image (In the group, R ⁶ and R ⁷ are each independently

(I) hydrogen atom, (ii) C1-8 alkyl group, (iii) -COOR ⁸ group (wherein R ⁸ is a hydrogen atom,
It represents a C1-8 alkyl group, a phenyl group, or a C1-4 alkyl group substituted with a phenyl group. ), (Iv)
Ar group (wherein Ar represents the same meaning as described above),
(V) heterocyclic groups, (vi) -COOR ⁸ group (wherein, R ⁸ are as defined above.), C1 -4 alkoxy group,
Hydroxyl, benzyloxy, -NR ¹² R ¹³ group (in radical, R
¹² and R ¹³ are each independently a hydrogen atom or C
Represents a 1-4 alkyl group. ), —NR ¹⁴ COOR ¹⁵ group (in the group, R ¹⁴ represents a hydrogen atom or a C1-4 alkyl group, R ¹⁵ represents a hydrogen atom, a C1-8 alkyl group, a phenyl group, or a C1-4 group substituted with a phenyl group. 4 alkyl group), C1 substituted with an Ar group or a heterocyclic group
~ 8 alkyl group (provided that one carbon atom of the C1-8 alkyl group may be replaced by one sulfur atom), or together with the carbon atom to which R ⁶ and R ⁷ are bonded. Represents a C3-7 cycloalkyl group. ) Is represented.

However, E is --O--CO--NR ^3-, --O
-CO-O -, - O- CS-NR 3 - , or -O-CS
Excluding compounds in which —O—, J is a single bond and A is a hydrogen atom. ] The sulfonyl amino acid derivative shown by these,
And a matrix metalloproteinase inhibitor containing a non-toxic salt thereof as an active ingredient,

(Ii) General formula (I)

Embedded image [In the formula, R ¹ represents a hydrogen atom or a C1-4 alkyl group, and R ² represents 1) hydrogen atom, 2) C1-8 alkyl group, 3) phenyl group, or 4) phenyl group, -OCOR ¹⁶ group. (In the group, R ¹⁶ is C1 to
Represents a 4-alkyl group. ), Or C1 substituted with a CONR ¹⁷ R ¹⁸ group (in which R ¹⁷ and R ¹⁸ each independently represent a hydrogen atom or a C1-4 alkyl group).
~ 4 alkyl groups,

E is 1) --CO--NR ³ --group (wherein R ³ is a hydrogen atom, C1 to
4 alkyl group, a phenyl group, or a C1-4 alkyl group substituted with a phenyl group. ), 2) -NR ³ -CO- group (wherein R ³ has the same meaning as described above), 3) -CO-O- group, 4) -O-CO- group, 5) -NR ³ —CO—NR ³ — group (wherein R ³ has the same meaning as described above), 6) —CO—CH ₂ — group, 7) —CO— group, 8) —O—CO—NR ³ —. Group (in the group, R ³ has the same meaning as described above), 9) —NR ³ —CO—O— group (in the group, R ³ has the same meaning as described above), 10) —O. —CO—O— group, 11) —CS—NR ³ — group (in the group, R ³ has the same meaning as described above), 12) —NR ³ —CS— group (wherein R ³ is as defined above). Have the same meaning), 13) —NR ³ —CS—NR ³ — group (in the group, R ³ has the same meaning as described above), 14) —O—CS—NR ³ — group (within the group, R ³ are as defined above.) 5) -NR ³ -CS-O- group (group, R ³ are as defined above.), 16) -CS-O- group, 17) -O-CS- group or 18,) -O Represents a -CS-O- group,

A is 1) a hydrogen atom, 2) a C1-8 alkyl group, 3) a C3-7 cycloalkyl group, or 4) an Ar group (wherein the Ar group represents a carbocycle or a heterocyclic aryl, and 1 From 3 C1-15 alkyl groups, C1
To 15 alkoxy group, halogen atom, nitro group, cyano group, guanidino group, amidino group, hydroxyl group, benzyloxy group, NR ⁹ R ¹⁰ group (wherein R ⁹ and R ¹⁰ are independently a hydrogen atom or represents a C1~4 alkyl group), -.. COOR ¹¹ group (wherein, R ¹¹ is represents a hydrogen atom or a C1~4 alkyl group), a trifluoromethyl group, substituted with a phenyl group or a heterocyclic group Good. )

J is 1) a single bond, 2) a C2-4 alkylene group, 3) a C2-4 alkenylene group, or

Embedded image (In the group, R ⁴ and R ⁵ are each independently (i)
Hydrogen atom, (ii) C1-4 alkyl group, (iii) C1
4 alkoxy group, or together with the carbon atom to which R ⁴ and R ⁵ are bonded, represents a C3-7 cycloalkyl group. )

G is

Embedded image 1) — (CH ₂ ) _m — group (wherein m represents 2, 3 or 4) or

[0031]

Embedded image (In the group, R ⁶ and R ⁷ are each independently

[0032] (i) hydrogen atom, (ii) C1-8 alkyl group, (iii) -COOR ⁸ group (wherein, R ⁸ represents a hydrogen atom, substituted with C1-8 alkyl group, a phenyl group or a phenyl group, Represents a C1-4 alkyl group), (i
v) Ar group (wherein Ar represents the same meaning as described above), (v) heterocyclic group, (vi) —COOR ⁸ group (in the group, R ⁸ represents the same meaning as described above), C1~4 alkoxy group, hydroxyl group, benzyloxy group, -NR ¹² R ¹³ group (wherein, R ¹² and R ¹³ each independently represent a hydrogen atom or a C1~4 alkyl group.), - NR ¹⁴ C
OOR ¹⁵ group (in which R ¹⁴ represents a hydrogen atom or a C1-4 alkyl group, R ¹⁵ represents a hydrogen atom, a C1-8 alkyl group, a phenyl group, or a C1-4 group substituted with a phenyl group)
Represents a 4-alkyl group. ), A C1-8 alkyl group substituted with an Ar group or a heterocyclic group (provided that one carbon atom of the C1-8 alkyl group may be replaced with one sulfur atom), or R ⁶ and R ⁷ together with the carbon atom bonded represent C3~7 cycloalkyl group. ) Is represented.

However, E is --O--CO--NR ^3-, --O
-CO-O -, - O- CS-NR 3 - , or -O-CS
-O-, J is a single bond and A is a hydrogen atom, and

The following compounds: (1) N-[[4- (benzoylamino) phenyl] sulfonyl] glycine, (2) N-[[3- (benzoylamino) phenyl] sulfonyl] glycine, (3) N-
[[2- (Benzoylamino) phenyl] sulfonyl]
Glycine, (4) N-[[4- (acetylamino) phenyl] sulfonyl] glycine, (5) N-[[4- (phenylacetylamino) phenyl] sulfonyl] glycine, (6) N-[[4- [(Phenylethylcarbonyl) amino] phenyl] sulfonyl] glycine, (7)
N-[[4-[(Cinnamoylamino) phenyl] sulfonyl] glycine, (8) N-[[4- (N-phenylureido) phenyl] sulfonyl] glycine, (9) N
-[[4- (N-phenylthioureido) phenyl] sulfonyl] glycine, (10) N-[[4-[(benzyloxycarbonyl) amino] phenyl] sulfonyl]
glycine,

(11) N-[[4-[(phenoxymethylcarbonyl) amino] phenyl] sulfonyl] glycine, (12) N-[[4-[(benzyloxymethylcarbonyl) amino] phenyl] sulfonyl] glycine,
(13) N-[[4- (4-methoxybenzoylamino) phenyl] sulfonyl] glycine, (14) N-
[[4- (4-Fluorobenzoylamino) phenyl]
Sulfonyl] glycine, (15) N-[[4- (4-nitrobenzoylamino) phenyl] sulfonyl] glycine, (16) N-[[4- (3-Nitrobenzoylamino) phenyl] sulfonyl] glycine, (17) ) N-
[[4- (2-Nitrobenzoylamino) phenyl] sulfonyl] glycine, (18) N-[[4- (4-formylbenzoylamino) phenyl] sulfonyl] glycine, (19) N-[[4- (benzoyl) Amino) phenyl] sulfonyl] -D-α-phenylglycine, (2
0) N-[[4- (benzoylamino) phenyl] sulfonyl] -L-α-phenylglycine,

(21) N-[[4- (4-methylbenzoylamino) phenyl] sulfonyl] -D-α-phenylglycine, (22) N-[[4- (4-methylbenzoylamino) phenyl] sulfonyl ] -L-α-phenylglycine, (23) N-[[4- (4-methoxybenzoylamino) phenyl] sulfonyl] -D-α-phenylglycine, (24) N-[[4- (4-methoxy Benzoylamino) phenyl] sulfonyl] -L-α-phenylglycine, (25) N-[[4- (4-fluorobenzoylamino) phenyl] sulfonyl] -D-α-
Phenylglycine, (26) N-[[4- (4-fluorobenzoylamino) phenyl] sulfonyl] -L-α
-Phenylglycine, (27) N-[[4- (4-nitrobenzoylamino) phenyl] sulfonyl] -D-α
-Phenylglycine, (28) N-[[4- (4-nitrobenzoylamino) phenyl] sulfonyl] -L-α
-Phenylglycine, (29) N-[(4-pivaloyloxyphenyl) sulfonyl] -D, L-α-phenylglycine, (30) N-[(4-pivaloyloxyphenyl) sulfonyl] -D , L-phenylalanine,

(31) N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] glycine,
(32) N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] -D, L-alanine,
(33) N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] -β-alanine, (3
4) N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] -L-valine, (35) N
-[[4- (2,4-Dichlorobenzoylamino) phenyl] sulfonyl] -D, L-valine, (36) N-
[[4- (2,4-Dichlorobenzoylamino) phenyl] sulfonyl] -L-leucine, (37) N-[[4
-(2,4-Dichlorobenzoylamino) phenyl] sulfonyl] -D, L-leucine, (38) N-[[4-
(2,4-Dichlorobenzoylamino) phenyl] sulfonyl] -D, L-serine, (39) N-[[4-
(2,4-Dichlorobenzoylamino) phenyl] sulfonyl] -L-phenylalanine, (40) N-[[4
-(2,4-dichlorophenyl) phenyl] sulfonyl] -L-tyrosine,

(41) N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] -D, L-
Alanine methyl ester, (42) N-[[4-
(2,4-Dichlorobenzoylamino) phenyl] sulfonyl] -L-valine methyl ester, (43) N-
[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] -D, L-valine methyl ester,
(44) N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] -L-leucine methyl ester, (45) N-[[4- (2,4-dichlorobenzoylamino) phenyl] Sulfonyl] -D, L-serine methyl ester, (46) N-[[4- (2,4
-Dichlorobenzoylamino) phenyl] sulfonyl]
-L-tyrosine methyl ester, (47) N-[[4
-(3-Nitrobenzoylamino) phenyl] sulfonyl] -L-aspartic acid, (48) N-[[3- (3
-Nitrobenzoylamino) phenyl] sulfonyl]-
L-aspartic acid, (49) N-[[4- (3-aminobenzoylamino) phenyl] sulfonyl] -L-aspartic acid, (50) N-[[3- (3-aminobenzoylamino) phenyl] sulfonyl ] -L-aspartic acid,

(51) N-[[4- (benzoylamino) phenyl] sulfonyl] -L-glutamic acid, (5
2) N-[[4-[[(4-chlorobenzoylamino))
Phenyl] sulfonyl] -L-glutamic acid, (53)
N-[[4-[[(4-nitrobenzoylamino) phenyl] sulfonyl] -L-glutamic acid, (54) N-
[[4- [2- [4- (1-Pyrozinyl) phenyl] butyryloxy] phenyl] sulfonyl] -D, L-3-
Morpholinoalanine ethyl ester, (55) N-
[[4- [2- (4-Nitrophenyl) butyryloxy] phenyl] sulfonyl] -D, L-3-morpholinoalanine ethyl ester, (56) N-[[4- (2
-Methoxy-2-phenylacetyloxy) phenyl]
Sulfonyl] -D, L-3-morpholinoalanine ethyl ester, (57) N-[[4-[[[1- (4-nitrophenyl) cyclobutyl] carbonyl] oxy] phenyl] sulfonyl] -D, L- 3-morpholinoalanine ethyl ester, (58) N-[[3-methyl-4
-[2- [4- (1-Pyrrolidinyl) phenyl] butyryloxy] phenyl] sulfonyl] -t-butoxycarbonyl-L-lysine, (59) N-[[4- (2-phenylbutyryloxy) phenyl] sulfonyl. ] Glycine, (60) N-[[4- [2- [4- (1-pyrrolidinyl) phenyl] butyryloxy] phenyl] sulfonyl] -D, L-phenylalanine,

(61) N-[[4- [2- [4- (1-
Pyrrolidinyl) phenyl] butyryloxy] phenyl]
Sulfonyl] -D, L-aspartic acid, (62) N-
[[4-[[[1- (4-Nitrophenyl) cyclobutyl] carbonyl] oxy] phenyl] sulfonyl]-
D, L-aspartic acid, (63) 1-[[4- [2-
[4- (1-Pyrrolidinyl) phenyl] butyryloxy] phenyl] sulfonylamido-1-cyclopropanecarboxylic acid, (64) N-[[4- [2- [4- (1-
Pyrrolidinyl) phenyl] butyryloxy] phenyl]
Sulfonyl] -D, L-2- (2-furanyl) glycine, (65) N-[[4- [2- [4- (1-pyrrolidinyl) phenyl] butyryloxy] phenyl] sulfonyl] -D, L-2 -(2-thienyl) glycine, (6
6) N-[[4- [2- [4- (1-pyrrolidinyl) phenyl] butyryloxy] phenyl] sulfonyl] -L
-Valine, (67) N-[[4- [2- [4- (1-pyrrolidinyl) phenyl] butyryloxy] phenyl] sulfonyl] -S-carboxymethyl-L-cysteine,
(68) N-[[4- [2-ethyl-2- (4-methoxyphenyl) butyryloxy] phenyl] sulfonyl]
Glycine, (69) N-[[3-methyl-4- [2-
[4- (1-pyrrolidinyl) phenyl] butyryloxy] phenyl] sulfonyl] -L-lysine, (70) 5.
-[N-[[3-Methyl-4- [2- [4- (1-pyrrolidinyl) phenyl] butyryloxy] phenyl] sulfonyl] amino] pentanoic acid, and (71) N-
Excluding [(3-methyl-4-pivaloyloxyphenyl) sulfonyl] -β-alanine. ] The novel sulfonyl amino acid derivative shown by these, or their nontoxic salt, and

(Iii) A method for producing a sulfonylamino acid derivative represented by the general formula (I) and a non-toxic salt thereof.

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 ones. Also included are isomers formed by the presence of asymmetric carbon atoms, such as the presence of branched alkyl, alkoxy and alkylene groups.

In the general formula (I), R ¹ , R ³ , R ⁴ , R ⁵ and R
⁹ , R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , R ¹⁴ , R ¹⁶ , R ¹⁷ , R ¹⁸
And a C1-4 alkyl group represented by
Ethyl, propyl, butyl groups and their isomers.

In the general formula (I), R ² , R ⁶ , R ⁷ , R ⁸ and R
^The C1-8 alkyl group represented by ¹⁵ , A is a methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl group and isomers thereof.

In the general formula (I), the C1-4 alkyl group substituted by a phenyl group represented by R ² , R ³ , R ⁸ and R ¹⁵ means methyl and ethyl substituted by one phenyl group. , Propyl, butyl groups and their isomers.

In the general formula (I), the C1-4 alkoxy group represented by R ⁴ , R ⁵ , R ⁶ and R ⁷ is methoxy,
Ethoxy, propoxy, butoxy groups and their isomers.

In the general formula (I), C as a substituent of Ar
1-15 alkyl group means methyl, ethyl, propyl,
A butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl group and isomers thereof.

In the general formula (I), C as a substituent of Ar
1-15 alkoxy group means methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy,
Heptyloxy, octyloxy, nonyloxy, decyloxy, undecyloxy, dodecyloxy, tridecyloxy, tetradecyloxy, pentadecyloxy groups and isomers thereof.

In the general formula (I), the halogen atom in the substituent of the Ar group is a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.

C represented by J in the general formula (I)
The 2-4 alkylene group means ethylene, trimethylene, tetramethylene group and isomers thereof.

C represented by J in the general formula (I)
2-4 alkenylene groups include vinylene, propenylene,
Butenylene, butadinylene groups and their isomers.

In the general formula (I), a C3-7 cycloalkyl group represented by R ⁴ and R ⁵ together with a carbon atom bonded thereto, and a C3 represented by R ⁶ and R ⁷ together with a carbon atom bonded thereto. ~ 7 cycloalkyl group and C3-7 cycloalkyl group represented by A is cyclopropyl,
Cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl groups.

In the general formula (I), the carbocyclic aryl represented by Ar in the groups A, R ⁶ and R ⁷ is C5-1.
It is a 0 carbocyclic aryl. For example, C5-10 carbocyclic aryl includes benzene, pentalene, indene, naphthalene, azulene and the like.

In the general formula (I), the heterocyclic aryl represented by Ar in the A, R ⁶ and R ⁷ groups means 1 to 2 nitrogen atoms, 1 oxygen atom and / or 1 sulfur atom. 5 to 15 membered monocyclic or bicyclic heterocyclic aryl containing atoms. For example, a 5- to 15-membered monocyclic or bicyclic heterocyclic aryl containing 1 to 2 nitrogen atoms, 1 oxygen atom and / or 1 sulfur atom is pyrrole, imidazole, pyrazole, pyridine, Pyrazine, pyrimidine, pyridazine, azepine, diazepine, furan, pyran, oxepin, oxazepine, thiophene, thiain (thiopyran), thiepine, oxazole, isoxazole, thiazole, isothiazole, oxadiazole, oxazine, oxadiazine, oxaazepine,
Oxadiazepine, thiadiazole, thiazine, thiadiazine, thiazepine, thiadiazepine, indole, isoindole, benzofuran, isobenzofuran, benzothiophene, isobenzothiophene, indazole,
Quinoline, isoquinoline, phthalazine, naphthyridine,
Examples include quinoxaline, quinazoline, cinnoline, benzoxazole, benzothiazole, and benzimidazole ring.

In the general formula (I), the heterocycle represented by R ⁶ and R ⁷ and the heterocycle having a substituent of Ar are:
1-2 nitrogen atoms, 1 oxygen atom and / or 1
Represents a 5- to 15-membered monocyclic or bicyclic heterocycle containing one sulfur atom. The 5- to 15-membered monocyclic or bicyclic heterocyclic ring containing 1 to 2 nitrogen atoms, 1 oxygen atom and / or 1 sulfur atom has 1 to 2 nitrogen atoms as described above, 1
5 containing one oxygen atom and / or one sulfur atom
Partly or wholly saturated 15-membered monocyclic or bicyclic heterocyclic aryl is included.

For example, a 5- to 15-membered mono- or bicyclic heterocycle containing 1-2 nitrogen atoms, 1 oxygen atom and / or 1 sulfur atom is pyrroline, pyrrolidine, imidazoline, Imidazolidine, pyrazoline, pyrazolidine, piperidine, piperazine, tetrahydropyrimidine, tetrahydropyridazine, dihydrofuran, tetrahydrofuran, dihydropyran, tetrahydropyran, dihydrothiophene, tetrahydrothiophene, dihydrothiain (dihydrothiopyran), tetrahydrothiain (tetrahydrothiopyran) ), Dihydrooxazole, tetrahydrooxazole, dihydroisoxazole, tetrahydroisoxazole, dihydrothiazole, tetrahydrothiazole, dihydroisothiazole, tetrahydo Loisothiazole, morpholine, thiomorpholine, indoline, isoindoline, dihydrobenzofuran, perhydrobenzofuran, dihydroisobenzofuran, 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, perhydrocinnoline, dihydrobenzoxazole, perhydrobenzoxazole, dihydrobenzothiazole, perhydrobenzothiazole, dihydrobenzimidazole, perhydrobenzimidazole ring And the like.

The E group in the present invention is a benzene ring on the right side,
It is assumed that the J group is bonded to the left side. For example, E group -CO-NR ³ - in the case of J-CO-NR ³ - and represents a benzene ring. The non-toxic salt in the present invention includes all salts. For example, common salt, acid addition salt,
A hydrate salt etc. are mentioned.

[Salt] 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 and the like).

[Acid Addition Salt] The compound of the present invention represented by the general formula (I) can be converted into the corresponding acid addition salt by a known method. Non-toxic, water-soluble salts are preferred. Suitable acid addition salts include inorganic acid salts such as hydrochloride, hydrobromide, hydroiodide, sulfate, phosphate, nitrate or acetate, trifluoroacetate, lactate, Tartrate,
Oxalate, fumarate, maleate, citrate,
Examples thereof include organic acid salts such as benzoate, methanesulfonate, ethanesulfonate, benzenesulfonate, toluenesulfonate, isethionate, glucuronate and gluconate. 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 I (1)

[Chemical 21] (In the formula, A and G have the same meanings as described above.),

General formula I (2)

Embedded image (In the formula, A and G have the same meanings as described above.),

General formula I (3)

Embedded image (In the formula, A and G have the same meanings as described above.),

General formula I (4)

Embedded image (In the formula, A and G have the same meanings as described above.),

General formula I (5)

Embedded image (In the formula, A and G have the same meanings as described above.),

General formula I (6)

[Chemical formula 26] (In the formula, A and G have the same meanings as described above.),

General formula I (7)

Embedded image (In the formula, A and G have the same meanings as described above.),

General formula I (8)

Embedded image (In the formula, A and G have the same meanings as described above.),

General formula I (9)

[Chemical 29] (In the formula, A and G have the same meanings as described above.),

General formula I (10)

Embedded image (In the formula, A and G have the same meanings as described above.),

General formula I (11)

[Chemical 31] (In the formula, A and G have the same meanings as described above.),

General formula I (12)

Embedded image (In the formula, A and G have the same meanings as described above.),

Formula I (13)

[Chemical 33] (In the formula, A and G have the same meanings as described above.),

General formula I (14)

Embedded image (In the formula, A and G have the same meanings as described above.),

General formula I (15)

Embedded image (In the formula, A and G have the same meanings as described above.),

General formula I (16)

Embedded image (In the formula, A and G have the same meanings as described above.),

General formula I (17)

Embedded image (In the formula, A and G have the same meanings as described above.),

General formula I (18)

Embedded image (In the formula, A and G have the same meanings as described above.),

Formula I (19)

Embedded image (In the formula, R ¹ and E have the same meanings as described above.),

Formula I (20)

Embedded image (In the formula, R ¹ and E have the same meanings as described above.),

Formula I (21)

Embedded image (In the formula, R ¹ and E have the same meanings as described above.),

General formula I (22)

Embedded image (In the formula, R ¹ and E have the same meanings as described above.),

General formula I (23)

Embedded image (In the formula, R ¹ and E have the same meanings as described above.),

General formula I (24)

Embedded image (In the formula, A, R ⁴ and R ⁵ each have the same meaning as described above.), And a sulfonylamino acid derivative, an ester derivative thereof or a non-toxic salt thereof.

As preferred specific examples of the compound represented by the general formula (I), the compounds shown in the following Tables 1 to 23 and compounds having chemical names listed, their ester derivatives, their non-toxic salts and Examples are shown. And the compounds described in 1.

[0085]

[Table 1]

[0086]

[Table 2]

[0087]

[Table 3]

[0088]

[Table 4]

[0089]

[Table 5]

[0090]

[Table 6]

[0091]

[Table 7]

[0092]

[Table 8]

[0093]

[Table 9]

[0094]

[Table 10]

[0095]

[Table 11]

[0096]

[Table 12]

[0097]

[Table 13]

[0098]

[Table 14]

[0099]

[Table 15]

[0100]

[Table 16]

[0101]

[Table 17]

[0102]

[Table 18]

[0103]

[Table 19]

[0104]

[Table 20]

[0105]

[Table 21]

[0106]

[Table 22]

[0107]

[Table 23]

[0108]

[Table 24]

[0109]

[Table 25]

[0110]

[Table 26]

[0111]

[Table 27]

[0112]

[Table 28]

[0113]

[Table 29]

[0114]

[Table 30]

[0115]

[Table 31]

[0116]

[Table 32]

[0117]

[Table 33]

[0118]

[Table 34]

[0119]

[Table 35]

[0120]

[Table 36]

[0121]

[Table 37]

[0122]

[Table 38]

[0123]

[Table 39]

[0124]

[Table 40]

[0125]

[Table 41]

[0126]

[Method for producing the compound of the present invention]

(1) Of the compounds of the present invention represented by the general formula (I),
Any of the A-J-E- group, the substituent of Ar in A, the R ⁶ or R ⁷ group in G and the -COOR ² group is -COOH.
A compound which does not represent a group or a group containing it, and neither the substituent of Ar in A nor the group of R ⁶ or R ^{7 in} G represents an amino group, a hydroxyl group or a group containing them, that is, in general Formula (I-1):

Embedded image (In the formula, R ^2-1 is a C1-8 alkyl group, a phenyl group, or a phenyl group or -OCOR ¹⁶ (R ¹⁶ has the same meaning as described above) or -CONR ¹⁷ R ¹⁸ (R ¹⁷ and R ¹⁸ are C1-4 substituted with the same meaning as described above.)
Represents an alkyl group, E ¹ , J ¹ and A ¹ are E, J, A
Has the same meaning as, but E ¹ is -O-CO-, or-
When representing an O-CS- group, J ¹ is a single bond and A ¹ does not represent a hydrogen atom, and A ¹ and G ¹ are A and G, respectively.
Has the same meaning as in the above, but the substituent of Ar in A ¹ and G
R ⁶ and R ⁷ therein do not represent a —COOH group, an amino group, a hydroxyl group or a group containing these groups, and other symbols have the same meanings as described above. The compound of the present invention represented by () can be produced by the following methods (a) to (k).

(A) Of the compounds of the present invention represented by general formula (I-1), compounds in which E ¹ represents a —CO—NR ³ — group, that is, general formula (Ia):

Embedded image (In the formula, E ^a represents a —CO—NR ³ — group, and other symbols have the same meanings as described above.) Is a compound represented by the general formula (II-a):

[0128]

Embedded image (Wherein all symbols have the same meanings as described above) and the compound represented by the general formula (III-a):

[0129]

Embedded image A ¹ -J ¹ -COOH (III-a) (wherein all symbols have the same meanings as described above) is subjected to an amidation reaction, and if necessary, subsequently It can be produced by subjecting it to a deprotection reaction.

The amidation reaction is known and, for example, (1)
Examples thereof include a method using an acid halide, (2) a method using a mixed acid anhydride, and (3) a method using a condensing agent.

[0131] These methods will be specifically described.
(1) The method using an acid halide is, for example, carboxylic acid in an organic solvent (chloroform, methylene chloride, diethyl ether, tetrahydrofuran, etc.) or without solvent, with an acid halide (oxalyl chloride, thionyl chloride, etc.) and −20 ° C. ~ At the reflux temperature, the resulting acid halide in the presence of a tertiary amine (pyridine, triethylamine, dimethylaniline, dimethylaminopyridine, etc.),
0-40 ° C in amine and organic solvent (chloroform, methylene chloride, diethyl ether, tetrahydrofuran, etc.)
It is carried out by reacting with.

(2) The method using a mixed acid anhydride is, for example, a carboxylic acid in an organic solvent (chloroform, methylene chloride, diethyl ether, tetrahydrofuran, etc.) or without a solvent, and a tertiary amine (pyridine, triethylamine, dimethylaniline). , Dimethylaminopyridine, etc.) in the presence of an acid halide (pivaloyl chloride, tosyl chloride, mesyl chloride, ethyl chloroformate, isobutyl chloroformate, etc.) at −20 to 40 ° C.,
The obtained mixed acid anhydride is used as an organic solvent (chloroform, methylene chloride, diethyl ether, tetrahydrofuran, etc.)
It is carried out by reacting with a corresponding amine at 0 to 40 ° C.

(3) Condensing agent (1,3-dicyclohexylcarbodiimide (DCC), 1-ethyl-3- [3-]
(Dimethylamino) propyl] carbodiimide (ED
C), 2-chloro-1-methylpyridinium iodine, etc.)
The method of using, for example, a carboxylic acid and an amine in an organic solvent (chloroform, methylene chloride, dimethylformamide, diethyl ether, etc.) or without a solvent, a tertiary amine (pyridine, triethylamine, dimethylaniline, dimethylaminopyridine, etc.) With or without the use of a condensing agent at 0-40 ° C.

It is desirable that the reactions (1), (2) and (3) are all carried out under an inert gas (argon, nitrogen, etc.) atmosphere under anhydrous conditions. The deprotection reaction is known, and examples thereof include (1) deprotection under alkaline conditions, (2) deprotection under acidic conditions, and (3) hydrogenolysis, and the like, and the deprotection reaction is selected depending on the properties of the protecting group.

A concrete explanation of these methods is as follows.
(1) For deprotection under alkaline conditions, for example, an organic solvent (methanol, tetrahydrofuran, dioxane, etc.)
Medium, alkali metal hydroxides (sodium hydroxide, potassium hydroxide, etc.), alkaline earth metal hydroxides (calcium hydroxide, etc.) or carbonates (sodium carbonate, potassium carbonate, etc.) or aqueous solutions thereof. The mixture is carried out at a temperature of 0-40 ° C.

(2) Deprotection under acid conditions can be carried out by using, for example, an organic solvent (methylene chloride, chloroform, dioxane,
Ethyl acetate, acetic acid, water or a mixed solvent thereof, etc.),
Use an organic acid (such as trifluoroacetic acid) or an inorganic acid (such as hydrogen chloride or hydrogen bromide) or a mixture thereof to give 0
It is carried out at a temperature of 120 ° C.

(3) Hydrogenolysis can be carried out by, for example, solvent [ether type (tetrahydrofuran, dioxane, diemethoxyethane, diethyl ether, etc.), alcohol type (methanol, ethanol, etc.), benzene type (benzene, toluene, etc.), amide type] (Dimethylformamide, etc.), water, ethyl acetate, acetic acid or a mixed solvent of two or more thereof, etc.]
In the presence of a catalyst (palladium-carbon, palladium black, palladium hydroxide, platinum dioxide, Raney nickel, etc.),
In the presence or absence of inorganic acids (hydrochloric acid, sulfuric acid, hypochlorous acid, boric acid, tetrafluoroboric acid, etc.) or organic acids (acetic acid, p-toluenesulfonic acid, oxalic acid, trifluoroacetic acid, formic acid, etc.) It is carried out at a temperature of 0 to 200 ° C. in a hydrogen atmosphere under normal pressure or under pressure or in the presence of ammonium formate.

(B) Among the compounds of the present invention represented by general formula (I-1), compounds in which E ¹ represents a —O—CO—NR ³ — group, that is, general formula (Ib):

Embedded image (In the formula, E ^b represents a —O—CO—NR ³ — group, and other symbols have the same meanings as described above.)
The compound represented by the general formula (II-a) and the general formula (III-b):

[0139]

Embedded image (In the formula, X represents a halogen atom, and other symbols have the same meanings as described above.) The compound can be produced by reacting it and, if necessary, subsequently subjecting it to a deprotection reaction.

This reaction is known, and, for example, in the presence or absence of a suitable organic solvent (acetonitrile, tetrahydrofuran etc.) and water, an organic base (4-dimethylaminopyridine etc.) or an inorganic base [alkali metal hydroxide] is used. (Sodium hydroxide, potassium hydroxide, etc.), alkaline earth metal hydroxide (calcium hydroxide, etc.) or carbonate (sodium carbonate, potassium carbonate, etc.)]
It is performed at a temperature of 0 ° C. The deprotection reaction is performed by the method described above.

(C) Compounds of the present invention represented by the general formula (I-1) in which E ¹ represents a —NR ³ —CO—NR ³ — group or a —NR ³ —CS—NR ³ — group, That is, the general formula (I-c):

[Chemical 51]

(Wherein E ^c represents a —NR ³ —CO—NR ³ — group or a —NR ³ —CS—NR ³ — group, and other symbols have the same meanings as described above). Is a compound represented by the general formula (II-a) and a general formula (III
-C):

Embedded image The compound represented by A ¹ -J ¹ -NHR ³ (III-c) (wherein all symbols have the same meanings as described above) and the general formula (IV-c):

Embedded image

It can be produced by reacting a compound represented by the formula (wherein T represents an oxygen atom or a sulfur atom), and if necessary, followed by a deprotection reaction. This reaction is known and, for example, in an organic solvent (dimethylformamide, dichloromethane, tetrahydrofuran, etc.), in the presence or absence of amines (triethylamine, pyridine, dimethylaminopyridine, etc.) 0-8
It is performed at a temperature of 0 ° C. The deprotection reaction is performed by the method described above. Alternatively, the general formula (II-
The compound represented by a) and the general formula (III-c1):

Embedded image A ¹ -J ¹ -N = C = O (III-c1) (wherein all symbols have the same meanings as described above), or a compound represented by the general formula (III-c2):

[0144]

Embedded image It can also be produced by reacting with a compound represented by the formula (in the formula, all symbols have the same meanings as described above), and if necessary, followed by a deprotection reaction.

This reaction is known, and for example, organic solvents (acetone, chloroform, methylene chloride, benzene,
Tetrahydrofuran, etc.) in the presence or absence of amines (triethylamine, pyridine, dimethylaminopyridine, etc.) at a temperature of 0 to 80 ° C., or the acid halide shown in (1) of the above amidation reaction. Is performed in the same manner as the method using. The deprotection reaction is performed by the method described above.

(D) Compounds of the present invention represented by the general formula (I-1) in which E ¹ represents a --CO--O-- group,
That is, general formula (Id):

Embedded image (In the formula, E ^d represents a —CO—O— group, and other symbols have the same meanings as described above.) Is a compound represented by the general formula (II-d):

[0147]

Embedded image (In the formula, all symbols have the same meanings as described above.) The compound represented by the general formula (III-a) is subjected to an esterification reaction, and if necessary, subsequently deprotected. It can be produced by subjecting it to a reaction.

The esterification reaction is known, and examples thereof include (1) a method using an acid halide, (2) a method using a mixed acid anhydride, and (3) a method using a condensing agent.

A concrete explanation of these methods is as follows.
(1) The method using an acid halide is, for example, carboxylic acid in an organic solvent (chloroform, methylene chloride, diethyl ether, tetrahydrofuran, etc.) or without solvent, with an acid halide (oxalyl chloride, thionyl chloride, etc.) and −20 ° C. ~ At the reflux temperature, the resulting acid halide in the presence of a tertiary amine (pyridine, triethylamine, dimethylaniline, dimethylaminopyridine, etc.),
In alcohol and an inert organic solvent (chloroform, methylene chloride, diethyl ether, tetrahydrofuran, etc.),
The reaction is carried out at 0 to 40 ° C.

(2) In the method using a mixed acid anhydride, for example, a carboxylic acid is used as an inert organic solvent (chloroform, methylene chloride, diethyl ether, tetrahydrofuran, etc.).
An acid halide (pivaloyl chloride, tosyl chloride, mesyl chloride, etc.) or an acid derivative (ethyl chloroformate, in the presence of a tertiary amine (pyridine, triethylamine, dimethylaniline, dimethylaminopyridine, etc.) in a medium or no solvent. Isobutyl chloroformate, etc.)
The mixture is reacted at 0 to 40 ° C., and the obtained mixed anhydride is reacted with an alcohol in an inert organic solvent (chloroform, methylene chloride, diethyl ether, tetrahydrofuran, etc.) in an amount of 0 to 4 ° C.
The reaction is carried out at 0 ° C.

(3) The method using a condensing agent (DCC, EDC, 2-chloro-1-methylpyridinium iodine, etc.) is carried out, for example, by using a carboxylic acid and an alcohol in an organic solvent (chloroform, methylene chloride, dimethylformamide, diethyl ether). Etc.) with or without a tertiary amine (pyridine, triethylamine, dimethylaniline, dimethylaminopyridine, etc.) in a solvent or without a solvent and using a condensing agent at 0 to 40 ° C. for reaction.

It is desirable that all of the reactions (1), (2) and (3) be carried out under an inert gas (argon, nitrogen, etc.) atmosphere under anhydrous conditions. The deprotection reaction is
It is performed by the method described above.

(E) Among the compounds of the present invention represented by the general formula (I-1), compounds in which E ¹ represents a —O—CO—O— group, that is, the general formula (Ie):

Embedded image

The compound represented by the formula (E ^e represents a —O—CO—O— group and the other symbols have the same meanings as described above), and is represented by the general formula (II-d). The compound can be produced by reacting the compound represented by the general formula (III-b) with the compound represented by the formula (III-b), followed by a deprotection reaction if necessary. This reaction is described in (b) above.
Method. The deprotection reaction is performed by the method described above.

(F) Of the compounds of the present invention represented by general formula (I-1), compounds in which E ¹ represents a —NR ³ —CO— group, that is, general formula (If):

Embedded image

(Wherein, E ^f represents a —NR ³ —CO— group, and other symbols have the same meanings as described above), and a compound represented by the general formula (II-f):

Embedded image (Wherein all symbols have the same meanings as described above) and the compound represented by the general formula (III-c) are subjected to an amidation reaction, and if necessary, subsequently deprotected. It can be produced by subjecting it to a reaction.
This amidation reaction is carried out by the method (a) described above. The deprotection reaction is performed by the method described above.

(G) Compounds of the present invention represented by the general formula (I-1) in which E ¹ represents a —O—CO— group,
That is, the general formula (I-g):

[Chemical formula 61]

(In the formula, E ^g represents a —O—CO— group,
Other symbols have the same meanings as described above. ) Is a compound represented by the general formula (II-f) and the general formula (III-g):

[0159]

Embedded image The compound represented by A ¹ -J ¹ -OH (III-g) (wherein all symbols have the same meanings as described above) is subjected to an esterification reaction, and, if necessary, subsequently. It can be produced by subjecting it to a deprotection reaction. This esterification reaction is carried out by the method (d) described above. The deprotection reaction is performed by the method described above.

(H) Of the compounds of the present invention represented by the general formula (I-1), compounds in which E ¹ represents a —NR ³ —CO—O— group, that is, the general formula (Ih)

Embedded image

(In the formula, E ^h represents a —NR ³ —CO—O— group, and other symbols have the same meanings as described above.) Is a compound represented by the general formula (II-h):

Embedded image (Wherein all symbols have the same meanings as described above), the compound represented by the general formula (III-c) is reacted, and if necessary, subsequently subjected to a deprotection reaction. Can be manufactured by. This reaction is carried out by the method (b) described above. The deprotection reaction is performed by the method described above.

(J) In the compounds of the present invention represented by the general formula (I-1), E ¹ is a --CO-- group or --CO--CH _2-.
A compound representing a group, that is, the general formula (Ij):

Embedded image

(In the formula, E ^j is a --CO-- group or --CO--
CH ₂ - represents a group and the other symbols have the same meanings as described above. ) Is a compound represented by the general formula (II-j-1):

Embedded image

(Wherein all symbols have the same meanings as described above) or a compound of the general formula (II-j-
2):

Embedded image

(Wherein all symbols have the same meanings as described above) and the general formula (III-j):

Embedded image A compound represented by (A ¹ -J ¹ ) ₂ CuLi (III-j) (wherein all symbols have the same meanings as described above) is reacted and, if necessary, subsequently deprotected. It can be produced by subjecting it to a reaction.

The reaction of this organic copper reagent is known, and, for example, in an organic solvent (tetrahydrofuran, ether, etc.),
An organocopper reagent is prepared using an organolithium reagent and inorganic copper (copper iodide, copper cyanide, etc.) at a temperature of 78 ° C to 0 ° C, and further reacted with an acid halide at a temperature of -78 ° C to 0 ° C. It is done by This reaction is preferably carried out under an inert gas (argon, nitrogen, etc.) atmosphere under anhydrous conditions. The deprotection reaction is performed by the method described above.

(J-1) Of the compounds of the present invention represented by the general formula (I-1), E ¹ is a —CO—NR ³ — group, —O—C
O-NR ³ -group, -NR ³ -CO-O- group, -CO-O-
A group, a —CO—CH ₂ — group, or a —O—CO—O— group, that is, a compound represented by the general formula (I-1-AA):

Embedded image

(In the formula, E ^1A is a —CO—NR ³ — group, —O
—CO—NR ³ — group, —NR ³ —CO—O— group, —CO—
O- group, -CO-CH ₂ - represents a group or -O-CO-O- group and the other symbols have the same meanings as described above. ) Is a compound represented by the general formula (XII):

Embedded image

(Wherein all symbols have the same meanings as described above), and a compound of the general formula (XIII):

Embedded image A compound represented by H ₂ N—G ¹ —COOR ^2-1 (XIII) (wherein all symbols have the same meanings as described above) is subjected to an amidation reaction, and if necessary, dehydrogenated. It can also be manufactured by protection. This amidation reaction is carried out by the method using the acid halide shown in (1) of the above-mentioned amidation reaction. The deprotection reaction is performed by the method described above.

(J-2) Among the compounds of the present invention represented by the general formula (I-1), E ¹ is a —CO—NR ³ — group, and —NR ³
—CO— group, —NR ³ —CO—NR ³ — group, —O—CO—
A compound representing an NR ³ — group or a —NR ³ —CO—O— group, that is, a compound represented by the general formula (I-1-AB):

Embedded image

(In the formula, E ^1B is a —CO—NR ³ — group, —N
R ³ —CO— group, —NR ³ —CO—NR ³ — group, —O—C
Represents an O—NR ³ — group or a —NR ³ —CO—O— group,
Other symbols have the same meanings as described above. ) Is a compound represented by the general formula (I-1-AB1):

Embedded image

(In the formula, E ^1BB is a —CO—NH— group, —N
H-CO- group, -NH-CO-NH- group, -O-CO-
Represents a NH-group or a -NH-CO-O- group, R ^B represents a protecting group for an amino group (eg, t-butoxycarbonyl group, benzyloxycarbonyl group, etc.), and other symbols have the same meanings as described above. Represent. )
The amino group in the E1 ^BB group is converted into an R ^3-1 group (in the group, R ^3-1 is C
It represents a 1-4 alkyl group, a phenyl group or a C1-4 alkyl group substituted with a phenyl group. After removing the protecting group (R ^B group), the compound can also be produced.

The R ^3-1 grouping of this amino group is known,
For example, in a suitable organic solvent (dimethylformamide, etc.),
Corresponding R ^{3-1 in} the presence of a base (sodium hydride, etc.)
It is carried out at 0 to 40 ° C. using a halide. Further, the deprotection reaction is carried out by the method described above.

(K) Of the compounds of the present invention represented by the general formula (I-1), E ¹ is —CS—NR ³ — group, and —NR ³ —C.
S- group, -NR ³ -CS-NR ³ - group, -O-CS-NR
³ - group, -NR ³ -CS-O- group, -CS-O-group, -O
A compound representing a -CS- group or a -O-CS-O- group,
That is, general formula (Ik):

Embedded image

(Wherein E ^k is a —CS—NR ³ — group, —NR
³ -CS- group, -NR ³ -CS-NR ³ - group, -O-CS
-NR ³ - group, -NR ³ -CS-O- group, -CS-O-
Represents a group, -O-CS- group or -O-CS-O- group, and other symbols have the same meanings as described above. ) Is a compound represented by the general formula (Ia), the general formula (Ib), the general formula (Ic) or the general formula (I-).
d), a compound of the general formula (Ie), a general formula (If), a general formula (Ig) or a general formula (Ih), that is, a general formula (Im):

[0176]

Embedded image (Wherein, E ^m is -CO-NR ³ - group, -NR ³ -CO-
Group, -NR ³ -CO-NR ³ - group, -O-CO-NR ³ -
Group, -NR ³ -CO-O- group, -CO-O-group, -O-
It represents a CO- group or a -O-CO-O- group, and other symbols have the same meanings as described above. ) And a compound of formula (III-k):

[0177]

[Chemical 76] It can be produced by reacting a Lawesson's Reagent represented by the formula (1) with a deprotection reaction if necessary.

The reaction of the Lawesson's reagent is known, and is carried out, for example, by reacting in an organic solvent (dioxane, benzene, toluene, xylene, etc.) at 20 to 150 ° C. This reaction is preferably carried out under an inert gas (argon, nitrogen, etc.) atmosphere under anhydrous conditions. The deprotection reaction is performed by the method described above.

(2) Of the compounds of the present invention represented by the general formula (I), the A-JE- group, the substituent of Ar in A, the R ⁶ or R ⁷ group in G and -COOR ² of A compound in which at least one group represents a -COOH group or a group containing it, or a substituent of Ar in A, R ⁶ or R ^{7 in} G represents an amino group, a hydroxyl group or a group containing them. That is, the general formula (I-2):

Embedded image

(Wherein G ² , E ² , J ² and A ² are G,
It has the same meaning as E, J, and A. However, A ² -J ² -E
² -group, a substituent of Ar in A ² , R ⁶ or R ⁷ group in G ² and at least one group of —COOR ² is —CO.
Represents a group containing an OH group or a --COOH group, or
Ar substituents in ^2, R ⁶ or R ⁷ groups in G ² represents a group containing an amino group, a hydroxyl group, or they, the other symbols are the same meanings as described above. The compound of the present invention represented by) can be produced by subjecting the compound represented by the general formula (I-1) produced by the above method to deprotection or hydrogenolysis under alkaline or acidic conditions.

The hydrolysis under alkaline conditions, the hydrolysis under acidic conditions, and the hydrogenolysis reaction are carried out by the methods described above. Further, a compound in which the substituent of Ar in A is an amino group, that is, a compound represented by the general formula (I-3):

Embedded image (In the formula, A ³ has the same meaning as A. However, the substituent of Ar in the A ³ group represents an amino group, and other symbols have the same meanings as described above.) , The general formula (I-4) produced by the above method:

Embedded image (In the formula, A ⁴ has the same meaning as A. However, the substituent of Ar in the A ⁴ group represents a nitro group, and the other symbols have the same meanings as described above.) It can also be produced by hydrogenolysis. Hydrogenolysis is performed by the method described above.

As can be easily understood by those skilled in the art, examples of the protecting group for the carboxy group and the hydroxyl group include t-butyl group, benzyl group and the like. Other than that, it can be easily and selectively eliminated. It is not particularly limited as long as it is a group.
For example, TWGreen, Protective Groups in Organic Sy
The one described in nthesis, Wiley, New York, 1991 is used. Examples of the amino-protecting group include a benzyloxycarbonyl group and a t-butoxycarbonyl group, but are not particularly limited as long as they can be easily and selectively eliminated. Examples of the protecting group for hydroxamic acid include a t-butyl group and a benzyl group, but other groups are not particularly limited as long as they can be easily and selectively removed. For example -C (CH _{3) 2} -OCH ₃ or the like is used. By properly using these protecting groups, the desired compound of the present invention can be easily produced.

General formula (II-a), general formula (II-d), general formula (II-f), general formula (II-h), general formula (II-j-
1) or the compound represented by the general formula (II-j-2) is
It can be produced by a known method, a method represented by the following reaction step formulas 1 to 3 or a method described in Examples.

[0184]

Embedded image

[0185]

Embedded image

[0186]

[Chemical formula 82]

In the above reaction scheme, Y is a hydroxyl-protecting group (eg, benzyl group, benzyloxycarbonyl group).
Represents a protective group for a carboxyl group (eg, benzyl group, methyl group, etc.), and other symbols have the same meanings as described above.

In the above reaction scheme, the compounds represented by the general formula (VI) and the general formula (VII) are a partial compound group of the compounds represented by the general formula (II-a). General formula (IX)
The compound represented by is a partial compound group of the compound represented by the general formula (II-d). The compound represented by the general formula (XI) is a partial compound group of the compounds represented by the general formula (II-f).

Each reaction in the above reaction scheme is carried out by a known method. The compounds represented by the formulas (V), (VIII), and (X) used as starting materials in the above process formulas are known per se or can be easily produced by known methods.

In each reaction in the present specification, the reaction product is obtained by a conventional purification means, for example, 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 performed for each reaction or may be performed after completion of several reactions.

Other starting materials and respective reagents in the present invention are known per se or can be produced by known methods.

[0192]

[Pharmacological activity] The following experiment proved that the compound of the present invention represented by the formula (I) has matrix metalloproteinase inhibitory activity. For example, the following results were obtained for gelatinase A inhibitory activity.

(1) Gelatinase A Inhibitory Activity [Experimental Method] 10 mM p-aminophenylmercuric acetate ( APMA) (10 μl) was added and preincubated at 37 ° C. for 1 hour to activate the enzyme. The activated enzyme thus prepared (7 μl /
tube, 98 μl), various concentrations of test compound or solution without addition of test compound (2 μl), 0.05% fluorescein isothiocyanate (FITC) -gelatin (1
00 μl) was added and the mixture was incubated at 37 ° C. for 2 hours. After stopping the enzymatic reaction by adding 0.1 M Tris-hydrochloric acid (containing 94.7% ethanol; pH 9.5) (750 μl), the mixture was stirred and allowed to stand at 0 ° C. for 30 minutes to separate a non-degraded substrate. The reaction mixture was centrifuged at 900 xg for 30 minutes.
The gelatinase activity was compared with the fluorescence intensity in the supernatant (Ex = 495n
It was calculated by measuring m and Em = 520 nm). The results are shown in Table 24.

[0194]

[Table 42] Table 24 Example No. IC ₅₀ (μM) 2 0.11 2 (10) 0.66 2 (11) 0.8 2 (35) 0.013 2 (63) 0.0023 3 (13) 0.0027 6 0.42 10 (1) 0.70

[0195]

[Toxicity] On the other hand, the toxicity of the compound of the present invention is very low, and it can be judged that the compound is sufficiently safe for use as a medicament.

[0196]

[Application to pharmaceuticals] In animals including humans, especially in humans, inhibiting matrix metalloprotease is associated with rheumatism, osteoarthritis, pathological bone resorption, osteoporosis, periodontal disease, interstitial nephritis, arteriosclerosis, emphysema. , Liver cirrhosis, corneal damage, metastatic invasion and proliferation of cancer cells, autoimmune diseases (Crohn's disease, Schuren's disease, etc.), diseases caused by transmigration and infiltration of leukocyte cells, prevention and / or treatment of angiogenesis, etc. Useful for.

In order to use the compound of the present invention represented by the general formula (I), its non-toxic acid addition salt, or its hydrate for the above purpose, it is usually systemically or topically, orally or parenterally. It is administered in the form of The dose varies depending on age, body weight, symptoms, therapeutic effect, administration method, processing time, etc.
Usually 1mg to 1000m per adult
Orally administered once to several times a day in the range of g, or 1 mg to 100 mg per adult per administration
Parenteral administration once to several times a day (preferably,
Intravenous administration) or continuous intravenous administration for 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-mentioned dose may be sufficient, or may be required beyond the range. 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 and the like for parenteral administration.

Solid compositions for oral administration include tablets,
Pills, capsules, powders, granules and the like are included. Capsules include hard capsules and soft capsules. In such a solid composition, the one or more active substances comprise at least one inert diluent, such as lactose, mannitol, glucose,
It is mixed with hydroxypropyl cellulose, microcrystalline cellulose, starch, polyvinylpyrrolidone, magnesium aluminometasilicate. The composition is prepared according to a standard method.
Additives other than inert diluents, such as lubricants such as magnesium stearate, disintegrants such as calcium fibrin glycolate, stabilizers such as lactose, solubilizers such as glutamic acid or aspartic acid. May be contained. Tablets or pills as needed
It may be coated with a film of a gastric or enteric substance such as gelatin, hydroxypropylcellulose or hydroxypropylmethylcellulose phthalate, or may be coated with two or more layers. Also included are capsules of absorbable materials such as gelatin. Liquid compositions for oral administration include pharmaceutically acceptable emulsions, solutions, syrups, elixirs and the like. In such liquid compositions, one or more active substances are contained in commonly used inert diluents (eg, purified water, ethanol). This composition is:
In addition to inert diluents, wetting agents, auxiliary agents such as suspending agents,
Sweetening agents, flavoring agents, fragrances and preservatives may be contained. Other compositions for oral administration include sprays which contain one or more active substances and are formulated in a manner known per se. This composition contains, in addition to the inert diluent, buffers such as sodium bisulfite, which provide isotonicity with stabilizers, e.g., isotonic agents such as sodium chloride, sodium citrate, or citric acid. You may. The method of manufacturing the spray is
For example, U.S. Pat.Nos. 2,868,691 and 3,095,355
It is described in detail in the issue.

The injections for parenteral administration according to the present invention include sterile aqueous or non-aqueous solutions, suspensions and emulsions. Aqueous solutions and suspensions include, for example, 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 also contain adjuvants such as preserving, wetting, emulsifying, dispersing, stabilizing (eg, lactose) and solubilizing agents (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 to produce sterile solid compositions, for example, sterilized or dissolved in sterile distilled water for injection or other solvents before use of the lyophilized product. Other compositions for parenteral administration include external solutions, ointments, containing one or more active substances, and formulated in a conventional manner.
It includes a liniment, a suppository for rectal administration, a pessary for vaginal administration, and the like.

[0200]

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 point and TLC
The solvent in parentheses shown in the above indicates the elution solvent or developing solvent used, and the ratio indicates the volume ratio. The solvent in parentheses shown in the NMR section indicates the solvent used for the measurement.

Reference Example 1 N-[(4-nitrophenyl) sulfonyl] glycine
t-butyl ester

[Chemical 83]

Glycine t-butyl ester hydrochloride (3
4-Nitrobenzenesulfonyl chloride (46.3 g) was added to a solution of 5 g) in pyridine (200 ml) at 0 ° C.
The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated, and the obtained crystals were washed with water and then with a mixed solution of hexane: ethyl acetate = 9: 1 and dried to obtain the title compound (61.4 g) having the following physical properties. TLC: Rf 0.18 (hexane: ethyl acetate = 4:
1).

Reference Example 2 N-[(4-aminophenyl) sulfonyl] glycine
t-butyl ester

Embedded image

The compound (57.1 g) produced in Reference Example 1 was dissolved in ethanol (200 ml) and tetrahydrofuran (200 ml).
ml) solution was added 10% palladium-carbon (2.2 g). The reaction mixture was stirred under a hydrogen atmosphere at room temperature for 3 hours. The reaction mixture was filtered through Celite (trade name),
The filtrate was concentrated. The obtained crystals were washed with a mixed solution of hexane: ethyl acetate = 4: 1 and dried to give the title compound (50 g) having the following physical data. TLC: Rf 0.36 (hexane: ethyl acetate = 1: 1
1).

Example 1 N-[[4- (p-toluoylamino) phenyl] sulfonyl] glycine t-butyl ester

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P-Toluoyl chloride (0.5 ml) was added to a pyridine (10 ml) solution of the compound (1.2 g) produced in Reference Example 2 under ice cooling. Reaction mixture at room temperature for 3
Stir for 0 minutes. 1N hydrochloric acid (100 ml) in the reaction mixture
And 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 obtained residue was washed with ether and dried to obtain the compound of the present invention (1.52 g) having the following physical properties. TLC: Rf 0.56 (hexane: ethyl acetate = 1: 1
1), NMR (CDCl ₃ ): δ 8.08-8.00 (1H, br.s), 7.86 (2H, d,
J = 9.2Hz), 7.82 (2H, d, J = 9.2Hz), 7.78 (2H, d, J = 8.2Hz),
7.31 (2H, d, J = 8.2Hz), 5.04 (1H, t, J = 5.4Hz), 3.67 (2H, d,
J = 5.4Hz), 2.44 (3H, s), 1.37 (9H, s).

Examples 1 (1) to 1 (91) By using the corresponding acid chloride instead of p-toluoyl chloride and carrying out the same procedure as in Example 1, the compounds of the present invention having the following physical properties were obtained. .

Example 1 (1) N-[[4- (isobutyrylamino) phenyl] sulfonyl] glycine t-butyl ester

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TLC: Rf 0.41 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 7.77 (2H, d, J = 9.0Hz), 7.68 (2H, d,
J = 9.0Hz), 5.15 (1H, t, J = 5.4Hz), 3.64 (2H, d, J = 5.4Hz),
2.56 (1H, m), 1.36 (9H, s), 1.25 (6H, d, J = 6.8Hz).

Example 1 (2) N-[[4- (acetylamino) phenyl] sulfonyl] glycine t-butyl ester

Embedded image

TLC: Rf 0.36 (hexane: ethyl acetate = 3: 7), NMR (CDCl ₃ ): δ 7.78 (2H, d, J = 8.8Hz), 7.76-7.72
(1H), 7.65 (2H, d, J = 8.8Hz), 5.11 (1H, t, J = 5.4Hz), 3.65
(2H, d, J = 5.4Hz), 2.21 (3H, s), 1.36 (9H, s).

Example 1 (3) N-[[4- (o-trioylamino) phenyl] sulfonyl] glycine t-butyl ester

Embedded image

TLC: Rf 0.64 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 7.83 (2H, d, J = 8.8Hz), 7.76 (2H, d,
J = 8.8Hz), 7.88-7.72 (1H), 7.52-7.22 (4H, m), 5.01 (1H,
t, J = 5.4Hz), 3.65 (2H, d, J = 5.4Hz), 2.49 (3H, s), 1.37 (9
H, s).

Example 1 (4) N-[[4- (m-trioylamino) phenyl] sulfonyl] glycine t-butyl ester

Embedded image

TLC: Rf 0.59 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.10-8.04 (1H, br.s), 7.85 (2H, d,
J = 9.2Hz), 7.80 (2H, d, J = 9.2Hz), 7.72-7.60 (2H, m), 7.4
3-7.36 (2H, m), 5.05 (1H, t, J = 5.4Hz), 3.67 (2H, d, J = 5.4H
z), 2.44 (3H, s), 1.37 (9H, s).

Example 1 (5) N-[[4- (2-chlorobenzoylamino) phenyl] sulfonyl] glycine t-butyl ester

Embedded image

TLC: Rf 0.52 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.22-8.12 (1H, br.s), 7.87 (2H, d,
J = 8.6Hz), 7.84-7.74 (1H, m), 7.79 (2H, d, J = 8.6Hz), 7.5
0-7.36 (3H, m), 5.03 (1H, t, J = 5.6Hz), 3.67 (2H, d, J = 5.6H
z), 1.36 (9H, s).

Example 1 (6) N-[[4- (3-chlorobenzoylamino) phenyl] sulfonyl] glycine t-butyl ester

Embedded image

TLC: Rf 0.58 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.02-7.94 (1H, br.s), 7.92-7.72
(6H, m), 7.61-7.40 (2H, m), 5.02 (1H, t, J = 5.4Hz), 3.68
(2H, d, J = 5.4Hz), 1.37 (9H, s).

Example 1 (7) N-[[4- (4-chlorobenzoylamino) phenyl] sulfonyl] glycine t-butyl ester

Embedded image

TLC: Rf 0.64 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.00-7.90 (1H, br.s), 7.87 (2H, d,
J = 8.6Hz), 7.83 (2H, d, J = 8.8Hz), 7.78 (2H, d, J = 8.6Hz),
7.49 (2H, d, J = 8.8Hz), 5.00 (1H, t, J = 5.4Hz), 3.67 (2H, d,
J = 5.4Hz), 1.37 (9H, s).

Example 1 (8) N-[[4- (2-methoxybenzoylamino) phenyl] sulfonyl] glycine t-butyl ester

Embedded image

TLC: Rf 0.42 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 10.08-10.00 (1H, br.s), 8.28 (1H,
dd, J = 2.0, 8.0Hz), 7.87 (2H, d, J = 9.4Hz), 7.82 (2H, d, J =
9.4Hz), 7.60-7.48 (1H, m), 7.21-7.11 (1H, m), 7.06 (1H,
d, J = 8.4Hz), 4.99 (1H, t, J = 5.4Hz), 4.09 (3H, s), 3.67 (2
H, d, J = 5.4Hz), 1.36 (9H, s).

Example 1 (9) N-[[4- (3-methoxybenzoylamino) phenyl] sulfonyl] glycine t-butyl ester

Embedded image

TLC: Rf 0.52 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.02-7.96 (1H, br.s), 7.87 (2H, d,
J = 9.2Hz), 7.80 (2H, d, J = 9.2Hz), 7.47-7.36 (3H, m), 7.1
5-7.08 (1H, m), 5.01 (1H, t, J = 5.4Hz), 3.88 (3H, s), 3.68
(2H, d, J = 5.4Hz), 1.37 (9H, s).

Example 1 (10) N-[[4- (benzoylamino) phenyl] sulfonyl] glycine t-butyl ester

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TLC: Rf 0.70 (ethyl acetate), NMR (CDCl ₃ ): δ 8.02 (1H, s), 7.9-7.8 (6H, m), 7.6
-7.3 (3H, m), 5.02 (1H, t, J = 5.4Hz), 3.68 (2H, d, J = 5.4H
z), 1.37 (9H, s).

Example 1 (11) N-[[4- (4-fluorobenzoylamino) phenyl] sulfonyl] glycine t-butyl ester

[Chemical 96]

TLC: Rf 0.53 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ + CD ₃ OD): δ 7.88 (2H, dd, J = 5.2, 8.8H)
z), 7.82-7.75 (4H, m), 7.11 (2H, t, J = 8.8Hz), 3.60 (2H,
s), 1.31 (9H, s).

Example 1 (12) N-[[4- (4-methoxybenzoylamino) phenyl] sulfonyl] glycine t-butyl ester

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TLC: Rf 0.40 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 7.94-7.90 (1H, br.s), 7.86 (2H, d,
J = 9.2Hz), 7.85 (2H, d, J = 8.8Hz), 7.79 (2H, d, J = 9.2Hz),
6.99 (2H, d, J = 8.8Hz), 5.00 (1H, t, J = 5.4Hz), 3.89 (3H,
s), 3.67 (2H, d, J = 5.4Hz), 1.37 (9H, s).

Example 1 (13) N-[[4- (2-nitrobenzoylamino) phenyl] sulfonyl] glycine t-butyl ester

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TLC: Rf 0.62 (ethyl acetate), NMR (CD ₃ OD): δ 8.19 (1H, d, J = 8.4Hz), 7.9-7.7 (7
H, m), 3.65 (2H, s), 1.35 (9H, s).

Example 1 (14) N-[[4- (3-Nitrobenzoylamino) phenyl] sulfonyl] glycine t-butyl ester

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TLC: Rf 0.72 (ethyl acetate), NMR (CDCl ₃ + CD ₃ OD): δ 8.85 (1H, s), 8.43 (1H, d, J)
= 8.0Hz), 8.35 (1H, d, J = 8.0Hz), 7.94 (2H, d, J = 8.8Hz),
7.85 (2H, d, J = 8.8Hz), 7.73 (1H, t, J = 8.0Hz), 3.68 (2H,
s), 1.38 (9H, s).

Example 1 (15) N-[[4- (4-nitrobenzoylamino) phenyl] sulfonyl] glycine t-butyl ester

[Chemical 100]

TLC: Rf 0.74 (ethyl acetate), NMR (DMSO-d ₆ ): δ 10.88 (1H, s), 8.39 (2H, d, J = 8.8
Hz), 8.20 (2H, d, J = 8.8Hz), 8.01 (1H, t, J = 6Hz), 7.97 (2
H, d, J = 8.8Hz), 7.79 (2H, d, J = 8.8Hz), 3.58 (2H, d, J = 6H
z), 1.32 (9H, s).

Example 1 (16) N-[[4- (4-ethylbenzoylamino) phenyl] sulfonyl] glycine t-butyl ester

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TLC: Rf 0.56 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.00-7.98 (1H, br.s), 7.87 (2H, d, J
= 8.4Hz), 7.81 (2H, d, J = 8.4Hz), 7.80 (2H, d, J = 8.2Hz),
7.34 (2H, d, J = 8.2Hz), 5.00 (1H, t, J = 5.4Hz), 3.67 (2H, d,
J = 5.4Hz), 2.74 (2H, q, J = 7.4Hz), 1.37 (9H, s), 1.28 (3H,
t, J = 7.4 Hz).

Example 1 (17) N-[[4- (4-Propylbenzoylamino) phenyl] sulfonyl] glycine t-butyl ester

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TLC: Rf 0.62 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.02-7.95 (1H, br.s), 7.86 (2H, d, J
= 8.8Hz), 7.81 (2H, d, J = 8.8Hz), 7.80 (2H, d, J = 8.4Hz),
7.31 (2H, d, J = 8.4Hz), 5.01 (1H, t, J = 5.4Hz), 3.67 (2H, d,
J = 5.4Hz), 2.67 (2H, t, J = 7.4Hz), 1.80-1.60 (2H, m), 1.3
7 (9H, s), 0.96 (3H, t, J = 7.4Hz).

Example 1 (18) N-[[4- (2-fluorobenzoylamino) phenyl] sulfonyl] glycine t-butyl ester

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TLC: Rf 0.53 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.65 (1H, d, br.s), 8.18 (1H, dt, J =
2.0, 8.0Hz), 7.88 (2H, d, J = 8.8Hz), 7.83 (2H, d, J = 8.8H
z), 7.64-7.51 (1H, m), 7.35 (1H, dt, J = 1.0, 7.4Hz), 7.2
8-7.15 (1H, m), 5.02 (1H, t, J = 5.4Hz), 3.68 (2H, d, J = 5.4H
z), 1.36 (9H, s).

Example 1 (19) N-[[4- (3-fluorobenzoylamino) phenyl] sulfonyl] glycine t-butyl ester

[Chemical 104]

TLC: Rf 0.53 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.00-7.93 (1H, br.s), 7.88 (2H, d, J
= 8.8Hz), 7.80 (2H, d, J = 8.8Hz), 7.68-7.44 (3H, m), 7.35
-7.27 (1H, m), 5.01 (1H, t, J = 5.4Hz), 3.68 (2H, d, J = 5.4H
z), 1.37 (9H, s).

Example 1 (20) N-[[4- (cyclohexylcarbonylamino) phenyl] sulfonyl] glycine t-butyl ester

Embedded image

TLC: Rf 0.55 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 7.80 (2H, d, J = 8.8Hz), 7.68 (2H, d, J =
8.8Hz), 7.44-7.32 (1H, br.s), 5.00 (1H, t, J = 5.0Hz),
3.65 (2H, d, J = 5.0Hz), 2.35-2.18 (1H, m), 2.04-1.20 (10
H, m), 1.36 (9H, s).

Example 1 (21) N-[[4- (4-trifluoromethylbenzoylamino) phenyl] sulfonyl] glycine t-butyl ester

[Chemical formula 106]

TLC: Rf 0.65 (hexane: ethyl acetate = 1: 1), NMR (DMSO-d ₆ ): δ 10.83 (1H, s), 8.18 (2H, d, J = 8.0H)
z), 8.04-7.95 (1H), 7.98 (2H, d, J = 8.8Hz), 7.91 (2H, d, J
= 8.0Hz), 7.77 (2H, d, J = 8.8Hz), 3.55 (2H, d, J = 6.2Hz),
1.32 (9H, s).

Example 1 (22) N-[[4- (2-thienylcarbonylamino) phenyl] sulfonyl] glycine t-butyl ester

[Chemical formula 107]

TLC: Rf 0.26 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 7.95 (1H, s), 7.84 (2H, d, J = 8.8Hz),
7.77 (2H, d, J = 8.8Hz), 7.68 (1H, dd, J = 1.0, 3.8Hz), 7.61
(1H, dd, J = 1.0, 4.8Hz), 7.16 (1H, dd, J = 3.8, 4.8Hz), 5.
05 (1H, t, J = 5.4Hz), 3.68 (2H, d, J = 5.4Hz), 1.37 (9H,
s).

Example 1 (23) N-[[4- (2-furylcarbonylamino) phenyl] sulfonyl] glycine t-butyl ester

Embedded image

TLC: Rf 0.19 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.25 (1H, s), 7.86-7.82 (4H, m), 7.5
5 (1H, d, J = 1.8Hz), 7.30 (1H, d, J = 3.6Hz), 6.60 (1H, dd, J =
1.8, 3.6Hz), 5.03 (1H, t, J = 5.6Hz), 3.68 (2H, d, J = 5.6H
z), 1.36 (9H, s).

Example 1 (24) N-[[4- (2-pyridylcarbonylamino) phenyl] sulfonyl] glycine t-butyl ester

Embedded image

TLC: Rf 0.45 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 10.33-10.20 (1H, br.s), 8.64-8.60
(1H, m), 8.31 (1H, d, J = 7.8Hz), 8.00-7.85 (1H, m), 7.95
(2H, d, J = 9.0Hz), 7.88 (2H, d, J = 9.0Hz), 7.53 (1H, m), 5.
02 (1H, t, J = 5.4Hz), 3.68 (2H, d, J = 5.4Hz), 1.36 (9H, s).

Example 1 (25) N-[[4- (3-pyridylcarbonylamino) phenyl] sulfonyl] glycine t-butyl ester

Embedded image

TLC: Rf 0.40 (ethyl acetate), NMR (CDCl ₃ ): δ 9.11 (1H, br.s), 8.81 (1H, dd, J = 1.
6, 4.8Hz), 8.27-8.20 (1H, m), 8.20-8.10 (1H, br.s),
7.88 (2H, d, J = 9.0Hz), 7.81 (2H, d, J = 9.0Hz), 7.53-7.44
(1H, m), 5.10 (1H, t, J = 5.4Hz), 3.69 (2H, d, J = 5.4Hz), 1.
37 (9H, s).

Example 1 (26) N-[[4- (4-pyridylcarbonylamino) phenyl] sulfonyl] glycine t-butyl ester

[Chemical 111]

TLC: Rf 0.36 (ethyl acetate), NMR (CDCl ₃ + CD ₃ OD (10 drops)): δ 8.76-8.71 (2H, m),
7.93 (2H, d, J = 9.0Hz), 7.89-7.82 (2H, m), 7.85 (2H, d, J =
9.0Hz), 3.66 (2H, s), 1.37 (9H, s).

Example 1 (27) N-[[4- (3-thienylcarbonylamino) phenyl] sulfonyl] glycine t-butyl ester

[Chemical 112]

TLC: Rf 0.27 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ + CD ₃ OD): δ 8.16 (1H, m), 7.87 (2H, d, J =
9.0Hz), 7.82 (2H, d, J = 9.0Hz), 7.61 (1H, m), 7.40 (1H,
m), 3.66 (2H, s), 1.36 (9H, s).

Example 1 (28) N-[[4- (3-furylcarbonylamino) phenyl] sulfonyl] glycine t-butyl ester

[Chemical 113]

TLC: Rf 0.29 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ + CD ₃ OD): δ 8.17 (1H, m), 7.84 (2H, d, J =
9.0Hz), 7.82 (2H, d, J = 9.0Hz), 7.49 (1H, m), 6.88 (1H,
m), 3.66 (2H, s), 1.37 (9H, s).

Example 1 (29) N-[[4- (4-methoxycarbonylbenzoylamino) phenyl] sulfonyl] glycine t-butyl ester

[Chemical 114]

TLC: Rf 0.43 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.05-7.98 (1H, br.s), 7.94 (2H, d, J
= 8.4Hz), 7.89 (2H, d, J = 9.0Hz), 7.82 (2H, d, J = 9.0Hz),
5.01 (1H, t, J = 5.4Hz), 3.97 (3H, s), 3.69 (2H, d, J = 5.4H
z), 1.37 (9H, s).

Example 1 (30) N-[[4- (4-cyanobenzoylamino) phenyl] sulfonyl] glycine t-butyl ester

[Chemical 115]

TLC: Rf 0.41 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.15 (1H, s), 8.00 (2H, d, J = 8.2Hz),
7.85 (2H, d, J = 9.0Hz), 7.80 (2H, d, J = 8.2Hz), 7.79 (2H, d, J
= 9.0Hz), 5.06 (1H, t, J = 5.4Hz), 3.68 (2H, d, J = 5.4Hz),
1.37 (9H, s).

Example 1 (31) N-[[4- (4-benzyloxybenzoylamino)
Phenyl] sulfonyl] glycine t-butyl ester

Embedded image

TLC: Rf 0.58 (hexane: ethyl acetate = 1: 1), NMR (DMSO-d ₆ ): δ 10.41 (1H, s), 8.04-7.88 (1H, s),
7.97 (2H, d, J = 8.4Hz), 7.96 (2H, d, J = 8.4Hz), 7.74 (2H, d, J
= 8.4Hz), 7.52-7.28 (5H, m), 7.16 (2H, d, J = 8.4Hz), 5.21
(2H, s), 3.56 (2H, s), 1.32 (9H, s).

Example 1 (32) N-[[4- (4-carboxybenzoylamino) phenyl] sulfonyl] glycine t-butyl ester

[Chemical 117] The following reaction was carried out as it was without measuring the physical properties.

Example 1 (33) N-[[4- (Cinnamoylamino) phenyl] sulfonyl] glycine t-butyl ester

Embedded image

TLC: Rf 0.50 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 7.85 (2H, d, J = 8.8Hz), 7.79 (1H, d, J =
15.6Hz), 7.77 (2H, d, J = 8.8Hz), 7.65-7.50 (3H, m), 7.46
-7.38 (3H, m), 6.56 (1H, d, J = 15.6Hz), 5.03 (1H, t, J = 5.4H
z), 3.67 (2H, d, J = 5.4Hz), 1.36 (9H, s).

Example 1 (34) N-[[4- (4-butylbenzoylamino) phenyl] sulfonyl] glycine t-butyl ester

[Chemical formula 119]

TLC: Rf 0.27 (hexane: ethyl acetate = 7: 3), NMR (CDCl ₃ ): δ 7.97 (1H, s), 7.87 (2H, d, J = 9.0Hz),
7.80 (2H, d, J = 9.0Hz), 7.79 (2H, d, J = 8.0Hz), 7.32 (2H, d, J
= 8.0Hz), 5.01 (1H, t, J = 5.4Hz), 3.68 (2H, d, J = 5.4Hz),
2.69 (2H, t, J = 7.4Hz), 1.70-1.50 (2H, m), 1.45-1.20 (2H,
m), 1.37 (9H, s), 0.94 (3H, t, J = 7.2Hz).

Example 1 (35) N-[[4- (4-pentylbenzoylamino) phenyl] sulfonyl] glycine t-butyl ester

Embedded image

TLC: Rf 0.28 (hexane: ethyl acetate = 7: 3), NMR (CDCl ₃ ): δ 7.99 (1H, s), 7.86 (2H, d, J = 9.0Hz),
7.80 (2H, d, J = 9.0Hz), 7.79 (2H, d, J = 8.2Hz), 7.31 (2H, d, J
= 8.2Hz), 5.02 (1H, t, J = 5.4Hz), 3.67 (2H, d, J = 5.4Hz),
2.68 (2H, t, J = 7.4Hz), 1.72-1.50 (2H, m), 1.45-1.20 (4H,
m), 1.36 (9H, s), 0.89 (3H, t, J = 6.6Hz).

Example 1 (36) N-[[4- (4-phenylbenzoylamino) phenyl] sulfonyl] glycine t-butyl ester

[Chemical 121]

TLC: Rf 0.67 (hexane: ethyl acetate = 1: 1), NMR (DMSO-d ₆ ): δ 10.61 (1H, s), 8.08 (2H, d, J = 8.4H)
z), 8.04-7.93 (1H, m), 8.00 (2H, d, J = 9.0Hz), 7.85 (2H, d,
J = 8.4Hz), 7.82-7.72 (2H), 7.77 (2H, d, J = 9.0Hz), 7.58-
7.36 (3H, m), 3.57 (2H, d, J = 6.4Hz), 1.32 (9H, s).

Example 1 (37) N-[[4- (benzoylamino) phenyl] sulfonyl] -L-valine.t-butyl ester

[Chemical formula 122]

TLC: Rf 0.39 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.02 (1H, s), 7.9-7.75 (6H, m), 7.65
-7.45 (3H, m), 5.14 (1H, d, J = 9.9Hz), 3.66 (1H, dd, J = 4.4,
9.9Hz), 2.05 (1H, m), 1.26 (9H, s), 1.00 (3H, d, J = 7Hz),
0.85 (3H, d, J = 7Hz).

Example 1 (38) N-[[4- (1-naphthoylamino) phenyl] sulfonyl] glycine t-butyl ester

[Chemical 123]

TLC: Rf 0.57 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.34-8.24 (1H, m), 8.10 (1H, s), 7.9
8 (1H, d, J = 8.0Hz), 7.94-7.85 (1H, m), 7.85-7.76 (4H, m),
7.72 (1H, dd, J = 1.2, 7.2Hz), 7.64-7.51 (2H, m), 7.47 (1
H, d, J = 7.2Hz), 5.03 (1H, t, J = 5.4Hz), 3.65 (2H, d, J = 5.4H
z), 1.38 (9H, s).

Example 1 (39) N-[[4- (2-naphthoylamino) phenyl] sulfonyl] glycine t-butyl ester

Embedded image

TLC: Rf 0.57 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.40 (1H, d, J = 0.8Hz), 8.23 (1H, s),
8.02-7.80 (8H, m), 7.68-7.54 (2H, m), 5.03 (1H, t, J = 5.2H
z), 3.68 (2H, d, J = 5.2Hz), 1.38 (9H, s).

Example 1 (40) N-[[4- (3-benzyloxybenzoylamino)
Phenyl] sulfonyl] glycine t-butyl ester

Embedded image

TLC: Rf 0.49 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 7.95 (1H, s), 7.87 (2H, d, J = 9.0Hz),
7.78 (2H, d, J = 9.0Hz), 7.54-7.32 (8H, m), 7.24-7.15 (1H,
m), 5.14 (2H, s), 5.00 (1H, t, J = 5.4Hz), 3.67 (2H, d, J = 5.4
Hz), 1.37 (9H, s).

Example 1 (41) N-[[4- (2-benzyloxybenzoylamino)
Phenyl] sulfonyl] glycine t-butyl ester

[Chemical formula 126]

TLC: Rf 0.53 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 10.25 (1H, s), 8.32 (1H, d, J = 7.8Hz),
7.66 (2H, d, J = 8.8Hz), 7.62-7.47 (5H, m), 7.32-7.22 (1H,
m), 7.27 (2H, d, J = 8.8Hz), 7.17 (2H, m), 5.23 (2H, s), 4.
94 (1H, t, J = 5.4Hz), 3.62 (2H, d, J = 5.4Hz), 1.34 (9H, s).

Example 1 (42) N-[[4- (benzoylamino) phenyl] sulfonyl] -L-aspartic acid di-t-butyl ester

Embedded image

TLC: Rf 0.46 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.02 (1H, s), 7.9-7.75 (6H, m), 7.65
-7.45 (3H, m), 5.63 (1H, d, J = 8.2Hz), 4.00 (1H, m), 2.82
(1H, dd, J = 4.6Hz, 16.8Hz), 2.72 (1H, dd, J = 4.8,16.8Hz),
1.44 (9H, s), 1.33 (9H, s).

Example 1 (43) N-[[4- (benzoylamino) phenyl] sulfonyl] -L-glutamic acid di-t-butyl ester

[Chemical 128]

TLC: Rf 0.42 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.08 (1H, s), 7.9-7.8 (6H, m), 7.65-
7.25 (3H, m), 5.26 (1H, d, J = 9.4Hz), 3.83 (1H, m), 2.40 (2
H, m), 2.15-1.65 (2H, m), 1.46 (9H, s), 1.28 (9H, s).

Example 1 (44) N-[[4- (phenylacetylamino) phenyl] sulfonyl] glycine t-butyl ester

[Chemical formula 129]

TLC: Rf 0.41 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 7.75 (2H, d, J = 8.8Hz), 7.57 (2H, d, J =
8.8Hz), 7.48-7.29 (6H, m), 5.03 (1H, t, J = 5.4Hz), 3.76
(2H, s), 3.63 (2H, d, J = 5.4Hz), 1.35 (9H, s).

Example 1 (45) N-[[4- (benzoylamino) phenyl] sulfonyl] -L-leucine t-butyl ester

Embedded image

TLC: Rf 0.45 (hexane: ethyl acetate = 1: 1), NMR (DMSO-d ₆ ): δ 10.29 (1H, s), 8.2-8.05 (1H), 7.9
6 (2H, dd, J = 1.6, 8.2Hz), 7.72 (2H, d, J = 8.8Hz), 7.6-7.4
5 (5H, m), 3.86 (1H, m), 1.8-1.5 (3H, m), 1.46 (9H, s), 0.
91 (3H, d, J = 6.2Hz), 0.90 (3H, d, J = 6.2Hz).

Example 1 (46) N-[[4- (benzoylamino) phenyl] sulfonyl] -D-leucine t-butyl ester

Embedded image

TLC: Rf 0.45 (hexane: ethyl acetate = 1: 1), NMR (DMSO-d ₆ ): δ 10.29 (1H, s), 8.2-8.05 (1H), 7.9
6 (2H, dd, J = 1.6, 8.0Hz), 7.72 (2H, d, J = 8.8Hz), 7.6-7.4
5 (5H, m), 3.86 (1H, m), 1.8-1.5 (3H, m), 1.46 (9H, s), 0.
91 (3H, d, J = 6.2Hz), 0.90 (3H, d, J = 6.2Hz).

Example 1 (47) N-[[4- (phenoxycarbonylamino) phenyl] sulfonyl] glycine t-butyl ester

[Chemical 132]

TLC: Rf 0.55 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 7.84 (2H, d, J = 8.8Hz), 7.59 (2H, d, J =
8.8Hz), 7.48-7.36 (2H, m), 7.33-7.16 (4H, m), 5.01 (1H,
t, J = 5.4Hz), 3.67 (2H, d, J = 5.4Hz), 1.37 (9H, s).

Example 1 (48) N-[[4- (4-dimethylaminobenzoylamino)
Phenyl] sulfonyl] glycine t-butyl ester

Embedded image

TLC: Rf 0.23 (hexane: ethyl acetate = 1: 1), NMR (DMSO-d ₆ ): δ 10.18 (1H, s), 8.0-7.85 (5H, m),
7.72 (2H, d, J = 8.8Hz), 6.77 (2H, d, J = 9.0Hz), 3.56 (2H, d,
J = 6.0Hz), 3.01 (6H, s), 1.32 (9H, s).

Example 1 (49) N-[[4- (benzoylamino) phenyl] sulfonyl] -D-valine.t-butyl ester

Embedded image

TLC: Rf 0.43 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 7.99 (1H, s), 7.9-7.75 (6H, m), 7.6-
7.45 (3H, m), 5.13 (1H, d, J = 9.8Hz), 3.65 (1H, dd, J = 4.4,
9.8Hz), 2.05 (1H, m), 1.26 (9H, s), 1.00 (3H, d, J = 6.8H
z), 0.85 (3H, d, J = 6.8Hz).

Example 1 (50) N-[[4- (benzoylamino) phenyl] sulfonyl] -L-phenylalanine t-butyl ester

[Chemical 135]

TLC: Rf 0.44 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.02 (1H, s), 7.87 (2H, m), 7.76 (4H,
s), 7.65-7.45 (3H, m), 7.3-7.1 (5H, m), 5.13 (1H, d, J = 9H
z), 4.10 (1H, dt, J = 9, 6Hz), 3.03 (2H, d, J = 6Hz), 1.23 (9
H, s).

Example 1 (51) N-[[4- (benzoylamino) phenyl] sulfonyl] -D-phenylalanine.t-butyl ester

[Chemical 136]

TLC: Rf 0.44 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 7.98 (1H, s), 7.88 (2H, m), 7.76 (4H,
s), 7.65-7.45 (3H, m), 7.3-7.1 (5H, m), 5.11 (1H, d, J = 9.2
Hz), 4.10 (1H, dt, J = 9.2, 6Hz), 3.03 (2H, d, J = 6Hz), 1.2
3 (9H, s).

Example 1 (52) N-[[4- (benzoylamino) phenyl] sulfonyl] -L-alanine t-butyl ester

[Chemical 137]

TLC: Rf 0.37 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.15 (1H, br.s), 7.89 (2H, dd, J = 1.6)
Hz, 8.4Hz), 7.81 (4H, s), 7.65-7.45 (3H, m), 5.30 (1H,
br.d, J = 8.2Hz), 3.86 (1H, m), 1.36 (3H, d, J = 7.2Hz), 1.3
2 (9H, s).

Example 1 (53) N-[[4- (benzoylamino) phenyl] sulfonyl] -D-alanine t-butyl ester

[Chemical 138]

TLC: Rf 0.37 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.10 (1H, br.s), 7.88 (2H, dd, J = 1.6)
Hz, 8.4Hz), 7.81 (4H, s), 7.65-7.45 (3H, m), 5.28 (1H,
d, J = 8.2Hz), 3.86 (1H, m), 1.36 (3H, d, J = 7Hz), 1.32 (9H,
s).

Example 1 (54) N-[[4- (benzoylamino) phenyl] sulfonyl] -t-butoxycarbonyl-L-lysine.t-butyl ester

Embedded image

TLC: Rf 0.28 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.13 (1H, br.s), 7.91 (2H, m), 7.83
(4H, s), 7.65-7.45 (3H, m), 5.23 (1H, d, J = 9Hz), 4.38 (1
H, m), 3.79 (1H, m), 3.03 (2H, m), 1.9-1.3 (6H, m), 1.44
(9H, s), 1.30 (9H, s).

Example 1 (55) N-[[4- (benzoylamino) phenyl] sulfonyl] -t-butoxycarbonyl-D-lysine.t-butyl ester

Embedded image

TLC: Rf 0.28 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.19 (1H, br.s), 7.91 (2H, m), 7.85
(2H, d, J = 8.8Hz), 7.80 (2H, d, J = 8.8Hz), 7.65-7.45 (3H,
m), 5.22 (1H, d, J = 8.8Hz), 4.57 (1H, m), 3.79 (1H, m), 3.
03 (2H, m), 1.90-1.25 (6H, m), 1.44 (9H, s), 1.30 (9H,
s).

Example 1 (56) N-[[4- (benzoylamino) phenyl] sulfonyl] -D-glutamic acid di-t-butyl ester

[Chemical 141]

TLC: Rf 0.41 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.11 (1H, s), 7.88 (2H, d, J = 8.4Hz),
7.81 (4H, s), 7.65-7.45 (3H, m), 5.26 (1H, d, J = 9Hz), 3.8
2 (1H, m), 2.4 (2H, m), 2.05 (1H, m), 1.79 (1H, m), 1.46 (9
H, s), 1.28 (9H, s).

Example 1 (57) N-[[4- (4-dodecylbenzoylamino) phenyl] sulfonyl] glycine t-butyl ester

[Chemical 142]

TLC: Rf 0.33 (hexane: ethyl acetate = 7: 3), NMR (CDCl ₃ ): δ 7.98 (1H, s), 7.86 (2H, d, J = 9.0Hz),
7.80 (2H, d, J = 9.0Hz), 7.79 (2H, d, J = 8.4Hz), 7.31 (2H, d, J
= 8.4Hz), 5.01 (1H, t, J = 5.4Hz), 3.67 (2H, d, J = 5.4Hz),
2.86 (2H, t, J = 7.4Hz), 1.74-1.50 (2H, m), 1.37 (9H, s),
1.36-1.10 (18H, m), 0.88 (3H, t, J = 6.8Hz).

Example 1 (58) 4- [N-[[4- (benzoylamino) phenyl] sulfonyl] amino] butanoic acid t-butyl ester

[Chemical 143]

TLC: Rf 0.31 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.09 (1H, s), 7.9-7.75 (6H, m), 7.65
-7.45 (3H, m), 4.80 (1H, t, J = 6.4Hz), 3.00 (2H, q, J = 6.4H
z), 2.27 (2H, t, J = 6.8Hz), 1.76 (2H, m), 1.43 (9H, s).

Example 1 (59) 2- [N-[[4- (benzoylamino) phenyl] sulfonyl] amino] -3-t-butoxy-L-propionic acid.t-butyl ester

[Chemical 144]

TLC: Rf 0.44 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.09 (1H, br.s), 7.9-7.75 (6H, m),
7.65-7.45 (3H, m), 5.45 (1H, d, J = 9.4Hz), 4.0-3.95 (1H,
m), 3.69 (1H, dd, J = 3, 8.5Hz), 3.52 (1H, dd, J = 3.2, 8.5H
z), 1.32 (9H, s), 1.11 (9H, s).

Example 1 (60) 2- [N-[[4- (benzoylamino) phenyl] sulfonyl] amino] -3-t-butoxy-D-propionic acid.t-butyl ester

Embedded image

TLC: Rf 0.44 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.04 (1H, br.s), 7.9-7.75 (6H, m),
7.65-7.45 (3H, m), 5.44 (1H, d, J = 9.2Hz), 4.0-3.95 (1H,
m), 3.69 (1H, dd, J = 3.0, 8.6Hz), 3.52 (1H, dd, J = 3.2, 8.
6Hz), 1.32 (9H, s), 1.11 (9H, s).

Example 1 (61) N-[[4- (benzoylamino) phenyl] sulfonyl] -D-aspartic acid.di-t-butyl ester

[Chemical 146]

TLC: Rf 0.40 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.17 (1H, s), 7.9-7.75 (6H, m), 7.6-
7.45 (3H, m), 5.64 (1H, d, J = 8.0Hz), 3.99 (1H, m), 2.81 (1
H, dd, J = 4.6, 16.8Hz), 2.72 (1H, dd, J = 4.6, 16.8Hz), 1.
43 (9H, s), 1.33 (9H, s).

Example 1 (62) N-[[4- (p-toluoylamino) phenyl] sulfonyl] -D-phenylalanine t-butyl ester

[Chemical 147]

TLC: Rf 0.43 (hexane: ethyl acetate = 1: 1), NMR (CD ₃ OD: CDCl ₃ = 1: 1): δ 7.9-7.8 (4H, m), 7.71 (2)
H, d, J = 8.8Hz), 7.35-7.1 (7H, m), 4.04 (1H, t, J = 6.6Hz),
2.98 (2H, d, J = 6.6Hz), 2.44 (3H, s), 1.23 (9H, s).

Example 1 (63) N-[[4- (4-pentylbenzoylamino) phenyl] sulfonyl] -D-phenylalanine t-butyl ester

Embedded image

TLC: Rf 0.66 (hexane: ethyl acetate = 3: 2), NMR (CDCl ₃ ): δ 7.95 (1H, s), 7.84-7.68 (6H, m), 7.3
5-7.08 (7H, m), 5.10 (1H, d, J = 10.0Hz), 4.14-4.00 (1H,
m), 3.02 (2H, d, J = 6.0Hz), 2.67 (2H, t, J = 7.8Hz), 1.72-1.
56 (2H, m), 1.48-1.25 (4H, m), 1.21 (9H, s), 0.89 (3H, t, J
= 5.0Hz).

Example 1 (64) N-[[4- (p-toluoylamino) phenyl] sulfonyl] -L-valine t-butyl ester

Embedded image

TLC: Rf 0.54 (hexane: ethyl acetate = 3: 2), NMR (CDCl ₃ ): δ 7.93 (1H, s), 7.83 (2H, d, J = 9.0Hz),
7.77 (2H, d, J = 9.0Hz), 7.76 (2H, d, J = 8.0Hz), 7.30 (2H, d, J
= 8.0Hz), 5.08 (1H, d, J = 10.8Hz), 3.62 (1H, dd, J = 4.4, 1
0.8Hz), 2.44 (3H, s), 2.15-1.90 (1H, m), 1.25 (9H, s),
1.00 (3H, d, J = 6.6Hz), 0.85 (3H, d, J = 6.6Hz).

Example 1 (65) N-[[4- (4-hexylbenzoylamino) phenyl] sulfonyl] glycine t-butyl ester

[Chemical 150]

TLC: Rf 0.26 (hexane: ethyl acetate = 7: 3), NMR (CDCl ₃ ): δ 8.04 (1H, s), 7.85 (2H, d, J = 9.0Hz),
7.79 (4H, m), 7.30 (2H, d, J = 8.0Hz), 5.04 (1H, t, J = 5.2H
z), 3.67 (2H, d, J = 5.2Hz), 2.68 (2H, t, J = 8.0Hz), 1.76-1.
50 (2H, m), 1.37 (9H, s), 1.35-1.20 (6H, m), 0.88 (3H, t, J
= 6.8Hz).

Example 1 (66) N-[[4- (4-heptylbenzoylamino) phenyl] sulfonyl] glycine t-butyl ester

Embedded image

TLC: Rf 0.29 (hexane: ethyl acetate = 7: 3), NMR (CDCl ₃ ): δ 8.03 (1H, s), 7.85 (2H, d, J = 9.0Hz),
7.79 (4H, m), 7.31 (2H, d, J = 8.2Hz), 5.03 (1H, t, J = 5.6H
z), 3.67 (2H, d, J = 5.6Hz), 2.68 (2H, t, J = 8.2Hz), 1.72-1.
50 (2H, m), 1.37 (9H, s), 1.35-1.10 (8H, m), 0.88 (3H, t, J
= 6.8Hz).

Example 1 (67) N-[[4- (4-isopropylbenzoylamino) phenyl] sulfonyl] glycine t-butyl ester

[Chemical 152]

TLC: Rf 0.19 (hexane: ethyl acetate = 7: 3), NMR (CDCl ₃ ): δ 8.01 (1H, s), 7.86 (2H, d, J = 9.0Hz),
7.82-7.72 (4H, m), 7.36 (2H, d, J = 8.4Hz), 5.01 (1H, t, J =
5.4Hz), 3.67 (2H, d, J = 5.4Hz), 2.99 (1H, m), 1.37 (9H,
s), 1.29 (6H, d, J = 6.8Hz).

Example 1 (68) N-[[4- (4-isobutylbenzoylamino) phenyl] sulfonyl] glycine t-butyl ester

Embedded image

TLC: Rf 0.23 (hexane: ethyl acetate = 7: 3), NMR (CDCl ₃ ): δ 8.04 (1H, s), 7.86 (2H, d, J = 9.0Hz),
7.82-7.72 (4H, m), 7.27 (2H, d, J = 8.2Hz), 5.03 (1H, t, J =
5.4Hz), 3.67 (2H, d, J = 5.4Hz), 2.56 (2H, d, J = 7.0Hz), 1.
91 (1H, m), 1.37 (9H, s), 0.92 (6H, d, J = 6.6Hz).

Example 1 (69) N-[[4- (benzoylamino) phenyl] sulfonyl] -2,2-dimethylglycine t-butyl ester

Embedded image

TLC: Rf 0.40 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.03 (1H, s), 7.9-7.75 (6H, m), 7.65
-7.45 (3H, m), 5.42 (1H, s), 1.45 (9H, s), 1.41 (6H, s).

Example 1 (70) 2- [N-[[4- (p-toluoylamino) phenyl] sulfonyl] amino] -3-t-butoxy-D-propionic acid.t-butyl ester

[0346]

Embedded image TLC: Rf 0.69 (hexane: ethyl acetate = 1: 1
1), NMR (CDCl ₃ ): δ 7.99 (1H, s), 7.85 (2H, d, J = 8.0Hz),
7.78 (4H, d, J = 8.0Hz), 7.30 (2H, d, J = 8.0Hz), 5.43 (1H, d, J
= 9.2Hz), 3.97 (1H, td, J = 3.0Hz, 9.2Hz), 3.69 (1H, dd, J =
3.0Hz, 8.6Hz), 3.51 (1H, dd, J = 3.0Hz, 8.6Hz), 2.43 (3
H, s), 1.31 (9H, s), 1.10 (9H, s).

Example 1 (71) N-[[4- (p-toluoylamino) phenyl] sulfonyl] -L-leucine t-butyl ester

[Chemical 156]

TLC: Rf 0.50 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 7.90 (1H, s), 7.85-7.70 (6H, m), 7.3
2 (2H, d, J = 8.0Hz), 5.02 (1H, d, J = 10.0Hz), 3.90-3.75 (1
H, m), 2.45 (3H, s), 1.9-1.75 (1H, m), 1.46 (2H, m), 1.26
(9H, s), 0.93 (6H, d, J = 6.6Hz).

Example 1 (72) N-[[4- (p-toluoylamino) phenyl] sulfonyl] -D-alanine t-butyl ester

[Chemical 157]

TLC: Rf 0.57 (hexane: ethyl acetate = 1: 1), NMR (DMSO-d ₆ ): δ 10.47 (1H, s), 8.08 (1H, d, J = 8.6H)
z) 7.96 (2H, d, J = 8.8Hz), 7.88 (2H, d, J = 8.8Hz), 7.74 (2
H, d, J = 8.8Hz), 7.35 (2H, d, J = 8.2Hz), 3.80-3.64 (1H, m),
2.39 (3H, s), 1.28 (9H, s), 1.15 (3H, d, J = 7.0Hz).

Example 1 (73) N-[[4- (p-toluoylamino) phenyl] sulfonyl] -D-valine t-butyl ester

[Chemical 158]

TLC: Rf 0.65 (hexane: ethyl acetate = 1: 1), NMR (DMSO-d ₆ ): δ 10.45 (1H, s), 8.02-7.92 (3H, m),
7.88 (2H, d, J = 8.0Hz), 7.72 (2H, d, J = 8.8Hz), 7.35 (2H, d, J
= 8.0Hz), 3.48-3.38 (1H, m), 2.39 (3H, s), 2.02-1.80 (1
H, m), 1.22 (9H, s), 0.83 (6H, t, J = 5.6Hz).

Example 1 (74) N-[[4- (p-toluoylamino) phenyl] sulfonyl] -D-leucine t-butyl ester

[Chemical 159]

TLC: Rf 0.68 (hexane: ethyl acetate = 1: 1), NMR (DMSO-d ₆ ): δ 10.45 (1H, s), 8.07 (1H, d, J = 9.0)
H), 7.95 (2H, d, J = 8.8Hz), 7.88 (2H, d, J = 8.2Hz), 7.71 (2
H, d, J = 8.8Hz), 7.35 (2H, d, J = 8.2Hz), 3.70-3.54 (1H, m),
2.39 (3H, s), 1.72-1.50 (1H, m), 1.44-1.30 (2H, m), 1.2
3 (9H, s), 0.84 (3H, d, J = 6.6Hz), 0.76 (3H, d, J = 6.6Hz).

Example 1 (75) N-[[2-Methyl-4- (p-toluoylamino) phenyl] sulfonyl] glycine t-butyl ester

[Chemical 160]

TLC: Rf 0.29 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 7.95 (2H, d, J = 8.3Hz), 7.77 (2H, d, J =
6.4Hz), 7.75-7.57 (2H, m), 7.31 (2H, d, J = 8.3Hz), 5.10
(1H, m), 3.63 (2H, d, J = 2.2Hz), 2.68 (3H, s), 2.44 (3H,
s), 1.37 (9H, s).

Example 1 (76) N-[[3-Methyl-4- (p-toluoylamino) phenyl] sulfonyl] glycine t-butyl ester

[Chemical 161]

TLC: Rf 0.48 (chloroform: methanol = 97: 3), NMR (CDCl ₃ ): δ 8.38 (1H, d, J = 8.4Hz), 7.82-7.73 (4
H, m), 7.33 (2H, d, J = 7.8Hz), 5.00 (1H, t, J = 4.7Hz), 3.67
(2H, d, J = 4.7Hz), 2.45 (3H, s), 2.40 (3H, s), 1.38 (9H,
s).

Example 1 (77) N-[[4- (2-hydroxy-4-methylbenzoylamino) phenyl] sulfonyl] -D-alanine.t-
Butyl ester

[Chemical 162]

TLC: Rf 0.29 (chloroform: methanol = 97: 3), NMR (CDCl ₃ ): δ 11.64 (1H, s), 8.09 (1H, br.s), 7.8
5 (2H, d, J = 8.3Hz), 7.74 (2H, d, J = 8.3Hz), 7.43 (1H, d, J =
7.5Hz), 6.86 (1H, s), 6.75 (1H, d, J = 7.5Hz), 5.25 (1H, t,
J = 7.6Hz), 3.87 (2H, quint, J = 7.6Hz), 2.37 (3H, s), 1.37
(3H, d, J = 7.6Hz), 1.32 (9H, s).

Example 1 (78) N-[[4- (benzoylamino) phenyl] sulfonyl] -L-tryptophan benzyl ester

[Chemical formula 163]

TLC: Rf 0.43 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 9.19 (1H, s), 7.94 (2H, dd, J = 1.4, 7.
8Hz), 7.68-7.40 (7H, m), 7.36-7.24 (5H, m), 7.18-6.98
(5H, m), 6.84 (1H, s), 4.91 (2H, s), 4.25 (1H, m), 3.30-3.
06 (2H, m).

Example 1 (79) N-[[4- (benzoylamino) phenyl] sulfonyl] -L-tyrosine benzyl ester

Embedded image

TLC: Rf 0.34 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ + CD ₃ OD (10 drops)): δ 8.58 (1H, s), 7.80-
7.78 (2H, m), 7.71 (2H, d, J = 8.8Hz), 7.65-7.29 (8H, m),
7.25-7.17 (2H, m), 6.81 (2H, d, J = 8.6Hz), 6.62 (2H, d, J =
8.6Hz), 4.97 (2H, s), 4.10 (1H, dd, J = 5.8Hz, 7.8Hz), 2.
99 (1H, dd, J = 5.8, 14.0Hz), 2.81 (1H, dd, J = 7.8Hz, 14.0H
z).

Example 1 (80) N-[[4- (benzoylamino) phenyl] sulfonyl] -D-tryptophan benzyl ester

Embedded image

TLC: Rf 0.34 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ + CD ₃ OD): δ 7.98-7.90 (2H, m), 7.63 (2)
H, d, J = 8.8Hz), 7.60-7.39 (6H, m), 7.35-7.25 (5H, m), 7.
17-6.97 (3H, m), 6.85 (1H, s), 4.91 (2H, s), 4.25 (1H, t, J
= 6.4Hz), 3.30-3.06 (2H, m).

Example 1 (81) N-[[4- (benzoylamino) phenyl] sulfonyl] -D-tyrosine benzyl ester

[Chemical 166]

TLC: Rf 0.31 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.64-8.57 (1H, m), 8.15 (1H, s), 7.9
1 (2H, d, J = 8.0Hz), 7.80-7.42 (6H, m), 7.40-7.20 (6H, m),
6.76 (2H, d, J = 8.4Hz), 6.58 (2H, d, J = 8.4Hz), 5.17 (1H,
d, J = 9.2Hz), 5.04 (2H, s), 4.18-4.04 (1H, m), 3.01 (1H, d
d, J = 5.0Hz, 14.2Hz), 2.75 (1H, dd, J = 7.8Hz, 14.2Hz).

Example 1 (82) N-[[4- (benzoylamino) phenyl] sulfonyl] -D-histidine benzyl ester

[Chemical 167]

TLC: Rf 0.31 (chloroform: methanol = 9: 1) NMR (CDCl ₃ + CD ₃ OD): δ 8.17 (1H, s), 7.96-7.80 (6
H, m), 7.68-7.42 (3H, m), 7.40-7.22 (5H, m), 7.04 (1H,
s), 5.10 (2H, s), 3.80 (1H, dd, J = 4.6Hz, 7.6Hz), 2.98 (1
H, dd, J = 4.6Hz, 14.6Hz), 2.81 (1H, dd, J = 7.6Hz, 14.6H
z).

Example 1 (83) 2- [N- [4- (benzoylamino) phenyl] sulfonylamino] 3- (pyridin-3-yl) propionic acid benzyl ester

[Chemical 168]

TLC: Rf 0.32 (hexane: ethyl acetate = 1: 5), NMR (CDCl ₃ ): δ 8.41 (1H, dd, J = 2.0Hz, 5.0Hz), 8.25
(1H, d, J = 2.0Hz), 8.08 (1H, s), 7.81 (2H, m), 7.74 (4H,
s), 7.65-7.45 (3H, m), 7.35-7.3 (4H, m), 7.25-7.15 (2H,
m), 7.09 (1H, dd, J = 5.0Hz, 8.0Hz), 5.58 (1H, d, J = 8.0H
z), 4.97 (1H, s), 4.27 (1H, dt, J = 6.0Hz, 8.0Hz), 3.05 (2
H, d, J = 6.0 Hz).

Example 1 (84) N-[[4- (p-toluoylamino) phenyl] sulfonyl] -D-tryptophan benzyl ester

[Chemical 169]

TLC: Rf 0.32 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ + CD ₃ OD): δ 7.81 (2H, d, J = 8.0Hz), 7.56
(4H, s), 7.43 (1H, d, J = 7.0Hz), 7.35-7.25 (6H, m), 7.15-
7.00 (4H, m), 6.81 (1H, s), 4.92 (2H, s), 4.25 (1H, m), 3.
18 (2H, m), 2.45 (3H, s).

Example 1 (85) N-[[4- (benzoylamino) phenyl] sulfonyl] glycine ethyl ester

Embedded image

TLC: Rf 0.26 (hexane: ethyl acetate = 1: 1), NMR (DMSO-d ₆ ): δ 10.59 (1H, s), 8.09 (1H, t, J = 6.2H)
z), 8.0-7.95 (4H, m), 7.77 (2H, d, J = 8.8Hz), 7.65-7.5 (3
H, m), 4.00 (2H, q, J = 7.0Hz), 3.68 (2H, d, J = 6.2Hz), 1.12
(3H, t, J = 7.0Hz).

Example 1 (86) N-[[4- (p-toluoylamino) phenyl] sulfonyl] -D-alanine pivaloyloxymethyl ester

[Chemical 171]

TLC: Rf 0.38 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.05 (1H, br.s), 7.82 (4H, s), 7.78
(2H, d, J = 8.0Hz), 7.31 (2H, d, J = 8.0Hz), 5.67 (1H, d, J = 1
4.6Hz), 5.59 (1H, d, J = 14.6Hz), 5.15 (1H, br.d, J = 8.8H
z), 4.03 (1H, m), 2.44 (3H, s), 1.39 (3H, d, J = 7.0Hz), 1.1
7 (9H, s).

Example 1 (87) N-[[4- (p-toluoylamino) phenyl] sulfonyl] -D-alanine dimethylaminocarbonylmethyl ester

Embedded image

TLC: Rf 0.42 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1), NMR (CDCl ₃ + CD ₃ OD (3 drops)): δ 7.82 (6H, m), 7.31 (2
H, d, J = 8.2Hz), 4.56 (1H, d, J = 14.6Hz), 4.37 (1H, d, J = 14.
6Hz), 4.10 (1H, q, J = 7.4Hz), 2.94 (3H, s), 2.90 (3H, s),
2.44 (3H, s), 1.46 (3H, d, J = 7.4Hz).

Example 1 (88) N-[[4- (p-toluoylamino) phenyl] sulfonyl] -D-alanine benzyl ester

[Chemical 173]

TLC: Rf 0.56 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1), NMR (DMSO-d ₆ ): δ 10.49 (1H, s), 7.96 (3H, m), 7.89
(2H, d, J = 8.0Hz), 7.74 (2H, d, J = 8.8Hz), 7.40-7.25 (7H,
m), 4.96 (2H, s), 3.94 (1H, m), 2.40 (3H, s), 1.19 (3H, d,
J = 7.2Hz).

Example 1 (89) N-[[4- (2-thienylcarbonylamino) phenyl] sulfonyl] -D-alanine t-butyl ester

Embedded image

TLC: Rf 0.25 (hexane: ethyl acetate = 2: 1), NMR (DMSO-d ₆ ): δ 10.51 (1H, s), 8.12-8.05 (2H, m),
7.94-7.88 (3H, m), 7.74 (2H, d, J = 8.8Hz), 7.24 (1H, t, J =
3.8Hz), 3.72 (1H, quint, J = 7.4Hz), 1.27 (9H, s), 1.14 (3
H, d, J = 7.4Hz).

Example 1 (90) N-[[3- (benzoylamino) phenyl] sulfonyl] glycine t-butyl ester

Embedded image

TLC: Rf 0.65 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.26-8.16 (2H, m), 8.00 (1H, t, J = 1.8)
Hz), 7.94-7.87 (2H, m), 7.66-7.46 (5H, m), 5.24 (1H, t, J
= 5.4Hz), 3.70 (2H, d, J = 5.4Hz), 1.35 (9H, s).

Example 1 (91) N-[[2- (benzoylamino) phenyl] sulfonyl] glycine t-butyl ester

[Chemical 176]

TLC: Rf 0.51 (hexane: ethyl acetate = 3: 2), NMR (CDCl ₃ ): δ 10.27 (1H, s), 8.73 (1H, d, J = 8.4Hz),
8.05-7.94 (2H, m), 7.90 (1H, dd, J = 1.8Hz, 8.0Hz), 7.70-
7.45 (4H, m), 7.30-7.18 (1H, m), 5.20 (1H, t, J = 5.2Hz),
3.61 (2H, d, J = 5.4Hz), 1.33 (9H, s).

Example 2 N-[[4- (p-toluoylamino) phenyl] sulfonyl] glycine

[Chemical 177]

A solution of the compound (1.45 g) produced in Example 1 in trifluoroacetic acid (10 ml) and water (1 ml) was stirred at room temperature for 1 hour. The reaction mixture was concentrated, the residue was washed with ether and dried to obtain the compound of the present invention (1.16 g) having the following physical data. TLC: Rf 0.48 (chlorophorm: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 10.46 (1H, s), 8.02-7.84 (1H),
7.97 (2H, d, J = 9.0Hz), 7.88 (2H, d, J = 8.0Hz), 7.75 (2H, d, J
= 9.0Hz), 7.34 (2H, d, J = 8.0Hz), 3.55 (2H, d, J = 6.2Hz),
2.40 (3H, s).

Examples 2 (1) to 2 (80) Instead of the compound prepared in Example 1, Examples 1 (1) to 2 (80)
A compound having the following physical properties can be obtained by using the compounds produced in 1 (77) and 1 (89) to 1 (91) in the same manner as in Example 2 or by converting to a corresponding salt by a conventional method. An invention compound was obtained.

Example 2 (1) N-[[4- (isobutyrylamino) phenyl] sulfonyl] glycine

[Chemical 178]

TLC: Rf 0.34 (chlorophorm: methanol: acetic acid = 16: 3: 1), NMR (CD ₃ OD): δ 7.80 (2H, d, J = 9.5Hz), 7.76 (2H, d,
J = 9.5Hz), 3.67 (2H, s), 2.64 (1H, m), 1.19 (6H, d, J = 6.8H
z).

Example 2 (2) N-[[4- (acetylamino) phenyl] sulfonyl] glycine

[Chemical 179]

TLC: Rf 0.23 (chlorophorm: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 10.26 (1H, s), 7.84 (1H, t, J = 6.0)
Hz), 7.73 (2H, d, J = 9.6Hz), 7.68 (2H, d, J = 9.6Hz), 3.52
(2H, d, J = 6.0Hz), 2.07 (3H, s).

Example 2 (3) N-[[4- (o-toluoylamino) phenyl] sulfonyl] glycine

[Chemical 180]

TLC: Rf 0.48 (chlorophorm: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 10.63 (1H, s), 7.91 (2H, d, J = 9.0
Hz), 7.96-7.84 (1H), 7.74 (2H, d, J = 9.0Hz), 7.51-7.24 (4
H, m), 3.54 (2H, d, J = 5.8Hz), 2.39 (3H, s).

Example 2 (4) N-[[4- (m-toluoylamino) phenyl] sulfonyl] glycine

[Chemical 181]

TLC: Rf 0.48 (chlorophorm: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 12.8-12.4 (1H, br.s), 10.49 (1
H, s), 7.96 (2H, d, J = 8.8Hz), 7.88 (1H, t, J = 6.2Hz), 7.75
(2H, d, J = 8.8Hz), 7.80-7.70 (2H, m), 7.50-7.36 (2H, m),
3.55 (2H, d, J = 6.2Hz), 2.41 (3H, s).

Example 2 (5) N-[[4- (2-chlorobenzoylamino) phenyl] sulfonyl] glycine

[Chemical 182]

TLC: Rf 0.42 (chlorophorm: methanol: acetic acid = 16: 3: 1), NMR (CD ₃ OD): δ 7.88 (2H, d, J = 9.4Hz), 7.83 (2H, d,
J = 9.4Hz), 7.60-7.38 (4H, m), 3.70 (2H, s).

Example 2 (6) N-[[4- (3-chlorobenzoylamino) phenyl] sulfonyl] glycine

[Chemical 183]

TLC: Rf 0.42 (chlorophorm: methanol: acetic acid = 16: 3: 1), NMR (CD ₃ OD): δ 7.99-7.94 (1H, m), 7.93 (2H, d, J =
9.0Hz), 7.93-7.80 (1H, m), 7.84 (2H, d, J = 9.0Hz), 7.64-
7.46 (2H, m), 3.69 (2H, s).

Example 2 (7) N-[[4- (4-chlorobenzoylamino) phenyl] sulfonyl] glycine

Embedded image

TLC: Rf 0.42 (chlorophorm: methanol: acetic acid = 16: 3: 1), NMR (CD ₃ OD): δ 7.94 (2H, d, J = 8.6Hz), 7.92 (2H, d,
J = 9.0Hz), 7.84 (2H, d, J = 9.0Hz), 7.53 (2H, d, J = 8.6Hz),
3.70 (2H, s).

Example 2 (8) N-[[4- (2-methoxybenzoylamino) phenyl] sulfonyl] glycine

[Chemical 185]

TLC: Rf 0.58 (chlorophorm: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 10.45 (1H, s), 7.91 (1H, t, J = 6.2)
Hz), 7.90 (2H, d, J = 8.8Hz), 7.75 (2H, d, J = 8.8Hz), 7.61
(1H, dd, J = 7.4, 1.6Hz), 7.52 (1H, ddd, J = 8.4, 7.4, 2.0H
z), 7.18 (1H, d, J = 8.0Hz), 7.07 (1H, td, J = 7.6Hz, 1.0H
z), 3.89 (3H, s), 3.56 (2H, d, J = 6.2Hz).

Example 2 (9) N-[[4- (3-methoxybenzoylamino) phenyl] sulfonyl] glycine

[Chemical 186]

TLC: Rf 0.44 (chlorophorm: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 10.52 (1H, s), 7.96 (2H, d, J = 8.8)
Hz), 7.91 (1H, t, J = 6.2Hz), 7.76 (2H, d, J = 8.8Hz), 7.58-
7.41 (3H, m), 7.21-7.14 (1H, m), 3.84 (3H, s), 3.56 (2H,
d, J = 6.2 Hz).

Example 2 (10) N-[[4- (benzoylamino) phenyl] sulfonyl] glycine

[Chemical 187]

TLC: Rf 0.19 (chlorophorm: methanol: acetic acid: water = 50: 10: 1: 1), NMR (CD ₃ OD): δ 8.0-7.8 (6H, m), 7.6-7.5 (3H, m) ,
3.70 (2H, s).

Example 2 (11) N-[[4- (4-fluorobenzoylamino) phenyl] sulfonyl] glycine

[Chemical 188]

TLC: Rf 0.36 (chlorophorm: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 10.56 (1H, s), 8.05 (2H, dd, J = 8.
8, 5.4Hz), 7.96 (2H, d, J = 9.2Hz), 7.91 (1H, t, J = 6.2Hz),
7.77 (2H, d, J = 9.2Hz), 3.56 (2H, d, J = 6.2Hz).

Example 2 (12) N-[[4- (4-methoxybenzoylamino) phenyl] sulfonyl] glycine

[Chemical 189]

TLC: Rf 0.43 (chlorophorm: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 10.39 (1H, s), 7.97 (2H, d, J = 8.8)
Hz), 7.95 (2H, d, J = 9.0Hz), 7.89 (1H, t, J = 6.2Hz), 7.75
(2H, d, J = 9.0Hz), 7.70 (2H, d, J = 8.8Hz), 3.84 (3H, s), 3.
55 (2H, d, J = 6.2Hz).

Example 2 (13) N-[[4- (2-nitrobenzoylamino) phenyl] sulfonyl] glycine

Embedded image

TLC: Rf 0.44 (chlorophorm: methanol: acetic acid = 2: 1: 0.1), NMR (DMSO-d ₆ ): δ 12.65 (1H, br.s), 11.02 (1H, s),
8.18 (1H, d, J = 7.8Hz), 8.0-7.7 (8H, m), 3.57 (2H, d, J = 6H
z).

Example 2 (14) N-[[4- (3-nitrobenzoylamino) phenyl] sulfonyl] glycine

[Chemical 191]

TLC: Rf 0.56 (chlorophorm: methanol: acetic acid = 2: 1: 0.1), NMR (DMSO-d ₆ ): δ 12.65 (1H, br.s), 10.89 (1H, s),
8.81 (1H, t, J = 2.0Hz), 8.5-8.4 (2H, m), 8.0-7.85 (4H, m),
7.81 (2H, d, J = 8.8Hz), 3.57 (2H, d, J = 6.0Hz).

Example 2 (15) N-[[4- (4-nitrobenzoylamino) phenyl] sulfonyl] glycine

[Chemical 192]

TLC: Rf 0.55 (chlorophorm: methanol: acetic acid = 2: 1: 0.1), NMR (DMSO-d ₆ ): δ 12.65 (1H, br.s), 10.88 (1H, s),
8.39 (2H, d, J = 9Hz), 8.20 (2H, d, J = 9Hz), 7.98 (d, J = 8.8H
z) + 7.96 (t, J = 6Hz) (3H), 7.80 (2H, d, J = 8.8Hz), 3.58 (2
H, d, J = 6.0 Hz).

Example 2 (16) N-[[4- (4-ethylbenzoylamino) phenyl] sulfonyl] glycine

[Chemical formula 193]

TLC: Rf 0.53 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (CD ₃ OD): δ 7.93 (2H, d, J = 9.0Hz), 7.87 (2H, d, J =
8.6Hz), 7.83 (2H, d, J = 9.0Hz), 7.36 (2H, d, J = 8.6Hz), 3.
69 (2H, s), 2.73 (2H, q, J = 7.6Hz), 1.27 (3H, t, J = 7.6H
z).

Example 2 (17) N-[[4- (4-propylbenzoylamino) phenyl] sulfonyl] glycine

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TLC: Rf 0.54 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (CD ₃ OD): δ 7.93 (2H, d, J = 9.0Hz), 7.86 (2H, d, J =
8.2Hz), 7.83 (2H, d, J = 9.0Hz), 7.33 (2H, d, J = 8.2Hz), 3.
69 (2H, s), 2.68 (2H, dd, J = 7.4, 8.2Hz), 1.80-1.60 (2H,
m), 0.96 (3H, t, J = 7.2Hz).

Example 2 (18) N-[[4- (2-fluorobenzoylamino) phenyl] sulfonyl] glycine

[Chemical 195]

TLC: Rf 0.48 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 13.40-11.60 (1H, br.s), 10.74 (1)
H, s), 7.96-7.84 (1H, t, J = 6.0Hz), 7.89 (2H, d, J = 8.8Hz),
7.76 (2H, d, J = 8.8Hz), 7.72-7.52 (2H, m), 7.42-7.28 (2
H, m), 3.55 (2H, d, J = 6.0Hz).

Example 2 (19) N-[[4- (3-fluorobenzoylamino) phenyl] sulfonyl] glycine

[Chemical 196]

TLC: Rf 0.38 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 13.40-11.60 (1H, br.s), 10.61 (1
H, s), 7.96 (2H, d, J = 8.8Hz), 7.92 (1H, t, J = 6.0Hz), 7.87
-7.72 (2H, m), 7.77 (2H, d, J = 8.8Hz), 7.67-7.40 (2H, m),
3.56 (2H, d, J = 6.0Hz).

Example 2 (20) N-[[4- (cyclohexylcarbonylamino) phenyl] sulfonyl] glycine

[Chemical 197]

TLC: Rf 0.43 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (CDCl ₃ + CD ₃ OD (10 drops)): δ 7.77 (2H, d, J = 8.8H)
z), 7.68 (2H, d, J = 8.8Hz), 3.71 (2H, s), 2.40-2.20 (1H,
m), 2.00-1.20 (10H, m).

Example 2 (21) N-[[4- (4-trifluoromethylbenzoylamino) phenyl] sulfonyl] glycine

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TLC: Rf 0.40 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 13.40-11.60 (1H, br.s), 10.76 (1
H, s), 8.16 (2H, d, J = 8.0Hz), 8.03-7.87 (1H, t, J = 6.2Hz),
7.97 (2H, d, J = 8.8Hz), 7.91 (2H, d, J = 8.0Hz), 7.78 (2H,
d, J = 8.8Hz), 3.57 (2H, d, J = 6.2Hz).

Example 2 (22) N-[[4- (2-thienylcarbonylamino) phenyl] sulfonyl] glycine

[Chemical formula 199]

TLC: Rf 0.47 (chloroform: methanol: acetic acid = 2: 1: 0.1), NMR (DMSO-d ₆ ): δ 12.60 (1H, br.s), 10.52 (1H, s),
8.06 (1H, d, J = 3.8Hz), 8.00-7.90 (4H, m), 7.77 (2H, d, J = 8.
8Hz), 7.25 (1H, dd, J = 3.8, 5.0Hz), 3.57 (2H, d, J = 5.8H
z).

Example 2 (23) N-[[4- (2-furylcarbonylamino) phenyl] sulfonyl] glycine

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TLC: Rf 0.45 (chloroform: methanol: acetic acid = 2: 1: 0.1), NMR (DMSO-d ₆ ): δ 12.65 (1H, br.s), 10.51 (1H, s),
8.00-7.90 (4H, m), 7.75 (2H, d, J = 8.8Hz), 7.40 (1H, d, J =
3.4Hz), 6.73 (1H, dd, J = 1.6Hz, 3.4Hz), 3.57 (2H, d, J = 6.
0Hz).

Example 2 (24) N-[[4- (2-pyridylcarbonylamino) phenyl] sulfonyl] glycine hydrochloride

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TLC: Rf 0.50 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 10.98 (1H, s), 8.76 (1H, d, J = 4.6H)
z), 8.24-8.02 (2H, m), 8.12 (2H, d, J = 8.8Hz), 8.01-7.82
(1H, br.s), 7.77 (2H, d, J = 8.8Hz), 7.74-7.65 (1H, m),
3.57 (2H, d, J = 5.4Hz).

Example 2 (25) N-[[4- (3-pyridylcarbonylamino) phenyl] sulfonyl] glycine

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TLC: Rf 0.25 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 13.50-11.50 (1H, br.s), 10.76 (1
H, s), 9.12 (1H, d, J = 1.8Hz), 8.77 (1H, dd, J = 1.8, 5.0H
z), 8.31 (1H, dt, J = 1.8, 8.2Hz), 7.97 (2H, d, J = 9.0Hz),
7.93 (1H, t, J = 5.4Hz), 7.79 (2H, d, J = 9.0Hz), 7.58 (1H, d
d, J = 5.0, 8.2Hz), 3.57 (2H, d, J = 5.4Hz).

Example 2 (26) N-[[4- (4-pyridylcarbonylamino) phenyl] sulfonyl] glycine

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TLC: Rf 0.20 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 13.20-12.00 (1H, br.s), 10.80 (1
H, s), 8.83-8.76 (2H, m), 8.02-7.90 (1H, t, J = 6.2Hz), 7.
97 (2H, d, J = 8.8Hz), 7.89-7.85 (2H, m), 7.79 (2H, d, J = 8.8
Hz), 3.57 (2H, d, J = 6.2Hz).

Example 2 (27) N-[[4- (3-thienylcarbonylamino) phenyl] sulfonyl] glycine

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TLC: Rf 0.45 (chloroform: methanol: acetic acid = 2: 1: 0.1), NMR (DMDO-d ₆ ): δ 12.5 (1H, br.s), 10.36 (1H, s),
8.40 (1H, m), 7.95-7.90 (3H, m), 7.76 (2H, d, J = 8.9Hz),
7.65 (2H, m), 3.57 (2H, d, J = 6Hz).

Example 2 (28) N-[[4- (3-furylcarbonylamino) phenyl] sulfonyl] glycine

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TLC: Rf 0.67 (chloroform: methanol: acetic acid = 2: 1: 0.1), NMR (DMSO-d ₆ ): δ 12.6 (1H, br.s), 10.23 (1H, s),
8.43 (1H, m), 7.95-7.85 (3H, m), 7.82 (1H, m), 7.76 (2H,
d, J = 8.7Hz), 7.01 (1H, m), 3.57 (2H, d, J = 6.0Hz).

Example 2 (29) N-[[4- (4-methoxycarbonylbenzoylamino) phenyl] sulfonyl] glycine

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TLC: Rf 0.41 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 13.50-11.50 (1H, br.s), 10.75 (1
H, s), 8.12 (2H, d, J = 9.2Hz), 8.07 (2H, d, J = 9.2Hz), 7.98
(2H, d, J = 8.8Hz), 7.94 (1H, t, J = 6.0Hz), 7.78 (2H, d, J = 8.
8Hz), 3.90 (3H, s), 3.58 (2H, d, J = 6.0Hz).

Example 2 (30) N-[[4- (4-cyanobenzoylamino) phenyl] sulfonyl] glycine

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TLC: Rf 0.34 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 13.50-11.50 (1H, br.s), 10.79 (1
H, s), 8.12 (2H, d, J = 8.8Hz), 8.04 (2H, d, J = 8.8Hz), 8.01
-7.90 (1H), 7.96 (2H, d, J = 8.8Hz), 7.79 (2H, d, J = 8.8Hz),
3.58 (2H, d, J = 6.2Hz).

Example 2 (31) N-[[4- (4-benzyloxybenzoylamino)
Phenyl] sulfonyl] glycine

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TLC: Rf 0.48 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 13.50-11.50 (1H, br.s), 10.41 (1
H, s), 7.97 (2H, d, J = 8.8Hz), 7.96 (2H, d, J = 8.8Hz), 7.90
(1H, t, J = 6.2Hz), 7.75 (2H, d, J = 8.8Hz), 7.54-7.28 (5H,
m), 7.16 (2H, d, J = 8.8Hz), 5.21 (2H, s), 3.57 (2H, d, J = 6.
2Hz).

Example 2 (32) N-[[4- (4-carboxybenzoylamino) phenyl] sulfonyl] glycine

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TLC: Rf 0.51 (chloroform: methanol: acetic acid = 2: 1: 0.1), NMR (DMSO-d ₆ ): δ 13.3-12.70 (1H, br.s), 10.74 (1)
H, s), 8.11 (2H, d, J = 9.0Hz), 8.06 (2H, d, J = 9.0Hz), 7.98
(2H, d, J = 8.8Hz), 7.94 (1H, t, J = 6.2Hz), 7.79 (2H, d, J = 8.
8Hz), 3.58 (2H, d, J = 6.2Hz).

Example 2 (33) N-[[4- (Cinnamoylamino) phenyl] sulfonyl] glycine

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TLC: Rf 0.45 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 12.80-12.40 (1H, br.s), 10.57 (1)
H, s), 7.91 (1H, t, J = 6.2Hz), 7.87 (2H, d, J = 8.8Hz), 7.75
(2H, d, J = 8.8Hz), 7.70-7.52 (3H, m), 7.50-7.38 (3H, m),
6.85 (1H, d, J = 15.8Hz), 3.56 (2H, d, J = 6.2Hz).

Example 2 (34) N-[[4- (4-butylbenzoylamino) phenyl] sulfonyl] glycine

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TLC: Rf 0.55 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 13.40-11.60 (1H, br.s), 10.47 (1)
H, s), 7.80 (1H, br.t, J = 6.0Hz), 7.96 (2H, d, J = 8.8Hz),
7.88 (2H, d, J = 8.2Hz), 7.75 (2H, d, J = 8.8Hz), 7.35 (2H, d,
J = 8.2Hz), 3.56 (2H, d, J = 6.0Hz), 2.64 (2H, t, J = 7.6Hz),
1.76-1.42 (2H, m), 1.42-1.10 (2H, m), 0.90 (3H, t, J = 7.4H
z).

Example 2 (35) N-[[4- (4-pentylbenzoylamino) phenyl] sulfonyl] glycine

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TLC: Rf 0.55 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 13.40-11.60 (1H, br.s), 10.48 (1
H, s), 7.90 (1H, br.t, J = 6.0Hz), 7.97 (2H, d, J = 8.8Hz),
7.89 (2H, d, J = 8.2Hz), 7.76 (2H, d, J = 8.8Hz), 7.35 (2H, d,
J = 8.2Hz), 3.56 (2H, d, J = 6.0Hz), 2.66 (2H, t, J = 7.0Hz),
1.72-1.48 (2H, m), 1.48-1.18 (4H, m), 0.87 (3H, t, J = 6.6H
z).

Example 2 (36) N-[[4- (4-phenylbenzoylamino) phenyl] sulfonyl] glycine

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TLC: Rf 0.50 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 13.40-11.60 (1H, br.s), 10.62 (1)
H, s), 8.08 (2H, d, J = 8.4Hz), 8.01 (2H, d, J = 8.8Hz), 7.93
(1H, t, J = 6.0Hz), 7.90-7.70 (2H, m), 7.85 (2H, d, J = 8.4H
z), 7.77 (2H, d, J = 8.8Hz), 7.60-7.36 (3H, m), 3.58 (2H,
d, J = 6.0 Hz).

Example 2 (37) N-[[(4-benzoylamino) phenyl] sulfonyl] -L-valine

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TLC: Rf 0.75 (chloroform: methanol: acetic acid = 2: 1: 0.1), NMR (DMSO-d ₆ ): δ 12.6 (1H, br.s), 10.57 (1H, s),
8.0-7.9 (5H, m), 7.75 (2H, d, J = 8.8Hz), 7.65-7.5 (3H, m),
3.51 (1H, dd, J = 6, 9.4Hz), 2.0-1.85 (1H, m), 0.83 (3H,
d, J = 6.8Hz), 0.81 (3H, d, J = 6.8Hz).

Example 2 (38) N-[[4- (1-naphthoylamino) phenyl] sulfonyl] glycine

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TLC: Rf 0.49 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 13.50-11.50 (1H, br.s), 10.92 (1
H, s), 8.26-7.86 (6H, m), 7.85-7.70 (3H, m), 7.68-7.50
(3H, m), 3.58 (2H, d, J = 5.8Hz).

Example 2 (39) N-[[4- (2-naphthoylamino) phenyl] sulfonyl] glycine

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TLC: Rf 0.49 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 13.50-11.50 (1H, br.s), 10.75 (1)
H, s), 8.61 (1H, s), 8.15-7.99 (6H, m), 7.94 (1H, t, J = 6.2
Hz), 7.81 (2H, d, J = 9.2Hz), 7.72-7.58 (2H, m), 3.59 (2H,
d, J = 6.2 Hz).

Example 2 (40) N-[[4- (3-benzyloxybenzoylamino)
Phenyl] sulfonyl] glycine

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TLC: Rf 0.54 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 13.50-11.50 (1H, br.s), 10.51 (1
H, s), 7.96 (2H, d, J = 8.8Hz), 7.90 (1H, t, J = 6.2Hz), 7.76
(2H, d, J = 8.8Hz), 7.62-7.22 (9H, m), 5.19 (2H, s), 3.56
(2H, d, J = 6.2Hz).

Example 2 (41) N-[[4- (2-benzyloxybenzoylamino)
Phenyl] sulfonyl] glycine

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TLC: Rf 0.73 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 13.50-11.50 (1H, br.s), 10.50 (1
H, s), 7.89 (1H, t, J = 6.2Hz), 7.78-7.67 (4H, m), 7.68 (1
H, dd, J = 1.6, 7.6Hz), 7.60-7.48 (3H, m), 7.44-7.25 (4H,
m), 7.10 (1H, dt, J = 0.8Hz, 7.6Hz), 5.24 (2H, s), 3.54 (2
H, d, J = 6.2 Hz).

Example 2 (42) N-[[4- (benzoylamino) phenyl] sulfonyl] -L-aspartic acid

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TLC: Rf 0.35 (chloroform: methanol: acetic acid = 2: 1: 0.1), NMR (CD ₃ OD): δ 8.0-7.8 (6H, m), 7.65-7.5 (3H, m),
4.22 (1H, t, J = 9.0Hz), 2.73 (2H, d, J = 6.0Hz).

Example 2 (43) N-[[4- (benzoylamino) phenyl] sulfonyl] -L-glutamic acid

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TLC: Rf 0.49 (chloroform: methanol: acetic acid = 2: 1: 0.1), NMR (CD ₃ OD): δ 8.00-7.80 (6H, m), 7.65-7.5 (3H, m),
3.93 (1H, dd, J = 2.8Hz, 9.0Hz), 2.41 (2H, t, J = 7.5Hz), 2.
15-1.95 (1H, m), 1.90-1.75 (1H, m).

Example 2 (44) N-[[4- (phenylacetylamino) phenyl] sulfonyl] glycine

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TLC: Rf 0.44 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 10.51 (1H, s), 7.86 (1H, t, J = 6.2H
z), 7.76 (2H, d, J = 8.8Hz), 7.69 (2H, d, J = 8.8Hz), 7.40-
7.18 (5H, m), 3.67 (2H, s), 3.53 (2H, d, J = 6.2Hz).

Example 2 (45) N-[[4- (benzoylamino) phenyl] sulfonyl] -L-leucine

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TLC: Rf 0.41 (chloroform: methanol: acetic acid = 2: 1: 0.1), NMR (DMSO-d ₆ ): δ 10.29 (1H, s), 8.16 (1H, br.t, J =
9.0Hz), 7.97 (2H, m), 7.72 (2H, d, J = 8.6Hz), 7.6-7.45 (5
H, m), 3.86 (1H, m), 1.8-1.5 (3H, m), 0.91 (6H, d, J = 5.4H
z).

Example 2 (46) N-[[4- (benzoylamino) phenyl] sulfonyl] -D-leucine

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TLC: Rf 0.41 (chloroform: methanol: acetic acid = 2: 1: 0.1), NMR (DMSO-d ₆ ): δ 10.29 (1H, s), 8.16 (1H, br.t, J =
9.0Hz), 7.97 (2H, m) 7.72 (2H, d, J = 8.8Hz), 7.6-7.45 (5H,
m), 3.86 (1H, m), 1.8-1.5 (3H, m), 0.90 (6H, d, J = 6.2H
z).

Example 2 (47) N-[[4- (phenoxycarbonylamino) phenyl] sulfonyl] glycine

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TLC: Rf 0.44 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 13.20-12.00 (1H, br.s), 10.64 (1)
H, s), 7.89 (1H, t, J = 6.2Hz), 7.75 (2H, d, J = 8.8Hz), 7.65
(2H, d, J = 8.8Hz), 7.51-7.38 (2H, m), 7.33-7.20 (3H, m),
3.55 (2H, d, J = 6.2Hz).

Example 2 (48) N-[[4- (4-dimethylaminobenzoylamino)
Phenyl] sulfonyl] glycine

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TLC: Rf 0.54 (chloroform: methanol: acetic acid = 2: 1: 0.1), NMR (DMSO-d ₆ ): δ 10.18 (1H, s), 8.0-7.8 (5H, m), 7.
73 (2H, d, J = 8.8Hz), 6.77 (2H, d, J = 9.0Hz), 3.55 (2H), 3.
03 (6H, s).

Example 2 (49) N-[[4- (benzoylamino) phenyl] sulfonyl] -D-valine

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TLC: Rf 0.73 (chloroform: methanol: acetic acid = 2: 1: 0.1), NMR (DMSO-d ₆ ): δ 12.6 (1H, br.s), 10.56 (1H, s),
8.0-7.85 (5H, m), 7.75 (2H, d, J = 8.8Hz), 7.65-7.5 (3H,
m), 3.51 (1H, dd, J = 6.1Hz, 9.3Hz), 2.0-1.85 (1H, m), 0.
83 (3H, d, J = 6.8Hz), 0.81 (3H, d, J = 6.8Hz).

Example 2 (50) N-[[4- (benzoylamino) phenyl] sulfonyl] -L-phenylalanine

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TLC: Rf 0.68 (chloroform: methanol: acetic acid = 2: 1: 0.1), NMR (DMSO-d ₆ ): δ 12.71 (1H, br.s), 10.54 (1H, s),
8.17 (1H, d, J = 9.0Hz), 7.97 (2H, m), 7.86 (2H, m), 7.65-7.
5 (5H, m), 7.25-7.1 (5H, m), 3.95-3.8 (1H, m), 2.94 (1H, d
d, J = 5.8Hz, 13.8Hz), 2.72 (1H, dd, J = 8.8Hz, 13.8Hz).

Example 2 (51) N-[[4- (benzoylamino) phenyl] sulfonyl] -D-phenylalanine

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TLC: Rf 0.68 (chloroform: methanol: acetic acid = 2: 1: 0.1), NMR (DMSO-d ₆ ): δ 12.71 (1H, br.s), 10.53 (1H, s),
8.17 (1H, d, J = 9.0Hz), 7.97 (2H, m), 7.86 (2H, m), 7.65-7.
5 (5H, m), 7.3-7.1 (5H, m), 3.95-3.8 (1H, m), 2.94 (1H, d
d, J = 5.8Hz, 13.8Hz), 2.73 (1H, dd, J = 8.4Hz, 13.8Hz).

Example 2 (52) N-[[4- (benzoylamino) phenyl] sulfonyl] -L-alanine

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TLC: Rf 0.62 (chloroform: methanol: acetic acid = 2: 1: 0.1), NMR (DMSO-d ₆ ): δ 12.6 (1H, br.s), 10.58 (1H, s),
8.04 (1H, d, J = 8.6Hz), 8.0-7.9 (4H, m), 7.76 (2H, d, J = 8.8
Hz), 7.65-7.5 (3H, m), 3.75 (1H, m), 1.16 (3H, d, J = 7.4H
z).

Example 2 (53) N-[[4- (benzoylamino) phenyl] sulfonyl] -D-alanine

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TLC: Rf 0.62 (chloroform: methanol: acetic acid = 2: 1: 0.1), NMR (DMSO-d ₆ ): δ 12.6 (1H, br.s), 10.58 (1H, s),
8.04 (1H, d, J = 8.6Hz), 8.0-7.9 (4H, m), 7.77 (2H, d, J = 8.8
Hz), 7.65-7.5 (3H, m), 3.76 (1H, m), 1.16 (3H, d, J = 7.4H
z).

Example 2 (54) N-[[4- (benzoylamino) phenyl] sulfonyl] -L-lysine

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TLC: Rf 0.19 (chloroform: methanol: acetic acid: water = 2: 1: 0.1: tailing), NMR (DMSO-d ₆ + CF ₃ CO ₂ H (1 drop)): δ 10.59 (1H, s) , 8.
05-7.95 (5H, m), 7.8-7.5 (4H, m), 3.7-3.6 (1H, m), 2.8-
2.65 (2H, m), 1.7-1.2 (6H, m).

Example 2 (55) N-[[4- (benzoylamino) phenyl] sulfonyl] -D-lysine

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TLC: Rf 0.19 (chloroform: methanol: acetic acid: water = 2: 1: 0.1: tailing), NMR (DMSO-d ₆ + CF ₃ CO ₂ H (1 drop)): δ 10.59 (1H, s) , 8.
05-7.95 (5H, m), 7.8-7.5 (4H, m), 3.7-3.6 (1H, m), 2.8-
2.65 (2H, m), 1.7-1.2 (6H, m).

Example 2 (56) N-[[4- (benzoylamino) phenyl] sulfonyl] -D-glutamic acid

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TLC: Rf 0.45 (chloroform: methanol: acetic acid = 2: 1: 0.1), NMR (DMSO-d ₆ ): δ 12.4 (2H, br.s), 10.57 (1H, s),
8.05 (1H, d, J = 9Hz), 7.97 (4H, m), 7.74 (2H, d, J = 8.8Hz),
7.65-7.5 (3H, m), 3.76 (1H, m), 2.23 (2H, t, J = 7.4Hz), 1.
95-1.55 (2H, m).

Example 2 (57) N-[[4- (4-dodecylbenzoylamino) phenyl] sulfonyl] glycine

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TLC: Rf 0.68 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 13.50-11.50 (1H, br.s), 10.46 (1
H, s), 7.97 (2H, d, J = 8.8Hz), 7.89 (1H, t, J = 6.2Hz), 7.88
(2H, d, J = 8.4Hz), 7.76 (2H, d, J = 8.8Hz), 7.34 (2H, d, J = 8.
4Hz), 3.55 (2H, d, J = 6.2Hz), 2.65 (2H, t, J = 7.8Hz), 1.70
-1.48 (2H, m), 1.40-1.10 (18H, m), 0.85 (3H, t, J = 6.6H
z).

Example 2 (58) 4- [N-[[4- (benzoylamino) phenyl] sulfonyl] amino] butanoic acid

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TLC: Rf 0.76 (chloroform: methanol: acetic acid = 2: 1: 0.1), NMR (DMSO-d ₆ ): δ 12.05 (1H, br.s), 10.59 (1H, s),
8.05-7.95 (4H, m), 7.76 (2H, d, J = 8.8Hz), 7.65-7.45 (4H,
m), 2.75 (2H, q, J = 6.8Hz), 2.22 (2H, d, J = 7.2Hz), 1.60
(2H, m).

Example 2 (59) N-[[4- (benzoylamino) phenyl] sulfonyl] -L-serine

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TLC: Rf 0.42 (chloroform: methanol: acetic acid = 2: 1: 0.1), NMR (DMSO-d ₆ ): δ 10.57 (1H, s), 8.0-7.95 (4H, m),
7.88 (1H, d, J = 8.6Hz), 7.76 (2H, d, J = 8.6Hz), 7.65-7.5 (3
H, m), 3.74 (1H, m), 3.49 (2H, d, J = 5.2Hz).

Example 2 (60) N-[[4- (benzoylamino) phenyl] sulfonyl] -D-serine

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TLC: Rf 0.42 (chloroform: methanol: acetic acid = 2: 1: 0.1), NMR (DMSO-d ₆ ): δ 10.57 (1H, s), 8.0-7.9 (4H, m), 7.
88 (1H, d, J = 8.6Hz), 7.76 (2H, d, J = 8.8Hz), 7.65-7.5 (3H,
m), 3.75 (1H, m), 3.49 (2H, d, J = 5.4Hz).

Example 2 (61) N-[[4- (benzoylamino) phenyl] sulfonyl] -D-aspartic acid

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TLC: Rf 0.35 (chloroform: methanol: acetic acid = 2: 1: 0.1), NMR (DMSO-d ₆ ): δ 10.57 (1H, s), 8.07 (1H, d, J = 8.6H)
z), 8.0-7.9 (4H, m), 7.76 (2H, d, J = 8.8Hz), 7.65-7.5 (3
H, m), 4.05 (1H, m), 2.59 (1H, dd, J = 6.6Hz, 16.8Hz), 2.4
0 (1H, dd, J = 6.6Hz, 16.8Hz).

Example 2 (62) N-[[4- (p-toluoylamino) phenyl] sulfonyl] -D-phenylalanine

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TLC: Rf 0.28 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1), NMR (DMSO-d ₆ ): δ 12.9-12.4 (1H, br.s), 10.44 (1H,
s), 8.17 (1H, d, J = 9.2Hz), 7.9-7.8 (4H, m), 7.54 (2H, d, J
= 8.6Hz), 7.36 (2H, d, J = 8.2Hz), 7.3-7.1 (5H, m), 3.9-3.
8 (1H, m), 2.93 (1H, dd, J = 6.0Hz, 14.0Hz), 2.72 (1H, dd, J
= 8.8Hz, 14.0Hz), 2.40 (3H, s).

Example 2 (63) N-[[4- (4-pentylbenzoylamino) phenyl] sulfonyl] -D-phenylalanine

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TLC: Rf 0.21 (chloroform: methanol: acetic acid = 95: 4: 1), NMR (DMSO-d ₆ ): δ 13.00-12.20 (1H, br.s), 10.40 (1
H, s), 8.11 (1H, d, J = 9.0Hz), 7.88 (2H, d, J = 8.6Hz), 7.84
(2H, d, J = 8.4Hz), 7.52 (2H, d, J = 8.6Hz), 7.34 (2H, d, J = 8.
4Hz), 7.28-7.08 (5H, m), 3.92-3.78 (1H, m), 2.93 (1H, d
d, J = 5.8Hz, 13.4Hz), 2.71 (1H, dd, J = 8.8Hz, 13.4Hz),
2.66 (2H, t, J = 8.2Hz), 1.70-1.50 (2H, m), 1.44-1.18 (4H,
m), 0.87 (3H, t, J = 6.8Hz).

Example 2 (64) N-[[4- (p-toluoylamino) phenyl] sulfonyl] -L-valine

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TLC: Rf 0.45 (chloroform: methanol: acetic acid = 45: 4: 1), NMR (DMSO-d ₆ ): δ 12.90-12.30 (1H, br.s), 10.45 (1)
H, s), 7.94 (1H, br.d, J = 9.6Hz), 7.95 (2H, d, J = 8.8Hz),
7.88 (2H, d, J = 8.2Hz), 7.73 (2H, d, J = 8.8Hz), 7.34 (2H, d,
J = 8.2Hz), 3.49 (1H, dd, J = 6.2Hz, 9.6Hz), 2.39 (3H, s),
2.00-1.90 (1H, m), 0.83 (3H, d, J = 6.8Hz), 0.80 (3H, d, J =
6.8Hz).

Example 2 (65) N-[[4- (4-hexylbenzoylamino) phenyl] sulfonyl] glycine

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TLC: Rf 0.18 (chloroform: methanol: acetic acid = 90: 10: 1), NMR (DMSO-d ₆ ): δ 13.40-12.00 (1H, br.s), 10.46 (1
H, s), 7.97 (3H, m), 7.88 (2H, d, J = 8.0Hz), 7.87 (1H), 7.
75 (2H, d, J = 8.8Hz), 7.34 (2H, d, J = 8.0Hz), 3.55 (2H, d, J =
5.8Hz), 2.66 (2H, t, J = 7.8Hz), 1.70-1.50 (2H, m), 1.40-
1.15 (6H, m), 0.86 (3H, t, J = 6.6Hz).

Example 2 (66) N-[[4- (4-heptylbenzoylamino) phenyl] sulfonyl] glycine

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TLC: Rf 0.18 (chloroform: methanol: acetic acid = 90: 10: 1), NMR (DMSO-d ₆ ): δ 13.00-12.40 (1H, br.s), 10.48 (1)
H, s), 7.97 (3H, m), 7.89 (2H, d, J = 8.2Hz), 7.87 (1H), 7.
77 (2H, d, J = 9.0Hz), 7.35 (2H, d, J = 8.2Hz), 3.57 (2H, d, J =
6.2Hz), 2.66 (2H, t, J = 7.8Hz), 1.70-1.44 (2H, m), 1.40-
1.10 (8H, m), 0.86 (3H, t, J = 7.0Hz).

Example 2 (67) N-[[4- (4-isopropylbenzoylamino) phenyl] sulfonyl] glycine

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TLC: Rf 0.51 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 13.20-12.00 (1H, br.s), 10.48 (1
H, s), 7.96 (3H, m), 7.89 (2H, d, J = 8.2Hz), 7.76 (2H, d, J =
8.8Hz), 7.41 (2H, d, J = 8.2Hz), 3.57 (2H, d, J = 6.0Hz), 2.
99 (1H, m), 1.24 (6H, d, J = 6.8Hz).

Example 2 (68) N-[[4- (4-isobutylbenzoylamino) phenyl] sulfonyl] glycine

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TLC: Rf 0.53 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 13.20-12.00 (1H, br.s), 10.49 (1
H, s), 7.96 (3H, m), 7.89 (2H, d, J = 8.2Hz), 7.76 (2H, d, J =
8.8Hz), 7.33 (2H, d, J = 8.2Hz), 3.57 (2H, d, J = 6.2Hz), 2.
54 (2H, d, J = 7.2Hz), 1.88 (1H, m), 0.89 (6H, d, J = 6.4Hz).

Example 2 (69) N-[[4- (benzoylamino) phenyl] sulfonyl] -2,2-dimethylglycine

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TLC: Rf 0.14 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1), NMR (DMSO-d ₆ ): δ 12.55 (1H, br.s), 10.56 (1H, s),
8.0-7.85 (5H, m), 7.77 (2H, d, J = 8.8Hz), 7.65-7.5 (3H,
m), 1.27 (6H, s).

Example 2 (70) N-[[4- (p-toluoylamino) phenyl] sulfonyl] -D-serine

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TLC: Rf 0.25 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 13.40-11.60 (1H, br.s), 10.47 (1)
H, s), 7.95 (2H, d, J = 8.8Hz), 7.88 (2H, d, J = 8.2Hz), 7.86
(1H, d, J = 8.4Hz), 7.75 (2H, d, J = 8.8Hz), 7.35 (2H, d, J = 8.
2Hz), 3.80-3.68 (1H, m), 3.53-3.47 (2H), 2.39 (3H, s).

Example 2 (71) N-[[4- (p-toluoylamino) phenyl] sulfonyl] -L-leucine

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TLC: Rf 0.22 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1), NMR (DMSO-d ₆ ): δ 12.55 (1H, br.s), 10.48 (1H, s),
8.04 (1H, d, J = 8.8Hz), 7.96 (2H, d, J = 8.8Hz), 7.89 (2H, d, J
= 8.2Hz), 7.73 (2H, d, J = 8.8Hz), 7.36 (2H, d, J = 8.2Hz),
3.65 (1H, m), 2.40 (3H, s), 1.59 (1H, m), 1.37 (2H, m), 0.
82 (3H, d, J = 6.6Hz), 0.72 (3H, d, J = 6.4Hz).

Example 2 (72) N-[[4- (p-toluoylamino) phenyl] sulfonyl] -D-alanine

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TLC: Rf 0.30 (chloroform: methanol: acetic acid = 90: 10: 1), NMR (DMSO-d ₆ ): δ 13.20-12.00 (1H, br.s), 10.48 (1)
H, s), 8.02 (1H, d, J = 8.2Hz), 7.97 (2H, d, J = 8.8Hz), 7.88
(2H, d, J = 8.4Hz), 7.75 (2H, d, J = 8.8Hz), 7.35 (2H, d, J = 8.
4Hz), 3.82-3.66 (1H, m), 2.39 (3H, s), 1.15 (3H, d, J = 7.0
Hz).

Example 2 (73) N-[[4- (p-toluoylamino) phenyl] sulfonyl] -D-valine

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TLC: Rf 0.53 (chloroform: methanol: acetic acid = 90: 10: 1), NMR (DMSO-d ₆ ): δ 12.80-12.40 (1H, br.s), 10.46 (1
H, s), 7.95 (2H, d, J = 8.2Hz), 7.94-7.90 (1H), 7.89 (2H,
d, J = 8.0Hz), 7.74 (2H, d, J = 8.2Hz), 7.35 (2H, d, J = 8.0H
z), 3.60-3.45 (1H, m), 2.39 (3H, s), 2.02-1.80 (1H, m),
0.81 (6H, t, J = 6.8Hz).

Example 2 (74) N-[[4- (p-toluoylamino) phenyl] sulfonyl] -D-leucine

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TLC: Rf 0.54 (chloroform: methanol: acetic acid = 90: 10: 1), NMR (DMSO-d ₆ ): δ 12.80-12.30 (1H, br.s), 10.46 (1
H, s), 8.02 (1H, d, J = 9.0Hz), 7.96 (2H, d, J = 8.8Hz), 7.89
(2H, d, J = 8.2Hz), 7.73 (2H, d, J = 8.8Hz), 7.35 (2H, d, J = 8.
2Hz), 3.75-3.55 (1H, m), 2.39 (3H, s), 1.70-1.48 (1H,
m), 1.46-1.30 (2H, m), 0.82 (3H, d, J = 6.6Hz), 0.72 (3H,
d, J = 6.6 Hz).

Example 2 (75) N-[[2-methyl-4- (p-toluoylamino) phenyl] sulfonyl] glycine

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TLC: Rf 0.61 (chloroform: methanol = 2: 1), NMR (d ₆ -DMSO): δ 10.38 (1H, s), 8.02 (1H, t, J = 3.6H)
z), 7.88 (2H, d, J = 8.1Hz), 7.80-7.77 (3H, m), 7.34 (2H,
d, J = 8.1Hz), 3.58 (2H, d, J = 3.6Hz), 2.59 (3H, s), 2.40 (3
H, s).

Example 2 (76) N-[[3-Methyl-4- (p-toluoylamino) phenyl] sulfonyl] glycine

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TLC: Rf 0.24 (chloroform: methanol = 2: 1), NMR (d ₆ -DMSO): δ 12.64 (1H, br.s), 9.88 (1H, s),
7.94 (1H, t, J = 6.2Hz), 7.85 (2H, d, J = 8.1Hz), 7.66 (3H,
m), 7.30 (2H, d, J = 8.1Hz), 3.55 (2H, d, J = 6.2Hz), 2.36 (3
H, s), 2.28 (3H, s).

Example 2 (77) N-[[4- (2-hydroxy-4-methylbenzoylamino) phenyl] sulfonyl] -D-alanine

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TLC: Rf 0.37 (chloroform: methanol = 2: 1), NMR (d ₆ -DMSO): δ 12.62 (1H, br.s), 11.66 (1H, s),
10.56 (1H, s), 8.06 (1H, d, J = 8.6Hz), 7.93-7.70 (5H, m),
6.82 (1H, s), 6.80 (1H, d, J = 7.2Hz), 3.76 (1H, m), 2.31 (3
H, s), 1.15 (3H, d, J = 7.2Hz).

Example 2 (78) N-[[4- (2-thienylcarbonylamino) phenyl] sulfonyl] -D-alanine

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TLC: Rf 0.21 (chloroform: methanol: water = 4: 1: 0.1), NMR (DMSO-d ₆ ): δ 12.60 (1H, br.s), 10.49 (1H, s),
8.05-7.98 (2H, m), 7.91-7.85 (3H, m), 7.73 (2H, d, J = 8.8H
z), 7.21 (1H, t, J = 3.8Hz), 3.77-3.68 (1H, m), 1.13 (3H,
d, J = 7.2 Hz).

Example 2 (79) N-[[3- (benzoylamino) phenyl] sulfonyl] glycine

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TLC: Rf 0.36 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 10.54 (1H, s), 8.33 (1H, s), 8.14-
7.90 (4H, m), 7.68-7.44 (5H, m), 3.60 (2H, d, J = 6.0Hz).

Example 2 (80) N-[[2- (benzoylamino) phenyl] sulfonyl] glycine

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TLC: Rf 0.34 (chloroform: methanol: acetic acid = 90: 10: 1), NMR (DMSO-d ₆ ): δ 13.00-12.60 (1H, br.s), 10.26 (1)
H, s), 8.67-8.56 (1H), 8.52-8.44 (1H, m), 8.02-7.92 (2H,
m), 7.87 (1H, dd, J = 1.4,7.8Hz), 7.74-7.54 (4H, m), 7.38
-7.27 (1H, m), 3.65 (2H, d, J = 4.6Hz).

Example 3 N-[[4- (2-aminobenzoylamino) phenyl] sulfonyl] glycine

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The compound (56) prepared in Example 2 (13)
9 mg) of N, N-dimethylformamide (7.5 ml)
And 10% palladium-carbon (100 mg) was added to a methanol (7.5 ml) solution, and ammonium formate (3
78 mg) was added. The reaction mixture was stirred at room temperature for 1 hour. The insoluble material was filtered and concentrated. The residue was washed with water and ether and dried to obtain the compound of the present invention having the following physical properties. TLC: Rf 0.47 (chlorophorm: methanol: acetic acid = 2: 1: 0.1), NMR (DMSO-d ₆ ): δ 12.60 (1H, br.s), 10.30 (1H, s),
7.95-7.85 (3H, m), 7.74 (2H, d, J = 8.8Hz), 7.64 (2H, d, J =
8Hz), 7.22 (1H, t, J = 8Hz), 6.76 (1H, d, J = 8Hz), 6.60 (1H,
t, J = 8Hz), 6.38 (2H, br), 3.56 (2H, d, J = 6.2Hz).

Examples 3 (1) -3 (13) Example 2 instead of the compound prepared in Example 2 (13).
(14), 2 (15), 2 (31), 2 (33), 2
(40), 2 (41), 1 (78), 1 (79), 1
Using the compounds produced in (80), 1 (81), 1 (82), 1 (83) and 1 (84), the compound of the present invention having the following physical properties was obtained by the same procedure as in Example 3. It was

Example 3 (1) N-[[4- (3-aminobenzoylamino) phenyl] sulfonyl] glycine

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TLC: Rf 0.39 (chlorophorm: methanol: acetic acid = 2: 1: 0.1), NMR (DMSO-d ₆ ): δ 10.41 (1H, s), 7.85-7.0 (3H, m),
7.74 (2H, d, J = 8.4Hz), 7.2-7.05 (3H, m), 6.77 (1H, d, J = 7.
6Hz), 3.56 (2H, d, J = 6Hz).

Example 3 (2) N-[[4- (4-aminobenzoylamino) phenyl] sulfonyl] glycine

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TLC: Rf 0.35 (chlorophorm: methanol: acetic acid = 2: 1: 0.1), NMR (DMSO-d ₆ ): δ 12.60 (1H, br.s), 10.08 (1H, s),
7.94 (2H, d, J = 8.8Hz), 7.86 (1H, t, J = 6Hz), 7.73 (4H, d, J =
8.8Hz), 7.72 (4H, d, J = 8.8Hz), 6.61 (2H, d, J = 8.8Hz), 5.
83 (2H, br), 3.55 (2H, d, J = 6Hz).

Example 3 (3) N-[[4- (4-hydroxybenzoylamino) phenyl] sulfonyl] glycine

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TLC: Rf 0.58 (chloroform: methanol: acetic acid = 20: 10: 1), NMR (DMSO-d ₆ ): δ 10.31 (1H, s), 8.01-7.82 (1H, m),
7.95 (2H, d, J = 8.8Hz), 7.87 (2H, d, J = 8.4Hz), 7.75 (2H, d, J
= 8.8Hz), 6.88 (2H, d, J = 8.4Hz), 3.53 (2H, m).

Example 3 (4) N-[[4-[(2-phenylethyl) carbonylamino] phenyl] sulfonyl] glycine

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TLC: Rf 0.45 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 10.29 (1H, s), 7.80-7.50 (5H, m),
7.36-7.08 (5H, m), 3.50-3.40 (2H, m), 3.00-2.78 (2H, m),
2.74-2.50 (2H, m).

Example 3 (5) N-[[4- (3-hydroxybenzoylamino) phenyl] sulfonyl] glycine

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TLC: Rf 0.24 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 10.48 (1H, s), 7.96 (2H, d, J = 8.8H)
z), 7.95-7.76 (1H, m), 7.75 (2H, d, J = 8.8Hz), 7.44-7.28
(3H, m), 7.40-6.95 (1H, m), 3.60-3.50 (2H, m).

Example 3 (6) N-[[4- (2-hydroxybenzoylamino) phenyl] sulfonyl] glycine

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TLC: Rf 0.38 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 13.20-10.80 (1H, br.s), 10.65 (1)
H, s), 8.00-7.84 (2H, m), 7.92 (2H, d, J = 8.8Hz), 7.78 (2
H, d, J = 8.8Hz), 7.44 (1H, m), 7.06-6.92 (2H, m), 3.60-3.4
8 (2H, m).

Example 3 (7) N-[[4- (benzoylamino) phenyl] sulfonyl] -L-tryptophan

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TLC: Rf 0.26 (chloroform: methanol: acetic acid = 90: 10: 1), NMR (DMSO-d ₆ ): δ 13.50-11.60 (1H, br.s), 10.78 (1)
H, s), 10.49 (1H, s), 8.12-8.00 (1H, m), 7.97 (2H, dd, J =
1.6Hz, 7.6Hz), 7.85 (2H, d, J = 9.0Hz), 7.64-7.49 (5H,
m), 7.37-7.25 (2H, m), 7.10-6.86 (3H, m), 4.00-3.80 (1
H, m), 3.06 (1H, dd, J = 6.6Hz, 14.4Hz), 2.87 (1H, dd, J = 7.
2Hz, 14.4Hz).

Example 3 (8) N-[[4- (benzoylamino) phenyl] sulfonyl] -L-tyrosine

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TLC: Rf 0.56 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 10.53 (1H, s), 9.25-9.05 (1H, br.
s), 8.00-7.93 (3H, m), 7.89 (2H, d, J = 8.8Hz), 7.61 (2H, d,
J = 8.8Hz), 7.60-7.48 (3H, m), 6.92 (2H, d, J = 8.4Hz), 6.6
0 (2H, d, J = 8.4Hz), 3.80-3.64 (1H, m), 2.80 (1H, dd, J = 5.8
Hz, 13.6Hz), 2.65 (1H, dd, J = 7.6Hz, 13.6Hz).

Example 3 (9) N-[[4- (benzoylamino) phenyl] sulfonyl] -D-tryptophan

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TLC: Rf 0.26 (chloroform: methanol: acetic acid = 90: 10: 1), NMR (DMSO-d ₆ ): δ 12.80-12.30 (1H, br.s), 10.79 (1)
H, s), 10.50 (1H, s), 8.09 (1H, d, J = 8.6Hz), 8.02-7.93 (2
H, m), 7.85 (2H, d, J = 8.8Hz), 7.68-7.50 (5H, m), 7.38-7.2
5 (2H, m), 7.11-6.87 (3H, m), 4.00-3.81 (1H, m), 3.05 (1
H, dd, J = 6.6Hz, 14.8Hz), 2.86 (1H, dd, J = 7.8Hz, 14.8H
z).

Example 3 (10) N-[[4- (benzoylamino) phenyl] sulfonyl] -D-tyrosine

Embedded image

TLC: Rf 0.56 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 12.80-12.00 (1H, br.s), 10.54 (1)
H, s), 9.20 (1H, s), 8.06 (1H, d, J = 8.8Hz), 8.02-7.93 (2
H, m), 7.89 (2H, d, J = 8.8Hz), 7.70-7.50 (5H, m), 6.92 (2H,
d, J = 8.4Hz), 6.61 (2H, d, J = 8.4Hz), 3.90-3.70 (1H, m),
2.81 (1H, dd, J = 6.4Hz, 13.6Hz), 2.62 (1H, dd, J = 8.2Hz, 1
3.6Hz).

Example 3 (11) N-[[4- (benzoylamino) phenyl] sulfonyl] -D-histidine

Embedded image

TLC: Rf 0.16 (chloroform: methanol: acetic acid = 14: 6: 1), NMR (DMSO-d ₆ ): δ 10.82 (1H, s), 8.29 (1H, s), 8.10
(2H, d, J = 9.0Hz), 8.04 (2H, d, J = 9.0Hz), 8.00-7.92 (2H,
m), 7.68-7.48 (4H, m), 7.45 (1H, s), 3.45-3.35 (1H, m),
3.05 (1H, dd, J = 3.6Hz, 15.6Hz), 2.70 (1H, dd, J = 9.0Hz, 1
5.6 Hz).

Example 3 (12) 2- [N- [4- (benzoylamino) phenyl] sulfonylamino]-(3-pyridyl) -D-alanine

Embedded image

TLC: Rf 0.35 (chloroform: methanol: acetic acid = 2: 1: 0.1), NMR (DMSO-d ₆ ): δ 12.84 (1H, br.s), 10.54 (1H, s),
8.37 (2H, m), 8.02 (1H, d, J = 9.0Hz), 7.96 (2H, m), 7.86 (2
H, d, J = 8.6Hz), 7.65-7.5 (6H, m), 7.21 (1H, dd, J = 4.9, 7.
5Hz), 3.89 (1H, m), 3.05-2.7 (2H, m).

Example 3 (13) N-[[4- (p-toluoylamino) phenyl] sulfonyl] -D-tryptophan

Embedded image

TLC: Rf 0.13 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1), NMR (DMSO-d ₆ ): δ 12.57 (1H, br.s), 10.8 (1H, s), 1
0.42 (1H, s), 8.13 (1H, d, J = 8.8Hz), 7.9-7.8 (4H, m), 7.5
9 (2H, d, J = 8.8Hz), 7.4-7.25 (4H, m), 7.1-6.9 (3H, m), 3.
95-3.85 (1H, m), 3.04 (1H, dd, J = 6.0Hz, 18.0Hz), 2.84 (1
H, dd, J = 7.4Hz, 18.0Hz), 2.39 (3H, s).

Reference Example 3 4- (benzyloxycarbonyloxy) benzenesulfonic acid sodium salt

Embedded image

[0582] Water (40 m) of sodium hydroxide (3.8 g)
l) Into the solution, sodium 4-hydroxybenzenesulfonate dihydrate salt (20 g) and tetrahydrofuran (2
8 ml) was added. Benzyl chloroformate (12.3 ml) was added to the reaction mixture at 0 ° C., and the mixture was stirred at the same temperature for 1 hr and at room temperature for 1 hr. The reaction mixture was concentrated under reduced pressure, and the precipitated crystals were filtered with water and washed. The crystals obtained were dried to give the title compound (18.1 g) having the following physical data. NMR (CD ₃ OD): δ 7.85 (2H, d, J = 8Hz), 7-50-7.30 (5
H, m), 7.25 (2H, d, J = 8Hz), 5.25 (2H, s).

Reference Example 4 4- (benzyloxycarbonyloxy) benzenesulfonyl chloride

Embedded image

[0584] A suspension of the compound (10.2 g) produced in Reference Example 3 in N, N-dimethylformamide (30 ml) was charged with 0.
At ° C, sulfonyl chloride (3.4 ml) was added. After stirring the reaction mixture at room temperature for 1 hour, the reaction mixture was poured into ice water (50 ml). The precipitated crystals were filtered, washed with water and dried to give the title compound (9.
6 g) was obtained. NMR (CD ₃ OD): δ 8.10 (2H, d, J = 8Hz), 7.50 (2H, d, J =
8Hz), 7.45-7.40 (5H, m), 5.30 (2H, s).

Example 4 N-[[4- (benzyloxycarbonyloxy) phenyl] sulfonyl] glycine t-butyl ester

Embedded image

Glycine t-butyl ester hydrochloride (1.
The compound (3.0 g) produced in Reference Example 4 was added to a pyridine (20 ml) solution of 5 g). The reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated, dissolved in ethyl acetate,
The extract was washed with 1N hydrochloric acid, water and saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated to obtain the compound of the present invention (2.4 g) having the following physical data. TLC: Rf 0.78 (hexane: ethyl acetate = 1: 1
1), NMR (CDCl ₃ ): δ 7.90 (2H, d, J = 8Hz), 7.50-7.30 (5
H, m), 7.35 (2H, d, J = 8Hz), 5.30 (2H, s), 5.05 (1H, t, J = 6H
z), 3.70 (2H, d, J = 6Hz), 1.40 (9H, s).

Reference Example 5 N-[(4-hydroxyphenyl) sulfonyl] glycine t-butyl ester

Embedded image

10% Palladium-carbon (200 mg) was added to a solution of the compound (2.3 g) produced in Example 4 in ethanol (50 ml). The reaction mixture under a hydrogen atmosphere,
Stir at room temperature for 2 hours. The reaction mixture was filtered through Celite (trade name), and the filtrate was concentrated. The residue was subjected to silica gel column chromatography (hexane: ethyl acetate =
Purification by 3: 1 → 2: 1) gave the title compound (1.5 g) having the following physical data. TLC: Rf 0.19 (hexane: ethyl acetate = 2:
1), NMR (CDCl ₃ ): δ 7.70 (2H, d, J = 8Hz), 6.90 (2H, d, J =
8Hz), 3.75 (1H, br.s), 3.60 (2H, br.s), 1.40 (9H, s).

Example 5 N-[[4- (benzoyloxy) phenyl] sulfonyl] glycine t-butyl ester

Embedded image

By using the compound prepared in Reference Example 5 instead of the compound prepared in Reference Example 2 and benzoyl chloride in place of p-toluoyl chloride, the following physical properties were obtained. A compound of the present invention having TLC: Rf 0.62 (hexane: ethyl acetate = 1: 1
1), NMR (CDCl ₃ ): δ 8.20 (2H, d, J = 7.2Hz), 7.95 (2H, d,
J = 9Hz), 7.68 (1H, t, J = 7.2Hz), 7.54 (2H, t, J = 7.2Hz), 7.
39 (2H, d, J = 9Hz), 5.07 (1H, t, J = 5.2Hz), 3.71 (2H, d, J = 5.
2Hz), 1.39 (9H, s).

Examples 5 (1) to 5 (6) Using the corresponding amino acid ester instead of glycine t-butyl ester / hydrochloride, the same operation as in Example 4 was performed, and the same procedure as in Reference Example 5 was performed. And the corresponding acid chloride or corresponding carboxylic acid in place of benzoyl chloride and a condensing agent [eg dicyclohexylcarbodiimide (DCC) or 1-ethyl-
3- [3- (dimethylamino) propyl] carbodiimide (EDC) and the like] to give a compound having the following physical properties by the same procedure as in Example 5 or by converting it to a corresponding salt by a conventional method. An invention compound was obtained.

Example 5 (1) N-[[4- (4-amidinobenzoyloxy) phenyl] sulfonyl] glycine t-butyl ester

[Chemical 277] TLC: Rf 0.41 (chloroform: methanol: acetic acid = 10: 2: 1).

Example 5 (2) N-[[4- (4-guanidinobenzoyloxy) phenyl] sulfonyl] glycine t-butyl ester

Embedded image TLC: Rf 0.35 (chloroform: methanol: acetic acid = 10: 2: 1)

Example 5 (3) N-[[4- (4-amidinobenzoyloxy) phenyl] sulfonyl] -L-phenylalanine t-butyl ester

Embedded image TLC: Rf 0.43 (chloroform: methanol: acetic acid = 10: 2: 1).

Example 5 (4) N-[[4- (benzoyloxy) phenyl] sulfonyl] glycine ethyl ester

[Chemical 280]

TLC: Rf 0.44 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.20 (2H, d, J = 7.0Hz), 7.95 (2H, d,
J = 8.7Hz), 7.68 (1H, m), 7.53 (2H, m), 7.40 (2H, d, J = 8.7H
z), 5.11 (1H, t, J = 5.4Hz), 4.13 (2H, q, J = 7.1Hz), 3.82 (2
H, d, J = 5.4Hz), 1.23 (3H, t, J = 7.1Hz).

Example 5 (5) N-[[4- (benzoyloxy) phenyl] sulfonyl] -β-alanine t-butyl ester

Embedded image

TLC: Rf 0.77 (ethyl acetate), NMR (CDCl ₃ ): δ 8.21 (2H, d, J = 8.0Hz), 7.95 (2H, d, J =
9.0Hz), 7.68 (1H, t, J = 8.0Hz), 7.54 (2H, t, J = 8.0Hz), 7.
40 (2H, d, J = 9.0Hz), 5.31 (1H, t, J = 6.0Hz), 3.19 (2H, q, J =
6.0Hz), 2.49 (2H, t, J = 6.0Hz), 1.44 (9H, s).

Example 5 (6) N-[[4- (4-amidinobenzoyloxy) phenyl] sulfonyl] -β-alanine t-butyl ester

Embedded image TLC: Rf 0.36 (chloroform: methanol: acetic acid = 10: 2: 1).

Example 6 N-[[4- (benzoyloxy) phenyl] sulfonyl] glycine

Embedded image

Using the compound prepared in Example 5 instead of the compound prepared in Example 1, the same procedure as in Example 2 was carried out to obtain the compound of the present invention having the following physical data. TLC: Rf 0.12 (chloroform: methanol: acetic acid: water = 90: 10: 1: 1), NMR (CDCl ₃ + CD ₃ OD): δ 8.16 (2H, d, J = 7.6Hz), 7.9
3 (2H, d, J = 9Hz), 7.66 (1H, t, J = 7.6Hz), 7.55 (2H, t, J = 7.6
Hz), 7.34 (2H, d, J = 9Hz), 3.77 (2H, s).

Examples 6 (1) to 6 (5) Instead of the compound prepared in Example 5, Examples 5 (1) to 6 (5)
The following physical properties were obtained by using the compounds prepared in 5 (3), 5 (5) and 5 (6) in the same manner as in Example 6 and, if necessary, converting the corresponding acid addition salt by a conventional method. A compound of the present invention having a value was obtained.

Example 6 (1) N-[[4- (4-amidinobenzoyloxy) phenyl] sulfonyl] glycine methanesulfonate

Embedded image

TLC: Rf 0.27 (chloroform: methanol: acetic acid = 3: 1: 1), NMR (DMSO-d ₆ ): δ 9.55 (2H, br.), 9.35 (2H, br.),
8.35 (2H, d, J = 8.0Hz), 8.00 (2H, d, J = 8.0Hz), 7.95 (d, J = 9H
z), 7.60 (2H, d, J = 9Hz), 3.60 (2H, br.), 3.40 (1H, br.),
2.40 (6H, s).

Example 6 (2) N-[[4- (4-guanidinobenzoyloxy) phenyl] sulfonyl] glycine methanesulfonate

Embedded image

TLC: Rf 0.45 (chloroform: methanol: acetic acid = 3: 1: 1), NMR (CD ₃ OD): δ 8.25 (2H, d, J = 8.0Hz), 7.95 (2H, d,
J = 8.0Hz), 7.45 (2H, d, J = 8.0Hz), 7.43 (2H, d, J = 8.0Hz),
3.73 (2H, s), 2.69 (3H, s).

Example 6 (3) N-[[4- (4-amidinobenzoyloxy) phenyl] sulfonyl] -L-phenylalanine acetic acid salt

[Chemical 286]

TLC: Rf 0.24 (chloroform: methanol: acetic acid = 10: 2: 1), NMR (CD ₃ COOD): δ 8.40 (2H, d, J = 7.5Hz), 8.05 (2H,
d, J = 7.5Hz), 7.80 (2H, d, J = 8.0Hz), 7.35 (2H, d, J = 8.0H
z), 7.30-7.15 (5H, m), 4.30 (1H, t, J = 6.0Hz), 3.20 (1H, d
d, J = 15.0Hz, 6.0Hz), 2.95 (1H, dd, J = 15.0Hz, 6.0Hz).

Example 6 (4) N-[[4- (benzoyloxy) phenyl] sulfonyl] -β-alanine

Embedded image

TLC: Rf 0.36 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1), NMR (CDCl ₃ + CD ₃ OD): δ 8.20 (2H, d, J = 7.0Hz), 7.95
(2H, d, J = 9.0Hz), 7.69 (1H, t, J = 7.0Hz), 7.55 (2H, t, J = 7.
0Hz), 7.40 (2H, d, J = 9.0Hz), 3.22 (2H, t, J = 6.0Hz), 2.55
(2H, t, J = 6.0Hz).

Example 6 (5) N-[[4- (4-amidinobenzoyloxy) phenyl] sulfonyl] -β-alanine

Embedded image

TLC: Rf 0.176 (chloroform: methanol: acetic acid = 10: 2: 1), NMR (CD ₃ COOD): δ 8.40 (2H, d, J = 7.5Hz), 8.05 (2H, d,
J = 7.5Hz), 8.00 (2H, d, J = 8.0Hz), 7.50 (2H, d, J = 8.0Hz),
3.25 (2H, t, J = 6.0Hz), 2.60 (2H, t, J = 6.0Hz).

Reference Example 6 4- (methoxycarbonyl) benzenesulfonyl chloride

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A suspension of 4-carboxybenzenesulfonyl chloride (2.2 g) in thionyl chloride (10 ml) was refluxed for 1 hour. After cooling the reaction mixture to room temperature,
Concentrated. The obtained residue was dissolved in methanol (10 ml) and stirred at room temperature for 1 hour. The reaction mixture was concentrated to give the title compound (2.3 g).

Reference Example 7 3- (Methoxycarbonyl) benzenesulfonyl chloride

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The title compound was obtained by the same procedure as in Reference Example 6 using 3-carboxybenzenesulfonyl chloride instead of 4-carboxybenzenesulfonyl chloride.

Example 7 N-[[4- (methoxycarbonyl) phenyl] sulfonyl] glycine t-butyl ester

Embedded image

By using the compound prepared in Reference Example 6 instead of the compound prepared in Reference Example 4, the compound of the present invention having the following physical data was obtained in the same manner as in Example 4. TLC: Rf 0.56 (hexane: ethyl acetate = 1: 1
1), NMR (CDCl ₃ ): δ 8.16 (2H, d, J = 8.8Hz), 7.93 (2H, d,
J = 8.8Hz), 5.09 (1H, t, J = 5.4Hz), 3.95 (3H, s), 3.70 (2H,
d, J = 5.4Hz), 1.34 (9H, s).

Examples 7 (1) to 7 (8) The present invention having the following physical properties was carried out in the same manner as in Example 7 using the amino acids corresponding to the compounds prepared in Reference Examples 6 and 7. The compound was obtained.

Example 7 (1) N-[[4- (methoxycarbonyl) phenyl] sulfonyl] -L-phenylalanine.t-butyl ester

Embedded image

TLC: Rf 0.59 (hexane: ethyl acetate = 2: 1), NMR (CDCl ₃ ): δ 8.10 (2H, d, J = 8.0Hz), 7.80 (2H, d,
J = 8.0Hz), 7.30-7.20 (3H, m), 7.20-7.10 (2H, m), 5.15 (1
H, d, J = 9.0Hz), 4.10 (1H, m), 3.95 (3H, s), 3.00 (2H, d, J =
6.0Hz), 1.20 (9H, s).

Example 7 (2) N-[[4- (methoxycarbonyl) phenyl] sulfonyl] -L-aspartic acid di-t-butyl ester

Embedded image

TLC: Rf 0.64 (hexane: ethyl acetate = 2: 1), NMR (CDCl ₃ ): δ 8.10 (2H, d, J = 8.0Hz), 7.90 (2H, d,
J = 8.0Hz), 5.65 (1H, d, J = 9.0Hz), 3.95 (1H, m), 3.90 (3H,
s), 2.75 (1H, dd, J = 15.0Hz, 5.0Hz), 2.65 (1H, dd, J = 15.0
Hz, 5.0Hz), 1.35 (9H, s), 1.25 (9H, s).

Example 7 (3) N-[[3- (methoxycarbonyl) phenyl] sulfonyl] glycine t-butyl ester

Embedded image TLC: Rf 0.45 (hexane: ethyl acetate = 2:
1).

Example 7 (4) N-[(4-methoxycarbonylphenyl) sulfonyl] -L-glutamic acid di-t-butyl ester

Embedded image

TLC: Rf 0.59 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.14 (2H, d, J = 9.0Hz), 7.90 (2H, d, J =
9.0Hz), 5.31 (1H, d, J = 9.0Hz), 3.96 (3H, s), 3.92-3.80
(1H, m), 2.43-2.35 (2H, m), 2.16-1.98 (1H, m), 1.88-1.6
6 (1H, m), 1.46 (9H, s), 1.24 (9H, s).

Example 7 (5) N-[(4-methoxycarbonylphenyl) sulfonyl] -L-aspartic acid di-t-butyl ester

Embedded image

TLC: Rf 0.83 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.15 (2H, d, J = 9.0Hz), 7.94 (2H, d, J =
9.0Hz), 5.72 (1H, d, J = 9.0Hz), 4.08-4.00 (1H, m), 3.96
(3H, s), 2.91-2.65 (2H, m), 1.43 (9H, s), 1.30 (9H, s).

Example 7 (6) N-[(3-methoxycarbonylphenyl) sulfonyl] -L-aspartic acid di-t-butyl ester

Embedded image

TLC: Rf 0.33 (hexane: ethyl acetate = 8: 2), NMR (CDCl ₃ ): δ 8.51 (1H, t, J = 2.0Hz), 8.24 (1H, dt, J
= 8.0Hz, 2.0Hz), 8.06 (1H, dt, J = 8.0Hz, 2.0Hz), 7.60 (1
H, t, J = 8.0Hz), 5.73 (1H, d, J = 9.0Hz), 4.10-4.01 (1H, m),
3.96 (3H, s), 2.91-2.66 (2H, m), 1.41 (9H, s), 1.27 (9H,
s).

Example 7 (7) N-[(3-methoxycarbonylphenyl) sulfonyl] -L-glutamic acid di-t-butyl ester

Embedded image

TLC: Rf 0.33 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 8.48 (1H, t, J = 2.0Hz), 8.23 (1H, dt, J
= 8.0Hz, 2.0Hz), 8.02 (1H, dt, J = 8.0Hz, 2.0Hz), 7.59 (1
H, t, J = 8.0Hz), 5.32 (1H, d, J = 9.0Hz), 3.96 (3H, s), 3.92
-3.81 (1H, m), 2.40 (2H, t, J = 8.0Hz), 2.13-1.96 (1H, m),
1.87-1.66 (1H, m), 1.46 (9H, s), 1.23 (9H, s).

Example 7 (8) N-[(4-methoxycarbonylphenyl) sulfonyl] -β-alanine t-butyl ester

Embedded image

TLC: Rf 0.43 (hexane: ethyl acetate = 2: 1), NMR (CDCl ₃ ): δ 8.20 (2H, d, J = 8.0Hz), 7.95 (2H, d, J =
8.0Hz), 5.40 (1H, t, J = 6.0Hz), 4.00 (3H, s), 3.20 (2H, d
t, J = 6.0Hz, 6.0Hz), 2.50 (3H, t, J = 6.0Hz), 1.45 (9H, s).

Example 8 N-[(4-Carboxyphenyl) sulfonyl] glycine t-butyl ester

Embedded image

The compound prepared in Example 7 (658 mg)
5N sodium hydroxide aqueous solution (0.8 ml) was added to the methanol (2 ml) and dioxane (2 ml) solution of. The reaction mixture was stirred at room temperature for 1 day. The reaction mixture was neutralized with 2N hydrochloric acid and extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography (dichloromethane: methanol:
Purification with acetic acid: water = 100: 10: 1: 1) gave the compound of the present invention (333 mg) having the following physical data. TLC: Rf 0.49 (chloroform: methanol: acetic acid: water = 90: 10: 1: 1), NMR (CD ₃ OD): δ 8.16 (2H, d, J = 8.8Hz), 7.94 (2H, d,
J = 8.8Hz), 3.69 (2H, s), 1.31 (9H, s).

Examples 8 (1) -8 (8) Instead of the compound prepared in Example 7, Examples 7 (1) -8
Using the compound prepared in 7 (8) and following the procedure of Example 8, the compound of the present invention having the following physical data was obtained.

Example 8 (1) [(4-Carboxyphenyl) sulfonyl] -L-phenylalanine t-butyl ester

Embedded image

TLC: Rf 0.25 (chloroform: methanol = 9: 1), NMR (CDCl ₃ ): δ 8.15 (2H, d, J = 8.0Hz), 7.85 (2H, d,
J = 8.0Hz), 7.30-7.20 (3H, m), 7.20-7.10 (2H, m), 5.30 (1
H, d, J = 9.0Hz), 4.15 (1H, m), 3.00 (2H, d, J = 6.0Hz), 1.25
(9H, s).

Example 8 (2) N-[(4-carboxyphenyl) sulfonyl] -L-
Aspartic acid / di-t-butyl ester

Embedded image

TLC: Rf 0.28 (chloroform: methanol = 9: 1), NMR (CDCl ₃ ): δ 8.20 (2H, d, J = 8.0Hz), 8.00 (2H, d,
J = 8.0Hz), 5.80 (1H, d, J = 9.0Hz), 4.05 (1H, m), 2.80 (2H,
m), 1.40 (9H, s), 1.30 (9H, s).

Example 8 (3) N-[(3-carboxyphenyl) sulfonyl] glycine t-butyl ester

Embedded image TLC: Rf 0.22 (chloroform: methanol = 9:
1).

Example 8 (4) N-[(4-carboxyphenyl) sulfonyl] -L-
Glutamic acid / di-t-butyl ester

[Chemical 304]

TLC: Rf 0.25 (chloroform: methanol = 9: 1), NMR (CDCl ₃ ): δ 8.30-8.10 (2H, br.d, J = 8.0Hz), 8.1
0-7.80 (2H, br.d, J = 8.0Hz), 5.50-5.30 (1H, br.d, J = 9.0
Hz), 4.00-3.78 (1H, m), 2.50-1.60 (8H, m), 1.43 (9H, s),
1.23 (9H, s).

Example 8 (5) N-[(4-carboxyphenyl) sulfonyl] -L-
Aspartic acid / di-t-butyl ester

Embedded image

TLC: Rf 0.30 (chloroform: methanol = 9: 1), NMR (CDCl ₃ ): δ 8.22-8.04 (2H, br.d, J = 8.0Hz), 7.9
6-7.76 (2H, br.d, J = 8.0Hz), 6.00-5.82 (1H, br.d, J = 9.0
Hz), 4.16-4.00 (1H, m), 2.92-2.63 (2H, m), 1.40 (9H, s),
1.25 (9H, s).

Example 8 (6) N-[(3-carboxyphenyl) sulfonyl] -L-
Aspartic acid / di-t-butyl ester

Embedded image

TLC: Rf 0.46 (chloroform: methanol: water = 8: 2: 0.1), NMR (CDCl ₃ ): δ 8.63 (1H, t, J = 2.0Hz), 8.29 (1H, dt, J)
= 8.0Hz, 2.0Hz), 8.12 (1H, dt, J = 8.0Hz, 2.0Hz), 7.64 (1
H, t, J = 8.0Hz), 6.00 (1H, d, J = 9.0Hz), 4.16-4.07 (1H, m),
2.94-2.69 (2H, m), 1.43 (9H, s), 1.28 (9H, s).

Example 8 (7) N-[(3-carboxyphenyl) sulfonyl] -L-
Glutamic acid / di-t-butyl ester

Embedded image

TLC: Rf 0.54 (chloroform: methanol: water = 8: 2: 0.1), NMR (CDCl ₃ ): δ 8.57 (1H, t, J = 2.0Hz), 8.29 (1H, dt, J)
= 8.0Hz, 2.0Hz), 8.08 (1H, dt, J = 8.0Hz, 2.0Hz), 7.63 (1
H, t, J = 8.0Hz), 5.61 (1H, d, J = 9.0Hz), 3.97-3.86 (1H, m),
2.42 (2H, t, J = 7.0Hz), 2.15-1.98 (1H, m), 1.90-1.72 (1
H, m), 1.47 (9H, s), 1.25 (9H, s).

Example 8 (8) N-[(4-carboxyphenyl) sulfonyl] -β-
Alanine t-butyl ester

Embedded image

TLC: Rf 0.31 (chloroform: methanol = 4: 1), NMR (CDCl ₃ ): δ 8.20 (2H, d, J = 8.0Hz), 7.95 (2H, d, J =
8.0Hz), 3.20 (2H, t, J = 6.0Hz), 2.45 (2H, t, J = 6.0Hz), 1.
45 (9H, s).

Example 9 N-[[4- (phenoxycarbonyl) phenyl] sulfonyl] glycine t-butyl ester

Embedded image

The compound prepared in Example 8 (221 mg)
Phenol (79 mg) in pyridine (3.5 ml) solution
And N, N-dimethylaminopyridine (9 mg) and dicyclohexylcarbodiimide (159 mg) were sequentially added. The reaction mixture was stirred overnight and concentrated. The residue was subjected to silica gel column chromatography (hexane: ethyl acetate =
5: 1) to obtain the compound of the present invention having the following physical properties.

TLC: Rf 0.77 (ethyl acetate), NMR (CDCl ₃ ): δ 8.35 (2H, d, J = 8.8Hz), 8.02 (2H, d,
J = 8.8Hz), 7.47 (2H, t, J = 6.0Hz), 7.31 (1H, t, J = 6.0Hz),
7.22 (2H, d, J = 6.0Hz), 5.16 (1H, t, J = 5.4Hz), 3.74 (2H, d,
J = 5.4Hz), 1.37 (9H, s).

Examples 9 (1) -9 (10) The same procedure as in Example 9 was carried out using the compounds prepared in Examples 8 and 8 (1) -8 (8) and the corresponding alcohols and amines. Alternatively, or by converting it into a corresponding salt by a conventional method, the compound of the present invention having the following physical property values was obtained.

Example 9 (1) N-[[4- (4-amidinophenoxycarbonyl) phenyl] sulfonyl] -L-phenylalanine.t-butyl ester

Embedded image

TLC: Rf 0.45 (chloroform: methanol: acetic acid = 10: 2: 1), NMR (CD ₃ OD): δ 8.25 (2H, d, J = 8.0Hz), 7.95 (2H, d,
J = 8.0Hz), 7.85 (2H, d, J = 8.0Hz), 7.55 (2H, d, J = 8.0Hz),
7.25-7.10 (5H, m), 4.00 (1H, t, J = 7.5Hz), 3.00 (1H, dd, J =
15.0Hz, 7.5Hz), 2.85 (1H, dd, J = 15.0Hz, 7.5Hz), 1.25 (9
H, s).

Example 9 (2) N-[[4- (4-amidinophenoxycarbonyl) phenyl] sulfonyl] -L-aspartic acid.di-t-
Butyl ester

[Chemical 311]

TLC: Rf 0.51 (chloroform: methanol: acetic acid = 10: 2: 1), NMR (CD ₃ OD): δ 8.35 (2H, d, J = 8.0Hz), 8.05 (2H, d,
J = 8.0Hz), 7.95 (2H, d, J = 9.0Hz), 7.55 (2H, d, J = 9.0Hz),
4.20 (1H, m), 2.60 (2H, m), 1.45 (9H, s), 1.30 (9H, s).

Example 9 (3) N-[[3- (4-amidinophenoxycarbonyl) phenyl] sulfonyl] glycine t-butyl ester

Embedded image

TLC: Rf 0.33 (chloroform: methanol: acetic acid = 10: 2: 1), NMR (CD ₃ OD): δ 8.60 (1H, s), 8.40 (1H, d, J = 8.0H)
z), 8.20 (1H, d, J = 8.0Hz), 7.95 (2H, d, J = 9.0Hz), 7.80 (1
H, t, J = 8.0Hz), 7.55 (2H, d, J = 9.0Hz), 3.75 (2H, s), 1.35
(9H, s).

Example 9 (4) N-[[4- (4-amidinophenoxycarbonyl) phenyl] sulfonyl] glycine t-butyl ester

Embedded image

TLC: Rf 0.45 (chloroform: methanol: acetic acid = 10: 2: 1), NMR (CD ₃ OD): δ 8.35 (2H, d, J = 8.0Hz), 8.05 (2H, d,
J = 8.0Hz), 7.95 (2H, d, J = 8.0Hz), 7.55 (2H, d, J = 8.0Hz),
3.75 (2H, s), 1.40 (9H, s).

Example 9 (5) N-[[4- (N-phenylcarbamoyl) phenyl]
Sulfonyl] glycine / t-butyl ester

Embedded image

TLC: Rf 0.40 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ + CD ₃ OD): δ 8.04 (2H, d, J = 8.8Hz), 7.9
5 (2H, d, J = 8.8Hz), 7.69 (2H, d, J = 8.0Hz), 7.39 (2H, t, J =
8.0Hz), 7.18 (1H, t, J = 8.0Hz), 3.70 (2H, s), 1.36 (9H,
s).

Example 9 (6) N-[[4- [N- (4-amidinophenyl) carbamoyl] phenyl] sulfonyl] -L-glutamic acid di-t-butyl ester

Embedded image

TLC: Rf 0.59 (chloroform: methanol: acetic acid = 10: 2: 1), NMR (CD ₃ OD): δ 8.07 (2H, d, J = 9.0Hz), 7.99 (2H, d, J =)
8.0Hz), 7.93 (2H, d, J = 9.0Hz), 7.80 (2H, d, J = 8.0Hz), 3.
84 (1H, m), 2.35-2.23 (2H, m), 2.03-1.85 (1H, m), 1.76-
1.55 (1H, m), 1.39 (9H, s), 1.21 (9H, s).

Example 9 (7) N-[[4- [N- (4-amidinophenyl) carbamoyl] phenyl] sulfonyl] -L-aspartic acid.
Di-t-butyl ester

Embedded image

TLC: Rf 0.59 (chloroform: methanol: acetic acid = 10: 2: 1), NMR (CD ₃ OD): δ 8.12 (2H, d, J = 9.0Hz), 8.04 (2H, d, J =
8.0Hz), 8.01 (2H, d, J = 9.0Hz), 7.85 (2H, d, J = 8.0Hz), 4.
18 (1H, dd, J = 7.0Hz, 6.0Hz), 2.70 (1H, dd, J = 16.0Hz, 6.0
Hz), 2.57 (1H, dd, J = 16.0Hz, 7.0Hz), 1.44 (9H, s), 1.29
(9H, s).

Example 9 (8) N-[[3- [N- (4-amidinophenyl) carbamoyl] phenyl] sulfonyl] -L-aspartic acid.
Di-t-butyl ester

Embedded image

TLC: Rf 0.59 (chloroform: methanol: acetic acid = 10: 2: 1), NMR (CD ₃ OD): δ 8.45 (1H, s), 8.20 (1H, d, J = 8.0Hz),
8.09 (1H, d, J = 8.0Hz), 8.05 (2H, d, J = 9.0Hz), 7.86 (2H, d, J
= 9.0Hz), 7.73 (1H, t, J = 8.0Hz), 4.21 (1H, dd, J = 7.0Hz,
6.0Hz), 2.70 (1H, dd, J = 16.0Hz, 6.0Hz), 2.57 (1H, dd, J =
16.0Hz, 7.0Hz), 1.43 (9H, s), 1.27 (9H, s).

Example 9 (9) N-[[3- [N- (4-amidinophenyl) carbamoyl] phenyl] sulfonyl] -L-glutamic acid di-t-butyl ester

Embedded image

TLC: Rf 0.59 (chloroform: methanol: acetic acid = 10: 2: 1), NMR (CD ₃ OD): δ 8.44 (1H, t, J = 2.0Hz), 8.22 (1H, dt, J)
= 8.0Hz, 2.0Hz), 8.08 (1H, dt, J = 8.0Hz, 2.0Hz), 8.06 (2
H, d, J = 9.0Hz), 7.87 (2H, d, J = 9.0Hz), 7.74 (1H, t, J = 8.0H
z), 3.92 (1H, dd, J = 9.0Hz, 5.0Hz), 2.37 (2H, m), 1.98 (1
H, m), 1.76 (1H, m), 1.45 (9H, s), 1.25 (9H, s).

Example 9 (10) N-[[4-[(4-amidinophenyloxy) carbonyl] phenyl] sulfonyl] -β-alanine t-butyl ester trifluoroacetate

Embedded image

TLC: Rf 0.35 (chloroform: methanol: acetic acid = 10: 2: 1), NMR (CD ₃ OD): δ 8.40 (2H, d, J = 8.0Hz), 8.05 (2H, d, J =)
8.0Hz), 7.95 (2H, d, J = 8.0Hz), 7.60 (2H, d, J = 8.0Hz), 3.
15 (2H, t, J = 6.0Hz), 2.45 (2H, t, J = 6.0Hz), 2.00 (3H, s),
1.45 (9H, s).

Example 10 N-[[4- (phenoxycarbonyl) phenyl] sulfonyl] glycine

[Chemical 320]

Using the compound prepared in Example 9 instead of the compound prepared in Example 1, the same procedure as in Example 2 was carried out to obtain the compound of the present invention having the following physical data.

TLC: Rf 0.22 (chloroform: methanol: acetic acid: water = 90: 10: 1: 1), NMR (CDCl ₃ + CD ₃ OD): δ 8.33 (2H, d, J = 8.8Hz), 8.0
2 (2H, d, J = 8.8Hz), 7.46 (2H, t, J = 7.4Hz), 7.33 (1H, t, J =
7.4Hz), 7.21 (2H, d, J = 7.4Hz), 3.81 (2H, s).

Examples 10 (1) to 10 (12) Examples 7, 8 and 9 (1) to 9 (10).
Using the compound prepared in, the same procedure as in Example 10,
If necessary, the compound of the present invention having the following physical properties was obtained by converting the corresponding acid addition salt by a conventional method.

Example 10 (1) N-[[4- (4-amidinophenoxycarbonyl) phenyl] sulfonyl] -L-phenylalanine methanesulfonate

[Chemical 321]

TLC: Rf 0.74 (chloroform: methanol: acetic acid = 3: 1: 1), NMR (CD ₃ OD): δ 8.20 (2H, d, J = 8.0Hz), 7.95 (2H, d,
J = 8.0Hz), 7.80 (2H, d, J = 8.0Hz), 7.60 (2H, d, J = 8.0Hz),
7.25-7.10 (5H, m), 4.10 (1H, dd, J = 9.0Hz, 5.0Hz), 3.10
(1H, dd, J = 14.0Hz, 5.0Hz), 2.85 (1H, dd, J = 14.0Hz, 9.0H
z), 2.70 (3H, s).

Example 10 (2) N-[[4- (4-amidinophenoxycarbonyl) phenyl] sulfonyl] -L-aspartic acid / methanesulfonate

Embedded image

TLC: Rf 0.21 (chloroform: methanol: acetic acid = 3: 1: 1), NMR (CD ₃ OD): δ 8.35 (2H, d, J = 8.0Hz), 8.10 (2H, d,
J = 8.0Hz), 7.95 (2H, d, J = 8.0Hz), 7.55 (2H, d, J = 8.0Hz),
4.30 (1H, t, J = 6.5Hz), 2.80 (2H, d, J = 6.5Hz), 2.70 (3H,
s).

Example 10 (3) N-[[3- (4-amidinophenoxycarbonyl) phenyl] sulfonyl] glycine methanesulfonate

Embedded image

TLC: Rf 0.27 (chloroform: methanol: acetic acid = 3: 1: 1), NMR (CD ₃ OD): δ 8.85 (1H, br.s), 8.40 (1H, d, J = 8.0)
Hz), 8.20 (1H, d, J = 8.0Hz), 7.95 (2H, d, J = 9.0Hz), 7.80
(1H, t, J = 8.0Hz), 7.60 (2H, d, J = 9.0Hz), 3.80 (2H, s), 2.
70 (3H, s).

Example 10 (4) N-[[4- (4-amidinophenoxycarbonyl) phenyl] sulfonyl] glycine methanesulfonate

Embedded image

TLC: Rf 0.30 (chloroform: methanol: acetic acid = 3: 1: 1), NMR (CD ₃ OD): δ 8.35 (2H, d, J = 8.0Hz), 8.05 (2H, d,
J = 8.0Hz), 7.95 (2H, d, J = 9.0Hz), 7.60 (2H, d, J = 9.0Hz),
3.80 (2H, s), 2.70 (3H, s).

Example 10 (5) N-[[4- (N-phenylcarbamoylphenyl) sulfonyl] glycine

Embedded image

TLC: Rf 0.04 (chloroform: methanol: acetic acid: water = 100: 10: 1: 1), NMR (CDCl ₃ + CD ₃ OD + DMSO-d ₆ ): δ 8.10 (2H, d, J = 8.
3Hz), 7.95 (2H, d, J = 8.3Hz), 7.75 (2H, d, J = 8.0Hz), 7.35
(2H, t, J = 8.0Hz), 7.13 (1H, t, J = 8.0Hz), 3.67 (2H, s).

Example 10 (6) N-[(4-methoxycarbonylphenyl) sulfonyl] glycine

Embedded image

TLC: Rf 0.16 (chloroform: methanol: acetic acid: water = 90: 10: 1: 1), NMR (CDCl ₃ + CD ₃ OD): δ 8.13 (2H, d, J = 8.8Hz), 7.9
0 (2H, d, J = 8.8Hz), 3.92 (3H, s), 3.74 (2H, s).

Example 10 (7) N-[(4-carboxyphenyl) sulfonyl] glycine

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TLC: Rf 0.02 (chloroform: methanol: acetic acid: water = 90: 10: 1: 1), NMR (DMSO-d ₆ ): δ 8.25 (1H, t, J = 6.2Hz), 8.08 (2H,
d, J = 8.8Hz), 7.89 (2H, d, J = 8.8Hz), 3.63 (2H, d, J = 6.2H
z).

Example 10 (8) N-[[4- [N- (4-amidinophenyl) carbamoyl] phenyl] sulfonyl] -L-glutamic acid

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TLC: Rf 0.51 (ethyl acetate: acetic acid:
Water = 3: 1: 1), NMR (d ₆ -DMSO + MeSO ₃ H (1 drop)): δ 10.85 (1H, s), 9.24
(2H, s), 8.98 (2H, s), 8.39 (1H, d, J = 9.0Hz), 8.15 (2H, d, J
= 9.0Hz), 8.03 (2H, d, J = 9.0Hz), 7.93 (2H, d, J = 9.0Hz),
7.87 (2H, d, J = 9.0Hz), 3.85 (1H, dt, J = 9.0Hz, 7.0Hz), 2.
23 (2H, t, J = 7.0Hz), 2.00-1.60 (2H, m).

Example 10 (9) N-[[4- [N- (4-amidinophenyl) carbamoyl] phenyl] sulfonyl] -L-aspartic acid

Embedded image

TLC: Rf 0.51 (ethyl acetate: acetic acid:
Water = 3: 1: 1), NMR (d ₆ -DMSO + MeSO ₃ H (1 drop)): δ 10.85 (1H, s), 9.24
(2H, s), 8.97 (2H, s), 8.43 (1H, d, J = 9.0Hz), 8.14 (2H, d, J
= 9.0Hz), 8.03 (2H, d, J = 9.0Hz), 7.95 (2H, d, J = 9.0Hz),
7.87 (2H, d, J = 9.0Hz), 4.13 (1H, dt, J = 9.0Hz, 6.0Hz), 2.
64 (1H, dd, J = 16.0Hz, 6.0Hz), 2.46 (1H, dd, J = 16.0Hz, 6.
0Hz).

Example 10 (10) N-[[3- [N- (4-amidinophenyl) carbamoyl] phenyl] sulfonyl] -L-aspartic acid

[Chemical 330]

TLC: Rf 0.67 (ethyl acetate: acetic acid:
Water = 3: 1: 1), NMR (d ₆ -DMSO + MeSO ₃ H (1 drop)): δ 10.88 (1H, s), 9.24
(2H, s), 8.95 (2H, s), 8.40 (1H, s), 8.23 (1H, d, J = 8.0Hz),
8.03 (2H, d, J = 9.0Hz), 8.02 (1H, d, J = 8.0Hz), 7.87 (2H, d,
J = 9.0Hz), 7.76 (1H, t, J = 8.0Hz), 4.14 (1H, m), 2.64 (1H,
dd, J = 16.0Hz, 6.0Hz), 2.46 (1H, dd, J = 16.0Hz, 6.0Hz).

Example 10 (11) N-[[3- [N- (4-amidinophenyl) carbamoyl] phenyl] sulfonyl] -L-glutamic acid

Embedded image

TLC: Rf 0.65 (ethyl acetate: acetic acid:
Water = 3: 1: 1), NMR (d ₆ -DMSO + MeSO ₃ H (1 drop)): δ 10.88 (1H, s), 9.24
(2H, s), 9.01 (2H, s), 8.37 (1H, s), 8.35 (1H, d, J = 8.0Hz),
8.24 (1H, d, J = 8.0Hz), 8.03 (2H, d, J = 9.0Hz), 8.01 (1H, d,
J = 8.0Hz), 7.87 (2H, d, J = 9.0Hz), 7.76 (1H, t, J = 8.0Hz),
3.85 (1H, m), 2.22 (2H, t, J = 7.0Hz), 1.90 (1H, m), 1.69 (1
H, m).

Example 10 (12) N-[[4-[(4-amidinophenyloxy) carbonyl] phenyl] sulfonyl] -β-alanine

Embedded image

TLC: Rf 0.34 (chloroform: methanol: acetic acid = 10: 2: 1), NMR (CD ₃ OD): δ 8.40 (2H, d, J = 8.0Hz), 8.05 (2H, d, J =)
8.0Hz), 7.95 (2H, d, J = 8.0Hz), 7.60 (2H, d, J = 8.0Hz), 3.
20 (2H, t, J = 6.5Hz), 2.75 (3H, s), 2.55 (2H, t, J = 6.5Hz).

Example 11 N-[[4- (N-phenylureido) phenyl] sulfonyl] glycine t-butyl ester

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Phenylisocyanate (500 μl) was added to a solution of the compound (1.20 g) produced in Reference Example 2 in acetone (20 ml). After stirring the mixed solution at room temperature for 24 hours, phenyl isocyanate (200 μm) was further added.
1) was added and stirred for 24 hours. Further, phenyl isocyanate (500 μl) was added, and the mixture was stirred for 12 hours. The reaction solution was concentrated, the residue was washed with ether and dried to obtain the compound of the present invention (1.40 g) having the following physical properties.

TLC: Rf 0.25 (hexane: ethyl acetate = 1: 1), NMR (CDCl ₃ ): δ 7.72-7.60 (1H), 7.66 (2H, d, J = 8.8H
z), 7.46-7.20 (5H, m), 7.28 (2H, d, J = 8.8Hz), 7.12-7.00
(1H, m), 5.39 (1H, t, J = 5.6Hz), 3.63 (2H, d, J = 5.6Hz), 1.
36 (9H, s).

Example 12 N-[[4- (N-phenylureido) phenyl] sulfonyl] glycine

Embedded image

Using the compound produced in Example 11 and following the same procedure as in Example 2, a compound of the present invention having the following physical properties was obtained. TLC: Rf 0.34 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 13.50-11.50 (1H, br.s), 9.08 (1)
H, s), 8.77 (1H, s), 7.82 (1H, t, J = 6.2Hz), 7.69 (2H, d, J =
9.0Hz), 7.60 (2H, d, J = 9.0Hz), 7.52-7.40 (2H, m), 7.28
(2H, t, J = 7.4Hz), 6.98 (1H, t, J = 7.4Hz), 3.53 (2H, d, J = 6.
2Hz).

Reference Example 8 2- (4-chlorosulfonyl) phenylacetophenone

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Deoxybenzoin (5.0 g) was added to the sulfonyl chloride (8.45 ml) solution in small portions at 0 ° C. After stirring the solution at 10 to 15 ° C for 30 minutes, 50
Stirred at 150C for 15 minutes. The reaction solution was poured into ice and extracted with ethyl acetate. The extract was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The obtained crystals were washed with ether and dried to give the compound of the present invention (2.25
g) was obtained. In addition, the ether layer was subjected to silica gel column chromatography (hexane: ethyl acetate = 17: 3).
The compound of the present invention (1.09 g; total 3.34 g) having the following physical properties was obtained. TLC: Rf 0.27 (hexane: ethyl acetate = 9:
1).

Example 13 N-[(4-benzoylmethylphenyl) sulfonyl]
Glycine t-butyl ester

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By using the compound prepared in Reference Example 8 and operating in the same manner as in Example 4, a compound of the present invention having the following physical properties was obtained. TLC: Rf 0.21 (hexane: ethyl acetate = 7:
3), NMR (CDCl ₃ ): δ 8.05-7.97 (2H, m), 7.83 (2H, d, J = 8.6
Hz), 7.65-7.45 (3H, m), 7.41 (2H, d, J = 8.6Hz), 5.05 (1H,
t, J = 5.4Hz), 4.35 (2H, s), 3.67 (2H, d, J = 5.4Hz), 1.34 (9
H, s).

Example 14 N-[(4-benzoylmethylphenyl) sulfonyl]
glycine

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Using the compound produced in Example 13 and the same procedure as in Example 3, the compound of the present invention having the following physical properties was obtained. TLC: Rf 0.56 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 13.50-11.50 (1H, br.s), 8.10-8.
00 (2H, m), 7.98 (1H, t, J = 6.2Hz), 7.74 (2H, d, J = 8.4Hz),
7,72-7.50 (3H, m), 7.45 (2H, d, J = 8.4Hz), 4.53 (2H, s),
3.57 (2H, d, J = 6.2Hz).

Example 14 (1) N- [4-[(4-methoxybenzoyl) methyl] sulfonyl] glycine

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Using the corresponding compound, the same operation as in Reference Example 8 and Example 14 was carried out to obtain N- [4-[(4
-Methoxybenzoyl) methyl] sulfonyl] glycine t-butyl ester was treated in the same manner as in Example 3 to obtain the compound of the present invention having the following physical properties.

TLC: Rf 0.35 (chloroform: methanol: acetic acid: water = 50: 10: 1: 1), NMR (CDCl ₃ + CD ₃ OD): δ 8.00 (2H, d, J = 8.8Hz), 7.82 ( 2
H, d, J = 8.3Hz), 7.41 (2H, d, J = 8.3Hz), 6.98 (2H, d, J = 8.8H
z), 4.36 (2H, s), 3.90 (3H, s), 3.71 (2H, s).

Reference Example 9 N-[[4- (benzoylamino) phenyl] sulfonyl] -Nt-butoxycarbonylglycine.t-butyl ester

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The compound prepared in Example 1 (10) (1.20
g) in acetonitrile (60 ml), 4-dimethylaminopyridine (37 mg) and di-t-butyl.
Dicarbonate (811 μl) was added. The mixture was stirred at room temperature for 30 minutes. The reaction solution was concentrated and extracted with ethyl acetate. The extracted solution was washed successively with water, saturated aqueous sodium hydrogen carbonate solution, water and saturated brine, dried over anhydrous magnesium sulfate and concentrated to give the compound of the present invention (1.61 g) having the following physical properties. TLC: Rf 0.61 (hexane: ethyl acetate = 1: 1
1).

Reference Example 10 N-[[4- (N-methyl-N-benzoylamino) phenyl] sulfonyl] -Nt-butoxycarbonylglycine.t-butyl ester

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To a solution of the compound (1.60 g) prepared in Reference Example 9 in dimethylformamide (20 ml) was added 60% sodium hydride (143 mg) at 0 ° C. Mix 1
Stirred for hours. Methyl iodide (558 μl) was added to the reaction solution.
Was added and stirred for 30 minutes. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was subjected to silica gel column chromatography (hexane: ethyl acetate =
The compound of the present invention (1.05 g) having the following physical properties was obtained after purification by 7: 3). TLC: Rf 0.54 (hexane: ethyl acetate = 1: 1
1).

Example 15 N-[[4- (N-methyl-N-benzoylamino) phenyl] sulfonyl] glycine

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Using the compound (1.00 g) produced in Reference Example 10 and following the same procedure as in Example 2, a compound of the present invention (641 mg) having the following physical properties was obtained. TLC: Rf 0.47 (chloroform: methanol: acetic acid = 16: 3: 1), NMR (DMSO-d ₆ ): δ 13.20-12.00 (1H, br.s), 8.00 (1
H, t, J = 5.8.0Hz), 7.65 (2H, d, J = 8.8Hz), 7.33 (2H, d, J = 8.
8Hz), 7.31-7.20 (5H, m), 3.51 (2H, d, J = 5.8Hz), 3.40 (3H,
s).

[0725]

[Formulation example]

Formulation Example 1 The following components were mixed in a conventional manner and then tableted to obtain 100 tablets each containing 50 mg of the active ingredient.・ N-[[4-[[(4-methylphenyl) carbonyl] amino] phenyl] sulfonyl] glycine …… 5.0 g ・ Carboxymethylcellulose calcium (disintegrant) …… 0.2 g ・ Magnesium stearate (lubricant) …… 0.1 g ・ Microcrystalline cellulose …… 4.7 g

Formulation Example 2 The following components were admixed in a conventional manner, the solution was sterilized in a conventional manner, filled in ampoules of 5 ml each, and lyophilized in a conventional manner to contain 20 mg of the active ingredient in 1 ampule. I got 100 ampoules.・ N-[[4-[[(4-methylphenyl) carbonyl] amino] phenyl] sulphonyl] glycine …… 2.00 g ・ Mannitol ………… 20 g ・ Distilled water …… 1000 ml

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical indication location A61K 31/34 A61K 31/34 31/38 31/38 31/405 31/405 31/415 31 / 415 31/44 31/44 C07C 311/29 7419-4H C07C 311/29 311/42 7419-4H 311/42 311/46 7419-4H 311/46 311/47 7419-4H 311/47 C07D 209/20 C07D 209/20 213/55 213/55 213/81 213/81 213/82 213/82 233/26 233/26 307/68 307/68 333/38 333/38 333/40 333/40 (72) Inventor Tohru Miyazaki 3-1-1 Sakurai, Shimamoto-cho, Mishima-gun, Osaka Prefecture Minase Research Laboratory, Ono Pharmaceutical Co., Ltd. (72) Inventor Hiroyuki Ohno 3-1-1 Sakurai, Shimamoto-cho, Mishima County, Osaka Prefecture Minase Research Laboratory, Ono Pharmaceutical Co., Ltd.

Claims (7)

[Claims] 1. A compound of the general formula (I) [In the formula, R ¹ represents a hydrogen atom or a C1~4 alkyl group,, R ² is 1) hydrogen atom, 2) C1-8 alkyl group, 3) a phenyl group or a 4) a phenyl group,, -OCOR ¹⁶ groups (wherein R ¹⁶ is C1 to
Represents a 4-alkyl group. ), Or C1 substituted with a CONR ¹⁷ R ¹⁸ group (in which R ¹⁷ and R ¹⁸ each independently represent a hydrogen atom or a C1-4 alkyl group).
Represent ~ 4 alkyl group, E is, 1) -CO-NR ³ - group (wherein, R ³ is a hydrogen atom, C1 to
4 alkyl group, a phenyl group, or a C1-4 alkyl group substituted with a phenyl group. ), 2) -NR ³ -CO- group (wherein R ³ has the same meaning as described above), 3) -CO-O- group, 4) -O-CO- group, 5) -NR ³ —CO—NR ³ — group (wherein R ³ has the same meaning as described above), 6) —CO—CH ₂ — group, 7) —CO— group, 8) —O—CO—NR ³ —. Group (in the group, R ³ has the same meaning as described above), 9) —NR ³ —CO—O— group (in the group, R ³ has the same meaning as described above), 10) —O—CO. —O— group, 11) —CS—NR ³ — group (in the group, R ³ has the same meaning as described above), 12) —NR ³ —CS— group (in the group, R ³ has the same meaning as described above). , 13) —NR ³ —CS—NR ³ — group (in the group, R ³ has the same meaning as described above), 14) —O—CS—NR ³ — group (in the group, R ³ Represents the same meaning as described above.), 15 (Wherein, R ³ are as defined above.) -NR ³ -CS-O- group, 16) -CS-O- group, 17) -O-CS- group or 18,) -O-CS Represents an —O— group, A is 1) a hydrogen atom, 2) a C1-8 alkyl group, 3) a C3-7 cycloalkyl group, or 4) an Ar group (wherein the Ar group is a carbocycle or a heterocyclic aryl). Represents 1 to 3 C1-15 alkyl groups, C1
To 15 alkoxy group, halogen atom, nitro group, cyano group, guanidino group, amidino group, hydroxyl group, benzyloxy group, NR ⁹ R ¹⁰ group (wherein R ⁹ and R ¹⁰ are independently a hydrogen atom or represents a C1~4 alkyl group), -.. COOR ¹¹ group (wherein, R ¹¹ is represents a hydrogen atom or a C1~4 alkyl group), a trifluoromethyl group, substituted with a phenyl group or a heterocyclic group Good. And J is 1) a single bond, 2) a C2-4 alkylene group, 3) a C2-4 alkenylene group, or (In the group, R ⁴ and R ⁵ are each independently (i)
Hydrogen atom, (ii) C1-4 alkyl group, (iii) C1
4 alkoxy group, or together with the carbon atom to which R ⁴ and R ⁵ are bonded, represents a C3-7 cycloalkyl group. And G is a 1)-(CH ₂ ) _m -group (wherein m represents 2, 3 or 4) or (In the group, R ⁶ and R ⁷ are each independently (i)
Hydrogen atom, (ii) C1-8 alkyl group, (iii) -CO
OR ⁸ group (wherein R ⁸ is a hydrogen atom, a C1-8 alkyl group,
It represents a phenyl group or a C1-4 alkyl group substituted with a phenyl group. ), (Iv) Ar group (wherein Ar represents the same meaning as described above), (v) heterocyclic group, (v
i) —COOR ⁸ group (wherein R ⁸ has the same meaning as described above), C1-4 alkoxy group, hydroxyl group, benzyloxy group, —NR ¹² R ¹³ group (wherein R ¹² and R ¹³ are each independently represent a hydrogen atom or a C1~4 alkyl group), -. NR ¹⁴ COOR ¹⁵ group (wherein, R ¹⁴ represents a hydrogen atom or a C1~4 alkyl group, R ¹⁵ represents a hydrogen atom, C1 ~ 8 alkyl group, a phenyl group, or a C1-4 alkyl group substituted with a phenyl group), Ar
A C1-8 alkyl group substituted with a group or a heterocyclic group (wherein one carbon atom of the C1-8 alkyl group is a sulfur atom 1
It may be replaced with an individual. ), Or R
⁶ and C ⁷ together with the carbon atom to which R ⁷ is attached
Represents a cycloalkyl group. ) Is represented. However, E is ^{-O-CO-NR 3 -,} - O-CO-O -, - O-CS
-NR ³ — or —O—CS—O—, excluding compounds in which J is a single bond and A is a hydrogen atom. ] The matrix metalloproteinase inhibitor containing the sulfonyl amino acid derivative shown by these, or those nontoxic salts as an active ingredient. 2. A compound of the general formula (I) [In the formula, R ¹ represents a hydrogen atom or a C1-4 alkyl group, and R ² represents 1) hydrogen atom, 2) C1-8 alkyl group, 3) phenyl group, or 4) phenyl group, -OCOR ¹⁶ group. (In the group, R ¹⁶ is C1 to
Represents a 4-alkyl group. ), Or C1 substituted with a CONR ¹⁷ R ¹⁸ group (in which R ¹⁷ and R ¹⁸ each independently represent a hydrogen atom or a C1-4 alkyl group).
Represent ~ 4 alkyl group, E is, 1) -CO-NR ³ - group (wherein, R ³ is a hydrogen atom, C1 to
4 alkyl group, a phenyl group, or a C1-4 alkyl group substituted with a phenyl group. ), 2) -NR ³ -CO- group (wherein R ³ has the same meaning as described above), 3) -CO-O- group, 4) -O-CO- group, 5) -NR ³ —CO—NR ³ — group (wherein R ³ has the same meaning as described above), 6) —CO—CH ₂ — group, 7) —CO— group, 8) —O—CO—NR ³ —. Group (in the group, R ³ has the same meaning as described above), 9) —NR ³ —CO—O— group (in the group, R ³ has the same meaning as described above), 10) —O—CO. —O— group, 11) —CS—NR ³ — group (in the group, R ³ has the same meaning as described above), 12) —NR ³ —CS— group (in the group, R ³ has the same meaning as described above). , 13) —NR ³ —CS—NR ³ — group (in the group, R ³ has the same meaning as described above), 14) —O—CS—NR ³ — group (in the group, R ³ Represents the same meaning as described above.), 15 (Wherein, R ³ are as defined above.) -NR ³ -CS-O- group, 16) -CS-O- group, 17) -O-CS- group or 18,) -O-CS Represents an —O— group, A is 1) a hydrogen atom, 2) a C1-8 alkyl group, 3) a C3-7 cycloalkyl group, or 4) an Ar group (wherein the Ar group is a carbocycle or a heterocyclic aryl). Represents 1 to 3 C1-15 alkyl groups, C1
To 15 alkoxy group, halogen atom, nitro group, cyano group, guanidino group, amidino group, hydroxyl group, benzyloxy group, NR ⁹ R ¹⁰ group (wherein R ⁹ and R ¹⁰ are independently a hydrogen atom or represents a C1~4 alkyl group), -.. COOR ¹¹ group (wherein, R ¹¹ is represents a hydrogen atom or a C1~4 alkyl group), a trifluoromethyl group, substituted with a phenyl group or a heterocyclic group Good. And J is 1) a single bond, 2) a C2-4 alkylene group, 3) a C2-4 alkenylene group, or (In the group, R ⁴ and R ⁵ are each independently (i)
Hydrogen atom, (ii) C1-4 alkyl group, (iii) C1
4 alkoxy group, or together with the carbon atom to which R ⁴ and R ⁵ are bonded, represents a C3-7 cycloalkyl group. And G is a 1)-(CH ₂ ) _m -group (wherein m represents 2, 3 or 4) or (In the group, R ⁶ and R ⁷ are each independently (i)
Hydrogen atom, (ii) C1-8 alkyl group, (iii) -CO
OR ⁸ group (wherein R ⁸ is a hydrogen atom, a C 1-8 alkyl group, a phenyl group, or a C 1-8 substituted with a phenyl group)
Represents a 4-alkyl group. ), (Iv) Ar group (in the group, A
r has the same meaning as described above. ), (V) heterocyclic group, (vi) -COOR ⁸ group (wherein R ⁸ has the same meaning as described above), C1-4 alkoxy group, hydroxyl group, benzyloxy group, -NR ¹² R ¹³ group. (In the group, R ¹² and R
Each ¹³ independently represents a hydrogen atom or a C1-4 alkyl group. ), —NR ¹⁴ COOR ¹⁵ group (in the group, R
¹⁴ represents a hydrogen atom or a C1~4 alkyl group, R ¹⁵
Represents a hydrogen atom, a C1-8 alkyl group, a phenyl group, or a C1-4 alkyl group substituted with a phenyl group. ), A C1-8 alkyl group substituted with an Ar group or a heterocyclic group (provided that one carbon atom of the C1-8 alkyl group may be replaced with one sulfur atom), or R ⁶ and R ⁷ together with the carbon atom bonded represent C3~7 cycloalkyl group. ) Is represented. However, E is ^{-O-CO-NR 3 -,} - O-CO-
O -, - O-CS- NR 3 - , or -O-CS-O-a and, J compound and A is a single bond is a hydrogen atom, and the following compounds: (1) N - [[ 4- (Benzoylamino) phenyl] sulfonyl] glycine, (2) N-[[3- (benzoylamino) phenyl] sulfonyl] glycine, (3) N-
[[2- (Benzoylamino) phenyl] sulfonyl]
Glycine, (4) N-[[4- (acetylamino) phenyl] sulfonyl] glycine, (5) N-[[4- (phenylacetylamino) phenyl] sulfonyl] glycine, (6) N-[[4- [(Phenylethylcarbonyl) amino] phenyl] sulfonyl] glycine, (7)
N-[[4-[(Cinnamoylamino) phenyl] sulfonyl] glycine, (8) N-[[4- (N-phenylureido) phenyl] sulfonyl] glycine, (9) N
-[[4- (N-phenylthioureido) phenyl] sulfonyl] glycine, (10) N-[[4-[(benzyloxycarbonyl) amino] phenyl] sulfonyl]
Glycine, (11) N-[[4-[(phenoxymethylcarbonyl) amino] phenyl] sulfonyl] glycine, (12) N-[[4-[(Benzyloxymethylcarbonyl) amino] phenyl] sulfonyl] glycine,
(13) N-[[4- (4-methoxybenzoylamino) phenyl] sulfonyl] glycine, (14) N-
[[4- (4-Fluorobenzoylamino) phenyl]
Sulfonyl] glycine, (15) N-[[4- (4-nitrobenzoylamino) phenyl] sulfonyl] glycine, (16) N-[[4- (3-Nitrobenzoylamino) phenyl] sulfonyl] glycine, (17) ) N-
[[4- (2-Nitrobenzoylamino) phenyl] sulfonyl] glycine, (18) N-[[4- (4-formylbenzoylamino) phenyl] sulfonyl] glycine, (19) N-[[4- (benzoyl) Amino) phenyl] sulfonyl] -D-α-phenylglycine, (2
0) N-[[4- (benzoylamino) phenyl] sulfonyl] -L-α-phenylglycine, (21) N-
[[4- (4-Methylbenzoylamino) phenyl] sulfonyl] -D-α-phenylglycine, (22) N-
[[4- (4-Methylbenzoylamino) phenyl] sulfonyl] -L-α-phenylglycine, (23) N-
[[4- (4-Methoxybenzoylamino) phenyl]
Sulfonyl] -D-α-phenylglycine, (24) N
-[[4- (4-Methoxybenzoylamino) phenyl] sulfonyl] -L-α-phenylglycine, (2
5) N-[[4- (4-fluorobenzoylamino) phenyl] sulfonyl] -D-α-phenylglycine,
(26) N-[[4- (4-Fluorobenzoylamino) phenyl] sulfonyl] -L-α-phenylglycine, (27) N-[[4- (4-Nitrobenzoylamino) phenyl] sulfonyl] -D -Α-phenylglycine, (28) N-[[4- (4-nitrobenzoylamino) phenyl] sulfonyl] -L-α-phenylglycine, (29) N-[(4-pivaloyloxyphenyl)
Sulfonyl] -D, L-α-phenylglycine, (3
0) N-[(4-pivaloyloxyphenyl) sulfonyl] -D, L-phenylalanine, (31) N-[[4
-(2,4-dichlorobenzoylamino) phenyl] sulfonyl] glycine, (32) N-[[4- (2,4-
Dichlorobenzoylamino) phenyl] sulfonyl]-
D, L-alanine, (33) N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] -β
-Alanine, (34) N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] -L-valine, (35) N-[[4- (2,4-dichlorobenzoylamino) phenyl] Sulfonyl] -D, L-valine,
(36) N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] -L-leucine, (3
7) N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] -D, L-leucine, (3
8) N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] -D, L-serine, (3
9) N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] -L-phenylalanine,
(40) N-[[4- (2,4-dichlorophenyl) phenyl] sulfonyl] -L-tyrosine, (41) N-
[[4- (2,4-Dichlorobenzoylamino) phenyl] sulfonyl] -D, L-alanine methyl ester, (42) N-[[4- (2,4-Dichlorobenzoylamino) phenyl] sulfonyl]- L-valine methyl ester, (43) N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] -D, L-
Valine methyl ester, (44) N-[[4- (2,
4-dichlorobenzoylamino) phenyl] sulfonyl] -L-leucine methyl ester, (45) N-
[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] -D, L-serine methyl ester,
(46) N-[[4- (2,4-Dichlorobenzoylamino) phenyl] sulfonyl] -L-tyrosine methyl ester, (47) N-[[4- (3-Nitrobenzoylamino) phenyl] sulfonyl] -L-aspartic acid, (48) N-[[3- (3-nitrobenzoylamino) phenyl] sulfonyl] -L-aspartic acid,
(49) N-[[4- (3-aminobenzoylamino)
Phenyl] sulfonyl] -L-aspartic acid, (5
0) N-[[3- (3-aminobenzoylamino) phenyl] sulfonyl] -L-aspartic acid, (51) N
-[[4- (benzoylamino) phenyl] sulfonyl] -L-glutamic acid, (52) N-[[4-
[[(4-chlorobenzoylamino) phenyl] sulfonyl] -L-glutamic acid, (53) N-[[4-
[[(4-Nitrobenzoylamino) phenyl] sulfonyl] -L-glutamic acid, (54) N-[[4- [2
-[4- (1-Pyrozinyl) phenyl] butyryloxy] phenyl] sulfonyl] -D, L-3-morpholinoalanine ethyl ester, (55) N-[[4- [2
-(4-Nitrophenyl) butyryloxy] phenyl]
Sulfonyl] -D, L-3-morpholinoalanine ethyl ester, (56) N-[[4- (2-methoxy-2
-Phenylacetyloxy) phenyl] sulfonyl]-
D, L-3-morpholinoalanine ethyl ester,
(57) N-[[4-[[1- (4-Nitrophenyl) cyclobutyl] carbonyl] oxy] phenyl] sulfonyl] -D, L-3-morpholinoalanine ethyl ester, (58) N-[[ 3-methyl-4- [2-
[4- (1-Pyrrolidinyl) phenyl] butyryloxy] phenyl] sulfonyl] -t-butoxycarbonyl-L-lysine, (59) N-[[4- (2-phenylbutyryloxy) phenyl] sulfonyl] glycine, ( 6
0) N-[[4- [2- [4- (1-pyrrolidinyl) phenyl] butyryloxy] phenyl] sulfonyl]-
D, L-phenylalanine, (61) N-[[4- [2
-[4- (1-Pyrrolidinyl) phenyl] butyryloxy] phenyl] sulfonyl] -D, L-aspartic acid, (62) N-[[4-[[1- (4-nitrophenyl) cyclobutyl] carbonyl] oxy ] Phenyl]
Sulfonyl] -D, L-aspartic acid, (63) 1-
[[4- [2- [4- (1-pyrrolidinyl) phenyl]]
Butyryloxy] phenyl] sulfonylamido-1-cyclopropanecarboxylic acid, (64) N-[[4- [2-
[4- (1-Pyrrolidinyl) phenyl] butyryloxy] phenyl] sulfonyl] -D, L-2- (2-furanyl) glycine, (65) N-[[4- [2- [4-
(1-Pyrrolidinyl) phenyl] butyryloxy] phenyl] sulfonyl] -D, L-2- (2-thienyl) glycine, (66) N-[[4- [2- [4- (1-pyrrolidinyl) phenyl] butyryloxy. ] Phenyl] sulfonyl] -L-valine, (67) N-[[4- [2-
[4- (1-Pyrrolidinyl) phenyl] butyryloxy] phenyl] sulfonyl] -S-carboxymethyl-
L-cysteine, (68) N-[[4- [2-ethyl-
2- (4-methoxyphenyl) butyryloxy] phenyl] sulfonyl] glycine, (69) N-[[3-methyl-4- [2- [4- (1-pyrrolidinyl) phenyl]]
Butyryloxy] phenyl] sulfonyl] -L-lysine, (70) 5- [N-[[3-methyl-4- [2-
Excludes [4- (1-pyrrolidinyl) phenyl] butyryloxy] phenyl] sulfonyl] amino] pentanoic acid, and (71) N-[(3-methyl-4-pivaloyloxyphenyl) sulfonyl] -β-alanine. ] The novel sulfonyl amino acid derivative shown by these, or those nontoxic salts. 3. E is —CO—NR ³ —, —NR ³ —CO
^{-, - NR 3 -CO-NR} 3 -, - O-CO-NR 3 -,
^{-NR 3 -CO-O -, -} CS-NR 3 -, - NR 3 -C
^{S -, - NR 3 -CS-} NR 3 -, - O-CS-NR
The compound according to claim 2, which is ^3- , -NR ³ -CS-O- (wherein R ³ has the same meaning as described in claim 2). 4. E is —CO—O—, —O—CO—, —
_{CO-CH 2 -, - CO} -, - O-CO-O -, - CS
The compound according to claim 2, which is -O-, -O-CS-, or -O-CS-O-. 5. The compound is N-[[4- (p-toluoylamino) phenyl] sulfonyl] glycine, N-
[[4- (isobutyrylamino) phenyl] sulfonyl] glycine, N-[[4- (acetylamino) phenyl] sulfonyl] glycine, N-[[4- (o-toluoylamino) phenyl] sulfonyl] glycine , N-
[[4- (m-Toluoylamino) phenyl] sulfonyl] glycine, N-[[4- (2-chlorobenzoylamino) phenyl] sulfonyl] glycine, N-[[4-
(3-Chlorobenzoylamino) phenyl] sulfonyl] glycine, N-[[4- (4-chlorobenzoylamino) phenyl] sulfonyl] glycine, N-[[4-
(2-Methoxybenzoylamino) phenyl] sulfonyl] glycine, N-[[4- (3-methoxybenzoylamino) phenyl] sulfonyl] glycine, N-[[4
-(4-Ethylbenzoylamino) phenyl] sulfonyl] glycine, N-[[4- (4-Propylbenzoylamino) phenyl] sulfonyl] glycine, N-[[4
-(2-Fluorobenzoylamino) phenyl] sulfonyl] glycine, N-[[4- (3-Fluorobenzoylamino) phenyl] sulfonyl] glycine, N-
[[4- (Cyclohexylcarbonylamino) phenyl] sulfonyl] glycine, N-[[4- (4-trifluoromethylbenzoylamino) phenyl] sulfonyl] glycine, N-[[4- (2-thienylcarbonylamino) phenyl] ] Sulfonyl] glycine, N-[[4
-(2-furylcarbonylamino) phenyl] sulfonyl] glycine, N-[[4- (2-pyridylcarbonylamino) phenyl] sulfonyl] glycine, N-[[4
-(3-Pyridylcarbonylamino) phenyl] sulfonyl] glycine, N-[[4- (4-pyridylcarbonylamino) phenyl] sulfonyl] glycine, N-
[[4- (3-thienylcarbonylamino) phenyl]
Sulfonyl] glycine, N-[[4- (3-furylcarbonylamino) phenyl] sulfonyl] glycine, N-
[[4- (4-methoxycarbonylbenzoylamino)
Phenyl] sulfonyl] glycine, N-[[4- (4-
Cyanobenzoylamino) phenyl] sulfonyl] glycine, N-[[4- (4-benzyloxybenzoylamino) phenyl] sulfonyl] glycine, N-[[4-
(4-Carboxybenzoylamino) phenyl] sulfonyl] glycine, N-[[4- (4-butylbenzoylamino) phenyl] sulfonyl] glycine, N-[[4
-(4-Pentylbenzoylamino) phenyl] sulfonyl] glycine, N-[[4- (4-phenylbenzoylamino) phenyl] sulfonyl] glycine, N-
[[4- (Benzoylamino) phenyl] sulfonyl]
-L-valine, N-[[4- (1-naphthoylamino)
Phenyl] sulfonyl] glycine, N-[[4- (2-
Naphthoylamino) phenyl] sulfonyl] glycine,
N-[[4- (3-benzyloxybenzoylamino)
Phenyl] sulfonyl] glycine, N-[[4- (2-
Benzyloxybenzoylamino) phenyl] sulfonyl] glycine, N-[[4- (benzoylamino) phenyl] sulfonyl] -L-aspartic acid, N-[[4
-(Benzoylamino) phenyl] sulfonyl] -L-
Leucine, N-[[4- (benzoylamino) phenyl] sulfonyl] -D-leucine, N-[[4- (phenoxycarbonylamino) phenyl] sulfonyl] glycine, N-[[4- (4-Dimethylaminobenzoyl) Amino) phenyl] sulfonyl] glycine, N-[[4-
(Benzoylamino) phenyl] sulfonyl] -D-valine, N-[[4- (benzoylamino) phenyl] sulfonyl] -L-phenylalanine, N-[[4- (benzoylamino) phenyl] sulfonyl] -D-phenylalanine , N-[[4- (Benzoylamino) phenyl] sulfonyl] -L-alanine, N-[[4- (Benzoylamino) phenyl] sulfonyl] -D-alanine, N-[[4- (Benzoylamino) phenyl] ] Sulfonyl] -L-lysine, N-[[4- (benzoylamino) phenyl] sulfonyl] -D-lysine, N-[[4
-(Benzoylamino) phenyl] sulfonyl] -D-
Glutamic acid, N-[[4- (4-dodecylbenzoylamino) phenyl] sulfonyl] glycine, 4- [N-
[[4- (Benzoylamino) phenyl] sulfonyl]
Amino] butanoic acid, N-[[4- (benzoylamino)
Phenyl] sulfonyl] -L-serine, N-[[4-
(Benzoylamino) phenyl] sulfonyl] -D-serine, N-[[4- (benzoylamino) phenyl] sulfonyl] -D-aspartic acid, N-[[4- (p-
Toluoylamino) phenyl] sulfonyl] -D-phenylalanine, N-[[4- (4-pentylbenzoylamino) phenyl] sulfonyl] -D-phenylalanine, N-[[4- (p-toluoylamino) phenyl]
Sulfonyl] -L-valine, N-[[4- (4-hexylbenzoylamino) phenyl] sulfonyl] glycine, N-[[4- (4-heptylbenzoylamino) phenyl] sulfonyl] glycine, N-[[4 -(4-Isopropylbenzoylamino) phenyl] sulfonyl]
Glycine, N-[[4- (4-isobutylbenzoylamino) phenyl] sulfonyl] glycine, N-[[4-
(Benzoylamino) phenyl] sulfonyl] -2,2
-Dimethylglycine, N-[[4- (p-toluoylamino) phenyl] sulfonyl] -D-serine, N-
[[4- (p-Toluoylamino) phenyl] sulfonyl] -L-leucine, N-[[4- (p-Toluoylamino) phenyl] sulfonyl] -D-alanine, N-
[[4- (p-Toluoylamino) phenyl] sulfonyl] -D-valine, N-[[4- (p-Toluoylamino) phenyl] sulfonyl] -D-leucine, N-
[[2-Methyl-4- (p-toluoylamino) phenyl] sulfonyl] glycine, N-[[3-Methyl-4-]
(P-Toluoylamino) phenyl] sulfonyl] glycine, N-[[4- (2-hydroxy-4-methylbenzoylamino) phenyl] sulfonyl] -D-alanine, N-[[4- (2-thienylcarbonyl) Amino) phenyl] sulfonyl] -D-alanine, N-[[3-
(Benzoylamino) phenyl] sulfonyl] glycine, N-[[2- (benzoylamino) phenyl] sulfonyl] glycine, N-[[4- (2-aminobenzoylamino) phenyl] sulfonyl] glycine, N-
[[4- (3-Aminobenzoylamino) phenyl] sulfonyl] glycine, N-[[4- (4-aminobenzoylamino) phenyl] sulfonyl] glycine, N-
[[4- (4-Hydroxybenzoylamino) phenyl] sulfonyl] glycine, N-[[4-[(2-phenylethyl) carbonylamino] phenyl] sulfonyl] glycine, N-[[4- (3-hydroxybenzoyl) Amino) phenyl] sulfonyl] glycine, N-
[[4- (2-Hydroxybenzoylamino) phenyl] sulfonyl] glycine, N-[[4- (Benzoylamino) phenyl] sulfonyl] -L-tryptophan, N-[[4- (Benzoylamino) phenyl] sulfonyl] -L-tyrosine, N-[[4- (benzoylamino) phenyl] sulfonyl] -D-tryptophan,
N-[[4- (benzoylamino) phenyl] sulfonyl] -D-tyrosine, N-[[4- (benzoylamino) phenyl] sulfonyl] -D-histidine, 2-
[N- [4- (benzoylamino) phenyl] sulfonylamino]-(3-pyridyl) -D-alanine, N-
[[4- (p-Toluoylamino) phenyl] sulfonyl] -D-tryptophan, N-[[4- (N-phenylcarbamoylphenyl) sulfonyl] glycine, N-
[[4- [N- (4-amidinophenyl) carbamoyl] phenyl] sulfonyl] -L-glutamic acid, N-
[[4- [N- (4-amidinophenyl) carbamoyl] phenyl] sulfonyl] -L-aspartic acid, N
-[[3- [N- (4-amidinophenyl) carbamoyl] phenyl] sulfonyl] -L-aspartic acid, N
-[[3- [N- (4-amidinophenyl) carbamoyl] phenyl] sulfonyl] -L-glutamic acid, N-
The compound according to claim 2, which is [[4- (N-methyl-N-benzoylamino) phenyl] sulfonyl] glycine, and an ester thereof and / or a non-toxic salt thereof. 6. The compound is N-[[4- (benzyloxycarbonyloxy) phenyl] sulfonyl] glycine, N-[[4- (benzoyloxy) phenyl] sulfonyl] glycine, N-[[4- (4 -Amidinobenzoyloxy) phenyl] sulfonyl] glycine, N-
[[4- (4-guanidinobenzoyloxy) phenyl] sulfonyl] glycine, N-[[4- (4-amidinobenzoyloxy) phenyl] sulfonyl] -L-phenylalanine, N-[[4- (benzoyloxy) phenyl ] Sulfonyl] -β-alanine, N-[[4-
(4-Amidinobenzoyloxy) phenyl] sulfonyl] -β-alanine, N-[[4- (phenoxycarbonyl) phenyl] sulfonyl] glycine, N-[[4-
(4-Amidinophenoxycarbonyl) phenyl] sulfonyl] -L-phenylalanine, N-[[4- (4-
Amidinophenoxycarbonyl) phenyl] sulfonyl] -L-aspartic acid, N-[[3- (4-amidinophenoxycarbonyl) phenyl] sulfonyl] glycine, N-[[4- (4-amidinophenoxycarbonyl) phenyl] sulfonyl] Glycine, N-[(4-methoxycarbonylphenyl) sulfonyl] glycine, N
-[(4-Carboxyphenyl) sulfonyl] glycine, N-[[4-[(4-amidinophenoxy) carbonyl] phenyl] sulfonyl] -β-alanine, N-
The compound according to claim 2, which is [(4-benzoylmethylphenyl) sulfonyl] glycine, N- [4-[(4-methoxybenzoyl) methyl] sulfonyl] glycine, or an ester thereof and / or a non-toxic salt thereof. . 7. The compound is N-[[4- (benzoylamino) phenyl] sulfonyl] glycine, N-[[3-
(Benzoylamino) phenyl] sulfonyl] glycine, N-[[2- (benzoylamino) phenyl] sulfonyl] glycine, N-[[4- (acetylamino) phenyl] sulfonyl] glycine, N-[[4- (phenyl Acetylamino) phenyl] sulfonyl] glycine,
N-[[4-[(phenylethylcarbonyl) amino]
Phenyl] sulfonyl] glycine, N-[[4- (cinnamoylamino) phenyl] sulfonyl] glycine, N
-[[4- (N-phenylureido) phenyl] sulfonyl] glycine, N-[[4- (N-phenylthioureido) phenyl] sulfonyl] glycine, N-[[4-
[(Benzyloxycarbonyl) amino] phenyl] sulfonyl] glycine, N-[[4-[(phenoxymethylcarbonyl) amino] phenyl] sulfonyl] glycine, N-[[4-[(benzyloxymethylcarbonyl) amino] phenyl ] Sulfonyl] glycine, N-
[[4- (4-Methoxybenzoylamino) phenyl]
Sulfonyl] glycine, N-[[4- (4-fluorobenzoylamino) phenyl] sulfonyl] glycine, N
-[[4- (4-Nitrobenzoylamino) phenyl]
Sulfonyl] glycine, N-[[4- (3-nitrobenzoylamino) phenyl] sulfonyl] glycine, N-
[[4- (2-Nitrobenzoylamino) phenyl] sulfonyl] glycine, N-[[4- (4-Formylbenzoylamino) phenyl] sulfonyl] glycine, N-
[[4- (Benzoylamino) phenyl] sulfonyl]
-D-α-phenylglycine, N-[[4- (benzoylamino) phenyl] sulfonyl] -L-α-phenylglycine, N-[[4- (4-methylbenzoylamino) phenyl] sulfonyl] -D- α-phenylglycine, N-[[4- (4-methylbenzoylamino) phenyl] sulfonyl] -L-α-phenylglycine, N-
[[4- (4-Methoxybenzoylamino) phenyl]
Sulfonyl] -D-α-phenylglycine, N-[[4
-(4-Methoxybenzoylamino) phenyl] sulfonyl] -L-α-phenylglycine, N-[[4- (4
-Fluorobenzoylamino) phenyl] sulfonyl]
-D-α-phenylglycine, N-[[4- (4-fluorobenzoylamino) phenyl] sulfonyl] -L-
α-phenylglycine, N-[[4- (4-nitrobenzoylamino) phenyl] sulfonyl] -D-α-phenylglycine, N-[[4- (4-nitrobenzoylamino) phenyl] sulfonyl] -L- α-phenylglycine, N-[(4-pivaloyloxyphenyl) sulfonyl] -D, L-α-phenylglycine, N-[(4-
Pivaloyloxyphenyl) sulfonyl] -D, L-phenylalanine, N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] glycine, N-
[[4- (2,4-Dichlorobenzoylamino) phenyl] sulfonyl] -D, L-alanine, N-[[4-
(2,4-Dichlorobenzoylamino) phenyl] sulfonyl] -β-alanine, N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] -L-
Valine, N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] -D, L-valine, N-
[[4- (2,4-Dichlorobenzoylamino) phenyl] sulfonyl] -L-leucine, N-[[4- (2,
4-dichlorobenzoylamino) phenyl] sulfonyl] -D, L-leucine, N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] -D,
L-serine, N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] -L-phenylalanine, N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] -L- Tyrosine, N-
[[4- (2,4-Dichlorobenzoylamino) phenyl] sulfonyl] -D, L-alanine methyl ester, N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] -L-valine -Methyl ester, N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] -D, L-valine methyl ester, N-[[4- (2,4-dichlorobenzoylamino) phenyl] Sulfonyl] -L-leucine methyl ester, N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] -D, L-serine.
Methyl ester, N-[[4- (2,4-dichlorobenzoylamino) phenyl] sulfonyl] -L-tyrosine methyl ester, N-[[4- (3-Nitrobenzoylamino) phenyl] sulfonyl] -L- Aspartic acid, N-[[3- (3-nitrobenzoylamino) phenyl] sulfonyl] -L-aspartic acid, N-[[4
-(3-Aminobenzoylamino) phenyl] sulfonyl] -L-aspartic acid, N-[[3- (3-aminobenzoylamino) phenyl] sulfonyl] -L-aspartic acid, N-[[4- (benzoylamino) ) Phenyl] sulfonyl] -L-glutamic acid, N-[[4-
[[(4-chlorobenzoylamino) phenyl] sulfonyl] -L-glutamic acid, N-[[4-[[(4-nitrobenzoylamino) phenyl] sulfonyl] -L-
Glutamic acid, N-[[4- [2- [4- (1-pyridinyl) phenyl] butyryloxy] phenyl] sulfonyl] -D, L-3-morpholinoalanine ethyl ester, N-[[4- [2- ( 4-Nitrophenyl) butyryloxy] phenyl] sulfonyl] -D, L-3-morpholinoalanine ethyl ester, N-[[4- (2-
Methoxy-2-phenylacetyloxy) phenyl] sulfonyl] -D, L-3-morpholinoalanine ethyl ester, N-[[4-[[[1- (4-nitrophenyl) cyclobutyl] carbonyl] oxy] phenyl] Sulfonyl] -D, L-3-morpholinoalanine ethyl ester, N-[[3-methyl-4- [2- [4- (1
-Pyrrolidinyl) phenyl] butyryloxy] phenyl] sulfonyl] -t-butoxycarbonyl-L-lysine, N-[[4- (2-phenylbutyryloxy) phenyl] sulfonyl] glycine, N-[[4- [2- [2- [4
-(1-Pyrrolidinyl) phenyl] butyryloxy] phenyl] sulfonyl] -D, L-phenylalanine, N
-[[4- [2- [4- (1-Pyrrolidinyl) phenyl] butyryloxy] phenyl] sulfonyl] -D, L
-Aspartic acid, N-[[4-[[[1- (4-nitrophenyl) cyclobutyl] carbonyl] oxy] phenyl] sulfonyl] -D, L-aspartic acid, 1-
[[4- [2- [4- (1-pyrrolidinyl) phenyl]]
Butyryloxy] phenyl] sulfonylamide] -1-
Cyclopropanecarboxylic acid, N-[[4- [2- [4-
(1-Pyrrolidinyl) phenyl] butyryloxy] phenyl] sulfonyl] -D, L-2- (2-furanyl) glycine, N-[[4- [2- [4- (1-pyrrolidinyl) phenyl] butyryloxy] phenyl] Sulfonyl] -D, L-2- (2-thienyl) glycine, N-
[[4- [2- [4- (1-pyrrolidinyl) phenyl]]
Butyryloxy] phenyl] sulfonyl] -L-valine, N-[[4- [2- [4- (1-pyrrolidinyl) phenyl] butyryloxy] phenyl] sulfonyl] -S
-Carboxymethyl-L-cysteine, N-[[4-
[2-Ethyl-2- (4-methoxyphenyl) butyryloxy] phenyl] sulfonyl] glycine, N-[[3
-Methyl-4- [2- [4- (1-pyrrolidinyl) phenyl] butyryloxy] phenyl] sulfonyl] -L-
Lysine, 5- [N-[[3-methyl-4- [2- [4-
(1-pyrrolidinyl) phenyl] butyryloxy] phenyl] sulfonyl] amino] pentanoic acid, and N-
The compound according to claim 2, which is [(3-methyl-4-pivaloyloxyphenyl) sulfonyl] -β-alanine, and an ester thereof and / or a non-toxic salt thereof.