Double Headed Protease Inhibitor

Specification Title of invention: Double-headed inhibitor of proteolytic enzyme Technical field

[0001] The present invention relates to a novel double-headed compound having proteolytic enzyme inhibitory activity, which is useful as a medicine, and a pharmaceutical composition containing the same, particularly for diseases in which symptoms are improved by enteropeptidase inhibition and/or trypsin inhibition. The present invention relates to a novel compound, a pharmaceutical composition containing the same, and a method for producing the same for prevention, alleviation and/or treatment. Background technology

[0002] Proteins derived from diet are decomposed by digestive enzymes and finally converted into amino acids or peptides and absorbed into the body. Its major proteolytic enzyme is trypsin. Enteropeptidase is a serine protease that is secreted by duodenal mucosal cells and converts trypsinogen secreted by the pancreas by diet into trypsin. It is also known that trypsin acts on protease precursors such as chymotrypsinogen, procarboxypeptidase, proelastase, and procolipase to activate various enzymes. Therefore, a compound that inhibits enteropeptidase and/or trypsin is expected to have an action of suppressing protein degradation and absorption, an action of suppressing lipid absorption, and an action of reducing carbohydrate digestive ability, and It is considered to be useful as an antidiabetic drug or an antidiabetic drug.

[0003] Patent Document 1 describes that a compound that inhibits both enteropeptidase and trypsin exhibits an antiobesity effect. Patent Document 2 reports that compounds having an inhibitory activity such as enteropeptidase, trypsin, plasmin, and kallikrein have an antiobesity effect. Patent Document 3 reports that administration of an enteropeptidase inhibitor has an antiobesity effect and an effect of improving type 2 diabetes. As a compound having trypsin inhibitory activity and useful for the prevention, alleviation and/or treatment of pancreatitis and reflux esophagitis, Patent Document 4 discloses camostat mesylate of the following formula, and chronic pancreatitis and It is used to treat reflux esophagitis.

Chemical 1

[0004] As a compound having trypsin inhibitory activity and useful for the prevention, alleviation and/or treatment of renal diseases and diseases involving trypsin, Patent Documents 5 and 6 disclose guanidinobenzoic acid compounds. There is no disclosure of the double-headed compound of. As a compound having enteropeptidase inhibitory activity and useful for the prevention, alleviation and/or treatment of obesity and diseases associated with abnormal fat metabolism, Patent Document 2 discloses a boron peptide. There is no disclosure of type compounds. As a compound having serine protease inhibitory activity, particularly enteropeptidase and trypsin inhibitory activity and useful for prevention, alleviation and/or treatment of obesity, diabetes and the like, Patent Documents 7 to 9 describe heteroarylcarboxylic acid esters. Although derivatives are disclosed, there is no disclosure of the double-headed compounds of the present invention. As a compound having enteropeptidase inhibitory activity and useful for prevention, alleviation and/or treatment of obesity, diabetes and the like, Patent Documents 3 and 10 to 12 disclose heterocyclic compounds. There is no disclosure of a double-headed compound of the invention. Prior art documents Patent literature

[0005] Patent Document 1: WO 2006/050999 Publication Patent Document 2: WO 2009/071601 Patent Publication Patent Document 3: WO 2015/122187 Patent Publication Patent Document 4: JP 52-089640 JP Patent Literature 5: International Publication No. 2013/039187 gazette Patent Document 6: International Publication No. 2014/142219 gazette Patent Document 7: International Publication No. 2011/071048 gazette Patent Document 8: International Publication No. 2012/169579 gazette Patent Document 9: International publication 2013/187533 gazette Patent documents 10: International publication 2015/122188 gazette Patent documents 11: International publication 2016/104630 gazette Patent documents 12: International publication 2016/158788 gazette Summary of the invention Problems to be Solved by the Invention

[0006] The present invention provides a novel double-headed compound useful for the prevention, alleviation and/or treatment of a disease whose symptoms are ameliorated by enteropeptidase inhibition and/or trypsin inhibition, a pharmaceutical composition containing the same, and a method for producing the same. .. Means for solving the problem

[0007] The inventors of the present invention have conducted earnest studies on compounds having enteropeptidase inhibitory activity and/or trypsin inhibitory activity and having very low blood exposure after oral administration, and as a result, enteropeptidase inhibitory activity and trypsin were found. A double-headed compound or a pharmaceutically acceptable salt thereof, in which two inhibitor molecules having at least one activity selected from inhibitory activities are linked by a single bond or a suitable spacer, has excellent enteropeptidase inhibitory activity and/or Or has trypsin inhibitory activity, strongly inhibits enteropeptidase and/or trypsin in the intestinal tract after oral administration, and has very low exposure to blood, and the symptoms are improved by enteropeptidase inhibition and/or trypsin inhibition The present invention has been completed by finding that it is useful for prevention, alleviation and/or treatment of diseases, particularly prevention, alleviation and/or treatment of obesity.

[0008] The present invention provides the following [1] to [29].

[1] The following general formula (I): [Chemical

Formula 2] [In the formula, A 1 and A 2 are each independently an inhibitor having at least one activity selected from enteropeptidase inhibitory activity and trypsin inhibitory activity. Is a residue; Z is a spacer connecting A 1 and A 2 , or a pharmaceutically acceptable salt thereof.

[2] A 1 and A 2 are each independently an inhibitor molecule selected from the following inhibitor molecule groups:

Chemical Formula 3

Chemical Formula 4

Chemical Formula 5

[Chemical

Formula 6] , or the following general formula (II) [Chemical

Formula 7] [ wherein , ring B and ring C are each independently an aryl group or a heteroaryl group; Each R 1 is independently a hydrogen atom or —COO—(C 1 -C 4 alkyl group); W is a single bond or a C 1 -C 4 alkylene group; X is — C(=O)-, -OC(=O)-, or -NG-SO 2 -; G is a hydrogen atom, a C 1 -C 4 alkyl group, or -COOR 2 ; R 2 is A C 1 -C 4 alkyl group which may be substituted with 1 to 5 aryl groups ; Y represents —NG 2 G 4 , —NG 2 —L 1 —COOH, —NG 2-L 1 -C (= O) -NH 2 , -NG 2 -L 1 -C (= O) -NG 3 -L 2 -COOH, -NG 2 -L 1 -C (= O) -NG 3 - L 2 -C(=O)-NG 3 -L 2 -COOH, -NG 2 -L 1 -C(=O)-NG 3 -L 2 -C(=O)-NH 2 , -NG 2 -L 3 --OH, or --NG 2 --(CH 2 --CH 2—O) q —CH 2 —CH 2 —COOH; q is an integer of 1 to 6; G 2 and G 3 are each independently a hydrogen atom or 1 to 5 —COOR 3 an optionally substituted phenyl group and -COOR in group 3 1-5 may be substituted with a substituent C is independently selected from the group consisting of group 1 -C 6 is an alkyl group; G 4 is a hydrogen atom, a C 1 -C 4 alkyl group, or a C 1 -C 4 alkoxy-C 1 -C 4 alkyl group; R 3Are each independently a hydrogen atom, or a C 1 -C 4 alkyl group optionally substituted with 1 to 5 aryl groups ; L 1 and L 2 are each independently 1 to 5 Independently from the group consisting of C 1 -C 6 alkylene groups optionally substituted with 1-5 C 1 -C 6 alkyl groups optionally substituted with 4 —COOR 4 groups , hydroxy groups and carboxy groups C 1 -C 6 alkylene group, C 1 -C 4 alkylene-phenylene group, or phenylene substituted with a C 7 -C 12 aralkyl group optionally substituted with 1 to 5 substituents selected from Is a -C 1 -C 4 alkylene group; L 3 is a C 1 -C 4 alkylene-phenylene group in which the phenylene moiety may be substituted with 1 to 3 —COOR 4 groups ; R 4's are each independently a hydrogen atom, or an aryl group; A C 1 -C 4 alkyl group which may be substituted with 1 to 5 substituents independently selected from the group consisting of trimethylsilyl groups ; R 5 and R 6 are each independently a hydrogen atom. , A halogen atom, a C 1 -C 4 alkyl group, a C 1 -C 4 alkoxy group, a carboxy group, or —C(═O)-NG 2 G 4 ; and s and t are each independently 1 to An integer of 4; multiple R 5 and/or multiple R 5

6 may be the same or different; or any one of R 5 and any one of R 6 may be bonded to each other to form a C 1 -C 4 alkyleneoxy group. may also be] indicates inhibitor residue formed by removing any one hydrogen atom or a hydroxyl group from the inhibitor molecule represented by; Z is a single bond, arylene, heteroarylene, or C 2 -C 30 alkylene group ( However, one or more methylene groups in the chain of the alkylene group are —C(═O)—, —NR 7 —, —O— , —SiR 8 R 9 —, —SO r —, arylene, and hetero. R 7 may be replaced by a group independently selected from the group consisting of arylene, R 7 is a hydrogen atom, or a C 1 -C 4 alkyl group, and R 8 and R 9Are each independently a C 1 -C 4 alkyl group, and r is an integer of 0 to 2), or a pharmaceutically acceptable salt thereof.

[3] In [2], A 1 and A 2 each independently represent an inhibitor residue obtained by removing any one hydrogen atom or hydroxy group from the inhibitor molecule represented by the general formula (II) . The described compound or a pharmaceutically acceptable salt thereof.

[4] A 1 is Formula 8]

or

Formula 9

has a structure represented by: A 2 is Formula 10]

or

formula 11

has a structure represented by: wherein the ring B 1 , ring B 2 , ring C 1 and ring C 2 are each independently an aryl group; each R 1 is independently a hydrogen atom or —COO—(C 1 -C 4 alkyl group); W 1 and W 2 is each independently a single bond or a C 1 -C 4 alkylene group; X 1 is —C(═O)—, —O—C(═O)—, or —NG 11 — SO 2 −; X 1′ is —NG Z —SO 2 —; X 2 is —C(═O)—, —C(═O)—O—, or —SO 2 —NG 12-, and; X 2 ' is -SO 2 -NG Z -, and; G 11 and G 12 are each independently a hydrogen atom, C 1 -C 4 alkyl group, or -COOR 2 be; G Z is a single bond connecting X 1′ or X 2′ and Z; R 2 is a C 1 -C 4 alkyl group optionally substituted with 1 to 5 aryl groups ; Y 1 is, -NG 21 -, - NG 21 -L 11-C(=O)-, -NG 21 -L 11 -C(=O)-NH-, -NG 21 -L 11 -C(=O)-NG 31 -L 21 -C(=O)-, -NG 21 -L 11 -C (= O) -NG 31 -L 21 -C (= O) -NH -, - NG 21 -L 3 -O-, or -NG 21 -G 4 ' - a and; Y 1′ is —NG 21 H, —NG 21 —L 11 —COOH, or —NG 21 —L 11 —C(═O)—NG 31 -L 21 -COOH; Y 2 is -NG 22 -, -C(=O)-L 12 -NG 22 -, -NH -C(=O)-L 12 -NG 22 -, -C. (=O)-L 22 -NG 32 -C(=O)-L 12 -NG 22 -, -NH -C(=O)-L 22 -NG 32 -C(=O)-L 12 -NG 22 —, —OL 3 —NG 22 —, or —G 4′ —NG 22 —; Y 2′Is HNG 22 −, HOOC-L 12 —NG 22 —, or HOOC-L 22 —NG 32 —C(═O)—L 12 —NG 22 —; G 21 , G 31 , G 22 and G 32 are each independently a hydrogen atom, or 1 to 5 independently selected from the group consisting of a phenyl group optionally substituted with 1 to 5 —COOR 3 groups and a —COOR 3 group; A C 1 -C 6 alkyl group which may be substituted with a substituent ; G 4′ represents a C 1 -C 4 alkylene group, or C 1A C 1 -C 4 alkyleneoxy-C 1 -C 4 alkylene group; R 3's each independently represent a hydrogen atom or a C 1 -C 4 alkyl group optionally substituted with 1 to 5 aryl groups; in it; L 11 , L 21 , L 12 , and L 22 are each independently 1-5 -COOR 4 in groups may be substituted one to five C 1 -C 6 alkyl group A C 1 -C 6 alkylene group which may be substituted with , a C 1 -C 4 alkylene-phenylene group, or a phenylene-C 1 -C 4An alkylene group; L 3 is a C 1 -C 4 alkylene-phenylene group in which the phenylene moiety may be substituted with 1 to 3 —COOR 4 groups ; R 4 is independently hydrogen. An atom or a C 1 -C 4 alkyl group optionally substituted with 1 to 5 substituents independently selected from the group consisting of an aryl group and a trimethylsilyl group ; R 5 and R 6 are each independently, a hydrogen atom, a halogen atom, C 1 -C 4 alkyl group, or a C 1 -C 4 alkoxy groups; s and t are each independently an integer of from 1 to 4; a plurality of R 5 and/or a plurality of R 6

May be the same or different; or any one of R 5 and any one of R 6 may be bonded to each other to form a C 1 -C 4 alkyleneoxy group. Well; the symbol

Chemical formula 12

represents a point of attachment to Z ] Z is a single bond, arylene, heteroarylene, or a C 2 -C 30 alkylene group (provided that one or more methylenes in the chain of the alkylene group are present. The group may be replaced with a group independently selected from the group consisting of —C(═O)—, —NR 7 —, —O—, arylene, and heteroarylene, and R 7 is a hydrogen atom, or The compound or a pharmaceutically acceptable salt thereof according to any one of [2] to [3], which is a C 1 -C 4 alkyl group) .

[5] A 1 is

Chemical 13

Or

Formula 14

has a structure represented by: A 2 is Formula 15]

or

formula 16

has a structure represented by: Z is a single bond, C 6 -C 12 arylene, - ( CH 2 -CH 2 -O) m -CH 2 -CH 2 -, - (CH 2 -O-CH 2 ) m -, - (CH 2 ) m - (C 6 -C 12 arylene) - (CH 2 ) m-Or -(CH 2 ) n- ; m is an integer of 1 to 6; and n is an integer of 2 to 12, the compound or a pharmaceutically acceptable salt thereof.

[6] A 1 is Formula 17]

or

formula 18

has a structure represented by: A 2 is Formula 19]

or

Formula 20

has a structure represented by [4] - [5] A compound or a pharmaceutically acceptable salt thereof according to any one of 1.

[7] A 1 has a structure represented by

Chemical formula 21

: A 2 is

Chemical formula 22

The compound or a pharmaceutically acceptable salt thereof according to any one of [4] to [6], which has a structure represented by:

[8] The compound of any one of [4] to [7] represented by the following general formula (III):

Chemical formula 23

or the following general formula (IV):

Chemical formula 24

, or a pharmaceutical thereof. Top acceptable salt.

[9] Each R 1 is independently a hydrogen atom or a tert-butoxycarbonyl group; W 1 and W 2 are each independently a single bond or a C 1 -C 4 alkylene group. ; X 1 is, -C (= O) -, - O-C (= O) -, or -NG 11 -SO 2 - and is, X 1 ' is, -NG Z -SO 2 - and is; X 2 is —C(═O)—, —C(═O)—O—, or —SO 2 —NG 12 —; X 2′ is —SO 2 —NG Z —; G 11 And G 12 are each independently a hydrogen atom, a C 1 -C 4 alkyl group, or —COOR 2 ; G Z is a single bond connecting X 1′ or X 2′ and Z; R 2 is a C 1 -C 4 alkyl group optionally substituted with 1 to 5 aryl groups ; Y 1But, -NG 21 -, - NG 21 -L 11 -C (= O) -, - NG 21 -L 11 -C (= O) -NH -, - NG 21 -L 11 -C (= O) - NG 31 -L 21 -C(=O)-, -NG 21 -L 11 -C(=O)-NG 31 -L 21 -C(=O)-NH-, -NG 21 -L 3 -O- or -NG 21 -G 4 ' - a and; Y 1' is, -NG 21 H, -NG 21 -L 11-COOH or -NG 21 -L 11 -C(=O)-NG 31 -L 21 -COOH; Y 2 is -NG 22 -, -C(=O)-L 12 -NG 22 -, -NH-C(=O)-L 12 -NG 22 -, -C(=O)-L 22 -NG 32 -C(=O)-L 12 -NG 22 -, -NH-C (=O) -L 22 -NG 32 -C(=O) -L 12 -NG 22 -, -O -L 3 -NG 22 -, or -G 4′ —NG 22 — and Y 2′ is HNG 22 —, HOOC-L 12 —NG 22 —, or HOOC-L 22 —NG 32 —C(═O)—L 12 —NG 22 — ; G 21 , G 31 , G 22 , and G 32 are each independently a hydrogen atom, or a 1-5 -COOR 3 phenyl groups and -COOR be substituted with groups 3 group consisting of radicals G 4′ which is a C 1 -C 6 alkyl group optionally substituted with 1 to 5 substituents independently selected from Is a C 1 -C 4 alkylene group or a C 1 -C 4 alkyleneoxy-C 1 -C 4 alkylene group; R 3 is independently a hydrogen atom, a benzyl group, or a tert-butyl group. Yes; L 11 , L 21 , L 12 , and L 22 each independently represent 1 to 5 C 1 -C 6 alkyl groups optionally substituted with 1 to 5 —COOR 4 groups. An optionally substituted C 1 -C 6 alkylene group, C 1 -C 4 alkylene-phenylene group, or phenylene-C 1Is a -C 4 alkylene group; L 3 is a C 1 -C 4 alkylene-phenylene group in which the phenylene moiety may be substituted with 1 to 3 -COOR 4 groups ; R 4 is each independently A hydrogen atom, a benzyl group, a 2-(trimethylsilyl)ethyl group, or a tert-butyl group; R 5 and R 6 are each independently a hydrogen atom, a halogen atom, a C 1 -C 4 alkyl group, Or a C 1 -C 4 alkoxy group; each R 5 may be the same or different; Z is a single bond, C 6 -C 12 arylene, --(CH 2

-CH 2 -O) m -CH 2 -CH 2 -, - (CH 2 -O-CH 2 ) m -, - (CH 2 ) m - (C 6 -C 12 arylene) - (CH 2 ) m - Or -(CH 2 ) n- ; m is an integer of 1 to 6; n is an integer of 2 to 12 ; or a pharmaceutically acceptable salt thereof.

[10] Each R 1 is independently a hydrogen atom or a tert-butoxycarbonyl group; W 1And W 2 are each independently a single bond or a C 1 -C 4 alkylene group; X 1 is —C(═O)—, —O—C(═O)—, or —NG 11 -SO 2 - a and; X 1 ' is, -NG Z -SO 2 - a and; X 2 is, -C (= O) -, - C (= O) -O-, or -SO 2 -NG 12 − is; X 2′ is —SO 2 —NG Z —; G 11 and G 12 are each independently a hydrogen atom, C 1-C 4 alkyl group, or -COOR 2 be; G Z is X 1 ' or X 2' is a single bond linking Z and; R 2 is substituted with 1-3 aryl radicals Is a C 1 -C 4 alkyl group; Y 1 is -NG 21 -, -NG 21 -L 11 -C(=O)-, -NG 21 -L 11 -C(=O)-NH- , -NG 21 -L 11 -C(=O)-NG 31 -L 21 -C(=O)-, -NG 21-L 11 -C (= O) -NG 31 -L 21 -C (= O) -NH-, or -NG 21 -L 3 -O- and is; Y 1 ' is, -NG 21 H, -NG 21 -L 11 -COOH or -NG 21 -L 11 -C(=O)-NG 31 -L 21 -COOH; Y 2 is -NG 22 -, -C(=O)-L 12 -. NG 22 -, -NH-C(=O)-L 12 -NG 22 -, -C(=O)-L 22-NG 32 -C(=O)-L 12 -NG 22 -, -NH -C(=O)-L 22 -NG 32 -C(=O)-L 12 -NG 22 -, or -O-L 3 -NG 22 - a and; Y 2 ' is, HNG 22 -, HOOC-L 12 -NG 22 -, or-L HOOC 22 -NG 32 -C (= O) -L 12 -NG 22 - a and; G 21 , G 31 , G 22 , and G 32 are each independently a hydrogen atom, or 1 to 3 independently selected from the group consisting of a phenyl group optionally substituted with 1 to 3 —COOR 3 groups and a —COOR 3 group; A C 1 -C 6 alkyl group which may be substituted with a substituent ; R 3 's each independently represent a hydrogen atom, a benzyl group, or a tert-butyl group; L 11 , L 21 , L 12 , and L 22 are each independently 1-5 -COOR 4 1-5 which may be substituted with groups C 1 -C 6 alkyl optionally C may be substituted with group 1 -C 6 alkylene group, C 1 -C 4 alkylene-phenylene group, or phenylene-C A C 1 -C 4 alkylene group; L 3 is a C 1 -C 2 alkylene-phenylene group in which the phenylene moiety may be substituted with 1 to 2 —COOR 4 groups ; R 4 is each independently And a hydrogen atom, a benzyl group, a 2-(trimethylsilyl)ethyl group, or a tert-butyl group; R 5 and R 6 are each independently a hydrogen atom, a halogen atom, a C 1 -C 4 alkyl group. Or a C 1 -C 4 alkoxy group; each R 5 may be the same or different; Z is a single bond, biphenylene, —(CH 2 —CH 2 —O)

m -CH 2 -CH 2 -, - (CH 2 -O-CH 2 ) m -, - (CH 2 ) m - biphenylene - (CH 2 ) m -, or - (CH 2 ) n - and is; m Is an integer of 1 to 6; and n is an integer of 2 to 12, the compound or a pharmaceutically acceptable salt thereof. [11] Each R 1 is a hydrogen atom; W 1 and W 2 are each independently a single bond or a C 1 -C 4 alkylene group;

X 1 is —C(═O)— or —NG 11 —SO 2 —; X 1′ is —NG Z —SO 2 —; X 2 is —C(═O)—, Or —SO 2 —NG 12 —; X 2′ is —SO 2 —NG Z —; G 11 and G 12 are each independently a hydrogen atom or —COOR 2 ; G Z Is a single bond connecting X 1′ or X 2′ and Z; R 2 is a C 1 -C 4 alkyl group optionally substituted by one phenyl group ; Y 1 is —NG 21 —; Y 1′ is —NG 21 H; Y 2 is —NG 22 —; Y 2′ is HNG 22 —; G 21 and G 22 are each independently a hydrogen atom or C 1 substituted with 1 to 3 carboxy groups. A C 3 alkyl group; R 5 and R 6Are each independently a hydrogen atom, a fluorine atom, a methyl group, or a methoxy group; each R 5 may be the same or different; Z is a single bond, [1,1' - biphenyl] -3,3'-diyl, - (CH 2 -CH 2 -O) m -CH 2 -CH 2 -, - (CH 2 -O-CH 2 ) m -, - (CH 2 ) m - ([1,1′-biphenyl]-3,3′-diyl)-(CH 2 ) m − or —(CH 2 ) n −; m is an integer of 1 to 6; n is The compound according to [10], which is an integer of 2 to 12, or a pharmaceutically acceptable salt thereof.

[12] the following general formula (V):

of 25

wherein, each R 1 is independently a hydrogen atom, or -COO- (C 1 -C 4 is an alkyl group); W 1 and W 2 is each independently a single bond or a C 1 -C 4 alkylene group; X 1 is —C(═O)—, or —NG 11 —SO 2 —; X 2 is —C(═O)— or —SO 2 —NG 12 —; G 11 and G 12 are each independently a hydrogen atom, C 1- C 4 alkyl group, or —COOR 2 ; R 2 is a C 1 -C 4 alkyl group optionally substituted with 1 to 5 aryl groups ; Y 1 is —NG 21 — , -NG 21 -L 11 -C (= O) -, - NG 21 -L 11 -C (= O) -NH -, - NG 21 -L 11 -C (= O) -NG 31 -L 21 - C(=O)-, -NG 21 -L 11 -C(=O)-NG 31 -L 21-C (= O) -NH -, - NG 21 -L 3 -O-, or -NG 21 -G 4 ' - a and; Y 2 is, -NG 22 -, - C (= O) -L 12 -NG 22 -, -NH -C(=O)-L 12 -NG 22 -, -C(=O)-L 22 -NG 32 -C(=O)-L 12 -NG 22 -, -NH- C(=O)-L 22 -NG 32 -C(=O)-L 12 -NG 22 -, -O -L 3 -NG 22 -, or -G 4′ —NG 22 —; G 21 , G 31 , G 22 and G 32 are each independently a hydrogen atom or a phenyl group optionally substituted with 1 to 5 —COOR 3 groups. And a C 1 -C 6 alkyl group optionally substituted by 1 to 5 substituents independently selected from the group consisting of —COOR 3 group ; G 4′ is C 1 -C 4 alkylene A group or a C 1 -C 4 alkyleneoxy-C 1 -C 4 alkylene group; R 3

Are each independently a hydrogen atom or a C 1 -C 4 alkyl group optionally substituted with 1 to 5 aryl groups ; L 11 , L 21 , L 12 and L 22 are each Independently, C 1 -C 6 alkylene group optionally substituted with 1 to 5 C 1 -C 6 alkyl groups optionally substituted with 1 to 5 --COOR 4 groups, C 1 - C 4 alkylene - phenylene group, or a phenylene -C 1 -C 4 an alkylene group; L 3 is a phenylene moiety 1-3 -COOR 4 a C substituted with groups 1 -C 4 alkylene-phenylene group; R 4 may be each independently substituted with a hydrogen atom, or 1 to 5 substituents independently selected from the group consisting of an aryl group and a trimethylsilyl group. A C 1 -C 4 alkyl group; each R 5 is independently a hydrogen atom, a halogen atom, a C 1 -C 4 alkyl group, or a C 1 -C 4 alkoxy group; Z is a single bond , C 6 -C 12 arylene, —(CH 2 —CH 2 —O) m —CH 2 —CH 2 —, —(CH 2 —O—CH 2 ) m -, - (CH 2 ) m - (C 6 -C 12 arylene) - (CH 2 ) m -, or - (CH 2 ) n - and is; m is an integer of 1 ~ 6; n is , an integer from 2 to 12 compound or a pharmaceutically acceptable salt thereof according to any one represented by [4-7] in.

[13] A compound represented by the following general formula (VI): [12] represented by

Chemical formula 26

or a pharmaceutically acceptable salt thereof.

[14] Each R 1 is independently a hydrogen atom or a tert-butoxycarbonyl group; W 1 and W 2 are each independently a single bond or C 1 -C 2 is an alkylene group; X 1 is —C(═O)— or —NG 11 —SO 2 —; X 2 is —C(═O)— or —SO 2 —NG 12 — Yes; G 11 and G 12 are each a hydrogen atom; Y 1 is -NG 21 -, -NG 21 -L 11 -C(=O)-, -NG 21 -L 11 -C(=O) -NH-, -NG 21 -L 11 -C(=O)-NG 31 -L 21-C (= O) -, - NG 21 -L 11 -C (= O) -NG 31 -L 21 -C (= O) -NH -, - NG 21 -L 3 -O-, or -NG 21 -G 4 ' - a and; Y 2 is, -NG 22 -, - C (= O) -L 12 -NG 22 -, - NH-C (= O) -L 12 -NG 22 -, - C ( =O)-L 22 -NG 32 -C(=O)-L 12 -NG 22 -, -NH -C(=O)-L 22 -NG 32 -C(=O)-L 12 —NG 22 —, —OL 3 —NG 22 —, or —G 4′ —NG 22 —; G 21 , G 31 , G 22 and G 32 each independently represent a hydrogen atom, Or a C 1 -C 3 alkyl group optionally substituted by 1 to 3 —COOR 3 groups ; G 4′ is a C 1 -C 2 alkylene group, or a C 1 -C 2 alkyleneoxy-C A 1- C 2 alkylene group;

R 3 is each independently a hydrogen atom or a tert-butyl group; L 11 , L 21 , L 12 and L 22 are each independently a C 1 -C 2 alkylene group; L 3 is a C 1 -C 4 alkylene-phenylene group in which the phenylene moiety may be substituted with 1 to 3 -COOR 4 groups ; R 4 is each independently a hydrogen atom or an aryl group; A C 1 -C 4 alkyl group which may be substituted with 1 to 5 substituents independently selected from the group consisting of trimethylsilyl groups ; each R 5 is independently a hydrogen atom, a halogen Atom, C 1

-C 4 alkyl group or C 1 -C 4 alkoxy group; Z is a single bond, biphenylene, -(CH 2 -CH 2 -O) m -CH 2 -CH 2 -, -(CH 2 -O -CH 2 ) m -, - (CH 2 ) m - biphenylene - (CH 2 ) m -, or - (CH 2 ) n - and it; m is an integer of 1 - 6; n is 2 to The compound according to [13], which is an integer of 12, or a pharmaceutically acceptable salt thereof.

[15] Each R 1 is each a hydrogen atom; W 1 and W 2 are each a single bond; X 1 is -C(=O)-; X 2 is -C(=O)-; Y 1 is, -NG 21 -, - NG 21 -L 3 -O-, or -NG 21 -G 4 ' - a and; Y 2 is, -NG 22 -, - O-L 3 -NG 22 -, Or —G 4′ —NG 22 —; G 21 and G 22 are each independently one to three C substituted by a carboxy group 1 -C 3 is an alkyl group; G 4 ' is C 1 -C 2 alkylene group, or a C 1 -C 2 alkyleneoxy Is a -C 1 -C 2 alkylene group; L 3 is a C 1 -C 2 alkylene-phenylene group in which the phenylene moiety may be substituted with 1 to 2 -COOR 4 groups ; and R 4 is Each independently a hydrogen atom or a C 1 -C 4 alkyl group optionally substituted by 1 to 5 substituents independently selected from the group consisting of an aryl group and a trimethylsilyl group ;

Each R 5 is independently a hydrogen atom, a fluorine atom, a methyl group or a methoxy group; Z is a single bond, [1,1′-biphenyl]-3,3′-diyl, —(CH 2 —CH 2 —O) m —CH 2 —CH 2 —, —(CH 2 —O—CH 2 ) m —, —(CH 2 ) m —([1,1′-biphenyl]-3,3′ - diyl) - (CH 2 ) m -, or - (CH 2 ) n - and it; m is an integer of 1 ~ 6; n is an integer of 2 to 12 a compound according to [14] Or a pharmaceutically acceptable salt thereof.

[16] A 1There

of 27

has a structure represented by: A 2 is Formula 28]

has a structure represented by: wherein each R 1 is independently a hydrogen atom or -COO —(C 1 -C 4 alkyl group); W 1 and W 2 are each independently a single bond or a C 1 -C 4 alkylene group; X 1 is —C(═O)— , -OC(=O)-, or -NG 11 -SO 2 -; X 2 is -C(=O)-, -C(=O)-O-, or -SO 2 -NG 12-, and; G 11 and G 12 are each independently a hydrogen atom, or a -COOR 2 be; R 2 is 1-5 aryl optionally C be substituted with group 1 -C 4 alkyl a group; Y 1 is, -NG 21 -, - NG 21 -L 11 -C (= O) -NH-, or -NG 21 -L 11 -C (= O) -NG 31 -L 21 -C (=O)-NH-; Y 2 is -NG 22 -, -NH -C(=O)-L 12 -NG 22.-, or-C -NH (= O) -L 22 -NG 32 -C (= O) -L 12 -NG 22 - a and; G 21 , G 31 , G 22 , and G 32 are each independently Te, hydrogen atom, or a 1-5 -COOR 3 group in a phenyl group and -COOR substituted 3 substituted with one to five substituents independently selected from the group consisting of radicals R 3 is independently a C 1 -C 6 alkyl group; R 3 is independently a hydrogen atom, or a C 1 -C 4 alkyl group optionally substituted with 1 to 5 aryl groups ; L 11 , L 21 , L

12 and L 22 are each independently C 1 -, which may be substituted with 1 to 5 C 1 -C 6 alkyl groups, which may be substituted with 1 to 5 -COOR 4 groups. A C 6 alkylene group, a C 1 -C 4 alkylene-phenylene group, or a phenylene-C 1 -C 4 alkylene group; R 4 s are each independently substituted with a hydrogen atom or 1 to 5 aryl groups. is a C even if 1 -C 4 an alkyl group; R 5 and R 6 are each independently a hydrogen atom, C 1 -C 4 alkyl group, or C 1

Is a -C 4 alkoxy group, or R 5 and R 6 may be bonded to each other to form a C 1 -C 4 alkyleneoxy group; the symbol

Chemical formula 29

represents a point of attachment to Z]. Z is —(CH 2 —CH 2 —O) m —CH 2 —CH 2 — or —(CH 2 ) n —; m is an integer of 1 to 6; n is 2 to 12 The compound or a pharmaceutically acceptable salt thereof according to any one of [1] to [6], which is an integer of

[17] A 1 has a structure represented by

Chemical Formula 30

: The compound or a pharmaceutically acceptable salt thereof according to [16], wherein A 2 has a structure represented by

Chemical Formula 31

.

[18] the following general formula (VII):

of 32

wherein, each R 1 is independently a hydrogen atom, or -COO- (C 1 -C 4 is an alkyl group); W 1 and W 2 is each independently a single bond or a C 1 -C 4 alkylene group; X 1 is —O—C(═O)—, or —NG 11 —SO 2 —; X 2 Is —C(═O)—O—, or —SO 2 —NG 12-, and; G 11 and G 12 are each independently a hydrogen atom, or a -COOR 2 be; R 2 is 1-5 aryl optionally C be substituted with group 1 -C 4 alkyl a group; Y 1 is, -NG 21 -, - NG 21 -L 11 -C (= O) -NH-, or -NG 21 -L 11 -C (= O) -NG 31 -L 21 -C (=O)-NH-; Y 2 is -NG 22 -, -NH -C(=O)-L 12 -NG 22.-, or-C -NH (= O) -L 22 -NG 32 -C (= O) -L 12 -NG 22 - a and; G 21 , G 31 , G 22 , and G 32 are each independently Te, hydrogen atom, or a 1-5 -COOR 3 group in a phenyl group and -COOR substituted 3 substituted with one to five substituents independently selected from the group consisting of radicals R 3 is independently a C 1 -C 6 alkyl group; R 3 is independently a hydrogen atom, or a C 1 -C 4 alkyl group optionally substituted with 1 to 5 aryl groups ; L 11 , L 21 , L

12 and L 22 are each independently C 1 -, which may be substituted with 1 to 5 C 1 -C 6 alkyl groups, which may be substituted with 1 to 5 -COOR 4 groups. A C 6 alkylene group, a C 1 -C 4 alkylene-phenylene group, or a phenylene-C 1 -C 4 alkylene group; R 4 s are each independently substituted with a hydrogen atom or 1-5 aryl groups. An optionally substituted C 1 -C 4 alkyl group; Z is —(CH 2 —CH 2 —O) m —CH 2 —CH 2 —, or —(CH

2 ) n −; m is an integer of 1 to 6; n is an integer of 2 to 12 ] [1] and [16] to [17] The compound or pharmaceutically acceptable salt thereof described.

[19] Each R 1 is independently a hydrogen atom or a tert-butoxycarbonyl group; W 1 and W 2 are each a C 1 -C 4 alkylene group; X 1 is —O— C (= O) -, or -NG 11 -SO 2 - a and; X 2 is, -C (= O) -O-, or -SO 2 -NG 12 - a and; G 11 and G 12 are each independently a hydrogen atom or —COOR 2 ; R 2 is a C 1 -C 4 alkyl group optionally substituted with 1 to 3 phenyl groups ; and Y 1 is -NG 21 -, - NG 21 -L 11 -C (= O) -NH-, or -NG 21 -L 11 -C (= O) -NG 31 -L 21 -C (= O) -NH- in There; Y 2 is, -NG 22 -, - NH-C (= O) -L 12 -NG 22 -, or-C -NH (= O) -L 22 -NG 32—C(═O)—L 12 —NG 22 —; G 21 , G 31 , G 22 and G 32 are each independently substituted with a hydrogen atom or 1 to 3 —COOR 3 groups. A C 1 -C 6 alkyl group optionally substituted with 1 to 3 substituents independently selected from the group consisting of an optionally substituted phenyl group and a —COOR 3 group ; R 3 is Each independently a hydrogen atom, a benzyl group, or a tert-butyl group; L 11 , L 21 , L 12 , and L 22 each independently substituted with 1 to 5 —COOR 4 groups; 1-5 C 1 that may be present

A C 1 -C 6 alkylene group which may be substituted with a -C 6 alkyl group, a C 1 -C 4 alkylene-phenylene group, or a phenylene-C 1 -C 4 alkylene group; R 4 are each independently Te, a hydrogen atom, a benzyl group, or a tert- butyl group; Z is, - (CH 2 -CH 2 -O) m -CH 2 -CH 2 -, or - (CH 2 ) n - and is; m Is an integer of 1 to 6; and n is an integer of 2 to 12, the compound or a pharmaceutically acceptable salt thereof. [20] Each R

1 is each independently a hydrogen atom or a tert-butoxycarbonyl group; W 1 and W 2 are each a C 1 -C 2 alkylene group; X 1 is —O—C(═O) -Or -NG 11 -SO 2 -; X 2 is -C(=O)-O-, or -SO 2 -NG 12 -; G 11 and G 12 are each independently A hydrogen atom or —COOR 2 ; R 2 is a C 1 -C 4 alkyl group optionally substituted by one phenyl group ; Y 1 is, -NG 21 -, - NG 21 -L 11 -C (= O) -NH-, or -NG 21 -L 11 -C (= O) -NG 31 -L 21 -C (= O) a -NH-; Y 2 is, -NG 22 -, - NH-C (= O) -L 12 -NG 22 -, or-C -NH (= O) -L 22 -NG 32 -C (= O) -L 12 -NG 22 - a and; G 21 , G 31 , G 22 , and G 32Are each independently a hydrogen atom, or 1 to 3 substituents independently selected from the group consisting of a phenyl group optionally substituted with one —COOR 3 group and a —COOR 3 group. R 1 is an optionally substituted C 1 -C 3 alkyl group; R 3 is each independently a hydrogen atom or a tert-butyl group; L 11 , L 21 , L 12 , and L 22 are Each independently, a C 1 -C 2 alkylene group optionally substituted with 1 to 2 C 1 -C 2 alkyl groups optionally substituted with 1 to 2 --COOR 4 groups, C 1 -C 2 alkylene-phenylene group, or phenylene-C 1 -C 2 is an alkylene group; R 4 are each independently a hydrogen atom, or tert- be butyl group; Z is - (CH 2 -CH 2 -O) m -CH 2 -CH 2 -, or - (CH 2 ) n −; m is an integer of 1 to 6; n is an integer of 2 to 12 ; or a pharmaceutically acceptable salt thereof.

[21] Each R 1 is a hydrogen atom; W 1 and W 2 are each a C 1 -C 2 alkylene group; X 1 is —NG 11 —SO 2 —; X 2 is —SO 2 —NG 12 —; G 11 and G 12 are each independently a hydrogen atom or —COOR 2 ; R 2 is 1 Is a C 1 -C 4 alkyl group which may be substituted with a phenyl group ; Y 1 is —NG 21 —; Y 2 is —NG 22 —; G 21 and G 22Are each independently a C 1 -C 3 alkyl group substituted with 1 to 3 substituents independently selected from the group consisting of a phenyl group substituted with one carboxy group and a carboxy group. Yes; Z is —(CH 2 —CH 2 —O) m —CH 2 —CH 2 — or —(CH 2 ) n —; m is an integer of 1 to 6; n is 2 The compound according to [20], which is an integer of 1 to 12, or a pharmaceutically acceptable salt thereof.

[22] the following general formula (VIII):

of 33

wherein, each R 1 is independently a hydrogen atom, or -COO- (C 1 -C 4 is an alkyl group); W 1 and W 2 are each independently a single bond or a C 1 -C 4 alkylene group; X 1 is —C(═O)— or —NG 11 —SO 2 —; X 2 Is —C(═O)— or —SO 2 —NG 12 —; G 11 and G 12 are each independently a hydrogen atom or —COOR 2 ; R 2 is 1-5. C 1 -C 4 alkyl group optionally substituted with 4 aryl groups; Y 1 is —NG 21-, - NG 21 -L 11 -C (= O) -NH-, or -NG 21 -L 11 -C (= O) -NG 31 -L 21 -C (= O) -NH- and is; Y 2 is -NG 22 -, -NH-C(=O)-L 12 -NG 22 -, or -NH-C(=O)-L 22 -NG 32 -C(=O)-L 12 -NG 22 −; G 21 , G 31 , G 22 and G 32 are each independently a hydrogen atom or 1 to 5 —COOR 3A C 1 -C 6 alkyl group optionally substituted with 1 to 5 substituents independently selected from the group consisting of a phenyl group optionally substituted with a group and a —COOR 3 group ; R 3 are each independently a hydrogen atom or a C 1 -C 4 alkyl group optionally substituted with 1 to 5 aryl groups ; L 11 , L 21 , L 12 and L 22 are each Each independently, a C 1 -C 6 alkylene group optionally substituted by 1 to 5 C 1 -C 6 alkyl groups optionally substituted by 1 to 5 --COOR 4 groups, C 1 -C 4 alkylene-phenylene group, or phenylene-C

1- C 4 alkylene group; R 4 is each independently a hydrogen atom, or a C 1- C 4 alkyl group optionally substituted with 1 to 5 aryl groups ; Z is (CH 2 —CH 2 —O) m —CH 2 —CH 2 — or —(CH 2 ) n —; m is an integer from 1 to 6; n is an integer from 2 to 12 ] compound or a pharmaceutically acceptable salt thereof according to any one of [1] and [16] to [17] represented by.

[23] Each R 1 is independently a hydrogen atom or a tert-butoxycarbonyl group; W 1 and W 2Are each independently a single bond or a C 1 -C 2 alkylene group; X 1 is -C(=O)- or -NG 11 -SO 2 -; X 2 is -C (= O) -, or -SO 2 -NG 12 - a and; G 11 and G 12 are each a hydrogen atom; Y 1 is -NG 21 -, - NG 21 -L 11 -C (= O ) -NH-, or -NG 21 -L 11 -C(=O)-NG 31 -L 21 -C(=O)-NH-; Y 2 is -NG 22 -, -NH-C(=O)-L 12 -NG 22 -, or -NH-C(=O)-L 22 -NG 32 -C(=O)-L 12 -. NG 22 —; G 21 , G 31 , G 22 and G 32 each independently represent a hydrogen atom or C 1 -C 3 which may be substituted with 1 to 3 —COOR 3 groups. An alkyl group; R 3 's each independently represent a hydrogen atom or a tert-butyl group; L 11 , L 21 , L 12

, And L 22 are each independently a C 1 -C 2 alkylene group; Z is —(CH 2 —CH 2 —O) m —CH 2 —CH 2 — or —(CH 2 ) n -Is a compound ; m is an integer of 1 to 6; n is an integer of 2 to 12 ; or a pharmaceutically acceptable salt thereof.

[24] Each R 1 is a hydrogen atom; W 1 and W 2 are each a single bond; X 1 is —C(═O)—; X 2But, -C (= O) - and is; Y 1 is -NG 21 - a and; Y 2 is, -NG 22 - a and; G 21 and G 22 are each independently 1-3 Is a C 1 -C 3 alkyl group substituted with a carboxy group of ; Z is —(CH 2 —CH 2 —O) m —CH 2 —CH 2 —; and m is an integer from 1 to 6. A compound according to certain [23] or a pharmaceutically acceptable salt thereof.

[25] (2S,2′S)-2,2′-((oxybis(ethane-2,1-diyl))bis((N-(4-((4-guanidinobenzoyl)oxy)benzyl)sulfamoyl) Azandiyl)) disuccinic acid; (2S,13S)-3,12-Bis(N-(4-((4-guanidinobenzoyl)oxy)benzyl)sulfamoyl)-6,9-dioxa-3,12-diazatetradecane-1,2,13 ,14-Tetracarboxylic acid; (2S,16S)-3,15-bis(N-(4-((4-guanidinobenzoyl)oxy)benzyl)sulfamoyl)-6,9,12-trioxa-3,15- Diazaheptadecane-1,2,16,17-tetracarboxylic acid; (2S,19S)-3,18-bis(N-(4-((4-guanidinobenzoyl)oxy)benzyl)sulfamoyl)-6 9,12,15-Tetraoxa-3,18-diazaicosane-1,2,19,20-tetracarboxylic acid; (2S,22S)-3,21-bis(N-(4-((4-guanidinobenzoyl) (Oxy)benzyl)sulfamoyl)-6,9,12,15,18-pentaoxa-3,21-diazatricosane-1,2,22,23-tetracarboxylic acid; (2S,25S)-3,24-bis(N -(4-((4-guanidinobenzoyl)oxy)benzyl)sulfamoyl)-6,9,12,15,18,21-hexaoxa-3,24-diazahexacosane-1,2,25,26-tetra Carboxylic acid; (2S,2'S)-2,2'-(Propane-1,3-diylbis((N-(4-((4-guanidinobenzoyl)oxy)benzyl)sulfamoyl)azanediyl)) disuccinic acid ; (2S, 2'S) -2, 2 '- (butane-1,4-diyl bis ((N- (4 - (( 4- guanidino-benzoyl) oxy) benzyl) sulfamoyl) azanediyl)) disuccinic acid; (2S,2'S)-2,2'-(Pentane-1,5-diylbis((N-(4-((4-guanidinobenzoyl)oxy)benzyl)sulfamoyl)azanediyl)) disuccinic acid: 3, 18-bis(((4-((4-guanidinobenzoyl)oxy)benzyl)oxy)carbonyl)-6,9,12,15-tetraoxa-3,18-diazaicosane-1,2,19,20-tetracarboxylic Acid; 2,2'-(1,20-bis(4-((4-guanidinobenzoyl)oxy)phenyl)-3,18-dioxo-2,19-dioxa-4,17-diazaicosane-4,17- Diyl)disuccinic acid; (3S,6S,25S,28S)-6,25-bis(carboxymethyl)-3,28-bis((((4-((4-guanidinobenzoyl)oxy)benzyl)oxy) (Carbonyl)amino)-4,7,24,27-tetraoxo-11,14,17,20-tetraoxa-5,8,23,26-tetraazatriacontane-1,30-diacid; (3S,6S, 23S,26S)-6,23-bis(carboxymethyl)-3,26-bis((((4-((4-guanidinobenzoyl)oxy)benzyl)oxy)carbonyl)amino)-4,7,22, 25-Tetraoxo-5,8,21,24-tetraazaoctacosane-1,28-dioic acid; (3S,22S)-3,22-bis(2-((3-carboxybenzyl)(((4- ((4-guanidinobenzoyl)oxy)benzyl)oxy)carbonyl)amino)acetamido)-4,21-dioxo-8,11,14,17-tetraoxa-5,20-diazatetracosane-1,24-di acid; (4S,7S,26S,29S)-4,7,26,29-Tetrakis(carboxymethyl)-3,30-bis(((4-((4-guanidinobenzoyl)oxy)benzyl)oxy)carbonyl)- 5,8,25,28-Tetraoxo-12,15,18,21-tetraoxa-3,6,9,24,27,30-hexaazadtriacontane-1,32-diacid; (3S,22S)- 3,22-bis((3-carboxybenzyl)(((4-((4-guanidinobenzoyl)oxy)benzyl)oxy)carbonyl)amino)-4,21-dioxo-8,11,14,17-tetraoxa -5,20-diazatetracosane-1,24-dioic acid; (2S,2'S)-2,2'-((((5,8,11,14-tetraoxa-2,17-diaza Octadecane-1,18-dioil)bis(3,1-phenylene))bis(methylene))bis((((4-((4-guanidinobenzoyl)oxy)benzyl)oxy)carbonyl)azanediyl)) disuccinic acid ; (2S, 2'S) -2, 2 '- ((((5,8,11,14-tetraoxa -2,17- diaza octadecane-1,18 Jioiru) bis (3,1-phenylene) ) Bis(methylene))bis((N-(4-((4-guanidinobenzoyl)oxy)benzyl)sulfamoyl)azandiyl)) disuccinic acid; 3,12-bis(10-guanidino-13-oxo-6,6 7,8,13-Tetrahydrodibenzo[b,f][1,4]dioxesin-4-carbonyl)-6,9-dioxa-3,12-diazatetradecane-1,2,13,14-tetracarboxylic acid ; (2S,13S)-3,12-Bis(10-guanidino-13-oxo-6,7,8,13-tetrahydrodibenzo[b,f][1,4]dioxesin-4-carbonyl)-6,9 -Dioxa-3,12-diazatetradecane-1,2,13,14-tetracarboxylic acid; (2R,13R)-3,12-bis(10-guanidino-13-oxo-6,7,8,13 -Tetrahydrodibenzo[b,f][1,4]dioxesin-4-carbonyl)-6,9-dioxa-3,12-diazatetradecane-1,2,13,14-tetracarboxylic acid; (2S,13S )-3,12-Bis(N-(4-((4-guanidinobenzoyl)oxy)benzyl)-N-methylsulfamoyl)-6,9-dioxa-3,12-diazatetradecane-1,2 , 13,14-Tetracarboxylic acid; 3,3′-(((ethane-1,2-diylbis(oxy))bis(ethane-2,1-diyl))bis((N-(4-((4 -Guanidinobenzoyl)oxy)benzyl)sulfamoyl)azanediyl))dipentanedioic acid; (2S,2'S) -2,2 '-((1,12-bis(4-((guanidinobenzoyl)oxy)phenyl) )-5,8-Dioxa-2,11-diazadodecanedisulfonyl)bis(azanediyl))disuccinic acid; (2S,13S)-3,12-bis(N-(3-((4-guanidinobenzoyl) )Oxy)benzyl)sulfamoyl)-6,9-dioxa-3,12-diazatetradecane-1,2,13,14-tetracarboxylic acid; (2S,2'S)-2,2'-((oxybis(ethane-2,1-diyl))bis((10-guanidino-13-oxo-6,7,8,13-tetrahydrodibenzo[b, f][1,4]dioxesine-4-carbonyl)azadiyl))disuccinic acid; (2S,16S)-3,15-bis(10-guanidino-13-oxo-6,7,8,13-tetrahydrodibenzo [B,f][1,4]dioxesin-4-carbonyl)-6,9,12-trioxa-3,15-diazaheptadecane-1,2,16,17-tetracarboxylic acid; (2S,2 'S)-2,2'-(([1,1'-biphenyl]-3,3'-diylbis(methylene))bis((10-guanidino-13-oxo-6,7,8,13-tetrahydro Dibenzo[b,f][1,4]dioxesin-4-carbonyl)azanediyl))disuccinic acid; (2S,2′S)-2,2′-((((oxybis(ethane-2,1- Diyl))bis(oxy))bis(3-carboxy-5,1-phenylene))bis(methylene))bis((10-guanidino-13-oxo-6,7,8,13-tetrahydrodibenzo[b, f][1,4]dioxesine-4-carbonyl)azandiyl))disuccinic acid; and (2S,2′S)-2,2′-((oxybis(ethane-2,1-diyl))bis(( 3-((4-guanidinobenzoyl)oxy)benzoyl)azandiyl))disuccinic acid

[1] to a compound according to any one of [7] or a pharmaceutically acceptable salt thereof selected from the group consisting of ..

[26] (2S,2'S)-2,2'-((oxybis(ethane-2,1-diyl))bis((N-(4-((4-guanidinobenzoyl)oxy)benzyl)sulfamoyl)azandiyl)) disuccinic acid; (2S, 13S) 3,12-bis (N- (4 - ((4- guanidino-benzoyl) oxy) benzyl) sulfamoyl) -6,9-dioxa-3,12-diaza tetradecane -1 ,2,13,14-Tetracarboxylic acid; (2S,2'S)-2,2'-(butane-1,4-diylbis((N-(4-((4-guanidinobenzoyl)oxy)benzyl)) (Sulfamoyl)azandiyl)) disuccinic acid; (2S,13S)-3,12-bis(10-guanidino-13-oxo-6,7,8,13-tetrahydrodibenzo[b,f][1,4]dioxesine -4-carbonyl)-6,9-dioxa-3,12-diazatetradecane-1,2,13,14-tetracarboxylic acid; (2S,2'S)-2,2'-((oxybis(ethane -2,1-Diyl))bis((10-guanidino-13-oxo-6,7,8,13-tetrahydrodibenzo[b,f][1,4]dioxesin-4-carbonyl)azanediyl)) Acid; (2S,16S)-3,15-bis(10-guanidino-13-oxo-6,7,8,13-tetrahydrodibenzo[b,f][1,4]dioxesin-4-carbonyl)-6 , 9,12-Trioxa-3,15-diazaheptadecane-1,2,16,17-tetracarboxylic acid; (2S,2'S)-2,2'-(([1,1'-biphenyl]-3,3'-diylbis(methylene))bis((10-guanidino-13-oxo-6,7,8 , 13-Tetrahydrodibenzo[b,f][1,4]dioxesin-4-carbonyl)azanediyl))disuccinic acid; and (2S,2′S)-2,2′-((((oxybis(ethane -2,1-Diyl))bis(oxy))bis(3-carboxy-5,1-phenylene))bis(methylene))bis((10-guanidino-13-oxo-6,7,8,13- Tetrahydrodibenzo[b,f][1,4]dioxesin-4-carbonyl)azandiyl)) Dissuccinic acid selected from the group [1] to [7] or a compound thereof. Top acceptable salt.

[27] The compound or pharmaceutically acceptable salt thereof according to any one of [1] to [26], which has a molecular weight of 1000 or more.

[28] A pharmaceutical composition comprising the compound according to any one of [1] to [27] or a pharmaceutically acceptable salt thereof.

[29] The pharmaceutical composition according to [28], for preventing, alleviating and/or treating obesity. Effect of the invention

[0009] The compound represented by the general formula (I) of the present invention or a pharmaceutically acceptable salt thereof has an excellent enteropeptidase inhibitory activity and/or an excellent trypsin inhibitory activity, and after oral administration, enteropeptidase and It has pharmacokinetic properties that strongly inhibit trypsin and/or have very low exposure to blood. Therefore, the compound represented by the general formula (I) or a pharmaceutically acceptable salt thereof can be used as a preventive or palliative agent for various diseases whose symptoms are improved by enteropeptidase inhibition and/or trypsin inhibition, such as obesity. And/or is useful as a therapeutic agent. The compound of the present invention is also useful as a highly safe drug in which side effects due to exposure to blood are reduced. MODE FOR CARRYING OUT THE INVENTION

[0010] Embodiments of the present invention will be described below. In the present specification, "compound represented by general formula (I)" and the like are also referred to as "compound (I)" and the like for convenience. Various substituents defined or exemplified below can be arbitrarily selected and combined. The present invention also includes embodiments in which the embodiments defined below are arbitrarily selected and combined.

[0011] The definition of each term used in the present specification is as follows.

[0012] As used herein, the term “inhibitor”, “inhibitor molecule”, and “inhibitor” of “inhibitor residue” means a compound having at least one activity selected from enteropeptidase inhibitory activity and trypsin inhibitory activity. means.

[0013] The “halogen atom” described in the present specification means a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom. As the halogen atom, a fluorine atom and a chlorine atom are preferable.

[0014] The “C 1 -C 4 alkyl group” described in the present specification means a linear or branched saturated hydrocarbon group having 1 to 4 carbon atoms. Examples of the C 1 -C 4 alkyl group include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, and a tert-butyl group. A methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, and a tert-butyl group are preferable. Further, the “C 1 -C 6 alkyl group” described in the present specification means a linear or branched saturated hydrocarbon group having 1 to 6 carbon atoms. The C 1 -C 6 alkyl group includes, in addition to the groups included in the above-mentioned “C 1 -C 4 alkyl group”, for example, an n-pentyl group, an isopentyl group, an n-hexyl group, an isohexyl group and the like. .. Methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, tert-butyl group, n-pentyl group, and n-hexyl group are preferred. "C 1 -C 4More preferred forms of “ alkyl group” and “C 1 -C 6 alkyl group” include, for example, C 1 -C 3 alkyl groups (ie, methyl group, ethyl group, n-propyl group, and isopropyl group, preferably methyl group, Examples thereof include an ethyl group and an n-propyl group), and a C 1 -C 2 alkyl group (that is, a methyl group and an ethyl group, preferably a methyl group).

[0015] The “C 1 -C 4 alkylene group” described in the present specification means a divalent group obtained by removing one arbitrary hydrogen atom from the above “C 1 -C 4 alkyl group”. Examples of the C 1 -C 4 alkylene group include methylene group, ethylene group, methylmethylene group, trimethylene group, ethylmethylene group, dimethylmethylene group, and tetramethylene group. A methylene group, an ethylene group, a methylmethylene group, a trimethylene group, and a tetramethylene group are preferable. The “C 1 -C 6 alkylene group” described in the present specification means a divalent group obtained by removing one arbitrary hydrogen atom from the above “C 1 -C 6 alkyl group”. As the C 1 -C 6 alkylene group, the above "C 1 -C 4In addition to the groups included in the “alkylene group”, for example, a pentamethylene group, a hexamethylene group and the like can be mentioned. Preferred are methylene group, ethylene group, methylmethylene group, trimethylene group, tetramethylene group, pentamethylene group, and hexamethylene group. More preferable forms of the “C 1 -C 4 alkylene group” and the “C 1 -C 6 alkylene group” include a C 1 -C 2 alkylene group (that is, a methylene group and an ethylene group, preferably a methylene group) and the like. To be The “C 2 -C 30 alkylene group described in the present specification (wherein one or more methylene groups in the chain of the alkylene group is —C(═O)—, —NR 7 —, —O— , —SiR 8 R 9 —, —SO r —, arylene, and heteroarylene may be replaced with a group independently selected from the group consisting of, R 7 is a hydrogen atom, or a C 1 -C 4 alkyl group, R 8 and R 9 are each independently a C 1 -C 4 alkyl group, and r is an integer of 0 to 2)” is a linear or branched chain having 2 to 30 carbon atoms. In the divalent group obtained by removing one arbitrary hydrogen atom from the saturated hydrocarbon group, one or more methylene groups in the chain are -C(=O)-, -NR 7 -, -O- , -SiR 8 R 9 -,-SO rMeans a group which may be replaced with a group independently selected from the group consisting of —, arylene, and heteroarylene, for example, —(CH 2 —CH 2 —C(═O)) M —CH 2 —CH 2 - (M is an integer of ~ 9 1), - (CH 2 -CH 2 -NR 7 ) M -CH 2 -CH 2 - (M is an integer of ~ 9 1), - (CH 2 - CH 2 —O) M —CH 2 —CH 2 — (M is an integer from 1 to 9), —(CH 2 —CH 2 —SiR 8 R 9 ) M—CH 2 —CH 2 — (M is an integer of 1 to 9), —(CH 2 —CH 2 —SO r ) M —CH 2 —CH 2 — (M is an integer of 1 to 9), -(CH 2 -CH 2 -arylene) M -CH 2 -CH 2- (M is an integer of 1 to 9), -(CH 2 -CH 2 -heteroarylene) M -CH 2 -CH 2 -( M is an integer of 1 to 9), —(CH 2 ) N — (N is an integer of 2 to 30) and the like. -(CH 2—CH 2 —O) m —CH 2 —CH 2 — (m is an integer of 1 to 6), —(CH 2 —O—CH 2 ) m — (m is an integer of 1 to 6), -(CH 2 ) m -(C 6 -C 12 arylene) -(CH 2 ) m- (m is an integer of 1 to 6) and -(CH 2 ) n- (n is an integer of 2 to 12 ) Yes) is preferred. -(CH 2 ) m -(C 6 -C 12 arylene) -(CH 2 ) m-(M is an integer of 1 to 6) is preferably -(CH 2 ) m -biphenylene-(CH 2 ) m- (m is an integer of 1 to 6), and more preferably -(CH 2 ) m - ([1,1'-biphenyl] -3,3'-diyl) - (CH 2 ) m is (m is an integer of 1-6) -.

[0017] The "phenylene group" described in the present specification means a divalent group obtained by removing any one hydrogen atom of a phenyl group. Examples of the phenylene group include an o-phenylene group, an m-phenylene group, and a p-phenylene group. The "biphenylene group" described in the present specification means a divalent group in which two phenylene groups are linked by a single bond. Examples of the biphenylene group include [1,1′-biphenyl]-2,2′-diyl group, [1,1′-biphenyl]-3,3′-diyl group, and [1,1′-biphenyl]. -4,4'-diyl group and the like are preferable, and [1,1'-biphenyl]-3,3'-diyl group is preferable.

[0018] The “aryl group” described in the present specification means a monocyclic or bicyclic aromatic hydrocarbon group having 6 to 12 ring-constituting carbon atoms (C 6 to C 12 ), for example, C 6 to C 11. .. For example, a monocyclic aryl group such as a phenyl group; a naphthyl group, a tetrahydronaphthyl group, an indenyl group, an indanyl group, and the like, which may have partially saturated ring constituent carbon atoms 9 to 12 (C 9 to C 12 ). , For example, a C 9 -C 11 bicyclic aryl group. As the aryl group, a phenyl group and a naphthyl group are preferable, and a phenyl group is more preferable.

[0019] The “arylene group” or “C 6 -C 12 arylene group” described in the present specification means a divalent group obtained by removing one arbitrary hydrogen atom from the above “aryl group”.

[0020] The “heteroaryl group” described in the present specification means a 5- to 11-membered monocyclic or bicyclic aromatic compound containing 1 to 4 heteroatoms selected from oxygen atom, sulfur atom and nitrogen atom in addition to carbon atoms. Group heterocyclic group, for example, pyrrolyl group, furyl group, thienyl group, pyrazolyl group, imidazolyl group, oxazolyl group, isoxazolyl group, thiazolyl group, isothiazolyl group, thiadiazolyl group, pyridyl group, pyrazinyl group, pyrimidinyl group, pyridazinyl 5- to 6-membered monocyclic heteroaryl groups containing 1 to 4 heteroatoms selected from oxygen atoms, sulfur atoms and nitrogen atoms in addition to carbon atoms such as groups and triazinyl groups; indolyl groups, indolinyl groups, isoindolinyl groups , Indazolyl group, tetrahydroindazolyl group, benzofuranyl group, dihydrobenzofuranyl group, dihydroisobenzofuranyl group, benzothiophenyl group, dihydrobenzothiophenyl group, dihydroisobenzothiophenyl group, benzoxazolyl group, Dihydrobenzoxazolyl group, benzothiazolyl group, dihydrobenzothiazolyl group, quinolyl group, tetrahydroquinolyl group, isoquinolyl group, tetrahydroisoquinolyl group, naphthyridinyl group, tetrahydronaphthyridinyl group, quinoxalinyl group, tetrahydroquinoxalyl In addition to carbon atoms such as a nyl group and a quinazolinyl group, an 8- to 11-membered bicyclic heteroaryl group containing 1 to 4 hetero atoms selected from oxygen atom, sulfur atom and nitrogen atom can be mentioned. Pyrrolyl group, furyl group, thienyl group, pyrazolyl group, imidazolyl group, oxazolyl group, isoxazolyl group, thiazolyl group, isothiazolyl group, thiadiazolyl group, pyridyl group, pyrazinyl group, pyrimidinyl group, pyridazinyl group, and triazinyl group are preferable, and pyrrolyl group , A furyl group, and a thienyl group are more preferable.

[0021] The "heteroarylene group" described in the present specification means a divalent group obtained by removing one arbitrary hydrogen atom from the above "heteroaryl group".

[0022] The "C 1 -C 4 alkoxy group" described in the present specification means a monovalent group in which the C 1 -C 4 alkyl group is bonded to an oxy group. Examples of the C 1 -C 4 alkoxy group include a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a sec-butoxy group, and a tert-butoxy group. A methoxy group, an ethoxy group, and an n-propoxy group are preferred.

[0023] "C described herein 1 -C 4 alkoxy -C 1 -C 4 and the alkyl group", said C 1 -C 4 alkyl group C 1 -C 4 means a group substituted with an alkoxy group. Examples of the C 1 -C 4 alkoxy-C 1 -C 4 alkyl group include methoxymethyl group, methoxyethyl group, ethoxymethyl group, ethoxyethyl group, n-propoxymethyl group, isopropoxymethyl group, n-butoxymethyl group. Group, isobutoxymethyl group, sec-butoxymethyl group, tert-butoxymethyl group and the like. A methoxymethyl group, a methoxyethyl group, an ethoxymethyl group, and an ethoxyethyl group are preferred.

[0024] The “C 1 -C 4 alkyleneoxy group” described in the present specification means a divalent group in which the C 1 -C 4 alkylene group is bonded to an oxy group. Examples of the C 1 -C 4 alkyleneoxy group include a methyleneoxy group, an ethyleneoxy group, a methylmethyleneoxy group, a trimethyleneoxy group, an ethylmethyleneoxy group, a dimethylmethyleneoxy group, and a tetramethyleneoxy group. .. Ethyleneoxy group, trimethyleneoxy group, and tetramethyleneoxy group are preferable.

[0025] The "C 7 -C 12 aralkyl group" described in the present specification means a group in which the C 1 -C 6 alkyl group is substituted with the aryl group. Examples of the C 7 -C 12 aralkyl group include a benzyl group and a phenethyl group. A benzyl group is preferred.

[0026] The "any one hydrogen atom" in the "group excluding any one hydrogen atom or hydroxy group" described in the present specification means any one hydrogen atom bonded to a carbon atom, a nitrogen atom, or an oxygen atom. means. The "any one hydroxy group" in the "group excluding any one hydrogen atom or hydroxy group" described in the present specification may be a hydroxy group or a hydroxy group existing in a carboxy group. Good.

[0027] As used herein, "room temperature" means a temperature in the range of 1 to 30°C, preferably 10 to 30°C.

[0028] Compound (I) One embodiment of the present invention is a compound represented by the following general formula (I) or a pharmaceutically acceptable salt thereof.

Chemical 34

[0029] In the general formula (I), A 1 and A 2 are each independently an inhibitor residue having at least one activity selected from enteropeptidase inhibitory activity and trypsin inhibitory activity; Z is A 1 and A 2 A spacer that connects A 2 and also includes a single bond. Here, the term “inhibitor residue” means an inhibitor residue obtained by removing a hydrogen atom or a hydroxy group from an inhibitor molecule having at least one activity selected from enteropeptidase inhibitory activity and trypsin inhibitory activity. Such inhibitors include, but are not limited to, the compounds described in Patent Documents 1 to 12 and the compounds synthesized in the present specification. Further, the “spacer” means a structure for connecting two residues, and includes, for example, a linker and the like.

[0030] In compound (I), A 1 and A 2 may have the same structure or different structures.

[0031] In one embodiment of the present invention, A 1 and A 2 are each independently the following inhibitors molecular groups:

formula 35

Formula 36

formula 37

Formula 38

inhibitor molecule selected from Or a compound represented by the following general formula (II) : embedded image [ wherein

, ring B and ring C are each independently an aryl group or a heteroaryl group; and each R 1 is independently a hydrogen atom. , Or —COO—(C 1 -C 4 alkyl group); W is a single bond or a C 1 -C 4 alkylene group; X is —C(═O)—, —OC( =O)-, or -NG-SO 2 -; G is a hydrogen atom, C 1 -C 4Alkyl group or —COOR 2 ; R 2 is a C 1 -C 4 alkyl group optionally substituted with 1 to 5 aryl groups ; Y is —NG 2 G 4 , —NG 2 -L 1 -COOH, -NG 2 -L 1 -C (= O) -NH 2 , -NG 2 -L 1 -C (= O) -NG 3 -L 2 -COOH, -NG 2 -L 1 - C(=O)-NG 3 -L 2 -C(=O)-NG 3 -L 2 -COOH, -NG 2 -L 1 -C (= O) -NG 3 -L 2 -C (= O) -NH 2 , -NG 2 -L 3 -OH, or -NG 2 - (CH 2 - CH 2 —O) q —CH 2 —CH 2 —COOH; q is an integer of 1 to 6; G 2 and G 3 are each independently a hydrogen atom or 1 to 5 — C 1 -C optionally substituted with 1 to 5 substituents independently selected from the group consisting of a phenyl group optionally substituted with a COOR 3 group and a —COOR 3 group 6 is an alkyl group; G 4 represents a hydrogen atom, C 1 -C 4 alkyl group, or a C 1 -C 4 alkoxy -C 1 -C 4 an alkyl group; R 3 are each independently a hydrogen atom Or a C 1 -C 4 alkyl group optionally substituted with 1 to 5 aryl groups ; L 1 and L 2 are each independently substituted with 1 to 5 —COOR 4 groups. 1 may be to five C 1 -C 6 alkyl-substituted C optionally in group 1 -C 6C 1 -C 6 alkylene group substituted by C 7 -C 12 aralkyl group optionally substituted by 1 to 5 substituents independently selected from the group consisting of alkylene group, hydroxy group and carboxy group , C 1 -C 4 alkylene - phenylene group, or a phenylene -C 1 -C 4 an alkylene group; L 3 is a phenylene moiety 1-3 -COOR 4 a C substituted with groups 1 - C 4 alkylene-phenylene group; R 4 s may be each independently substituted with a hydrogen atom or 1 to 5 substituents independently selected from the group consisting of an aryl group and a trimethylsilyl group. A good C 1 -C 4 alkyl group; R 5

And R 6 are each independently a hydrogen atom, a halogen atom, a C 1 -C 4 alkyl group, a C 1 -C 4 alkoxy group, a carboxy group, or —C(═O)-NG 2 G 4 ; s and t are each independently an integer of 1 to 4; a plurality of R 5 s and/or a plurality of R 6 s may be the same or different; or any one of R 5 s ; 1 and any one of R 6 may combine with each other to form a C 1 -C 4 alkyleneoxy group] , except for removing any one hydrogen atom or hydroxy group from the inhibitor molecule represented by shows the inhibitory agent residue; Z is a single bond, arylene, heteroarylene, or C 2 -C 30An alkylene group (provided that one or more methylene groups in the chain of the alkylene group are —C(═O)—, —NR 7 —, —O— , —SiR 8 R 9 —, —SO r —, arylene; , And heteroarylene may be replaced with a group independently selected from the group consisting of, R 7 is a hydrogen atom or a C 1 -C 4 alkyl group, and R 8 and R 9 are each independently. , C 1 -C 4 alkyl groups, and r is an integer of 0 to 2).

[0032] In one embodiment of the present invention, A 1 and A 2 are each independently an inhibitor residue obtained by removing any one hydrogen atom or hydroxy group from the inhibitor molecule represented by the general formula (II). Show.

[0033] In one embodiment of the present invention, A 1 is Formula 40]

or

formula 41

has a structure represented by: A 2 is Formula 42]

or

formula 43

has a structure represented by: [In the formula, ring B 1 , ring B 2 , ring C 1 and ring C 2 are each independently an aryl group; and each R 1 is independently a hydrogen atom or —COO—( C 1 -C 4 alkyl group); W 1 and W 2 are each independently a single bond, or C 1-C 4 an alkylene group; X 1 is, -C (= O) -, - O-C (= O) -, or -NG 11 -SO 2 - a and; X 1 ' is, -NG Z - SO 2 −; X 2 is —C(═O)—, —C(═O)—O—, or —SO 2 —NG 12 —; X 2′ is —SO 2 —NG Z -, and; G 11 and G 12 are each independently a hydrogen atom, C 1 -C 4 alkyl group, or -COOR 2And a; G Z is X 1 ' or X 2' is a single bond linking Z and; R 2 is 1-5 aryl group optionally substituted C 1 -C 4 alkyl group There; Y 1 is, -NG 21 -, - NG 21 -L 11 -C (= O) -, - NG 21 -L 11 -C (= O) -NH -, - NG 21 -L 11 -C ( =O)-NG 31 -L 21 -C(=O)-, -NG 21 -L 11 -C(=O)-NG 31-L 21 -C (= O) -NH -, - NG 21 -L 3 -O-, or -NG 21 -G 4 ' - a and; Y 1' is, -NG 21 H, -NG 21 -L 11 -COOH or -NG 21 -L 11 -C(=O)-NG 31 -L 21 -COOH; Y 2 is -NG 22 -, -C(=O)-L 12 -NG 22 -. , -NH-C (= O) -L 12 -NG 22 -, - C (= O) -L 22-NG 32 -C(=O)-L 12 -NG 22 -, -NH -C(=O)-L 22 -NG 32 -C(=O)-L 12 -NG 22 -, -OL 3 -NG 22 -, or -G 4 ' -NG 22 - a and; Y 2' is, HNG 22 -, HOOC-L 12 -NG 22 -, or-L HOOC 22 -NG 32 -C (= O) - L 12 —NG 22 —; G 21 , G 31 , G 22 , and G 32 are each independently selected from the group consisting of a hydrogen atom, or a phenyl group optionally substituted with 1 to 5 —COOR 3 groups, and a —COOR 3 group. Is a C 1 -C 6 alkyl group optionally substituted with 1 to 5 substituents ; G 4′ is a C 1 -C 4 alkylene group, or a C 1 -C 4 alkyleneoxy-C 1 -C 4 alkylene group; R 3's each independently represent a hydrogen atom or a C 1 -C 4 alkyl group optionally substituted with 1 to 5 aryl groups ; L 11, L 21 , L 12 and L 22 are each independently substituted with 1 to 5 C 1 -C 6 alkyl groups optionally substituted with 1 to 5 —COOR 4 groups. A C 1 -C 6 alkylene group, a C 1 -C 4 alkylene-phenylene group, or a phenylene-C 1 -C 4 alkylene group; L 3 is a --COOR 4 group having 1 to 3 phenylene moieties. An optionally substituted C 1 -C 4 alkylene-phenylene group; each R 4 is independently a hydrogen atom, or 1 to 5 independently selected from the group consisting of an aryl group and a trimethylsilyl group; C optionally substituted with a substituent of

1- C 4 alkyl group; R 5 and R 6 are each independently a hydrogen atom, a halogen atom, a C 1 -C 4 alkyl group, or a C 1 -C 4 alkoxy group; and s and t are , Each independently an integer of 1 to 4; a plurality of R 5 s and/or a plurality of R 6 s may be the same or different; or any one of R 5 s and R s; Any one of 6 may be bonded to each other to form a C 1 -C 4 alkyleneoxy group; the symbol

Chemical formula 44

represents a point of attachment to Z ], Z is a single bond, arylene or hetero. Arylene, or C 2A -C 30 alkylene group, provided that one or more methylene groups in the chain of the alkylene group are independent of the group consisting of -C(=O)-, -NR 7 -, -O-, arylene, and heteroarylene. R 7 is a hydrogen atom or a C 1 -C 4 alkyl group).

[0034] Embodiments of each substituent of compound (I) are as follows.

[0035] In one embodiment, the aryl groups in Ring B and Ring C are each independently a C 6 to C 12 aryl group, preferably a phenyl group or a naphthyl group, more preferably a phenyl group. In one embodiment, the heteroaryl groups in Ring B and Ring C are each independently a 5- to 11-membered single-membered group containing 1 to 4 heteroatoms selected from oxygen atom, sulfur atom and nitrogen atom in addition to carbon atom. It is a cyclic or bicyclic aromatic heterocyclic group, preferably a pyrrolyl group, a furyl group, and a thienyl group, more preferably a thienyl group. In one embodiment, Ring B and Ring C are each independently an aryl group, preferably both are phenyl groups. In one embodiment, ring B and ring C are each independently a phenyl group, a naphthyl group, or a thienyl group, and preferably ring B and ring C are both phenyl groups.

[0036] In one embodiment, ring B 1 , ring B 2 , ring C 1 and ring C 2 are each independently a phenyl group or a naphthyl group, preferably ring B 1 , ring B 2 , ring C 1 , And ring C 2 are both phenyl groups.

[0037] In one embodiment, R 1 "-COO- (C in 1 -C 4 C alkyl group)" 1 -C 4 alkyl groups include methyl group, ethyl group, n- propyl group, an isopropyl group, n- butyl group Or a tert-butyl group. In one embodiment, R 1 is a hydrogen atom or a tert-butoxycarbonyl group, preferably a hydrogen atom.

[0038] In one embodiment, W is a C 1 -C 4 alkylene group, such as a methylene group, an ethylene group, a trimethylene group, or a tetramethylene group, preferably a C 1 -C 2 alkylene group, such as a methylene group. In another embodiment, W is a single bond or a C 1 -C 2 alkylene group, preferably a single bond or a methylene group.

[0039] In one embodiment, W 1 is a C 1 -C 4 alkylene group, such as a methylene group, an ethylene group, a trimethylene group, or a tetramethylene group, preferably a C 1 -C 2 alkylene group, such as a methylene group. In another embodiment, W 1 is a single bond or a C 1 -C 4 alkylene group, preferably a single bond or a C 1 -C 2 alkylene group, more preferably a single bond or a methylene group. Yes, and more preferably a single bond. In one embodiment, W 2 is a C 1 -C 4 alkylene group, such as a methylene group, an ethylene group, a trimethylene group, or a tetramethylene group, preferably a C 1 -C 2 alkylene group, such as a methylene group. In another embodiment, W 2 is a single bond or C It is a 1- C 4 alkylene group, preferably a single bond, or a C 1 -C 2 alkylene group, more preferably a single bond, ora methylene group, and further preferably a single bond. Industrial availability

[0708] The compound represented by the general formula (I) of the present invention or a pharmaceutically acceptable salt thereof has an excellent enteropeptidase inhibitory activity and/or an excellent trypsin inhibitory activity, and after oral administration, enteropeptidase and It has pharmacokinetic properties that strongly inhibit trypsin and/or have very low exposure to blood. Therefore, according to the present invention, it is a highly safe drug in which side effects due to exposure of a compound to blood are reduced, and prevention of various diseases associated with enteropeptidase inhibition and/or trypsin inhibition, such as obesity. An agent useful as an agent, a palliative and/or a therapeutic agent can be provided.

claims

Claim 1

Following general formula (I):

Chemical formula 1

wherein, A 1 and A 2 are each independently an inhibitor residue having at least one activity selected from enteropeptidase inhibitory activity and trypsin inhibitory activity And Z is a spacer that connects A 1 and A 2. ] or a pharmaceutically acceptable salt thereof.

Claim 2

A 1 and A 2 are each independently an inhibitor molecule selected from the following inhibitor molecule groups:

Chemical formula 2

Chemical formula 3

Chemical formula 4

[Chemical

formula 5] , or the following general formula (II) [ Wherein

, ring B and ring C are each independently an aryl group or a heteroaryl group; each R 1 is independently a hydrogen atom, or —COO—(C 1 -C 4 alkyl group); W is a single bond or a C 1 -C 4 alkylene group; X is -C(=O)-, -OC(=O)-, or -NG —SO 2 —; G is a hydrogen atom, a C 1 -C 4 alkyl group, or —COOR 2By and; R 2 is 1-5 aryl group optionally substituted C 1 -C 4 an alkyl group; Y is -NG 2 G 4 , -NG 2 -L 1 -COOH, - NG 2 -L 1 -C(=O)-NH 2 , -NG 2 -L 1 -C(=O)-NG 3 -L 2 -COOH, -NG 2 -L 1 -C(=O)-NG 3 -L 2 -C(=O)-NG 3 -L 2 -COOH, -NG 2- L 1 -C(=O)-NG 3 -L 2 -C(=O)-NH 2 , -NG 2 -L 3 -OH, or -NG 2 -(CH 2 -CH 2 -O) q —CH 2 —CH 2 —COOH; q is an integer of 1 to 6; G 2 and G 3 are each independently a hydrogen atom, or substituted with 1 to 5 —COOR 3 groups; An optionally substituted phenyl group and a —COOR 3 group, which is a C 1 -C 6 alkyl group optionally substituted with 1 to 5 substituents independently selected from the group consisting of : G 4 is a hydrogen atom, a C 1 -C 4 alkyl group, or a C 1 -C 4 alkoxy-C 1 -C 4 alkyl group; R 3 is independently a hydrogen atom, or 1 to 5 Is an optionally substituted C 1 -C 4 alkyl group; L 1 and L 2 are each independently 1 to 5 optionally substituted with 1 to 5 —COOR 4 groups; five C 1 -C 6 alkyl group substituted by a C even if 1 -C 6 alkylene group, substituted with 1 to 5 substituents selected independently from the group consisting of hydroxy and carboxy groups May have C 7A C 1 -C 6 alkylene group substituted with a -C 12 aralkyl group, a C 1 -C 4 alkylene-phenylene group, or a phenylene-C 1 -C 4 alkylene group; L 3 has a phenylene moiety of 1 to 3; C 1 -C 4 alkylene-phenylene group optionally substituted with 4 —COOR 4 groups ; R 4 is independently a hydrogen atom, or is independently selected from the group consisting of an aryl group and a trimethylsilyl group. Is a C 1 -C 4 alkyl group which may be substituted with 1 to 5 substituents ; R 5 and R 6 are each independently a hydrogen atom, a halogen atom, C 1

-C 4 alkyl group, C 1 -C 4 alkoxy group, carboxy group, or -C(=O)-NG 2 G 4 ; s and t are each independently an integer of 1 to 4; A plurality of R 5 s and/or a plurality of R 6 s may be the same or different, respectively; or, any one of R 5 s and any one of R 6 s are bonded to each other to form C 1 -C 4 may form an alkyleneoxy group] to represent an inhibitor residue obtained by removing any one hydrogen atom or hydroxy group from the inhibitor molecule; Z is a single bond, arylene, or heteroarylene. Or a C 2 -C 30 alkylene group (provided that one or more methylene groups in the chain of the alkylene group are —C(═O)—, —NR 7It may be replaced with a group independently selected from the group consisting of —, —O— , —SiR 8 R 9 —, —SO r —, arylene, and heteroarylene, and R 7 is a hydrogen atom or C 1 Is a -C 4 alkyl group, R 8 and R 9 are each independently a C 1 -C 4 alkyl group, and r is an integer of 0 to 2) . Or a pharmaceutically acceptable salt thereof.

Claim 3

The compound according to claim 2, wherein A 1 and A 2 each independently represent an inhibitor residue obtained by removing any one hydrogen atom or hydroxy group from the inhibitor molecule represented by the general formula (II) . Or a pharmaceutically acceptable salt thereof.

Claim 4

A 1 is Formula 7]

or

Formula 8

has a structure represented by: A 2 is

Chem 9

or

Formula 10

has a structure represented by: wherein the ring B 1 , Ring B 2 , ring C 1 and ring C 2 are each independently an aryl group; each R 1 is independently a hydrogen atom or —COO—(C 1 -C 4 alkyl group) by and; W 1 and W 2 are each independently a single bond, or a C 1 -C 4An alkylene group; X 1 is —C(═O)—, —O—C(═O)—, or —NG 11 —SO 2 —; X 1′ is —NG Z —SO 2 — by and; X 2 is, -C (= O) -, - C (= O) -O-, or -SO 2 -NG 12 - a and; X 2 ' are, -SO 2 -NG Z - a is ; G 11 and G 12 are each independently a hydrogen atom, C 1 -C 4 alkyl group, or -COOR 2 be; G Z is a single bond connecting Z 1′ or X 2′ and Z; R 2 is a C 1 -C 4 alkyl group optionally substituted by 1 to 5 aryl groups ; Y 1 is, -NG 21 -, - NG 21 -L 11 -C (= O) -, - NG 21 -L 11 -C (= O) -NH -, - NG 21 -L 11 -C (= O) - NG 31 -L 21 -C(=O)-, -NG 21 -L 11 -C(=O)-NG 31 -L 21-C (= O) -NH -, - NG 21 -L 3 -O-, or -NG 21 -G 4 ' - a and; Y 1' is, -NG 21 H, -NG 21 -L 11 -COOH Or -NG 21 -L 11 -C(=O)-NG 31 -L 21 -COOH; Y 2 is -NG 22 -, -C(=O)-L 12 -NG 22 -, -NH. -C(=O)-L 12 -NG 22 -, -C(=O)-L 22 -NG 32-C(=O)-L 12 -NG 22 -, -NH -C(=O)-L 22 -NG 32 -C(=O)-L 12 -NG 22 -, -OL 3 -NG 22 -, or -G 4 ' -NG 22 - a and; Y 2' is, HNG 22 -, HOOC-L 12 -NG 22 -, or-L HOOC 22 -NG 32 -C (= O) -L 12 - NG 22- is; G 21 , G 31 , G 22 and G 32 are each independently selected from the group consisting of a hydrogen atom, or a phenyl group optionally substituted with 1 to 5 —COOR 3 groups, and a —COOR 3 group. A C 1 -C 6 alkyl group which may be substituted with 5 to 5 substituents ; G 4′ is a C 1 -C 4 alkylene group, or a C 1 -C 4 alkyleneoxy-C 1 -C 4 An alkylene group; R 3's each independently represent a hydrogen atom or a C 1 -C 4 alkyl group optionally substituted with 1 to 5 aryl groups ; L 11 , L 21, L 12 and L 22 are each independently C optionally substituted with 1-5 C 1 -C 6 alkyl groups optionally substituted with 1-5 -COOR 4 groups. A 1- C 6 alkylene group, a C 1 -C 4 alkylene-phenylene group, or a phenylene-C 1 -C 4 alkylene group; L 3 is a phenylene moiety substituted with 1 to 3 -COOR 4 groups. Optionally a C 1 -C 4 alkylene-phenylene group; R 4 is each independently a hydrogen atom, or 1 to 5 substituents independently selected from the group consisting of an aryl group and a trimethylsilyl group. C 1 -C optionally substituted with

4 is an alkyl group; R 5 and R 6 are each independently a hydrogen atom, a halogen atom, C 1 -C 4 alkyl group, or a C 1 -C 4 alkoxy groups; s and t are each independently And is an integer of 1 to 4; a plurality of R 5 s and/or a plurality of R 6 s may be the same or different; or any one of R 5 s and R 6 s . One of them may be bonded to each other to form a C 1 -C 4 alkyleneoxy group; the symbol

Chemical formula 11

represents a point of attachment to Z ], Z is a single bond, arylene, heteroarylene, or C 2 -C 30An alkylene group, provided that one or more methylene groups in the chain of the alkylene group are independently selected from the group consisting of -C(=O)-, -NR 7 -, -O-, arylene, and heteroarylene. R 7 is a hydrogen atom or a C 1 -C 4 alkyl group), and the compound or a pharmaceutically acceptable compound thereof according to any one of claims 2 to 3. salt.

Claim 5

A 1 is Formula 12]

or

formula 13

has a structure represented by: A 2 is Formula 14]

or

formula 15

has a structure represented by: Z is a single bond, C 6 -C 12 arylene, -(CH 2 -CH 2 -O) m -CH 2 -CH 2 -, -(CH 2 -O-CH 2 ) m -, -(CH 2 ) m -(C 6 -C 12Arylene) - (CH 2 ) m -, or - (CH 2 ) n - and it; m is an integer of 1 ~ 6; n is an integer of 2 to 12 A compound according to claim 4 or A pharmaceutically acceptable salt thereof.

Claim 6

A 1 is Formula 16]

or

Formula 17

has a structure represented by: A 2 is

Formula 18

or

Formula 19

any of claims 4-5 having the structure represented by Or a pharmaceutically acceptable salt thereof.

Claim 7

A 1 is Formula 20]

has a structure represented by: A 2 is Formula 21]

allowed the compound or a pharmaceutically according to any one of claims 4-6 having the structure represented by Ru salt.

Claim 8

The compound or a pharmaceutically acceptable salt thereof according to any one of claims 4 to 7, which is represented by the following general formula (III):

Chemical formula 22

or the following general formula (IV):

Chemical formula 23

..

Claim 9

Each R 1 is independently a hydrogen atom or a tert-butoxycarbonyl group; W 1 and W 2 are each independently a single bond or a C 1 -C 4 alkylene group; X 1 but, -C (= O) -, - O-C (= O) -, or -NG 11 -SO 2 - a and; X 1 ' is, -NG Z -SO 2 - a and; X 2 is, -C (= O) -, - C (= O) -O-, or -SO 2 -NG 12 - a and; X 2 ' are, -SO 2 -NG Z-, and; G 11 and G 12 are each independently a hydrogen atom, C 1 -C 4 alkyl group, or -COOR 2 be; G Z is X 1 ' or X 2' couples Z and A single bond; R 2 is a C 1 -C 4 alkyl group which may be substituted with 1 to 5 aryl groups ; Y 1 is —NG 21 —, —NG 21 —L 11 —C (=O)-, -NG 21 -L 11 -C(=O)-NH-, -NG 21 -L 11 -C(=O)-NG 31 -L 21 -C(=O)-, -NG 21 -L 11 -C(=O)-NG 31 -L 21 -C(=O)-NH-,- NG 21 -L 3 -O-, or -NG 21 -G 4 ' - a and; Y 1' is, -NG 21 H, -NG 21 -L 11 -COOH, or -NG 21 -L 11 -C ( ═O)—NG 31 —L 21 —COOH; Y 2 is —NG 22-, -C(=O)-L 12 -NG 22 -, -NH -C(=O)-L 12 -NG 22 -, -C(=O)-L 22 -NG 32 -C(=O) -L 12 -NG 22 -, -NH -C(=O)-L 22 -NG 32 -C(=O)-L 12 -NG 22 -, -O -L 3 -NG 22 -, or -G 4 ' -NG 22 - a and; Y 2' is, HNG 22 -, HOOC-L 12 -NG 22 -, or HOOC-L 22 -NG 32 -C(=O)-L 12 -NG 22 -; G 21 , G 31 , G 22 and G 32 each independently represent a hydrogen atom or 1 to 5 -COOR. A C 1 -C 6 alkyl group optionally substituted with 1 to 5 substituents independently selected from the group consisting of a phenyl group optionally substituted with 3 groups and a —COOR 3 group ; G 4′ is a C 1 -C 4 alkylene group or a C 1 -C 4 alkyleneoxy-C 1 -C 4 alkylene group;

R 3 is each independently a hydrogen atom, a benzyl group or a tert-butyl group; L 11 , L 21 , L 12 and L 22 are each independently 1 to 5 —COOR 4 C 1 -C 6 alkylene group optionally substituted by 1 to 5 C 1 -C 6 alkyl groups optionally substituted by groups, C 1 -C 4 alkylene-phenylene group, or phenylene-C 1 Is a -C 4 alkylene group; L 3 is C 1 -C 4 in which the phenylene moiety may be substituted with 1 to 3 -COOR 4 groups. An alkylene-phenylene group; R 4 is each independently a hydrogen atom, a benzyl group, a 2-(trimethylsilyl)ethyl group, or a tert-butyl group; R 5 and R 6 are each independently A hydrogen atom, a halogen atom, a C 1 -C 4 alkyl group, or a C 1 -C 4 alkoxy group; each R 5 may be the same or different; Z is a single bond, C 6 --C 12 arylene, --(CH 2 --CH 2 --O) m --CH 2 --CH 2 --, --(CH 2 --O--CH 2 ) m -, - (CH 2 ) m - (C 6 -C 12 arylene) - (CH 2 ) m -, or - (CH 2 ) n - and it; m is an integer of 1 ~ 6; n is The compound or pharmaceutically acceptable salt thereof according to claim 8, which is an integer of 2 to 12 .

Claim 10

Each R 1 is independently a hydrogen atom or a tert-butoxycarbonyl group; W 1 and W 2 are each independently a single bond or a C 1 -C 4 alkylene group; X 1 but, -C (= O) -, - O-C (= O) -, or -NG 11 -SO 2 - a and; X 1 ' is, -NG Z -SO 2 - a and; X 2 is, -C (= O) -, - C (= O) -O-, or -SO 2 -NG 12 - a and; X 2 ' are, -SO 2 -NG Z-, and; G 11 and G 12 are each independently a hydrogen atom, C 1 -C 4 alkyl group, or -COOR 2 be; G Z is X 1 ' or X 2' couples Z and A single bond; R 2 is a C 1 -C 4 alkyl group which may be substituted with 1 to 3 aryl groups ; Y 1 is —NG 21 —, —NG 21 —L 11 —C (=O)-, -NG 21 -L 11 -C(=O)-NH-, -NG 21 -L 11 -C(=O)-NG 31 -L 21 -C(=O)-, -NG 21 -L 11 -C(=O)-NG 31 -L 21 -C(=O)-NH-, or -NG 21 -L 3 -O- and is; Y 1 ' is, -NG 21 H, -NG 21 -L 11 -COOH, or -NG 21 -L 11 -C (= O) -NG 31 -L 21 -COOH; Y 2 is -NG 22 -, -C(=O)-L 12 -NG 22-, -NH-C(=O)-L 12 -NG 22 -, -C(=O)-L 22 -NG 32 -C(=O)-L 12 -NG 22 -, -NH -C(= O) -L 22 -NG 32 -C (= O) -L 12 -NG 22 -, or-L -O 3 -NG 22 - a and; Y 2 ' is, HNG 22 -, HOOC-L 12 -NG 22 -or HOOC-L 22 -NG 32 -C(=O)-L 12 -NG 22 -;

G 21 , G 31 , G 22 and G 32 each independently represent a hydrogen atom or a group consisting of a phenyl group optionally substituted with 1 to 3 —COOR 3 groups and a —COOR 3 group. An independently selected C 1 -C 6 alkyl group optionally substituted with 1 to 3 substituents ; R 3 's each independently represent a hydrogen atom, a benzyl group, or a tert-butyl group; in it; L 11 , L 21 , L 12 , and L 22 are each independently 1-5 -COOR 4 in groups may be substituted one to five C 1 -C 6 alkyl group C 1 -C optionally substituted with A 6 alkylene group, a C 1 -C 4 alkylene-phenylene group, or a phenylene-C 1 -C 4 alkylene group; L 3 may have a phenylene moiety substituted with 1 to 2 -COOR 4 groups. C 1 -C 2 alkylene-phenylene group; R 4 is each independently a hydrogen atom, benzyl group, 2-(trimethylsilyl)ethyl group, or tert-butyl group; R 5 and R 6 are Each independently a hydrogen atom, a halogen atom, a C 1 -C 4 alkyl group, or a C 1 -C 4 alkoxy group; each R 5May be the same or different; Z is a single bond, biphenylene, -(CH 2 -CH 2 -O) m -CH 2 -CH 2 -, -(CH 2 -O-CH 2 ) M −, —(CH 2 ) m —biphenylene —(CH 2 ) m −, or —(CH 2 ) n −; m is an integer of 1 to 6; n is an integer of 2 to 12 is a compound or a pharmaceutically acceptable salt thereof according to claim 9.

Claim 11

Each R 1 is a hydrogen atom; W 1 and W 2 are each independently a single bond or a C 1 -C 4 alkylene group; X 1 is —C(═O)—, or -NG 11 -SO 2 - a and; X 1 ' is, -NG Z -SO 2 - a and; X 2 is, -C (= O) -, or -SO 2 -NG 12 - a and; X 2 ' is, -SO 2 -NG Z - a and; G 11And G 12 are each independently a hydrogen atom or —COOR 2 ; G Z is X 1′ or a single bond connecting X 2′ and Z; R 2 is one phenyl group A C 1 -C 4 alkyl group which may be substituted with ; Y 1 is —NG 21 —; Y 1′ is —NG 21 H; Y 2 is —NG 22 — ; Y 2 ' is, HNG 22 - a and; G 21And G 22 are each independently a hydrogen atom or a C 1 -C 3 alkyl group substituted with 1 to 3 carboxy groups ; R 5 and R 6 are each independently a hydrogen atom, A fluorine atom, a methyl group, or a methoxy group; each R 5 may be the same or different; Z is a single bond, [1,1′-biphenyl]-3,3′-diyl , -(CH 2 -CH 2 -O) m -CH 2 -CH 2 -, -(CH 2 -O-CH 2 ) m -, -(CH 2 ) m -([1,1'-biphenyl]- 3,3'-diyl)-(CH 2 ) 11. The compound or a pharmaceutically acceptable salt thereof according to claim 10, which is m − or —(CH 2 ) n −; m is an integer of 1 to 6; and n is an integer of 2 to 12. ..

Claim 12

Following general formula (V):

of 24

wherein, each R 1 is independently a hydrogen atom, or -COO- (C 1 -C 4 is an alkyl group); W 1 and W 2 is , Each independently a single bond or a C 1 -C 4 alkylene group; X 1 is —C(═O)— or —NG 11 —SO 2 —; X 2 is —C( ═O)—, or —SO 2 —NG 12 —; G 11 and G 12 are each independently a hydrogen atom, C 1-C 4 alkyl group or -COOR 2 ; R 2 is a C 1 -C 4 alkyl group optionally substituted with 1 to 5 aryl groups ; Y 1 is -NG 21 -, -NG 21 -L 11 -C (= O) -, - NG 21 -L 11 -C (= O) -NH -, - NG 21 -L 11 -C (= O) -NG 31 -L 21 -C (=O)-, -NG 21 -L 11 -C(=O)-NG 31 -L 21 -C(=O)-NH-, -NG 21 -L 3 -O-, or -NG 21 -G 4 ' - a and; Y 2 is, -NG 22 -, - C (= O) -L 12 -NG 22 -, - NH-C (= O ) -L 12 -NG 22 -, -C(=O)-L 22 -NG 32 -C(=O)-L 12 -NG 22 -, -NH -C(=O)-L 22 -NG 32 -. C(=O)-L 12 -NG 22 -, -OL 3 -NG 22 -, or -G 4'- NG 22 −; G 21 , G 31 , G 22 , and G 32 are each independently a hydrogen atom, or a phenyl group optionally substituted with 1 to 5 —COOR 3 groups, and —COOR 3 A C 1 -C 6 alkyl group which may be substituted with 1 to 5 substituents independently selected from the group consisting of groups ; G 4′ is a C 1 -C 4 alkylene group, or C 1 -C 4 alkyleneoxy-C 1 -C 4 alkylene group; R 3's each independently represent a hydrogen atom or C 1 -C optionally substituted by 1 to 5 aryl groups. 4 alkyl groups; L 11 , L 21 , L 12 and L 22 each independently represent 1 to 5 C 1 -C optionally substituted with 1 to 5 —COOR 4 groups. A C 1 -C 6 alkylene group which may be substituted with a 6 alkyl group, a C 1 -C 4 alkylene-phenylene group, or a phenylene-C 1 -C 4 alkylene group; L 3 has a phenylene moiety of 1 to A C 1 -C 4 alkylene-phenylene group optionally substituted with 3 —COOR 4 groups ; R 4

Are each independently a hydrogen atom, or a C 1 -C 4 alkyl group optionally substituted with 1 to 5 substituents independently selected from the group consisting of an aryl group and a trimethylsilyl group ; Each R 5 is independently a hydrogen atom, a halogen atom, a C 1 -C 4 alkyl group, or a C 1 -C 4 alkoxy group; Z is a single bond, C 6 -C 12 arylene, -( CH 2 —CH 2 —O) m —CH 2 —CH 2 —, —(CH 2 —O—CH 2 ) m —, —(CH 2 ) m-(C 6 -C 12 arylene)-(CH 2 ) m- , or -(CH 2 ) n- ; m is an integer of 1 to 6; n is an integer of 2 to 12] The compound or a pharmaceutically acceptable salt thereof according to any one of claims 4 to 7, which is represented by:

Claim 13

The compound according to claim 12 represented by the following general formula (VI):

Chemical Formula 25

or a pharmaceutically acceptable salt thereof.

Claim 14

Each R 1 is independently a hydrogen atom or a tert-butoxycarbonyl group; W 1 and W 2 are each independently a single bond or a C 1 -C 2 alkylene group; X 1 Is -C(=O)-, or -NG 11 -SO 2 -; X 2 is -C(=O)-, or -SO 2 -NG 12 -; G 11 and G 12 are , Each is a hydrogen atom; Y 1 is —NG 21 —, —NG 21 —L 11-C(=O)-, -NG 21 -L 11 -C(=O)-NH-, -NG 21 -L 11 -C(=O)-NG 31 -L 21 -C(=O)-, -NG 21 -L 11 -C (= O) -NG 31 -L 21 -C (= O) -NH -, - NG 21 -L 3 -O-, or -NG 21 -G 4 ' - a and; Y 2 is -NG 22 -, -C(=O)-L 12 -NG 22 -, -NH -C(=O)-L 12 -NG 22 -, -C(=O)-L 22 -NG 32 -C(=O)-L 12 -NG 22 -, -NH -C(=O)-L 22 -NG 32 -C(=O)-L 12 -NG 22 -, -O -L 3 —NG 22 — or —G 4′ —NG 22 —; G 21 , G 31 , G 22 and G 32 each independently represent a hydrogen atom or 1 to 3 —COOR 3 groups. in optionally substituted C even if 1 -C 3 is an alkyl group; G 4 ' is, C A C 1 -C 2 alkylene group or a C 1 -C 2 alkyleneoxy-C 1 -C 2 alkylene group; R 3 's each independently represent a hydrogen atom or a tert-butyl group; L 11 , L 21 , L 12 , and L 22 are each independently, C 1 -C 2 an alkylene group; L 3 is a phenylene moiety 1-3 -COOR 4 a C substituted with group 1 A C 4 alkylene-phenylene group; R 4Are each independently a hydrogen atom, or a C 1 -C 4 alkyl group optionally substituted by 1 to 5 substituents independently selected from the group consisting of an aryl group and a trimethylsilyl group ; Each R 5 is independently a hydrogen atom, a halogen atom, a C 1 -C 4 alkyl group, or a C 1 -C 4 alkoxy group; Z is a single bond, biphenylene, —(CH 2 —CH 2 -O) m -CH 2 -CH 2 -, -(CH 2 -O-CH 2 ) m -, -(CH 2 ) m -biphenylene-(CH 2 ) m-Or -(CH 2 ) n- ; m is an integer of 1 to 6; n is an integer of 2 to 12 ; or the pharmaceutically acceptable salt thereof.

Claim 15

Each R 1 is a hydrogen atom; W 1 and W 2 are each a single bond; X 1 is —C(═O)—; X 2 is —C(═O)— There; Y 1 is, -NG 21 -, - NG 21 -L 3 -O-, or -NG 21 -G 4 ' - a and; Y 2 is, -NG 22 -, - O-L 3 -NG 22 -, or -G 4 ' -NG 22 - a and; G 21And G 22 are each independently a C 1 -C 3 alkyl group substituted with 1 to 3 carboxy groups ; G 4′ is a C 1 -C 2 alkylene group, or C 1 -C 2 An alkyleneoxy-C 1 -C 2 alkylene group; L 3 is a C 1 -C 2 alkylene-phenylene group in which the phenylene moiety may be substituted with 1 to 2 -COOR 4 groups ; R 4 Are each independently a hydrogen atom or C 1 -C 4 which may be substituted with 1 to 5 substituents independently selected from the group consisting of an aryl group and a trimethylsilyl group. An alkyl group; each R 5 is independently a hydrogen atom, a fluorine atom, a methyl group, or a methoxy group, Z is a single bond, [1,1′-biphenyl]-3,3′— Diyl, -(CH 2 -CH 2 -O) m -CH 2 -CH 2 -, -(CH 2 -O-CH 2 ) m -, -(CH 2 ) m -([1,1'-biphenyl] 3,3'-diyl) - (CH 2 ) m -, or - (CH 2 ) n - and it; m is an integer of 1 ~ 6; n is an integer from 2 to 12 claim 14. The compound according to 14 or a pharmaceutically acceptable salt thereof.

Claim 16

A 1 is Formula 26]

has a structure represented by: A 2 is

of 27

has a structure represented by: wherein each R 1 is independently a hydrogen atom, or —COO—(C 1 -C 4 alkyl group); W 1 and W 2 are each independently a single bond or a C 1 -C 4 alkylene group; X 1 is —C(═O )-, -OC(=O)-, or -NG 11 -SO 2 -; X 2 is -C(=O)-, -C(=O)-O-, or -SO 2-NG 12 - a and; G 11 and G 12 are each independently a hydrogen atom, or a -COOR 2 be; R 2 is 1-5 optionally substituted by an aryl group C 1 - C 4 is an alkyl group; Y 1 is, -NG 21 -, - NG 21 -L 11 -C (= O) -NH-, or -NG 21 -L 11 -C (= O) -NG 31 -L 21 —C(═O)—NH—; Y 2 is —NG 22 —, —NH —C(═O)-L 12-NG 22 -, or-C -NH (= O) -L 22 -NG 32 -C (= O) -L 12 -NG 22 - a and; G 21 , G 31 , G 22 , and G 32 is, each independently a hydrogen atom, or a 1-5 -COOR 3 optionally substituted with groups which may phenyl and -COOR 3 with one to five substituents independently selected from the group consisting of radicals An optionally substituted C 1 -C 6 alkyl group; R 3's each independently represent a hydrogen atom or a C 1 -C 4 alkyl group optionally substituted by 1 to 5 aryl groups; And L 11 , L

21 , L 12 and L 22 may each independently be substituted with 1 to 5 C 1 -C 6 alkyl groups which may be substituted with 1 to 5 —COOR 4 groups. A C 1 -C 6 alkylene group, a C 1 -C 4 alkylene-phenylene group, or a phenylene-C 1 -C 4 alkylene group; each R 4 independently represents a hydrogen atom or 1 to 5 aryl groups. A C 1 -C 4 alkyl group which may be substituted with a group; R 5 and R 6 are each independently a hydrogen atom, C 1 -C 4

Alkyl group, or a C 1 -C 4 alkoxy group, or, R 5 and R 6 , taken together, C 1 -C 4 may form an alkylene group; symbol Formula 28]

is a Z Represents a bonding point of] Z is —(CH 2 —CH 2 —O) m —CH 2 —CH 2 —, or —(CH 2 ) n —; m is an integer of 1 to 6; The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 6 , wherein n is an integer of 2 to 12 .

Claim 17

A 1 is Formula 29]

has a structure represented by: A 2 is Formula 30]

the compound or a pharmaceutically acceptable salt thereof according to claim 16 having the structure represented by.

Claim 18

Following general formula (VII):

of 31

wherein, each R 1 is independently a hydrogen atom, or -COO- (C 1 -C 4 is an alkyl group); W 1 and W 2 is , Each independently a single bond or a C 1 -C 4 alkylene group; X 1 is —O—C(═O)— or —NG 11 —SO 2 —; X 2 is — C(═O)—O—, or —SO 2 —NG 12 —; G 11 and G 12 are each independently a hydrogen atom, or —COOR 2By and; R 2 is 1-5 aryl group optionally substituted C 1 -C 4 is an alkyl group; Y 1 is -NG 21 -, - NG 21 -L 11 -C (= O)-NH-, or -NG 21 -L 11 -C(=O)-NG 31 -L 21 -C(=O)-NH-; Y 2 is -NG 22 -, -NH -C. (=O)-L 12 -NG 22 -, or -NH-C(=O)-L 22 -NG 32 -C(=O)-L 12 -NG 22-, and; G 21 , G 31 , G 22 , and G 32 are each independently a hydrogen atom, or a 1-5 -COOR 3 an optionally substituted phenyl group and -COOR in group 3 group Is a C 1 -C 6 alkyl group optionally substituted with 1 to 5 substituents independently selected from the group consisting of ; R 3's are each independently a hydrogen atom, or 1 to 5 C 1 -C 4 alkyl group which may be substituted with 4 aryl groups; L 11 , L 21 , L 12 and L 22 each independently represent 1 to 5 —COOR 4 groups. 1-5 optionally substituted C 1A C 1 -C 6 alkylene group which may be substituted with a -C 6 alkyl group, a C 1 -C 4 alkylene-phenylene group, or a phenylene-C 1 -C 4 alkylene group; R 4 are each independently Is a hydrogen atom or a C 1 -C 4 alkyl group which may be substituted with 1 to 5 aryl groups ; Z is —(CH 2 —CH 2 —O) m —CH 2 —CH 2 -Or -(CH 2 ) n- ; m is an integer of 1 to 6; n is an integer of 2 to 12]

The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 and 16 to 17, which is represented by:

Claim 19

Each R 1 is independently a hydrogen atom or a tert-butoxycarbonyl group; W 1 and W 2 are each a C 1 -C 4 alkylene group; X 1 is —OC(= O)-, or -NG 11 -SO 2 -; X 2 is -C(=O)-O-, or -SO 2 -NG 12 -; G 11 and G 12 are each independently Is a hydrogen atom or —COOR 2 ; R 2 is C 1 -C 4 which may be substituted with 1 to 3 phenyl groups. An alkyl group; Y 1 is, -NG 21 -, - NG 21 -L 11 -C (= O) -NH-, or -NG 21 -L 11 -C (= O) -NG 31 -L 21 - C (= O) -NH- and is; Y 2 is, -NG 22 -, - NH-C (= O) -L 12 -NG 22 -, or-C -NH (= O) -L 22 -NG 32 —C(═O)—L 12 —NG 22 —; G 21 , G 31 , G 22 and G 32 are each independently a hydrogen atom, or 1 to 3 independently selected from the group consisting of a phenyl group optionally substituted with 1 to 3 —COOR 3 groups and a —COOR 3 group; A C 1 -C 6 alkyl group which may be substituted with a substituent ; R 3 's each independently represent a hydrogen atom, a benzyl group, or a tert-butyl group; L 11 , L 21 , L 12 , and L 22 are each independently 1-5 -COOR 4 1-5 which may be substituted with groups C 1 -C 6 alkyl optionally C may be substituted with group 1 -C 6 alkylene group, C 1 -C 4 alkylene-phenylene group, or phenylene-C 1- C 4 alkylene group; R 4 is each independently a hydrogen atom, a benzyl group, or a tert-butyl group; Z is —(CH 2 —CH 2 —O) m —CH 2 — CH 2 − or —(CH 2 ) n −; m is an integer of 1 to 6; n is an integer of 2 to 12 ; or a pharmaceutically acceptable compound thereof. salt.

Claim 20

Each R 1 is independently a hydrogen atom or a tert-butoxycarbonyl group; W 1 and W 2 are each a C 1 -C 2 alkylene group; X 1 is —O—C(= O)-, or -NG 11 -SO 2 -; X 2 is -C(=O)-O- or -SO 2 -NG 12 -; G 11 and G 12 are each independently Is a hydrogen atom or —COOR 2 , and R 2 is C 1 -C 4 which may be substituted with one phenyl group. An alkyl group; Y 1 is, -NG 21 -, - NG 21 -L 11 -C (= O) -NH-, or -NG 21 -L 11 -C (= O) -NG 31 -L 21 - C (= O) -NH- and is; Y 2 is, -NG 22 -, - NH-C (= O) -L 12 -NG 22 -, or-C -NH (= O) -L 22 -NG 32 —C(═O)—L 12 —NG 22 —; G 21 , G 31 , G 22 and G 32 are each independently a hydrogen atom, or 1 to 3 substituents independently selected from the group consisting of a phenyl group optionally substituted with one —COOR 3 group and a —COOR 3 group; A C 1 -C 3 alkyl group which may be substituted with ; R 3 is each independently a hydrogen atom or a tert-butyl group; L 11 , L 21 , L 12 and L 22 are , Each independently a C 1 -C 2 alkylene group optionally substituted by 1 to 2 C 1 -C 2 alkyl groups optionally substituted by 1 to 2 --COOR 4 groups, C 1- C 2 alkylene-phenylene group or phenylene-C 1—C 2 alkylene group; R 4 is each independently a hydrogen atom or a tert-butyl group; Z is —(CH 2 —CH 2 —O) m —CH 2 —CH 2 —; or - (CH 2 ) n a and -; ; m is an integer of 1 ~ 6 n is an integer from 2 to 12 acceptable salt compound or a pharmaceutically according to claim 19.

Claim 21

Each R 1 is each a hydrogen atom; W 1 and W 2 are each a C 1 -C 2 alkylene group; X 1 is —NG 11 —SO 2 —; X 2 is —SO 2 -NG 12 -; G 11 and G 12 each independently represent a hydrogen atom or -COOR 2 ; R 2 represents C 1 -C 4 which may be substituted with one phenyl group. An alkyl group; Y 1 is -NG 21 - a and; Y 2 is, -NG 22 - a and; G 21 and G 22 are each independently a group consisting of one phenyl group and a carboxy group substituted with a carboxy group A C 1 -C 3 alkyl group substituted with 1 to 3 substituents independently selected from : Z is —(CH 2 —CH 2 —O) m —CH 2 —CH 2 —, Or -(CH 2 ) n- ; m is an integer of 1 to 6; n is an integer of 2 to 12 ; or the pharmaceutically acceptable salt thereof.

Claim 22

Following general formula (VIII):

of 32

wherein, each R 1 is independently a hydrogen atom, or -COO- (C 1 -C 4 is an alkyl group); W 1 and W 2 is , Each independently a single bond or a C 1 -C 4 alkylene group; X 1 is —C(═O)— or —NG 11 —SO 2 —; X 2 is —C( ═O)—, or —SO 2 —NG 12 —; G 11 and G 12 are each independently a hydrogen atom, or —COOR 2By and; R 2 is 1-5 aryl group optionally substituted C 1 -C 4 is an alkyl group; Y 1 is -NG 21 -, - NG 21 -L 11 -C (= O)-NH-, or -NG 21 -L 11 -C(=O)-NG 31 -L 21 -C(=O)-NH-; Y 2 is -NG 22 -, -NH -C. (=O)-L 12 -NG 22 -, or -NH-C(=O)-L 22 -NG 32 -C(=O)-L 12 -NG 22-, and; G 21 , G 31 , G 22 , and G 32 are each independently a hydrogen atom, or a 1-5 -COOR 3 an optionally substituted phenyl group and -COOR in group 3 group Is a C 1 -C 6 alkyl group optionally substituted with 1 to 5 substituents independently selected from the group consisting of ; R 3's are each independently a hydrogen atom, or 1 to 5 C 1 -C 4 alkyl group which may be substituted with 4 aryl groups; L 11 , L 21 , L 12 and L 22 each independently represent 1 to 5 —COOR 4 groups. 1-5 optionally substituted C 1A C 1 -C 6 alkylene group which may be substituted with a -C 6 alkyl group, a C 1 -C 4 alkylene-phenylene group, or a phenylene-C 1 -C 4 alkylene group; R 4 are each independently Is a hydrogen atom or a C 1 -C 4 alkyl group which may be substituted with 1 to 5 aryl groups ; Z is —(CH 2 —CH 2 —O) m —CH 2 —CH 2 -Or -(CH 2 ) n- ; m is an integer of 1 to 6; n is an integer of 2 to 12]

The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 and 16 to 17, which is represented by:

Claim 23

Each R 1 is independently a hydrogen atom or a tert-butoxycarbonyl group; W 1 and W 2 are each independently a single bond or a C 1 -C 2 alkylene group; X 1 Is -C(=O)-, or -NG 11 -SO 2 -; X 2 is -C(=O)-, or -SO 2 -NG 12 -; G 11 and G 12 are , Each is a hydrogen atom; Y 1 is —NG 21 —, —NG 21 —L 11-C(=O)-NH-, or -NG 21 -L 11 -C(=O)-NG 31 -L 21 -C(=O)-NH-; Y 2 is -NG 22 -, -NH-C(=O)-L 12 -NG 22 -, or -NH-C(=O)-L 22 -NG 32 -C(=O)-L 12 -NG 22 -; G 21 , G 31 , G 22 and G 32 are each independently a hydrogen atom or C 1 -C 3 which may be substituted with 1 to 3 —COOR 3 groups. An alkyl group; R 3 are each independently a hydrogen atom, or a tert- butyl group; L 11 , L 21 , L 12 , and L 22 are each independently C 1 -C 2 alkylene a group; Z is - (CH 2 -CH 2 -O) m -CH 2 -CH 2 -, or - (CH 2 ) n - and it; m is an integer of 1 ~ 6; n is The compound according to claim 22, which is an integer of 2 to 12, or a pharmaceutically acceptable salt thereof.

Claim 24

Each R 1 is a hydrogen atom; W 1 and W 2 are each a single bond; X 1 is —C(═O)—; X 2 is —C(═O)— There; Y 1 is -NG 21 - a and; Y 2 is, -NG 22 - a and; G 21 and G 22 are each independently, C substituted with 1 to 3 carboxy groups 1 - A C 3 alkyl group; Z is —(CH 2 —CH 2 —O) m —CH 2 -CH 2 - and it is; m is an integer of 1-6 compound or a pharmaceutically acceptable salt thereof according to claim 23.

Claim 25

(2S,2'S)-2,2'-((oxybis(ethane-2,1-diyl))bis((N-(4-((4-guanidinobenzoyl)oxy)benzyl)sulfamoyl)azandiyl)) disuccinic acid; (2S, 13S) 3,12-bis (N- (4 - ((4- guanidino-benzoyl) oxy) benzyl) sulfamoyl) -6,9-dioxa-3,12-diaza tetradecane -1 ,2,13,14-Tetracarboxylic acid; (2S,16S)-3,15-bis(N-(4-((4-guanidinobenzoyl)oxy)benzyl)sulfamoyl)-6,9,12-trioxa- 3,15-diazaheptadecane-1,2,16,17-tetracarboxylic acid; (2S,19S)-3,18-bis(N-(4-((4-guanidinobenzoyl)oxy)benzyl)sulfamoyl )-6,9,12,15-Tetraoxa-3,18-diazaicosane-1,2,19,20-tetracarboxylic acid; (2S,22S)-3,21-bis(N-(4-((4 -Guanidinobenzoyl)oxy)benzyl)sulfamoyl)-6,9,12,15,18-pentaoxa-3,21-diazatricosane-1,2,22,23-tetracarboxylic acid; (2S,25S)-3,24 -Bis(N-(4-((4-guanidinobenzoyl)oxy)benzyl)sulfamoyl)-6,9,12,15,18,21-hexaoxa-3,24-diazahexacosane-1,2,25 , 26-Tetracarboxylic acid; (2S,2'S)-2,2'-(Propane-1,3-diylbis((N-(4-((4-guanidinobenzoyl)oxy)benzyl)sulfamoyl)azandiyl) ) Disuccinic acid; (2S, 2'S) -2,2 ' - ( butane-1,4-diyl bis ((N- (4 - (( 4- guanidino-benzoyl) oxy) benzyl) sulfamoyl) azanediyl)) disuccinic acid; (2S ,2'S)-2,2'-(Pentane-1,5-diylbis((N-(4-((4-guanidinobenzoyl)oxy)benzyl)sulfamoyl)azanediyl)) disuccinic acid: 3,18- Bis(((4-((4-guanidinobenzoyl)oxy)benzyl)oxy)carbonyl)-6,9,12,15-tetraoxa-3,18-diazaicosane-1,2,19,20-tetracarboxylic acid; 2,2'-(1,20-bis(4-((4-guanidinobenzoyl)oxy)phenyl)-3,18-dioxo-2,19-dioxa-4,17-diazaicosane-4,17-diyl) Disuccinic acid; (3S,6S,25S,28S)-6,25-bis(carboxymethyl)-3,28-bis((((4-((4-guanidinobenzoyl)oxy)benzyl)oxy)carbonyl) (Amino)-4,7,24,27-tetraoxo-11,14,17,20-tetraoxa-5,8,23,26-tetraazatriacontane-1,30-diacid; (3S,6S,23S, 26S)-6,23-bis(carboxymethyl)-3,26-bis((((4-((4-guanidinobenzoyl)oxy)benzyl)oxy)carbonyl)amino)-4,7,22,25- Tetraoxo-5,8,21,24-tetraazaoctacosane-1,28-dioic acid; (3S,22S)-3,22-bis(2-((3-carboxybenzyl)(((4-((4-guanidinobenzoyl)oxy)benzyl)oxy)carbonyl)amino)acetamide)-4,21- Dioxo-8,11,14,17-tetraoxa-5,20-diazatetracosane-1,24-dioic acid; (4S,7S,26S,29S)-4,7,26,29-tetrakis(carboxymethyl )-3,30-Bis(((4-((4-guanidinobenzoyl)oxy)benzyl)oxy)carbonyl)-5,8,25,28-tetraoxo-12,15,18,21-tetraoxa-3, 6,9,24,27,30-hexaazadtriacontane-1,32-diacid; (3S,22S)-3,22-bis((3-carboxybenzyl)(((4-((4-guanidino Benzoyl)oxy)benzyl)oxy)carbonyl)amino)-4,21-dioxo-8,11,14,17-tetraoxa-5,20-diazatetracosane-1,24-dioic acid; (2S,2′ S)-2,2'-((((5,8,11,14-Tetraoxa-2,17-diazaoctadecane-1,18-dioyl)bis(3,1-phenylene))bis(methylene)) Bis(((((4-((4-guanidinobenzoyl)oxy)benzyl)oxy)carbonyl)azanediyl))disuccinic acid; (2S,2′S)-2,2′-((((5,8, 11,14-Tetraoxa-2,17-diazaoctadecane-1,18-dioyl)bis(3,1-phenylene))bis(methylene))bis((N-(4-((4-guanidinobenzoyl)oxy ) Benzyl) sulfamoyl) azandiyl))) disuccinic acid; 3,12-Bis(10-guanidino-13-oxo-6,7,8,13-tetrahydrodibenzo[b,f][1,4]dioxesin-4-carbonyl)-6,9-dioxa-3,12 -Diazatetradecane-1,2,13,14-tetracarboxylic acid; (2S,13S)-3,12-bis(10-guanidino-13-oxo-6,7,8,13-tetrahydrodibenzo[b, f][1,4]dioxesin-4-carbonyl)-6,9-dioxa-3,12-diazatetradecane-1,2,13,14-tetracarboxylic acid; (2R,13R)-3,12- Bis(10-guanidino-13-oxo-6,7,8,13-tetrahydrodibenzo[b,f][1,4]dioxesin-4-carbonyl)-6,9-dioxa-3,12-diazatetradecane -1,2,13,14-Tetracarboxylic acid; (2S,13S)-3,12-bis(N-(4-((4-guanidinobenzoyl)oxy)benzyl)-N-methylsulfamoyl)- 6,9 -Dioxa-3,12-diazatetradecane-1,2,13,14- tetracarboxylic acid; 3,3'-(((ethane-1,2-diylbis(oxy))bis(ethane-2 , 1-Diyl))bis((N-(4-((4-guanidinobenzoyl)oxy)benzyl)sulfamoyl)azandiyl))dipentanedioic acid; (2S,2′S) -2,2 ′-((1 , 12-bis(4-((4-guanidinobenzoyl)oxy)phenyl)-5,8-dioxa-2,11-diazadodecanedisulfonyl)bis(azandiyl))disuccinic acid; (2S,13S)-3,12-Bis(N-(3-((4-guanidinobenzoyl)oxy)benzyl)sulfamoyl)-6,9-dioxa-3,12-diazatetradecane-1,2,13 , 14-Tetracarboxylic acid; (2S,2'S)-2,2'-((oxybis(ethane-2,1-diyl))bis((10-guanidino-13-oxo-6,7,8, 13-Tetrahydrodibenzo[b,f][1,4]dioxesine-4-carbonyl)azanediyl))disuccinic acid; (2S,16S)-3,15-bis(10-guanidino-13-oxo-6,7 ,8,13-Tetrahydrodibenzo[b,f][1,4]dioxesin-4-carbonyl)-6,9,12-trioxa-3,15-diazaheptadecane-1,2,16,17-tetra Carboxylic acid; (2S,2'S)-2,2'-(([1,1'-biphenyl]-3,3'-diylbis(methylene))bis((10-guanidino-13-oxo-6, 7,8,13-Tetrahydrodibenzo[b,f][1,4]dioxesin-4-carbonyl)azanediyl))disuccinic acid; (2S,2′S)-2,2′-((((oxybis (Ethane-2,1-diyl))bis(oxy))bis(3-carboxy-5,1-phenylene))bis(methylene))bis((10-guanidino-13-oxo-6,7,8, 13-Tetrahydrodibenzo[b,f][1,4]dioxesine-4-carbonyl)azadiyl))disuccinic acid; and (2S,2′S)-2,2′-((oxybis(ethane-2,1 -Diyl))bis((3-((4-guanidinobenzoyl)oxy)benzoyl)azanediyl))disuccinic acid The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 7, which is selected from the group consisting of:

Claim 26

(2S,2'S)-2,2'-((oxybis(ethane-2,1-diyl))bis((N-(4-((4-guanidinobenzoyl)oxy)benzyl)sulfamoyl)azandiyl)) disuccinic acid; (2S, 13S) 3,12-bis (N- (4 - ((4- guanidino-benzoyl) oxy) benzyl) sulfamoyl) -6,9-dioxa-3,12-diaza tetradecane -1 ,2,13,14-Tetracarboxylic acid; (2S,2'S)-2,2'-(butane-1,4-diylbis((N-(4-((4-guanidinobenzoyl)oxy)benzyl) sulfamoyl) azanediyl)) disuccinic acid; (2S, 13S)-3,12-bis (10-guanidino-13-oxo -6,7,8,13- tetrahydropyran dibenzo [b, f] [1,4] Jiokiseshin -4-carbonyl)-6,9-dioxa-3,12-diazatetradecane-1,2,13,14-tetracarboxylic acid; (2S,2'S)-2,2'-((oxybis(ethane -2,1-Diyl))bis((10-guanidino-13-oxo-6,7,8,13-tetrahydrodibenzo[b,f][1,4]dioxesin-4-carbonyl)azanediyl)) Acid; (2S,16S)-3,15-bis(10-guanidino-13-oxo-6,7,8,13-tetrahydrodibenzo[b,f][1,4]dioxesin-4-carbonyl)-6 , 9,12-Trioxa-3,15-diazaheptadecane-1,2,16,17-tetracarboxylic acid; (2S,2'S)-2,2'-(([1,1'-biphenyl]-3,3'-diylbis(methylene))bis((10-guanidino-13-oxo-6,7,8 , 13-Tetrahydrodibenzo[b,f][1,4]dioxesin-4-carbonyl)azanediyl)) disuccinic acid; and (2S,2′S)-2,2′-((((oxybis(ethane -2,1-Diyl))bis(oxy))bis(3-carboxy-5,1-phenylene))bis(methylene))bis((10-guanidino-13-oxo-6,7,8,13- The compound according to any one of claims 1 to 7 or a pharmaceutically acceptable compound thereof, which is selected from the group consisting of tetrahydrodibenzo[b,f][1,4]dioxesin-4-carbonyl)azanediyl))disuccinic acid. Salt.

Claim 27

The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 26, which has a molecular weight of 1000 or more.

Claim 28

A pharmaceutical composition comprising the compound according to any one of claims 1 to 27 or a pharmaceutically acceptable salt thereof.

Claim 29

29. The pharmaceutical composition according to claim 28, for preventing, alleviating and/or treating obesity.