KR20080080305A - Thrombopoietin activity modulating compounds and methods - Google Patents

Abstract

Disclosed herein are amide containing heterocyclic compounds, pharmaceutical compositions comprising the compounds, methods of modulating the activity a thrombopoietin receptor using the compounds, methods of identifying compounds as thrombopoietin receptor modulators, and methods of treating disease by administering the compounds to a patient in need thereof.

Description

Thrombopoietin activity modulating compounds and methods for regulating the same

Technical field

The present invention relates to compounds and methods in the chemical and pharmaceutical fields. More particularly, the present invention relates to compounds that modulate one or more thrombopoietin activity and / or bind to the thrombopoietin receptor, methods of making and using the compounds.

Background technology

Thrombopoietin (TPO), called c-Mpl ligand, mpl ligand, megapoietin and megakaryocyte growth and development factors, has been shown to be involved in platelet production. See, eg, Wendling, F., et. al., Biotherapy 10 (4): 269-77 (1998); Kuter DJ. et al., The Oncologist, 1: 98-106 (1996); Metcalf, Nature 369: 519-520 (1994), which is incorporated herein by reference in its entirety. TPO has been cloned and its amino acid sequence and cDNA sequence encoding it are known. See, eg, U.S. 5,766,581; Kuter, D.J. et al., Proc. Natl. Acad. Sci., 91: 11104-11108 (1994); de Sauvage F.V., et al., Nature, 369: 533-538 (1994); Lok, S. et al., Nature 369: 565-568 (1994); Wending, F. et al., Nature, 369: 571-574 (1994), all of which are incorporated herein by reference in their entirety.

In certain instances, TPO activity is shown by TPO binding to the TPO receptor (also called MPL). TPO receptors have been cloned and their amino acid sequences are known. See, eg, Vigon et al., Proc. Natl. Acad. Sci., 89: 5640-5644 (1992), which is incorporated herein by reference in its entirety.

In certain instances, TPO modulators may be useful for treating a variety of hematopoietic conditions, such as, but not limited to, thrombocytopenia. See, eg, Baser et al. Blood 89: 3118-3128 (1997); Fanucchi et al. New Engl. J. Med. 336: 404-409 (1997), which is incorporated herein by reference in its entirety. For example, platelet levels may be reduced in certain chemotherapy patients, such as, but not limited to, chemotherapy and / or radiation therapy patients for cancer treatment. In certain instances, the aforementioned patients are treated with selective TPO modulators to increase platelet counts. In certain instances, the selective TPO modulator stimulates glial cells, and the nerve cells damaged by the stimulation can be repaired.

Summary of the Invention

In certain embodiments, the present invention provides a compound of Formula (I), (II), (III), (IV), (V) or (VI), a pharmaceutically acceptable salt, ester, amide or prodrug thereof.

In the above formula,

R ¹ is hydrogen, halogen, OR ¹⁴ , NO ₂ , CN, NR ¹⁴ R ¹⁵ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ hetero Alkyl, CO ₂ R ¹⁴ , CONR ¹⁴ R ¹⁵ , SO ₃ R ¹⁴ , SO ₂ NR ¹⁴ R ¹⁵ and carboxylic acid bioisostere;

Each R ² is a group consisting of hydrogen, halogen, OR ¹⁴ , NR ¹⁴ R ¹⁵ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, and optionally substituted C ₁ -C ₆ heteroalkyl Independently from;

R ³ and R ⁴ are independently selected from the group consisting of hydrogen, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl and optionally substituted C ₁ -C ₆ heteroalkyl;

R ⁵ is selected from the group consisting of hydrogen, halogen, OR ¹⁴ , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ haloheteroalkyl;

R ⁶ consists of optionally substituted C ₁ -C ₁₀ alkyl, optionally substituted C ₁ -C ₁₀ haloalkyl and optionally substituted C ₁ -C ₁₀ heteroalkyl, each optionally substituted with substituted aryl or substituted heteroaryl selected from the group, or, R ⁶ is ^{_{(CH 2) m R 18,}} C (O) NHR 18, C≡CR 18, CR 3 = CR 4 R 18 , and is selected from the group consisting of CR ³ = R ^18;

R ⁷ is selected from the group consisting of CO ₂ R ¹⁴ , CONR ¹⁴ R ¹⁵ , SO ₃ R ¹⁴ , SO ₂ NR ¹⁴ R ¹⁵ and a carboxylic acid bioequivalent;

Each of R ⁸ and R ⁹ is hydrogen, OR ¹⁶ , NR ¹⁶ R ¹⁷ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ heteroalkyl, (CH ₂ ) _m R ¹⁸ and none independently; R ⁸ and R ⁹ together form an optionally substituted olefin; R ⁸ and R ⁹ are joined to form an optionally substituted C ₃ -C ₈ ring;

R ¹⁰ is hydrogen, halogen, oxo, OR ¹⁶ , NR ¹⁶ R ¹⁷ , SR ¹⁶ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl and optionally substituted C ₁ -C ₆ hetero Selected from the group consisting of alkyl;

R ¹¹ is selected from the group consisting of hydrogen, halogen, OR ¹⁴ , NR ¹⁴ R ¹⁵ and SR ¹⁴ ; R ¹¹ and R ⁴ are joined to form an optionally substituted heterocycle;

R ¹² is selected from the group consisting of hydrogen, halogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ haloheteroalkyl;

R ¹³ is hydrogen, halogen, CN, NO ₂ , CO ₂ R ¹⁴ , S (O) _m R ¹⁴ , C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl and C ₁ -C ₄ haloheteroalkyl;

R ¹⁴ is selected from the group consisting of hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ heterohaloalkyl;

R ¹⁵ is selected from the group consisting of hydrogen, SO ₂ R ¹⁹ , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ heterohaloalkyl;

A group of R ¹⁶ and R ¹⁷ consisting of hydrogen, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ heteroalkyl, and (CH ₂ ) _m R ¹⁸ Each independently selected from; R ¹⁶ and R ¹⁷ If either is optionally substituted C ₂ -C ₆ alkyl, the other is none; R ¹⁶ and R ¹⁷ are joined to form an optionally substituted C ₃ -C ₈ ring;

R ¹⁸ is selected from an optionally substituted monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle, wherein R ¹⁸ comprises a nonaromatic heterocycle or carbocycle When attached, the attachment position may be on a nonaromatic heterocycle or carbocycle or aromatic ring system;

R ¹⁹ is selected from the group consisting of hydrogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl and optionally substituted aryl;

D is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle;

E is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle;

L is NH or none;

Q is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle;

U is selected from the group consisting of O, NR ⁴ , CR ³ R ⁴ , CO and none;

W is selected from the group consisting of O, NR ⁴ , CR ³ R ⁴ , CO and none;

X is N or CR ⁵ ;

Y is 1 to 4 atomic spacers comprising one or more groups selected from optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ heteroalkyl, optionally substituted phenyl and optionally substituted heteroaryl;

Z is absent; 2 to 5 atomic spacers selected from optionally substituted C ₆ -C ₁₀ aryl and optionally substituted C ₁ -C ₈ heteroaryl, each optionally bonded with an optionally substituted non-aromatic heterocycle or carbocycle; And _{1 selected} from optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ heteroalkyl, and optionally substituted C ₁ -C ₆ haloalkyl, each optionally optionally conjugated with optionally substituted C ₆ -C ₁₀ aryl; To 5 atomic spacers;

m is 0, 1, 2 or 3;

n is 0 or 1;

Each optionally substituted group is alkyl, heteroalkyl, haloalkyl, heterohaloalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, non-aromatic heterocycle, hydroxy, alkoxy, aryloxy, mercapto, alkylthio, Arylthio, cyano, halo, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, S-sulfone Amido, N-sulfonamido, C-carboxy, O-carboxy, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, trihalomethanesulfonyl, = O, = S, amino and amino Substituted or unsubstituted with one or more groups independently selected from the group consisting of protected derivatives of groups;

로 디하이드로피라졸릴렌을 형성하는 경우, (i) X가 N이고 W가 NH이면 D는 나프틸이 아니고, (ii) X가 CH이고, W가 NH이고, Z가 페닐이고, R¹⁰ 또는 R¹¹이 -(CH₂)_0-6OH이면, D는 페닐이 아니고, (iii)

는 피라졸릴이나 임의 치환된 5-하이드록시피라졸릴이 아니고, (iv) U는 NH가 아니고;Provided that Y is a compound of formula (I) or (II)

When forming dihydropyrazolylene, (i) D is not naphthyl if X is N and W is NH, (ii) X is CH, W is NH, Z is phenyl, R ¹⁰ or If R ¹¹ _is- (CH ₂ ) _0-6 OH, then D is not phenyl, and (iii)

Is not pyrazolyl or optionally substituted 5-hydroxypyrazolyl, and (iv) U is not NH;

Further, provided that X is N and W is NH, then D is not phenyl;

Additionally, in the compounds of Formula (III) or (VI), if X is N and W is NH, then R ⁶ , R ¹⁰ and R ^{11 do not} comprise carboxylic, amido, ester or sulfurate functional groups or carboxylic acid equivalents. Do not.

In certain embodiments, the present invention provides a compound of Formula (I), (II) or (III), a pharmaceutically acceptable salt, ester, amide or prodrug thereof.

[Formula I]

[Formula II]

[Formula III]

In the above formula,

R ¹ is hydrogen, halogen, OR ¹⁴ , NO ₂ , CN, NR ¹⁴ R ¹⁵ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ hetero Alkyl, CO ₂ R ¹⁴ , CONR ¹⁴ R ¹⁵ , SO ₃ R ¹⁴ , SO ₂ NR ¹⁴ R ¹⁵ and a carboxylic acid bioequivalent;

Each R ² is a group consisting of hydrogen, halogen, OR ¹⁴ , NR ¹⁴ R ¹⁵ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, and optionally substituted C ₁ -C ₆ heteroalkyl Independently from;

R ³ and R ⁴ are independently selected from the group consisting of hydrogen, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl and optionally substituted C ₁ -C ₆ heteroalkyl;

R ⁵ is selected from the group consisting of hydrogen, halogen, OR ¹⁴ , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ haloheteroalkyl;

R ⁶ is optionally substituted C ₁ -C ₁₀ alkyl, optionally substituted C ₁ -C ₁₀ haloalkyl, optionally substituted C ₁ -C ₁₀ heteroalkyl, (CH ₂ ) _m R ¹⁸ , C (O) NHR ¹⁸ , C≡CR ¹⁸ , CR ³ = CR ⁴ R ¹⁸ and CR ³ = R ¹⁸ ;

R ⁷ is selected from the group consisting of CO ₂ R ¹⁴ , CONR ¹⁴ R ¹⁵ , SO ₃ R ¹⁴ , SO ₂ NR ¹⁴ R ¹⁵ and a carboxylic acid bioequivalent;

Each of R ⁸ and R ⁹ is hydrogen, OR ¹⁶ , NR ¹⁶ R ¹⁷ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ heteroalkyl, (CH ₂ ) _m R ¹⁸ and none independently; R ⁸ and R ⁹ together form an optionally substituted olefin; R ⁸ and R ⁹ are joined to form an optionally substituted C ₃ -C ₈ ring;

R ¹⁰ is hydrogen, halogen, oxo, OR ¹⁶ , NR ¹⁶ R ¹⁷ , SR ¹⁶ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl and optionally substituted C ₁ -C ₆ hetero Selected from the group consisting of alkyl;

R ¹¹ is selected from the group consisting of hydrogen, halogen, OR ¹⁴ , NR ¹⁴ R ¹⁵ and SR ¹⁴ ; R ¹¹ and R ⁴ are joined to form an optionally substituted heterocycle;

R ¹² is selected from the group consisting of hydrogen, halogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ haloheteroalkyl;

R ¹⁴ is selected from the group consisting of hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ heterohaloalkyl;

R ¹⁵ is selected from the group consisting of hydrogen, SO ₂ R ¹⁹ , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ heterohaloalkyl;

A group of R ¹⁶ and R ¹⁷ consisting of hydrogen, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ heteroalkyl, and (CH ₂ ) _m R ¹⁸ Each independently selected from; R ¹⁶ and R ¹⁷ If either is optionally substituted C ₂ -C ₆ alkyl, the other is none; R ¹⁶ and R ¹⁷ are joined to form an optionally substituted C ₃ -C ₈ ring;

R ¹⁸ is selected from an optionally substituted monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle, wherein R ¹⁸ comprises a nonaromatic heterocycle or carbocycle When attached, the attachment position may be on a nonaromatic heterocycle or carbocycle or aromatic ring system;

R ¹⁹ is selected from the group consisting of hydrogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl and optionally substituted aryl;

D is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle;

E is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle;

L is NH or none;

Q is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle;

U is selected from the group consisting of O, NR ⁴ , CR ³ R ⁴ , CO and none;

W is selected from the group consisting of O, NR ⁴ , CR ³ R ⁴ , CO and none;

X is N or CR ⁵ ;

Y is 1 to 4 atomic spacers comprising one or more groups selected from optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ heteroalkyl, optionally substituted phenyl and optionally substituted heteroaryl;

Z is absent; 2 to 5 atomic spacers selected from optionally substituted C ₆ -C ₁₀ aryl and optionally substituted C ₁ -C ₈ heteroaryl, each optionally bonded with an optionally substituted non-aromatic heterocycle or carbocycle; And _{1 selected} from optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ heteroalkyl, and optionally substituted C ₁ -C ₆ haloalkyl, each optionally optionally conjugated with optionally substituted C ₆ -C ₁₀ aryl; To 5 atomic spacers;

m is 0, 1, 2 or 3;

n is 0 or 1;

Each optionally substituted group is alkyl, heteroalkyl, haloalkyl, heterohaloalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, non-aromatic heterocycle, hydroxy, alkoxy, aryloxy, mercapto, alkylthio, Arylthio, cyano, halo, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, S-sulfon Amido, N-sulfonamido, C-carboxy, O-carboxy, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, trihalomethanesulfonyl, = O, = S, amino and amino Substituted or unsubstituted with one or more groups independently selected from the group consisting of protected derivatives of groups;

로 디하이드로피라졸릴렌을 형성하는 경우, (i) X가 N이고 W가 NH이면 D는 나프틸이 아니고, (ii) X가 CH이고, W가 NH이고, Z가 페닐이고, R¹⁰ 또는 R¹¹이 -(CH₂)_0-6OH이면, D는 페닐이 아니고, (iii)

는 피라졸릴이나 임의 치환된 5-하이드록시피라졸릴이 아니고, (iv) U는 NH가 아니고;Provided that Y is in the compound of Formula I or II

When forming dihydropyrazolylene, (i) D is not naphthyl if X is N and W is NH, (ii) X is CH, W is NH, Z is phenyl, R ¹⁰ or If R ¹¹ _is- (CH ₂ ) _0-6 OH, then D is not phenyl, and (iii)

Is not pyrazolyl or optionally substituted 5-hydroxypyrazolyl, and (iv) U is not NH;

Further, provided that X is N and W is NH, then D is not phenyl;

Further, provided that X is N and W is NH in the compound of formula III, R ⁶ , R ¹⁰ And R ¹¹ does not include carboxylic, amido, ester, or sulfurate functional groups or carboxylic acid bioisomers.

In certain embodiments, the present invention provides a compound of Formula (I), (II) or (III), a pharmaceutically acceptable salt, ester, amide or prodrug thereof as mentioned above.

In the formula

(여기서, A, B 및 C는 O, S 및 NR²⁰으로 이루어진 그룹으로부터 각각 독립적으로 선택된다)로 이루어진 그룹으로부터 선택된 카복실산 생동등체로 이루어진 그룹으로부터 선택되고; R ¹ is halogen; OR ¹⁴ ; NO ₂ ; CN; NR ¹⁴ R ¹⁵ ; C ₁ -C ₄ alkyl; C ₁ -C ₄ haloalkyl; Optionally substituted C ₁ -C ₄ heteroalkyl; CO ₂ R ¹⁴ ; CONR ¹⁴ R ¹⁵ ; SO ₃ R ¹⁴ ; SO ₂ NR ¹⁴ R ¹⁵ ; And tetrazole, NHSO ₂ R ¹⁹ , OC (S) NR ¹⁴ R ¹⁵ , SC (O) NR ¹⁴ R ¹⁵ and

Wherein A, B and C are each independently selected from the group consisting of O, S and NR ²⁰ ;

Each R ² is hydrogen, halogen, OR ¹⁴ , NR ¹⁴ R ¹⁵ , C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl and C ₁ -C ₄ heteroalkyl and C ₁ -C ₄ Independently selected from the group consisting of heterohaloalkyl;

R ³ and R ⁴ are independently selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl and optionally substituted C ₁ -C ₄ heteroalkyl;

R ⁵ is selected from the group consisting of hydrogen, OR ¹⁴ , C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl and C ₁ -C ₄ halo heteroalkyl;

R ⁶ is C ₁ -C ₁₀ alkyl, C ₁ -C ₁₀ haloalkyl, optionally substituted C ₁ -C ₁₀ heteroalkyl, (CH ₂ ) _m R ¹⁸ , C (O) NHR ¹⁸ , C≡CR ¹⁸ , CR ³ = CR ⁴ R ¹⁸ and CR ³ = R ¹⁸ ;

(여기서, A, B 및 C는 O, S 및 N으로 이루어진 그룹으로부터 각각 독립적으로 선택된다)로 이루어진 그룹으로부터 선택된 카복실산 생동등체로 이루어진 그룹으로부터 선택되고;R ⁷ is CO ₂ R ¹⁴ ; CONR ¹⁴ R ¹⁵ ; SO ₃ R ¹⁴ ; SO ₂ NR ¹⁴ R ¹⁵ ; And tetrazole, NHSO ₂ R ¹⁹ , OC (S) NR ¹⁴ R ¹⁵ , SC (O) NR ¹⁴ R ¹⁵ and

Wherein A, B and C are each independently selected from the group consisting of O, S and N; and are selected from the group consisting of carboxylic acid bioequivalents selected from the group consisting of;

Each of R ⁸ and R ⁹ is hydrogen, OR ¹⁶ , NR ¹⁶ R ¹⁷ , C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, optionally substituted C ₁ -C ₄ heteroalkyl, (CH ₂ ) _m R Independently selected from ¹⁸ and none; R ⁸ and R ⁹ together form an optionally substituted olefin; R ⁸ and R ⁹ are joined to form an optionally substituted C ₃ -C ₈ ring;

R ¹⁰ is selected from the group consisting of hydrogen, halogen, oxo, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl and optionally substituted C ₁ -C ₄ heteroalkyl;

R ¹¹ is selected from the group consisting of hydrogen, halogen, OR ¹⁴ , NR ¹⁴ R ¹⁵ and SR ¹⁴ ; R ¹¹ and R ⁴ are joined to form an optionally substituted heterocycle;

R ¹² is selected from the group consisting of hydrogen, halogen, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl and C ₁ -C ₄ haloheteroalkyl;

R ¹³ is hydrogen, halogen, CN, NO ₂ , CO ₂ R ¹⁴ , S (O) _m R ¹⁴ , C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl and C ₁ -C ₄ haloheteroalkyl;

R ¹⁴ is selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl and C ₁ -C ₄ heterohaloalkyl;

R ¹⁵ is selected from the group consisting of hydrogen, SO ₂ R ¹⁹ , C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl and C ₁ -C ₄ heteroalkyl;

R ¹⁶ and R ¹⁷ are each independently selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, optionally substituted C ₁ -C ₄ heteroalkyl and (CH ₂ ) _m R ¹⁸ ; R ¹⁶ and R ¹⁷ If either is C ₂ -C ₆ alkyl, the other is none; R ¹⁶ and R ¹⁷ are joined to form an optionally substituted C ₄ -C ₇ ring;

R ¹⁹ is selected from the group consisting of hydrogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl and aryl;

D is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle;

E is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle;

G is selected from the group consisting of O, S and NR ¹⁴ ;

J is O, S, NR ¹⁴ And CR ¹⁴ R ¹⁵ ;

K is O or S;

Q is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle;

U is selected from the group consisting of O, NR ⁴ , CR ³ R ⁴ , CO and none;

W is selected from the group consisting of O, NR ⁴ , CR ³ R ⁴ , CO and none;

X is N or CR ⁵ ;

,

,

및

로 이루어진 그룹으로부터 선택되고;Y is

,

,

And

Is selected from the group consisting of;

Z is absent; 2 to 5 atomic spacers selected from optionally substituted C ₆ -C ₁₀ aryl and optionally substituted C ₁ -C ₈ heteroaryl, each optionally bonded with an optionally substituted non-aromatic heterocycle or carbocycle; And _{1 selected} from optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ heteroalkyl, and optionally substituted C ₁ -C ₆ haloalkyl, each optionally optionally conjugated with optionally substituted C ₆ -C ₁₀ aryl; To 5 atomic spacers;

m is 0, 1, 2 or 3;

n is 0 or 1;

로 디하이드로피라졸릴렌을 형성하는 경우, (i) X가 N이고 W가 NH이면 D는 나프틸이 아니고, (ii) X가 CH이고, W가 NH이고, Z가 페닐이고, R¹⁰ 또는 R¹¹이 -(CH₂)_0-6OH이면, D는 페닐이 아니고, (iii)

는 피라졸릴이나 임의 치환된 5-하이드록시피라졸릴이 아니고, (iv) U는 NH가 아니고;Provided that Y is a compound of formula (I) or (II)

When forming dihydropyrazolylene, (i) D is not naphthyl if X is N and W is NH, (ii) X is CH, W is NH, Z is phenyl, R ¹⁰ or If R ¹¹ _is- (CH ₂ ) _0-6 OH, then D is not phenyl, and (iii)

Is not pyrazolyl or optionally substituted 5-hydroxypyrazolyl, and (iv) U is not NH;

Further provided that if X is N and W is NH, then D is not phenyl;

Further, provided that X is N and W is NH in the compound of formula III, R ⁶ , R ¹⁰ And R ¹¹ does not include carboxylic, amido, ester, or sulfurate functional groups or carboxylic acid bioisomers.

In certain embodiments, the present invention provides a compound of Formula IV, V or VI, a pharmaceutically acceptable salt, ester, amide or prodrug thereof.

[Formula IV]

[Formula V]

[Formula VI]

In the above formula,

R ¹ is hydrogen, halogen, OR ¹⁴ , NO ₂ , CN, NR ¹⁴ R ¹⁵ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ hetero Alkyl, CO ₂ R ¹⁴ , CONR ¹⁴ R ¹⁵ , SO ₃ R ¹⁴ , SO ₂ NR ¹⁴ R ¹⁵ and a carboxylic acid bioequivalent;

Each R ² is a group consisting of hydrogen, halogen, OR ¹⁴ , NR ¹⁴ R ¹⁵ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, and optionally substituted C ₁ -C ₆ heteroalkyl Independently from;

R ³ and R ⁴ are independently selected from the group consisting of hydrogen, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl and optionally substituted C ₁ -C ₆ heteroalkyl;

R ⁵ is selected from the group consisting of hydrogen, halogen, OR ¹⁴ , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ haloheteroalkyl;

R ⁶ is optionally substituted C ₁ -C ₁₀ alkyl, optionally substituted C ₁ -C ₁₀ haloalkyl, optionally substituted C ₁ -C ₁₀ heteroalkyl, (CH ₂ ) _m R ¹⁸ , C (O) NHR ¹⁸ , C≡CR ¹⁸ , CR ³ = CR ⁴ R ¹⁸ and CR ³ = R ¹⁸ ;

R ⁷ is selected from the group consisting of CO ₂ R ¹⁴ , CONR ¹⁴ R ¹⁵ , SO ₃ R ¹⁴ , SO ₂ NR ¹⁴ R ¹⁵ and a carboxylic acid bioequivalent;

Each of R ⁸ and R ⁹ is hydrogen, OR ¹⁶ , NR ¹⁶ R ¹⁷ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ heteroalkyl, (CH ₂ ) _m independently from R ¹⁸ and none; R ⁸ and R ⁹ together form an optionally substituted olefin; R ⁸ and R ⁹ are joined to form an optionally substituted C ₃ -C ₈ ring;

R ¹⁰ is hydrogen, halogen, oxo, OR ¹⁶ , NR ¹⁶ R ¹⁷ , SR ¹⁶ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl and optionally substituted C ₁ -C ₆ hetero Selected from the group consisting of alkyl;

R ¹¹ is selected from the group consisting of hydrogen, halogen, OR ¹⁴ , NR ¹⁴ R ¹⁵ and SR ¹⁴ ; R ¹¹ and R ⁴ are joined to form an optionally substituted heterocycle;

R ¹² is selected from the group consisting of hydrogen, halogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ haloheteroalkyl;

R ¹³ is hydrogen, halogen, CN, NO ₂ , CO ₂ R ¹⁴ , S (O) _m R ¹⁴ , C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl and C ₁ -C ₄ haloheteroalkyl;

R ¹⁴ is selected from the group consisting of hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ heterohaloalkyl;

R ¹⁵ is selected from the group consisting of hydrogen, SO ₂ R ¹⁹ , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ heterohaloalkyl;

A group of R ¹⁶ and R ¹⁷ consisting of hydrogen, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ heteroalkyl, and (CH ₂ ) _m R ¹⁸ Each independently selected from; R ¹⁶ and R ¹⁷ If either is optionally substituted C ₂ -C ₆ alkyl, the other is none; R ¹⁶ and R ¹⁷ are joined to form an optionally substituted C ₃ -C ₈ ring;

R ¹⁸ is selected from an optionally substituted monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle, wherein R ¹⁸ comprises a nonaromatic heterocycle or carbocycle When attached, the attachment position may be on a nonaromatic heterocycle or carbocycle or aromatic ring system;

R ¹⁹ is selected from the group consisting of hydrogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl and optionally substituted aryl;

D is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle;

E is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle;

L is NH or none;

Q is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle;

U is selected from the group consisting of O, NR ⁴ , CR ³ R ⁴ , CO and none;

W is selected from the group consisting of O, NR ⁴ , CR ³ R ⁴ , CO and none;

X is N or CR ⁵ ;

Z is absent; 2 to 5 atomic spacers selected from optionally substituted C ₆ -C ₁₀ aryl and optionally substituted C ₁ -C ₈ heteroaryl, each optionally bonded with an optionally substituted non-aromatic heterocycle or carbocycle; And _{1 selected} from optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ heteroalkyl, and optionally substituted C ₁ -C ₆ haloalkyl, each optionally optionally conjugated with optionally substituted C ₆ -C ₁₀ aryl; To 5 atomic spacers;

m is 0, 1, 2 or 3;

n is 0 or 1;

Each optionally substituted group is alkyl, heteroalkyl, haloalkyl, heterohaloalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, non-aromatic heterocycle, hydroxy, alkoxy, aryloxy, mercapto, alkylthio, Arylthio, cyano, halo, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, S-sulfon Amido, N-sulfonamido, C-carboxy, O-carboxy, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, trihalomethanesulfonyl, = O, = S, amino and amino Substituted or unsubstituted with one or more groups independently selected from the group consisting of protected derivatives of groups;

Provided that when X is N and W is NH, then D is not phenyl;

Further, provided that when X is N and W is NH in the compound of formula VI, R ⁶ , R ¹⁰ And R ¹¹ does not include carboxylic, amido, ester, or sulfurate functional groups or carboxylic acid bioisomers.

In certain embodiments, the present invention provides a compound of Formula IV, V or VI, a pharmaceutically acceptable salt, ester, amide or prodrug thereof.

In the formula

(여기서, A, B 및 C는 O, S 및 N으로 이루어진 그룹으로부터 각각 독립적으로 선택된다)로 이루어진 그룹으로부터 선택된 카복실산 생동등체로 이루어진 그룹으로부터 선택되고; R ¹ is hydrogen; halogen; OR ¹⁴ ; NO ₂ ; CN; NR ¹⁴ R ¹⁵ ; Optionally substituted C ₁ -C ₆ alkyl; Optionally substituted C ₁ -C ₆ haloalkyl; Optionally substituted C ₁ -C ₆ heteroalkyl; CO ₂ R ¹⁴ ; CONR ¹⁴ R ¹⁵ ; SO ₃ R ¹⁴ ; SO ₂ NR ¹⁴ R ¹⁵ ; And tetrazole, NHSO ₂ R ¹⁹ , OC (S) NR ¹⁴ R ¹⁵ , SC (O) NR ¹⁴ R ¹⁵ and

Wherein A, B and C are each independently selected from the group consisting of O, S and N; and are selected from the group consisting of carboxylic acid bioequivalents selected from the group consisting of;

R ² is selected from the group consisting of hydrogen, halogen, OR ¹⁴ , NR ¹⁴ R ¹⁵ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl and optionally substituted C ₁ -C ₆ heteroalkyl Independently selected;

(여기서, A, B 및 C는 O, S 및 N으로 이루어진 그룹으로부터 각각 독립적으로 선택된다)로 이루어진 그룹으로부터 선택된 카복실산 생동등체로 이루어진 그룹으로부터 선택된다.R ⁷ is CO ₂ R ¹⁴ ; CONR ¹⁴ R ¹⁵ ; SO ₃ R ¹⁴ ; SO ₂ NR ¹⁴ R ¹⁵ ; And tetrazole, NHSO ₂ R ¹⁹ , OC (S) NR ¹⁴ R ¹⁵ , SC (O) NR ¹⁴ R ¹⁵ and

Wherein A, B and C are each independently selected from the group consisting of O, S and N).

In certain embodiments, the present invention provides a compound of Formula (I), (II), (III), (IV), (V) or (VI), a pharmaceutically acceptable salt, ester, amide or prodrug thereof.

[Formula I]

[Formula II]

[Formula III]

[Formula IV]

[Formula V]

[Formula VI]

In the above formula,

R ¹ is hydrogen, halogen, OR ¹⁴ , NO ₂ , CN, NR ¹⁴ R ¹⁵ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ hetero Alkyl, CO ₂ R ¹⁴ , CONR ¹⁴ R ¹⁵ , SO ₃ R ¹⁴ , SO ₂ NR ¹⁴ R ¹⁵ and a carboxylic acid bioequivalent;

Each R ² is a group consisting of hydrogen, halogen, OR ¹⁴ , NR ¹⁴ R ¹⁵ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, and optionally substituted C ₁ -C ₆ heteroalkyl Independently from;

R ³ and R ⁴ are independently selected from the group consisting of hydrogen, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl and optionally substituted C ₁ -C ₆ heteroalkyl;

R ⁵ is selected from the group consisting of hydrogen, halogen, OR ¹⁴ , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ haloheteroalkyl;

R ⁶ consists of optionally substituted C ₁ -C ₁₀ alkyl, optionally substituted C ₁ -C ₁₀ haloalkyl and optionally substituted C ₁ -C ₁₀ heteroalkyl, each optionally substituted with substituted aryl or substituted heteroaryl selected from the group, or, R ⁶ is ^{_{(CH 2) m R 18,}} C (O) NHR 18, C≡CR 18, CR 3 = CR 4 R 18 , and is selected from the group consisting of CR ³ = R ^18;

R ⁷ is selected from the group consisting of CO ₂ R ¹⁴ , CONR ¹⁴ R ¹⁵ , SO ₃ R ¹⁴ , SO ₂ NR ¹⁴ R ¹⁵ and a carboxylic acid bioequivalent;

Each of R ⁸ and R ⁹ is hydrogen, OR ¹⁶ , NR ¹⁶ R ¹⁷ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ heteroalkyl, (CH ₂ ) _m R ¹⁸ and none independently; R ⁸ and R ⁹ together form an optionally substituted olefin; R ⁸ and R ⁹ are joined to form an optionally substituted C ₃ -C ₈ ring;

R ¹⁰ is hydrogen, halogen, oxo, OR ¹⁶ , NR ¹⁶ R ¹⁷ , SR ¹⁶ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl and optionally substituted C ₁ -C ₆ hetero Selected from the group consisting of alkyl;

R ¹¹ is selected from the group consisting of hydrogen, halogen, OR ¹⁴ , NR ¹⁴ R ¹⁵ and SR ¹⁴ ; R ¹¹ and R ⁴ are joined to form an optionally substituted heterocycle;

R ¹² is selected from the group consisting of hydrogen, halogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ haloheteroalkyl;

R ¹³ is hydrogen, halogen, CN, NO ₂ , CO ₂ R ¹⁴ , S (O) _m R ¹⁴ , C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl and C ₁ -C ₄ haloheteroalkyl;

R ¹⁴ is selected from the group consisting of hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ heterohaloalkyl;

R ¹⁵ is selected from the group consisting of hydrogen, SO ₂ R ¹⁹ , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ heterohaloalkyl;

R¹⁶ And R¹⁷This hydrogen, optionally substituted C_One-C₆ Alkyl, optionally substituted C_One-C₆ Haloalkyl, optionally substituted C_One-C₆ Heteroalkyl and (CH₂)_mR¹⁸Each independently selected from the group consisting of; R¹⁶ And R¹⁷ Any of which C is optionally substituted₂-C₆ If alkyl, the other is none; R¹⁶ And R¹⁷This is optionally substituted C₃-C₈ To form a ring;

R ¹⁸ is selected from an optionally substituted monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle, wherein R ¹⁸ comprises a nonaromatic heterocycle or carbocycle When attached, the attachment position may be on a nonaromatic heterocycle or carbocycle or aromatic ring system;

R ¹⁹ is selected from the group consisting of hydrogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl and optionally substituted aryl;

D is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle;

E is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle;

L is NH or none;

Q is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle;

U is selected from the group consisting of O, NR ⁴ , CR ³ R ⁴ , CO and none;

W is selected from the group consisting of O, NR ⁴ , CR ³ R ⁴ , CO and none;

X is N or CR ⁵ ;

Y is 1 to 4 atomic spacers comprising one or more groups selected from optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ heteroalkyl, optionally substituted phenyl and optionally substituted heteroaryl;

Z is absent; 2 to 5 atomic spacers selected from optionally substituted C ₆ -C ₁₀ aryl and optionally substituted C ₁ -C ₈ heteroaryl, each optionally bonded with an optionally substituted non-aromatic heterocycle or carbocycle; And _{1 selected} from optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ heteroalkyl, and optionally substituted C ₁ -C ₆ haloalkyl, each optionally optionally conjugated with optionally substituted C ₆ -C ₁₀ aryl; To 5 atomic spacers;

m is 0, 1, 2 or 3;

n is 0 or 1;

Provided that X is N, W is NH, Y is not -N = CR ¹² -which forms dihydropyrazole, and Z or R ⁶ is not an optionally substituted non-aromatic ring bonded with an optionally substituted aromatic ring or ; X is N, W is NH, R ⁶ is alkoxy, optionally substituted alkyl, optionally substituted aryl or optionally substituted heteroaryl, and -N = CR ¹² -wherein Z forms dihydropyrazole, Z D is not phenyl unless is an optionally substituted non-aromatic ring combined with an optionally substituted aromatic ring;

Provided that when X is N, W is NH and Y is -N = CR ¹² -which forms dihydropyrazole, then D is not naphthyl;

(당해 화학식에서, A, B, C 및 V는 O, S 및 NR²⁰으로 이루어진 그룹으로부터 각각 독립적으로 선택된다)인 헤테로사이클릭 메틸렌 치환기이거나; D가 페닐이고, R¹⁰과 R¹¹ 중 어느 하나가 -(CH₂)_0-6OH이고, X가 C이고, W가 NH이고, Z가 방향족이고, R⁶이 알콕시, 임의 치환된 알킬, 임의 치환된 아릴 또는 임의 치환된 헤테로아릴이면; Y는 디하이드로피라졸을 형성하는 -N=CR¹²-이 아니고;Provided that U is NH; Or any one of R ¹⁰ and R ¹¹ forms D-hydroxypyrazole, X is N and W is NH; E and any of R ¹⁰ and R ¹¹ form 5-hydroxypyrazole, X is N and W is NH; E is phenyl, either R ¹⁰ or R ¹¹ is — (CH ₂ ) _0-6 OH, X is C, W is NH, R ⁶ is optionally substituted aryl or optionally substituted heteroaryl, Z is absent, optionally substituted alkyl, optionally substituted aryl or optionally substituted heteroaryl; E is phenyl, either R ¹⁰ or R ¹¹ is — (CH ₂ ) _0-6 OH, X is N, W is NH, no Z, optionally substituted alkyl, optionally substituted aryl or optionally Substituted heteroaryl, R ⁶ is C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy,-(CH ₂ ) _0-6 OR ²⁰ , optionally substituted aryl, optionally substituted heteroaryl, NR ²¹ R ²² or Represented by Formula VII

(Wherein A, B, C and V are each independently selected from the group consisting of O, S and NR ²⁰ ), they are heterocyclic methylene substituents; D is phenyl, one of R ¹⁰ and R ¹¹ is — (CH ₂ ) _0-6 OH, X is C, W is NH, Z is aromatic, R ⁶ is alkoxy, optionally substituted alkyl, Optionally substituted aryl or optionally substituted heteroaryl; Y is not -N = CR ¹² -which forms dihydropyrazole;

R ²⁰ is selected from the group consisting of hydrogen, substituted alkyl, substituted aryl and substituted heteroaryl;

R ²¹ And R ²² is each independently selected from the group consisting of hydrogen, alkyl and aryl; R ²¹ And together with N to which R ²² is attached, a 5- or 6-membered saturated ring containing one or less other heteroatoms selected from oxygen and nitrogen.

In certain embodiments, the present invention,

3 '-{[1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidenemethyl] amino} -2'-hydroxy ratio Phenyl-3-carboxylic acid (compound 101);

2,4-dihydroxybenzoic acid N '-{1- [1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] Ethyl} hydrazide (Compound 102);

3- {3-[(5-chloro-2-hydroxy-3 ', 4'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl } Benzoic acid (compound 103);

3- {3-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid (compound 104);

3 '-{[1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidenemethyl] amino} -4-fluoro-2 '-Hydroxybiphenyl-3-carboxylic acid (compound 105);

2- (3 '-{[1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindol-3-ylidenemethyl] amino} -2'- Hydroxybiphenyl-3-yl) -2-methylpropionic acid (compound 106);

3 '-{[1- (3,4-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidenemethyl] amino} -2'-hydroxy ratio Phenyl-3-carboxylic acid (compound 107);

4- {3-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid (compound 108);

3- {3-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-6-trifluoromethyl-2,3-dihydroindole- 1-yl} benzoic acid (Compound 109);

3- {3-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-6-trifluoromethyl-2,3-dihydroindole- 1-yl} benzoic acid methyl ester (Compound 110);

3- {3-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid methyl ester (Compound 111);

3- {3-[(5-fluoro-2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindole-1- Monobenzoic acid (compound 112);

3- {3- [1- (3,5-Dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylideneamino] -2-oxo-2,3 -Dihydrobenzooxazol-7-yl} benzoic acid (compound 113);

3- {3-[(2-hydroxy-5,3 ', 4'-trimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid (Compound 114);

3-hydroxybenzoic acid N '-{1- [1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] ethyl} high Drazide (Compound 115);

1- (3,5-dimethylphenyl) -3- {1- [2- (4-hydroxyphenyl) -2-oxo-ethylamino] ethylidene} -6-trifluoromethyl-1,3-di Hydroindol-2-ones (compound 116);

3- {3-[(5-fluoro-2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-6-trifluoromethyl-2,3 -Dihydroindol-1-yl} benzoic acid (compound 117);

3- {3-[(2-hydroxy-3 ', 4'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-6-trifluoromethyl-2,3-dihydroindole- 1-yl} benzoic acid (Compound 118);

3- {3-[(2-hydroxy-3 ', 4'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid (compound 119);

3- {3-[(2-hydroxy-3 ', 4'-dimethylbiphenyl-3-ylamino) methylidene] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid (compound 120);

4- {3-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-ylamino) methylidene] -2-oxo-2,3-dihydroindol-1-yl} butyric acid (compound 121);

2-chloro-3- (4-{[1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindol-3-ylidenemethyl] amino}- 3-hydroxyphenyl) acrylic acid (compound 122);

4-hydroxybenzoic acid N '-{1- [1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] ethyl} high Drazide (Compound 123);

3- {3-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -5-nitro-2-oxo-2,3-dihydroindol-1-yl } Benzoic acid (compound 124);

3- {3-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-ylamino) methylidene] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid (compound 125);

3- {3-[(2-hydroxy-5,3 ', 5'-trimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid (Compound 126);

4-Aminobenzoic acid N '-{1- [1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] ethyl} hydra Zide (compound 127);

3- (7- {N '-[1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino}- 1H-indol-3-yl) propionic acid (compound 128);

4- {3- [N '-(4-methylbenzoyl) hydrazinomethylidene] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid (Compound 129);

3- {2-oxo-6-trifluoromethyl-3- [4- (3-trifluoromethylphenyl) -1 H-pyrrol-2-ylmethylidene] -2,3-dihydroindol-1-yl } Benzoic acid (compound 130);

3- (7- {N '-[1- (3,4-dimethylphenyl) -3-methyl-5-oxo-1,5-dihydropyrazole-4-ylidene] hydrazino} -1H- Indol-3-yl) propionic acid (compound 131);

3- (3-{[4- (3,4-dimethylphenyl) thiazol-2-ylamino] methylidene} -2-oxo-6-trifluoromethyl-2,3-dihydroindole-1- Yl) benzoic acid (compound 132);

3- (3-{[4- (4-phenyl) thiazol-2-ylamino] methylene} -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl) benzoic acid ( Compound 133);

3- {3-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-ylamino) methylene] -2-oxo-6-trifluoromethyl-2,3-dihydroindole-1 -Yl} benzoic acid (compound 134);

3- {3-[(4- (4-methylphenyl) -2-thiazolylamino) methylene] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic acid (compound 135);

3- {3-[(3,4-Dimethylbenzoylhydrazino) methylidene] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic acid (Compound 136);

3- {3-[(4-chlorobenzoylhydrazino) methylidene] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic acid (Compound 137);

3- {3-[(4-methoxybenzoylhydrazino) methylidene] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic acid (Compound 138);

3- {3-[(3,4-dimethylbenzoylhydrazino) methylidene] -2-oxo-6-chloro-2,3-dihydroindol-1-yl} benzoic acid (Compound 139);

1- (3,4-dimethylphenyl) -3- [1- (2,4-dihydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 140);

1- (3,4-dimethylphenyl) -3- [1- (4-hydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 141);

1- (3,4-dimethylphenyl) -3-[(2,4-dihydroxybenzoylhydrazino) methylidene] -2-oxo-2,3-dihydroindole (Compound 142);

1- (3,5-dimethylphenyl) -3- [1- (2,4-dihydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 143);

1- (3,5-dimethylphenyl) -3- [1- (4-hydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 144);

1- (3,5-dimethylphenyl) -3-[(2,4-dihydroxybenzoylhydrazino) methylidene] -2-oxo-2,3-dihydroindole (Compound 145);

1- (3,5-dimethylphenyl) -3-[(4-hydroxybenzoylhydrazino) methylidene] -2-oxo-2,3-dihydroindole (Compound 146);

3- (3- [1- (3,4-Dihydroxybenzoylhydrazino) ethylidene] -2-oxo-6-chloro-2,3-dihydroindol-1-yl) benzoic acid (Compound 147) ;

1- (3,4-dimethylphenyl) -3-[(4-hydroxybenzoylhydrazino) methylidene] -2-oxo-2,3-dihydroindole (Compound 148);

1- (3,4-dimethylphenyl) -3-[(3,5-diisopropyl-2-hydroxybenzoylhydrazino) methylidene] -2-oxo-2,3-dihydroindole (Compound 149 );

1- (3,5-dimethylphenyl) -3- [1- (3,4-dihydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 150);

1- (3,4-dimethylphenyl) -3- [1- (3,4-dihydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 151);

3- (6-chloro-3-[(2-hydroxy-3,5-diisopropylbenzoylhydrazino) methylidene] -2-oxo-2,3-dihydroindol-1-yl) benzoic acid ( Compound 152);

1- (3,4-dimethylphenyl) -3- [1- (2,5-dihydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 153);

1- (3,4-dimethylphenyl) -3- [1- (3-nitro-4-hydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 154);

1- (3,4-dimethylphenyl) -3- [1- (3-aminosulfonyl-4-chlorobenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 155) ;

1- (3,4-dimethylphenyl) -3- [1- (3-amino-4-hydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 156);

1- (3,4-dimethylphenyl) -3- [1- (4-methoxy-2-hydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 157) ;

3- {3- (1- (3,5-Dimethylphenyl) -2-oxo-2,3-dihydro-3-indoledene) methylamino-2-hydroxyphenyl} benzoic acid (Compound 158);

3- {3- (3- (3,5-Dimethylphenyl) -2-hydroxyphenyl) aminomethylidene) -2-oxo-2,3-dihydro-1-indolyl} benzoic acid (Compound 159);

3- {3- (1- (3,4-Dimethylphenyl) -2-oxo-2,3-dihydro-3-indoledene) methylamino-2-hydroxyphenyl} benzoic acid (Compound 160);

4- {1- (6-Fluoro-2-oxo-2,3-dihydro-3- (2- (3,5-dimethylphenyl) -aminocarbonylphenyl) aminomethylidene) indolyl} butanoic acid (Compound 161);

4- {1- (6-Chloro-2-oxo-2,3-dihydro-3- (2-hydroxy-3- (3,5-dimethylphenyl) -phenyl) aminomethylidene) indolyl} moiety Carbonic acid (compound 162);

3- {1- (6-Chloro-2-oxo-2,3-dihydro-3- (2-hydroxy-3- (3,5-dimethylphenyl) -phenyl) aminomethylidene) indolyl} benzoic acid (Compound 163);

4- {1- (5-Fluoro-2-oxo-2,3-dihydro-3- (2-hydroxy-3- (3,5-dimethylphenyl) -phenyl) aminomethylidene) indolyl} Butanoic acid (compound 164);

3- {3- (1- (1- (3,5-Dimethylphenyl) -6-trifluoromethyl-2-oxo-2,3-dihydro-3-indoledene) ethylamino) -2-hydro Oxyphenyl} benzoic acid (compound 165);

3- {3- (1- (1- (3,4-Dimethylphenyl) -6-trifluoromethyl-2-oxo-2,3-dihydro-3-indoledene) ethylamino) -2-hydro Oxyphenyl} benzoic acid (compound 166);

3- {1- (6-Trifluoromethyl-2-oxo-2,3-dihydro-3- (5-chloro-2-hydroxy-3-cyclohexylphenyl) hydrazono) indolyl} benzoic acid (Compound 167);

3- {1- (5-fluoro-2-oxo-2,3-dihydro-3- (1- (5-chloro-2-hydroxy-3-cyclohexylphenyl) amino) ethylidene) indolyl } Benzoic acid (compound 168);

3- {1- (5-Fluoro-2-oxo-2,3-dihydro-3- (5-chloro-2-hydroxy-3-cyclohexylphenyl) aminomethylidene) indolyl} benzoic acid (compound 169);

4- {2-hydroxy-3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolylidene) methylaminophenyl} butanoic acid ( Compound 170);

4- {2-hydroxy-3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) indolylidene) methylaminophenyl} butanoic acid ( Compound 171);

3- {3- (7- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) -3-indolylidene) methylamino) indolyl} Propanoic acid (compound 172);

3- {3- (7- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) -3-indolylidene) methylamino) indolyl} Propanoic acid (compound 173);

4- {2-hydroxy-3- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolylidene) methylaminophenyl} butanoic acid (Compound 174);

2-Chloro-3- {3-hydroxy-4- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolylidene) methylaminophenyl} propenic acid (Compound 175) ;

2-chloro-3- {3-hydroxy-4- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) indolylidene) methylaminophenyl } Propenoic acid (compound 176);

2-ethyl-3- {3-hydroxy-4- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) indolylidene) methylaminophenyl } Propenic acid (Compound 177);

2-ethyl-3- {3-hydroxy-4- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolylidene) methylaminophenyl } Propenoic acid (compound 178);

2-ethyl-3- {3-hydroxy-4- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolylidene) methylaminophenyl} propenoic acid (Compound 179) ;

4- {2-hydroxy-3- (4- (2- (3,4-dimethylphenyl) -3-oxo-3,4-dihydro-5-methyl) pyrazolidene) methylaminophenyl} butanoic acid (Compound 180);

(Z) -4- {1- (2,5-dioxo-3- (3- (3,5-dimethylphenyl) -2-hydroxyphenyl) aminomethylidene) pyrrolidinyl} butanoic acid (Compound 181 );

(E) -4- {1- (2,5-dioxo-3- (3- (3,5-dimethylphenyl) -2-hydroxyphenyl) aminomethylidene) pyrrolidinyl} butanoic acid (Compound 182 );

(Z) -3- {1- (2,5-dioxo-3- (3- (3,5-dimethylphenyl) -2-hydroxyphenyl) aminomethylidene) pyrrolidinyl} benzoic acid (Compound 183) ;

(E) -3- {1- (2,5-dioxo-3- (3- (3,5-dimethylphenyl) -2-hydroxyphenyl) aminomethylidene) pyrrolidinyl} benzoic acid (Compound 184) ;

4- {3- (4-oxo-2-thioxo-5- (3- (3,5-dimethylphenyl) -2-hydroxyphenyl) hydrozono)} butanoic acid (Compound 185);

3- {2- (3- (1- (3.5-Dimethylphenyl) -6-chloro-2-oxo-2,3-dihydroindoledene) methylamino) phenylamino} benzoic acid (Compound 186);

3- {2- (3- (1- (3,5-Dimethylphenyl) -6-trifluoromethyl-2-oxo-2,3-dihydroindoledene) methylamino) phenylamino} benzoic acid (compound 187);

3- {2- (4- (2- (3,5-Dimethylphenyl) -5-methyl-3-oxo-3,4-dihydropyrazolidene) methylamino) phenylamino} benzoic acid (Compound 188);

(±) -3-methyl-5- {2-hydroxy-3- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) Indolylidene) methylamino) phenyl} pentanoic acid (Compound 189);

(±) -3- {1- (6-chloro-2-oxo-2,3-dihydro-3- (3- (1- (3,5-dimethylphenyl) -2-oxo-2,3- Dihydro) indolyl) aminomethylidene) indolyl} benzoic acid (Compound 190);

3- {4- (3-hydroxy-6-methyl-2- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indole Ryl) hydrazono) pyridinyl} benzoic acid (compound 191);

3- {4- (3-hydroxy-6-methyl-2- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indole Lidene) methylamino) pyridinyl} benzoic acid (compound 192);

3- {4- (3-hydroxy-2- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylamino ) Pyridinyl} benzoic acid (compound 193);

3- {4- (3-hydroxy-2- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolyl) hydrazo No) pyridinyl} benzoic acid (compound 194);

3- {5- (4-hydroxy-3- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylamino ) Pyridinyl} benzoic acid (compound 195);

3- {5- (4-hydroxy-3- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolyl) hydrazo No) pyridinyl} benzoic acid (compound 196);

3- {5- (4-hydroxy-3- (4- (3-oxo-3,4-dihydro-5-methyl-2- (3,4-dimethylphenyl) pyrazolyl) hydrazono) pyrid Dinyl} benzoic acid (compound 197);

4- {2- (3-Oxo-3,4-dihydro-5-methyl-4- (3- (3,4-dimethylphenyl) phenyl) hydrozono) pyrazolyl} butanoic acid (Compound 198);

3- {2-amino-5-methyl-3- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolylidene) methyl Amino) phenyl} benzoic acid (compound 199);

3- {1- (5-Fluoro-2-oxo-2,3-dihydro-3- (3- (3,4-dimethylphenyl) phenyl) aminomethylidene) indolyl} benzoic acid (Compound 200);

4- {2- (5-Methyl-2-oxo-2,3-dihydro-4- (3- (3,4-dimethylphenyl) phenyl) aminomethylidene) pyrazolyl} butanoic acid (Compound 201);

(3- (5-fluoro-2-hydroxy-3- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) indolene ) Methylamino) -1-pyrazolyl) acetic acid (compound 202);

(3- (5-fluoro-2-hydroxy-3- (3- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indoledene) methylamino) -1- Pyrazolyl) acetic acid (compound 203);

4- {2- (5-Methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-phenyl) ethyl) phenyl) aminomethylidene) pyrazolyl} butanoic acid ( Compound 204);

4- {2- (5-Methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-phenyl) ethyl) phenyl) hydrazono) pyrazolyl} butanoic acid ( Compound 205);

4- {2- (5-methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (4-methyl) phenyl) ethyl) phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 206);

4- {2- (5-methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3-methyl) phenyl) ethyl) phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 207);

4- {2- (5-methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methyl) phenyl) ethyl) phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 208);

4- {2- (5-methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (1-naphthyl) ethyl) phenyl) hydrazono) pyrazolyl } Butanoic acid (compound 209);

3- {1- (5-Nitro-2-oxo-2,3-dihydro-3- (2-hydroxy-3- (3,5-dimethylphenyl) phenyl) aminomethylidene) indolyl} benzoic acid ( Compound 210);

3- {1- (5-Nitro-2-oxo-2,3-dihydro-3- (5-fluoro-2-hydroxy-3- (3,5-dimethylphenyl) phenyl) aminomethylidene) Indolyl} benzoic acid (compound 211);

2-hydroxy-3- {3- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolene) methylamino} benzoic acid (Compound 212);

2-hydroxy-3- {3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolene) methylamino} benzoic acid (Compound 213) ;

4- {2- (5-methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3- (3-methyl-1-butenyl) phenyl) aminomethylidene) pyrazolyl} Butanoic acid (compound 214);

4- {2- (5-Methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3-heptanylphenyl) hydrazono) pyrazolyl} butanoic acid (Compound 215);

4- {2- (5-methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3- (2- (4-methyl) phenyl) ethenylphenyl) hydrazono) pyra Jolyl} butanoic acid (compound 216);

4- {2- (5-methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3- (2- (3-methyl) phenyl) ethenylphenyl) hydrazono) pyra Jolyl} butanoic acid (compound 217);

4- {1- (2-Oxo-2,3-dihydro-3- (2-hydroxy-3- (2- (2-methyl) phenyl) ethylphenyl) hydrazono) indolyl} butanoic acid ( Compound 218);

2- {1- (2-Oxo-2,3-dihydro-3- (2-hydroxy-3- (3,5-dimethylphenyl) phenyl) hydrazono) indolyl} acetic acid (Compound 219);

2- {1- (2-Oxo-2,3-dihydro-3- (2-hydroxy-3- (2- (2-methyl) phenyl) ethylphenyl) hydrazono) indolyl} acetic acid (compound 220);

4- {4- (2- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) indolylidene) methylamino) thiazolyl} Benzoic acid (compound 221);

3- {1- (5-Nitro-2-oxo-2,3-dihydro-3- (2-hydroxy-5-methyl-3- (1-adamantane) phenyl) aminomethylidene) indolyl } Benzoic acid (compound 222);

3- {1- (6-Trifluoromethyl-2-oxo-2,3-dihydro-3- (4-hydroxy-5- (3,4-dimethylphenyl) pyridinyl) hydrazono) indole Ryl} benzoic acid (compound 223);

4- {2- (5-Methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3- (2- (2-methyl) phenyl) -ethylphenyl) aminomethylidene) pyra Jolyl} butanoic acid (compound 224);

4- (2- (5-Methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3- (2- (2-fluoro) phenyl) -ethylphenyl) aminomethylidene) A compound selected from the group consisting of pyrazolyl} butanoic acid (compound 225) or a pharmaceutically acceptable salt, ester or prodrug thereof.

In certain embodiments, the present invention,

4- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (1-naphthyl) -ethyl) phenyl) aminomethyl Lidene) pyrazolyl} butanoic acid (Compound 226);

4- (2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (3,5-dimethylphenyl) -ethyl) phenyl) Aminomethylidene) pyrazolyl} butanoic acid (Compound 227);

4- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-methoxyphenyl) -ethyl) phenyl) amino Methylidene) pyrazolyl} butanoic acid (Compound 228);

4- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-fluoro-3-methyl-phenyl) ethyl ) Phenyl) aminomethylidene) pyrazolyl} butanoic acid (Compound 229);

4- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-fluoro-3-methyl-phenyl) ethyl ) Phenyl) aminomethylidene) pyrazolyl} butanoic acid (compound 230);

4- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (4-phenylphenyl) -ethyl) phenyl) aminomethyl Lidene) pyrazolyl} butanoic acid (Compound 231);

4- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-cyanophenyl) -ethyl) phenyl) amino Methylidene) pyrazolyl} butanoic acid (Compound 232);

4- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-chlorophenyl) -ethyl) phenyl) aminomethyl Lidene) pyrazolyl} butanoic acid (Compound 233);

4- (2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2,6-dimethylphenyl) -ethyl) phenyl) Aminomethylidene) pyrazolyl} butanoic acid (Compound 234);

3- {2- (5-Trifluoromethyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-trifluoromethylphenyl) ethyl) Phenyl) aminomethylidene) pyrazolyl} benzoic acid (compound 235);

3- {2- (5-Trifluoromethyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-fluorophenyl) -ethyl) Phenyl) aminomethylidene) pyrazolyl} benzoic acid (compound 236);

3- {2- (5-trifluoromethyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-methyl-phenyl) ethyl) phenyl ) Aminomethylidene) pyrazolyl} benzoic acid (compound 237);

3- {2- (5-Trifluoromethyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2,5-dimethyl-phenyl) ethyl ) Phenyl) aminomethylidene) pyrazolyl} benzoic acid (compound 238);

3- {2- (5-Trifluoromethyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2,6-dimethyl-phenyl) ethyl ) Phenyl) aminomethylidene) pyrazolyl} benzoic acid (Compound 239);

3- {2- (5-phenyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2,5-dimethylphenyl) -ethyl) phenyl) Aminomethylidene) pyrazolyl} benzoic acid (compound 240);

3- {2- (5-tert-butyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2,5-dimethylphenyl) -ethyl ) Phenyl) aminomethylidene) pyrazolyl} benzoic acid (compound 241);

3- {2- (5-methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-methylphenyl) -ethyl) phenyl) aminomethylidene ) Pyrazolyl} benzoic acid (compound 242);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-fluorophenyl) -ethyl) phenyl) hydro Lazono) pyrazolyl} butanoic acid (Compound 243);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dimethylphenyl) -ethyl) phenyl) hydrazono ) Pyrazolyl} butanoic acid (Compound 244);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (4-phenylphenyl) -ethyl) phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 245);

4- (2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methoxyphenyl) -ethyl) phenyl) hydrazono) Pyrazolyl} butanoic acid (Compound 246);

4- {2- (5-Methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluoro-3-methylphenyl) -ethyl) phenyl) hydro Lazono) pyrazolyl} butanoic acid (Compound 247);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-trifluoromethylphenyl) -ethyl) phenyl) hydrazono ) Pyrazolyl} butanoic acid (Compound 248);

4- (2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-cyanophenyl) ethyl) -phenyl) hydrazono) Pyrazolyl} butanoic acid (compound 249);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-chlorophenyl) ethyl) -phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 250);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dimethylphenyl) -ethyl) phenyl) hydrazono ) Pyrazolyl} butanoic acid (Compound 251);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-ethylphenyl) -ethyl) phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 252);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dichlorophenyl) -ethyl) phenyl) hydrazono ) Pyrazolyl} butanoic acid (compound 253);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,5-dimethylphenyl) -ethyl) phenyl) hydrazono ) Pyrazolyl} butanoic acid (Compound 254);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluoro-6-trifluoro-methylphenyl) ethyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 255);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indanyl) phenyl) -hydrazono) pyrazolyl} butanoic acid ( Compound 256);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indenyl) phenyl) -hydrazono) pyrazolyl} butanoic acid ( Compound 257);

(±) -4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (1-indanylmethyl) phenyl) -hydrazono) pyra Jolyl} butanoic acid (compound 258);

(±) -3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (1-indanylmethyl) phenyl) -hydrazono) pyra Jolyl} benzoic acid (compound 259);

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methylphenyl) ethyl) -phenyl) hydrazono) pyrazolyl } Benzoic acid (compound 260);

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluoro-3-methylphenyl) -ethyl) phenyl) hydro Lazono) pyrazolyl} benzoic acid (compound 261);

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluorophenyl) -ethyl) phenyl) hydrazono) Pyrazolyl} benzoic acid (compound 262);

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dimethylphenyl) -ethyl) phenyl) hydrazono ) Pyrazolyl} benzoic acid (compound 263);

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dichlorophenyl) -ethyl) phenyl) hydrazono ) Pyrazolyl} benzoic acid (compound 264);

3- (2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methyl-6-trifluoromethylphenyl) ethyl) phenyl) Hydrazono) pyrazolyl} benzoic acid (compound 265);

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indanyl) phenyl) -hydrazono) pyrazolyl} benzoic acid (compound 266);

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indenyl) phenyl) -hydrazono) pyrazolyl} benzoic acid (compound 267);

(E) -4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,4-difluorophenyl)-) Tenyl) phenyl) aminomethylidene) pyrazolyl} butanoic acid (Compound 268);

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-4- (3,4-dimethylphenyl) -2-pyridyl) hydrazono) pyra Jolyl} benzoic acid (compound 269);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-6-methyl-4- (3,4-dimethylphenyl) -2-pyridyl) hydro Lazono) pyrazolyl} butanoic acid (Compound 270);

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-2- (3,4-dimethylphenyl)-4-pyridyl) hydrazono) pyra Jolyl} benzoic acid (compound 271);

3- (2- (5-methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-2- (3,5-dimethylphenyl)-4-pyridyl) hydrazono) pyra Jolyl} benzoic acid (compound 272);

3- {1- (6-Trifluoromethyl-2-oxo-2,3-dihydro-3- (2-hydroxy-3- (2- (2-methylphenyl) -ethyl) phenyl) hydrazono ) Indolyl} benzoic acid (compound 273);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3-benzylphenyl) hydrazono) -pyrazolyl} butanoic acid (Compound 274);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3- (3-methylphenyl) propyl) -phenyl) hydrazono) pyrazolyl } Butanoic acid (compound 275);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3-phenylpropyl) -phenyl) hydrazono) pyrazolyl} butanoic acid ( Compound 276);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3- (2-methylphenyl) propyl) -phenyl) hydrazono) pyrazolyl } Butanoic acid (compound 277);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,4-difluorophenyl) -ethyl) phenyl) hydro Lazono) pyrazolyl} butanoic acid (Compound 278);

(E) -4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-pyridyl) ethyl) -phenyl) hydro Lazono) pyrazolyl} butanoic acid (Compound 279);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z)-(2-hydroxy-3- (2- (2,6-dimethylphenyl)-(Z)- Ethenyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 280);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-benzofuranyl) phenyl) -hydrazono) pyrazolyl} butanoic acid (Compound 281);

(Z) -4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-bromoethenyl) phenyl) -hydrazono) pyra Jolyl} butanoic acid (compound 282);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z)-(2-hydroxy-3- (3-methyl-1-butenyl) phenyl) -hydrazono ) Pyrazolyl} butanoic acid (compound 283);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z)-(2-hydroxy-3- (2-cyclopropylethenyl) -phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 284);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3-methylbutyl) phenyl) -hydrazono) pyrazolyl} butanoic acid ( Compound 285);

4- (2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-5-fluoro-3- (3,5-dimethylphenyl) phenyl) hydrazono) Pyrazolyl} butanoic acid (compound 286);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3,4-dimethylphenyl) phenyl) -hydrazono) pyrazolyl} part Carbonic acid (compound 287);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (5-chloro-2-hydroxy-3-cyclohexylphenyl) -hydrazono) pyrazolyl} butanoic acid ( Compound 288);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3,5-dimethylphenyl) phenyl) -hydrazono) pyrazolyl} part Carbonic acid (compound 289);

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3,5-dimethylphenyl) phenyl) -hydrazono) pyrazolyl} benzoic acid (Compound 290);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (5-chloro-2-hydroxy-3-cyclohexylphenyl) -hydrazono) pyrazolyl} butanoic acid ( Compound 291);

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3,4-dimethylphenyl) phenyl) -hydrazono) pyrazolyl} benzoic acid (Compound 292);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3- (2-methylphenyl) propyl) -phenyl) hydrazono) pyrazolyl } Butanoic acid (compound 293);

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-benzofuranyl) phenyl) -hydrazono) pyrazolyl} benzoic acid ( Compound 294);

4- (2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3- (2-fluorophenyl) propyl) -phenyl) hydrazono) Pyrazolyl} butanoic acid (compound 295);

3- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (3,4-dimethylphenyl) -phenyl) aminomethylidene) pyra Jolyl} benzoic acid (compound 296);

3- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (3,5-dimethylphenyl) -phenyl) aminomethylidene) pyra Jolyl} benzoic acid (compound 297);

4- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (3,4-dimethylphenyl) -phenyl) aminomethylidene) pyra Jolyl} butanoic acid (compound 298);

3- {1- (2-Oxo-2,3-dihydro-3- (2-hydroxy-3- (3,5-dimethylphenyl) -phenyl) hydrazono) indolyl} propionic acid (Compound 299) ;

3- {1- (2-Oxo-2,3-dihydro-3- (2-hydroxy-3-benzylphenyl) hydrazono) -indolyl} benzoic acid (Compound 300);

3- {1- (2-Oxo-2,3-dihydro-3- (2-hydroxy-3- (2- (2-methylphenyl) ethyl) phenyl) -hydrazono) indolyl} propionic acid (compound 301);

3- {1- (6-Chloro-2-oxo-2,3-dihydro-3 (Z)-(2-hydroxy-3- (3- (3-methylphenyl) propyl) -phenyl) aminomethylidene ) Indolyl} benzoic acid (compound 302);

(±) -3- {1- (6-chloro-2-oxo-2,3-dihydro-3 (Z)-(2-hydroxy-3- (1,2-dihydro-1-methyl- 2-indolylphenyl) aminomethylidene) indolyl} benzoic acid (Compound 303);

4- {2- (5-Methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3- (2-methylphenylcarbonyl-amino) phenyl) hydrazono) pyrazolyl} part Carbonic acid (compound 304);

4- (2- (5-methyl-3-oxo-3,4-dihydro-4- (5-chloro-2-hydroxy-3- (2-methylphenyl-carbonylamino) phenyl) hydrazono) Pyrazolyl} butanoic acid (Compound 305);

3- {2-Hydroxy-3- (2-oxo-2,3-dihydro-l- (2- (2-fluorophenyl) ethyl) indolylidene) -hydrazinophenyl} benzoic acid (Compound 306 );

3- {2-Hydroxy-3- (2-oxo-2,3-dihydro-l- (2- (2-chlorophenyl) ethyl) indolylidene) -hydrazinophenyl} benzoic acid (Compound 307) ;

3- {3-hydroxy-2- (5-methyl-3-oxo-2,3-dihydro-2- (3,4-dimethylphenyl) -pyrazolylidene) hydrazino-4-pyridyl} Benzoic acid (compound 308);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl } Benzoic acid (compound 309);

3- {3-Hydroxy-2- (2-oxo-2,3-dihydro-l- (3,5-dimethylphenyl) -3-indolylidene-hydrazino) -4-pyridyl} benzoic acid (Compound 310);

3- {1- (2-Oxo-2,3-dihydro-3- (3-hydroxy-6-methyl-4- (3,4-dimethylphenyl)-2-pyridyl) hydrazono) indole Ryl} benzoic acid (compound 311);

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-6-methyl-4- (3,4-dimethylphenyl) -2-pyridyl) hydro Lazono) pyrazolyl} benzoic acid (compound 312);

3- {3-hydroxy-4- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) -6-trifluoromethyl-3-indolylidenehydrazino)- 2-pyridyl} benzoic acid (Compound 313);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-2- (3,5-dimethylphenyl)-4-pyridyl) hydrazono) pyra Jolyl} butanoic acid (compound 314);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-5-phenyl-2-benzothienyl) -hydrazono) pyrazolyl} butanoic acid ( Compound 315);

3- {3-hydroxy-2- (5-methyl-3-oxo-2,3-dihydro-2- (3,4-dimethylphenyl) -4-pyrazolidene) hydrazino-5-benzo Thienyl} benzoic acid (compound 316);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (3- (2,3-dimethoxycarbonylphenyl) phenyl) -hydrazono) pyrazolyl} butanoic acid ( Compound 317);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z)-(2-hydroxy-3,5-diisopropylphenyl) -carbonylhydrazinomethylidene) Pyrazolyl} butanoic acid (compound 318);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z)-(2-hydroxy-3- (3,5-dimethylphenyl) phenyl) -aminomethylidene) pyra Jolyl} butanoic acid (Compound 319);

(±) -4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2,3-dihydro-1-methyl-2-oxo -3-indolyl) methyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 320);

3- {1- (2-Oxo-2,3-dihydro-5-fluoro-3- (2-hydroxy-3- (2- (2-methylphenyl) ethyl) phenyl) -hydrazono) indole Ryl} propionic acid (compound 321);

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,5-dimethylphenyl) -ethyl) phenyl) hydrazono ) Pyrazolyl} benzoic acid (compound 322);

(±) -3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2,3-dihydro-1-methyl-2-oxo -3-indolyl) methyl) phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 323);

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (l, 2-dihydro-1-methyl-2-oxo-3-indole) Lilydene) methyl) phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 324);

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (5-fluoro-2- methylphenyl) -ethyl) phenyl) hydro Lazono) pyrazolyl} benzoic acid (compound 325);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4 (E)-(2-hydroxy-3- (2- (2,4-difluorophenyl) -ethenyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 326);

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3-methylphenyl) hydrazono) -pyrazolyl} benzoic acid (Compound 327);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (1,2-dihydro-1-methyl-2-oxo-3-indole Lilydene) methyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 328);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (5-fluoro-2-methylphenyl) -ethyl) phenyl) hydro Lazono) pyrazolyl} butanoic acid (Compound 329);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-difluorophenyl) -ethyl) phenyl) hydro Lazono) pyrazolyl} butanoic acid (Compound 330);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (256-dimethylphenyl) -ethenyl) phenyl) hydro Lazono) pyrazolyl} butanoic acid (Compound 331);

4- {2- (5-methyl ~ 3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-methylphenyl) -ethenyl) phenyl) hydrazo No) pyrazolyl} butanoic acid (Compound 332);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (5-fluoro-2-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 333);

4- (2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (Z)-(2- (5-fluoro-2-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 334);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (3-fluorophenyl) ethenyl) phenyl) hydro Lazono) pyrazolyl} butanoic acid (Compound 335);

4- {2- (5-methyl-3-oxo-23-dihydro-4- (2-hydroxy-3 (E)-(2- (4-fluorophenyl) ethenyl) phenyl) hydrazono ) Pyrazolyl} butanoic acid (compound 336);

4- (2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-fluorophenyl) -ethenyl) phenyl) Hydrazono) pyrazolyl} butanoic acid (compound 337);

4- {2- (5-Methyl-3-oxo-2.3-dihydro-4- (2-hydroxy-3 (E)-(2-phenylethenyl) -phenyl) hydrazono) pyrazolyl} part Carbonic acid (compound 338);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-phenylethynyl) -phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 339);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methylphenyl) ethynyl) -phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 340);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dimethylphenyl) -ethynyl) phenyl) hydrazo No) pyrazolyl} butanoic acid (Compound 341);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluorophenyl) ethynyl) -phenyl) hydrazono ) Pyrazolyl} butanoic acid (Compound 342);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-trifluoromethylphenyl) -ethynyl) phenyl) hydrazo No) pyrazolyl} butanoic acid (Compound 343);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-trifluoromethyl-phenyl) ethynyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 344);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (1-methyl-1-indenyl-2-) phenyl) -hydrazono ) Pyrazolyl} butanoic acid (Compound 345);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3,3-dimethyl-2-indenyl) phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 346);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-5-methoxy-3- (2-indenyl) -phenyl) hydrazono) pyra Jolyl} butanoic acid (Compound 347);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (4,7-dimethyl-2-indenyl) phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 348);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (4,7-difluoro-2-indenyl) phenyl) hydrazono ) Pyrazolyl} butanoic acid (compound 349);

3- {2-hydroxy-3- (2-oxo-2,3-dihydro-6-trifluoromethyl-1- (2- (2-methylphenyl) -ethyl) -3 (Z) -indolily Den) methylaminophenyl} benzoic acid (compound 350);

3- {2-hydroxy-3- (2-oxo-2,3-dihydro-6-trifluoromethyl-1- (2-indenyl) -3 (Z) -indolylidene) methylaminophenyl } Benzoic acid (compound 351);

(±) 4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (l, 2,3,4-tetrahydro)- Naphthyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 352);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro) -naphthyl) phenyl) hydrazo No) pyrazolyl} butanoic acid (compound 353);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(1-indanylidene) -methylphenyl) hydrazono) pyrazolyl } Butanoic acid (compound 354);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (5-fluoro-2-trifluoromethylphenyl) Ethenyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 355);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (6-fluoro-2-trifluoro-methylphenyl ) Ethenyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 356);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (6-fluoro-2-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 357);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (4-fluoro-2-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 358);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (3-fluoro-2-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 359);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,6-difluorophenyl) -ethenyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 360);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,5-difluorophenyl) -ethenyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 361);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (4-fluoro-2-trifluoro-methylphenyl ) Ethenyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 362);

4- (2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,4-difluorophenyl) -ethynyl) phenyl) Hydrazono) pyrazolyl} butanoic acid (compound 363);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(1- (l, 2,3,4-tetrahydro)- Naphthalidene) methylphenyl) hydrazono) pyrazolyl} butanoic acid (Compound 364);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-fluoro-5-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 365);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (3,5-dimethyl-4-isoxazolyl) Ethenyl) phenyl) hydrazono) pyrazolyl) butanoic acid (Compound 366);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,5-dimethyl-4-isoxazolyl) ethyl) phenyl ) Hydrazono) pyrazolyl} butanoic acid (compound 367);

3- {2-hydroxy-3- (2-oxo-2,3-dihydro-1- (2 (E)-(2-methylphenyl) ethenyl) -3 (Z) -indolylidene) methylamino Phenyl} benzoic acid (compound 368);

3- {2-hydroxy-3- (2-oxo-2,3-dihydro-1- (2 (E)-(2,4-difluorophenyl) ethenyl) -3 (Z) -indole Lilydene) methylaminophenyl} benzoic acid (compound 369);

3- {2-Hydroxy-3- (2-oxo-2,3-dihydro-l- (2-indenyl) -3 (Z) -indolylidene) methyl-aminophenyl} benzoic acid (Compound 370) ;

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (5-fluoro-2-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 371);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3-methylphenyl) hydrazono) -pyrazolyl} butanoic acid (Compound 372);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indanylidenemethyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 373);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indanylmethyl) phenyl) hydrazono) pyrazolyl} butanoic acid ( Compound 374);

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,4-difluorophenyl) -ethenyl ) Phenyl) hydrazono) pyrazolyl} benzoic acid (compound 375);

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,6-difluorophenyl) -ethenyl ) Phenyl) hydrazono) pyrazolyl} benzoic acid (compound 376);

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (4-fluoro-2-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 377);

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-fluoro-6-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 378);

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,3-difluorophenyl) -ethenyl ) Phenyl) hydrazono) pyrazolyl} benzoic acid (compound 379);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,3-difluorophenyl) -ethenyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 380);

4- (2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-fluoro-4-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 381);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-chlorophenyl) -ethenyl) phenyl) hydr Lazono) pyrazolyl} butanoic acid (Compound 382);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,6-dichlorophenyl) -ethenyl) phenyl ) Hydrazono) pyrazolyl} butanoic acid (compound 383);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (3-chlorophenyl) -ethenyl) phenyl) hydr Razono) pyrazolyl} butanoic acid (compound 384);

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,5-difluorophenyl) -ethenyl ) Phenyl) hydrazono) pyrazolyl} benzoic acid (compound 385);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-chloro-4-fluorophenyl) ethenyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 386);

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-trifluoromethyl-4-fluorophenyl ) Ethenyl) phenyl) hydrazono) pyrazolyl} benzoic acid (compound 387);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,4-dichlorophenyl) -ethenyl) phenyl ) Hydrazono) pyrazolyl} butanoic acid (compound 388);

In 3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-chloromethyl-4-fluorophenyl) Tenyl) phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 389);

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,4-dichloromethylphenyl) ethenyl) phenyl) Hydrazono) pyrazolyl} benzoic acid (compound 390);

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro) -naphthyl) phenyl) hydrazo No) pyrazolyl} benzoic acid (Compound 391);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-8-fluoro) -naphthyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 392);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-8-methyl) -naphthyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 393);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-7-methyl) -naphthyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 394);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-7-fluoro) -naphthyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 395);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-6-fluoro) -naphthyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 396);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-5-fluoro) -naphthyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 397);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-8-chloro) -naphthyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 398);

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-7-fluoro) -naphthyl ) Phenyl) hydrazono) pyrazolyl} provides a compound selected from the group consisting of benzoic acid (compound 399) or a pharmaceutically acceptable salt, ester or prodrug thereof.

In certain embodiments, the compound of Formula (I), (II), (III), (IV), (V) or (VI) is a selective TPO modulator. In certain embodiments, the compound of Formula (I), (II), (III), (IV), (V) or (VI) is a TPO mimic.

In certain embodiments, the present invention provides a method of modulating TPO activity. This particular method involves contacting one or more compounds according to the invention with a cell. Certain methods include, but are not limited to, contacting the TPO and / or TPO receptor with one or more compounds according to the present invention.

In certain embodiments, the invention is capable of modulating TPO activity, comprising the steps of: a) contacting a cell capable of TPO activity with a compound according to the invention, b) monitoring the effect of the compound on cells. Provided are methods for identifying a compound. In certain embodiments, the cell exhibits a TPO receptor.

In certain embodiments, the present invention provides a method of treating a patient, comprising administering a compound according to the invention to the patient. In certain embodiments, the patient is a thrombocytopenia patient. In certain embodiments, one or more compounds according to the invention are administered before, during or after chemotherapy, bone marrow transplantation and / or radiation therapy. In certain embodiments, one or more compounds according to the present invention are administered to patients with aplastic anemia, myeloid failure and / or idiopathic thrombocytopenia. In certain embodiments, one or more compounds according to the invention are administered to a patient with a neurological disease. In certain embodiments, one or more compounds according to the present invention are administered to a patient with amyotrophic lateral sclerosis, multiple sclerosis or multiple dystrophy. In certain embodiments, one or more compounds according to the present invention are administered to a patient with nerve injury, including but not limited to spinal cord injury.

In certain embodiments, the invention provides a pharmaceutical composition comprising i) a physiologically acceptable carrier, diluent or excipient or combination thereof and ii) one or more compounds according to the invention.

In certain embodiments, the present invention provides selective TPO modulators. In certain embodiments, the present invention provides selective TPO receptor agonists. In certain embodiments, the present invention provides selective TPO receptor antagonists. In certain embodiments, the present invention provides selective TPO partial agonists. In certain embodiments, the present invention provides selective TPO receptor binding compounds. In certain embodiments, the present invention provides a TPO mimetic.

The foregoing description and the following detailed description are to be understood as illustrative only and not as limiting the scope of the claimed invention. In this application, the use of the singular includes the plural unless stated otherwise. In this application, the use of “or” means “and / or” unless stated otherwise. Moreover, the terms "comprising" and other forms thereof, such as "comprises" and "included," are not in a limiting sense.

The headings used herein do not limit the subject matter described as being used solely for systematic description. All documents or portions of documents cited herein, for example, but not limited to, patents, patent applications, documents, books, manuals and articles are incorporated herein by reference in their entirety.

Justice

Unless otherwise defined, the nomenclature used in connection with the experimental processes and techniques of analytical chemistry, synthetic organic chemistry, medical chemistry, and pharmacy as described herein is known to those skilled in the art. Standard chemical symbols are used interchangeably with the full name represented by the symbol. Thus, for example, the terms “hydrogen” and “H” have the same meaning. Standard techniques are used for chemical synthesis, chemical analysis, pharmaceutical preparation, formulation and delivery, and treatment of patients. Nucleotide synthesis, tissue culture and transformation (eg electroporation, lipofection) can be used for reaction and purification techniques, for example using kits according to the manufacturer's instructions or in the art. The techniques and processes described above are generally carried out in accordance with conventional methods known in the art or in various general and more detailed literature cited and described throughout the present application. It may be practiced as described. See, eg, Sambrook et al. Molecular Cloning: A Laboratory Manual (2d ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N. Y. (1989), which is incorporated herein by reference.

As used herein, the following terms have the following meanings unless stated otherwise.

The term “selective binding compound” refers to a compound that selectively binds to any site of one or more targets.

The term “selective TPO receptor binding compound” refers to a compound that selectively binds to any site of the TPO receptor.

The term “selectively binds” refers to the ability of a selective binding compound to bind to a target receptor with an affinity greater than that for binding to a non-target receptor. In certain embodiments, selective binding indicates binding to the target with an affinity of at least 10, at least 50, at least 100, at least 250, at least 500, or at least 1000 times greater than the affinity for the non-target receptor.

The term “target receptor” refers to a receptor or site of receptor that can be bound by a selective binding compound. In certain embodiments, the target receptor is a TPO receptor.

The term “modulator” refers to a compound that modifies activity. For example, modulators can increase or decrease the degree of specific activity relative to the degree of activity in the absence of the modulator. In certain embodiments, the modulator is an inhibitor that reduces the degree of one or more activities. In certain embodiments, the inhibitor completely inhibits one or more biological properties. In certain embodiments, modulators are activators that increase the degree of one or more activities. In certain embodiments, the presence of a modulator exhibits activity that does not appear in the absence of the modulator.

The term “selective modulator” refers to a compound that selectively modulates target activity.

The term “selective TPO modulator” refers to a compound that selectively modulates one or more TPO activities. The term “selective TPO modulator” includes, but is not limited to, a “TPO mimetic” which refers to a compound that, when present, exhibits one or more TPO activities. TPO mimetics are described in WO 03 / 103686A1 and WO 01/21180, which are hereby incorporated by reference in their entirety.

The term “selectively modulating” refers to the ability of a selective modulator to modulate target activity to a greater extent than to modulate nontarget activity.

The term “target activity” refers to a biological activity that can be modulated by selective modulators. Examples of specific target activities include, but are not limited to, binding affinity, signal induction, enzymatic activity, proliferation and / or differentiation of progenitor cells, platelet production and alleviation of symptoms of a disease or condition.

The term “TPO activity” refers to a biological activity that is caused directly or indirectly due to the presence of TPO. Exemplary TPO activity includes, but is not limited to, proliferation and / or differentiation of progenitor cells that produce platelets, hematopoiesis, growth and / or development of glial cells, recovery of nerve cells and alleviation of thrombocytopenia .

The term “thrombocytopenia” refers to a condition where the concentration of platelets in the blood of a patient is lower than the normal level of a healthy person. In certain embodiments, the platelet count in thrombocytopenia is less than 450,000, less than 400,000, less than 350,000, less than 300,000, less than 250,000, less than 200,000, less than 150,000, less than 140,000, less than 130,000, less than 120,000, less than 110,000, less than 100,000 per microliter of blood. , Less than 75,000 or less than 50,000.

The term “receptor mediated activity” refers to any biological activity caused directly or indirectly by binding of a ligand to a receptor.

The term “agonist” refers to a compound in which the biological activity of the receptor caused by the presence of the compound is the same as the biological activity due to the presence of a ligand that occurs naturally to the receptor.

The term “partially agonist” denotes a compound in which the biological activity of the receptor caused by the presence of the compound is of the same type or degree of activity that is lower than the biological activity due to the presence of a ligand that occurs naturally to the receptor.

The term “antagonist” refers to a compound in which the presence of the compound reduces the degree of biological activity of the receptor. In certain embodiments, the presence of the antagonist is completely blocked due to the biological activity of the receptor.

The term "alkyl" refers to an aliphatic hydrocarbon group. Alkyl may be “saturated alkyl” containing no alkene or alkyne groups at all. The alkyl group may be an "unsaturated alkyl" comprising one or more alkenes or alkyne groups. Saturated alkyl or unsaturated alkyl may be branched or straight chain. Alkyl may be cyclic or acyclic. Cyclic alkyl includes polycyclic systems, including conjugated alkyl rings. Alkyl may be substituted or unsubstituted. Alkyl is, but is not limited to, optionally substituted, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertiary butyl, pentyl, hexyl, ethenyl, propenyl, butenyl, cyclopropyl, cyclobutyl , Cyclopentyl, cyclohexyl and the like.

In certain embodiments, alkyl contains 1 to 20 carbon atoms (where numerical ranges are indicated herein (eg, 1 to 20) represent each integer in a given range, for example, 1 to 20 carbon atoms It means that an alkyl group can contain up to 20 carbon atoms, including only 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc. The term "alkyl" includes the case where there is no limitation on the carbon number range).

The term "lower alkyl" refers to alkyl having 1 to 5 carbon atoms. The term “intermediate alkyl” means alkyl containing 5 to 10 carbon atoms. Alkyl may be represented by “C ₁ -C ₄ alkyl” or a similar designation. For example, “C ₁ -C ₄ alkyl” refers to alkyl having 1, 2, 3 or 4 carbon atoms, for example, the alkyl is methyl, ethyl, propyl, iso-propyl, n-butyl, iso- Butyl, secondary-butyl, tert-butyl, ethenyl, propenyl, butenyl, ethynyl, propynyl and butynyl.

The term “alkenyl” refers to an alkyl group comprising one or more carbon-carbon double bonds.

The term “alkynyl” refers to an alkyl group comprising one or more carbon-carbon triple bonds.

The term “haloalkyl” means alkyl in which one or more hydrogen atoms have been replaced with halogen atoms. In certain embodiments, when two or more hydrogen atoms are replaced with halogen atoms, the halogen atoms are all the same. In certain embodiments, not all halogen atoms are identical to each other.

The term “heteroalkyl” denotes a group comprising alkyl and one or more heteroatoms. Particular heteroalkyls are acylalkyls in which one or more heteroatoms are present in the alkyl chain. Examples of heteroalkyls include, but are not limited to, CH ₃ C (═O) CH ₂ —, CH ₃ C (═O) CH ₂ CH ₂ —, CH ₃ CH ₂ C (═O) CH ₂ CH ₂ —, CH ₃ C (═O) CH ₂ CH ₂ CH ₂ —, CH ₃ OCH ₂ CH ₂ —, CH ₃ NHCH ₂ — and the like.

The term “linear alkoxy” denotes a group comprising the formula — (CH ₂ ) pO—, where p is any integer. Straight chain alkoxy does not include substituted or branched alkoxy groups.

The term “non-chain-alkoxy-heteroalkyl” refers to any heteroalkyl that is not a straight chain alkoxy heteroalkyl. Thus, for example, non-linear alkoxyheteroalkyl includes, but is not limited to, 2,2-isopropyloxy; 1,2-propyloxy; 1,1-ethyloxy; Methylamino; Ethylamino; Propylamino; Methylpyrrolidino; And methylpiperidino.

The term “olefin” refers to a C═C bond.

The term “heterohaloalkyl” refers to heteroalkyl in which one or more hydrogen atoms have been replaced with halogen atoms.

The term “carbocycle” refers to a group comprising a covalently closed ring, wherein each atom forming the ring is a carbon atom. Carbocycle rings may be formed by three, four, five, six, seven, eight, nine, or more than nine carbon atoms. Carbocycles may be optionally substituted.

The term “heterocycle” refers to a group comprising a covalently closed ring in which one or more atoms forming the ring is a heteroatom. Heterocycle rings may be formed by three, four, five, six, seven, eight, nine or more atoms. Any number of atoms of interest may be a heteroatom (ie, a heterocycle ring may comprise three, four, five, six, seven, eight, nine or more heteroatoms). In heterocycle rings comprising two or more heteroatoms, the two or more heteroatoms may be the same or different from one another. Heterocycles may be optionally substituted. The bond to the heterocycle may be through a heteroatom or a carbon atom. For example, the bond to the benzo-conjugated derivative may be through the carbon of the benzenoid ring. Examples of heterocycles include, but are not limited to, the following.

Wherein D, E, F and G independently represent a heteroatom. Each of D, E, F, and G may be the same or different from each other.

The term “heteroatom” refers to an atom other than carbon or hydrogen. Heteroatoms are typically independently selected from oxygen, sulfur, nitrogen, and phosphorus. In embodiments in which two or more heteroatoms are present, the two or more heteroatoms may all be the same as each other or some or all of the two or more heteroatoms may be different from each other.

The term “aromatic” refers to a group comprising a covalently closed ring having an unlocalized π-electron field. Aromatic rings can be formed by five, six, seven, eight, nine or more atoms. Aromatics can be optionally substituted. Examples of aromatic groups include, but are not limited to, phenyl, naphthalenyl, phenanthrenyl, anthracenyl, tetralinyl, fluorenyl, indenyl and indanyl. The term aromatic is connected, for example, via any of the ring-forming carbon atoms and is aryl, heteroaryl, cycloalkyl, non-aromatic heterocycle, halo, hydroxy, amino, cyano, nitro, alkylamido, acyl, C ₁ -C ₆ alkoxy, C ₁ -C ₆ alkyl, C ₁ -C ₆ hydroxyalkyl, C ₁ -C ₆ aminoalkyl, C ₁ -C ₆ alkylamino, alkylsulphenyl, alkylsulfinyl, alkylsulfonyl, Benzenoid groups optionally containing one or more substituents selected from sulfamoyl, or trifluoromethyl. In certain embodiments, aromatic groups are substituted in one or more para, meta and / or auto positions. Examples of aromatic groups including substituents include, but are not limited to, phenyl, 3-halophenyl, 4-halophenyl, 3-hydroxyphenyl, 4-hydroxyphenyl, 3-aminophenyl, 4-aminophenyl, 3 -Methylphenyl, 4-methylphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 4-trifluoromethoxyphenyl, 3-cyanophenyl, 4-cyanophenyl, dimethylphenyl, naphthyl, hydroxynaphthyl, Hydroxymethylphenyl, (trifluoromethyl) phenyl, alkoxyphenyl, 4-morpholin-4-ylphenyl, 4-pyrrolidin-1-ylphenyl, 4-pyrazolylphenyl, 4-triazolylphenyl and 4- (2-oxopyrrolidin-1-yl) phenyl.

The term “aryl” refers to an aromatic group wherein each atom forming the ring is a carbon atom. Aryl rings may be formed by five, six, seven, eight, nine, or more than nine carbon atoms. Aryl groups may be optionally substituted.

The term “heteroaryl” refers to an aromatic group in which one or more atoms forming the aromatic ring is a heteroatom. Heteroaryl rings may be formed by three, four, five, six, seven, eight, nine or more atoms. Heteroaryl groups may be optionally substituted. Examples of heteroaryl groups include, but are not limited to, aromatic C, including one oxygen or sulfur atom or up to four nitrogen atoms or comprising a combination of one oxygen or sulfur atom and up to two nitrogen atoms. It includes a bonded derivatives _3-8 heterocyclic group, or substituted derivatives thereof, for example benzo ring formed of carbon atoms linked through any one of a-and pyrido. In certain embodiments, a heteroaryl group, halo, hydroxy, amino, cyano, nitro, alkylamino, acyl, C _{1 -6} alkoxy, C _{1 -6} alkyl, C _{1 -6} alkyl, hydroxy, C _{1 -6} amino alkyl, is optionally substituted with C _{1 -6} alkylamino, alkyl sulfonic phenyl, alkylsulfinyl, alkylsulfonyl, sulfamoyl, or one or more substituents independently selected from trifluoromethyl. Examples of heteroaryl groups include, but are not limited to, furan, benzofuran, thiophene, benzothiophene, pyrrole, pyridine, indole, oxazole, benzoxazole, isoxazole, benzisoxazole, thiazole, benzothia Sol, isothiazole, imidazole, benzimidazole, pyrazole, indazole, tetrazole, quinoline, isoquinoline, pyridazine, pyrimidine, purine and pyrazine, furazane, 1,2,3-oxadiazole, 1,2,3-thiadiazole, 1,2,4-thiadiazole, triazole, benzotriazole, putridine, phenoxazole, oxadiazole, benzopyrazole, quinolyzine, cinnoline, Unsubstituted, mono- or di-substituted derivatives of phthalazine, quinazoline and quinoxaline. In a particular embodiment, the substituents are halo, hydroxy, cyano, OC _{1 -6} alkyl, C _{1 -6} alkyl, hydroxy -C _{1 -6} alkyl and amino -C _{1 -6} alkyl.

The term “nonaromatic ring” refers to a group comprising a covalently closed ring that does not have an unlocalized π-electron field.

The term “cycloalkyl” denotes a group comprising a non-aromatic ring where each atom forming the ring is a carbon atom. Cycloalkyl rings may be formed by three, four, five, six, seven, eight, nine, or more than nine carbon atoms. Cycloalkyls can include polycyclic systems, such as conjugated ring systems. Cycloalkyl may be optionally substituted. In certain embodiments, cycloalkyls include one or more unsaturated bonds. Examples of cycloalkyl include, but are not limited to, cyclopropane, cyclobutane, cyclopentane, cyclopentene, cyclopentadiene, cyclohexane, cyclohexene, 1,3-cyclohexadiene, 1,4-cyclohexadiene, Cycloheptane and cycloheptene.

The term "non-aromatic heterocycle" refers to a group comprising a non-aromatic ring in which one or more atoms forming the ring is a heteroatom. Non-aromatic heterocycles may be formed by three, four, five, six, seven, eight, nine or more atoms. Non-aromatic heterocycles may be optionally substituted. In certain embodiments, non-aromatic heterocycles include one or more carbonyl or thiocarbonyl groups, such as oxo- and thio-containing groups. Examples of non-aromatic heterocycles include, but are not limited to, lactams, lactones, cyclic imides, cyclic thiimides, cyclic carbamates, tetrahydrothiopyrans, 4 H -pyrans, tetrahydropyrans, piperidine , 1,3-dioxin, 1,3-dioxane, 1,4-dioxin, 1,4-dioxane, piperazine, 1,3-oxatian, 1,4-oxatine, 1,4- Oxatian, tetrahydro-1,4-thiazine, 2H -1,2-oxazine, maleimide, succinimide, barbituric acid, thiobarbituric acid, dioxopiperazine, hydantoin, dihydrouracil , Morpholine, trioxane, hexahydro-1,3,5-triazine, tetrahydrothiophene, tetrahydrofuran, pyrroline, pyrrolidine, pyrrolidone, pyrrolidion, pyrazoline, pyrazolidine, Imidazoline, imidazolidine, 1,3-dioxol, 1,3-dioxolane, 1,3-dithiol, 1,3-dithiolane, isoxazolin, isoxazolidine, oxazoline, oxa Zolidine, oxazolidinone, tee Azoline, thiazolidine and 1,3-oxathiolane.

The term “arylalkyl” refers to a group comprising an aryl group bonded to an alkyl group.

The term “carbocycloalkyl” refers to a group comprising a carbocyclic cycloalkyl ring. Carbocycloalkyl rings may be formed by three, four, five, six, seven, eight, nine, or more than nine carbon atoms. Carbocycloalkyl may be optionally substituted.

The term “ring” refers to all covalently closed structures. Rings include, for example, carbocycles such as aryl and cycloalkyl, heterocycles such as heteroaryl and nonaromatic heterocycles, aromatics such as aryl and heteroaryl, and nonaromatics such as cycloalkyl and nonaromatic Heterocycle). The ring may be optionally substituted. The ring may form part of a ring system.

The term “ring system” refers to a single ring or two or more rings, and when two or more rings are present, the two or more rings are joined. The term “conjugated” refers to a structure in which two or more rings share one or more bonds.

(여기서, A, B 및 C는 O, S 및 N으로부터 각각 독립적으로 선택된다)를 포함한다.The term “carboxylic acid isomeric” refers to a group that is biologically equivalent to a carboxylic acid. For example, carboxylic acid bioequivalents include, but are not limited to, tetrazole, NHSO ₂ R ¹⁵ , OC (S) NR ¹⁰ R ¹¹ , SC (O) NR ¹⁰ R ¹¹ , thiazolidinedione, oxazolidine Dione and 1-oxa-2,4-diazolidine-3,5-dione. In certain embodiments, the carboxylic acid bioisomer is

Wherein A, B, and C are each independently selected from O, S, and N.

The term “spacer” refers to an atom or group of atoms that separates two or more groups from each other by the desired number of atoms. For example, in certain embodiments, it is preferable to separate two or more groups by one, two, three, four, five, six or more atoms. In certain embodiments, any atom or group of atoms may be used to separate the group by the desired number of atoms. The spacer may be optionally substituted. In certain embodiments, the spacer comprises saturated or unsaturated alkyl, heteroalkyl and / or haloalkyl. In certain embodiments, the spacer comprises an atom that is part of a ring.

(여기서, A 및 B는 목적하는 원자 개수에 의해 분리되는 그룹을 나타낸다)를 포함한다. 2개 원자 스페이서의 예는 이에 제한되는 것은 아니지만,

(여기서, A 및 B는 목적하는 원자 개수에 의해 분리되는 그룹을 나타낸다)를 포함한다. Specific examples of spacers are described for illustrative purposes only and do not limit the above definition. Examples of one atomic spacers include, but are not limited to

(Where A and B represent groups separated by the desired number of atoms). Examples of two atom spacers include, but are not limited to

(Where A and B represent groups separated by the desired number of atoms).

Examples of three atom spacers include, but are not limited to

(여기서, A 및 B는 목적하는 원자 개수에 의해 분리되는 그룹을 나타낸다)을 포함한다. 상기 예로부터 분명한 바와 같이, 목적하는 분리를 생성하는 원자는 그 자체가 그룹의 부분일 수 있다. 당해 그룹의 예로는 알킬, 헤테로알킬, 할로알킬, 헤테로할로알킬, 사이클로알킬, 아릴, 아릴알킬, 헤테로아릴, 비방향족 헤테로사이클 또는 임의 치환될 수 있는 치환된 알킬일 수 있다. 따라서, 용어 “1개 내지 5개 원자 스페이서”는 1개, 2개, 3개, 4개 또는 5개 원자에 의해 2개의 그룹을 분리시키는 스페이서를 나타내며 스페이서를 구성하는 그룹의 전체 크기를 나타내는 것은 아니다.

Where A and B represent groups separated by the desired number of atoms. As is apparent from the above examples, the atoms that produce the desired separation may themselves be part of a group. Examples of such groups may be alkyl, heteroalkyl, haloalkyl, heterohaloalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, nonaromatic heterocycle or substituted alkyl which may be optionally substituted. Thus, the term “one to five atom spacers” refers to a spacer that separates two groups by one, two, three, four, or five atoms, and refers to the total size of the groups that make up the spacer. no.

에서 A와 B가 “연결되어 환을 형성"한다면, 생성 환은 A, B, C 및 연결기를 포함한다. 다른 언급이 없으면, 연결기는 임의의 길이이며, 임의로 치환될 수 있다. 상기 예로 나타내는 생성 구조는, 이에 제한되는 것은 아니지만,

,

,

,

,

,

등을 포함한다.As used herein, the term “bonded to form a ring” refers to a case where two atoms bonded to one atom or to atoms (the atoms themselves are bonded to each other) are each bonded to a linker to form a ring structure. Indicates. The resulting ring contains two atoms that are linked to form a ring, an atom (or atoms) that has been linked to the atom, and a linking group. E.g,

In which A and B are “connected to form a ring”, the resulting ring includes A, B, C and a linking group. Unless otherwise indicated, the linking group is of any length and may be optionally substituted. Is not limited to this,

,

,

,

,

,

And the like.

에서 A 및 B가 연결된다면, 생성 환은 A, B, A와 B를 연결하고 있는 2개의 원자 및 연결기를 포함한다. 생성된 구조의 예는 이에 제한되는 것은 아니지만,

,

등을 포함한다.In certain embodiments, two substituents that form a ring with each other do not immediately bond to the same atom. E.g,

If A and B are linked, the resulting ring includes A, B, two atoms and a linking group connecting A and B. Examples of generated structures are not limited to this,

,

And the like.

에서 A와 B가 연결되어 환을 형성하는 경우, 생성된 환은 A, B, A와 B를 연결하고 있는 3개의 원자 및 연결기를 포함한다. 생성된 구조의 예는 이에 제한되는 것은 아니지만

등을 포함한다.In certain embodiments, atoms forming a ring with each other are separated by three or more atoms. E.g,

When A and B are connected to form a ring, the generated ring includes A, B, three atoms and a linking group connecting A and B. Examples of generated structures are not limited to this

And the like.

에서 A와 B가 “함께 결합을 형성"한다면, 생성된 구조는

이다.As used herein, the term “to form a bond together” refers to the case where there are no two substituents on neighboring atoms and the bond between neighboring atoms is a double bond. E.g,

If A and B “form a bond together”, then the resulting structure

to be.

에서 X가 N인 경우, R' 또는 R'' 중 어느 하나가 "없음"은 3개 그룹만이 N에 결합됨을 의미한다.The term “none” refers to a group that does not exist in the structure. Example structure

Where X is N, then neither "R" nor "R" means that only three groups are bonded to N.

Substituents “R” represented by themselves without reference to numerals represent substituents selected from alkyl, cycloalkyl, aryl, heteroaryl (bonded via a ring carbon) and nonaromatic heterocycle (bonded through a ring carbon).

The term “O-carboxy” refers to a group of the formula RC (═O) O—.

The term “C-carboxy” refers to a group of the formula —C (═O) OR.

The term “acetyl” refers to the group —C (═O) CH ₃ .

The term “trihalomethanesulfonyl” refers to a group of formula X ₃ CS (═O) ₂ —, wherein X is halogen.

The term “cyano” refers to a group of the formula —CN.

The term “isocyanato” refers to a group of the formula —NCO.

The term "thiocyanato" refers to a group of the formula -CNS.

The term “isothiocyanato” refers to a group of the formula —NCS.

The term “sulfonyl” refers to a group of the formula —S (═O) —R.

The term “S-sulfonamido” refers to a group of the formula —S (═O) ₂ NR.

The term “N-sulfonamido” refers to a group of the formula RS (═O) ₂ NH—.

The term “trihalomethanesulfonamido” refers to a group of formula X ₃ CS (═O) ₂ NR—.

The term “O-carbamyl” refers to a group of the formula —OC (═O) —NR.

The term “N-carbamyl” refers to a group of the formula ROC (═O) —NH—.

The term "O-thiocarbamyl" denotes a group of the formula -OC (= S) -NR.

The term "N-thiocarbamyl" refers to a group of the formula ROC (= S) NH-.

The term "C-amido" denotes a group of the formula -C (= 0) -NR ₂ .

The term "N-amido" denotes a group of the formula RC (= 0) NH-.

The term "oxo" refers to a group of formula = O.

의 구조식을 가지며, 여기서 2개의 라디칼은 환의 임의의 위치일 수 있다.The term "dihydropyrazolylene" refers to the 2-radical of an optionally substituted dihydropyrazole ring, wherein the dihydropyrazole ring is

Wherein the two radicals may be at any position of the ring.

의 구조식을 가지며, 당해 라디칼은 환의 임의의 위치일 수 있다. The term “pyrazolyl” refers to a radical of the pyrazole ring, wherein the pyrazole ring

Wherein the radical may be any position of the ring.

The term "ester" refers to the formula-(R) _n COOR 'wherein R and R' are alkyl, cycloalkyl, aryl, heteroaryl (bonded through a ring carbon) and nonaromatic heterocycle (bonded through a ring carbon) And independently from each other from the group consisting of n is 0 or 1).

The term "amide" refers to the formula-(R) _n -C (O) NHR 'or-(R) _n -NHC (O) R' wherein R and R 'are alkyl, cycloalkyl, aryl, heteroaryl (ring And heteroaryl cycles (bonded through carbon) and heteroarylcycles (bonded via ring carbon), independently of one another, n is 0 or 1).

The terms "amine", "hydroxy" and "carboxyl" include esterified or amidated groups. Processes and specific groups for the reaction of esterification and amidation are known to those skilled in the art and are described, for example, in Greene and Wuts, Protective Groups in Organic Synthesis, 3rd Ed., John Wiley & Sons, New York , NY, 1999, which is incorporated herein by reference in its entirety.

Unless stated otherwise, the term “optionally substituted” means that no hydrogen groups are replaced at all, or one or more hydrogen atoms are alkyl, heteroalkyl, haloalkyl, heterohaloalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, nonaromatic Heterocycle, hydroxy, alkoxy, aryloxy, mercapto, alkylthio, cyano, halo, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl , C-amido, N-amido, S-sulfonamido, N-sulfonamido, C-carboxy, O-carboxy, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, trihal Groups substituted individually and independently from one or more selected groups from romethanesulfonyl, amino, mono- and di-substituted amino groups and protective derivatives of amino groups. The protective derivatives mentioned (and protecting groups which can form such protective derivatives) are known to those skilled in the art and can be found, for example, in Greene and Wuts, supra. In certain embodiments in which two or more hydrogen atoms are substituted, the substituent groups may together form a ring.

In the specification, groups and substituents may be selected by those skilled in the art to provide stable moieties and compounds.

The term "carrier" refers to a compound that facilitates the introduction of another compound into cells or tissues. For example, dimethyl sulfoxide (DMSO) is a carrier commonly used to enhance the introduction of certain organic compounds into cellular tissues.

The term “pharmaceutical agent” refers to a chemical compound or composition that can induce a desired therapeutic effect in a patient. In certain embodiments, the pharmaceutical formulation includes an active agent that is an formulation that induces a desired therapeutic effect. In certain embodiments, the pharmaceutical formulation comprises a prodrug. In certain embodiments, the pharmaceutical formulation includes inert ingredients such as carriers, excipients, and the like.

The term "therapeutically effective amount" refers to an amount of pharmaceutical agent sufficient to achieve the desired therapeutic effect.

The term “prodrug” refers to a pharmaceutical agent that is converted in the body from a less active form to a more active equivalent.

The term "pharmaceutically acceptable" refers to a formulation of a compound that, when administered to a patient, does not significantly destroy the physiological activity, pharmacological activity, and / or other properties of the compound. In certain embodiments, pharmaceutically acceptable formulations do not cause severe irritation to the patient.

The term "co-administration" refers to the administration of one or more pharmaceutical agents to a patient. In certain embodiments, co-administered pharmaceutical formulations are administered together in a single dosage unit. In certain embodiments, the co-administered pharmaceutical formulations are each administered separately. In certain embodiments, co-administered pharmaceutical agents are administered simultaneously. In certain embodiments, co-administered pharmaceutical formulations are administered at different times.

The term "patient" includes human and animal subjects.

The term “substantially pure” means that the subject species (eg, compound) is predominantly present (ie, more abundant than other individual species on a molar basis in the composition). In certain embodiments, the substantially purified fraction is a composition comprising at least about 50% (by moles) of all species present in the subject species. In certain embodiments, the substantially pure composition will comprise greater than about 80%, greater than 85%, greater than 90%, greater than 95% or greater than 99% of all species present in the composition. In certain embodiments, the subject species is purified to have the essential identity (pollution species not detected in the composition by conventional methods of detection), and the composition consists essentially of a single species.

The term “tissue-selective” refers to the ability of a compound to modulate biological activity in a particular tissue to a lesser or greater extent than the biological activity in other tissues. The biological activity in different tissues may be the same or may be different. Biological activity in different tissues may be mediated by the same type of target receptor. For example, in certain embodiments, tissue-selective compounds may modulate receptors that mediate biological activity in certain tissues but may not, or to a lesser extent, mediate biological activity in other tissue types.

The term "monitoring" means observing any effect or the absence of any effect. In certain embodiments, the cells are monitored after contact with the compounds according to the invention. Examples of effects that can be monitored include, but are not limited to, changes in cellular phenotype, cell proliferation, receptor activity, or interaction of the receptor with a compound known to bind to the receptor.

The term "cell phenotype" refers to physical or biological properties. Examples of properties that make up the phenotype include, but are not limited to, cell size, cell proliferation, cell differentiation, cell viability, apoptosis (apoptosis) or the use of metabolic nutrients (eg, glucose uptake). . Certain changes or absence of changes in cellular phenotypes are readily monitored using methods known to those skilled in the art.

The term "cell proliferation rate" refers to the rate at which cells divide. In certain embodiments, the cells remain intact in the organism. In certain embodiments, the cells are cultured in vitro. The number of cells cultured in a vessel can be quantified by one skilled in the art (eg, by using a microscope to count cell numbers using a microscope in a defined area or by using an experimental instrument that measures the density of the fineness in a suitable medium). One skilled in the art can calculate the rate of cell proliferation by measuring the number of cells more than once.

The term "contacting" refers to bringing two or more materials close enough to interact. In certain embodiments, “contacting” may be performed in a container such as a test tube, petri dish, or the like. In certain embodiments, "contacting" may be performed in the presence of additional material. In certain embodiments, “contacting” can be performed in the presence of cells. In certain embodiments, one or more substances to be contacted may be inside the cell. The cells may be living or dead. The cells may be intact or damaged.

Specific compounds

Certain compounds that modulate one or more TPO activities and / or bind to TPO receptors contribute to the maintenance of health. In certain embodiments, the compounds according to the invention are useful for the treatment of various diseases or conditions.

In certain embodiments, the present invention provides selective TPO modulators. In certain embodiments, the present invention provides selective TPO receptor binding agents. In certain embodiments, the present invention provides methods of making and using the selective TPO modulators and / or selective TPO receptor binders. In certain embodiments, the selective TPO modulator is an agonist, partial agonist and / or antagonist for the TPO receptor.

In certain embodiments, the present invention relates to a compound of formula (I), (II), (III), (IV), (V) or (VI) or a pharmaceutically acceptable salt, ester, amide or prodrug thereof.

[Formula I]

[Formula II]

[Formula III]

[Formula IV]

[Formula V]

[Formula VI]

(여기서, A, B 및 C는 O, S 및 N으로부터 각각 독립적으로 선택된다)로 이루어진 그룹으로부터 선택된다.In certain embodiments, R ¹ is hydrogen, halogen, OR ¹⁴ , NO ₂ , CN, NR ¹⁴ R ¹⁵ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ heteroalkyl, CO ₂ R ¹⁴ , CONR ¹⁴ R ¹⁵ , SO ₃ R ¹⁴ , SO ₂ NR ¹⁴ R ¹⁵ and a carboxylic acid bioequivalent. In certain embodiments, the carboxylic acid bioisomers are tetrazole, NHSO ₂ R ¹⁹ , OC (S) NR ¹⁴ R ¹⁵ , SC (O) NR ¹⁴ R ¹⁵ and

Wherein A, B and C are each independently selected from O, S and N.

In certain embodiments, each R ² is hydrogen, halogen, OR ¹⁴ , NR ¹⁴ R ¹⁵ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, and optionally substituted C ₁ -C ₆ Independently from heteroalkyl.

In certain embodiments, R ³ And R ⁴ is independently selected from hydrogen, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, and optionally substituted C ₁ -C ₆ heteroalkyl.

In certain embodiments, R ⁵ is hydrogen, halogen, OR ¹⁴ , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl, and C ₁ -C ₆ Haloheteroalkyl.

In certain embodiments, R ⁶ is optionally substituted C ₁ -C ₁₀ alkyl, optionally substituted C ₁ -C ₁₀ haloalkyl or optionally substituted C ₁ -C ₁₀ , each optionally bonded with substituted aryl or substituted heteroaryl Or is selected from heteroalkyl, R ⁶ is (CH ₂ ) _m R ¹⁸ or C (O) NHR ¹⁸ . In certain embodiments, R ⁶ is optionally substituted C ₁ -C ₁₀ alkyl, optionally substituted C ₁ -C ₁₀ haloalkyl or optionally substituted C ₁ -C ₁₀ , each optionally bonded with substituted aryl or substituted heteroaryl Or R ⁶ is selected from (CH ₂ ) _m R ¹⁸ , C (O) NHR ¹⁸ , C≡CR ¹⁸ , CR ³ = CR ⁴ R ¹⁸ and CR ³ = R ¹⁸ .

(여기서, A, B 및 C는 O, S 및 N으로부터 각각 독립적으로 선택된다)로 이루어진 그룹으로부터 선택된다.In certain embodiments, R ⁷ is selected from the group consisting of CO ₂ R ¹⁴ , CONR ¹⁴ R ¹⁵ , SO ₃ R ¹⁴ , SO ₂ NR ¹⁴ R ^15, and a carboxylic acid bioisotope. In certain embodiments, the carboxylic acid bioisomers are tetrazole, NHSO ₂ R ¹⁹ , OC (S) NR ¹⁴ R ¹⁵ , SC (O) NR ¹⁴ R ¹⁵ and

Wherein A, B and C are each independently selected from O, S and N.

In certain embodiments, each of R ⁸ and R ⁹ is hydrogen, OR ¹⁶ , NR ¹⁶ R ¹⁷ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ heteroalkyl, (CH ₂ ) _m R ¹⁸ and none independently; R ⁸ and R ⁹ together form an optionally substituted olefin; R ⁸ and R ⁹ are joined to form an optionally substituted C ₃ -C ₈ ring.

In certain embodiments, R ¹⁰ is hydrogen, halogen, oxo, OR ¹⁶ , NR ¹⁶ R ¹⁷ , SR ¹⁶ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl and optionally substituted C ₁ -C ₆ heteroalkyl.

In certain embodiments, R ¹¹ is selected from the group consisting of hydrogen, halogen, OR ¹⁴ , NR ¹⁴ R ¹⁵ and SR ¹⁴ . In certain embodiments, R ¹¹ and R ⁴ are joined to form an optionally substituted heterocycle.

In certain embodiments, R ¹² is selected from the group consisting of hydrogen, halogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl, and C ₁ -C ₆ haloheteroalkyl.

In certain embodiments, R ¹³ is hydrogen, halogen, CN, NO ₂ , CO ₂ R ¹⁴ , S (O) _m R ¹⁴ , C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ hetero Alkyl and C ₁ -C ₄ haloheteroalkyl.

In certain embodiments, R ¹⁴ is selected from the group consisting of hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl, and C ₁ -C ₆ heterohaloalkyl.

In certain embodiments, R ¹⁵ is from a group consisting of hydrogen, SO ₂ R ¹⁹ , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl, and C ₁ -C ₆ heterohaloalkyl Is selected.

In certain embodiments, R ¹⁶ and R ¹⁷ are hydrogen, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ heteroalkyl, and (CH ₂ ) _m R Each independently selected from the group consisting of ¹⁸ ; In certain embodiments, R ¹⁶ and R ¹⁷ If either is optionally substituted C ₂ -C ₆ alkyl, the other is none. In certain embodiments, R ¹⁶ and R ¹⁷ are joined to form an optionally substituted C ₃ -C ₈ ring.

In certain embodiments, R ¹⁸ is selected from an optionally substituted monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle, wherein R ¹⁸ is a nonaromatic heterocycle or carbo Where a cycle is included, the attachment site can be on a nonaromatic heterocycle or carbocycle or aromatic ring system.

In certain embodiments, R ¹⁹ is selected from the group consisting of hydrogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl and optionally substituted aryl.

In certain embodiments, D is a monocyclic or bicyclic aromatic ring system, optionally containing one or more heteroatoms and optionally conjugated with a non-aromatic heterocycle or carbocycle.

In certain embodiments, E is a monocyclic or bicyclic aromatic ring system, optionally containing one or more heteroatoms and optionally conjugated with a non-aromatic heterocycle or carbocycle.

In certain embodiments, L is NH or none.

In certain embodiments, Q is a monocyclic or bicyclic aromatic ring system, optionally containing one or more heteroatoms and optionally conjugated with a non-aromatic heterocycle or carbocycle.

In certain embodiments, U is selected from the group consisting of O, NR ⁴ , CR ³ R ⁴ , CO and none.

In certain embodiments, W is selected from the group consisting of O, NR ⁴ , CR ³ R ⁴ , CO and none.

In certain embodiments, X is N or CR ⁵ .

로 디하이드로피라졸릴렌을 형성하는 경우, (i) X가 N이고 W가 NH이면 D는 나프틸이 아니고, (ii) X가 CH이고, W가 NH이고, Z가 페닐이고, R¹⁰ 또는 R¹¹이 -(CH₂)_0-6OH이면, D는 페닐이 아니고, (iii)

는 피라졸릴이나 임의 치환된 5-하이드록시피라졸릴이 아니고, (iv) U는 NH가 아니다. 특정 양태에서, X가 N이고 W가 NH이면 D는 페닐이 아니다.In certain embodiments, Y is 1-4 atoms comprising one or more groups selected from optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ heteroalkyl, optionally substituted phenyl, and optionally substituted heteroaryl Spacer. In certain embodiments, Y is in the compound of Formula I or II

When forming dihydropyrazolylene, (i) D is not naphthyl if X is N and W is NH, (ii) X is CH, W is NH, Z is phenyl, R ¹⁰ or If R ¹¹ _is- (CH ₂ ) _0-6 OH, then D is not phenyl, and (iii)

Is not pyrazolyl or optionally substituted 5-hydroxypyrazolyl, and (iv) U is not NH. In certain embodiments, D is not phenyl when X is N and W is NH.

In certain embodiments, Z is absent; 2 to 5 atomic spacers selected from optionally substituted C ₆ -C ₁₀ aryl and optionally substituted C ₁ -C ₈ heteroaryl, each optionally bonded with an optionally substituted non-aromatic heterocycle or carbocycle; And _{1 selected} from optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ heteroalkyl, and optionally substituted C ₁ -C ₆ haloalkyl, each optionally optionally conjugated with optionally substituted C ₆ -C ₁₀ aryl; To 5 atomic spacers.

In certain embodiments, m is 0, 1 or 2. In certain embodiments, m is 0, 1, 2 or 3.

In certain embodiments n is 0 or 1.

In certain embodiments, when X is N and W is NH in the compound of Formula III or VI, R ⁶ , R ¹⁰ And R ¹¹ does not include carboxylic, amido, ester, or sulfurate functional groups or carboxylic acid bioisomers.

In certain embodiments in which two or more specific groups are present, the two or more specific groups are each independently selected and thus may be the same or different from one another. For example, certain compounds of the invention may comprise two or more R ¹⁴ Include a group. The two or more R ¹⁴ groups are each independently selected. Thus, in certain embodiments, R ¹⁴ The groups are all identical to each other. In certain embodiments, R ¹⁴ The groups are all different from each other. In certain embodiments, R ¹⁴ Some of the groups are identical to each other and some are different from each other. This independent selection applies to all groups present in at least one of the compounds.

In certain embodiments, the compound of Formula (I), (II), (III), (IV), (V) or (VI) is a selective TPO modulator. In certain embodiments, the compound of Formula (I), (II), (III), (IV), (V) or (VI) is a selective TPO receptor agonist. In certain embodiments, the compound of Formula (I), (II), (III), (IV), (V) or (VI) is a selective TPO receptor antagonist. In certain embodiments, the compound of Formula (I), (II), (III), (IV), (V) or (VI) is a selective TPO receptor partial agonist. In certain embodiments, the compound of Formula (I), (II), (III), (IV), (V) or (VI) is a tissue-selective TPO modulator. In certain embodiments, the compound of Formula (I), (II), (III), (IV), (V) or (VI) is a selective TPO receptor binding compound. In certain embodiments, the compound of Formula (I), (II), (III), (IV), (V) or (VI) is a TPO mimic

In certain embodiments, the present invention,

3 '-{[1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-3-ylidenemethyl] amino} -2'-hydroxybiphenyl -3-carboxylic acid (compound 101);

2,4-dihydroxybenzoic acid N '-{1- [1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] Ethyl} hydrazide (Compound 102);

3- {3-[(5-chloro-2-hydroxy-3 ', 4'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl } Benzoic acid (compound 103);

3- {3-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid (compound 104);

3 '-{[1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidenemethyl] amino} -4-fluoro-2 '-Hydroxybiphenyl-3-carboxylic acid (compound 105);

2- (3 '-{[1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidenemethyl] amino} -2'- Hydroxybiphenyl-3-yl) -2-methylpropionic acid (compound 106);

3 '-{[1- (3,4-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidenemethyl] amino} -2'-hydroxy ratio Phenyl-3-carboxylic acid (compound 107);

4- {3-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid (compound 108);

3- {3-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-6-trifluoromethyl-2,3-dihydroindole- 1-yl} benzoic acid (Compound 109);

3- {3-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-6-trifluoromethyl-2,3-dihydroindole- 1-yl} benzoic acid methyl ester (Compound 110);

3- {3-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid methyl ester (Compound 111);

3- {3-[(5-fluoro-2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindole-1- Monobenzoic acid (compound 112);

3- {3- [1- (3,5-Dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylideneamino] -2-oxo-2,3 -Dihydrobenzooxazol-7-yl} benzoic acid (compound 113);

3- {3-[(2-hydroxy-5,3 ', 4'-trimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid (Compound 114);

3-hydroxy benzoic acid N '-{1- [1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] ethyl} high Drazide (Compound 115);

1- (3,5-dimethylphenyl) -3- {1- [2- (4-hydroxyphenyl) -2-oxo-ethylamino] ethylidene} -6-trifluoromethyl-1,3-di Hydroindol-2-ones (compound 116);

3- {3-[(5-fluoro-2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-6-trifluoromethyl-2,3 -Dihydroindol-1-yl} benzoic acid (compound 117);

3- {3-[(2-hydroxy-3 ', 4'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-6-trifluoromethyl-2,3-dihydroindole- 1-yl} benzoic acid (Compound 118);

3- {3-[(2-hydroxy-3 ', 4'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid (compound 119);

3- {3-[(2-hydroxy-3 ', 4'-dimethylbiphenyl-3-ylamino) methylidene] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid (compound 120);

4- {3-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-ylamino) methylidene] -2-oxo-2,3-dihydroindol-1-yl} butyric acid (compound 121);

2-chloro-3- (4-{[1- (335-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindol-3-ylidenemethyl] amino} -3- Hydroxyphenyl) acrylic acid (compound 122);

4-hydroxybenzoic acid N '-{1- [1- (3,5-dimethylphenyl) -2-oxo-6-trifluoro methyl-1,2-dihydroindole-3-ylidene] ethyl} high Drazide (Compound 123);

3- {3-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -5-nitro-2-oxo-2,3-dihydroindol-1-yl } Benzoic acid (compound 124);

3- {3-[(2-Hydroxy-3,5'-dimethylbiphenyl-3-ylamino) methylidene] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid (Compound 125 );

3- {3-[(2-hydroxy-5,3 ', 5'-trimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid (Compound 126);

4-Aminobenzoic acid N '-{l- [1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] ethyl} hydra Zide (compound 127);

3- (7- {N '-[1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino}- 1H-indol-3-yl) propionic acid (compound 128);

4- {3- [N '-(4-methylbenzoyl) hydrazinomethylidene] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid (Compound 129);

3- {2-oxo-6-trifluoromethyl-3- [4- (3-trifluoromethylphenyl) -1 H-pyrrol-2-ylmethylidene] -2,3-dihydroindol-1-yl } Benzoic acid (compound 130);

3- (7- {N '-[1- (3,4-dimethylphenyl) -3-methyl-5-oxo-1,5-dihydropyrazole-4-ylidene] hydrazino} -lH- Indol-3-yl) propionic acid (compound 131);

3- (3-{[4- (3,4-dimethylphenyl) thiazol-2-ylamino] methylidene} -2-oxo-6-trifluoromethyl-2,3-dihydroindole-1- Yl) benzoic acid (compound 132);

3- (3-{[4- (4-methoxyphenyl) thiazol-2-ylamino] methylene} -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl) Benzoic acid (compound 133);

3- {3-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-ylamino) methylene] -2-oxo-6-trifluoromethyl-2,3-dihydroindole-1 -Yl} benzoic acid (compound 134);

3- {3-[(4- (4-methylphenyl) -2-thiazolylamino) methylene] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic acid (compound 135);

3- {3-[(3,4-Dimethylbenzoylhydrazino) methylidene] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic acid (Compound 136);

3- {3-[(4-chlorobenzoylhydrazino) methylidene] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic acid (Compound 137);

3- {3-[(4-methoxybenzoylhydrazino) methylidene] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic acid (Compound 138);

3- {3-[(3,4-dimethylbenzoylhydrazino) methylidene] -2-oxo-6-chloro-2,3-dihydroindol-1-yl} benzoic acid (Compound 139);

1- (3,4-dimethylphenyl) -3- [1- (2,4-dihydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 140);

1- (3,4-dimethylphenyl) -3- [1- (4-hydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 141);

1- (3,4-dimethylphenyl) -3-[(2,4-dihydroxybenzoylhydrazino) methylidene] -2-oxo-2,3-dihydroindole (Compound 142);

1- (3,5-dimethylphenyl) -3- [1- (2,4-dihydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 143);

1- (3,5-dimethylphenyl) -3- [1- (4-hydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 144);

1- (3,5-dimethylphenyl) -3-[(2,4-dihydroxybenzoylhydrazino) methylidene] -2-oxo-2,3-dihydroindole (Compound 145);

1- (3,5-dimethylphenyl) -3-[(4-hydroxybenzoylhydrazino) methylidene] -2-oxo-2,3-dihydroindole (Compound 146);

3- (3- [1- (3,4-Dihydroxybenzoylhydrazino) ethylidene] -2-oxo-6-chloro-2,3-dihydroindol-1-yl) benzoic acid (Compound 147) ;

1- (3,4-dimethylphenyl) -3-[(4-hydroxybenzoylhydrazino) methylidene] -2-oxo-2,3-dihydro indole (Compound 148);

1- (3,4-dimethylphenyl) -3-[(3,5-diisopropyl-2-hydroxybenzoylhydrazino) methylidene] -2-oxo-2,3-dihydroindole (Compound 149 );

1- (3,5-dimethylphenyl) -3- [1- (3,4-dihydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 150);

1- (3,4-dimethylphenyl) -3- [1- (3,4-dihydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 151);

3- (6-chloro-3-[(2-hydroxy-3,5-diisopropylbenzoylhydrazino) methylidene] -2-oxo-2,3-dihydroindol-1-yl) benzoic acid ( Compound 152);

1- (3,4-dimethylphenyl) -3- [1- (2,5-dihydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 153);

1- (3,4-dimethylphenyl) -3- [1- (3-nitro-4-hydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 154);

1- (3,4-dimethylphenyl) -3- [1- (3-aminosulfonyl-4-chlorobenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydro indole (Compound 155) ;

1- (3,4-dimethylphenyl) -3- [1- (3-amino-4-hydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 156);

1- (3,4-dimethylphenyl) -3- [1- (4-methoxy-2-hydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 157) ;

3- {3- (1- (3,5-Dimethylphenyl) -2-oxo-2,3-dihydro-3-indoledene) methylamino-2-hydroxyphenyl} benzoic acid (Compound 158);

3- {3- (3- (3,5-Dimethylphenyl) -2-hydroxyphenyl) aminomethylidene) -2-oxo-2,3-dihydro-1-indolyl} benzoic acid (Compound 159);

3- {3- (1- (3,4-Dimethylphenyl) -2-oxo-dihydro-3-indoledene) methylamino-2-hydroxyphenyl} benzoic acid (Compound 160);

4- {1- (6-Fluoro-2-oxo-2,3-dihydro-3- (2- (3,5-dimethylphenyl) -aminocarbonylphenyl) aminomethylidene) indolyl} butanoic acid (Compound 161);

4- {1- (6-Chloro-2-oxo-2,3-dihydro-3- (2-hydroxy-3- (3,5-dimethylphenyl) -phenyl) aminomethylidene) indolyl} moiety Carbonic acid (compound 162);

3- {1- (6-Chloro-2-oxo-2,3-dihydro-3- (2-hydroxy-3- (3,5-dimethylphenyl) -phenyl) aminomethylidene) indolyl} benzoic acid (Compound 163);

4- {1- (5-Fluoro-2-oxo-2,3-dihydro-3- (2-hydroxy-3- (3,5-dimethylphenyl) -phenyl) aminomethylidene) indolyl} Butanoic acid (compound 164);

3- {3- (1- (1- (3,5-Dimethylphenyl) -6-trifluoromethyl-2-oxo-2,3-dihydro-3-indolidene) ethylamino) -2-hydro Oxyphenyl} benzoic acid (compound 165);

3- {3- (1- (1- (3,4-Dimethylphenyl) -6-trifluoromethyl-2-oxo-2,3-dihydro-3-indoledene) ethylamino) -2-hydro Oxyphenyl} benzoic acid (compound 166);

3- {1- (6-Trifluoromethyl-2-oxo-2,3-dihydro-3- (5-chloro-2-hydroxy-3-cyclohexylphenyl) hydrazono) indolyl} benzoic acid (Compound 167);

3- {1- (5-fluoro-2-oxo-2,3-dihydro-3- (1- (5-chloro-2-hydroxy-3-cyclohexylphenyl) amino) ethylidene) indolyl } Benzoic acid (compound 168);

3- {1- (5-Fluoro-2-oxo-2,3-dihydro-3- (5-chloro-2-hydroxy-3-cyclohexylphenyl) aminomethylidene) indolyl} benzoic acid (compound 169);

4- {2-hydroxy-3- (6-trifluoromethyl-2-oxo-233-dihydro-1- (3,5-dimethylphenyl) indolylidene) methylaminophenyl} butanoic acid (Compound 170 );

4- {2-hydroxy-3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) indolylidene) methylaminophenyl} butanoic acid ( Compound 171);

3- {3- (7- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) -3-indolylidene) methylamino) indolyl} Propanoic acid (compound 172);

3- {3- (7- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) -3-indolylidene) methylamino) indolyl} Propanoic acid (compound 173);

4- {2-hydroxy-3- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolylidene) methylaminophenyl} butanoic acid (Compound 174);

2-Chloro-3- {3-hydroxy-4- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolylidene) methylaminophenyl} propenoic acid (Compound 175) ;

2-chloro-3- {3-hydroxy-4- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) indolylidene) methylaminophenyl } Propenic acid (Compound 176);

2-ethyl-3- {3-hydroxy-4- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) indolylidene) methylaminophenyl } Propenic acid (Compound 177);

2-ethyl-3- {3-hydroxy-4- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolylidene) methylaminophenyl } Propenoic acid (compound 178);

2-Ethyl-3- {3-hydroxy-4- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolylidene) methylaminophenyl} propenic acid (Compound 179) ;

4- {2-hydroxy-3- (4- (2- (3,4-dimethylphenyl) -3-oxo-3,4-dihydro-5-methyl) pyrazolidene) methylaminophenyl} butanoic acid (Compound 180);

(Z) -4- {1- (2,5-dioxo-3- (3- (3,5-dimethylphenyl) -2-hydroxyphenylaminomethylidene) pyrrolidinyl} butanoic acid (Compound 181) ;

(E) -4- {1- (2,5-dioxo-3- (3- (3,5-dimethylphenyl) -2-hydroxyphenylaminomethylidene) pyrrolidinyl} butanoic acid (Compound 182) ;

(Z) -3- {1- (2,5-dioxo-3- (3- (3,5-dimethylphenyl) -2-hydroxyphenylaminomethylidene) pyrrolidinyl} benzoic acid (Compound 183);

(E) -3- {1- (2,5-dioxo-3- (3- (3,5-dimethylphenyl) -2-hydroxyphenylaminomethylidene) pyrrolidinyl} benzoic acid (Compound 184);

4- {3- (4-oxo-2-thioxo-5- (3- (3,5-dimethylphenyl) -2-hydroxyphenylhydrozono) thiazolidinyl} butanoic acid (Compound 185);

3- {2- (3- (1- (3,5-Dimethylphenyl) -6-chloro-2-oxo-2,3-dihydroindoledene) methylamino) phenylamino} benzoic acid (Compound 186);

3- {2- (3- (1- (3,5-Dimethylphenyl) -6-trifluoromethyl-2-oxo-2,3-dihydroindoledene) methylamino) phenylamino} benzoic acid (compound 187);

3- {2- (4- (2- (3,5-Dimethylphenyl) -5-methyl-3-oxo-3,4-dihydropyrazolidene) methylamino) phenylamino} benzoic acid (Compound 188);

(±) -3-methyl-5- {2-hydroxy-3- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) Indolylidene) methylamino) phenyl} pentanoic acid (Compound 189);

(±) -3- {1- (6-chloro-2-oxo-2,3-dihydro-3- (3- (1- (3,5-dimethylphenyl) -2-oxo-2,3- Dihydro) indolyl) aminomethylidene) indolyl} benzoic acid (compound 190);

3- {4- (3-hydroxy-6-methyl-2- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indole Ryl) hydrazono) pyridinyl} benzoic acid (compound 191);

3- {4- (3-hydroxy-6-methyl-2- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indole Lidene) methylamino) pyridinyl} benzoic acid (compound 192);

3- {4- (3-hydroxy-2- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylamino ) Pyridinyl} benzoic acid (compound 193);

3- {4- (3-hydroxy-2- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolyl) hydrazo No) pyridinyl} benzoic acid (Compound 194);

3- {5- (4-hydroxy-3- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylamino ) Pyridinyl} benzoic acid (compound 195);

3- {5- (4-hydroxy-3- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolyl) hydrazo No) pyridinyl} benzoic acid (compound 196);

3- {5- (4-hydroxy-3- (4- (3-oxo-3,4-dihydro-5-methyl-2- (3,4-dimethylphenyl) pyrazolyl) hydrazono) pyrid Dinyl} benzoic acid (compound 197);

4- {2- (3-Oxo-3,4-dihydro-5-methyl-4- (3- (3,4-dimethylphenyl) phenyl) hydrozono) pyrazolyl} butanoic acid (Compound 198);

3- {2-amino-5-methyl-3- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolylidene) methyl Amino) phenyl} benzoic acid (compound 199);

3- {1- (5-Fluoro-2-oxo-2,3-dihydro-3- (3- (3,4-dimethylphenyl) phenyl) aminomethylidene) indolyl} benzoic acid (Compound 200);

4- {2- (5-methyl-2-oxo-2,3-dihydro-4- (3- (3,4-dimethylphenyl) phenyl) aminomethylidene) pyrazolyl} butanoic acid (Compound 201);

(3- (5-fluoro-2-hydroxy-3- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) indolene ) Methylamino) -1-pyrazolyl) acetic acid (compound 202);

(3- (5-fluoro-2-hydroxy-3- (3- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indoledene) methylamino) -1- Pyrazolyl) acetic acid (compound 203);

4- {2- (5-Methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-phenyl) ethyl) phenyl) aminomethylidene) pyrazolyl} butanoic acid ( Compound 204);

4- {2- (5-Methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-phenyl) ethyl) phenyl) hydrazono) pyrazolyl} butanoic acid ( Compound 205);

4- {2- (5-methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (4-methyl) phenyl) ethyl) phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 206);

4- {2- (5-methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3-methyl) phenyl) ethyl) phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 207);

4- {2- (5-methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methyl) phenyl) ethyl) phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 208);

4- {2- (5-methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (1-naphthyl) ethyl) phenyl) hydrazono) pyrazolyl } Butanoic acid (compound 209);

3- {1- (5-Nitro-2-oxo-2,3-dihydro-3- (2-hydroxy-3- (3,5-dimethylphenyl) phenyl) aminomethylidene) indolyl} benzoic acid ( Compound 210);

3- {1- (5-Nitro-2-oxo-2,3-dihydro-3- (5-fluoro-2-hydroxy-3- (3,5-dimethylphenyl) phenyl) aminomethylidene) Indolyl} benzoic acid (compound 211);

2-hydroxy-3- {3- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolene) methylamino} benzoic acid (Compound 212);

2-hydroxy-3- {3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolene) methylamino} benzoic acid (Compound 213) ;

4- {2- (5-methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3- (3-methyl-1-butenyl) phenyl) aminomethylidene) pyrazolyl} Butanoic acid (compound 214);

4- {2- (5-Methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3-heptanylphenyl) hydrazono) pyrazolyl} butanoic acid (Compound 215);

4- {2- (5-methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3- (2- (4-methyl) phenyl) ethenylphenyl) hydrazono) pyra Jolyl} butanoic acid (compound 216);

4- {2-5-methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3- (2- (3-methyl) phenyl) ethenylphenyl) hydrazono) pyrazolyl } Butanoic acid (compound 217);

4- {1- (2-Oxo-2,3-dihydro-3- (2-hydroxy-3- (2- (2-methyl) phenyl) ethylphenyl) hydrazono) indolyl} butanoic acid ( Compound 218);

2- {1- (2-Oxo-2,3-dihydro-3- (2-hydroxy-3- (3,5-dimethylphenyl) phenyl) hydrazono) indolyl} acetic acid (Compound 219);

2- {1- (2-Oxo-2,3-dihydro-3- (2-hydroxy-3- (2- (2-methyl) phenyl) ethylphenyl) hydrazono) indolyl} acetic acid (compound 220);

4- {4- (2- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) indolylidene) methylamino) thiazolyl} Benzoic acid (compound 221);

3- {1- (5-Nitro-2-oxo-2,3-dihydro-3- (2-hydroxy-5-methyl-3- (1-adamantane) phenyl) aminomethylidene) indolyl } Benzoic acid (compound 222);

3- {1- (6-Trifluoromethyl-2-oxo-2,3-dihydro-3 ~ (4-hydroxy-5- (3,4-dimethylphenyl) pyridinyl) hydrazono) indole Ryl} benzoic acid (Compound 223);

4- {2- (5-Methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3- (2- (2-methyl) phenyl) -ethylphenyl) aminomethylidene) pyra Jolyl} butanoic acid (compound 224);

4- (2- (5-Methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3- (2- (2-fluoro) phenyl) -ethylphenyl) aminomethylidene) Pyrazolyl} butanoic acid (compound 225);

4- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (1-naphthyl) -ethyl) phenyl) aminomethyl Lidene) pyrazolyl} butanoic acid (Compound 226);

4- (2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (3,5-dimethylphenyl) -ethyl) phenyl) Aminomethylidene) pyrazolyl} butanoic acid (Compound 227);

4- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-methoxyphenyl) -ethyl) phenyl) amino Methylidene) pyrazolyl} butanoic acid (Compound 228);

4- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-fluoro-3-methyl-phenyl) ethyl ) Phenyl) aminomethylidene) pyrazolyl} butanoic acid (Compound 229);

4- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-fluoro-3-methyl-phenyl) ethyl ) Phenyl) aminomethylidene) pyrazolyl} butanoic acid (compound 230);

4- (2- (5-Methyl-3-oxo-3.4-dihydro-4 (Z)-(2-hydroxy-3- (2- (4-phenylphenyl) -ethyl) phenyl) aminomethylidene) Pyrazolyl} butanoic acid (Compound 231);

4- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-cyanophenyl) -ethyl) phenyl) amino Methylidene) pyrazolyl} butanoic acid (Compound 232);

4- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-chlorophenyl) -ethyl) phenyl) aminomethyl Lidene) pyrazolyl} butanoic acid (Compound 233);

4- (2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2,6-dimethylphenyl) -ethyl) phenyl) Aminomethylidene) pyrazolyl} butanoic acid (Compound 234);

3- {2- (5-Trifluoromethyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-trifluoromethylphenyl) ethyl) Phenyl) aminomethylidene) pyrazolyl} benzoic acid (Compound 235);

3- {2- (5-Trifluoromethyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-fluorophenyl) -ethyl) Phenyl) aminomethylidene) pyrazolyl} benzoic acid (Compound 236);

3- {2- (5-trifluoromethyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-methyl-phenyl) ethyl) phenyl ) Aminomethylidene) pyrazolyl} benzoic acid (compound 237);

3- {2- (5-Trifluoromethyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2,5-dimethyl-phenyl) ethyl ) Phenyl) aminomethylidene) pyrazolyl} benzoic acid (compound 238);

3- {2- (5-Trifluoromethyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2,6-dimethyl-phenyl) ethyl ) Phenyl) aminomethylidene) pyrazolyl} benzoic acid (Compound 239);

3- {2- (5-phenyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2,5-dimethylphenyl) -ethyl) phenyl) Aminomethylidene) pyrazolyl} benzoic acid (compound 240);

3- {2- (5-tert-butyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2,5-dimethylphenyl) -ethyl ) Phenyl) aminomethylidene) pyrazolyl} benzoic acid (compound 241);

3- {2- (5-methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-methylphenyl) -ethyl) phenyl) aminomethylidene ) Pyrazolyl} benzoic acid (compound 242);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-fluorophenyl) -ethyl) phenyl) hydro Lazono) pyrazolyl} butanoic acid (Compound 243);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dimethylphenyl) -ethyl) phenyl) hydrazono ) Pyrazolyl} butanoic acid (Compound 244);

4- {2- (5-Methyl-3-oxo-2.3-dihydro-4- (2-hydroxy-3- (2- (4-phenylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl} Butanoic acid (compound 245);

4- (2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methoxyphenyl) -ethyl) phenyl) hydrazono) Pyrazolyl} butanoic acid (Compound 246);

4- {2- (5-Methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluoro-3-methylphenyl) -ethyl) phenyl) hydro Lazono) pyrazolyl} butanoic acid (Compound 247);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-trifluoromethylphenyl) -ethyl) phenyl) hydrazono ) Pyrazolyl} butanoic acid (compound 248);

4- (2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-cyanophenyl) ethyl) -phenyl) hydrazono) Pyrazolyl} butanoic acid (compound 249);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-chlorophenyl) ethyl) -phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 250);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dimethylphenyl) -ethyl) phenyl) hydrazono ) Pyrazolyl} butanoic acid (Compound 251);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-ethylphenyl) -ethyl) phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 252);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dichlorophenyl) -ethyl) phenyl) hydrazono ) Pyrazolyl} butanoic acid (Compound 253);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,5-dimethylphenyl) -ethyl) phenyl) hydrazono ) Pyrazolyl} butanoic acid (compound 254);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluoro-6-trifluoro-methylphenyl) ethyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 255);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indanyl) phenyl) -hydrazono) pyrazolyl} butanoic acid ( Compound 256);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indenyl) phenyl) -hydrazono) pyrazolyl} butanoic acid ( Compound 257);

(±) -4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (1-indanylmethyl) phenyl) -hydrazono) pyra Jolyl} butanoic acid (compound 258);

(±) -3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (1-indanylmethyl) phenyl) -hydrazono) pyra Jolyl} benzoic acid (compound 259);

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methylphenyl) ethyl) -phenyl) hydrazono) pyrazolyl } Benzoic acid (compound 260);

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluoro-3-methylphenyl) -ethyl) phenyl) hydro Lazono) pyrazolyl} benzoic acid (compound 261);

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluorophenyl) -ethyl) phenyl) hydrazono) Pyrazolyl} benzoic acid (compound 262);

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dimethylphenyl) -ethyl) phenyl) hydrazono ) Pyrazolyl} benzoic acid (compound 263);

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dichlorophenyl) -ethyl) phenyl) hydrazono ) Pyrazolyl} benzoic acid (compound 264);

3- (2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methyl-6-trifluoromethylphenyl) ethyl) phenyl) Hydrazono) pyrazolyl} benzoic acid (compound 265);

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indanyl) phenyl) -hydrazono) pyrazolyl} benzoic acid (compound 266);

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indenyl) phenyl) -hydrazono) pyrazolyl} benzoic acid (compound 267);

(E) -4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,4-difluorophenyl)-) Tenyl) phenyl) aminomethylidene) pyrazolyl} butanoic acid (Compound 268);

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-4- (3,4-dimethylphenyl) -2-pyridyl) hydrazono) pyra Jolyl} benzoic acid (compound 269);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-6-methyl-4- (3,4-dimethylphenyl) -2-pyridyl) hydro Lazono) pyrazolyl} butanoic acid (Compound 270);

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-2- (3,4-dimethylphenyl)-4-pyridyl) hydrazono) pyra Jolyl} benzoic acid (compound 271);

3- (2- (5-methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-2- (3,5-dimethylphenyl)-4-pyridyl) hydrazono) pyra Jolyl} benzoic acid (compound 272);

3- {1- (6-Trifluoromethyl-2-oxo-2,3-dihydro-3- (2-hydroxy-3- (2- (2-methylphenyl) -ethyl) phenyl) hydrazono ) Indolyl} benzoic acid (Compound 273);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3-benzylphenyl) hydrazono) -pyrazolyl} butanoic acid (Compound 274);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3- (3-methylphenyl) propyl) -phenyl) hydrazono) pyrazolyl } Butanoic acid (compound 275);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3-phenylpropyl) -phenyl) hydrazono) pyrazolyl} butanoic acid ( Compound 276);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3- (2-methylphenyl) propyl) -phenyl) hydrazono) pyrazolyl } Butanoic acid (compound 277);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,4-difluorophenyl) -ethyl) phenyl) hydro Lazono) pyrazolyl} butanoic acid (Compound 278);

(E) -4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-pyridyl) ethyl) -phenyl) hydro Lazono) pyrazolyl} butanoic acid (Compound 279);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z)-(2-hydroxy-3- (2- (2,6-dimethylphenyl)-(Z)- Ethenyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 280);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-benzofuranyl) phenyl) -hydrazono) pyrazolyl} butanoic acid (Compound 281);

(Z) -4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-bromoethenyl) phenyl) -hydrazono) pyra Jolyl} butanoic acid (compound 282);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z)-(2-hydroxy-3- (3-methyl-1-butenyl) phenyl) -hydrazono ) Pyrazolyl} butanoic acid (compound 283);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z)-(2-hydroxy-3- (2-cyclopropylethenyl) -phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 284);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3-methylbutyl) phenyl) -hydrazono) pyrazolyl} butanoic acid ( Compound 285);

4- (2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-5-fluoro-3- (3,5-dimethylphenyl) phenyl) hydrazono) Pyrazolyl} butanoic acid (compound 286);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3,4-dimethylphenyl) phenyl) -hydrazono) pyrazolyl} part Carbonic acid (compound 287);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (5-chloro-2-hydroxy-3-cyclohexylphenyl) -hydrazono) pyrazolyl} butanoic acid ( Compound 288);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3,5-dimethylphenyl) phenyl) -hydrazono) pyrazolyl} part Carbonic acid (compound 289);

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3,5-dimethylphenyl) phenyl) -hydrazono) pyrazolyl} benzoic acid (Compound 290);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (5-chloro-2-hydroxy-3-cyclohexylphenyl) -hydrazono) pyrazolyl} butanoic acid ( Compound 291);

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3,4-dimethylphenyl) phenyl) -hydrazono) pyrazolyl} benzoic acid (Compound 292);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3- (2-methylphenyl) propyl) -phenyl) hydrazono) pyrazolyl } Butanoic acid (compound 293);

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-benzofuranyl) phenyl) -hydrazono) pyrazolyl} benzoic acid ( Compound 294);

4- (2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3- (2-fluorophenyl) propyl) -phenyl) hydrazono) Pyrazolyl} butanoic acid (compound 295);

3- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (3,4-dimethylphenyl) -phenyl) aminomethylidene) pyra Jolyl} benzoic acid (compound 296);

3- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (3,5-dimethylphenyl) -phenyl) aminomethylidene) pyra Jolyl} benzoic acid (compound 297);

4- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (3,4-dimethylphenyl) -phenyl) aminomethylidene) pyra Jolyl} butanoic acid (compound 298);

3- {1- (2-Oxo-2,3-dihydro-3- (2-hydroxy-3- (3,5-dimethylphenyl) -phenyl) hydrazono) indolyl} propionic acid (Compound 299) ;

3- {1- (2-Oxo-2,3-dihydro-3- (2-hydroxy-3-benzylphenyl) hydrazono) -indolyl} benzoic acid (Compound 300);

3- {1- (2-Oxo-2,3-dihydro-3- (2-hydroxy-3- (2- (2-methylphenyl) ethyl) phenyl) -hydrazono) indolyl} propionic acid (compound 301);

3- {1- (6-Chloro-2-oxo-2,3-dihydro-3 (Z)-(2-hydroxy-3- (3- (3-methylphenyl) propyl) -phenyl) aminomethylidene ) Indolyl} benzoic acid (compound 302);

(±) -3- {1- (6-chloro-2-oxo-2,3-dihydro-3 (Z)-(2-hydroxy-3- (1,2-dihydro-1-methyl- 2-indolylphenyl) aminomethylidene) indolyl} benzoic acid (Compound 303);

4- {2- (5-Methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3- (2-methylphenylcarbonyl-amino) phenyl) hydrazono) pyrazolyl} part Carbonic acid (compound 304);

4- (2- (5-methyl-3-oxo-3,4-dihydro-4- (5-chloro-2-hydroxy-3- (2-methylphenyl-carbonylamino) phenyl) hydrazono) Pyrazolyl} butanoic acid (Compound 305);

3- {2-Hydroxy-3- (2-oxo-2,3-dihydro-l- (2- (2-fluorophenyl) ethyl) indolylidene) -hydrazinophenyl} benzoic acid (Compound 306 );

3- {2-Hydroxy-3- (2-oxo-2,3-dihydro-l- (2- (2-chlorophenyl) ethyl) indolylidene) -hydrazinophenyl} benzoic acid (Compound 307) ;

3- {3-hydroxy-2- (5-methyl-3-oxo-2,3-dihydro-2- (3,4-dimethylphenyl) -pyrazolylidene) hydrazino-4-pyridyl} Benzoic acid (compound 308);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl } Benzoic acid (compound 309);

3- {3-Hydroxy-2- (2-oxo-2,3-dihydro-l- (3,5-dimethylphenyl) -3-indolylidene-hydrazino) -4-pyridyl} benzoic acid (Compound 310);

3- {1- (2-Oxo-2,3-dihydro-3- (3-hydroxy-6-methyl-4- (3,4-dimethylphenyl)-2-pyridyl) hydrazono) indole Ryl} benzoic acid (compound 311);

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-6-methyl-4- (3,4-dimethylphenyl) -2-pyridyl) hydro Lazono) pyrazolyl} benzoic acid (Compound 312);

3- {3-hydroxy-4- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) -6-trifluoromethyl-3-indolylidenehydrazino)- 2-pyridyl} benzoic acid (compound 313);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-2- (3,5-dimethylphenyl)-4-pyridyl) hydrazono) pyra Jolyl} butanoic acid (compound 314);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-5-phenyl-2-benzothienyl) -hydrazono) pyrazolyl} butanoic acid ( Compound 315);

3- {3-hydroxy-2- (5-methyl-3-oxo-2,3-dihydro-2- (3,4-dimethylphenyl) -4-pyrazolidene) hydrazino-5-benzo Thienyl} benzoic acid (compound 316);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (3- (2,3-dimethoxycarbonylphenyl) phenyl) -hydrazono) pyrazolyl} butanoic acid ( Compound 317);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z)-(2-hydroxy-3,5-diisopropylphenyl) carbonylhydrazinomethylidene) pyra Jolyl} butanoic acid (compound 318);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z)-(2-hydroxy-3- (3,5-dimethylphenyl) phenyl) -aminomethylidene) pyra Jolyl} butanoic acid (Compound 319);

(±) -4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2,3-dihydro-1-methyl-2-oxo -3-indolyl) methyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 320);

3- {1- (2-Oxo-2,3-dihydro-5-fluoro-3- (2-hydroxy-3- (2- (2-methylphenyl) ethyl) phenyl) -hydrazono) indole Ryl} propionic acid (compound 321);

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,5-dimethylphenyl) -ethyl) phenyl) hydrazono ) Pyrazolyl} benzoic acid (compound 322);

(±) -3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2,3-dihydro-1-methyl-2-oxo -3-indolyl) methyl) phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 323);

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (1,2-dihydro-1-methyl-2-oxo-3-indole) Lilydene) methyl) phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 324);

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (5-fluoro-2-methylphenyl) -ethyl) phenyl) hydro Lazono) pyrazolyl} benzoic acid (compound 325);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4 (E)-(2-hydroxy-3- (2- (2,4-difluorophenyl) -ethenyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 326);

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3-methylphenyl) hydrazono) -pyrazolyl} benzoic acid (Compound 327);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (1,2-dihydro-1-methyl-2-oxo-3-indole Lilydene) methyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 328);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (5-fluoro-2-methylphenyl) -ethyl) phenyl) hydro Lazono) pyrazolyl} butanoic acid (Compound 329);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-difluorophenyl) -ethyl) phenyl) hydro Razono) pyrazolyl} butanoic acid (Compound 330);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,6-dimethylphenyl) -ethenyl) phenyl ) Hydrazono) pyrazolyl} butanoic acid (Compound 331);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-methylphenyl) -ethenyl) phenyl) hydrazo No) pyrazolyl} butanoic acid (Compound 332);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (5-fluoro-2-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 333);

4- (2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (Z)-(2- (5-fluoro-2-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 334);

4- (2- (5-methyl-3-oxo-2;) 3-dihydro-4- (2-hydroxy-3 (E)-(2- (3-fluorophenyl) ethenyl) phenyl) Hydrazono) pyrazolyl} butanoic acid (Compound 335);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (4-fluorophenyl) ethenyl) phenyl) hydro Razono) pyrazolyl} butanoic acid (Compound 336);

4- (2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-fluorophenyl) -ethenyl) phenyl) Hydrazono) pyrazolyl} butanoic acid (compound 337);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2-phenylethenyl) -phenyl) hydrazono) pyrazolyl } Butanoic acid (compound 338);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-phenylethynyl) -phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 339);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methylphenyl) ethynyl) -phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 340);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dimethylphenyl) -ethynyl) phenyl) hydrazo No) pyrazolyl} butanoic acid (Compound 341);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluorophenyl) ethynyl) -phenyl) hydrazono ) Pyrazolyl} butanoic acid (Compound 342);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-trifluorophenyl) -ethynyl) phenyl) hydrazo No) pyrazolyl} butanoic acid (Compound 343);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-trifluoromethyl-phenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 344);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (1-methyl-1-indenyl-2-) phenyl) -hydrazono ) Pyrazolyl} butanoic acid (Compound 345);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3,3-dimethyl-2-indenyl) phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 346);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-5-methoxy-3- (2-indenyl) -phenyl) hydrazono) pyra Jolyl} butanoic acid (Compound 347);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (4,7-dimethyl-2-indenyl) phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 348);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (4,7-difluoro-2-indenyl) phenyl) hydrazono ) Pyrazolyl} butanoic acid (compound 349);

3- {2-hydroxy-3- (2-oxo-2,3-dihydro-6-trifluoromethyl-1- (2- (2-methylphenyl) -ethyl) -3 (Z) -indolene ) Methylaminophenyl} benzoic acid (compound 350);

3- {2-hydroxy-3- (2-oxo-2,3-dihydro-6-trifluoromethyl-1- (2-indenyl) -3 (Z) -indolylidene) methylaminophenyl } Benzoic acid (compound 351);

(±) 4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (1,2,3,4-tetrahydro)- Naphthyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 352);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro) -naphthyl) phenyl) hydrazo No) pyrazolyl} butanoic acid (Compound 353);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(1-indanylidene) -methylphenyl) hydrazono) pyrazolyl } Butanoic acid (compound 354);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (5-fluoro-2-trifluoromethylphenyl) Ethenyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 355);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (6-fluoro-2-trifluoro-methylphenyl ) Ethenyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 356);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (6-fluoro-2-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 357);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (4-fluoro-2-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 358);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (3-fluoro-2-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 359);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,6-difluorophenyl) -ethenyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (compound 360);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,5-difluorophenyl) -ethenyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (compound 361);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (4-fluoro-2-trifluoro-methylphenyl ) Ethenyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 362);

4- (2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,4-difluorophenyl) -ethynyl) phenyl) Hydrazono) pyrazolyl} butanoic acid (compound 363);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(1- (1,2,3,4-tetrahydro)- Naphthylidene) methylphenyl) hydrazono) pyrazolyl} butanoic acid (Compound 364);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-fluoro-5-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (compound 365);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (3,5-dimethyl-4-isoxazolyl) Ethenyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 366);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,5-dimethyl-4-isoxazolyl) ethyl) phenyl ) Hydrazono) pyrazolyl} butanoic acid (compound 367);

3- {2-hydroxy-3- (2-oxo-2,3-dihydro-1- (2 (E)-(2-methylphenyl) ethenyl) -3 (Z) -indolylidene) methylamino Phenyl) benzoic acid (compound 368);

3- {2-hydroxy-3- (2-oxo-2,3-dihydro-1- (2 (E)-(2,4-difluorophenyl) ethenyl) -3 (Z) -indole Lilydene) methylaminophenyl} benzoic acid (compound 369);

3- {2-Hydroxy-3- (2-oxo-2,3-dihydro-l- (2-indenyl) -3 (Z) -indolylidene) methyl-aminophenyl} benzoic acid (Compound 370) ;

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (5-fluoro-2-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} benzoic acid (compound 371);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3-methylphenyl) hydrazono) -pyrazolyl} butanoic acid (Compound 372);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indanylidenemethyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 373);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indanylmethyl) phenyl) hydrazono) pyrazolyl} butanoic acid ( Compound 374);

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,4-difluorophenyl) -ethenyl ) Phenyl) hydrazono) pyrazolyl} benzoic acid (compound 375);

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,6-difluorophenyl) -ethenyl ) Phenyl) hydrazono) pyrazolyl} benzoic acid (compound 376);

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (4-fluoro-2-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} benzoic acid (compound 377);

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-fluoro-6-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 378);

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,3-difluorophenyl) -ethenyl ) Phenyl) hydrazono) pyrazolyl} benzoic acid (compound 379);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,3-difluorophenyl) -ethenyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 380);

4- (2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-fluoro-4-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 381);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-chlorophenyl) -ethenyl) phenyl) hydr Lazono) pyrazolyl} butanoic acid (Compound 382);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,6-dichlorophenyl) -ethenyl) phenyl ) Hydrazono) pyrazolyl} butanoic acid (compound 383);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (3-chlorophenyl) -ethenyl) phenyl) hydr Lazono) pyrazolyl} butanoic acid (Compound 384);

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,5-difluorophenyl) -ethenyl ) Phenyl) hydrazono) pyrazolyl} benzoic acid (compound 385);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-chloro-4-fluorophenyl) ethenyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 386);

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-trifluoromethyl-4-fluorophenyl ) Ethenyl) phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 387);

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,4-dichloro) -ethenyl) phenyl) Hydrazono) pyrazolyl} butanoic acid (compound 388);

In 3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-chloromethyl-4-fluorophenyl) Tenyl) phenyl) hydrazono) pyrazolyl} benzoic acid (compound 389);

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,4-dichloromethylphenyl) ethenyl) phenyl) Hydrazono) pyrazolyl} benzoic acid (compound 390);

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro) -naphthyl) phenyl) hydrazo No) pyrazolyl} benzoic acid (Compound 391);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-8-fluoro) -naphthyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 392);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-8-methyl) -naphthyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 393);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-7-methyl) -naphthyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 394);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-7-fluoro) -naphthyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 395);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-6-fluoro) -naphthyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 396);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-5-fluoro) -naphthyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 397);

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-8-chloro) -naphthyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 398);

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-7-fluoro) -naphthyl ) Phenyl) hydrazono) pyrazolyl} provides a compound selected from the group consisting of benzoic acid (compound 399) or a pharmaceutically acceptable salt, ester, amide or prodrug thereof. In certain embodiments, the compound is a selective TPO modulator.

Certain compounds of the present invention may exist as stereoisomers, including optical isomers. Each enantiomer, all stereoisomers, racemics of such stereoisomers may be isolated herein by methods known to those skilled in the art or may be excluded by synthetic methods known to those skilled in the art to obtain superior yield over other enantiomers. Sieve mixtures.

Specific synthesis methods

In certain embodiments, certain compounds of the invention can be synthesized according to the following schemes.

The process of Scheme 1 is a multi-step synthetic sequence, starting with the cross-coupling of a phenylboronic acid, such as formula 2, with a palladium catalyst of aryl bromide, such as formula 1. After deprotection of the methyl ether, nitrification and hydrogenation yield a biphenyl amino group such as structure 4. The amino group was then diazotized under standard conditions and treated with a suitable coupling partner to yield the final product, Structural Formula 6. "R" may be 0, 1, 2 or 3, and each R is independently selected from the group in the "optionally substituted" definition described above.

The process of Scheme II is a multi-step synthetic sequence starting with a copper catalyzed cross-coupling reaction of oxindole, such as formula 7, to provide the N-substituted oxindole of formula 8. Next, the N-substituted oxindole is coupled with the diazonium salt of the biphenyl amino acid as in formula 4 to obtain the final product, formula 9. "R" may be 0, 1, 2 or 3, and each R is independently selected from the group in the "optionally substituted" definition described above.

The process of Scheme III is a multi-step synthetic sequence beginning with the copper-catalyzed cross-coupling of an oxindole, such as formula 7, with aryl or alkyl bromide, to produce the N-substituted oxindole of formula 8. The compound is then converted to the compound of formula 10 by reaction with dimethylformamide dimethylacetal (or equivalent) or triethylautoformate. Next, the resulting compound is reacted with an amine to produce the compound of formula 11. "R" may be 0, 1, 2 or 3, and each R is independently selected from the group in the "optionally substituted" definition described above.

The process of Scheme IV is a single synthetic step wherein the arylated oxindole of Scheme 8 from Scheme I is combined with a suitably substituted pyrrocarboxaldehyde of Scheme 12 under a base to produce a compound of Scheme 13. "R" may be 0, 1, 2 or 3, and each R is independently selected from the group in the "optionally substituted" definition described above.

The process of Scheme V is a single synthetic step in which the reaction product of Formula 14 or a specific synthetic equivalent is reacted with phosgene to produce the compound of Formula 15. "R" may be 0, 1, 2 or 3, and each R is independently selected from the group in the "optionally substituted" definition described above.

The process of Scheme VI is a multi-step synthetic sequence beginning with the production of benzothiophene from the aryl thioether of formula 16. The resulting compound is then converted to the compound of formula 19 by reaction with a diazonium salt of formula 18.

The process of Scheme VII is a multi-step synthetic sequence beginning with the Witig olefination reaction of benzaldehyde such as Formula 20 with phosphonium bromide such as Formula 21 to produce the olefin of Formula 22. Reduction of nitro groups (and / or olefins) affords phenyl amines of the formula 23. The amino group is then diazotized under standard conditions and treated with a suitable coupling partner to yield a final product of 24. "R" is selected from the group in the "optionally substituted" definition above.

The process of Scheme VIII is a multi-step synthetic sequence beginning with the enamine or enol ether formation reaction of the N-substituted oxindole or analog thereof of formula 25. Next, the resulting compound is converted to formula 27 through reaction with an amine partner. "R" may be 0, 1, 2 or 3, and each R is independently selected from the group in the "optionally substituted" definition described above.

The general process of Scheme IX begins with the diazotization of the amine compound of formula 28 under standard conditions and the coupling reaction with the compound of formula 25 to yield the hydrazone compound of formula 29. "R" may be 0, 1, 2 or 3, and each R is independently selected from the group in the "optionally substituted" definition described above.

Those skilled in the art will appreciate that analogous synthetic schemes can be used to synthesize similar compounds. Those skilled in the art will recognize that the compounds according to the invention can be synthesized using other synthetic schemes. In certain embodiments, the present invention provides salts corresponding to the compounds provided herein.

In certain embodiments, the present invention provides salts corresponding to selective TPO modulators. In certain embodiments, the invention provides salts corresponding to selective TPO receptor binders. In certain embodiments, the salt is obtained by reacting the compound with an acid such as hydrochloric acid, bromic acid, sulfuric acid, nitric acid, phosphoric acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like. In certain embodiments, the salt reacts the compound with a base, such as an ammonium salt, an alkali metal salt such as sodium or potassium salt, an alkaline earth metal salt such as calcium or magnesium salt, choline, dicyclohexylamine, N-methyl-D-glucamine, Organic base salts such as tris (hydroxymethyl) methylamine, 4- (2-hydroxyethyl) -morpholine, 1- (2-hydroxyethyl) -pyrrolidine, ethanolamine and amino acids such as arginine, lysine and the like Obtained by producing a salt of a fruit. In certain embodiments, the salt is obtained by reacting the free acid form of the selective TPO modulator or selective TPO binder with multiple molar equivalents of bases such as bis-sodium, bis-ethanolamine and the like.

In certain embodiments, the salts corresponding to the compounds of the present invention are acetate, ammonium, benzenesulfonate, benzoate, bicarbonate, bisulfate, bitatrate, borate, bromide, calcium edetate, chamlate, carbonate, chloride, collie Nate, Clavulanate, Citrate, Dihydrochloride, Diphosphate, Edetate, Edicillate, Estoleate, Ecylate, Fumarate, Gluceptate, Gluconate, Glutamate, Glycol arsanylate, Hexylene Socinate, Hydrabanin, Hydrobromide, Hydrochloride, Hydroxynaphthoate, Iodide, Isetionate, Lactate, Lactobionate, Laurate, Magnesium, Maleate, Maleate, Mandelate, Mucate , Naphsylate, nitrate, N-methylglucamine, oxalate, pamoate (M ), Palmitate, pantothenate, phosphate, polygalacturonate, potassium, salicylate, sodium, stearate, subacetate, succinate, sulfate, tannate, tartrate, theolate, tosylate, Triethiodide, tromethamine, trimethylammonium and valerate salts.

In certain embodiments, one or more carbon atoms of the compound of the present invention is replaced with silicon. See, eg, WO 03/037905 Al; Tacke and Zilch, Endeavor, New Series, 10, 191-197 (1986); Bains and Tacke, Curr. Opin. Drug Discov Devel. Jul: 6 (4): 526-43 (2003), incorporated herein by reference in its entirety. In certain embodiments, a compound of the present invention comprising at least one silicon atom may have the desired properties, including but not limited to, for example, greater safety and / or a patient, as compared to the same compound where the carbon atom is not replaced with a silicon atom. Has a longer half-life in.

Specific inspection

In certain embodiments, the test can be used to determine the TPO modulating activity level of a compound of the invention. For example, the efficacy of the compounds of the invention as selective TPO modulators is described by Lamb, et al., Nucleic Acids Research, 23: 3283-3289 (1995) and / or Seidel et al., Proc. Nat. Acad. Sci. USA; 92: 3041- 3045 (1995), which can be determined via a luciferase test, as described in the entirety herein.

See also, Bartley et al., Cell, 77: 1117-1124 (1994) and / or Cwirla, et al., Science, 276: 1696-1699 (1997), incorporated herein by reference in its entirety. As described herein, in vitro proliferation and / or differentiation assays may also be used.

Certain pharmaceutical preparations

In certain embodiments, one or more selective TPO modulators or pharmaceutically acceptable salts, esters, amides and / or prodrugs thereof are combined alone or in combination with one or more pharmaceutically acceptable carriers to obtain a pharmaceutical formulation. Techniques for formulating and administering compounds of the invention can be found, for example, in "Remington's Pharmaceutical Sciences," Mack Publishing Co., Easton, PA, 18th edition, 1990, which is incorporated herein by reference in its entirety. have.

In certain embodiments, pharmaceutical formulations comprising one or more compounds of the invention are known techniques, including but not limited to, for example, mixing, dissolving, granulating, dragging-making, levigating , Emulsification, encapsulation, entrapping or tableting processes.

In certain embodiments, pharmaceutical formulations comprising one or more compounds of the invention are liquids (eg, suspensions, elixirs and / or solutions). In this particular embodiment, liquid pharmaceutical formulations comprising one or more compounds of the present invention include ingredients known to those skilled in the art, including but not limited to, water, glycols, oils, alcohols, flavoring agents, preservatives and coloring agents. Are prepared using.

In certain embodiments, pharmaceutical formulations comprising one or more compounds of the invention are solids (eg, powders, tablets and / or capsules). In this particular embodiment, solid pharmaceutical formulations comprising one or more compounds of the invention are ingredients known to those skilled in the art, including but not limited to, for example, starch, sugars, diluents, granulating agents, lubricants, binders and bores. It is prepared using the release.

In certain embodiments, pharmaceutical formulations comprising one or more compounds of the present invention are formulated in depot form. Such depot preparations are generally more functional than the non-depot preparations. In certain embodiments, the agent is administered by implantation (eg, subcutaneously or intramuscularly) or by intramuscular infusion. In certain embodiments, depot preparations are prepared using suitable polymers or hydrophobic materials (such as emulsions in suitable oils) or ion exchange resins or poorly soluble derivatives such as poorly soluble salts.

In certain embodiments, pharmaceutical formulations comprising one or more compounds of the invention comprise a delivery system. Examples of delivery systems include, but are not limited to, liposomes and emulsions. Certain delivery systems are useful for preparing certain pharmaceutical formulations, including formulations that include hydrophobic compounds. In certain embodiments, certain organic solvents are used, such as dimethylsulfoxide.

In certain embodiments, pharmaceutical formulations comprising one or more compounds of the invention comprise one or more tissue-specific delivery molecules designed to deliver a pharmaceutical formulation to a particular tissue or cell type. For example, in certain embodiments, the pharmaceutical formulation comprises liposomes coated with tissue-specific antibodies.

In certain embodiments, pharmaceutical formulations comprising one or more compounds of the invention comprise a co-solvent system. Specific examples of such co-solvent systems include benzyl alcohol, nonpolar surfactants, water miscible organic polymers, and water phases. In certain embodiments, such co-solvent systems are used for hydrophobic compounds. Non-limiting examples of such co-solvent systems are VPD, an anhydrous ethanol solution comprising 3% w / v benzyl alcohol, 8% w / v nonpolar surfactant polysorbate 80 ^™ and 65% w / v polyethylene glycol 300 Co-solvent system. The proportion of co-solvent systems can vary considerably without significantly modifying solubility and toxicity properties. Moreover, the type of co-solvent component may vary. For example, other surfactants may be used in place of polysorbate 80, fraction sizes of polyethylene glycol may vary, other biocompatible polymers such as polyvinyl pyrrolidone may replace polyethylene glycol, Other sugars or polysaccharides can replace dextrose.

In certain embodiments, pharmaceutical formulations comprising one or more compounds of the invention comprise a sustained release system. Non-limiting examples of sustained-release systems are semipermeable matrices of solid hydrophobic polymers. In certain embodiments, the sustained release system may release the compound for hours, days, weeks, or months, depending on its chemical nature.

Certain compounds used in the pharmaceutical formulations of the present invention may be provided as pharmaceutically acceptable salts with pharmaceutically suitable counterions. Pharmaceutically acceptable salts can be produced with a number of acids, including but not limited to hydrochloric acid, sulfuric acid, acetic acid, lactic acid, tartaric acid, malic acid, succinic acid and the like.

In certain embodiments, pharmaceutical formulations comprising one or more compounds of the present invention comprise a therapeutically effective amount of the active ingredient. In certain embodiments, the therapeutically effective amount is an amount sufficient to prevent, alleviate or ameliorate the symptoms or prolong the life of the disease in the subject to be treated. A therapeutically effective amount can be readily determined by one skilled in the art.

In certain embodiments, pharmaceutical formulations comprising one or more compounds of the invention are formulated as prodrugs. In certain embodiments, prodrugs are useful because they are easier to administer than the corresponding active form. For example, in certain cases, the prodrug is more bioavailable (eg, via oral administration) than the corresponding active form. In certain cases, prodrugs may improve solubility compared to corresponding active forms. In certain embodiments, the prodrug is an ester. In certain embodiments, the prodrugs have lower water solubility compared to the corresponding active form. In certain cases, the prodrugs have good permeability across cell membranes that are soluble in migration. In certain embodiments, the ester in the prodrug is metabolically hydrolyzed to a carboxylic acid. In certain cases, the carboxylic acid containing the compound is the corresponding active form. In certain embodiments, the prodrug comprises a short peptide (polyamino acid) linked to an acid group. In certain embodiments, the peptide is metabolized to produce the corresponding active form.

In certain embodiments, pharmaceutical formulations comprising one or more compounds of the invention are useful for treating a condition or disorder in a mammal, particularly a human patient. Suitable routes of administration include, but are not limited to, oral, rectal, transmucosal, intestinal, enteral, topical, suppository, inhalation, intramedullary, intraventricular, intraperitoneal, intranasal, intraocular and parenteral (e.g., veins, muscles, Bone marrow and subcutaneous). In certain embodiments, pharmaceutical intramedullary administration is for topical rather than systemic exposure. For example, pharmaceutical preparations may be injected directly into the desired effect site (eg kidney or heart site).

In certain embodiments, pharmaceutical formulations comprising one or more compounds of the invention are administered in dosage unit form (eg, tablets, capsules, bolus, etc.). In certain embodiments, the dosage unit comprises a selective TPO modulator at a dose of about 1 μg / kg to about 50 mg / kg of body weight. In certain embodiments, the dosage unit comprises a selective TPO modulator at a dose of about 2 μg / kg to about 25 mg / kg of body weight. In certain embodiments, the dosage unit comprises a selective TPO modulator at a dose of about 10 μg / kg to about 5 mg / kg of body weight. In certain embodiments, the pharmaceutical formulation is administered as needed, once daily, twice daily, three times daily or four or five times daily. Those skilled in the art understand that the dosage, frequency and duration of administration may vary depending on many factors, including but not limited to, the desired biological properties, the patient's condition, resistance to pharmaceutical agents.

In certain embodiments, pharmaceutical formulations comprising a compound of the present invention are prepared for oral administration. In this particular embodiment, the pharmaceutical formulation is formulated by combining one or more compounds of the present invention with one or more pharmaceutically acceptable carriers. Certain carriers are formulated for oral ingestion of the compounds of the present invention in tablets, pills, dragees, capsules, solutions, gels, syrups, slurries, suspensions and the like. In certain embodiments, oral pharmaceutical formulations are obtained by mixing one or more compounds of the invention with one or more solid excipients. Suitable excipients include, but are not limited to, fillers such as sugar, lactose, sucrose, mannitol or sorbitol; For example corn starch, wheat starch, rice starch, potato starch, gelatin, tragacanthum gum, methyl cellulose, hydroxypropylmethyl-cellulose, sodium carboxymethylcellulose and / or polyvinylpyrrolidone (PVP) Cellulose preparations such as; In certain embodiments, the mixture is optionally milled and an adjuvant is optionally added. In certain embodiments, the pharmaceutical formulation is obtained to form a tablet or dragee nucleus. In certain embodiments, disintegrants (eg, cross-linked polyvinyl pyrrolidone, agar or salts thereof such as alginic acid or sodium alginate) are added.

In certain embodiments, the dragee nucleus is provided coated. In this particular embodiment, concentrated sugar solutions can be used, the sugar solutions comprising gum arabic, talc, polyvinyl pyrrolidone, carbopol gel, polyethylene glycol and / or titanium dioxide, lacquer solutions and suitable organic solvents or solvent mixtures. May be optionally contained. Dyes or pigments may be added to the tablets or dragee coatings.

In certain embodiments, the pharmaceutical formulation for oral administration is a one-touch-fit capsule made of gelatin. Certain one-touch-fitting capsules include one or more compounds of the present invention, mixed with one or more fillers such as lactose, binders such as starch and / or lubricants such as talc or magnesium stearate and optionally stabilizers. In certain embodiments, the pharmaceutical formulation for oral administration is a soft, sealed capsule of gelatin and a plasticizer such as glycerol or sorbitol. In certain soft capsules, one or more compounds of the invention are dissolved or suspended in a suitable solution such as fatty, oil, liquid paraffin or liquid polyethylene glycol. In addition, stabilizers may be added.

In certain embodiments, the pharmaceutical formulation is prepared for oral administration. Certain pharmaceutical preparations are tablets or lozenges formulated in conventional manner.

In certain embodiments, the pharmaceutical formulation is prepared for infusion administration (eg, intravenous, subcutaneous, intramuscular, etc.). In certain embodiments, the pharmaceutical formulation comprises a carrier and is formulated with an aqueous solution, such as water or a physiologically acceptable Hanks's solution, Ringer's solution or physiological saline buffer. In certain embodiments, other ingredients are included, such as those that enhance solubility or are used as preservatives. In certain embodiments, suspensions for infusion are prepared using suitable liquid carriers, suspending agents and the like. Certain injectable pharmaceutical formulations are prepared in unit dose form (eg, ampoules or multi-dose containers). Certain injectable pharmaceutical formulations are suspensions, solvents or emulsions in oils or aqueous vehicles, and may include formulation agents such as suspending agents, stabilizers and / or dispersing agents. Specific solvents suitable for injectable pharmaceutical formulations include, but are not limited to, lipophilic solvents and fatty oils such as sesame oil, synthetic fatty acid esters such as ethyl oleate or triglycerides, and liposomes. Aqueous injection suspensions may contain components which increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol or dextran. Optionally, the suspension may also include suitable stabilizers or suitable agents which increase the solubility of the compound to allow for the preparation of highly concentrated solutions.

In certain embodiments, the pharmaceutical formulation is prepared for transmucosal administration. In certain embodiments, penetrants suitable for the barrier to be permeated are used in the formulation. Such penetrants are generally known to those skilled in the art.

 In certain embodiments, the pharmaceutical formulation is prepared for inhaled administration. Certain inhaled pharmaceutical formulations are prepared in the form of pressurized packs or aerosol sprays in nebulizers. Certain pharmaceutical preparations include propellants such as dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. In certain embodiments using pressurized aerosols, the dosage unit can be determined by a valve delivering a metered amount. In certain embodiments, capsules and cartridges used in an inhaler or insufflator may be formulated. Particular formulations include powder mixtures of the compounds of the invention with a suitable powder base such as lactose or starch.

In certain embodiments, the pharmaceutical formulation is prepared for rectal administration such as suppositories or retention enema. Certain pharmaceutical preparations include known ingredients such as cocoa butter and / or other glycerides.

In certain embodiments, the pharmaceutical formulation is prepared for topical administration. Certain pharmaceutical formulations include mixed wetting bases such as ointments or creams. Examples of suitable ointment bases include, but are not limited to, water-in-oil emulsions such as petroleum, petroleum and volatile silicones, lanolin and Eucerin ^™ (Beiersdorf, Cincinnati, Ohio). Examples of suitable cream bases include, but are not limited to, Nivea ^TM (Beiersdorf, Cincinnati, Ohio), Cold Cream (USP), Purpose Cream ^TM (Johnson & Co.) Johnson, New Brunswick, NJ), hydrophilic ointment (USP) and Lubriderm ^™ (manufactured by Pfizer, Morris Plains, NJ).

In certain embodiments, the formulation, route of administration, and dose of the pharmaceutical formulation of the present invention may be selected in consideration of the condition of the particular patient. See, eg, Fingl et at 1975, in "The Pharmacological Basis of Therapeutics", Ch. 1 p. 1, the entirety of which is incorporated herein by reference. In certain embodiments, the pharmaceutical formulation is administered in a single dose. In certain embodiments, the pharmaceutical formulations may be administered in two or more dose series administered for one or more days. In certain embodiments, the pharmaceutical formulation of the invention comprises about 0.1% to 500%, 5% to 200%, 10% to 100%, 15% to 85% and 25% to 75%, or 40 of a given human dose. Is administered to the patient in% to 60%. In the absence of a dose for a given person, the dose for a suitable person can be estimated from ED ₅₀ or ID ₅₀ values or other suitable values obtained from other in vitro or in vivo tests.

In certain embodiments, the daily dosage regimen for a patient comprises an oral dose of 0.1 mg to 2000 mg, 5 mg to 1500 mg, 10 mg to 1000 mg, 20 mg to 500 mg, 30 mg to 200 mg, or 40 mg to 100 mg of the compound of the invention. In certain embodiments, the daily dose regimen is administered in a single daily dose. In certain embodiments, the daily dose regimen is administered in two, three or four doses or more.

In certain embodiments, the pharmaceutical formulations of the invention are administered by continuous intravenous infusion. In certain embodiments, the compositions of the present invention is administered from 0.1 mg to 500 mg daily.

In certain embodiments, the pharmaceutical formulations of the invention are administered for a continuous treatment period. For example, the pharmaceutical formulations of the present invention can be administered for days, weeks, months or years.

Dosage, interval of administration, and duration of treatment can be adjusted to achieve the desired effect. In certain embodiments, the dosage and interval of administration can be adjusted to maintain the desired concentration of the compound in the patient. For example, in certain embodiments, the dosage and interval of administration are adjusted to provide a plasma concentration of the compound of the invention in an amount sufficient to achieve the desired effect. In certain embodiments, the plasma concentration is maintained above the minimum effective concentration (MEC). In certain embodiments, the pharmaceutical formulations of the present invention are administered in a dosage regimen designed for concentrations above MEC, for a time of 10 to 90%, for a time of 30 to 90% or for a time of 50 to 90%.

In certain embodiments, the pharmaceutical formulation is administered topically and the dosage regimen is adjusted to obtain the desired topical concentration of the compound of the invention.

In certain embodiments, the pharmaceutical formulation may be present in a pack or dispenser device which may comprise one or more unit dosage forms comprising the active ingredient. The pack may comprise metal or plastic foil, for example a blister pack. The pack or dispenser device may be accompanied by instructions for administration. In addition, the pack or dispenser may involve a label attached to a container in the form of a governmental regulation that regulates the manufacture, use, or sale of the drug, which label may be used for human or animal administration. The form is approved by the ministry. Such labels may be approved and labeled by the US FDA, for example, for prescription drugs or approved product inserts. Compositions comprising a compound of the present invention formulated in a suitable pharmaceutical carrier may also be prepared, placed in a suitable container, and labeled for indications.

In certain embodiments, the pharmaceutical formulation is in powder form for treatment to be used in a suitable vehicle, eg, sterile pyrogen-free water.

Specific combination therapies

In certain embodiments, one or more pharmaceutical agents of the present invention are co-administered with one or more other pharmaceutical agents. In certain embodiments, the one or more other pharmaceutical agents are designed to treat the same disease or condition as the one or more pharmaceutical agents of the present invention. In certain embodiments, the one or more other pharmaceutical agents are designed to treat a disease or condition different from one or more pharmaceutical agents of the invention. In certain embodiments, the one or more other pharmaceutical agents are designed to treat the side effects of one or more pharmaceutical agents of the invention. In certain embodiments, one or more pharmaceutical agents of the present invention are co-administered with another pharmaceutical agent to treat side effects of the other pharmaceutical agent. In certain embodiments, one or more pharmaceutical agents of the present invention and one or more other pharmaceutical agents are administered simultaneously. In certain embodiments, one or more pharmaceutical agents of the present invention and one or more other pharmaceutical agents are administered at different times. In certain embodiments, one or more pharmaceutical formulations of the invention and one or more other pharmaceutical formulations are prepared together in a single dosage form. In certain embodiments, one or more pharmaceutical formulations of the invention and one or more other pharmaceutical formulations are prepared separately.

Examples of pharmaceutical agents that may be co-administered with the pharmaceutical agents of the present invention include, but are not limited to, anticancer agents including chemotherapy and radiation therapy; Corticosteroids including, but not limited to, predriesone; Immunoglobulins, including but not limited to venous immunoglobulins (IVIg); Analgesics such as acetaminophen; Anti-inflammatory agents including, but not limited to, nonsteroidal anti-inflammatory agents such as ibuprofen, COX-1 inhibitors and COX-2 inhibitors; Salicylates; Antibiotic; Antiviral agents; Antifungal agents; Antidiabetic agents such as biguanides, glucosidase inhibitors, insulin, sulfonylureas and thiazolidendiones; Adrenaline modifiers; diuretic; Hormonal agents such as anabolic steroids, androgens, estrogens, calcitonin, progestins, somatostanes, and thyroid hormones; Immunomodulators; Muscle relaxant; Antihistamines; Osteoporosis agents such as biphosphonates, calcitonin and estrogens; Prostaglandins, antitumor agents; Antipsychotics; sedative; Poison oak or poison sumac products; Antibodies; And vaccines.

Specific indications

In certain embodiments, the present invention provides a method of treatment comprising administering one or more compounds of the present invention to a patient. In certain embodiments, the patient is a thrombocytopenia patient. In certain embodiments, thrombocytopenia is caused by chemotherapy and / or radiation therapy treatment. In certain embodiments, thrombocytopenia is due to bone marrow failure caused by bone marrow transplantation and / or aplastic anemia. In certain embodiments, thrombocytopenia is idiopathic. In certain embodiments, one or more compounds of the present invention are administered to a patient who collects and / or collects peripheral blood progenitor cells and undergoes platelet counting. The administration can be carried out before, during and / or after the blood collection.

In certain embodiments, one or more compounds of the invention are administered to a neurological condition, including but not limited to, for example, neurological disease and neurological damage patients. The disease includes, but is not limited to, amyotrophic lateral sclerosis, multiple sclerosis and multiple dystrophy. Nervous system damage includes, but is not limited to, spinal cord injury or peripheral nerve damage, including but not limited to injury after trauma or stroke. In certain embodiments, one or more compounds of the invention are used to promote growth and / or development of glial cells. In certain embodiments, compounds of the invention are used to treat psychiatric disorders including, but not limited to, cognitive disorders.

The following examples, including the experiments and results obtained, are provided for illustration of the invention and not for the purpose of limiting the invention. When the formula represents an atom with unfilled valence, it is understood that the valence is filled with one or more hydrogen atoms.

Example 1

3 '-{[1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3 (Z) -ylidenemethyl] amino} -2'- Hydroxybiphenyl-3-carboxylic Acid (Compound 101)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 13.05 (s, 1H), 11.35 (d, J = 13.3 Hz, 1H), 9.40 (s, 1H), 8.12 (t, J = 1.6 Hz, 1H), 7.97 (d, J = 7.9 Hz, 1H), 7.95 (ddd, J = 7.7, 1.6, 1.3 Hz, 1H), 7.81-7.78 (m, 2H), 7.60 (t, J = 7.7 Hz, 1H), 7.44 (dq, J = 7.9, 0.9 Hz, 1H), 7.14 (t, J = 7.8 Hz, 1H), 7.12 (s, 1H), 7.11 (m, 2H), 7.07 (dd, J = 7.8, 1.5 Hz, 1H), 6.94 (q, J = 0.9 Hz, 1H), 2.36 (s, 6H).

Example 2

2,4-dihydroxybenzoic acid N '-{l- [1- (3,5-dimethylphenyl) -2-oxo-6-trifluoro methyl-1,2-dihydroindole-3 (Z)- Ilidene] ethyl} hydrazide (Compound 102)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, CD ₃ OD) δ 8.49 (s, 1H), 7.71 (m, 1H), 7.67 (m, 1H), 7.34 (m, 1H), 7.16 (s, 1H), 7.04 (s , 2H), 6.93 (s, 1H), 6.39 (m, 1H), 6.34 (s, 1H), 2.64 (s, 3H), 2.41 (s, 6H).

Example 3

3- {3-[(5-chloro-2-hydroxy-3 ', 4'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl } Benzoic Acid (Compound 103)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO-d ₆ ) δ 13.29 (s, 1H), 12.95 (s, 1H), 9.36 (s, 1H), 8.08 (t, J = 1.7 Hz, 1H), 8.04 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.82 (m, 2H), 7.74 (t, J = 7.7 Hz, 1H), 7.65 (d, J = 2.6 Hz, 1H), 7.34 (m, 1H), 7.33 (td, J = 7.6, 1.3 Hz, 1H), 7.27 (dd, J = 8.0, 1.8 Hz, 1H), 7.23 (d, J = 8.0 Hz, 1H), 7.22 (td, J = 7.6, 0.9 Hz, 1H), 6.94 (dm, J = 7.6 Hz, 1H), 6.93 (d, J = 2.6 Hz, 1H), 2.28 (s, 3H), 2.27 (s, 3H).

Example 4

3- {3-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid (compound 104)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) 13.29 (s, 1H), 13.04 (s, 1H), 9.11 (s, 1H), 8.08 (t, J = J = 1.8 Hz, 1H), 8.04 (ddd, J = J = 7.7, 1.8, 1.2 Hz, 1H), 7.83 (ddd, J = 7.7, 1.8, 1.2 Hz, 1H), 7.75 (m, 1H), 7.74 (t, J = 7.7 Hz, 1H), 7.69 (dd, J = 7.7, 1.6 Hz, 1H), 7.31 (td, J = 7.6, 1.3 Hz, 1H), 7.22 (td, J = 7.6, 0.9 Hz, 1H), 7.15 (m, 2H), 7.06 ( t, J = 7.7 Hz, 1H), 7.00 (m, 1H), 6.95 (m, 1H), 6.94 (dd, J = 7.7, 1.6 Hz, 1H), 2.33 (s, 6H).

Example 5

3 '-{[1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3 (Z) -ylidenemethyl] amino} -4-fluoro Rho-2'-hydroxybiphenyl-3-carboxylic acid (Compound 105)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.35 (s, 1H), 11.34 (d, J = 13.3 Hz, 1H), 9.41 (s, 1H), 9.08 (d, J = 13.3 Hz, 1H) , 8.01 (dd, J = 7.2, 2.3 Hz, 1H), 7.96 (d, J = 7.9 Hz, 1H), 7.79 (dd, J = 7.9, 1.5 Hz, 1H), 7.78 (ddd, J = 8.4, 4.4 , 2.3 Hz, 1H), 7.44 (dq, J = 7.9, 0.9 Hz, 1H), 7.42 (dd, J = 10.6, 8.4 Hz, 1H), 7.13 (t, J = 7.9 Hz, 1H), 7.12 (m , 1H), 7.10 (m, 2H), 7.06 (dd, J = 7.9, 1.5 Hz, 1H), 6.94 (m, 1H), 2.36 (s, 6H).

Example 6

2- (3 '-{[1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3 (Z) -ylidenemethyl] amino}- 2'-hydroxybiphenyl-3-yl) -2-methylpropionic acid (compound 106)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 12.39 (s, 1H), 11.36 (d, J = 13.3 Hz, 1H), 9.32 (s, 1H), 9.08 (d, J = 13.3 Hz, 1H) , 7.97 (d, J = 7.9 Hz, 1H), 7.76 (dd, J = 7.9, 1.5 Hz, 1H), 7.54 (m, 1H), 7.45-7.42 (m, 3H), 7.35 (m, 1H), 7.12 (t, J = 7.9 Hz, 1H), 7.12 (m, 1H), 7.11 (m, 2H), 7.02 (dd, J = 7.9, 1.5 Hz, 1H), 6.95 (q, J = 0.8 Hz, 1H ), 2.37 (s, 6H), 1.52 (s, 6H).

Example 7

3 '-{[1- (3,4-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3 (Z) -ylidenemethyl] amino} -2'- Hydroxybiphenyl-3-carboxylic Acid (Compound 107)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.03 (s, 1H), 11.31 (d, J = 13.7 Hz, 1H), 9.38 (s, 1H), 9.06 (d, J = 13.7 Hz, 1H) , 8.09 (t, J = 1.5 Hz, 1H), 7.91-7.95 (m, 2H), 7.77 (m, 2H), 7.58 (t, J = 7.3 Hz), 7.41 (dd, J = 7.8, 1.0 Hz, 1H), 7.34 (d, J = 7.8 Hz, 1H), 7.26 (d, J = 2.0 Hz, 1H), 7.19 (dd, J = 7.8, 2.0 Hz, 1H), 7.11 (t, J = 7.8 Hz, 1H), 7.04 (dd, J = 7.8, 1.5 Hz, 1H), 6.90 (d, J = 1.5 Hz, 1H), 2.29 (s, 3H), 2.28 (s, 3H).

Example 8

4- {3-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid (compound 108)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.18 (s, 1H), 13.05 (s, 1H), 9.13 (s, 1H), 8.14 (d, J = 8.5 Hz, 2H), 7.75 (m, 1H ), 7.70 (m, 2H), 7.69 (dd, J = 7.8, 1.6 Hz, 1H), 7.32 (td, J = 7.6, 1.2 Hz, 1H), 7.23 (td, J = 7.6, 0.7 Hz, 1H) , 7.15 (s, 2H), 7.06 (t, J = 7.8 Hz, 1H), 7.03 (m, 1H), 7.00 (s, 1H), 6.94 (dd, J = 7.8, 1.6 Hz, 1H), 2.33 ( s, 6H).

Example 9

3- {3-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-6-trifluoromethyl-2,3-dihydroindole- 1-yl} benzoic acid (Compound 109)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO-d ₆ ) δ 13.30 (s, 1H), 13.20 (s, 1H), 9.27 (s, 1H), 8.11 (t, J = 1.8 Hz, 1H), 8.07 (ddd, J = 7.8, 1.8, 1.2 Hz, 1H), 7.94 (d, J = 7.9 Hz, 1H), 7.86 (ddd, J = 7.8, 1.8, 1.2 Hz, 1H), 7.77 (t, J = 7.8 Hz, 1H) , 7.74 (dd, J = 7.8, 1.6 Hz, 1H), 7.56 (dq, J = 7.9, 0.7 Hz, 1H), 7.15 (m, 2H), 7.09 (t, J = 7.8 Hz, 1H), 7.08 ( m, 1H), 7.01 (m, 1H), 6.99 (dd, J = 7.8, 1.6 Hz, 1H), 2.33 (s, 6H).

Example 10

3- {3-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-6-trifluoromethyl-2,3-dihydroindole- 1-yl} benzoic acid methyl ester (Compound 110)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.20 (s, 1H), 9.27 (s, 1H), 8.15 (dd, J = 2.1, 1.6 Hz, 1H), 8.10 (ddd, J = 7.9, 1.6, 1.1 Hz, 1H), 7.94 (d, J = 7.9 Hz, 1H), 7.90 (ddd, J = 7.9, 2.1, 1.1 Hz, 1H), 7.80 (t, J = 7.9 Hz, 1H), 7.74 (dd, J = 7.9, 1.6 Hz, 1H), 7.57 (dq, J = 7.9, 0.8 Hz, 1H), 7.15 (m, 2H), 7.09 (t, J = 7.9 Hz, 1H), 7.08 (m, 1H), 7.01 (m, 1H), 7.00 (dd, J = 7.9, 1.6 Hz, 1H), 3.90 (s, 3H), 2.33 (s, 6H).

Example 11

3- {3-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid methyl ester (Compound 111)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO-d ₆ ) δ 13.04 (s, 1H), 9.11 (s, 1H), 8.12 (m, 1H), 8.06 (ddd, J = 7.8, 1.6, 1.2 Hz, 1H), 7.87 (ddd, J = 7.8, 2.2, 1.2 Hz, 1H), 7.77 (t, J = 7.8 Hz, 1H), 7.75 (m, 1H), 7.69 (dd, J = 7.8, 1.6 Hz, 1H), 7.31 ( td, J = 7.6, 1.2 Hz, 1H), 7.22 (td, J = 7.6, 0.9 Hz, 1H), 7.15 (m, 2H), 7.06 (t, J = 7.8 Hz, 1H), 7.00 (m, 1H ), 6.95 (m, 1H), 6.94 (dd, J = 7.8, 1.6 Hz, 1H), 3.90 (s, 3H), 2.33 (s, 6H).

Example 12

3- {3-[(5-fluoro-2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindole-1- Benzoic acid (compound 112)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.29 (s, 1H), 12.97 (s, 1H), 9.06 (s, 1H), 8.08 (m, 1H), 8.04 (ddd, J = 7.8, 2.2, 1.1 Hz, 1H), 7.83 (m, 1H), 7.81 (d, J = 7.6 Hz, 1H), 7.74 (t, J = 7.8 Hz, 1H), 7.45 (dd, J = 9.5, 3.0 Hz, 1H) , 7.33 (t, J = 7.6 Hz, 1H), 7.22 (t, J = 7.6 Hz, 1H), 7.19 (s, 2H), 7.02 (s, 1H), 6.94 (d, J = 1.6 Hz, 1H) , 6.75 (dd, J = 9.5, 3.0 Hz, 1H), 2.33 (s, 6H).

Example 13

3- {3- [1- (3,5-Dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylideneamino] -2-oxo-2,3 -Dihydrobenzooxazol-7-yl} benzoic acid (compound 113)

As described in Scheme V, 3 '-{N'-[1- (3,5) in dichloromethane (6 mL) and 1: 1 saturated aqueous sodium bicarbonate / 2.0M aqueous sodium hydroxide (6 mL). -Dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid ( 153 mg, 0.28 mmol, 1.0 equiv) was added to triphosgen (83 mg, 0.28 mmol, 3.0 equiv) at room temperature. The mixture was stirred for 4 hours and acidified with 6M HCl. The organic layer was removed and the aqueous layer was extracted twice with dichloromethane. The extracted organics were washed once with water and once with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (concentration gradient: 9: 1 hexanes / EtOAc to 3: 2 hexanes / EtOAc to 59.9: 40: 0.1 hexanes / EtOAc / HOAc) and triturated with methanol to give compound 113. Obtained. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.25 (s, 1H), 8.45 (dd, J = 2.0, 1.5 Hz, 1H), 8.09 (ddd, J = 7.8, 2.0, 1.0 Hz, 1H), 8.05 (ddd, J = 8.3, 1.5, 1.0 Hz, 1H), 7.86 (d, J = 8.1 Hz, 1H), 7.73 (dd, J = 7.8, 7.8 Hz, 1H), 7.64 (dd, J = 8.0, 1.2 Hz, 1H), 7.46 (m, 2H), 7.36 (dd, J = 7.8, 1.2 Hz, 1H), 7.21 (s, 3H), 6.86 (d, J = 1.6 Hz, 1H), 2.38 (s, 6H).

Example 14

3- {3-[(2-hydroxy-5,3 ', 4'-trimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid (Compound 114)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.28 (s, 1H), 13.03 (s, 1H), 8.81 (s, 1H), 8.08 (dd, J = 1.5, 1.0 Hz, 1H), 8.04 ( ddd, J = 7.8, 1.5, 1.5 Hz, 1H), 7.83 (ddd, J = 7.9, 2.2, 1.2 Hz, 1H), 7.75 (m, 2H), 7.51 (d, J = 2.1 Hz, 1H), 7.30 (m, 2H), 7.23 (m, 3H), 6.94 (d, J = 7.9 Hz, 1H), 6.76 (dd, J = 2.1, 0.7 Hz, 1H), 2.34 (s, 3H), 2.27 (s, 3H), 2.26 (s, 3H).

Example 15

3-hydroxybenzoic acid N '-{1- [1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3 (Z) -ylidene] Ethyl} hydrazide (compound 115)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 11.76 (s, 1H), 11.08 (s, 1H), 9.84 (s, 1H), 7.70 (d, J = 8.3 Hz, 1H), 7.35 (m, 4H), 7.13 (s, 1H), 7.07 (s, 2H), 7.02 (dt, J = 5.2, 3.7 Hz, 1H), 6.92 (d, J = 1.5 Hz, 1H), 2.58 (s, 3H), 2.36 (s, 6 H).

Example 16

1- (3,5-dimethylphenyl) -3 (Z)-{l- [2- (4-hydroxyphenyl) -2-oxo-ethylamino] ethylidene} -6-trifluoromethyl-l, 3-dihydroindol-2-one (compound 116)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, Methanol-d ₄ ) δ 8.54 (s, 1 H), 7.98 (d, J = 8.8 Hz, 2 H), 7.65 (d, J = 8.3 Hz, 1 H), 7.32 (d , J = 7.8 Hz, 1 H), 7.15 (s, 1 H), 7.03 (s, 2 H), 6.93 (s, 1 H), 6.90 (d, J = 8.3 Hz, 2 H), 5.14 (s , 2H), 2.67 (s, 3H), 2.41 (s, 6H).

Example 17

3- {3-[(5-fluoro-2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-6-trifluoromethyl-2,3 -Dihydroindol-1-yl} benzoic acid (compound 117)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.28 (s, 1H), 13.09 (s, 1H), 9.18 (s, 1H), 8.09 (d, J = 2 Hz, 1H), 8.07 (m, 1H), 8.0 (d, J = 7.8 Hz, 1H), 7.87 (m, 1H), 7.77 (t, J = 7.9 Hz, 1H), 7.58 (d, J = 7.8 Hz, 1H), 7.52 (dd, J = 9.4, 3.1 Hz, 1H), 7.19 (s, 2H), 7.07 (s, 1H), 7.03 (s, 1H), 6.82 (dd, J = 9.5 Hz, 1H), 2.33 (s, 6H).

Example 18

3- {3-[(2-hydroxy-3 ', 4'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-6-trifluoromethyl-2,3-dihydroindole- 1-yl} benzoic acid (Compound 118)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.28 (s, 1H), 13.18 (s, 1H), 9.23 (s, 1H), 8.11 (t, J = 1.7 Hz, 1H), 8.07 (dd, J = 7.6, 1.2 Hz, 1H), 7.94 (d, J = 7.8 Hz, IH), 7.85 (m, 1H), 7.78 (d, J = 8.1 Hz, 1H), 7.73 (m, 1H), 7.57 ( t, J = 8.8 Hz, 1H), 7.33 (s, 1H), 7.24 (dd, J = 13.9, 4.9 Hz, 2H), 7.09 (m, 1H), 6.99 (dd, J = 7.7, 1.6 Hz, 1H ), 2.26 (s, 3H), 2.25 (s, 3H).

Example 19

3- {3-[(2-hydroxy-3 ', 4'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid (compound 119)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.28 (s, 1H), 13.04 (s, 1H), 9.09 (s, 1H), 8.08 (m, 1H), 8.04 (dt, J = 7.8, 1.4 Hz, 1H), 7.83 (ddd, J = 8.0, 2.2, 1.2 Hz, 1H), 7.74 (t, J = 7.7 Hz, 2H), 7.68 (dd, J = 7.8, 1.5 Hz, 1H), 7.31 (m , 2H), 7.23 (m, 3H), 7.06 (t, J = 7.9 Hz, 1H), 6.94 (dt, J = 5.9, 3.9 Hz, 2H), 2.26 (s, 3H), 2.25 (s, 3H) .

Example 20

3- {3 (Z)-[(2-hydroxy-3 ', 4'-dimethylbiphenyl-3-ylamino) methylidene] -2-oxo-2,3-dihydroindol-1-yl} Benzoic Acid (Compound 120)

This compound was prepared as described in Scheme III. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.23 (s, 1H), 11.15 (d, J = 13.2 Hz, 1H), 9.08 (s, 1H), 8.88 (dd, J = 13.18 Hz, 1H) , 8.04 (m, 1H), 7.99 (m, 1H), 7.81 (m, 2H), 7.70 (m, 2H), 7.33 (s, 1H), 7.24 (m, 2H), 7.09 (m, 3H), 6.93 (m, 2 H), 2.27 (s, 3 H), 2.26 (s, 3 H).

Example 21

4- {3 (Z)-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} Butyric Acid (Compound 121)

This compound was prepared as described in Scheme III. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.02 (s, 1H), 12.14 (s, 1H), 9.06 (s, 1H), 7.63 (dd, J = 7.8, 1.5 Hz, 2H), 7.33 ( td, J = 7.7, 1.1 Hz, 1H), 7.21 (t, 1H), 7.13 (m, 3H), 7.03 (t, J = 7.8 Hz, 1H), 7.00 (s, 1H), 6.91 (m, 1H ), 3.85 (t, J = 6.8 Hz, 2H), 2.33 (m, 8H), 1.88 (t, J = 6.8 Hz, 2H).

Example 22

2-Chloro-3- (4-{[1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydrodroindole-3 (Z) -ylidenemethyl ] Amino} -3-hydroxyphenyl) acrylic acid (compound 122)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 11.20 (d, J = 14.2 Hz, 1 H), 10.6 (br s, 1 H), 9.06 (d, J = 12.7 Hz, 1 H), 7.94 ( d, J = 8.3 Hz, 1 H), 7.75 (d, J = 8.8 Hz, 1 H), 7.63 (s, 2 H), 7.43 (d, J = 8.8 Hz, 1 H), 7.45-7.29 (m , 1 H), 7.13 (s, 1 H), 7.11 (s, 2 H), 6.94 (s, 1 H), 2.37 (s, 6 H).

Example 23

4-hydroxybenzoic acid N '-{1- [1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3 (Z) -ylidene] Ethyl} hydrazide (compound 123)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 12.04 (s, 1H), 10.92 (s, 1H), 10.11 (s, 1H), 7.82 (dt, J = 6.0, 4.8 Hz, 2H), 7.66 (d , J = 8.2 Hz, 1H), 7.33 (d, J = 7.8 Hz, 1H), 7.12 (s, 1H), 7.06 (s, 2H), 6.91 (s, 1H), 6.85 (d, J = 8.3 Hz , 2H), 2.60 (s, 3H), 2.36 (s, 6H).

Example 24

3- {3-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -5-nitro-2-oxo-2,3-dihydroindol-1-yl } Benzoic Acid (Compound 124)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.29 (s, 1H), 13.11 (s, 1H), 9.29 (s, 1H), 8.52 (d, J = 2.4 Hz, 1H), 8.20 (dd, J = 8.8, 2.4 Hz, 1H), 8.10 (m, 2H), 7.84 (m, 2H), 7.78 (dd, J = 7.8, 7.8 Hz, 1H), 7.15 (d, J = 0.9 Hz, 2H), 7.10 (m, 2H), 7.01 (dd, J = 7.6, 1.6 Hz, 2H), 2.33 (s, 6H).

Example 25

3- {3 (Z)-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-ylamino) methylidene] -2-oxo-2,3-dihydroindol-1-yl} Benzoic Acid (Compound 125)

This compound was prepared as described in Scheme III. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.2 (s, 1H), 11.17 (d, J = 13.7 Hz, 1H), 9.11 (s, 1H), 8.89 (d, J = 13.2 Hz, 1H) , 8.04 (t, J = 1.8 Hz, 1H), 7.99 (m, 1H), 7.80 (m, 2H), 7.71 (m, 2H), 7.14 (m, 2H), 7.10 (m, 2H), 7.06 ( m, 1H), 7.00 (s, 1H), 6.94 (m, 2H), 2.32 (s, 6H).

Example 26

3- {3-[(2-hydroxy-5,3 ', 5'-trimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid (Compound 126)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, CD ₃ OD-d ₄ ) δ 8.10 (m, 2H), 7.75 (d, J = 6.8 Hz, 1H), 7.68 (m, 2H), 7.54 (d, J 2.0 Hz, 1H ), 7.26 (ddd, J = 7.8, 7.3, 1.0 Hz, 1H), 7.19 (dd, J = 7.3, 7.3 Hz, 1H), 7.10 (s, 2H), 6.99 (s, 1H), 6.93 (d, J = 7.8 Hz, 1H), 6.74 (d, J = 2.0 Hz, 1H), 2.36 (s, 3H), 2.35 (s, 6H).

Example 27

4-Aminobenzoic acid N '-{1- [1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3 (Z) -ylidene] ethyl } Hyrazide (Compound 127)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 11.83 (s, 1H), 10.71 (s, 1H), 7.67 (m, 3H), 7.35 (d, J = 7.8 Hz, 1H), 7.12 (s, 1H), 7.06 (s, 2H), 6.91 (s, 2H), 6.60 (d, J = 8.8 Hz, 2H), 5.84 (s, 2H), 2.57 (s, 3H), 2.36 (s, 6H).

Example 28

3- (7- {N '-[1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino}- l-indol-3-yl) propionic acid (compound 128)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.48 (s, 1H), 12.11 (s, 1H), 10.78 (s, 1H), 8.39 (d, J = 8.3 Hz, 1H), 7.56 (d, J = 8.1 Hz, 1H), 7.39 (d, J = 7.8 Hz, 1H), 7.27 (d, J = 2.7 Hz, 1H), 7.18 (s, 2H), 7.11 (m, 1H), 7.05 (t, J = 7.7 Hz, 1H), 7.00 (s, 1H), 2.98 (t, J = 7.32 Hz, 2H), 2.63 (t, J = 7.8 Hz, 2H), 2.37 (s, 6H).

Example 29

4- {3 (Z)-[N '-(4-Methylbenzoyl) hydrazinomethylidene] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid (Compound 129)

This compound was prepared as described in Scheme III. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.8 (s, 1 H), 8.17 (d, J = 8.3 Hz, 2 H), 7.82 (d, J = 7.8 Hz, 2 H), 7.78 (d , J = 7.8 Hz, 1 H), 7.70 (J = 8.3 Hz, 2 H), 7.46 (dd, J = 7.8, 7.8 Hz, 1 H), 7.43 (d, J = 8.3 Hz, 2 H), 7.28 (dd, J = 7.8, 7.8 Hz, 1 H), 7.00 (d, J = 7.8 Hz, 1 H), 2.40 (s, 3 H).

Example 30

3- {2-oxo-6-trifluoromethyl-3 (Z)-[4- (3-trifluoromethylphenyl) -lH-pyrrol-2-ylmethylidene] -2,3-dihydroindole- 1-yl} benzoic acid (Compound 130)

This compound was prepared as described in Scheme IV. ¹ H NMR (500 MHz, Acetone-d ₆ ) δ 13.70 (s, 1H), 8.27 (s, 1H), 8.2 (d, J = 7.8 Hz, 1H), 7.91 (m, 5H), 7.82 (m, 5H), 7.59 (s, 1H), 7.47 (d, J = 7.8 Hz, 1H), 7.13 (s, 1H), 6.74 (m, 1H).

Example 31

3- (7- {N '-[1- (3,4-dimethylphenyl) -3-methyl-5-oxo-1,5-dihydropyrazole-4-ylidene] hydrazino} -lH- Indol-3-yl) propionic acid (compound 131)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 12.10 (s, 1H), 10.62 (s, 1H), 7.75 (s, 1H), 7.67 (d, J = 8.1 Hz, 1H), 7.49 (d, J = 7.8 Hz, 1H), 7.27 (d, J = 6.8 Hz, 1H), 7.22 (d, J = 8.3 Hz, 1H), 7.09 (t, J = 7.8 Hz, 1H), 2.97 (t, J = 7.4 Hz, 1H), 2.62 (t, J = 7.8 Hz, 1H), 2.43 (s, 3H), 2.28 (s, 3H), 2.24 (s, 3H).

Example 32

3- (3 (Z)-{[4- (3,4-dimethylphenyl) thiazol-2-ylamino] methylidene} -2-oxo-6-trifluoromethyl-2,3-dihydroindole -1-yl) benzoic acid (compound 132)

This compound was prepared as described in Scheme III. ¹ H NMR (500 MHz, Acetone-d ₆ ) δ 8.98 (s, 1H), 8.24 (s, 1H), 8.16 (d, J = 7.8 Hz, 1H), 7.99 (d, J = 7.8 Hz, 1H) , 7.88 (d, J = 8.5 Hz, 1H), 7.79 (m, 2H), 7.74 (d, J = 7.8 Hz, 1H), 7.48 (s, IH), 7.47 (d, J = 9.0 Hz, 1H) , 7.21 (m, 2 H), 2.33 (s, 3 H), 2.29 (s, 3 H).

Example 33

3- (3 (Z)-{[4- (4-methoxyphenyl) thiazol-2-ylamino] methylene} -2-oxo-6-trifluoromethyl-2,3-dihydroindole-1 -Yl) benzoic acid (compound 133)

This compound was prepared as described in Scheme III. ¹ H NMR (500 MHz, Acetone-d ₆ ) δ 8.98 (s, 1H), 8.24 (s, 1H), 8.16 (dt, J = 7.8, 1.2 Hz, 1H), 8.00 (d, J = 8.1 Hz, 1H), 7.96 (d, J = 9.3 Hz, 2H), 7.88 (d, J = 7.8 Hz, 1H), 7.79 (t, J = 7.8 Hz, 1H), 7.46 (d, J = 7.3 Hz, 1H) , 7.41 (s, 1 H), 7.19 (s, 1 H), 7.01 (d, J = 8.8 Hz, 2H), 3.85 (s, 3H).

Example 34

3- {3 (Z)-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-ylamino) methylene] -2-oxo-6-trifluoromethyl-2,3-dihydro Indol-1-yl} benzoic acid (compound 134)

This compound was prepared as described in Scheme III. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 11.35 (d, J = 13.4 Hz, 1H), 9.24 (s, 1H), 9.10 (d, J = 13.2 Hz, 1H), 8.00 (m, 2H) , 7.99 (d, J = 8.3 Hz, 1H), 7.74 (m, 2H), 7.68 (t, J = 7.6 Hz, 1H), 7.46 (d, J = 7.3 Hz, 1H), 7.14 (s, 2H) , 7.08 (t, J = 7.9 Hz, 1H), 7.03 (s, 1H), 6.99 (m, 2H), 2.32 (s, 6H).

Example 35

3- {3 (Z)-[(4- (4-methylphenyl) -2-thiazolylamino) methylene] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} Benzoic Acid (Compound 135)

This compound was prepared as described in Scheme III. ¹ H NMR (500 MHz, DMSO-d ₆ ) 13.25 (s, 2H), 11.81 (d, J = 12.1, 1H), 11.41 (d, J = 13.0, 1H), 8.96 (d, J = 12.1, 1H ), 8.59 (d, J = 13.0, 1H), 8.35 (m, 1H), 8.11-8.00 (m, 5H), 7.93 (d, J = 8.2, 2H), 7.84 (d, J = 8.2, 2H) , 7.84 (m, 1H), 7.81-7.72 (m, 3H), 7.67 (m, 1H), 7.65 (s, 1H), 7.55 (m, 1H), 7.47 (dq, J = 7.9, 0.7, 1H) , 7.27 (d, J = 8.1, 4H), 7.04 (s, 1H), 6.98 (s, 1H), 2.35 (s, 3H), 2.34 (s, 3H).

Example 36

3- {3 (Z)-[(3,4-dimethylbenzoylhydrazino) methylidene] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic acid (compound 136)

This compound was prepared as described in Scheme III. ¹ H NMR (500 MHz, DMSO-d ₆ ) 13.24 (br s, 1H), 11.30 (d, J = 13.0, 1H), 10.28 (d, J = 13.0, 1H), 8.42 (br s, 1H), 8.10-7.96 (m, 2H), 7.82-7.64 (m, 4H), 7.38 (d, J = 8.1, 1H), 7.31 (d, J = 7.6, 1H), 7.01 (s, 1H), 6.95 (br s, 1 H), 2.31 (s, 6 H).

Example 37

3- {3 (Z)-[(4-chlorobenzoylhydrazino) methylidene] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic acid (Compound 137)

This compound was prepared as described in Scheme III. ¹ H NMR (500 MHz, DMSO-d ₆ ) 15.42 (s, 1H), 13.24 (s, 1H), 11.47 (s, 1H), 8.43 (s, 1H), 8.10-7.89 (m, 4H), 7.84 -7.70 (m, 3H), 7.65 (d, J = 8.4, 2H), 7.38 (d, J = 7.7, 1H), 7.01 (s, 1H).

Example 38

3- {3 (Z)-[(4-methoxybenzoylhydrazino) methylidene] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic acid (Compound 138 )

This compound was prepared as described in Scheme III. ¹ H NMR (500 MHz, DMSO-d ₆ ) 11.32 (s, 1H), 11.30 (d, J = 12.2, 1H), 10.27 (d, J = 12.2, 1H), 8.43 (s, 1H), 8.11- 7.65 (m, 7H), 7.38 (d, J = 8.1, 1H), 7.09 (d, J = 8.5, 2H), 7.01 (s, 1H), 3.85 (s, 3H).

Example 39

3- {3 (Z)-[(3,4-Dimethylbenzoylhydrazino) methylidene] -2-oxo-6-chloro-2,3-dihydroindol-l-yl} benzoic acid (Compound 139)

This compound was prepared as described in Scheme III. ¹ H NMR (500 MHz, DMSO-d ₆ ) 13.22 (s, 1H), 11.20 (br, 2H), 8.25 (s, 1H), 8.05-7.93 (m, 4H), 7.88 (m, 1H), 7.78 (m, 1H), 7.74-7.69 (m, 5H), 7.68-7.64 (m, 3H), 7.60 (m, 2H), 7.54 (s, 1H), 7.32-7.29 (m, 2H), 7.14 (m , 1H), 7.07 (dd, J = 8.2, 1.9, 1H), 6.83 (d, J = 1.9, 1H), 6.78 (m, 1H), 2.30 (s, 12H).

Example 40

1- (3,4-dimethylphenyl) -3 (Z)-[1- (2,4-dihydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 140 )

This compound was prepared as described in Scheme VIII. ¹ H NMR (300 MHz, DMSO-d ₆ ) 11.76 (s, 1H), 11.43 (s, 1H), 10.73 (s, 1H), 10.25 (s, 1H), 7.73 (d, J = 8.6, 1H) , 7.51 (m, 1H), 7.32 (d, J = 8.1, 1H), 7.21 (d, J = 2.0, 1H), 7.14 (dd, J = 8.1, 2.0, 1H), 7.07-6.99 (m, 2H ), 6.79 (m, 1H), 6.38 (dd, J = 8.6, 2.4, 1H), 6.34 (d, J = 2.4, 1H), 2.47 (s, 3H), 2.30 (s, 3H), 2.29 (s , 3H).

Example 41

1- (3,4-dimethylphenyl) -3 (Z)-[1- (4-hydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 141)

This compound was prepared as described in Scheme VIII. ¹ H NMR (300 MHz, DMSO-d ₆ ) 11.44 (s, 1H), 10.75 (s, 1H), 10.21 (s, 1H), 7.81 (d, J = 8.8, 2H), 7.51 (m, 1H) , 7.32 (d, J = 8.2, 1H), 7.21 (d, J = 2.0, 1H), 7.14 (dd, J = 8.2, 2.0, 1H), 7.07-6.99 (m, 2H), 6.88 (d, J = 8.8, 2H), 6.79 (m, 1H), 2.47 (s, 3H), 2.30 (s, 3H), 2.29 (s, 3H).

Example 42

1- (3,4-dimethylphenyl) -3 (Z)-[(2,4-dihydroxybenzoylhydrazino) methylidene] -2-oxo-2,3-dihydroindole (Compound 142)

This compound was prepared as described in Scheme VIII. ¹ H NMR (300 MHz, DMSO-d ₆ ) 12.04 (s, 1H), 11.94 (s, 1H), 11.02 (s, 1H), 10.28 (s, 1H), 10.25 (s, 1H), 9.64 (d , J = 11.5, 1H), 8.11 (s, 1H), 7.80 (m, 1H), 7.76-7.70 (m, 2H), 7.58 (d, J = 10.4, 1H), 7.55-7.50 (m, 2H) , 7.42 (d, J = 11.5, 1H), 7.34-7.27 (m, 2H), 7.23 (d, J = 1.6, 1H), 7.18-6.96 (m, 7H), 6.79-6.71 (m, 2H), 6.40-6.31 (m, 4H), 2.29 (s, 6H), 2.28 (s, 3H), 2.27 (s, 3H).

Example 43

1- (3,5-dimethylphenyl) -3 (Z)-[1- (2,4-dihydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (compound 143)

This compound was prepared as described in Scheme VIII. ¹ H NMR (300 MHz, DMSO-d ₆ ) 11.77 (s, 1H), 11.44 (s, 1H), 10.73 (s, 1H), 10.26 (s, 1H), 7.73 (d, J = 8.8, 1H) , 7.51 (m, 1H), 7.09-7.01 (m, 5H), 6.82 (m, 1H), 6.38 (dd, J = 8.8, 2.3, 1H), 6.34 (d, J = 2.3, 1H), 2.47 ( s, 3H), 2.35 (s, 6H).

Example 44

1- (3,5-dimethylphenyl) -3 (Z)-[1- (4-hydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 144)

This compound was prepared as described in Scheme VIII. ¹ H NMR (300 MHz, DMSO-d ₆ ) 11.45 (s, 1H), 10.76 (s, 1H), 10.22 (s, 1H), 7.81 (d, J = 8.8, 2H), 7.51 (m, 1H) , 7.09-6.97 (m, 5H), 6.88 (d, J = 8.8, 2H), 6.82 (m, 1H), 2.48 (s, 3H), 2.35 (s, 6H).

Example 45

1- (3,5-dimethylphenyl) -3 (Z)-[(2,4-dihydroxybenzoylhydrazino) methylidene] -2-oxo-2,3-dihydroindole (Compound 145)

This compound was prepared as described in Scheme VIII. ¹ H NMR (300 MHz, DMSO-d ₆ ) 11.98 (m, 2H), 11.02 (s, 2H), 10.28 (s, 1H), 10.26 (s, 1H), 9.65 (d, J = 11.6, 1H) , 8.12 (s, 1H), 7.80 (m, 1H), 7.77-7.70 (m, 2H), 7.56-7.50 (m, 2H), 7.42 (d, J = 11.6, 1H), 7.08-6.96 (m, 10H), 6.83-6.72 (m, 2H), 6.40-6.31 (m, 4H), 2.35 (s, 6H), 2.33 (s, 6H).

Example 46

1- (3,5-dimethylphenyl) -3 (Z)-[(4-hydroxybenzoylhydrazino) methylidene] -2-oxo-2,3-dihydroindole (Compound 146)

This compound was prepared as described in Scheme VIII. ¹ H NMR (300 MHz, DMSO-d ₆ ) 11.00 (s, 2H), 10.20 (s, 1H), 10.19 (s, 1H), 9.65 (m, 1H), 8.10 (s, 1H), 7.84-7.74 (m, 5H), 7.54 (m, 1H), 7.40 (d, J = 10.3, 1H), 7.10-6.95 (m, 10H), 6.91-6.84 (m, 4H), 6.78 (m, 1H), 3.18 (s, 1 H), 3.16 (s, 1 H), 2.35 (s, 6 H), 2.33 (s, 6 H).

Example 47

3- (3 (Z)-[1- (3,4-Dihydroxybenzoylhydrazino) ethylidene] -2-oxo-6-chloro-2,3-dihydroindol-1-yl) benzoic acid ( Compound 147)

This compound was prepared as described in Scheme III. ¹ H NMR (500 MHz, DMSO-d ₆ ) 11.55 (s, 1H), 8.02 (dt, J = 7.6, 1.5, 1H), 7.98 (t, J = 1.5, 1H), 7.78-7.65 (m, 4H ), 7.53 (d, J = 8.2, 1H), 7.30 (d, J = 8.2, 1H), 7.10 (dd, J = 8.2, 2.0, 1H), 6.84 (d, J = 2.0, 1H), 2.52 ( s, 3H), 2.30 (s, 6H).

Example 48

1- (3,4-dimethylphenyl) -3 (Z)-[(4-hydroxybenzoylhydrazino) methylidene] -2-oxo-2,3-dihydroindole (Compound 148)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 10.99 (s, 2H), 10.19 (s, 1H), 10.18 (s, 1H), 9.64 (d, J = 12.0, 1H), 8.09 (s, 1H) , 7.83-7.74 (m, 5H), 7.54 (m, 1H), 7.40 (m, 1H), 7.31 (d, J = 8.0, 1H), 7.29 (d, J = 8.0, 1H), 7.23 (m, 1H), 7.18-7.14 (m, 2H), 7.10 (dd, J = 8.0, 2.0, 1H), 7.07-7.02 (m, 2H), 7.00-6.97 (m, 3H), 6.89-6.84 (m, 4H ), 6.77 (m, 1H), 6.73 (m, 1H), 2.30 (s, 3H), 2.29 (s, 3H), 2.28 (s, 3H), 2.27 (s, 3H).

Example 49

1- (3,4-dimethylphenyl) -3 (Z)-[(3,5-diisopropyl-2-hydroxybenzoylhydrazino) methylidene] -2-oxo-2,3-dihydroindole (Compound 149)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 12.29 (s, 1H), 12.22 (s, 1H), 11.52 (s, 2H), 9.71 (d, J = 10.6, 1H), 8.14 (s, 1H) , 7.82 (m, 1H), 7.68-7.58 (m, 2H), 7.54-7.48 (m, 2H), 7.34-7.23 (m, 5H), 7.19-7.16 (m, 2H), 7.13-6.96 (m, 5H), 6.78 (m, 1H), 6.74 (m, 1H), 3.27 (m, 2H), 2.86 (m, 2H), 2.31 (s, 3H), 2.30 (s, 3H), 2.29 (s, 3H ), 2.28 (s, 3H), 1.23 (d, J = 6.8, 6H), 1.23 (d, J = 6.8, 6H), 1.20 (d, J = 6.8, 6H), 1.20 (d, J = 6.8, 6H).

Example 50

1- (3,5-dimethylphenyl) -3 (Z)-[1- (3,4-dihydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 150 )

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 11.47 (s, 1H), 7.51 (m, 1H), 7.35 (d, J = 1.5, 1H), 7.30 (dd, J = 8.3, 1.5, 1H), 7.10-7.01 (m, 5H), 6.86-6.80 (m, 2H), 2.47 (s, 3H), 2.35 (s, 6H).

Example 51

1- (3,4-dimethylphenyl) -3 (Z)-[1- (3,4-dihydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 151 )

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 11.47 (br s, 1H), 10.68 (br s, 1H), 9.70 (br s, 1H), 9.31 (br s, 1H), 7.50 (m, 1H) , 7.36-7.27 (m, 3H), 7.21 (s, 1H), 7.14 (m, 1H), 7.06-6.99 (m, 2H), 6.83 (m, 1H), 6.79 (m, 1H), 2.47 (s , 3H), 2.30 (s, 3H), 2.29 (s, 3H).

Example 52

3- (6-chloro-3 (Z)-[(2-hydroxy-3,5-diisopropylbenzoylhydrazino) methylidene] -2-oxo-2,3-dihydroindol-1-yl ) Benzoic acid (Compound 152)

This compound was prepared as described in Scheme III. ¹ H NMR (500 MHz, DMSO-d ₆ ) 13.22 (s, 2H), 12.25 (s, 1H), 12.16 (s, 1H), 11.58 (s, 2H), 8.32- 8.25 (m, 2H), 8.06 -7.94 (m, 5H), 7.81-7.55 (m, 9H), 7.33-7.24 (m, 2H), 7.20-7.04 (m, 2H), 6.83 (d, J = 1.6, 1H), 6.79 (d, J = 1.6, 1H), 3.26 (m, 2H), 2.86 (m, 2H), 1.23 (d, J = 6.3, 6H), 1.22 (d, J = 6.3, 6H), 1.20 (d, J = 6.8 , 6H), 1.19 (d, J = 6.8, 6H).

Example 53

1- (3,4-dimethylphenyl) -3 (Z)-[1- (2,5-dihydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 153 )

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 11.49 (s, 1H), 10.77 (s, 1H), 10.72 (s, 1H), 9.14 (s, 1H), 7.51 (m, 1H), 7.32 (d , J = 8.0, 1H), 7.23 (d, J = 3.0, 1H), 7.21 (d, J = 2.0, 1H), 7.14 (dd, J = 8.0, 2.0, 1H), 7.06-7.00 (m, 2H ), 6.89 (dd, J = 8.8, 3.0, 1H), 6.83 (d, J = 8.8, 1H), 6.79 (m, 1H), 2.48 (s, 3H), 2.30 (s, 3H), 2.29 (s , 3H).

Example 54

1- (3,4-dimethylphenyl) -3 (Z)-[1- (3-nitro-4-hydroxybenzoylhydrazino) ethylidene-2-oxo-2,3-dihydroindole (Compound 154 )

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 11.30 (s, 1H), 9.84 (s, 1H), 8.36 (d, J = 2.3, 1H), 7.98 (dd, J = 8.7, 2.3, 1H), 7.42 (ddd, J = 7.7, 1.2, 0.5, 1H), 7.29 (d, J = 7.9, 1H), 7.16 (d, J = 8.7, 1H), 7.16 (d, J = 2.1, 1H), 7.10 ( dd, J = 7.9, 2.1, 1H), 6.96 (td, J = 7.7, 1.2, 1H), 6.90 (td, J = 7.7, 1.2, 1H), 6.76 (ddd, J = 7.7, 1.2, 0.5, 1H ), 5.05 (br s, 1 H), 2.60 (s, 3 H), 2.29 (s, 3 H), 2.28 (s, 3 H).

Example 55

1- (3,4-dimethylphenyl) -3 (Z- [1- (3-aminosulfonyl-4-chlorobenzoylhydrazino) ethylidene]-2-oxo-2,3-dihydroindole (compound 155)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 11-48 (s, 1H), 11.29 (s, 1H), 8.52 (d, J = 2.2, 1H), 8.13 (dd, J = 8.3, 2.2, 1H ), 7.86 (d, J = 8.3, 1H), 7.79 (s, 2H), 7.52 (m, 1H), 7.32 (d, J = 8.0, 1H), 7.22 (d, J = 2.2, 1H), 7.15 (dd, J = 8.0, 2.2, 1H), 7.07-7.01 (m, 2H), 6.79 (m, 1H), 2.50 (m, 3H), 2.30 (s, 3H), 2.29 (s, 3H).

Example 56

1- (3,4-dimethylphenyl) -3 (Z)-[1- (3-amino-4-hydroxybenzoylhydrazino) thilidene] -2-oxo-2,3-dihydroindole ( Compound 156)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 7.54-7.42 (m, 3H), 7.31 (m, 1H), 7.17 (s, 1H), 7.11 (m, 1H), 7.08-7.00 (m, 2H) , 6.88 (br s, 1H), 6.78 (m, 1H), 4.61 (br s, 1H), 3.91 (s, 2H), 2.53 (s, 3H), 2.34 (s, 3H), 2.33 (s, 3H ).

Example 57

1- (3,4-dimethylphenyl) -3 (Z)-[1- (4-methoxy-2-hydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole ( Compound 157)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 11.91 (s, 1H), 11.44 (s, 1H), 10.83 (s, 1H), 7.83 (d, J = 8.8, 1H), 7.51 (m, 1H) , 7.32 (d, J = 8.0, 1H), 7.21 (d, J = 1.9, 1H), 7.14 (dd, J = 8.0, 1.9, 1H), 7.06-7.00 (m, 2H), 6.79 (m, 1H ), 6.57 (dd, J = 8.8, 2.4, 1H), 6.51 (d, J = 2.4, 1H), 3.80 (s, 3H), 2.48 (s, 3H), 2.30 (s, 3H), 2.29 (s , 3H).

Example 58

3- (3 (Z)-(1- (3,5-dimethylphenyl) -2-oxo-2,3-dihydro-3-indoledene) methylamino-2-hydroxyphenyl) benzoic acid (Compound 158)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 11.16 (d, J = 13.0, 1H), 9.26 (s, 1H), 8.84 (d, J = 13.0, 1H), 8.12 (t, J = 1.7, 1H ), 7.94 (ddd, J = 7.7, 1.7, 1.2, 1H), 7.81-7.72 (m, 3H), 7.60 (t, J = 7.7, 1H), 7.13-7.05 (m, 6H), 7.01 (dd, J = 7.7, 1.5, 1H), 6.85 (m, 1H), 2.35 (s, 6H).

Example 59

3- {3 (Z)-(3- (3,5-dimethylphenyl) -2-hydroxyphenyl) aminomethylidene) -2-oxo-2,3-dihydro-1-indolyl} benzoic acid (compound 159)

This compound was prepared as described in Scheme III. ¹ H NMR (500 MHz, DMSO-d ₆ ) 11.20 (d, J = 13.1, 1H), 9.17 (br s, 1 H), 8.95 (d, J = 13.1, 1 H), 8.02 (s, 1H), 7.97 (d, J = 7.7, 1H), 7.76-1.66 (m, 4H), 7.14 (s, 2H), 7.07 (t, J = 7.7, 1H), 7.00 (s, 1H), 6.97 (d, J = 7.7, 1H), 6.90-6.86 (m, 2H), 2.32 (s, 6H).

Example 60

3- {3 (Z)-(1- (3,4-Dimethylphenyl) -2-oxo-2,3-dihydro-3-indoledene) methylamino-2-hydroxyphenyl} benzoic acid (Compound 160)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 13.03 (s, 1H), 11.14 (d, J = 13.0, 1H), 9.25 (s, 1H), 8.83 (d, J = 13.0, 1H), 8.11 ( t, J = 1.7, 1H), 7.94 (ddd, J = 7.7, 1.7, 1.1, 1H), 7.80-7.75 (m, 2H), 7.73 (dd, J = 7.8, 1.5, 1H), 7.59 (t, J = 7.7, 1H), 7.32 (d, J = 8.0, 1H), 7.25 (d, J = 2.1, 1H), 7.18 (dd, J = 8.0, 2.1, 1H), 7.10 (t, J = 7.8, 1H), 7.07-7.03 (m, 2H), 7.00 (dd, J = 7.8, 1.5, 1H), 6.81 (m, 1H), 2.30 (s, 3H), 2.30 (s, 3H).

Example 61

4- {1- (6-Fluoro-2-oxo-2,3-dihydro-3 (Z)-(2- (3,5-dimethylphenyl) -aminocarbonylphenyl) aminomethylidene) indolyl Butanoic Acid (Compound 161)

This compound was prepared as described in Scheme III. ¹ H NMR (500 MHz, DMSO-d ₆ ) 12.11 (s, 1H), 12.00 (d, J = 12.8, 1H), 10.32 (s, 1H), 8.67 (d, J = 12.8, 1H), 7.84 ( d, J = 8.2, 1H), 7.80 (dd, J = 7.9, 1.5, 1H), 7.63 (m, 1H), 7.60 (dd, J = 9.3, 2.6, 1H), 7.35 (s, 2H), 7.23 (m, 1H), 7.01 (dd, J = 8.5, 4.3, 1H), 6.91 (ddd, J = 9.5, 8.5, 2.6, 1H), 6.79 (s, 1H), 3.77 (t, J = 7.3, 2H ), 2.29 (s, 6H), 2.26 (t, J = 7.3, 2H), 1.80 (qn, J = 7.3, 3H).

Example 62

4- {1- (6-Chloro-2-oxo-2,3-dihydro-3 (Z)-(2-hydroxy-3- (3,5-dimethylphenyl) -phenyl) aminomethylidene) indole Reyl} Butanoic Acid (Compound 162)

This compound was prepared as described in Scheme III. ¹ H NMR (500 MHz, DMSO-d ₆ ) 11.25 (d, J = 12.9, 1H), 10.68 (s, 1H), 8.65 (d, J = 12.9, 1H), 8.05 (s, 1H), 7.60 ( d, J = 8.0, 1H), 7.57 (dd, J = 7.9, 1.3, 1H), 7.16 (d, J = 1.8, 1H), 7.11 (m, 2H), 7.02 (dd, J = 7.9, 7.7, 1H), 7.02 (m, 1H), 7.00 (dd, J = 8.0, 1.8, 1H), 6.94 (dd, J = 7.7, 1.3, 1H), 3.94 (t, J = 7.2, 2H), 2.43 (t , J = 7.2, 2H), 2.35 (m, 6H), 2.01 (qn, J = 7.2, 2H).

Example 63

3- {1- (6-Chloro-2-oxo-2,3-dihydro-3 (Z)-(2-hydroxy-3- (3,5-dimethylphenyl) -phenyl) aminomethylidene) indole Reyl} benzoic acid (Compound 163)

This compound was prepared as described in Scheme III. ¹ H NMR (500 MHz, DMSO-d ₆ ) 13.25 (s, 1H), 11.17 (d, J = 13.3, 1H), 9.15 (s, 1H), 8.94 (d, J = 13.3, 1H), 8.03- 7.99 (m, 2H), 7.80 (m, 1H), 7.80 (d, J = 8.1, 1H), 7.72 (t, J = 7.8, 1H), 7.70 (d, J = 7.8, 1H), 7.16 (dd , J = 8.13 1.9, 1H), 7.14 (s, 2H), 7.06 (t, J = 7.8, 1H), 7.00 (s, 1H), 6.97 (dd, J = 7.8, 1.2, 1H), 6.88 (d , J = 1.9, 1H), 2.32 (s, 6H).

Example 64

4- {1- (5-Fluoro-2-oxo-2,3-dihydro-3 (Z)-(2-hydroxy-3- (3,5-dimethylphenyl) -phenyl) aminomethylidene) Indolyl} butanoic acid (compound 164)

This compound was prepared as described in Scheme III. ¹ H NMR (500 MHz, DMSO-d ₆ ) 11.30 (d, J = 12.8, 1H), 10.69 (s, 1H), 8.69 (d, J = 12.8, 1H), 8.06 (s, 1H), 7.58 ( dd, J = 8.2, 1.4, 1H), 7.45 (dd, J = 9.3, 2.6, 1H), 7.11 (m, 2H), 7.07-7.01 (m, 3H), 6.94 (dd, J = 7.7, 1.5, 1H), 6.86 (ddd, J = 9.7, 8.2, 2.6, 1H), 3.92 (t, J = 7.2, 2H), 2.41 (t, J = 7.2, 2H), 2.35 (m, 6H), 2.00 (qn , J = 7.2, 2H).

Example 65

3- {3- (1- (1- (1- (3,5-Dimethylphenyl) -6-trifluoromethyl-2-oxo-2,3-dihydro-3 (Z) -indolene) ethylamino)- 2-hydroxyphenyl} benzoic acid (Compound 165)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 11.86 (s, 1H), 8.31 (t, J = 1.5, 1H), 8.06 (d, J = 7.8, 1H), 7.77 (d, J = 7.8, 1H ), 7.53 (t, J = 7.8, 1H), 7.46 (d, J = 8.1, 1H), 7.33 (dq, J = 8.1, 0.9, 1H), 7.30 (dd, J = 7.7, 1.3, 1H), 7.13 (dd, J = 7.7, 1.3, 1H), 7.06 (s, 2H), 7.02 (t, J = 7.7, 1H), 6.99-6.97 (m, 2H), 2.42 (s, 3H), 2.37 (s , 6H).

Example 66

3- {3- (1- (1- (3,4-Dimethylphenyl) -6-trifluoromethyl-2-oxo-2,3-dihydro-3 (Z) -indoledene) ethylamino)- 2-hydroxyphenyl} benzoic acid (compound 166)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 11.91 (s, 1H), 8.32 (br s, 1H), 8.06 (d, J = 7.8, 1H), 7.76 (d, J = 7.8, 1H), 7.54 (t, J = 7.8, 1H), 7.48 (d, J = 8.1, 1H), 7.35-7.28 (m, 3H), 7.18 (s, 1H), 7.16-7.10 (m, 2H), 7.08 (s, 1H), 7.04 (t, J = 7.6, 1H), 2.49 (s, 3H), 2.33 (s, 3H), 2.32 (s, 3H).

Example 67

3- {1- (6-Trifluoromethyl-2-oxo-2,3-dihydro-3- (5-chloro-2-hydroxy-3-cyclohexylphenyl) hydrazono) indolyl} benzoic acid (Compound 167)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) 13.30 (s, 1H), 13.03 (s, 1H), 9.44 (s, 1H), 8.11 (dd, J = 2.1, 1.7, 1H), 8.08 (ddd, J = 7.8, 1.7, 1.2, 1H), 7.99 (d, J = 8.0, 1H), 7.85 (ddd, J = 7.8, 2.1, 1.2, 1H), 7.77 (t, J = 7.8, 1H), 7.56 ( d, J = 2.5, 1H), 7.54 (dq, J = 8.0, 0.8, 1H), 7.04 (m, 1H), 6.92 (d, J = 2.5, 1H), 2.97 (m, 1H), 1.81-1.67 (m, 5H), 1.44-1.31 (m, 4H), 1.25 (m, 1H).

Example 68

3- {1- (5-Fluoro-2-oxo-2,3-dihydro-3- (1- (5-chloro-2-hydroxy-3 (Z) -cyclohexylphenyl) amino) ethylidene ) Indolyl} benzoic acid (Compound 168)

This compound was prepared as described in Scheme III. ¹ H NMR (500 MHz, DMSO-d ₆ ) 11.93 (s, 1H), 8.00-7.97 (m, 2H), 7.72-7.66 (m, 2H), 7.34 (dd, J = 10.1, 1.8, 1H), 7.23 (d, J = 2.5, 1H), 7.12 (d, J = 2.5, 1H), 6.91-6.84 (m, 2H), 2.95 (m, 1H), 2.49 (s, 3H), 1.82-1.67 (m , 5H), 1.43-1.32 (m, 4H), 1.29-1.20 (m, 1H).

Example 69

3- {1- (5-Fluoro-2-oxo-2,3-dihydro-3- (5-chloro-2-hydroxy-3 (Z) -cyclohexylphenyl) aminomethylidene) indolyl} Benzoic Acid (Compound 169)

This compound was prepared as described in Scheme III. ¹ H NMR (500 MHz, DMSO-d ₆ ) 11.09 (d, J = 13.2, 1H), 9.38 (br s, 1 H), 8.91 (d, J = 13.2, 1H), 8.02 (t, J = 1.8, 1H), 7.99 (ddd, J = 7.8, 1.8, 1.2, 1H), 7.77 (ddd, J = 7.8, 1.8, 1.2, 1H), 7.70 (t, J = 7.8, 1H), 7.67 (m, 1H) , 7.66 (d, J = 2.3, 1H), 6.90 (d, J = 2.3, 1H), 6.90-6.87 (m, 2H), 2.95 (m, 1H), 1.81-1.66 (m, 5H), 1.44- 1.22 (m, 5 H).

Example 70

4- {2-hydroxy-3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) -3 (Z) -indolylidene) methyl Aminophenyl} butanoic acid (compound 170)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 11.27 (d, J = 13.6, 1H), 9.01 (d, J = 13.6, 1H), 7.94 (d, J = 8.1, 1H), 7.60 (d, J = 7.6, 1H), 7.41 (d, J = 8.1, 1H), 7.12 (s, 1H), 7.10 (s, 2H), 6.94 (t, J = 7.6, 1H), 6.93 (s, 1H), 6.88 (d, J = 7.6, IH), 2.65 (t, J = 7.4, 2H), 2.37 (s, 6H), 2.23 (t, J = 7.4, 2H), 1.77 (qn, J = 7.4, 2H).

Example 71

4- {2-hydroxy-3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) -3 (Z) -indolilidene) Methylaminophenyl} butanoic acid (Compound 171)

This compound was prepared as described in Scheme VIII. ¹ H NMR (300 MHz, DMSO-d ₆ ) 8.72 (s, 1H), 7.76 (d, J = 7.6, 1H), 7.44 (m, 1H), 7.38-7.30 (m, 2H), 7.22 (d, J = 1.7, 1H), 7.15 (dd, J = 8.0, 1.7, 1H), 6.97-6.89 (m, 3H), 2.70 (t, J = 7.2, 2H), 2.36 (s, 6H), 2.33 (t, J = 7.2, 2H), 1.87 (qn, J = 7.2, 2H).

Example 72

3- {3- (7- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) -3 (Z) -indolylidene) methylamino) Indolyl} propanoic acid (Compound 172)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 12.10 (s, 1H), 11.32 (m, 1H), 10.94 (d, J = 12.8, 1H), 8.92 (d, J = 12.8, 1H), 7.95 ( d, J = 7.8, 1H), 7.43 (d, J = 7.8, 1H), 7.40 (m, 1H), 7.30 (d, J = 7.8, 1H), 7.19 (d, J = 2.4, 1H), 7.14 (m, 1H), 7.12 (m, 2H), 7.09 (t, J = 7.8, 1H), 6.94 (m, 1H), 2.94 (t, J = 7.6, 2H), 2.61 (t, J = 7.6, 2H), 2.37 (s, 6H).

Example 73

3- {3- (7- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) -3 (Z) -indolylidene) methylamino) Indolyl} propanoic acid (Compound 173)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 12.09 (s, 1H), 11.33 (d, J = 2.2, 1H), 10.92 (d, J = 12.8, 1H), 8.91 (d, J = 12.8, 1H ), 7.94 (d, J = 8.0, 1H), 7.43 (d, J = 8.0, 1H), 7.40 (m, 1H), 7.37 (d, J = 8.0, 1H), 7.30-7.28 (m, 2H) , 7.22 (dd, J = 8.0, 2.0, 1H), 7.19 (d, J = 2.2, 1H), 7.09 (t, J = 8.0, 1H), 6.92 (d, J = 1.6, 1H), 2.94 (t , J = 7.7, 2H), 2.60 (t, J = 7.7, 2H), 2.32 (s, 3H), 2.31 (s, 3H).

Example 74

4- {2-hydroxy-3- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) -3 (Z) -indolylidene) methylaminophenyl} butanoic acid (compound 174)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 12.07 (s, 1H), 11.08 (d, J = 13.0, 1H), 8.77 (d, J = 13.0, 1H), 7.74 (m, 1H), 7.54 ( d, J = 7.8, 1H), 7.10-7.02 (m, 5H), 6.91 (m, 1H), 6.85-6.81 (m, 2H), 2.64 (m, 2H), 2.36 (s, 6H), 2.23 ( m, 2H), 1.77 (m, 2H).

Example 75

2-chloro-3 (Z)-{3-hydroxy-4- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) -3 (Z) -indolylidene) methyl Aminophenyl} propenic acid (compound 175)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 13.48 (br s, 1H), 11.06 (d, J = 12.6, 1H), 10.61 (s, 1H), 8.84 (d, J = 12.6, 1H), 7.85 (s, 1H), 7.78-7.73 (m, 3H), 7.41 (d, J = 7.4, 1H), 7.10-7.05 (m, 5H), 6.84 (m, 1H), 2.36 (s, 6H).

Example 76

2-chloro-3 (Z)-{3-hydroxy-4- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) -3 (Z ) -Indolylidene) methylaminophenyl} propenic acid (Compound 176)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 13.53 (s, 1H), 11.22 (d, J = 13.2, 1H), 10.72 (s, 1H), 9.08 (d, J = 13.2, 1H), 7.95 ( d, J = 7.8, 1H), 7.87 (s, 1H), 7.81 (d, J = 8.5, 1H), 7.75 (d, J = 1.8, 1H), 7.44 (m, 1H), 7.43 (dd, J = 8.5, 1.8, 1H), 7.36 (d, J = 8.0, 1H), 7.28 (d, J = 2.1, 1H), 7.21 (dd, J = 8.0, 2.1, 1H), 6.92 (m, 1H), 2.32 (s, 3 H), 2.31 (s, 3 H).

Example 77

2-ethyl-3 (E)-{3-hydroxy-4- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) -3 (Z ) -Indolylidene) methylaminophenyl} propene acid (Compound 177)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, Acetone-d ₆ ) 11.42 (d, J = 12.9, 1H), 9.53 (s, 1H), 8.93 (d, J = 12.9, 1H), 7.87 (d, J = 8.1, 1H ), 7.73 (d, J = 8.1, 1H), 7.59 (s, 1H), 7.38 (m, 1H), 7.36 (d, J = 8.1, 1H), 7.32 (d, J = 2.1, 1H), 7.25 (dd, J = 8.1, 2.1, 1H), 7.22 (d, J = 1.7, 1H), 7.11 (dd, J = 8.1, 1.7, 1H), 7.06 (m, 1H), 2.59 (q, J = 7.4 , 2H), 2.36 (s, 6H), 1.19 (t, J = 7.4, 3H).

Example 78

2-ethyl-3 (E)-{3-hydroxy-4- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) -3 (Z ) -Indolylidene) methylaminophenyl} propenoic acid (Compound 178)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, Acetone-d ₆ ) 11.42 (d, J = 12.8, 1H), 9.54 (s, 1H), 8.94 (d, J = 12.8, 1H), 7.87 (d, J = 8.0, 1H ), 7.74 (d, J = 8.5, 1H), 7.59 (s, 1H), 7.38 (dq, J = 8.0, 0.9, 1H), 7.22 (d, J = 1.7, 1H), 7.16 (m, 2H) , 7.13 (m, 1H), 7.11 (dd, J = 8.5, 1.7, 1H), 7.08 (s, 1H), 2.59 (q, J = 7.4, 2H), 2.40 (m, 6H), 1.19 (t, J = 7.4, 3H).

Example 79

2-ethyl-3 (E)-{3-hydroxy-4- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) -3 (Z) -indolylidene) methyl Aminophenyl} propenic acid (compound 179)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, Acetone-d ₆ ) 11.24 (d, J = 12.3, 1H), 9.40 (br s, 1H), 8.71 (d, J = 12.3, 1H), 7.70 (m, 1H), 7.67 (d, J = 8.4, 1H), 7.59 (s, 1H), 7.21 (d, J = 1.8, 1H), 7.14 (m, 2H), 7.11-7.02 (m, 4H), 6.90 (m, 1H) , 2.60 (q, J = 7.4, 2H), 2.39 (s, 6H), 1.19 (t, J = 7.4, 3H).

Example 80

4- {2-hydroxy-3- (4 (Z)-(2- (3,4-dimethylphenyl) -3-oxo-3,4-dihydro-5-methyl) pyrazolidene) methylaminophenyl Butanoic Acid (Compound 180)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, Methanol-d ₄ ) 8.46 (s, 1H), 7.58 (s, 1H), 7.49 (d, J = 8.3, 1H), 7.43 (m, 1H), 7.14 (d, J = 8.3, 1H), 7.01-6.88 (m, 2H), 6.92 (t, J = 7.3, 1H), 2.70 (t, J = 7.3, 2H), 2.35 (t, J = 7.3, 2H), 2.31 (s , 3H), 2.29 (s, 3H), 2.25 (s, 3H), 1.87 (qn, J = 7.3, 2H).

Example 81

(Z) -4- {1- (2,5-dioxo-3- (3- (3,5-dimethylphenyl) -2-hydroxyphenylaminomethylidene) pyrrolidinyl} butanoic acid (Compound 181)

This compound was prepared as described in Scheme VIII. ¹ H NMR (300 MHz, CDCl ₃ ) 10.08 (d, J = 12.8, 1H), 7.30 (dt, J = 12.8, 0.8, 1H), 7.06 (s, 3H), 7.03 (dd, J = 7.8, 1.8 , 1H), 6.95 (t, J = 7.8, 1H), 6.89 (dd, J = 7.8, 1.8, 1H), 3.64 (t, J = 6.8, 2H), 3.35 (d, J = 0.8, 2H), 2.40 (t, J = 7.4, 2H), 2.37 (s, 6H), 1.97 (m, 2H).

Example 82

(E) -4- {1- (2,5-dioxo-3- (3- (3,5-dimethylphenyl) -2-hydroxyphenylaminomethylidene) pyrrolidinyl} butanoic acid (Compound 182)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, CDCl ₃ ) 7.91 (dt, J = 13.8, 1.5, 1H), 7.13 (dd, J = 7.8, 1.6, 1H), 7.06 (s, 1H), 7.04 (s, 2H), 6.99 (t, J = 7.8, 1H), 6.90 (dd, J = 7.8, 1.6, 1H), 6.81 (d, J = 13.8, 1H), 3.64 (t, J = 6.7, 2H), 3.23 (d, J = 1.5, 2H), 2.39 (t, J = 7.3, 2H), 2.38 (s, 6H), 1.96 (m, 2H).

Example 83

(Z) -3- {1- (2,5-dioxo-3- (3- (3,5-dimethylphenyl) -2-hydroxyphenylaminomethylidene) pyrrolidinyl} benzoic acid (Compound 183)

This compound was prepared as described in Scheme VIII. ¹ H NMR (300 MHz, Acetone-d ₆ ) 10.28 (d, J = 12.8, 1H), 8.15 (m, 1H), 8.04 (ddd, J = 7.9, 1.7, 1.2, 1H), 7.90 (s, 1H ), 7.82 (dt, J = 12.8, 1.1, 1H), 7.72 (ddd, J = 7.9, 2.1, 1.2, 1H), 7.63 (t, J = 7.9, 1H), 7.34 (dd, J = 7.8, 1.5 , 1H), 7.08 (m, 2H), 7.00 (m, 1H), 6.98 (t, J = 7.8, 1H), 6.86 (dd, J = 7.8, 1.5, 1H), 3.54 (d, J = 1.1, 2H), 2.33 (s, 3H), 2.33 (s, 3H).

Example 84

(E) -3- {1- (2,5-dioxo-3- (3- (3,5-dimethylphenyl) -2-hydroxyphenylaminomethylidene) pyrrolidinyl} benzoic acid (Compound 184)

This compound was prepared as described in Scheme VIII. ¹ H NMR (300 MHz, Acetone-d ₆ ) 8.12 (m, 1H), 8.04 (dt, J = 7.8, 1.5, 1H), 7.98 (dt, J = 13.6, 1.8, 1H), 7.84 (d, J = 13.6, 1H), 7.69 (ddd, J = 7.8, 2.0, 1.5, 1H), 7.63 (t, J = 7.8, 1H), 7.33 (dd, J = 7.8, 1.6, 1H), 7.09 (m, 2H ), 7.01 (t, J = 7.8, 1H), 7.01 (m, 1H), 6.92 (dd, J = 7.8, 1.6, 1H), 3.57 (d, J = 1.8, 2H), 2.34 (m, 6H) .

Example 85

4- {3- (4-Oxo-2-thioxo-5- (3- (3,5-dimethylphenyl) -2-hydroxyphenylhydrozono) thiazolidinyl} butanoic acid (Compound 185)

This compound was prepared as described in Scheme I. ¹ H NMR (500 MHz, Methanol-d ₄ ) 8.51 (s, 1H), 7.13-7.09 (m, 2H), 7.02-6.89 (m, 3H), 4.21 (m, 2H), 2.36 (s, 3H ), 2.35 (s, 3H), 2.33 (m, 2H), 2.03 (m, 2H).

Example 86

3- {2- (3 (Z)-(1- (3.5-dimethylphenyl) -6-chloro-2-oxo-2,3-dihydroindolidene) methylamino) phenylamino} benzoic acid (Compound 186)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 10.96 (d, J = 13.0, 1H), 8.90 (d, J = 13.0, 1H), 7.94 (m, 1H), 7.82 (m, 1H), 7.75 ( d, J = 8.2, 1H), 7.34-7.28 (m, 2H), 7.27-7.24 (m, 2H), 7.24 (t, J = 7.8, 1H), 7.13 (td, J = 7.6, 1.2, 1H) , 7.10 (dd, J = 8.2, 2.0, 1H), 7.07 (m, 1H), 6.97 (m, 2H), 6.93 (m, 1H), 6.68 (d, J = 2.0, 1H), 2.32 (s, 6H).

Example 87

3- {2- (3- (1- (3,5-Dimethylphenyl) -6-trifluoromethyl-2-oxo-2,3-dihydroindoledene) methylamino) phenylamino} benzoic acid (compound 187)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 11.13 (d, J = 13.2, 1H), 9.07 (d, J = 13.2, 1H), 7.99 (s, 1H), 7.95 (d, J = 8.0, 1H ), 7.88 (m, 1H), 7.42 (dd, J = 8.0, 1.0, 1H), 7.34 (td, J = 7.5, 1.1, 1H), 7.32-7.26 (m, 3H), 7.25 (t, J = 7.6, 1H), 7.17 (td, J = 7.5, 1.1, 1H), 7.10 (m, IH), 7.00 (m, 2H), 6.95 (m, 1H), 6.86 (d, J = 1.0, 1H), 2.33 (s, 6 H).

Example 88

3- {2- (4- (2- (3,5-Dimethylphenyl) -5-methyl-3-oxo-3,4-dihydropyrazolidene) methylamino) phenylamino} benzoic acid (Compound 188)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 11.50 (d, J = 12.0, 1H), 8.66 (d, J = 12.0, 1H), 8.08 (s, 1H), 7.86 (m, 1H), 7.67 ( d, J = 2.0, 1H), 7.62 (dd, J = 8.3, 2.0, 1H), 7.38-7.33 (m, 2H), 7.32-7.29 (m, 2H), 7.30 (t, J = 7.7, 1H) , 7.23 (td, J = 7.6, 1.3, 1H), 7.10 (d, J = 8.3, 1H), 7.02 (m, 1H), 2.28 (s, 3H), 2.21 (s, 3H), 2.18 (s, 3H).

Example 89

(±) -3-methyl-5- {2-hydroxy-3- (3 (Z)-(6-trifluoromethyl-2-oxo-2,3-dihydro-1- (335-dimethylphenyl ) Indolylidene) methylamino) phenyl} pentanoic acid (Compound 189)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 11.29 (d, J = 13.4, 1H), 9.01 (d, J = 13.4, 1H), 7.94 (d, J = 8.0, 1H), 7.58 (dd, J = 8.0, 1.5, 1H), 7.41 (dq, J = 8.0, 0.7, 1H), 7.13 (m, 1H), 7.10 (m, 2H), 6.95-6.91 (m, 2H), 6.89 (dd, J = 7.7, 1.5, 1H), 2.71-2.58 (m, 2H), 2.37 (s, 6H), 2.31 (dd, J = 15.0, 5.5, 1H), 2.04 (dd, J = 15.0, 8.5, 1H), 1.87 (m, 1H), 1.56 (m, 1H), 1.42 (m, 1H), 0.95 (d, J = 6.6, 3H).

Example 90

(±) -3- {1- (6-chloro-2-oxo-2,3-dihydro-3- (3 (Z)-(1- (3,5-dimethylphenyl) -2-oxo-2 , 3-dihydro) indolyl) aminomethylidene) indolyl} benzoic acid (Compound 190)

This compound was prepared as described in Scheme III. ¹ H NMR (500 MHz, DMSO-d ₆ ) 13.20 (s, 1H), 7.93 (ddd, J = 7.8, 1.6, 1.1, 1H), 7.73 (m, 1H), 7.58 (t, J = 7.8, 1H ), 7.35 (m, 1H), 7.30 (dd, J = 7.8, 1.8, 1H), 7.23 (td, J = 7.7, 1.2, 1H), 7.14-7.08 (m, 4H), 7.00 (s, 2H) , 6.89 (t, J = 7.7, 1H), 6.67 (d, J = 7.8, 1H), 6.63 (d, J = 2.0, 1H), 6.31 (m, 1H), 2.33 (s, 6H).

Example 91

3- {4- (3-hydroxy-6-methyl-2- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indole Reyl) hydrazono) pyridinyl} benzoic acid (Compound 191)

This compound was prepared as described in Scheme IX. ¹ H NMR (300 MHz, DMSO-d ₆ ) 8.52 (s, 1H), 8.16 (m, 1H), 7.98 (m, 1H), 7.96 (m, 1H), 7.60-7.52 (m, 2H), 7.59 (t, J = 7.8, 1H), 7.20-7.16 (m, 3H), 6.98 (s, 1H), 2.50 (s, 3H), 2.37 (s, 6H).

Example 92

3- {4- (3-hydroxy-6-methyl-2- (3 (Z)-(6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethyl Phenyl) indoledene) methylamino) pyridinyl} benzoic acid (Compound 192)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 9.06 (s, 1H), 8.55 (s, 1H), 8.20 (m, 1H), 7.99 (d, J = 7.8, 1H), 7.93 (d, J = 7.8, 1H), 7.61 (s, 1H), 7.56 (t, J = 7.8, 1H), 7.48 (d, J = 7.8, 1H), 7.13 (m, 1H), 7.11 (m, 2H), 6.94 ( m, 1H), 2.50 (s, 3H), 2.37 (s, 6H).

Example 93

3- {4- (3-hydroxy-2- (3 (Z)-(6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene ) Methylamino) pyridinyl} benzoic acid (Compound 193)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 9.13 (d, J = 12.9, 1H), 8.52 (s, 1H), 8.24 (m, 1H), 8.17 (m, 1H), 8.03-7.99 (m, 2H), 7.84 (m, 1H), 7.65 (t, J = 7.7, 1H), 7.50 (dq, J = 7.9, 0.6, 1H), 7.14 (m, 1H), 7.12 (m, 2H), 6.95 ( q, J = 0.85 1H), 2.37 (s, 6H).

Example 94

3- {4- (3-hydroxy-2- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolyl) hydrazo No) pyridinyl} benzoic acid (Compound 194)

This compound was prepared as described in Scheme IX. ¹ H NMR (500 MHz, DMSO-d ₆ ) 13.22 (s, 1H), 8.50 (s, 1H), 8.21 (m, 1H), 8.16 (d, J = 7.7, 1H), 8.04 (d, J = 7.8, 1H), 8.01 (d, J = 7.7, 1H), 7.80 (d, J = 5.4, 1H), 7.68 (t, J = 7.7, 1H), 7.60 (dq, J = 7.8, 0.7, 1H) , 7.19 (m, 1H), 7.17 (m, 2H), 6.98 (m, 1H), 2.37 (s, 3H), 2.37 (s, 3H).

Example 95

3- {5- (4-hydroxy-3- (3 (Z)-(6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene ) Methylamino) pyridinyl} benzoic acid (Compound 195)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 11.10 (d, J = 13.8, 1H), 8.95 (d, J = 13.8, 1H), 8.39 (t, J = 1.7, 1H), 8.35 (d, J = 1.3, 1H), 8.10 (d, J = 1.3, 1H), 7.98 (ddd, J = 7.7, 1.7, 1.2, 1H), 7.88 (ddd, J = 7.7, 1.7, 1.2, 1H), 7.86 (d , J = 7.9, 1H), 7.53 (t, J = 7.7, 1H), 7.43 (dq, J = 7.9, 0.9, 1H), 7.12 (m, 1H), 7.10 (m, 2H), 6.94 (m, 1H), 2.37 (s, 6H).

Example 96

3- {5- (4-hydroxy-3- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolyl) hydrazo No) pyridinyl} benzoic acid (Compound 196)

This compound was prepared as described in Scheme IX. ¹ H NMR (300 MHz, DMSO-d ₆ ) 12.91 (s, 1H), 8.39 (t, J = 1.7, 1H), 8.17 (d, J = 1.4, 1H), 8.06 (d, J = 1.4, 1H ), 7.99 (m, 1H), 7.94-7.86 (m, 2H), 7.53 (m, 1H), 7.53 (t, J = 7.7, 1H), 7.18-7.15 (m, 3H), 6.97 (m, 1H ), 2.37 (s, 6 H).

Example 97

3- {5- (4-hydroxy-3- (4- (3-oxo-3,4-dihydro-5-methyl-2- (3,4-dimethylphenyl) pyrazolyl) hydrazono) pyrid Dinyl} benzoic acid (compound 197)

This compound was prepared as described in Scheme IX. ¹ H NMR (500 MHz, DMSO-d ₆ ) 13.43 (s, 1H), 12.99 (s, 1H), 12.33 (s, 1H), 8.40 (t, J = 1.6, 1H), 8.16 (s, 1H) , 8.10 (s, 1H), 7.99 (m, 1H), 7.91 (m, 1H), 7.71 (m, 1H), 7.63 (dd, J = 8.1, 1.9, 1H), 7.55 (t, J = 7.7, 1H), 7.21 (d, J = 8.1, 1H), 2.31 (s, 3H), 2.27 (s, 3H), 2.23 (s, 3H).

Example 98

4- {2- (3-Oxo-3,4-dihydro-5-methyl-4- (3- (3,4-dimethylphenyl) phenyl) hydrozono) pyrazolyl} butanoic acid (Compound 198)

This compound was prepared as described in Scheme I. ¹ H NMR (300 MHz, CDCl-d ₃ ) 13.45 (s, 1H), 7.58 (s, 1H), 7.47-7.31 (m, 4H), 7.26 (s, 1H), 7.22 (d, J = 7.7, 1H), 3.84 (t, J = 6.8, 2H), 2.42 (t, J = 6.8, 2H), 2.34 (s, 3H), 2.07 (qn, J = 6.8, 2H), 2.31 (s, 3H), 2.27 (s, 3 H).

Example 99

3- {2-amino-5-methyl-3- (3 (Z)-(6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolyl Den) methylamino) phenyl} benzoic acid (compound 199)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 10.91 (d, J = 13.1, 1H), 8.94 (d, J = 13.1, 1H), 7.98-7.93 (m, 3H), 7.65 (m, 1H), 7.62 (t, J = 7.6, 1H), 7.43-7.40 (m, 2H), 7.12 (m, 1H), 7.09 (m, 2H), 6.93 (d, J = 1.4, 1H), 6.81 (m, 1H ), 4.38 (br s, 2 H), 2.36 (s, 6 H), 2.33 (s, 3 H).

Example 100

3- {1- (5-Fluoro-2-oxo-2,3-dihydro-3 (Z)-(3- (3,4-dimethylphenyl) phenyl) aminomethylidene) indolyl} benzoic acid (Compound 200)

This compound was prepared as described in Scheme III. ¹ H NMR (500 MHz, DMSO-d ₆ ) 13.23 (s, 1H), 10.85 (d, J = 12.8, 1H), 8.96 (d, J = 12.8, 1H), 8.06 (m, 1H), 7.99 ( m, 1H), 7.82-7.78 (m, 2H), 7.74-7.69 (m, 2H), 7.56 (s, 1H), 7.51-7.39 (m, 4H), 7.26 (d, J = 7.8, 1H), 6.94-6.86 (m, 2 H), 2.32 (s, 3 H), 2.28 (s, 3 H).

Example 101

4- {2- (5-Methyl-2-oxo-2,3-dihydro-4 (Z)-(3- (3,4-dimethylphenyl) phenyl) aminomethylidene) pyrazolyl} butanoic acid (Compound 201)

This compound was prepared as described in Scheme VIII. ¹ H NMR (300 MHz, Methanol-d ₄ ) 8.52 (s, 1H), 7.63 (s, 1H), 7.49-7.43 (m, 2H), 7.41-7.30 (m, 2H), 7.23-7.09 (m, 2H), 3.80 (t, J = 6.8, 2H), 2.34 (s, 3H), 2.30 (s, 3H), 2.28 (m, 2H), 2.26 (s, 3H), 2.01 (qn, J = 6.8, 2H).

Example 102

(3- (5-fluoro-2-hydroxy-3- (3 (Z)-(6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl ) Indolidene) methylamino) -1-pyrazolyl) acetic acid (Compound 202)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 13.26 (s, 1H), 11.35 (s, 1H), 11.26 (d, J = 13.0, 1H), 9.06 (d, J = 13.0, 1H), 7.97 ( d, J = 2.4, 1H), 7.93 (d, J = 7.9, 1H), 7.71 (dd, J = 10.3, 2.8, 1H), 7.46 (dq, J = 7.9, 0.9, 1H), 7.42 (dd, J = 9.5, 2.8, 1H), 7.36 (d, J = 8.0, 1H), 7.29 (d, J = 2.1, 1H), 7.22 (dd, J = 8.0, 2.1, 1H), 7.03 (d, J = 2.4, 1H), 6.94 (m, 1H), 5.15 (s, 2H), 2.32 (s, 3H), 2.31 (s, 3H).

Example 103

(3- (5-fluoro-2-hydroxy-3- (3 (Z)-(2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indoledene) methylamino) -1-pyrazolyl) acetic acid (compound 203)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 13.26 (s, 1H), 11.30 (s, 1H), 11.13 (d, J = 12.7, 1H), 8.83 (d, J = 12.7, 1H), 7.96 ( d, J = 2.4, 1H), 7.75 (m, 1H), 7.66 (dd, J = 10.4, 2.8, IH), 7.35 (dd, J = 9.6, 2.8, 1H), 7.11-7.07 (m, 5H) , 7.01 (d, J = 2.4, 1H), 6.87 (m, 1H), 5.14 (s, 2H), 2.36 (s, 6H).

Example 104

4- {2- (5-Methyl-2-oxo-2,3-dihydro-4 (Z)-(2-hydroxy-3- (2-phenyl) ethyl) phenyl) aminomethylidene) pyrazolyl} Butanoic Acid (Compound 204)

This compound was prepared as described in Scheme VIII. ¹ H NMR (300 MHz, Methanol-d ₄ ) 8.47 (s, 1H), 7.42 (m, 1H), 7.28-7.14 (m, 5H), 6.94-6.85 (m, 2H), 3.81 (t, J = 6.7, 2H), 3.02-2.84 (m, 4H), 2.32 (t, J = 7.6, 2H), 2.26 (s, 3H), 2.00 (m, 2H).

Example 105

4- {2- (5-Methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-phenyl) ethyl) phenyl) hydrazono) pyrazolyl} butanoic acid ( Compound 205)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, Methanol-d ₄ ) 7.54 (m, 1H), 7.28-7.12 (m, 5H), 6.92-6.84 (m, 2H), 3.79 (t, J = 6.8, 2H), 3.00- 2.84 (m, 4H), 2.34 (t, J = 7.4, 2H), 2.26 (s, 3H), 2.01 (m, 2H).

Example 106

4- {2- (5-methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (4-methyl) phenyl) ethyl) phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 206)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, Methanol-d ₄ ) 7.53 (m, 1H), 7.11-7.03 (m, 4H), 6.91-6.86 (m, 2H), 3.79 (t, J = 6.6, 2H), 2.93 ( m, 2H), 2.85 (m, 2H), 2.34 (t, J = 7.3, 2H), 2.28 (s, 3H), 2.26 (s, 3H), 2.01 (m, 2H).

Example 107

4- {2- (5-methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3-methyl) phenyl) ethyl) phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 207)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, Methanol-d ₄ ) 7.53 (m, 1H), 7.12 (m, 1H), 7.04-6.87 (m, 5H), 3.79 (t, J = 6.6, 2H), 2.98-2.82 ( m, 4H), 2.34 (t, J = 7.3, 2H), 2.29 (s, 3H), 2.26 (s, 3H), 2.01 (m, 2H).

Example 108

4- {2- (5-methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methyl) phenyl) ethyl) phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 208)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, Methanol-d ₄ ) 7.54 (m, 1H), 7.16-7.04 (m, 4H), 6.93-6.84 (m, 2H), 3.80 (t, J = 6.7, 2H), 2.90 ( m, 4H), 2.34 (t, J = 7.3, 2H), 2.28 (s, 3H), 2.26 (s, 3H), 2.01 (m, 2H).

Example 109

4- {2- (5-methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (1-naphthyl) ethyl) phenyl) hydrazono) pyrazolyl Butanoic Acid (Compound 209)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, Methanol-d ₄ ) 8.17 (d, J = 7.9, 1H), 7.86 (d, J = 7.9, 1H), 7.71 (d, J = 7.9, 1H), 7.57-7.43 (m , 3H), 7.36 (m, 1H), 7.31 (m, 1H), 6.91-6.86 (m, 2H), 3.80 (t, J = 6.6, 2H), 3.37 (dd, J = 9.2, 6.5, 2H) , 3.09 (dd, J = 9.2, 6.5, 2H), 2.35 (t, J = 7.3, 2H), 2.27 (s, 3H), 2.02 (m, 2H).

Example 110

3- {1- (5-Nitro-2-oxo-2,3-dihydro-3 (Z)-(2-hydroxy-3- (3,5-dimethylphenyl) phenyl) aminomethylidene) indolyl } Benzoic Acid (Compound 210)

This compound was prepared as described in Scheme III. ¹ H NMR (500 MHz, DMSO-d ₆ ) 13.28 (s, 1H), 11.26 (d, J = 13.4, 1H), 9.29 (d, J = 13.4, 1H), 9.26 (s, 1H), 8.82 ( d, J = 2.4, 1H), 8.06-8.03 (m, 2H), 8.02 (dd, J = 8.8, 2.4, 1H), 7.82 (ddd, J = 8.1, 2.1, 1.3, 1H), 7.79 (m, 1H), 7.75 (t, J = 8.1, 1H), 7.14 (m, 2H), 7.09 (t, J = 7.7, 1H), 7.06 (d, J = 8.8, 1H), 7.01 (dd, J = 7.7 , 1.5, 1H), 7.01 (m, 1H), 2.33 (s, 6H).

Example 111

3- {1- (5-Nitro-2-oxo-2,3-dihydro-3 (Z)-(5-fluoro-2-hydroxy-3- (3,5-dimethylphenyl) phenyl) amino Methylidene) indolyl} benzoic acid (Compound 211)

This compound was prepared as described in Scheme III. ¹ H NMR (300 MHz, Acetone-d ₆ ) 11.43 (d, J = 13.3, 1H), 9.15 (d, J = 13.3, 1H), 8.67 (d, J = 2.3, 1H), 8.24 (t, J = 1.7, 1H), 8.15 (m, 1H), 8.08 (dd, J = 8.8, 2.3, 1H), 7.88 (m, 1H), 7.78 (t, J = 7.8, 1H), 7.66 (dd, J = 10.0, 2.9, 1H), 7.14 (m, 2H), 7.14 (d, J = 8.8, 1H), 7.04 (m, 1H), 6.78 (dd, J = 9.2, 2.9, 1H), 2.34 (s, 6H ).

Example 112

2-hydroxy-3- {3 (Z)-(2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolene) methylamino} benzoic acid (Compound 212)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 11.02 (d, J = 12.8, 1H), 8.84 (d, J = 12.8, 1H), 7.96 (dd, J = 8.1, 1.5, 1H), 7.74 (m , 1H), 7.52 (dd, J = 8.1, 1.5, 1H), 7.10-7.06 (m, 5H), 7.04 (t, J = 8.1, 1H), 6.85 (m, 1H), 2.36 (s, 3H) , 2.36 (s, 3 H).

Example 113

2-hydroxy-3- {3 (Z)-(6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indoledene) methylamino} benzoic acid ( Compound 213)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 11.18 (d, J = 12.9, 1H), 9.07 (d, J = 12.9, 1H), 8.00 (dd, J = 8.0, 1.4, 1H), 7.93 (d , J = 7.8, 1H), 7.57 (dd, J = 8.0, 1.4, 1H), 7.44 (dq, J = 7.8, 0.9, 1H), 7.36 (d, J = 8.1, 1H), 7.28 (d, J = 2.1, 1H), 7.21 (dd, J = 8.1, 2.1, 1H), 7.06 (t, J = 8.0, 1H), 6.92 (m, 1H), 2.32 (s, 3H), 2.31 (s, 3H) .

Example 114

4- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (3-methyl-l (Z) -butenyl) phenyl) amino Methylidene) pyrazolyl} butanoic acid (Compound 214)

This compound was prepared as described in Scheme VIII. ¹ H NMR (300 MHz, Methanol-d ₄ ) 8.49 (s, 1H), 7.49 (d5 J = 7.6, 1H), 7.02-6.90 (m, 2H), 6.30 (d, J = 11.1, 1H), 5.65 (dd, J = 11.1, 10.3, 1H), 3.80 (t, J = 6.7, 2H), 2.66 (m, 1H), 2.31 (t, J = 7.5, 2H), 2.27 (s, 3H), 2.00 ( m, 2H), 1.01 (d, J = 6.7, 6H).

Example 115

4- {2- (5-Methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3-heptanylphenyl) hydrazono) pyrazolyl} butanoic acid (Compound 215)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, Methanol-d ₄ ) 7.53 (dd, J = 7.6, 1.5, 1H), 6.97 (dd, J = 7.6, 1.5, 1H), 6.91 (t, J = 7.6, 1H), 3.79 (t, J = 6.7, 2H), 2.65 (t, J = 7.7, 2H), 2.34 (t, J = 7.3, 2H), 2.26 (s, 3H), 2.01 (m, 2H), 1.60 (m, 2H), 1.42-1.27 (m, 8H), 0.90 (t, J = 6.8, 3H).

Example 116

4- {2- (5-methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3 (Z)-(2- (4-methyl) phenyl) ethenylphenyl) hydrazo No) pyrazolyl} butanoic acid (Compound 216)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, Methanol-d ₄ ) 7.60 (d, J = 7.9, 1H), 7.50-7.41 (m, 4H), 7.21-7.08 (m, 3H), 7.01 (t, J = 7.9, 1H ), 3.79 (t, J = 6.6, 2H), 2.34 (s, 3H), 2.34 (t, J = 7.3, 2H), 2.27 (s, 3H), 2.01 (m, 2H).

Example 117

4- {2- (5-methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3 (Z)-(2- (3-methyl) phenyl) ethenylphenyl) hydrazo No) pyrazolyl} butanoic acid (Compound 217)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, Methanol-d ₄ ) 7.59 (d, J = 7.8, 1H), 7.09-6.95 (m, 4H), 6.88 (d, J = 7.8, 1H), 6.79 (t, J = 7.8 , 1H), 6.73 (d, J = 12.2, 1H), 6.59 (d, J = 12.2, 1H), 3.79 (t, J = 6.7, 2H), 2.34 (t, J = 7.3, 2H), 2.27 ( s, 3H), 2.20 (s, 3H), 2.01 (m, 2H).

Example 118

4- {1- (2-Oxo-2,3-dihydro-3- (2-hydroxy-3- (2- (2-methyl) phenyl) ethylphenyl) hydrazono) indolyl} butanoic acid ( Compound 218)

This compound was prepared as described in Scheme VII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 13.04 (s, 1H), 9.13 (br s, 1H), 7.61 (dd, J = 7.7, 0.7, 1H), 7.51 (dd, J = 7.7, 1.6, 1H), 7.33 (td, J = 7.7, 1.2, 1H), 7.23 (m, 1H), 7.20 (d, J = 7.7, 1H), 7.16-7.07 (m, 4H), 6.91 (t, J = 7.7 , 1H), 6.83 (dd, J = 7.7, 1.5, 1H), 3.84 (t, J = 7.1, 2H), 2.89-2.79 (m, 4H), 2.32 (t, J = 7.1, 2H), 2.29 ( s, 3H), 1.88 (qn, J = 7.1, 2H).

Example 119

2- {1- (2-Oxo-2,3-dihydro-3- (2-hydroxy-3- (3,5-dimethylphenyl) phenyl) hydrazono) indolyl} acetic acid (Compound 219)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, Methanol-d ₄ ) 7.66 (dd, J = 7.7, 1.6, 1H), 7.65 (m, 1H), 7.27 (td, J = 7.7, 1.1, 1H), 7.14-7.10 (m , 3H), 7.01 (m, 1H), 6.99 (t, J = 7.7, 1H), 6.95 (d, J = 7.7, 1H), 6.89 (dd, J = 7.7, 1.6, 1H), 4.55 (s, 2H), 2.36 (s, 6H).

Example 120

2- {1- (2-Oxo-2,3-dihydro-3- (2-hydroxy-3- (2- (2-methyl) phenyl) ethylphenyl) hydrazono) indolyl} acetic acid (compound 220)

This compound was prepared as described in Scheme VII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 12.95 (s, 1H), 9.16 (s, 1H), 7.62 (dd, J = 7.6, 1.0, 1H), 7.53 (dd, J = 7.7, 1.6, 1H ), 7.30 (td, J = 7.6, 1.2, 1H), 7.23 (m, 1H), 7.16-7.07 (m, 5H), 6.91 (t, J = 7.7, 1H), 6.84 (dd, J = 7.7, 1.6, 1H), 4.59 (s, 2H), 2.89-2.79 (m, 4H), 2.29 (s, 3H).

Example 121

4- (4- (2- (3 (Z)-(6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) indolylidene) methylamino) Thiazolyl} benzoic acid (compound 221)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO-d ₆ ) 12.99 (s, 2H), 11.83 (d, J = 12.2, 1H), 11.39 (d, J = 12.2, 1H), 8.95 (d, J = 12.2, 1H ), 8.56 (d, J = 12.2, 1H), 8.32 (d, J = 7.8, 1H), 8.16 (d, J = 8.5, 2H), 8.08 (d, J = 8.5, 2H), 8.08 (m, 1H), 8.03 (d, J = 8.5, 2H), 8.02 (d, J = 8.5, 2H), 7.93 (s, 1H), 7.91 (s, 1H), 7.51 (d, J = 7.8, 1H), 7.44 (dq, J = 7.8, 0.9, 1H), 7.37 (d, J = 7.9, IH), 7.36 (d, J = 7.9, 1H), 7.30 (d, J = 2.1, 1H), 7.24 (d, J = 2.1, 1H), 7.23 (dd, J = 7.9, 2.1, 1H), 7.18 (dd, J = 7.9, 2.1, 1H), 6.91 (m, 1H), 6.85 (m, 1H), 2.32 (s , 3H), 2.31 (s, 3H), 2.31 (s, 3H), 2.30 (s, 3H).

Example 122

3- {1- (5-Nitro-2-oxo-2,3-dihydro-3 (Z)-(2-hydroxy-5-methyl-3- (1-adamantane) phenyl) aminomethylidene ) Indolyl} benzoic acid (Compound 222)

This compound was prepared as described in Scheme III. ¹ H NMR (500 MHz, DMSO-d ₆ ) 13.28 (s, 1H), 11.22 (d, J = 13.7, 1H), 9.19 (d, J = 13.7, 1H), 8.81 (d, J = 2.4, 1H ), 8.40 (s, 1H), 8.09-8.04 (m, 2H), 8.01 (dd, J = 8.8, 2.4, 1H), 7.83-7.73 (m, 2H), 7.50 (d, J = 1.5, 1H) , 7.07 (d, J = 8.8, 1H), 6.79 (d, J = 1.5, 1H), 2.33 (s, 3H), 2.09-2.06 (m, 6H), 2.05-2.02 (m, 3H), 1.75- 1.72 (m, 6 H).

Example 123

3- {1- (6-Trifluoromethyl-2-oxo-2,3-dihydro-3- (4-hydroxy-5- (3,4-dimethylphenyl) pyridinyl) hydrazono) indole Reyl} benzoic acid (Compound 223)

This compound was prepared as described in Scheme I. ¹ H NMR (500 MHz, Methanol-d ₄ ) 8.25 (s, 1H), 8.11 (dt, J = 7.7, 1.6, 1H), 8.07 (t, J = 1.6, 1H), 7.90 (d, J = 7.8 , 1H), 7.82 (m, 1H), 7.66 (t, J = 7.7, 1H), 7.62 (m, 1H), 7.48 (m, 1H), 7.42 (m, 1H), 7.34 (m, 1H), 7.17 (d, J = 7.8, 1 H), 7.08 (br s, 1 H), 2.30 (s, 3 H), 2.28 (s, 3 H).

Example 124

4- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-methyl) phenyl) -ethylphenyl) aminomethyl Liden) pyrazolyl} butanoic acid (Compound 224)

This compound was prepared as described in Scheme VIII. ¹ H NMR (300 MHz, Methanol-d ₄ ) 8.47 (s, 1H), 7.43 (m, 1H), 7.15-7.03 (m, 4H), 6.93-6.86 (m, 2H), 3.81 (t, J = 6.8, 2H), 2.90 (m, 4H), 2.32 (t, J = 7.4, 2H), 2.27 (s, 3H), 2.26 (s, 3H), 2.00 (m, 2H).

Example 125

4- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-fluoro) phenyl) -ethylphenyl) amino Methylidene) pyrazolyl} butanoic acid (Compound 225)

This compound was prepared as described in Scheme VIII. ¹ H NMR (300 MHz, Methanol-d ₄ ) 8.47 (s, 1H), 7.43 (m, 1H), 7.23-7.14 (m, 2H), 7.07-6.97 (m, 2H), 6.90-6.85 (m, 2H), 3.81 (t, J = 6.8, 2H), 2.96 (m, 4H), 2.32 (t, J = 7.3, 2H), 2.26 (s, 3H), 2.00 (m, 2H).

Example 126

4- {2- (5-methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (1-naphthyl) ethyl) phenyl) aminomethylidene ) Pyrazolyl} butanoic acid (Compound 226)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO) 8.48 (s, 1H), 8.17 (d, J = 8.6 Hz, 1H), 7.85 (d, J = 7.4 Hz, 1H), 7.71 (d, J = 7.4 Hz, 1H ), 7.55-7.28 (m, 5H), 6.91-6.88 (m, 2H), 3.82 (t, J = 6.7 Hz, 2H), 3.37 (dd, J = 9.3, 6.4 Hz, 2H), 3.10 (dd, J = 9.3, 6.4 Hz, 2H), 2.33 (t, J = 7.5 Hz, 2H), 2.27 (s, 3H), 2.01 (m, 2H).

Example 127

4- (2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (3,5-dimethylphenyl) -ethyl) phenyl) Aminomethylidene) pyrazolyl} butanoic acid (Compound 227)

This compound was prepared as described in Scheme VIII. ¹ H NMR (300 MHz, CD ₃ OD) 8.47 (br s, 1 H), 7.42 (m, 1 H), 6.94-6.88 (m, 2 H), 6.82-6.79 (m, 3H), 3.80 (t, J = 6.7 Hz, 2H), 2.92 (m, 2H), 2.79 (m, 2H), 2.32 (t, J = 7.5 Hz, 2H), 2.26 (s, 3H), 2.24 (s, 6H), 2.00 (m, 2H).

Example 128

4- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-methoxyphenyl) -ethyl) phenyl) amino Methylidene) pyrazolyl} butanoic acid (Compound 228)

This compound was prepared as described in Scheme VIII. ¹ H NMR (300 MHz, CD ₃ OD) 8.47 (s, 1H), 7.41 (m, IH), 7.24-7.04 (m, 3H), 6.94-6.78 (m, 4H), 3.82 (s, 3H), 3.81 (m. 2H), 2.89 (s, 4H), 2.36-2.24 (m, 5H), 2.01 (m, 2H).

Example 129

4- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-fluoro-3-methyl-phenyl) ethyl ) Phenyl) aminomethylidene) pyrazolyl} butanoic acid (Compound 229)

This compound was prepared as described in Scheme VIII. ¹ H NMR (300 MHz, CD ₃ OD) 7.47-7.30 (m, 1H), 7.07-6.85 (m, 6H), 3.82 (m, 2H), 2.98-2.88 (m, 4H), 2.30-2.20 (m , 8H), 2.00 (m, 2H).

Example 130

4- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-fluoro-3-methyl-phenyl) ethyl ) Phenyl) aminomethylidene) pyrazolyl} butanoic acid (Compound 230)

This compound was prepared as described in Scheme VIII. ¹ H NMR (300 MHz, CD ₃ OD) 8.45 (s, 1H), 7.64 (d, J = 7.6 Hz, 1H), 7.56-7.32 (m, 4H), 7.16 (m, 1H), 6.91 (s, 2H), 3.81 (t, J = 6.5 Hz, 2H), 3.12-2.93 (m, 4H), 2.29 (t, J = 7.4 Hz, 2H), 2.25 (m, 3H), 2.00 (m, 2H).

Example 131

4- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (4-phenylphenyl) -ethyl) phenyl) aminomethyl Liden) pyrazolyl} butanoic acid (Compound 231)

This compound was prepared as described in Scheme VIII. ¹ H NMR (300 MHz, CD ₃ OD) 7.59-7.56 (m, 3H), 7.51 (d, J = 7.8 Hz, 2H), 7.46-7.37 (m, 4H), 7.33-7.26 (m, 4H), 6.95-6.91 (m, 2H), 3.81 (t, J = 6.5 Hz, 2H), 3.04-2.92 (m, 4H), 2.32 (t, J = 7.7 Hz, 2H), 2.27 (s, 3H), 2.02 (m, 2 H).

Example 132

4- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-cyanophenyl) -ethyl) phenyl) amino Methylidene) pyrazolyl} butanoic acid (Compound 232)

This compound was prepared as described in Scheme VIII. ¹ H NMR (300 MHz, CD ₃ OD) 8.45 (s, 1H), 7.65 (d, J = 7.5 Hz, 1H), 7.55 (t, J = 7.5 Hz, 1H), 7.48-7.32 (m, 3H) , 6.92-6.81 (m, 2H), 3.80 (t, J = 6.7 Hz, 2H), 3.13 (m, 2H), 3.05 (m, 2H), 2.30 (m, 2H), 2.26 (s, 3H), 2.01 (m, 2 H).

Example 133

4- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-chlorophenyl) -ethyl) phenyl) aminomethyl Liden) pyrazolyl} butanoic acid (Compound 233)

This compound was prepared as described in Scheme VIII. ¹ H NMR (300 MHz, CD ₃ OD) 8.47 (s, 1H), 7.43 (m, 1H), 7.35 (m, 1H), 7.24-7.14 (m, 3H), 6.93-6.85 (m, 2H), 3.81 (t, J = 6.7 Hz, 2H), 3.08-2.94 (m, 4H), 2.32 (t, J = 7.5 Hz, 2H), 2.26 (s, 3H), 2.00 (m, 2H).

Example 134

4- (2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2,6-dimethylphenyl) -ethyl) phenyl) Aminomethylidene) pyrazolyl} butanoic acid (Compound 234)

This compound was prepared as described in Scheme VIII. ¹ H NMR (300 MHz, CD ₃ OD) 8.48 (s, 1 H), 7.45 (m, 1 H), 6.98-6.87 (m, 5 H), 3.81 (t, J = 6.9 Hz, 2H), 2.93 (m, 2H), 2.83 (m, 2H), 2.32 (t, J = 7.1 Hz, 2H), 2.29 (s, 6H), 2.27 (s, 3H), 2.00 (m, 2H).

Example 135

3- {2- (5-Trifluoromethyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-trifluoromethylphenyl) ethyl) Phenyl) aminomethylidene) pyrazolyl} benzoic acid

This compound was prepared as described in Scheme VIII. ¹ H NMR (300 MHz, DMSO) 8.81 (s, 1 H), 8.66 (dd, J = 2.2, 1.5 Hz, 1H), 8.24 (ddd, J = 8.2, 2.2, 1.1 Hz, 1H), 7.84 (ddd, .J = 7.7, 1.5, 1.1 Hz, 1H), 7.78 (dd, J = 8.0, 1.6 Hz, 1H), 7.70 (m, 1H), 7.66-7.59 (m, 3H), 7.44 (m, 1H), 7.03 (dd, J = 7.7, 1.6 Hz, 1H), 6.97 (dd, J = 8.0, 7.7 Hz, 1H), 3.05-2.93 (m, 4H).

Example 136

3- {2- (5-Trifluoromethyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-fluorophenyl) -ethyl) Phenyl) aminomethylidene) pyrazolyl} benzoic acid (Compound 236)

This compound was prepared as described in Scheme VIII. ¹ H NMR (300 MHz, DMSO) 9.84 (s, 1H), 8.79 (s, 1H), 8.65 (dd, J = 2.2, 1.6 Hz, 1H), 8.23 (ddd, J = 8.2, 2.2, 1.1 Hz, 1H), 7.84 (ddd, J = 7.8, 1.6, 1.1 Hz, 1H), 7.75 (m, lH), 7.62 (dd, J = 8.2, 7.8 Hz, 1H), 7.33 (m, 1H), 7.25 (m , 1H), 7.18-7.09 (m, 2H), 7.01 (dd, J = 7.8, 1.5 Hz, 1H), 6.93 (t, J = 7.8 Hz, 1H), 3.00-2.85 (m, 4H).

Example 137

3- {2- (5-trifluoromethyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-methyl-phenyl) ethyl) phenyl ) Aminomethylidene) pyrazolyl} benzoic acid (Compound 237)

This compound was prepared as described in Scheme VIII. ¹ H NMR (300 MHz, DMSO) 9.80 (s, 1H), 8.80 (m, 1H), 8.65 (dd, J = 2.2, 1.5 Hz, 1H), 8.23 (ddd, J = 8.2, 2.2, 1.1 Hz, 1H), 7.84 (ddd, J = 7.8, 1.5, 1.1 Hz, 1H), 7.77 (m, 1H), 7.63 (dd, J = 8.2, 7.8 Hz, 1H), 7.22 (m, 1H), 7.17-7.05 (m, 4H), 6.96 (t, J = 7.8 Hz, 1H), 2.90 (m, 2H), 2.82 (m, 2H), 2.29 (s, 3H).

Example 138

3- {2- (5-Trifluoromethyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2,5-dimethyl-phenyl) ethyl ) Phenyl) aminomethylidene) pyrazolyl} benzoic acid (Compound 238)

This compound was prepared as described in Scheme VIII. ¹ H NMR (300 MHz, CD ₃ OD) 8.65 (dd, J = 2.2, 1.6 Hz, 1H), 8.60 (s, 1H), 8.23 (ddd, J = 8.1, 2.2, 1.0 Hz, 1H), 7.92 ( ddd, J = 7.8, 1.6, 1.0 Hz, 1H), 7.56 (dd, J = 8.1, 7.8 Hz, 1H), 7.47 (m, 1H), 7.00-6.86 (m, 5H), 2.93 (m, 2H) , 2.85 (m, 2H), 2.25 (s, 3H), 2.24 (s, 3H).

Example 139

3- {2- (5-Trifluoromethyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2,6-dimethyl-phenyl) ethyl ) Phenyl) aminomethylidene) pyrazolyl} benzoic acid (Compound 239)

This compound was prepared as described in Scheme VIII. ¹ H NMR (300 MHz, CD ₃ OD) 8.66 (dd, J = 2.1, 1.6 Hz, 1H), 8.60 (s, 1H), 8.25 (ddd, J = 8.1, 2.1, 1.0 Hz, 1H), 7.92 ( ddd, J = 7.7, 1.6, 1.0 Hz, 1H), 7.57 (dd, J = 8.1, 7.7 Hz, 1H), 7.48 (m, 1H), 6.99-6.94 (m, 5H), 2.95 (m, 2H) , 2.85 (m, 2 H), 2.31 (s, 6 H).

Example 140

3- {2- (5-phenyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2,5-dimethylphenyl) -ethyl) phenyl) Aminomethylidene) pyrazolyl} benzoic acid (Compound 240)

This compound was prepared as described in Scheme VIII. ¹ H NMR (300 MHz, DMSO) 8.79 (dd, J = 2.1, 1.6 Hz, 1H), 8.69 (br s, 1 H), 8.36 (ddd, J = 8.2, 2.1, 1.1 Hz, 1H), 7.94-7.89 (m, 2H), 7.78 (ddd, J = 7.8, 1.6, 1.1 Hz, 1H), 7.67-7.51 (m, 5H), 7.08-7.00 (m, 3H), 6.96-6.88 (m, 2H), 2.87 (m, 2H), 2.77 (m, 2H), 2.25 (s, 6H).

Example 141

3- {2- (5-tert-butyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2,5-dimethylphenyl) -ethyl ) Phenyl) aminomethylidene) pyrazolyl} benzoic acid (Compound 241)

This compound was prepared as described in Scheme VIII. ¹ H NMR (300 MHz, CD ₃ OD) 8.65 (dd, J = 2.1, 1.7 Hz, 1H), 8.58 (s, 1H), 8.25 (m, 1H), 7.83 (m, 1H), 7.50 (t, J = 7.9 Hz, 1H), 7.36 (m, 1H), 6.99-6.84 (m, 5H), 2.95-2.80 (m, 4H), 2.24 (s, 3H), 2.23 (s, 3H), 1.47 (s , 9H).

Example 142

3- {2- (5-methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-methylphenyl> ethyl) phenyl) aminomethylidene) Pyrazolyl} Benzoic Acid (Compound 242)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500MHz, DMSO) 11.86 (d, J = 13.6 Hz, 1H), 9.50 (br s, 1H), 8.71 (d, J = 13.6 Hz, 1H), 8.66 (dd, J = 2.1, 1.6 Hz , 1H), 8.26 (ddd, J = 8.1, 2.1, 1.1 Hz, 1H), 7.71 (ddd, J = 7.7, 1.6, 1.1 Hz, 1H), 7.64 (dd, J = 8.0, 1.5 Hz, 1H), 7.53 (dd, J = 8.2, 7.7 Hz, 1H), 7.22 (m, 1H), 7.16-7.07 (m, 3H), 6.98 (dd, J = 7.6, 1.5 Hz, 1H), 6.94 (m, 1H) , 2.88 (m, 2H), 2.82 (m, 2H), 2.32 (s, 3H), 2.29 (s, 3H).

Example 143

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-fluorophenyl) -ethyl) phenyl) hydro Lazono) pyrazolyl} butanoic acid (Compound 243)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, CD ₃ OD) 7.53 (m, 1H), 7.23-7.15 (m, 2H), 7.07-6.97 (m, 2H), 6.91-6.83 (m, 2H), 3.79 (t, J = 6.6 Hz, 2H), 2.95 (s, 4H), 2.34 (t, J = 7.3 Hz, 2H), 2.26 (s, 3H), 2.01 (m, 2H).

Example 144

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dimethylphenyl) -ethyl) phenyl) hydrazono ) Pyrazolyl} butanoic acid (Compound 244)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, CD ₃ OD) 7.54 (m, 1H), 6.93-6.88 (m, 2H), 6.83-6.79 (m, 3H), 3.79 (t, J = 6.6 Hz, 2H), 2.92 ( m, 2H), 2.80 (m, 2H), 2.34 (t, J = 7.4 Hz, 2H), 2.26 (s, 3H), 2.25 (s, 6H), 2.01 (m, 2H).

Example 145

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (4-phenylphenyl) -ethyl) phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 245)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, CD ₃ OD) 7.61-7.49 (m, 5H), 7.41 (t, J = 7.4 Hz, 2H), 7.33-7.26 (m, 3H), 6.96-6.87 (m, 2H), 3.80 (t, J = 6.7 Hz, 2H), 3.02-2.94 (m, 4H), 2.33 (t, J = 7.4 Hz, 2H), 2.26 (s, 3H), 2.01 (m, 2H).

Example 146

4- (2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methoxyphenyl) -ethyl) phenyl) hydrazono) Pyrazolyl} butanoic acid (Compound 246)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, CD ₃ OD) 7.51 (m, 1H), 7.19-7.04 (m, 2H), 6.93-6.78 (m, 4H), 3.82 (s, 3H), 3.79 (t, J = 6.8 Hz, 2H), 2.88 (s, 4H), 2.34 (t, J = 7.5 Hz, 2H), 2.25 (s, 3H), 2.01 (m, 2H).

Example 147

4- {2- (5-Methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluoro-3-methylphenyl) -ethyl) phenyl) hydro Lazono) pyrazolyl} butanoic acid (Compound 247)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, CD ₃ OD) 7.52 (m, 1H), 7.22-6.83 (m, 5H), 3.79 (t, J = 6.7 Hz, 2H), 2.92 (s, 4H), 2.34 (t, J = 7.5 Hz, 2H), 2.26-2.22 (m, 6H), 2.01 (qn, J = 7.0 Hz, 2H).

Example 148

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-trifluoromethylphenyl) -ethyl) phenyl) hydrazono Pyrazolyl} Butanoic Acid (Compound 248)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, CD ₃ OD) 7.65 (d, J = 7.6 Hz, 1H), 7.58-7.47 (m, 2H), 7.44-7.32 (m, 2H), 6.96-6.86 (m, 2H), 3.79 (t, J = 6.6 Hz, 2H), 3.07 (m, 2H), 2.97 (m, 2H), 2.35 (t, J = 7.5 Hz, 2H), 2.26 (s, 3H), 2.01 (m, 2H ).

Example 149

4- (2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-cyanophenyl) ethyl) -phenyl) hydrazono) Pyrazolyl} butanoic acid (Compound 249)

This compound was prepared as described in Scheme VII. ¹ H NMR (300MHz, DMSO) 9.60 (s, 1H), 7.78 (d, J = 7.5 Hz, 1H), 7.64 (t, J = 7.5 Hz, 1H), 7.53-7.47 (m, 2H), 7.41 ( t, J = 7.5 Hz, 1H), 6.95-6.84 (m, 2H), 3.69 (t, J = 6.6 Hz, 2H), 3.05 (m, 2H), 2.99 (m, 2H), 2.26 (t, J = 7.0 Hz, 2H), 2.20 (s, 3H), 1.86 (m, 2H).

Example 150

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-chlorophenyl) ethyl) phenyl) hydrazono) pyrazolyl } Butanoic Acid (Compound 250)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, CD ₃ OD) 7.53 (m, 1H), 7.35 (m, 1H), 7.24-7.14 (m, 3H), 6.92-6.83 (m, 2H), 3.79 (t, J = 6.7 Hz, 2H), 3.08-2.92 (m, 4H), 2.34 (t, J = 7.3 Hz, 2H), 2.26 (s, 3H), 2.01 (m, 2H).

Example 151

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dimethylphenyl) -ethyl) phenyl) hydrazono ) Pyrazolyl} butanoic acid (Compound 251)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, CD ₃ OD) 7.54 (d, J = 7.6 Hz, 1H), 6.97-6.85 (m, 5H), 3.79 (t, J = 6.7 Hz, 2H), 2.93 (m, 2H) , 2.82 (m, 2H), 2.34 (t, J = 7.4 Hz, 2H), 2.30 (s, 6H), 2.26 (s, 3H), 2.01 (m, 2H).

Example 152

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-ethylphenyl) -ethyl) phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 252)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, CD ₃ OD) 7.54 (m, 1H), 7.19-7.06 (m, 4H), 6.93-6.86 (m, 2H), 3.79 (t, J = 6.7 Hz, 2H), 2.92 ( s, 4H), 2.66 (q, J = 7.5 Hz, 2H), 2.34 (t, J = 7.3 Hz, 2H), 2.26 (s, 3H), 2.01 (m, 2H), 1.19 (t, J = 7.5 Hz, 3H).

Example 153

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dichlorophenyl) -ethyl) phenyl) hydrazono ) Pyrazolyl} butanoic acid (Compound 253)

This compound was prepared as described in Scheme VII. ¹ H NMR (300MHz, DMSO) 13.60 (s, 1H), 12.07 (s, 1H), 9.43 (s, 1H), 7.50-7.43 (m, 3H), 7.27 (m, 1H), 6.91 (m, 1H ), 6.83 (m, 1H), 3.69 (t, J = 6.7 Hz, 2H), 3.15 (m, 2H), 2.89 (m, 2H), 2.25 (t, J = 7.6 Hz, 2H), 2.20 (s , 3H), 1.85 (m, 2H).

Example 154

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,5-dimethylphenyl) -ethyl) phenyl) hydrazono ) Pyrazolyl} Butanoic Acid (Compound 254)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, CD ₃ OD) 7.54 (m, 1H), 7.00-6.95 (m, 2H), 6.92-6.85 (m, 3H), 3.79 (t, J = 6.7 Hz, 2H), 2.93- 2.80 (m, 4H), 2.34 (t, J = 7.4 Hz, 2H), 2.26 (s, 3H), 2.24 (s, 3H), 2.22 (s, 3H), 2.01 (m, 2H).

Example 155

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluoro-6-trifluoro-methylphenyl) ethyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 255)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, CD ₃ OD) 7.56 (m, 1H), 7.52 (m, 1H), 7.47-7.31 (m, 2H), 6.96-6.87 (m, 2H), 3.80 (t, J = 6.7 Hz, 2H), 3.11 (m, 2H), 2.95 (m, 2H), 2.34 (t, J = 7.4 Hz, 2H), 2.26 (s, 3H), 2.01 (m, 2H).

Example 156

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indanyl) phenyl) -hydrazono) pyrazolyl} butanoic acid ( Compound 256)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, CD ₃ OD) 7.55 (dd, J = 7.9, 1.5 Hz, 1H), 7.24-7.20 (m, 2H), 7.16-7.12 (m, 2H), 7.06 (dd, J = 7.9 , 1.5 Hz, 1H), 6.92 (t, J = 7.9 Hz, 1H), 4.01 (m, 1H), 3.80 (t, J = 6.7 Hz, 2H), 3.35 (dd, J = 15.3, 8.2 Hz, 2H ), 3.02 (dd, J = 15.3, 7.6 Hz, 2H), 2.34 (t, J = 7.4 Hz, 2H), 2.26 (s, 3H), 2.01 (m, 2H).

Example 157

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indenyl) phenyl) -hydrazono) pyrazolyl} butanoic acid ( Compound 257)

This compound was prepared as described in Scheme VII. ¹ H NMR (500MHz, DMSO) 12.11 (br s, 1H), 9.53 (br s, 1H), 7.59 (m, 1H), 7.52-7.45 (m, 3H), 7.36 (m, 1H), 7.28 (m , 1H), 7.19 (m, 1H), 7.10 (m, 1H), 3.89 (s, 2H), 3.70 (t, J = 6.7 Hz, 2H), 2.26 (t, J = 7.2 Hz, 2H), 2.21 (s, 3 H), 1.87 (m, 2 H).

Example 158

(±) -4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (1-indanylmethyl) phenyl) -hydrazono) pyra Jolyl} butanoic acid (compound 258)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, CD ₃ OD) 7.58 (dd, J = 7.7, 1.1 Hz, 1H), 7.19 (m, 1H), 7.13-7.06 (m, 3H), 6.98-6.91 (m, 2H), 3.79 (t, J = 6.7 Hz, 2H), 3.51 (m, 1H), 3.19 (dd, J = 13.8, 6.1 Hz, 1H), 2.93 (m, 1H), 2.78 (m, 1H), 2.72 (dd , J = 13.8, 9.4 Hz, 1H), 2.34 (t, J = 7.3 Hz, 2H), 2.27 (s, 3H), 2.10 (m, 1H), 2.01 (m, 2H), 1.78 (m, 1H) .

Example 159

(±) -3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (1-indanylmethyl) phenyl) -hydrazono) pyra Zolyl} Benzoic Acid (Compound 259)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, CD ₃ OD) 8.58 (dd, J = 1.9, 1.5 Hz, 1H), 8.49 (s, 1H), 8.12 (m, 1H), 7.83 (ddd, J = 7.8, 1.5, 1.0 Hz, 1H), 7.62 (dd, J = 7.6, 1.7 Hz, 1H), 7.48 (t, J = 7.8 Hz, 1H), 7.19 (m, 1H), 7.15-7.07 (m, 3H), 7.00-6.93 (m, 2H), 3.53 (m, 1H), 3.21 (dd, J = 14.0, 5.8 Hz, 1H), 2.94 (m, 1H), 2.80 (m, 1H), 2.74 (dd, J = 14.0, 9.4 Hz, 1H), 2.38 (s, 3H), 2.12 (m, 1H), 1.80 (m, 1H).

Example 160

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methylphenyl) ethyl) -phenyl) hydrazono) pyrazolyl Benzoic Acid (Compound 260)

This compound was prepared as described in Scheme VII. ¹ H NMR (500MHz, DMSO) 13.78 (s, 1H), 9.64 (s, 1H), 8.56 (t, J = 1.6 Hz, 1H), 8.20 (m, 1H), 7.79 (m, 1H), 7.60 ( t, J = 7.9 Hz, 1H), 7.56 (m, 1H), 7.22 (m, 1H), 7.16-7.08 (m, 3H), 7.02 (d, J = 7.5 Hz, 1H), 6.97 (t, J = 7.5 Hz, 1H), 3.60 (m, 2H), 2.90 (m, 2H), 2.83 (m, 2H), 2.35 (s, 3H), 2.29 (s, 3H), 1.76 (m, 2H).

Example 161

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluoro-3-methylphenyl) -ethyl) phenyl) hydro Lazono) pyrazolyl} benzoic acid (Compound 261)

This compound was prepared as described in Scheme VII. ¹ H NMR (500 MHz, DMSO) 13.75 (br s, 1H), 13.15 (br s, 1H), 9.66 (br s, 1H), 8.55 (dd, J = 2.2, 1.6 Hz, 1H), 8.20 (ddd, J = 8.2, 2.2, 1.0 Hz, 1H), 7.79 (ddd, J = 7.8, 1.6, 1.0 Hz, 1H), 7.60 (dd, J = 8.2, 7.8 Hz, 1H), 7.55 (dd, J = 7.4, 2.2 Hz, 1H), 7.16-7.10 (m, 2H), 7.01 (t, J = 7.4 Hz, 1H), 6.99-6.93 (m, 2H), 2.94 (m, 2H), 2.88 (m, 2H), 2.34 (s, 3 H), 2.23 (d, J = 1.7 Hz, 3 H).

Example 162

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluorophenyl) -ethyl) phenyl) hydrazono) Pyrazolyl} benzoic acid (Compound 262)

This compound was prepared as described in Scheme VII. ¹ H NMR (500MHz, DMSO) 13.75 (s, 1H), 9.68 (s, 1H), 8.55 (t, J = 1.7 Hz, 1H), 8.20 (m, 1H), 7.78 (m, 1H), 7.59 ( t, J = 7.9 Hz, 1H), 7.55 (m, 1H), 7.33 (m, 1H), 7.25 (m, 1H), 7.17-7.11 (m, 2H), 6.97-6.92 (m, 2H), 2.95 (m, 2H), 2.90 (m, 2H), 2.34 (s, 3H).

Example 163

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dimethylphenyl) -ethyl) phenyl) hydrazono ) Prazolyl} Benzoic Acid (Compound 263)

This compound was prepared as described in Scheme VII. ¹ H NMR (500MHz, DMSO) 13.79 (s, 1H), 9.55 (s, 1H), 8.56 (t, J = 1.7 Hz, 1H), 8.20 (ddd, J = 7.9, 1.7, 1.1 Hz, 1H), 7.79 (ddd, J = 7.9, 1.7, 1.1 Hz, 1H), 7.60 (t, J = 7.9 Hz, 1H), 7.57 (dd, J = 7.8, 1.6 Hz, 1H), 7.05-6.98 (m, 5H) , 2.83 (m, 2H), 2.78 (m, 2H), 2.35 (s, 3H), 2.32 (s, 6H).

Example 164

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dichlorophenyl) -ethyl) phenyl) hydrazono ) Pyrazolyl} benzoic acid (Compound 264)

This compound was prepared as described in Scheme VII. ¹ H NMR (500MHz, DMSO) 9.59 (br s, 1H), 8.55 (s, 1H), 8.20 (d, J = 7.6 Hz, 1H), 7.78 (d, J = 7.6 Hz, 1H), 7.64-7.54 (m, 2H), 7.48-7.43 (m, 2H), 7.28 (dd, J = 8.4, 7.5 Hz, 1H), 7.00-6.86 (m, 2H), 3.17 (m, 2H), 2.93 (m, 2H ), 2.35 (s, 3 H).

Example 165

3- (2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methyl-6-trifluoromethylphenyl) ethyl) phenyl) Hydrazono) pyrazolyl} benzoic acid (Compound 265)

This compound was prepared as described in Scheme VII. ¹ H NMR (500MHz, DMSO) 9.58 (br s, 1H), 8.55 (s, 1H), 8.21 (d, J = 7.6 Hz, 1H), 7.79 (m, 1H), 7.64-7.50 (m, 5H) , 7.02-6.88 (m, 2H), 3.04 (m, 2H), 2.92 (m, 2H), 2.35 (s, 3H).

Example 166

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indanyl) phenyl) -hydrazono) pyrazolyl} benzoic acid (compound 266)

This compound was prepared as described in Scheme VII. ¹ H NMR (500 MHz, DMSO) 13.78 (br s, 1 H), 9.67 (br s, 1 H), 8.56 (s, 1 H), 8.20 (d, J = 7.9 Hz, 1 H), 7.78 (m, 1 H), 7.60 (t, J = 7.9 Hz, 1H), 7.56 (d, J = 7.7 Hz, 1H), 7.28-7.12 (m, 5H), 6.98 (t, J = 7.6 Hz, 1H), 4.03 (m, 1H ), 3.29 (dd, J = 15.6, 7.9 Hz, 2H), 2.98 (dd, J = 15.6, 8.1 Hz, 2H), 2.35 (s, 3H).

Example 167

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indenyl) phenyl) -hydrazono) pyrazolyl} benzoic acid (compound 267)

This compound was prepared as described in Scheme VII. ¹ H NMR (500MHz, DMSO) 8.57 (s, 1H), 8.21 (d, J = 8.0 Hz, 1H), 7.79 (m, 1H), 7.65 (d, J = 8.0 Hz, 1H), 7.60 (t, J = 8.0 Hz, 1H), 7.53-7.50 (m, 2H), 7.47 (m, 1H), 7.41 (m, 1H), 7.29 (t, J = 7.4 Hz, 1H), 7.20 (t, J = 7.4 Hz, 1H), 7.13 (t, J = 7.6 Hz, 1H), 3.91 (s, 2H), 2.36 (s, 3H).

Example 168

(E) -4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,4-difluorophenyl)-) Tenyl) phenyl) aminomethylidene) pyrazolyl} butanoic acid (Compound 268)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, CD ₃ OD) 8.48 (br s, 1 H), 7.78 (m, 1 H), 7.57-7.43 (m, 3 H), 7.25 (d, J = 15.8 Hz, 1 H), 7.03-6.95 (m, 3H), 3.81 (t, J = 6.5 Hz, 2H), 2.27 (t, J = 7.7 Hz, 2H), 2.26 (s, 3H), 2.00 (m, 2H).

Example 169

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-4- (3,4-dimethylphenyl) -2-pyridyl) hydrazono) pyra Zolyl} Benzoic Acid (Compound 269)

This compound was prepared as described in Scheme VII. ¹ H NMR (500 MHz, CD ₃ OD) 8.62 (m, 1H), 8.21 (m, 1H), 8.03 (m, 1H), 7.93-7.87 (m, 2H), 7.61 (m, 1H), 7.58- 7.53 (m, 2H), 7.37 (m, 1H), 2.42 (s, 3H), 2.38 (s, 3H), 2.37 (s, 3H).

Example 170

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-6-methyl-4- (3,4-dimethylphenyl) -2-pyridyl) hydro Lazono) pyrazolyl} butanoic acid (Compound 270)

This compound was prepared as described in Scheme VII. ¹ H NMR (500 MHz, CD ₃ OD) 7.66 (s, 1H), 7.55 (s, 1H), 7.49 (d, J = 7.1 Hz, 1H), 7.33 (d, J = 7.1 Hz, 1H), 3.79 (t, J = 6.6 Hz, 2H), 2.62 (s, 3H), 2.37 (s, 3H), 2.35 (s, 3H), 2.35 (m, 2H), 2.28 (s, 3H), 2.01 (m, 2H).

Example 171

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-2- (3,4-dimethylphenyl) -4-pyridyl) hydrazono) pyra Zolyl} Benzoic Acid (Compound 271)

This compound was prepared as described in Scheme VII. ¹ H NMR (500 MHz, CD ₃ OD) 8.62 (s, 1H), 8.23-8.12 (m, 2H), 7.97 (m, 1H), 7.89 (m, 1H), 7.60- 7.51 (m, 3H), 7.41 (m, 1 H), 2.42 (s, 3 H), 2.39 (s, 3 H), 2.39 (s, 3 H).

Example 172

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-2- (3,5-dimethylphenyl) -4-pyridyl) hydrazono) pyra Zolyl} Benzoic Acid (Compound 272)

This compound was prepared as described in Scheme VII. ¹ H NMR (500 MHz, CD ₃ OD) 8.52 (t, J = 1.6 Hz, 1H), 8.17 (d, J = 6.3 Hz, 1H), 8.14 (m, 1H), 7.87 (d, J = 6.3 Hz , 1H), 7.81 (d, J = 7.8 Hz, 1H), 7.49 (t, J = 7.8 Hz, 1H), 7.37 (s, 2H), 7.31 (s, 1H), 2.44 (s, 6H), 2.38 (s, 3 H).

Example 173

3- {1- (6-Trifluoromethyl-2-oxo-2,3-dihydro-3- (2-hydroxy-3- (2- (2-methylphenyl) -ethyl) phenyl) hydrazono ) Indolyl} benzoic acid (Compound 273)

This compound was prepared as described in Scheme VII. ¹ H NMR (500MHz, DMSO) 13.20 (s, 1H), 9.34 (s, 1H), 8.11 (dd, J = 2.0, 1.6 Hz, 1H), 8.08 (ddd, J = 7.8, 1.6, 1.2 Hz, 1H ), 7.92 (d, J = 8.0 Hz, 1H), 7.86 (ddd, J = 7.8, 2.0, 1.2 Hz, 1H), 7.77 (t, J = 7.8 Hz, 1H), 7.62 (dd, J = 7.8, 1.7 Hz, 1H), 7.55 (dq, J = 8.0, 0.6 Hz, 1H), 7.22 (m, 1H), 7.15-7.07 (m, 3H), 7.06 (m, 1H), 6.95 (t, J = 7.8 Hz, 1H), 6.91 (dd, J = 7.8, 1.7 Hz, 1H), 2.88 (m, 2H), 2.82 (m, 2H), 2.28 (s, 3H).

Example 174

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3-benzylphenyl) hydrazono) -pyrazolyl} butanoic acid (Compound 274)

This compound was prepared as described in Scheme VII. ¹ H NMR (500 MHz, DMSO) 7.49 (d, J = 7.7 Hz, 1H), 7.30-7.26 (m, 2H), 7.23-7.16 (m, 3H), 6.92 (t, J = 7.7 Hz, IH), 6.86 (dd, J = 7.7, 1.4 Hz, 1H), 4.02 (s, 2H), 3.69 (t, J = 6.7 Hz, 2H), 2.24 (t, J = 7.2 Hz, 2H), 2.19 (s, 3H ), 1.85 (m, 2 H).

Example 175

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3- (3-methylphenyl) propyl) -phenyl) hydrazono) pyrazolyl Butanoic Acid (Compound 275)

This compound was prepared as described in Scheme VII. ¹ H NMR (500MHz, DMSO) 9.43 (s, 1H), 7.47 (d, J = 7.4 Hz, 1H), 7.16 (t, J = 7.4 Hz, 1H), 7.03-6.90 (m, 5H), 3.69 ( t, J = 6.8 Hz, 2H), 2.67 (t, J = 7.7 Hz, 2H), 2.58 (m, 2H), 2.27 (s, 3H), 2.25 (t, J = 7.3 Hz, 2H), 2.19 ( s, 3H), 1.85 (m, 4H).

Example 176

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3-phenylpropyl) -phenyl) hydrazono) pyrazolyl} butanoic acid ( Compound 276)

This compound was prepared as described in Scheme VII. ¹ H NMR (500MHz, DMSO) 9.44 (s, 1H), 7.47 (d, J = 7.4 Hz, 1H), 7.28 (t, J = 7.4 Hz, 2H), 7.21 (m, 2H), 7.17 (tt, J = 7.4, 1.4 Hz, 1H), 6.96 (dd, J = 7.4, 1.6 Hz, 1H), 6.92 (t, J = 7.4 Hz, 1H), 3.69 (t, J = 6.8 Hz, 2H), 2.68 ( t, J = 7.7 Hz, 2H), 2.62 (m, 2H), 2.25 (t, J = 7.2 Hz, 2H), 2.19 (s, 3H), 1.86 (t, J = 7.4 Hz, 4H).

Example 177

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3- (2-methylphenyl) propyl) -phenyl) hydrazono) pyrazolyl Butanoic Acid (Compound 277)

This compound was prepared as described in Scheme VII. ¹ H NMR (500MHz, DMSO) 13.59 (s, 1H), 12.09 (s, 1H), 9.45 (s, 1H), 7.48 (dd, J = 7.8, 1.2 Hz, 1H), 7.15-7.04 (m, 4H ), 6.98 (dd, J = 7.8, 1.2 Hz, 1H), 6.93 (t, J = 7.8 Hz, 1H), 3.69 (t, J = 6.7 Hz, 2H), 2.72 (t, J = 7.7 Hz, 2H ), 2.60 (t, J = 8.1 Hz, 2H), 2.25 (t, J = 7.3 Hz, 2H), 2.23 (s, 3H), 2.19 (s, 3H), 1.86 (m, 2H), 1.78 (m , 2H).

Example 178

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,4-difluorophenyl) -ethyl) phenyl) hydro Lazono) pyrazolyl} butanoic acid (Compound 278)

This compound was prepared as described in Scheme VII. ¹ H NMR (300MHz, DMSO) 7.48 (m, 1H), 7.34 (td, J = 8.5, 6.9 Hz, 1H), 7.16 (ddd, J = 10.2, 9.5, 2.4 Hz, 1H), 7.01 (tdd, J = 8.5, 2.4, 0.8 Hz, 1H), 6.94-6.84 (m, 2H), 3.69 (t, J = 6.7 Hz, 2H), 2.95-2.80 (m, 4H), 2.25 (t, J = 7.2 Hz, 2H), 2.19 (s, 3H), 1.86 (m, 2H).

Example 179

(E) -4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-pyridyl) ethyl) -phenyl) hydro Lazono) pyrazolyl} butanoic acid (Compound 279)

This compound was prepared as described in Scheme VII. ¹ H NMR (500 MHz, CD ₃ OD) 8.56 (br s, 1 H), 8.19 (br s, 1 H), 7.77 (m, 1 H), 7.55 (dd, J = 7.8, 1.5 Hz, 1 H), 7.38- 7.28 (m, 2H), 6.98 (dd, J = 7.8, 1.5 Hz, 1H), 6.89 (t, J = 7.8 Hz, 1H), 3.80 (t, J = 6.7 Hz, 2H), 3.17 (m, 2H ), 3.08 (m, 2H), 2.35 (m, 2H), 2.26 (s, 3H), 2.01 (m, 2H).

Example 180

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z)-(2-hydroxy-3- (2- (2,6-dimethylphenyl)-(Z)- Ethenyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 280)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, CD ₃ OD) 7.48 (d, J = 7.0 Hz, 1H), 7.09-6.95 (m, 3H), 6.88 (d, J = 12.1 Hz, 1H), 6.70 (d, J = 12.1 Hz, 1H), 6.55 (t, J = 7.8 Hz, 1H), 6.44 (d, J = 7.8 Hz, 1H), 3.79 (t, J = 6.7 Hz, 2H), 2.34 (t, J = 7.5 Hz , 2H), 2.24 (s, 3H), 2.13 (s, 6H), 2.01 (m, 2H).

Example 181

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-benzofuranyl) phenyl) -hydrazono) pyrazolyl} butanoic acid (Compound 281)

This compound was prepared as described in Scheme VII. ¹ H NMR (500MHz, DMSO) 7.71 (d, J = 7.4 Hz, 1H), 7.69-7.62 (m, 3H), 7.48 (s, 1H), 7.34 (t, J = 7.4 Hz, 1H), 7.27 ( t, J = 7.4 Hz, 1H), 7.17 (m, 1H), 3.71 (t, J = 6.6 Hz, 2H), 2.26 (t, J = 7.1 Hz, 2H), 2.22 (s, 3H), 1.87 ( m, 2H).

Example 182

(Z) -4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-bromoethenyl) phenyl) -hydrazono) pyra Jolyl} butanoic acid (compound 282)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, CD ₃ OD) 7.71-7.59 (m, 2H), 7.48 (d, J = 7.9 Hz, 1H), 7.41 (d, J = 13.8 Hz, 1H), 7.25-7.19 (m, 2H), 7.09-6.95 (m, 3H), 6.71 (d, J = 7.9 Hz, 1H), 3.79 (t, J = 6.6 Hz, 4H), 2.34 (t, J = 7.3 Hz, 4H), 2.26 ( s, 6H), 2.01 (m, 4H).

Example 183

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z)-(2-hydroxy-3- (3-methyl-1-butenyl) phenyl) -hydrazono ) Pyrazolyl} butanoic acid (Compound 283)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, CD ₃ OD) 7.60 (dd, J = 7.3, 1.6 Hz, 1H), 7.00-6.90 (m, 2H), 6.30 (d, J = 11.3 Hz, 1H), 5.65 (dd, J = 11.3, 10.4 Hz, 1H), 3.79 (t, J = 6.6 Hz, 2H), 2.68 (m, 1H), 2.34 (t, J = 7.3 Hz, 2H), 2.26 (s, 3H), 2.01 ( m, 2H), 1.01 (d, J = 6.6 Hz, 6H).

Example 184

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z)-(2-hydroxy-3- (2-cyclopropylethenyl) -phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 284)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, CD ₃ OD) 7.59 (d, J = 7.8 Hz, 1H), 7.22 (d, J = 7.8 Hz, 1H), 6.95 (t, J = 7.8 Hz, 1H), 6.33 (d , J = 11.0 Hz, 1H), 5.21 (t, J = 11.0 Hz, 1H), 3.79 (t, J = 6.6 Hz, 2H), 2.33 (t, J = 7.4 Hz, 2H), 2.26 (s, 3H ), 2.01 (m, 2H), 1.71 (m, 1H), 0.81 (m, 2H), 0.48 (m, 2H).

Example 185

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3-methylbutyl) phenyl) -hydrazono) pyrazolyl} butanoic acid ( Compound 285)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, CD ₃ OD) 7.51 (d, J = 7.6 Hz, 1H), 6.96 (d, J = 7.6 Hz, 1H), 6.91 (t, J = 7.6 Hz, 1H), 3.78 (t , J = 6.6 Hz, 2H), 2.66 (t, J = 7.9 Hz, 2H), 2.32 (t, J = 7.4 Hz, 2H), 2.25 (s, 3H), 2.01 (m, 2H), 1.62 (m , 1H), 1.49 (m, 2H), 0.97 (d, J = 6.6 Hz, 6H).

Example 186

4- (2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-5-fluoro-3- (3,5-dimethylphenyl) phenyl) hydrazono) Pyrazolyl} butanoic acid (Compound 286)

This compound was prepared as described in Scheme I. ¹ H NMR (300 MHz, CD ₃ OD) 7.38 (dd, J = 9.4, 3.1 Hz, 1H), 7.13 (s, 2H), 7.04 (s, 1H), 6.78 (dd, J = 9.2, 3.1 Hz, 1H), 3.78 (t, J = 6.1 Hz, 2H), 2.36 (s, 6H), 2.33 (t, J = 7.3 Hz, 2H), 2.27 (s, 3H), 2.00 (m, 2H).

Example 187

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3,4-dimethylphenyl) phenyl) -hydrazono) pyrazolyl} part Carbonic Acid (Compound 287)

This compound was prepared as described in Scheme I. ¹ H NMR (300 MHz, CD ₃ OD) 7.66 (m, 1H), 7.28 (s, 1H), 7.23-7.20 (m, 2H), 7.08-6.99 (m, 2H), 3.78 (t, J = 6.7 Hz, 2H), 2.33 (m, 2H), 2.32 (s, 3H), 2.31 (s, 3H), 2.27 (s, 3H), 2.00 (m, 2H).

Example 188

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (5-chloro-2-hydroxy-3-cyclohexylphenyl) -hydrazono) pyrazolyl} butanoic acid ( Compound 288)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, CD ₃ OD) 7.47 (d, J = 2.0 Hz, 1H), 6.96 (d, J = 2.0 Hz, 1H), 3.78 (t, J = 6.8 Hz, 2H), 2.93 (m , 1H), 2.34 (t, J = 7.1 Hz, 2H), 2.26 (s, 3H), 2.00 (m, 2H), 1.91-1.72 (m, 5H), 1.58-1.27 (m, 5H).

Example 189

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3,5-dimethylphenyl) phenyl) -hydrazono) pyrazolyl} part Carbonic Acid (Compound 289)

This compound was prepared as described in Scheme I. ¹ H NMR (500 MHz, Acetone-d ₆ ) 10.58 (br s, 1H), 8.28 (br s, 1H), 7.70 (dd, J = 7.6, 1.9 Hz, 1H), 7.11 (m, 2H), 7.08 (t, J = 7.6 Hz, 1H), 7.04 (dd, J = 7.6, 1.9 Hz, 1H), 7.03 (m, 1H), 3.78 (t, J = 7.0 Hz, 2H), 2.38 (t, J = 7.4 Hz, 2H), 2.34 (m, 6H), 2.23 (s, 3H), 2.00 (m, 2H).

Example 190

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3,5-dimethylphenyl) phenyl) -hydrazono) pyrazolyl} benzoic acid (Compound 290)

This compound was prepared as described in Scheme I. ¹ H NMR (500MHz, DMSO) 13.75 (s, 1H), 9.56 (s, 1H), 8.56 (t, J = 1.8 Hz, 1H), 8.19 (ddd, J = 8.0, 1.8, 1.0 Hz, 1H), 7.78 (ddd, J = 8.O, 1.8, 1.0 Hz, 1H), 7.68 (dd, J = 5.5, 4.1 Hz, 1H), 7.59 (t, J = 8.0 Hz, 1H), 7.17 (m, 2H) , 7.11 (d, J = 4.1 Hz, 1H), 7.11 (d, J = 5.5 Hz, 1H), 7.03 (s, 1H), 2.36 (s, 3H), 2.34 (s, 6H).

Example 191

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (5-chloro-2-hydroxy-3-cyclohexylphenyl) -hydrazono) pyrazolyl} butanoic acid ( Compound 291)

This compound was prepared as described in Scheme VII. ¹ H NMR (300MHz, DMSO) 8.53 (m, 1H), 8.19 (d, J = 7.7 Hz, 1H), 7.79 (d, J = 1.1 Hz, 1H), 7.59 (t, J = 7.7 Hz, 1H) , 7.48 (d, J = 2.2 Hz, 1H), 7.04 (d, J = 2.2 Hz, 1H), 2.97 (m, 1H), 2.35 (s, 3H), 1.84-1.67 (m, 6H), 1.46- 1.20 (m, 4 H).

Example 192

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3,4-dimethylphenyl) phenyl) -hydrazono) pyrazolyl} benzoic acid (Compound 292)

This compound was prepared as described in Scheme I. ¹ H NMR (300 MHz, CD ₃ OD) 8.60 (s, 1H), 8.17 (d, J = 7.8 Hz, 1H), 7.84 (d, J = 7.8 Hz, 1H), 7.71 (m, 1H), 7.50 (t, J = 7.8 Hz, 1H), 7.30 (m, 1H), 7.25-7.22 (m, 2H), 7.10-7.02 (m, 2H), 2.39 (s, 3H), 2.33 (s, 3H), 2.32 (s, 3 H).

Example 193

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3- (2-methylphenyl) propyl) -phenyl) hydrazono) pyrazolyl Butanoic Acid (Compound 293)

This compound was prepared as described in Scheme VII. ¹ H NMR (300MHz, DMSO) 13.75 (s, 1H), 9.61 (s, 1H), 8.55 (t, J = 1.6 Hz, 1H), 8.20 (dd, J = 7.9, 1.2 Hz, 1H), 7.78 ( d, J = 7.9 Hz, 1H), 7.59 (t, J = 7.9 Hz, 1H), 7.55 (dd, J = 7.9, 1.2 Hz, 1H), 7.16-7.03 (m, 5H), 6.97 (t, J = 7.9 Hz, 1H), 2.75 (t, J = 7.8 Hz, 2H), 2.62 (t, J = 7.8 Hz, 2H), 2.34 (s, 3H), 2.23 (s, 3H), 1.80 (m, 2H ).

Example 194

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-benzofuranyl) phenyl) -hydrazono) pyrazolyl} benzoic acid ( Compound 294)

This compound was prepared as described in Scheme VII. ¹ H NMR (500MHz, DMSO) 8.57 (t, J = 1.7 Hz, 1H), 8.20 (m, 1H), 7.80 (m, 1H), 7.75 (m, 1H), 7.73 (m, 1H), 7.70 ( dd, J = 7.9, 1.3 Hz, 1H), 7.65 (d, J = 1.9 Hz, 1H), 7.61 (t, J = 7.9 Hz, 1H), 7.49 (m, 1H), 7.36 (td, J = 7.5 , 1.2 Hz, 1H), 7.29 (td, J = 7.5, 0.8 Hz, 1H), 7.24 (t, J = 7.9 Hz, 1H), 2.36 (s, 3H).

Example 195

4- (2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3- (2-fluorophenyl) propyl) -phenyl) hydrazono) Pyrazolyl} butanoic acid (Compound 295)

This compound was prepared as described in Scheme VII. ¹ H NMR (300MHz, DMSO) 13.74 (s, 1H), 9.61 (s, 1H), 8.55 (t, J = 1.6 Hz, 1H), 8.20 (m, 1H), 7.78 (m, 1H), 7.59 ( t, J = 7.9 Hz, 1H), 7.54 (m, 1H), 7.31 (m, 1H), 7.24 (m, 1H), 7.16- 7.11 (m, 2H), 7.02 (m, 1H), 6.97 (t , J = 7.7 Hz, 1H), 2.72 (t, J = 7.7 Hz, 2H), 2.67 (t, J = 7.7 Hz, 2H), 2.34 (s, 3H), 1.85 (m, 2H).

Example 196

3- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (3,4-dimethylphenyl) -phenyl) aminomethylidene) pyra Zolyl} Benzoic Acid (Compound 296)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500MHz, DMSO) 11.77 (m, 1H), 9.37 (s, 1H), 8.73 (m, 1H), 8.64 (m, 1H), 8.25 (ddd, J = 8.1, 2.2, 1.0 Hz, 1H ), 7.76 (m, 1H), 7.70 (ddd, J = 7.7, 1.6, 1.0 Hz, 1H), 7.52 (dd, J = 8.1, 7.7 Hz, 1H), 7.34 (m, 1H), 7.26 (dd, J = 7.8, 1.7 Hz, 1H), 7.23 (d, J = 7.8 Hz, 1H), 7.10-7.05 (m, 2H), 2.33 (s, 3H), 2.29 (s, 3H), 2.27 (s, 3H ).

Example 197

3- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (3,5-dimethylphenyl) -phenyl) aminomethylidene) Pyrazolyl} Benzoic Acid (Compound 297)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500MHz, DMSO) 11.78 (s, 1H), 8.74 (br s, 1H), 8.65 (m, 1H), 8.24 (m, 1H), 7.76 (m, 1H), 7.70 (m, 1H) , 7.52 (t, J = 7.9 Hz, IH), 7.16 (s, 2H), 7.10-7.05 (m, 2H), 7.01 (s, 1H), 2.33 (s, 9H).

Example 198

4- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (3,4-dimethylphenyl) -phenyl) aminomethylidene) pyra Jolyl} butanoic acid (Compound 298)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500MHz, DMSO) 8.53 (s, 1H), 7.64 (m, 1H), 7.33 (d, J = 1.6 Hz, 1H), 7.25 (dd, J = 7.7, 1.6 Hz, 1H), 7.21 ( d, J = 7.7 Hz, 1H), 7.02-6.97 (m, 2H), 3.64 (t, J = 6.7 Hz, 2H), 2.27 (s, 3H), 2.26 (s, 3H), 2.19 (t, J = 7.4 Hz, 2H), 2.18 (s, 3H), 1.82 (m, 2H).

Example 199

3- {1- (2-Oxo-2,3-dihydro-3- (2-hydroxy-3- (3,5-dimethylphenyl) -phenyl) hydrazono) indolyl} propionic acid (Compound 299)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, CD ₃ OD) 7.63 (dd, J = 7.7, 1.6 Hz, 1H), 7.61 (m, 1H), 7.27 (td, J = 7.7, 1.2 Hz, 1H), 7.12-7.08 ( m, 4H), 7.00 (m, 1H), 6.98 (t, J = 7.7 Hz, 1H), 6.88 (dd, J = 7.7, 1.6 Hz, 1H), 4.10 (t, J = 7.2 Hz, 2H), 2.71 (t, J = 7.2 Hz, 2H), 2.36 (s, 6H).

Example 200

3- {1- (2-Oxo-2,3-dihydro-3- (2-hydroxy-3-benzylphenyl) hydrazono) -indolyl} benzoic acid (Compound 300)

This compound was prepared as described in Scheme VII. ¹ H NMR (500 MHz, DMSO) 13.01 (s, 1 H), 9.37 (br s, 1 H), 8.07 (dd, J = 2.0, 1.7 Hz, 1H), 8.05 (ddd, J = 7.8, 1.7, 1.2 Hz, 1H), 7.82 (ddd, J = 7.8, 2.0, 1.2 Hz, 1H), 7.74 (t, J = 7.8 Hz, 1H), 7.72 (dd, J = 7.5, 1.0 Hz, 1H), 7.57 (dd, J = 8.1, 1.5 Hz, 1H), 7.29 (td, J = 7.5, 1.0 Hz, 1H), 7.28 (t, J = 7.1 Hz, 2H), 7.23 (m, 2H), 7.20 (td, J = 7.5, 1.0 Hz, 1H), 7.18 (tt, J = 7.1, 1.5 Hz, 1H), 6.94-6.90 (m, 2H), 6.75 (dd, J = 7.7, 1.5 Hz, 1H), 4.02 (s, 2H).

Example 201

3- {1- (2-Oxo-2,3-dihydro-3- (2-hydroxy-3- (2- (2-methylphenyl) ethyl) phenyl) -hydrazono) indolyl} propionic acid (compound 301)

This compound was prepared as described in Scheme VII. ¹ H NMR (500 MHz, CD ₃ OD) 7.61 (d, J = 7.6 Hz, 1H), 7.49 (dd, J = 8.O3 1.4 Hz, 1H), 7.29 (td, J = 7.6, 0.9 Hz, 1H ), 7.17-7.03 (m, 6H), 6.86 (dd, J = 8.0, 7.5 Hz, 1H), 6.73 (dd, J = 7.5, 1.4 Hz, 1H), 4.13 (t, J = 7.3 Hz, 2H) , 2.90 (s, 4H), 2.71 (t, J = 7.3 Hz, 2H), 2.30 (s, 3H).

Example 202

3- {1- (6-Chloro-2-oxo-2,3-dihydro-3 (Z)-(2-hydroxy-3- (3- (3-methylphenyl) propyl) -phenyl) aminomethylidene ) Indolyl} benzoic acid (Compound 302)

This compound was prepared as described in Scheme VIII. ¹ H NMR (50OMHz, DMSO) 11.13 (d, J = 13.4 Hz, 1H), 9.17 (br s, 1H), 8.89 (d, J = 13.4 Hz, 1H), 8.03-8.00 (m, 2H), 7.79 (m, 1H), 7.78 (d, J = 8.1 Hz, 1H), 7.72 (t, J = 7.9 Hz, 1H), 7.55 (dd, J = 7.9, 1.5 Hz, 1H), 7.15 (t, J = 7.5 Hz, 1H), 7.14 (dd, J = 8.1, 2.0 Hz, 1H), 7.02-6.96 (m, 3H), 6.93 (t, J = 7.9 Hz, 1H), 6.88 (dd, J = 7.9, 1.5 Hz, 1H), 6.86 (d, J = 2.0 Hz, 1H), 2.67 (t, J = 7.7 Hz, 2H), 2.58 (m, 2H), 2.27 (s, 3H), 1.83 (m, 2H).

Example 203

(±) -3- {1- (6-chloro-2-oxo-2,3-dihydro-3 (Z)-(2-hydroxy-3- (1,2-dihydro-1-methyl- 2-indolylphenyl) aminomethylidene) indolyl} benzoic acid (Compound 303)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, DMSO) 11.14 (d, J = 13.2 Hz, 1 H), 9.78 (br s, 1 H), 8.94 (d, J = 13.2 Hz, 1 H), 8.03-7.99 (m, 2H), 7.79 (m, 1H), 7.79 (d, J = 8.1 Hz, 1H), 7.72 (t, J = 7.7 Hz, 1H), 7.67 (dd, J = 8.1, 1.2 Hz, 1H), 7.16 (dd, J = 8.1, 2.0 Hz, 1H), 7.14-7.08 (m, 3H), 7.03 (t, J = 7.8 Hz, 1H), 6.87 (d, J = 2.0 Hz, 1H), 6.76-6.70 (m, 2H), 4.65 (dd, J = 11.2, 8.7 Hz, 1H), 3.41 (dd, J = 15.6, 8.7 Hz, 1H), 2.72 (dd, J = 15.6, 11.2 Hz, 1H), 2.62 (s, 3H).

Example 204

4- {2- (5-Methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3- (2-methylphenylcarbonyl-amino) phenyl) hydrazono) pyrazolyl} part Carbonic Acid (Compound 304)

This compound was prepared as described in Scheme VII. ¹ H NMR (500 MHz, DMSO) 13.57 (br s, 1H), 12.12 (br s, 1H), 10.50 (s, 1H), 10.27 (br s, 1H), 7.63 (m, 1H), 7.54 (m, 1H), 7.45 (m, 1H), 7.37-7.32 (m, 2H), 7.24 (m, 1H), 7.02 (m, 1H), 3.70 (t, J = 6.7 Hz, 2H), 2.44 (s, 3H ), 2.26 (t, J = 7.3 Hz, 2H), 2.21 (s, 3H), 1.87 (m, 2H).

Example 205

4- (2- (5-methyl-3-oxo-3,4-dihydro-4- (5-chloro-2-hydroxy-3- (2-methylphenyl-carbonylamino) phenyl) hydrazono) Pyrazolyl} butanoic acid (Compound 305)

This compound was prepared as described in Scheme VII. ¹ H NMR (500 MHz, DMSO) 10.30 (br s, 1 H), 7.65 (d, J = 7.3 Hz, 1 H), 7.48-7.40 (m, 3H), 7.36-7.32 (m, 2H), 3.69 (t, J = 6.7 Hz, 2H), 2.43 (s, 3H), 2.26 (t, J = 7.3 Hz, 2H), 2.21 (s, 3H), 1.86 (m, 2H).

Example 206

3- {2-Hydroxy-3- (2-oxo-2,3-dihydro-l- (2- (2-fluorophenyl) ethyl) indolylidene) -hydrazinophenyl} benzoic acid (Compound 306 )

This compound was prepared as described in Scheme IX. ¹ H NMR (500MHz, DMSO) 13.03 (s, 1H), 12.97 (s, 1H), 9.23 (s, 1H), 8.12 (t, J = 1.7 Hz, 1H), 7.95 (ddd, J = 7.7, 1.7 , 1.2 Hz, 1H), 7.79 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.67 (dd, J = 8.1, 1.6 Hz, 1H), 7.62 (m, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.34-7.23 (m, 3H), 7.15-7.07 (m, 5H), 6.98 (dd, J = 7.7, 1.6 Hz, 1H), 4.04 (dd, J = 7.2, 6.8 Hz, 2H ), 3.02 (t, J = 7.2 Hz, 2H).

Example 207

3- {2-Hydroxy-3- (2-oxo-2,3-dihydro-l- (2- (2-chlorophenyl) ethyl) indolilidene) -hydrazinophenyl} benzoic acid (Compound 307)

This compound was prepared as described in Scheme IX. ¹ H NMR (500MHz, DMSO) 13.03 (s, 1H), 12.97 (s, 1H), 9.23 (s, 1H), 8.12 (t, J = 1.6 Hz, 1H), 7.94 (ddd, J = 7.7, 1.6 , 1.2 Hz, 1H), 7.79 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.68 (dd, J = 7.8, 1.6 Hz, 1H), 7.62 (m, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.41 (m, 1H), 7.34 (m, 1H), 7.29 (td, J = 7.7, 1.2 Hz, 1H), 7.27-7.22 (m, 2H), 7.13-7.06 (m, 3H ), 6.98 (dd, J = 7.8, 1.6 Hz, 1H), 4.05 (t, J = 7.3 Hz, 2H), 3.10 (t, J = 7.3 Hz, 2H).

Example 208

3- {3-hydroxy-2- (5-methyl-3-oxo-2,3-dihydro-2- (3,4-dimethylphenyl) -pyrazolylidene) hydrazino-4-pyridyl} Benzoic Acid (Compound 308)

This compound was prepared as described in Scheme IX. ¹ H NMR (500MHz, DMSO) 8.53 (t, J = 1.6 Hz, 1H), 8.20-8.15 (m, 2H), 8.04 (ddd, J = 7.7, 1.6, 1.1 Hz, 1H), 7.71-7.64 (m , 3H), 7.61 (dd, J = 8.4, 2.3 Hz, 1H), 7.22 (d, J = 8.4 Hz, 1H), 2.34 (s, 3H) 3 2.27 (s, 3H), 2.23 (s, 3H) .

Example 209

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methylphenyl) -ethyl) phenyl) hydrazono) pyra Zolyl} Benzoic Acid (Compound 309)

This compound was prepared as described in Scheme VII. ¹ H NMR (500MHz, DMSO) 13.75 (s, 1H), 9.66 (s, 1H), 8.10 (d, J = 8.8 Hz, 2H), 8.04 (d, J = 8.8 Hz, 2H), 7.56 (d, J = 7.6 Hz, 1H), 7.22 (dd, J = 7.3, 1.6 Hz, 1H), 7.16-7.08 (m, 3H), 7.02 (d, J = 7.6 Hz, 1H), 6.97 (t, J = 7.6 Hz, 1H), 2.93-2.87 (m, 2H), 2.86-2.80 (m, 2H), 2.35 (s, 3H), 2.29 (s, 3H).

Example 210

3- {3-Hydroxy-2- (2-oxo-2,3-dihydro-l- (3,5-dimethylphenyl) -3-indolylidene-hydrazino)-4-pyridyl} benzoic acid (Compound 310)

This compound was prepared as described in Scheme IX. ¹ H NMR (500MHz, DMSO) 13.02 (br s, 1H), 9.68 (br s, 1H), 8.52 (br s, 1H), 8.25 (br s, 1H), 8.16 (br s, 1H), 7.96 ( d, J = 7.1 Hz, 1H), 7.76 (d, J = 7.1 Hz, 1H), 7.61 (t, J = 7.7 Hz, 1H), 7.60 (m, 1H), 7.35 (td, J = 7.6, 1.2 Hz, 1H), 7.21 (td, J = 7.6, 0.7 Hz, 1H), 7.16-7.13 (m, 3H), 6.89 (d, J = 7.6 Hz, 1H), 2.37 (s, 6H).

Example 211

3- {1- (2-oxo-2,3-dihydro-3- (3-hydroxy-6-methyl-4- (3,4-dimethylphenyl) -2-pyridyl) hydrazono) indole Reel} Benzoic Acid (Compound 311)

This compound was prepared as described in Scheme VII. ¹ H NMR (500MHz, DMSO) 12.93 (s, 1H), 8.07 (t, J = 1.7 Hz, 1H), 8.04 (m, 1H), 7.81-7.74 (m, 2H), 7.74-7.60 (m, 3H ), 7.42 (s, 1H), 7.35 (t, J = 7.6 Hz, 1H), 7.23 (t, J = 7.6 Hz, 1H), 7.20 (d, J = 7.9 Hz, 1H), 6.92 (d, J = 7.6 Hz, 1H), 2.47 (s, 3H), 2.28 (s, 3H), 2.27 (s, 3H).

Example 212

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-6-methyl-4- (3,4-dimethylphenyl) -2-pyridyl) hydro Lazono) pyrazolyl} benzoic acid (Compound 312)

This compound was prepared as described in Scheme VII. ¹ H NMR (500MHz, DMSO) 8.50 (dd, J = 2.1, 1.6 Hz, 1H), 8.15 (ddd, J = 8.1, 2.1, 1.0 Hz, 1H), 7.82 (ddd, J = 7.7, 1.6, 1.0 Hz , 1H), 7.71 (s, 1H), 7.62-7.54 (m, 2H), 7.62 (dd, J = 8.1, 7.7 Hz, 1H), 7.34 (d, J = 7.8 Hz, 1H), 2.63 (s, 3H), 2.38 (s, 3H), 2.32 (s, 6H).

Example 213

3- {3-hydroxy-4- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) -6-trifluoromethyl-3-indolylidenehydrazino)- 2-pyridyl} benzoic acid (Compound 313)

This compound was prepared as described in Scheme IX. ¹ H NMR (500MHz, DMSO) 13.25 (s, 1H), 8.42 (t, J = 1.5 Hz, 1H), 8.32 (d, J = 6.1 Hz, 1H), 8.10 (dd, J = 7.8, 1.5 Hz, 1H), 8.10 (m, 1H), 8.03 (d, J = 7.9 Hz, 1H), 7.93 (d, J = 6.1 Hz, 1H), 7.72 (t, J = 7.8 Hz, 1H), 7.61 (dq, J = 7.9, 0.8 Hz, 1H), 7.19 (m, 1H), 7.17 (m, 2H), 6.99 (m, 1H), 2.37 (s, 6H).

Example 214

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-2- (3,5-dimethylphenyl) -4-pyridyl) hydrazono) pyra Jolyl} butanoic acid (compound 314)

This compound was prepared as described in Scheme VII. ¹ H NMR (500 MHz, CD ₃ OD) 7.89 (m, 1H), 7.80 (m, 1H), 7.45 (s, 2H), 7.19 (s, 1H), 3.79 (t, J = 6.6 Hz, 2H) , 2.41 (s, 6H), 2.36 (t, J = 7.3 Hz, 2H), 2.28 (s, 3H), 2.01 (m, 2H).

Example 215

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-5-phenyl-2-benzothienyl) -hydrazono) pyrazolyl} butanoic acid ( Compound 315)

This compound was prepared as described in Scheme VI. ¹ H NMR (500MHz, DMSO) 12.13 (s, 1H), 11.25 (s, 1H), 8.04 (d, J = 1.8 Hz, 1H), 7.89 (d, J = 8.4 Hz, 1H), 7.74 (m, 2H), 7.70 (dd, J = 8.4, 1.8 Hz, 1H), 7.51 (t, J = 7.6 Hz, 2H), 7.40 (tt, J = 7.6, 1.0 Hz, 1H), 3.85 (t, J = 6.7 Hz, 2H), 2.31-2.23 (m, 5H), 1.92 (m, 2H).

Example 216

3- {3-hydroxy-2- (5-methyl-3-oxo-2,3-dihydro-2- (3,4-dimethylphenyl) -4-pyrazolidene) hydrazino-5-benzo Thienyl} benzoic acid (Compound 316)

This compound was prepared as described in Scheme VI. ¹ H NMR (500MHz, DMSO) 8.29 (t, J = 1.6 Hz, 1H), 8.18 (d, J = 1.7 Hz, 1H), 8.01 (ddd, J = 7.8, 1.6, 0.9 Hz, 1H), 7.97 ( ddd, J = 7.8, 1.6, 0.9 Hz, 1H), 7.96 (d, J = 8.3 Hz, 1H), 7.73 (dd, J = 8.3, 1.7 Hz, 1H), 7.69 (d, J = 1.7 Hz, 1H ), 7.64 (t, J = 7.8 Hz, 1H), 7.62 (dd, J = 8.3, 1.7 Hz, 1H), 7.22 (d, J = 8.3 Hz, 1H), 2.31 (s, 3H), 2.28 (s , 3H), 2.24 (s, 3H).

Example 217

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (3- (2,3-dimethoxycarbonylphenyl) phenyl) -hydrazono) pyrazolyl} butanoic acid ( Compound 317)

This compound was prepared as described in Scheme I. ¹ H NMR (500MHz, DMSO) 12.13 (s, 1H), 7.99 (dd, J = 7.6, 1.2 Hz, 1H), 7.75 (dd, J = 7.6, 1.2 Hz, 1H), 7.71 (t, J = 7.6 Hz, 1H), 7.58-7.55 (m, 2H), 7.50 (m, 1H), 7.15 (m, 1H), 3.86 (s, 3H), 3.69 (t, J = 7.0 Hz, 2H), 3.63 (s , 3H), 2.26 (t, J = 7.0 Hz, 2H), 2.18 (s, 3H), 1.86 (qn, J = 7.0 Hz, 2H).

Example 218

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z)-(2-hydroxy-3,5-diisopropylphenyl) -carbonylhydrazinomethylidene) Pyrazolyl} butanoic acid (Compound 318)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, CD ₃ OD) 7.77 (br s, 1 H), 7.30-7.23 (m, 2H), 3.84 (t, J = 6.7 Hz, 2H), 2.96-2.82 (m, 2H), 2.34 (t, J = 7.5 Hz, 2H), 2.20 (s, 3H), 2.03 (m, 2H), 1.28 (d, J = 7.0 Hz, 6H), 1.23 (d, J = 6.7 Hz, 6H).

Example 219

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z)-(2-hydroxy-3- (3,5-dimethylphenyl) phenyl) -aminomethylidene) pyra Jolyl} butanoic acid (Compound 319)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500 MHz, CD ₃ OD) 8.52 (br s, 1H), 7.55 (m, 1H), 7.11-7.09 (m, 2H), 7.06-7.01 (m, 3H), 3.79 (t, J = 6.8 Hz, 2H), 2.36 (s, 6H), 2.29 (t, J = 7.5 Hz, 2H), 2.27 (s, 3H), 1.99 (m, 2H).

Example 220

(±) -4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2,3-dihydro-1-methyl-2-oxo -3-indolyl) methyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 320)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, CD ₃ OD) 7.64 (dd, J = 8.0, 1.3 Hz, 1H), 7.32 (td, J = 7.7, 0.9 Hz, 1H), 7.01-6.91 (m, 2H), 6.84 ( dd, J = 8.0, 7.6 Hz, 1H), 6.78 (m, 1H), 6.62 (dd, J = 7.6, 1.3 Hz, 1H), 3.79 (t, J = 6.7 Hz, 2H), 3.51 (d, J = 14.4 Hz, 1H), 3.20 (s, 3H), 2.81 (d, J = 14.4 Hz, 1H), 2.33 (t, J = 7.5 Hz, 3H), 2.27 (s, 3H), 2.01 (m, 2H ).

Example 221

3- {1- (2-Oxo-2,3-dihydro-5-fluoro-3- (2-hydroxy-3- (2- (2-methylphenyl) ethyl) phenyl) -hydrazono) indole Reyl} propionic acid (Compound 321)

This compound was prepared as described in Scheme VII. ¹ H NMR (500MHz, DMSO) 13.10 (s, 1H), 9.24 (s, 1H), 8.08 (t, J = I.8 Hz, 1H), 8.04 (m, 1H), 7.82 (m, 1H), 7.74 (t, J = 7.7 Hz, 1H), 7.61 (dd, J = 7.9, 1.6 Hz, 1H), 7.55 (dd, J = 8.2, 2.6 Hz, 1H), 7.22 (m, 1H), 7.16-7.07 (m, 4H), 6.96-6.92 (m, 2H), 6.88 (dd, J = 7.6, 1.6 Hz, 1H), 2.87 (m, 2H), 2.81 (m, 2H), 2.28 (s, 3H).

Example 222

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,5-dimethylphenyl) -ethyl) phenyl) hydrazono ) Prazolyl} Benzoic Acid (Compound 322)

This compound was prepared as described in Scheme VII. ¹ H NMR (500MHz, DMSO) 13.77 (s, 1H), 9.62 (s, 1H), 8.56 (m, 1H), 8.21 (m, 1H), 7.78 (d, J = 7.8 Hz, 1H), 7.63- 7.53 (m, 2H), 7.08-6.88 (m, 5H), 2.87 (m, 2H), 2.77 (m, 2H), 2.35 (s, 3H), 2.25 (s, 3H), 2.24 (s, 3H) .

Example 223

(±) -3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2,3-dihydro-1-methyl-2-oxo -3-indolyl) methyl) phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 323)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, CD ₃ OD) 8.59 (dd, J = 2.1, 1.6 Hz, 1H), 8.19 (ddd, J = 8.2, 2.1, 1.0 Hz, 1H), 7.82 (ddd, J = 7.7, 1.6 , 1.0 Hz, 1H), 7.60 (dd, J = 8.1, 1.4 Hz, 1H), 7.49 (dd, J = 8.2, 7.7 Hz, 1H), 7.32 (td, J = 7.6, 1.2 Hz, IH), 7.00 -6.93 (m, 2H), 6.83-6.79 (m, 2H), 6.60 (dd, J = 7.6, 1.4 Hz, 1H), 3.51 (d, J = 14.4 Hz, 1H), 3.20 (s, 3H), 2.80 (d, J = 14.4 Hz, 1 H), 2.34 (s, 3 H).

Example 224

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (l, 2-dihydro-1-methyl-2-oxo-3-indole) Liliden) methyl) phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 324)

This compound was prepared as described in Scheme VII. ¹ H NMR (500MHz, DMSO) 13.65 (br s, 1H), 13.16 (br s, 1H), 10.54 (s, 1H), 8.53 (dd, J = 2.1, 1.6 Hz, 1H), 8.20 (ddd, J = 8.2, 2.1, 1.0 Hz, IH), 7.84-7.76 (m, 3H), 7.59 (dd, J = 8.2, 7.9 Hz, 1H), 7.46 (m, 1H), 7.40 (d, J = 7.6 Hz, 1H), 7.34 (td, J = 7.6, 1.0 Hz, 1H), 7.16 (m, 1H), 7.07 (d, J = 7.6 Hz, 1H), 6.93 (td, J = 7.6, 1.0 Hz, 1H), 3.24 (s, 3 H), 2.37 (s, 3 H).

Example 225

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (5-fluoro-2-methylphenyl) -ethyl) phenyl) hydro Lazono) pyrazolyl} benzoic acid (Compound 325)

This compound was prepared as described in Scheme VII. ¹ H NMR (500MHz, DMSO) 13.77 (s, 1H), 13.15 (s, 1H), 9.66 (s, 1H), 8.55 (dd, J = 2.1, 1.6 Hz, 1H), 8.20 (ddd, J = 8.2 , 2.1, 1.0 Hz, 1H), 7.79 (ddd, J = 7.8, 1.6, 1.1 Hz, 1H), 7.60 (dd, J = 8.2, 7.8 Hz, 1H), 7.57 (dd, J = 7.9, 1.6 Hz, 1H), 7.17 (dd, J = 8.2, 6.1 Hz, 1H), 7.07 (dd, J = 10.3, 2.8 Hz, 1H), 7.02 (dd, J = 7.6, 1.6 Hz, 1H), 6.97 (m, 1H ), 6.92 (ddd, J = 8.6, 8.2, 2.8 Hz, 1H), 2.90 (m, 2H), 2.83 (m, 2H), 2.35 (s, 3H), 2.25 (s, 3H).

Example 226

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4 (E)-(2-hydroxy-3- (2- (2,4-difluophenyl) -ethenyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 326)

This compound was prepared as described in Scheme VII. ¹ H NMR (300MHz, DMSO) 7.85 (m, 1H), 7.62-7.45 (m, 3H), 7.36-7.14 (m, 3H), 7.01 (m, 1H), 3.69 (t, J = 6.5 Hz, 2H ), 2.25 (t, J = 7.2 Hz, 2H), 2.20 (s, 3H), 1.86 (m, 2H).

Example 227

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3-methylphenyl) hydrazono) -pyrazolyl} benzoic acid (Compound 327)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, CD ₃ OD) 8.61 (dd, J = 2.1, 1.5 Hz, 1H), 8.20 (ddd, J = 8.1, 2.1, 1.0 Hz, 1H), 7.84 (ddd, J = 7.7, 1.5 , 1.0 Hz, 1H), 7.54 (m, 1H), 7.52 (dd, J = 8.1, 7.7 Hz, 1H), 6.97 (m, 1H), 6.88 (t, J = 7.8 Hz, 1H), 2.36 (s , 3H), 2.28 (s, 3H).

Example 228

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (l, 2-dihydro-1-methyl-2-oxo-3-indole) Liliden) methyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 328)

This compound was prepared as described in Scheme VII. ¹ H NMR (500 MHz, DMSO) 13.54 (s, 1 H), 10.41 (br s, 1 H), 8.42 (br, 1 H), 7.76 (s, 1 H), 7.74 (m, 1 H), 7.43-7.37 (m, 2H), 7.33 (t, J = 7.8 Hz, 1H), 7.12 (t, J = 7.8 Hz, 1H), 7.06 (d, J = 7.8 Hz, 1H), 6.92 (t, J = 7.8 Hz, 1H) , 3.69 (t, J = 6.6 Hz, 2H), 3.23 (s, 3H), 2.26 (t, J = 7.1 Hz, 2H), 2.21 (s, 3H), 1.87 (m, 2H).

Example 229

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (5-fluoro-2-methylphenyl) -ethyl) phenyl) hydro Lazono) pyrazolyl} butanoic acid (Compound 329)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, CD ₃ OD) 7.53 (m, 1H), 7.09 (dd, J = 8.4, 6.1 Hz, 1H), 6.93-6.84 (m, 3H), 6.78 (td, J = 8.4, 2.8 Hz, 1H), 3.79 (t, J = 6.7 Hz, 2H), 2.96-2.82 (m, 4H), 2.35 (t, J = 7.4 Hz, 2H), 2.25 (s, 3H), 2.23 (s, 3H ), 2.01 (m, 2 H).

Example 230

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-difluorophenyl) -ethyl) phenyl) hydro Lazono) pyrazolyl} butanoic acid (Compound 330)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, CD ₃ OD) 7.53 (m, 1H), 7.21 (m, 1H), 6.91-6.76 (m, 4H), 3.79 (t, J = 6.6 Hz, 2H), 3.03-2.92 ( m, 4H), 2.34 (t, J = 7.3 Hz, 2H), 2.26 (s, 3H), 2.01 (m, 2H).

Example 231

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,6-dimethylphenyl) -ethenyl) phenyl ) Hyrazono) pyrazolyl} butanoic acid (Compound 331)

This compound was prepared as described in Scheme VII.

Example 232

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-methylphenyl) -ethenyl) phenyl) hydrazo No) pyrazolyl} butanoic acid (Compound 332)

This compound was prepared as described in Scheme VII.

Example 233

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (5-fluoro-2-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 333)

This compound was prepared as described in Scheme VII. ¹ H NMR (300 MHz, CD ₃ OD) 7.63 (d, J = 8.0 Hz, 1H), 7.49-7.29 (m, 4H), 7.18 (dd, J = 8.3, 6.2 Hz, 1H), 7.03 (m, 1H), 6.89 (td, J = 8.3, 2.3 Hz, 1H), 3.79 (t, J = 6.6 Hz, 2H), 2.40 (s, 3H), 2.34 (t, J = 7.4 Hz, 2H), 2.26 ( s, 3H), 2.01 (m, 2H).

The compound can be prepared as described in Scheme VII.

Example 234

4- (2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (Z)-(2- (5-fluoro-2-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 334)

The compound can be prepared as described in Scheme VII.

Example 235

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (3-fluorophenyl) ethenyl) phenyl) hydro Lazono) pyrazolyl} butanoic acid (Compound 335)

The compound can be prepared as described in Scheme VII.

Example 236

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (4-fluorophenyl) ethenyl) phenyl) hydro Lazono) pyrazolyl} butanoic acid (Compound 336)

The compound can be prepared as described in Scheme VII.

Example 237

4- (2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-fluorophenyl) -ethenyl) phenyl) Hydrazono) pyrazolyl} butanoic acid (Compound 337)

The compound can be prepared as described in Scheme VII.

Example 238

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2-phenylethenyl) -phenyl) hydrazono) pyrazolyl Butanoic Acid (Compound 338)

The compound can be prepared as described in Scheme VII.

Example 239

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-phenylethynyl) -phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 339)

The compound can be prepared as described in Scheme VII.

Example 240

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methylphenyl) ethynyl) -phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 340)

The compound can be prepared as described in Scheme VII.

Example 241

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dimethylphenyl) -ethynyl) phenyl) hydrazo Pyrazolyl} butanoic acid (Compound 341)

The compound can be prepared as described in Scheme VII.

Example 242

4- (2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluorophenyl) ethynyl) phenyl) hydrazono) Pyrazolyl} butanoic acid (Compound 342)

The compound can be prepared as described in Scheme VII.

Example 243

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-trifluoromethylphenyl) -ethynyl) phenyl) hydrazo No) pyrazolyl} butanoic acid (Compound 342)

The compound can be prepared as described in Scheme VII.

Example 244

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-trifluoromethyl-phenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 344)

The compound can be prepared as described in Scheme VII.

Example 245

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (1-methyl-1-indenyl-2-) phenyl) -hydrazono ) Pyrazolyl} butanoic acid (Compound 345)

The compound can be prepared as described in Scheme VII.

Example 246

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3,3-dimethyl-2-indenyl) phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 346)

The compound can be prepared as described in Scheme VII.

Example 247

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-5-methoxy-3- (2-indenyl) -phenyl) hydrazono) pyra Zolyl} Butanoic Acid (Compound 347)

The compound can be prepared as described in Scheme VII.

Example 248

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (4,7-dimethyl-2-indenyl) phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 348)

The compound can be prepared as described in Scheme VII.

Example 249

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (4,7-difluoro-2-indenyl) phenyl) hydrazono ) Pyrazolyl} butanoic acid (Compound 349)

The compound can be prepared as described in Scheme VII.

Example 250

3- {2-hydroxy-3- (2-oxo-2,3-dihydro-6-trifluoromethyl-1- (2- (2-methylphenyl) -ethyl) -3 (Z) -indolily Den) methylaminophenyl} benzoic acid (compound 350)

This compound was prepared as described in Scheme VIII. ¹ H NMR (500MHz, DMSO) 13.05 (s, 1H), 11.29 (d, J = 13.4 Hz, 1H), 9.39 (s, 1H), 8.95 (d, J = 13.4 Hz, 1H), 8.13 (m, 1H), 7.95 (dd, J = 7.8, 1.0 Hz, 1H), 7.83 (d, J = 8.1 Hz, 1H), 7.80 (m, 1H), 7.75 (d, J = 8.1 Hz, 1H), 7.61 ( t, J = 7.8 Hz, 1H), 7.31 (d, J = 7.8 Hz, 1H), 7.20 (m, 1H), 7.16-7.07 (m, 5H), 7.05 (d, J = 7.8 Hz, 1H), 4.06 (t, J = 7.4 Hz, 2H), 2.93 (t, J = 7.4 Hz, 2H), 2.32 (s, 3H).

Example 251

3- {2-hydroxy-3- (2-oxo-2,3-dihydro-6-trifluoromethyl-1- (2-indenyl) -3 (Z) -indolylidene) methylaminophenyl Benzoic Acid (Compound 351)

The compound may be prepared as described in Scheme VIII.

Example 252

(±) 4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (1,2,3,4-tetrahydro)- Naphthyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 352)

This compound was prepared as described in Scheme VII. ¹ H NMR (500 MHz, CD ₃ OD) 7.57 (dd, J = 8.0, 1.6 Hz, 1H), 7.11-7.04 (m, 5H), 7.00 (t, J = 8.0 Hz, 1H), 3.79 (t, J = 6.7 Hz, 2H), 3.39 (m, 1H), 3.05-2.80 (m, 4H), 2.34 (t, J = 7.3 Hz, 2H), 2.26 (s, 3H), 2.01 (m, 2H), 2.10-1.91 (m, 2 H).

Example 253

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro) -naphthyl) phenyl) hydrazo Pyrazolyl} butanoic acid (Compound 353)

The compound can be prepared as described in Scheme VII.

Example 254

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(1-indanylidene) -methylphenyl) hydrazono) pyrazolyl Butanoic Acid (Compound 354)

The compound can be prepared as described in Scheme VII.

Example 255

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (5-fluoro-2-trifluoromethylphenyl) Ethenyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 355)

The compound can be prepared as described in Scheme VII.

Example 256

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (6-fluoro-2-trifluoro-methylphenyl ) Ethenyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 356)

The compound can be prepared as described in Scheme VII.

Example 257

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- {2-hydroxy-3 (E)-(2- (6-fluoro-2-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 357)

The compound can be prepared as described in Scheme VII.

Example 258

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (4-fluoro-2-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 358)

The compound can be prepared as described in Scheme VII.

Example 259

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (3-fluoro-2-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 359)

The compound can be prepared as described in Scheme VII.

Example 260

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,6-difluorophenyl) -ethenyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 360)

The compound can be prepared as described in Scheme VII.

Example 261

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,5-difluorophenyl) -ethenyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 361)

The compound can be prepared as described in Scheme VII.

Example 262

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (4-fluoro-2-trifluoro-methylphenyl ) Ethenyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 362)

The compound can be prepared as described in Scheme VII.

Example 263

4- (2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,4-difluorophenyl) -ethynyl) phenyl) Hydrazono) pyrazolyl} butanoic acid (Compound 363)

The compound can be prepared as described in Scheme VII.

Example 264

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(1- (l, 2,3,4-tetrahydro)- Naphthylidene) methylphenyl) hydrazono) pyrazolyl} butanoic acid (Compound 364)

The compound can be prepared as described in Scheme VII.

Example 265

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-fluoro-5-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 365)

The compound can be prepared as described in Scheme VII.

Example 266

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (3,5-dimethyl-4-isoxazolyl) Ethenyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 366)

The compound can be prepared as described in Scheme VII.

Example 267

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,5-dimethyl-4-isoxazolyl) ethyl) phenyl ) Hyrazono) pyrazolyl} butanoic acid (Compound 367)

The compound can be prepared as described in Scheme VII.

Example 268

3- {2-hydroxy-3- (2-oxo-2,3-dihydro-1- (2 (E)-(2-methylphenyl) ethenyl) -3 (Z) -indolylidene) methylamino Phenyl} benzoic acid (Compound 368)

The compound may be prepared as described in Scheme VIII.

Example 269

3- {2-hydroxy-3- (2-oxo-2,3-dihydro-1- (2 (E)-(2,4-difluorophenyl) ethenyl) -3 (Z) -indole Liliden) methylaminophenyl} benzoic acid (Compound 369)

The compound may be prepared as described in Scheme VIII.

Example 270

3- {2-Hydroxy-3- (2-oxo-2,3-dihydro-l- (2-indenyl) -3 (Z) -indolylidene) methyl-aminophenyl} benzoic acid (Compound 370)

The compound may be prepared as described in Scheme VIII.

Example 271

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (5-fluoro-2-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 371)

This compound was prepared as described in Scheme VII. ¹ H NMR (500MHz, DMSO) 13.72 (s, 1H), 13.13 (br s, 1H), 10.23 (s, 1H), 8.54 (dd, J = 2.1, 1.6 Hz, 1H), 8.21 (ddd, J = 8.0, 2.1, 1.0 Hz, 1H), 7.79 (ddd, J = 7.8, 1.6, 1.0 Hz, 1H), 7.65 (dd, J = 7.9, 1.3 Hz, 1H), 7.60 (dd, J = 8.0, 7.8 Hz , 1H), 7.60 (dd, J = 7.9, 1.3 Hz, 1H), 7.55 (dd, J = 10.6, 2.8 Hz, 1H), 7.50 (d, J = 15.9 Hz, 1H), 7.35 (dd, J = 15.9, 1.5 Hz, 1H), 7.26 (dd, J = 8.4, 6.2 Hz, 1H), 7.07 (t, J = 7.9 Hz, 1H), 7.04 (td, J = 8.4, 2.8 Hz, 1H), 2.39 ( s, 3H), 2.35 (s, 3H).

Example 272

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3-methylphenyl) hydrazono) -pyrazolyl} butanoic acid (Compound 372)

This compound was prepared as described in Scheme VII. ¹ H NMR (500MHz, DMSO) 13.57 (br s, 1H), 12.11 (br s, 1H), 9.45 (br s, 1H), 7.46 (d, J = 7.8 Hz, 1H), 6.95 (m, 1H) , 6.89 (t, J = 7.8 Hz, 1H), 3.69 (t, J = 6.8 Hz, 2H), 2.25 (t, J = 7.2 Hz, 2H), 2.24 (s, 3H), 2.19 (s, 3H) , 1.86 (m, 2 H).

Example 273

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indanylidenemethyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 373)

The compound can be prepared as described in Scheme VII.

Example 274

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indanylmethyl) phenyl) hydrazono) pyrazolyl} butanoic acid ( Compound 374)

The compound can be prepared as described in Scheme VII.

Example 275

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,4-difluorophenyl) -ethenyl ) Phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 375)

The compound can be prepared as described in Scheme VII.

Example 276

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,6-difluorophenyl) -ethenyl ) Phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 376)

The compound can be prepared as described in Scheme VII.

Example 277

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (4-fluoro-2-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 377)

The compound can be prepared as described in Scheme VII.

Example 278

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-fluoro-6-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 378)

The compound can be prepared as described in Scheme VII.

Example 279

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,3-difluorophenyl) -ethenyl ) Phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 379)

The compound can be prepared as described in Scheme VII.

Example 280

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,3-difluorophenyl) -ethenyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 380)

The compound can be prepared as described in Scheme VII.

Example 281

4- (2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-fluoro-4-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 381)

The compound can be prepared as described in Scheme VII.

Example 282

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-chlorophenyl) -ethenyl) phenyl) hydr Lazono) pyrazolyl} butanoic acid (Compound 382)

The compound can be prepared as described in Scheme VII.

Example 283

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,6-dichlorophenyl) -ethenyl) phenyl ) Hyrazono) pyrazolyl} butanoic acid (Compound 383)

The compound can be prepared as described in Scheme VII.

Example 284

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (3-chlorophenyl) -ethenyl) phenyl) hydr Lazono) pyrazolyl} butanoic acid (Compound 384)

The compound can be prepared as described in Scheme VII.

Example 285

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,5-difluorophenyl) -ethenyl ) Phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 385)

The compound can be prepared as described in Scheme VII.

Example 286

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-chloro-4-fluorophenyl) ethenyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 386)

The compound can be prepared as described in Scheme VII.

Example 287

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-trifluoromethyl-4-fluorophenyl ) Ethenyl) phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 387)

The compound can be prepared as described in Scheme VII.

Example 288

4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,4-dichlorophenyl) -ethenyl) phenyl ) Hyrazono) pyrazolyl} butanoic acid (Compound 388)

The compound can be prepared as described in Scheme VII.

Example 289

In 3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-chloromethyl-4-fluorophenyl) Tenyl) phenyl) hydrazono) pyrazolyl} benzoic acid (compound 389)

The compound can be prepared as described in Scheme VII.

Example 290

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,4-dichloromethylphenyl) ethenyl) phenyl) Hydrazono) pyrazolyl} benzoic acid (Compound 390)

The compound can be prepared as described in Scheme VII.

Example 291

3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro) -naphthyl) phenyl) hydrazo No) pyrazolyl} benzoic acid (Compound 353)

The compound can be prepared as described in Scheme VII.

Example 292

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-8-fluoro) -naphthyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 392)

The compound can be prepared as described in Scheme VII.

Example 293

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-8-methyl) -naphthyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 393)

The compound can be prepared as described in Scheme VII.

Example 294

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-7-methyl) -naphthyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 394)

The compound can be prepared as described in Scheme VII.

Example 295

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-7-fluoro) -naphthyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 395)

The compound can be prepared as described in Scheme VII.

Example 296

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-6-fluoro) -naphthyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 396)

The compound can be prepared as described in Scheme VII.

Example 297

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-5-fluoro) -naphthyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 397)

The compound can be prepared as described in Scheme VII.

Example 298

4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-8-chloro) -naphthyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 398)

The compound can be prepared as described in Scheme VII.

Example 299

3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-7-fluoro) -naphthyl ) Phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 399)

The compound can be prepared as described in Scheme VII.

Claims (40)

A compound of formula (I), (II), (III), (IV), (V) or (VI), a pharmaceutically acceptable salt, ester, amide or prodrug thereof. [Formula I]

[Formula II]

[Formula III]

[Formula IV]

[Formula V]

[Formula VI]

In the above formula, R ¹ is hydrogen, halogen, OR ¹⁴ , NO ₂ , CN, NR ¹⁴ R ¹⁵ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ hetero Alkyl, CO ₂ R ¹⁴ , CONR ¹⁴ R ¹⁵ , SO ₃ R ¹⁴ , SO ₂ NR ¹⁴ R ¹⁵ and a carboxylic acid bioequivalent; Each R ² is a group consisting of hydrogen, halogen, OR ¹⁴ , NR ¹⁴ R ¹⁵ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, and optionally substituted C ₁ -C ₆ heteroalkyl Independently from; R ³ and R ⁴ are independently selected from the group consisting of hydrogen, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl and optionally substituted C ₁ -C ₆ heteroalkyl; R ⁵ is selected from the group consisting of hydrogen, halogen, OR ¹⁴ , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ haloheteroalkyl; R ⁶ consists of optionally substituted C ₁ -C ₁₀ alkyl, optionally substituted C ₁ -C ₁₀ haloalkyl and optionally substituted C ₁ -C ₁₀ heteroalkyl, each optionally substituted with substituted aryl or substituted heteroaryl selected from the group, or, R ⁶ is ^{_{(CH 2) m R 18,}} C (O) NHR 18, C≡CR 18, CR 3 = CR 4 R 18 , and is selected from the group consisting of CR ³ = R ^18; R ⁷ is selected from the group consisting of CO ₂ R ¹⁴ , CONR ¹⁴ R ¹⁵ , SO ₃ R ¹⁴ , SO ₂ NR ¹⁴ R ¹⁵ and a carboxylic acid bioequivalent; Each of R ⁸ and R ⁹ is hydrogen, OR ¹⁶ , NR ¹⁶ R ¹⁷ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ heteroalkyl, (CH ₂ ) _m R ¹⁸ and none independently; R ⁸ and R ⁹ together form an optionally substituted olefin; R ⁸ and R ⁹ are joined to form an optionally substituted C ₃ -C ₈ ring; R ¹⁰ is hydrogen, halogen, oxo, OR ¹⁶ , NR ¹⁶ R ¹⁷ , SR ¹⁶ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl and optionally substituted C ₁ -C ₆ hetero Selected from the group consisting of alkyl; R ¹¹ is selected from the group consisting of hydrogen, halogen, OR ¹⁴ , NR ¹⁴ R ¹⁵ and SR ¹⁴ ; R ¹¹ and R ⁴ are joined to form an optionally substituted heterocycle; R ¹² is selected from the group consisting of hydrogen, halogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ haloheteroalkyl; R ¹³ is hydrogen, halogen, CN, NO ₂ , CO ₂ R ¹⁴ , S (O) _m R ¹⁴ , C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl and C ₁ -C ₄ haloheteroalkyl; R ¹⁴ is selected from the group consisting of hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ heterohaloalkyl; R ¹⁵ is selected from the group consisting of hydrogen, SO ₂ R ¹⁹ , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ heterohaloalkyl; A group of R ¹⁶ and R ¹⁷ consisting of hydrogen, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ heteroalkyl, and (CH ₂ ) _m R ¹⁸ Each independently selected from; R ¹⁶ and R ¹⁷ If either is optionally substituted C ₂ -C ₆ alkyl, the other is none; R ¹⁶ and R ¹⁷ are joined to form an optionally substituted C ₃ -C ₈ ring; R ¹⁸ is selected from an optionally substituted monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle, wherein R ¹⁸ comprises a nonaromatic heterocycle or carbocycle When attached, the attachment position may be on a nonaromatic heterocycle or carbocycle or aromatic ring system; R ¹⁹ is selected from the group consisting of hydrogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl and optionally substituted aryl; D is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle; E is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle; L is NH or none; Q is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle; U is selected from the group consisting of O, NR ⁴ , CR ³ R ⁴ , CO and none; W is selected from the group consisting of O, NR ⁴ , CR ³ R ⁴ , CO and none; X is N or CR ⁵ ; Y is 1 to 4 atomic spacers comprising one or more groups selected from optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ heteroalkyl, optionally substituted phenyl and optionally substituted heteroaryl; Z is absent; 2 to 5 atomic spacers selected from optionally substituted C ₆ -C ₁₀ aryl and optionally substituted C ₁ -C ₈ heteroaryl, each optionally bonded with an optionally substituted non-aromatic heterocycle or carbocycle; And _{1 selected} from optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ heteroalkyl, and optionally substituted C ₁ -C ₆ haloalkyl, each optionally optionally conjugated with optionally substituted C ₆ -C ₁₀ aryl; To 5 atomic spacers; m is 0, 1, 2 or 3; n is 0 or 1; Each optionally substituted group is alkyl, heteroalkyl, haloalkyl, heterohaloalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, non-aromatic heterocycle, hydroxy, alkoxy, aryloxy, mercapto, alkylthio, Arylthio, cyano, halo, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, S-sulfon Amido, N-sulfonamido, C-carboxy, O-carboxy, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, trihalomethanesulfonyl, = O, = S, amino and amino Substituted or unsubstituted with one or more groups independently selected from the group consisting of protected derivatives of groups; Provided that Y is a compound of formula (I) or (II)

When forming dihydropyrazolylene, (i) D is not naphthyl if X is N and W is NH, (ii) X is CH, W is NH, Z is phenyl, R ¹⁰ or If R ¹¹ _is- (CH ₂ ) _0-6 OH, then D is not phenyl, and (iii)

Is not pyrazolyl or optionally substituted 5-hydroxypyrazolyl, and (iv) U is not NH; Further, provided that X is N and W is NH, then D is not phenyl; Additionally, in the compounds of Formula (III) or (VI), if X is N and W is NH, then R ⁶ , R ¹⁰ and R ^{11 do not} comprise carboxylic, amido, ester or sulfurate functional groups or carboxylic acid equivalents. Do not. A compound of formula (I), (II) or (III), a pharmaceutically acceptable salt, ester, amide or prodrug thereof. [Formula I]

[Formula II]

[Formula III]

In the above formula, R ¹ is hydrogen, halogen, OR ¹⁴ , NO ₂ , CN, NR ¹⁴ R ¹⁵ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ hetero Alkyl, CO ₂ R ¹⁴ , CONR ¹⁴ R ¹⁵ , SO ₃ R ¹⁴ , SO ₂ NR ¹⁴ R ¹⁵ and a carboxylic acid bioequivalent; Each R ² is a group consisting of hydrogen, halogen, OR ¹⁴ , NR ¹⁴ R ¹⁵ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, and optionally substituted C ₁ -C ₆ heteroalkyl Independently from; R ³ and R ⁴ are independently selected from the group consisting of hydrogen, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl and optionally substituted C ₁ -C ₆ heteroalkyl; R ⁵ is selected from the group consisting of hydrogen, halogen, OR ¹⁴ , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ haloheteroalkyl; R ⁶ is optionally substituted C ₁ -C ₁₀ alkyl, optionally substituted C ₁ -C ₁₀ haloalkyl, optionally substituted C ₁ -C ₁₀ heteroalkyl, (CH ₂ ) _m R ¹⁸ , C (O) NHR ¹⁸ , C≡CR ¹⁸ , CR ³ = CR ⁴ R ¹⁸ and CR ³ = R ¹⁸ ; R ⁷ is selected from the group consisting of CO ₂ R ¹⁴ , CONR ¹⁴ R ¹⁵ , SO ₃ R ¹⁴ , SO ₂ NR ¹⁴ R ¹⁵ and a carboxylic acid bioequivalent; Each of R ⁸ and R ⁹ is hydrogen, OR ¹⁶ , NR ¹⁶ R ¹⁷ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ heteroalkyl, (CH ₂ ) _m R ¹⁸ and none independently; R ⁸ and R ⁹ together form an optionally substituted olefin; R ⁸ and R ⁹ are joined to form an optionally substituted C ₃ -C ₈ ring; R ¹⁰ is hydrogen, halogen, oxo, OR ¹⁶ , NR ¹⁶ R ¹⁷ , SR ¹⁶ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl and optionally substituted C ₁ -C ₆ hetero Selected from the group consisting of alkyl; R ¹¹ is selected from the group consisting of hydrogen, halogen, OR ¹⁴ , NR ¹⁴ R ¹⁵ and SR ¹⁴ ; R ¹¹ and R ⁴ are joined to form an optionally substituted heterocycle; R ¹² is selected from the group consisting of hydrogen, halogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ haloheteroalkyl; R ¹⁴ is selected from the group consisting of hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ heterohaloalkyl; R ¹⁵ is selected from the group consisting of hydrogen, SO ₂ R ¹⁹ , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ heterohaloalkyl; A group of R ¹⁶ and R ¹⁷ consisting of hydrogen, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ heteroalkyl, and (CH ₂ ) _m R ¹⁸ Each independently selected from; R ¹⁶ and R ¹⁷ If either is optionally substituted C ₂ -C ₆ alkyl, the other is none; R ¹⁶ and R ¹⁷ are joined to form an optionally substituted C ₃ -C ₈ ring; R ¹⁸ is selected from an optionally substituted monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle, wherein R ¹⁸ comprises a nonaromatic heterocycle or carbocycle When attached, the attachment position may be on a nonaromatic heterocycle or carbocycle or aromatic ring system; R ¹⁹ is selected from the group consisting of hydrogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl and optionally substituted aryl; D is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle; E is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle; L is NH or none; Q is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle; U is selected from the group consisting of O, NR ⁴ , CR ³ R ⁴ , CO and none; W is selected from the group consisting of O, NR ⁴ , CR ³ R ⁴ , CO and none; X is N or CR ⁵ ; Y is 1 to 4 atomic spacers comprising one or more groups selected from optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ heteroalkyl, optionally substituted phenyl and optionally substituted heteroaryl; Z is absent; 2 to 5 atomic spacers selected from optionally substituted C ₆ -C ₁₀ aryl and optionally substituted C ₁ -C ₈ heteroaryl, each optionally bonded with an optionally substituted non-aromatic heterocycle or carbocycle; And _{1 selected} from optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ heteroalkyl, and optionally substituted C ₁ -C ₆ haloalkyl, each optionally optionally conjugated with optionally substituted C ₆ -C ₁₀ aryl; To 5 atomic spacers; m is 0, 1, 2 or 3; n is 0 or 1; Each optionally substituted group is alkyl, heteroalkyl, haloalkyl, heterohaloalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, non-aromatic heterocycle, hydroxy, alkoxy, aryloxy, mercapto, alkylthio, Arylthio, cyano, halo, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, S-sulfon Amido, N-sulfonamido, C-carboxy, O-carboxy, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, trihalomethanesulfonyl, = O, = S, amino and amino Substituted or unsubstituted with one or more groups independently selected from the group consisting of protected derivatives of groups; Provided that Y is a compound of formula (I) or (II)

When forming dihydropyrazolylene, (i) D is not naphthyl if X is N and W is NH, (ii) X is CH, W is NH, Z is phenyl, R ¹⁰ or If R ¹¹ _is- (CH ₂ ) _0-6 OH, then D is not phenyl, and (iii)

Is not pyrazolyl or optionally substituted 5-hydroxypyrazolyl, and (iv) U is not NH; Further, provided that X is N and W is NH, then D is not phenyl; Further, provided that X is N and W is NH in the compound of formula III, R ⁶ , R ¹⁰ And R ¹¹ does not include carboxylic, amido, ester, or sulfurate functional groups or carboxylic acid bioisomers. The method of claim 2, R ¹ is halogen; OR ¹⁴ ; NO ₂ ; CN; NR ¹⁴ R ¹⁵ ; C ₁ -C ₄ alkyl; C ₁ -C ₄ haloalkyl; Optionally substituted C ₁ -C ₄ heteroalkyl; CO ₂ R ¹⁴ ; CONR ¹⁴ R ¹⁵ ; SO ₃ R ¹⁴ ; SO ₂ NR ¹⁴ R ¹⁵ ; And tetrazole, NHSO ₂ R ¹⁹ , OC (S) NR ¹⁴ R ¹⁵ , SC (O) NR ¹⁴ R ¹⁵ and

Wherein A, B and C are each independently selected from the group consisting of O, S and NR ²⁰ ; Each R ² is hydrogen, halogen, OR ¹⁴ , NR ¹⁴ R ¹⁵ , C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl, and C ₁ -C ₄ Independently selected from the group consisting of heterohaloalkyl; R ³ and R ⁴ are independently selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl and optionally substituted C ₁ -C ₄ heteroalkyl; R ⁵ is selected from the group consisting of hydrogen, OR ¹⁴ , C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl and C ₁ -C ₄ haloheteroalkyl; R ⁶ is C ₁ -C ₁₀ alkyl, C ₁ -C ₁₀ haloalkyl, optionally substituted C ₁ -C ₁₀ heteroalkyl, (CH ₂ ) _m R ¹⁸ , C (O) NHR ¹⁸ , C≡CR ¹⁸ , CR ³ = CR ⁴ R ¹⁸ and CR ³ = R ¹⁸ ; R ⁷ is CO ₂ R ¹⁴ ; CONR ¹⁴ R ¹⁵ ; SO ₃ R ¹⁴ ; SO ₂ NR ¹⁴ R ¹⁵ ; And tetrazole, NHSO ₂ R ¹⁹ , OC (S) NR ¹⁴ R ¹⁵ , SC (O) NR ¹⁴ R ¹⁵ and

Wherein A, B and C are each independently selected from the group consisting of O, S and N; and are selected from the group consisting of carboxylic acid bioequivalents selected from the group consisting of; Each of R ⁸ and R ⁹ is hydrogen, OR ¹⁶ , NR ¹⁶ R ¹⁷ , C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, optionally substituted C ₁ -C ₄ heteroalkyl, (CH ₂ ) _m R Independently selected from ¹⁸ and none; R ⁸ and R ⁹ together form an optionally substituted olefin; R ⁸ and R ⁹ are joined to form an optionally substituted C ₃ -C ₈ ring; R ¹⁰ is selected from the group consisting of hydrogen, halogen, oxo, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl and optionally substituted C ₁ -C ₄ heteroalkyl; R ¹¹ is selected from the group consisting of hydrogen, halogen, OR ¹⁴ , NR ¹⁴ R ¹⁵ and SR ¹⁴ ; R ¹¹ and R ⁴ are joined to form an optionally substituted heterocycle; R ¹² is selected from the group consisting of hydrogen, halogen, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl and C ₁ -C ₄ haloheteroalkyl; R ¹³ is hydrogen, halogen, CN, NO ₂ , CO ₂ R ¹⁴ , S (O) _m R ¹⁴ , C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl and C ₁ -C ₄ haloheteroalkyl; R ¹⁴ is selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl and C ₁ -C ₄ heterohaloalkyl; R ¹⁵ is selected from the group consisting of hydrogen, SO ₂ R ¹⁹ , C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl and C ₁ -C ₄ heteroalkyl; R ¹⁶ and R ¹⁷ are each independently selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, optionally substituted C ₁ -C ₄ heteroalkyl and (CH ₂ ) _m R ¹⁸ ; R ¹⁶ and R ¹⁷ If either is C ₂ -C ₆ alkyl, the other is none; R ¹⁶ and R ¹⁷ are joined to form an optionally substituted C ₄ -C ₇ ring; R ¹⁹ is selected from the group consisting of hydrogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl and aryl; G is selected from the group consisting of O, S and NR ¹⁴ ; J is O, S, NR ¹⁴ And CR ¹⁴ R ¹⁵ ; K is O or S; Y is

,

,

And

Compound selected from the group consisting of. A compound of Formula IV, V or VI, a pharmaceutically acceptable salt, ester, amide or prodrug thereof. [Formula IV]

[Formula V]

[Formula VI]

In the above formula, R ¹ is hydrogen, halogen, OR ¹⁴ , NO ₂ , CN, NR ¹⁴ R ¹⁵ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ hetero Alkyl, CO ₂ R ¹⁴ , CONR ¹⁴ R ¹⁵ , SO ₃ R ¹⁴ , SO ₂ NR ¹⁴ R ¹⁵ and a carboxylic acid bioequivalent; Each R ² is a group consisting of hydrogen, halogen, OR ¹⁴ , NR ¹⁴ R ¹⁵ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, and optionally substituted C ₁ -C ₆ heteroalkyl Independently from; R ³ and R ⁴ are independently selected from the group consisting of hydrogen, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl and optionally substituted C ₁ -C ₆ heteroalkyl; R ⁵ is selected from the group consisting of hydrogen, halogen, OR ¹⁴ , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ haloheteroalkyl; R ⁶ is optionally substituted C ₁ -C ₁₀ alkyl, optionally substituted C ₁ -C ₁₀ haloalkyl, optionally substituted C ₁ -C ₁₀ heteroalkyl, (CH ₂ ) _m R ¹⁸ , C (O) NHR ¹⁸ , C≡CR ¹⁸ , CR ³ = CR ⁴ R ¹⁸ and CR ³ = R ¹⁸ ; R ⁷ is selected from the group consisting of CO ₂ R ¹⁴ , CONR ¹⁴ R ¹⁵ , SO ₃ R ¹⁴ , SO ₂ NR ¹⁴ R ¹⁵ and a carboxylic acid bioequivalent; Each of R ⁸ and R ⁹ is hydrogen, OR ¹⁶ , NR ¹⁶ R ¹⁷ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ heteroalkyl, (CH ₂ ) _m R ¹⁸ and none independently; R ⁸ and R ⁹ together form an optionally substituted olefin; R ⁸ and R ⁹ are joined to form an optionally substituted C ₃ -C ₈ ring; R ¹⁰ is hydrogen, halogen, oxo, OR ¹⁶ , NR ¹⁶ R ¹⁷ , SR ¹⁶ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl and optionally substituted C ₁ -C ₆ hetero Selected from the group consisting of alkyl; R ¹¹ is selected from the group consisting of hydrogen, halogen, OR ¹⁴ , NR ¹⁴ R ¹⁵ and SR ¹⁴ ; R ¹¹ and R ⁴ are joined to form an optionally substituted heterocycle; R ¹² is selected from the group consisting of hydrogen, halogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ haloheteroalkyl; R ¹³ is hydrogen, halogen, CN, NO ₂ , CO ₂ R ¹⁴ , S (O) _m R ¹⁴ , C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl and C ₁ -C ₄ haloheteroalkyl; R ¹⁴ is selected from the group consisting of hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ heterohaloalkyl; R ¹⁵ is selected from the group consisting of hydrogen, SO ₂ R ¹⁹ , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ heterohaloalkyl; R ¹⁶ and R ^{17 consist} of hydrogen, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ heteroalkyl, and (CH ₂ ) _m R ¹⁸ Each independently selected from the group; R ¹⁶ and R ¹⁷ If either is optionally substituted C ₂ -C ₆ alkyl, the other is none; R ¹⁶ and R ¹⁷ are joined to form an optionally substituted C ₃ -C ₈ ring; R ¹⁸ is selected from an optionally substituted monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle, wherein R ¹⁸ comprises a nonaromatic heterocycle or carbocycle When attached, the attachment position may be on a nonaromatic heterocycle or carbocycle or aromatic ring system; R ¹⁹ is selected from the group consisting of hydrogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl and optionally substituted aryl; D is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle; E is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle; L is NH or none; Q is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle; U is selected from the group consisting of O, NR ⁴ , CR ³ R ⁴ , CO and none; W is selected from the group consisting of O, NR ⁴ , CR ³ R ⁴ , CO and none; X is N or CR ⁵ ; Z is absent; 2 to 5 atomic spacers selected from optionally substituted C ₆ -C ₁₀ aryl and optionally substituted C ₁ -C ₈ heteroaryl, each optionally bonded with an optionally substituted non-aromatic heterocycle or carbocycle; And _{1 selected} from optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ heteroalkyl, and optionally substituted C ₁ -C ₆ haloalkyl, each optionally optionally conjugated with optionally substituted C ₆ -C ₁₀ aryl; To 5 atomic spacers; m is 0, 1, 2 or 3; n is 0 or 1; Each optionally substituted group is alkyl, heteroalkyl, haloalkyl, heterohaloalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, non-aromatic heterocycle, hydroxy, alkoxy, aryloxy, mercapto, alkylthio, Arylthio, cyano, halo, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, S-sulfone Amido, N-sulfonamido, C-carboxy, O-carboxy, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, trihalomethanesulfonyl, = O, = S, amino and amino Substituted or unsubstituted with one or more groups independently selected from the group consisting of protected derivatives of groups; Provided that when X is N and W is NH, then D is not phenyl; Further, provided that when X is N and W is NH in the compound of formula VI, R ⁶ , R ¹⁰ And R ¹¹ does not include carboxylic, amido, ester, or sulfurate functional groups or carboxylic acid bioisomers. The compound of claim 4, wherein R ¹ is hydrogen; halogen; OR ¹⁴ ; NO ₂ ; CN; NR ¹⁴ R ¹⁵ ; Optionally substituted C ₁ -C ₆ alkyl; Optionally substituted C ₁ -C ₆ haloalkyl; Optionally substituted C ₁ -C ₆ heteroalkyl; CO ₂ R ¹⁴ ; CONR ¹⁴ R ¹⁵ ; SO ₃ R ¹⁴ ; SO ₂ NR ¹⁴ R ¹⁵ ; And tetrazole, NHSO ₂ R ¹⁹ , OC (S) NR ¹⁴ R ¹⁵ , SC (O) NR ¹⁴ R ¹⁵ and

Wherein A, B and C are each independently selected from the group consisting of O, S and N; and are selected from the group consisting of carboxylic acid bioequivalents selected from the group consisting of; R ⁷ is CO ₂ R ¹⁴ ; CONR ¹⁴ R ¹⁵ ; SO ₃ R ¹⁴ ; SO ₂ NR ¹⁴ R ¹⁵ ; And tetrazole, NHSO ₂ R ¹⁹ , OC (S) NR ¹⁴ R ¹⁵ , SC (O) NR ¹⁴ R ¹⁵ and

Wherein A, B, and C are each independently selected from the group consisting of O, S, and N. A compound selected from the group consisting of carboxylic acid bioisomers selected from the group consisting of: A compound of formula (I), (II), (III), (IV), (V) or (VI), a pharmaceutically acceptable salt, ester, amide or prodrug thereof. [Formula I]

[Formula II]

[Formula III]

[Formula IV]

[Formula V]

[Formula VI]

In the above formula, R ¹ is hydrogen, halogen, OR ¹⁴ , NO ₂ , CN, NR ¹⁴ R ¹⁵ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ hetero Alkyl, CO ₂ R ¹⁴ , CONR ¹⁴ R ¹⁵ , SO ₃ R ¹⁴ , SO ₂ NR ¹⁴ R ¹⁵ and a carboxylic acid bioequivalent; Each R ² is a group consisting of hydrogen, halogen, OR ¹⁴ , NR ¹⁴ R ¹⁵ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, and optionally substituted C ₁ -C ₆ heteroalkyl Independently from; R ³ and R ⁴ are independently selected from the group consisting of hydrogen, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl and optionally substituted C ₁ -C ₆ heteroalkyl; R ⁵ is selected from the group consisting of hydrogen, halogen, OR ¹⁴ , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ haloheteroalkyl; R ⁶ consists of optionally substituted C ₁ -C ₁₀ alkyl, optionally substituted C ₁ -C ₁₀ haloalkyl and optionally substituted C ₁ -C ₁₀ heteroalkyl, each optionally substituted with substituted aryl or substituted heteroaryl selected from the group, or, R ⁶ is ^{_{(CH 2) m R 18,}} C (O) NHR 18, C≡CR 18, CR 3 = CR 4 R 18 , and is selected from the group consisting of CR ³ = R ^18; R ⁷ is selected from the group consisting of CO ₂ R ¹⁴ , CONR ¹⁴ R ¹⁵ , SO ₃ R ¹⁴ , SO ₂ NR ¹⁴ R ¹⁵ and a carboxylic acid bioequivalent; Each of R ⁸ and R ⁹ is hydrogen, OR ¹⁶ , NR ¹⁶ R ¹⁷ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ heteroalkyl, (CH ₂ ) _m R ¹⁸ and none independently; R ⁸ and R ⁹ together form an optionally substituted olefin; R ⁸ and R ⁹ are joined to form an optionally substituted C ₃ -C ₈ ring; R ¹⁰ is hydrogen, halogen, oxo, OR ¹⁶ , NR ¹⁶ R ¹⁷ , SR ¹⁶ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl and optionally substituted C ₁ -C ₆ hetero Selected from the group consisting of alkyl; R ¹¹ is selected from the group consisting of hydrogen, halogen, OR ¹⁴ , NR ¹⁴ R ¹⁵ and SR ¹⁴ ; R ¹¹ and R ⁴ are joined to form an optionally substituted heterocycle; R ¹² is selected from the group consisting of hydrogen, halogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ haloheteroalkyl; R ¹³ is hydrogen, halogen, CN, NO ₂ , CO ₂ R ¹⁴ , S (O) _m R ¹⁴ , C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl and C ₁ -C ₄ haloheteroalkyl; R ¹⁴ is selected from the group consisting of hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ heterohaloalkyl; R ¹⁵ is selected from the group consisting of hydrogen, SO ₂ R ¹⁹ , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ heterohaloalkyl; A group of R ¹⁶ and R ¹⁷ consisting of hydrogen, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ heteroalkyl, and (CH ₂ ) _m R ¹⁸ Each independently selected from; R ¹⁶ and R ¹⁷ If either is optionally substituted C ₂ -C ₆ alkyl, the other is none; R ¹⁶ and R ¹⁷ are joined to form an optionally substituted C ₃ -C ₈ ring; R ¹⁸ is selected from an optionally substituted monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle, wherein R ¹⁸ comprises a nonaromatic heterocycle or carbocycle When attached, the attachment position may be on a nonaromatic heterocycle or carbocycle or aromatic ring system; R ¹⁹ is selected from the group consisting of hydrogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl and optionally substituted aryl; D is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle; E is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle; L is NH or none; Q is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle; U is selected from the group consisting of O, NR ⁴ , CR ³ R ⁴ , CO and none; W is selected from the group consisting of O, NR ⁴ , CR ³ R ⁴ , CO and none; X is N or CR ⁵ ; Y is 1 to 4 atomic spacers comprising one or more groups selected from optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ heteroalkyl, optionally substituted phenyl and optionally substituted heteroaryl; Z is absent; 2 to 5 atomic spacers selected from optionally substituted C ₆ -C ₁₀ aryl and optionally substituted C ₁ -C ₈ heteroaryl, each optionally bonded with an optionally substituted non-aromatic heterocycle or carbocycle; And _{1 selected} from optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ heteroalkyl, and optionally substituted C ₁ -C ₆ haloalkyl, each optionally optionally conjugated with optionally substituted C ₆ -C ₁₀ aryl; To 5 atomic spacers; m is 0, 1, 2 or 3; n is 0 or 1; Provided that X is N, W is NH, Y is not -N = CR ¹² -which forms dihydropyrazole, and Z or R ⁶ is not an optionally substituted non-aromatic ring bonded with an optionally substituted aromatic ring or ; X is N, W is NH, R ⁶ is alkoxy, optionally substituted alkyl, optionally substituted aryl or optionally substituted heteroaryl, and -N = CR ¹² -wherein Z forms dihydropyrazole, Z D is not phenyl unless is an optionally substituted non-aromatic ring combined with an optionally substituted aromatic ring; Provided that when X is N, W is NH and Y is -N = CR ¹² -which forms dihydropyrazole, then D is not naphthyl; Provided that U is NH; Or any one of R ¹⁰ and R ¹¹ forms D-hydroxypyrazole, X is N and W is NH; E and any of R ¹⁰ and R ¹¹ form 5-hydroxypyrazole, X is N and W is NH; E is phenyl, either R ¹⁰ or R ¹¹ is — (CH ₂ ) _0-6 OH, X is C, W is NH, R ⁶ is optionally substituted aryl or optionally substituted heteroaryl, Z is absent, optionally substituted alkyl, optionally substituted aryl or optionally substituted heteroaryl; E is phenyl, either R ¹⁰ or R ¹¹ is — (CH ₂ ) _0-6 OH, X is N, W is NH, no Z, optionally substituted alkyl, optionally substituted aryl or optionally Substituted heteroaryl, R ⁶ is C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy,-(CH ₂ ) _0-6 OR ²⁰ , optionally substituted aryl, optionally substituted heteroaryl, NR ²¹ R ²² or Represented by Formula VII

Is a heterocyclic methylene substituent (wherein A, B, C and V are each independently selected from the group consisting of O, S and NR ²⁰ ); D is phenyl, one of R ¹⁰ and R ¹¹ is — (CH ₂ ) _0-6 OH, X is C, W is NH, Z is aromatic, R ⁶ is alkoxy, optionally substituted alkyl, Optionally substituted aryl or optionally substituted heteroaryl; Y is not -N = CR ¹² -which forms dihydropyrazole; R ²⁰ is selected from the group consisting of hydrogen, substituted alkyl, substituted aryl, and substituted heteroaryl; R ²¹ And R ²² is each independently selected from the group consisting of hydrogen, alkyl and aryl; R ²¹ And a 5 or 6 membered saturated ring containing up to one other heteroatom selected from oxygen and nitrogen together with N to which R ²² is attached. Compounds of Formula I, II, III, IV, V or VI. [Formula I]

[Formula II]

[Formula III]

[Formula IV]

[Formula V]

[Formula VI]

In the above formula, R ¹ is hydrogen, halogen, OR ¹⁴ , NO ₂ , CN, NR ¹⁴ R ¹⁵ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ hetero Alkyl, CO ₂ R ¹⁴ , CONR ¹⁴ R ¹⁵ , SO ₃ R ¹⁴ , SO ₂ NR ¹⁴ R ¹⁵ and a carboxylic acid bioequivalent; R ² is selected from the group consisting of hydrogen, halogen, OR ¹⁴ , NR ¹⁴ R ¹⁵ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl and optionally substituted C ₁ -C ₆ heteroalkyl Independently selected; R ³ and R ⁴ are independently selected from the group consisting of hydrogen, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl and optionally substituted C ₁ -C ₆ heteroalkyl; R ⁵ is selected from the group consisting of hydrogen, halogen, OR ¹⁴ , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ haloheteroalkyl; R ⁶ consists of optionally substituted C ₁ -C ₁₀ alkyl, optionally substituted C ₁ -C ₁₀ haloalkyl and optionally substituted C ₁ -C ₁₀ heteroalkyl, each optionally substituted with substituted aryl or substituted heteroaryl Is selected from the group or R ⁶ is (CH ₂ ) _m R ¹⁸ Or C (O) NHR ¹⁸ ; R ⁷ is selected from the group consisting of CO ₂ R ¹⁴ , CONR ¹⁴ R ¹⁵ , SO ₃ R ¹⁴ , SO ₂ NR ¹⁴ R ¹⁵ and a carboxylic acid bioequivalent; R ⁸ and R ⁹ are hydrogen, OR ¹⁶ , NR ¹⁶ R ¹⁷ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ heteroalkyl, (CH ₂ ) each independently selected from _m R ¹⁸ and none; R ⁸ and R ⁹ together form an optionally substituted olefin; R ⁸ and R ⁹ are joined to form an optionally substituted C ₃ -C ₈ ring; R ¹⁰ is hydrogen, halogen, oxo, OR ¹⁶ , NR ¹⁶ R ¹⁷ , SR ¹⁶ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl and optionally substituted C ₁ -C ₆ hetero Selected from the group consisting of alkyl; R ¹¹ is selected from the group consisting of hydrogen, halogen, OR ¹⁴ , NR ¹⁴ R ¹⁵ and SR ¹⁴ ; R ¹¹ and R ⁴ are joined to form an optionally substituted heterocycle; R ¹² is selected from the group consisting of hydrogen, halogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ haloheteroalkyl; R ¹³ is hydrogen, halogen, CN, NO ₂ , CO ₂ R ¹⁴ , S (O) _m R ¹⁴ , C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl and C ₁ -C ₄ haloheteroalkyl; R ¹⁴ is selected from the group consisting of hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ heterohaloalkyl; R ¹⁵ is selected from the group consisting of hydrogen, SO ₂ R ¹⁹ , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ heterohaloalkyl; A group of R ¹⁶ and R ¹⁷ consisting of hydrogen, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ heteroalkyl, and (CH ₂ ) _m R ¹⁸ Each independently selected from; R ¹⁶ and R ¹⁷ If either is optionally substituted C ₂ -C ₆ alkyl, the other is none; R ¹⁶ and R ¹⁷ are joined to form an optionally substituted C ₃ -C ₈ ring; R ¹⁸ is selected from an optionally substituted monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle; R ¹⁹ is selected from the group consisting of hydrogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl and optionally substituted aryl; D is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle; E is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle; L is NH or none; Q is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle; U is selected from the group consisting of O, NR ⁴ , CR ³ R ⁴ , CO and none; W is selected from the group consisting of O, NR ⁴ , CR ³ R ⁴ , CO and none; X is N or CR ⁵ ; Y is 1 to 4 atomic spacers comprising one or more groups selected from optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ heteroalkyl, optionally substituted phenyl and optionally substituted heteroaryl; Z is absent; 2 to 5 atomic spacers selected from optionally substituted C ₆ -C ₁₀ aryl and optionally substituted C ₁ -C ₈ heteroaryl, each optionally bonded with an optionally substituted non-aromatic heterocycle or carbocycle; And _{1 selected} from optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ heteroalkyl, and optionally substituted C ₁ -C ₆ haloalkyl, each optionally optionally conjugated with optionally substituted C ₆ -C ₁₀ aryl; To 5 atomic spacers; m is 0, 1 or 2; n is 0 or 1; Each optionally substituted group is alkyl, heteroalkyl, haloalkyl, heterohaloalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, non-aromatic heterocycle, hydroxy, alkoxy, aryloxy, mercapto, alkylthio, Arylthio, cyano, halo, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, S-sulfon Amido, N-sulfonamido, C-carboxy, O-carboxy, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, trihalomethanesulfonyl, = O, = S, amino and amino Substituted or unsubstituted with one or more groups independently selected from the group consisting of protected derivatives of groups; Provided that Y is a compound of formula (I) or (II)

When forming dihydropyrazolylene, (i) D is not naphthyl if X is N and W is NH, (ii) X is CH, W is NH, Z is phenyl, R ¹⁰ or If R ¹¹ _is- (CH ₂ ) _0-6 OH, then D is not phenyl, and (iii)

Is not pyrazolyl or optionally substituted 5-hydroxypyrazolyl, and (iv) U is not NH; Further provided that if X is N and W is NH, then D is not phenyl; Additionally, in the compounds of Formula (III) or (VI), if X is N and W is NH, then R ⁶ , R ¹⁰ and R ^{11 do not} comprise carboxylic, amido, ester or sulfurate functional groups or carboxylic acid equivalents. Do not. Compounds of formula (I), (II) or (III). [Formula I]

[Formula II]

[Formula III]

In the above formula, R ¹ is hydrogen, halogen, OR ¹⁴ , NO ₂ , CN, NR ¹⁴ R ¹⁵ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ hetero Alkyl, CO ₂ R ¹⁴ , CONR ¹⁴ R ¹⁵ , SO ₃ R ¹⁴ , SO ₂ NR ¹⁴ R ¹⁵ and a carboxylic acid bioequivalent; R ² is selected from the group consisting of hydrogen, halogen, OR ¹⁴ , NR ¹⁴ R ¹⁵ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl and optionally substituted C ₁ -C ₆ heteroalkyl Independently selected; R ³ and R ⁴ are independently selected from the group consisting of hydrogen, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl and optionally substituted C ₁ -C ₆ heteroalkyl; R ⁵ is selected from the group consisting of hydrogen, halogen, OR ¹⁴ , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ haloheteroalkyl; R ⁶ is optionally substituted C ₁ -C ₁₀ alkyl, optionally substituted C ₁ -C ₁₀ haloalkyl, optionally substituted C ₁ -C ₁₀ heteroalkyl, (CH ₂ ) _m R ¹⁸ And C (O) NHR ¹⁸ ; R ⁷ is selected from the group consisting of CO ₂ R ¹⁴ , CONR ¹⁴ R ¹⁵ , SO ₃ R ¹⁴ , SO ₂ NR ¹⁴ R ¹⁵ and a carboxylic acid bioequivalent; R ⁸ and R ⁹ are hydrogen, OR ¹⁶ , NR ¹⁶ R ¹⁷ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ heteroalkyl, (CH ₂ ) each independently selected from _m R ¹⁸ and none; R ⁸ and R ⁹ together form an optionally substituted olefin; R ⁸ and R ⁹ are joined to form an optionally substituted C ₃ -C ₈ ring; R ¹⁰ is hydrogen, halogen, oxo, OR ¹⁶ , NR ¹⁶ R ¹⁷ , SR ¹⁶ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl and optionally substituted C ₁ -C ₆ hetero Selected from the group consisting of alkyl; R ¹¹ is selected from the group consisting of hydrogen, halogen, OR ¹⁴ , NR ¹⁴ R ¹⁵ and SR ¹⁴ ; R ¹¹ and R ⁴ are joined to form an optionally substituted heterocycle; R ¹² is selected from the group consisting of hydrogen, halogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ haloheteroalkyl; R ¹⁴ is selected from the group consisting of hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ heterohaloalkyl; R ¹⁵ is selected from the group consisting of hydrogen, SO ₂ R ¹⁹ , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ heterohaloalkyl; A group of R ¹⁶ and R ¹⁷ consisting of hydrogen, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ heteroalkyl, and (CH ₂ ) _m R ¹⁸ Each independently selected from; R ¹⁶ and R ¹⁷ If either is optionally substituted C ₂ -C ₆ alkyl, the other is none; R ¹⁶ and R ¹⁷ are joined to form an optionally substituted C ₃ -C ₈ ring; R ¹⁸ is selected from an optionally substituted monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle; R ¹⁹ is selected from the group consisting of hydrogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl and optionally substituted aryl; D is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle; E is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle; L is NH or none; Q is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle; U is selected from the group consisting of O, NR ⁴ , CR ³ R ⁴ , CO and none; W is selected from the group consisting of O, NR ⁴ , CR ³ R ⁴ , CO and none; X is N or CR ⁵ ; Y is 1 to 4 atomic spacers comprising one or more groups selected from optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ heteroalkyl, optionally substituted phenyl and optionally substituted heteroaryl; Z is absent; 2 to 5 atomic spacers selected from optionally substituted C ₆ -C ₁₀ aryl and optionally substituted C ₁ -C ₈ heteroaryl, each optionally bonded with an optionally substituted non-aromatic heterocycle or carbocycle; And _{1 selected} from optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ heteroalkyl, and optionally substituted C ₁ -C ₆ haloalkyl, each optionally optionally conjugated with optionally substituted C ₆ -C ₁₀ aryl; To 5 atomic spacers; m is 0, 1 or 2; n is 0 or 1; Provided that Y is a compound of formula (I) or (II)

When forming dihydropyrazolylene, (i) D is not naphthyl if X is N and W is NH, (ii) X is CH, W is NH, Z is phenyl, R ¹⁰ or If R ¹¹ _is- (CH ₂ ) _0-6 OH, then D is not phenyl, and (iii)

Is not pyrazolyl or optionally substituted 5-hydroxypyrazolyl, and (iv) U is not NH; Further provided that if X is N and W is NH, then D is not phenyl; Further, provided that X is N and W is NH in the compound of formula III, R ⁶ , R ¹⁰ And R ¹¹ does not include carboxylic, amido, ester, or sulfurate functional groups or carboxylic acid bioisomers. The method of claim 2, R ¹ is halogen; OR ¹⁴ ; NO ₂ ; CN; NR ¹⁴ R ¹⁵ ; C ₁ -C ₄ alkyl; C ₁ -C ₄ haloalkyl; Optionally substituted C ₁ -C ₄ heteroalkyl; CO ₂ R ¹⁴ ; CONR ¹⁴ R ¹⁵ ; SO ₃ R ¹⁴ ; SO ₂ NR ¹⁴ R ¹⁵ ; And tetrazole, NHSO ₂ R ¹⁹ , OC (S) NR ¹⁴ R ¹⁵ , SC (O) NR ¹⁴ R ¹⁵ and

Wherein A, B and C are each independently selected from the group consisting of O, S and NR ²⁰ ; R ² is hydrogen, halogen, OR ¹⁴ , NR ¹⁴ R ¹⁵ , C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl and C ₁ -C ₄ Independently selected from the group consisting of heterohaloalkyl; R ³ and R ⁴ are independently selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl and optionally substituted C ₁ -C ₄ heteroalkyl; R ⁵ is selected from the group consisting of hydrogen, OR ¹⁴ , C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl and C ₁ -C ₄ haloheteroalkyl; R ⁶ is C ₁ -C ₁₀ alkyl, C ₁ -C ₁₀ haloalkyl, optionally substituted C ₁ -C ₁₀ heteroalkyl, (CH ₂ ) _m R ¹⁸ And C (O) NHR ¹⁸ ; R ⁷ is CO ₂ R ¹⁴ ; CONR ¹⁴ R ¹⁵ ; SO ₃ R ¹⁴ ; SO ₂ NR ¹⁴ R ¹⁵ ; And tetrazole, NHSO ₂ R ¹⁹ , OC (S) NR ¹⁴ R ¹⁵ , SC (O) NR ¹⁴ R ¹⁵ and

Wherein A, B and C are each independently selected from the group consisting of O, S and N; and are selected from the group consisting of carboxylic acid bioequivalents selected from the group consisting of; R ⁸ and R ⁹ is ^{hydrogen, OR 16, NR 16 R 17} , C 1 -C 4 alkyl, C ₁ -C ₄ haloalkyl, an optionally substituted C ₁ - C ₄ alkyl, heteroaryl, (CH _{2) m} R ¹⁸ and Each independently selected from none; R ⁸ and R ⁹ together form an optionally substituted olefin; R ⁸ and R ⁹ are joined to form an optionally substituted C ₃ -C ₈ ring; R ¹⁰ is selected from the group consisting of hydrogen, halogen, oxo, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl and optionally substituted C ₁ -C ₄ heteroalkyl; R ¹² is selected from the group consisting of hydrogen, halogen, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl and C ₁ -C ₄ haloheteroalkyl; R ¹³ is hydrogen, halogen, CN, NO ₂ , CO ₂ R ¹⁴ , S (O) _m R ¹⁴ , C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl and C ₁ -C ₄ haloheteroalkyl; R ¹⁴ is selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl and C ₁ -C ₄ heterohaloalkyl; R ¹⁵ is selected from the group consisting of hydrogen, SO ₂ R ¹⁹ , C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl and C ₁ -C ₄ heteroalkyl; R¹⁶ And R¹⁷2 hydrogen, C_One-C₄ Alkyl, C_One-C₄ Haloalkyl, optionally substituted C_One-C₄ Heteroalkyls and (CH₂)_mR¹⁸Each independently selected from the group consisting of; R¹⁶ And R¹⁷ Which one is C₂-C₆ If alkyl, the other is none; R¹⁶ And R¹⁷This is optionally substituted C₄-C₇ To form a ring; R ¹⁹ is selected from the group consisting of hydrogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl and aryl; G is selected from the group consisting of O, S and NR ¹⁴ ; J is O, S, NR ¹⁴ And CR ¹⁴ R ¹⁵ ; K is O or S; L is NH or none; Y is

,

,

And

It is selected from the group consisting of. A compound of Formula IV, V or VI, a pharmaceutically acceptable salt, ester, amide or prodrug thereof. [Formula IV]

[Formula V]

[Formula VI]

In the above formula, R ¹ is hydrogen, halogen, OR ¹⁴ , NO ₂ , CN, NR ¹⁴ R ¹⁵ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ hetero Alkyl, CO ₂ R ¹⁴ , CONR ¹⁴ R ¹⁵ , SO ₃ R ¹⁴ , SO ₂ NR ¹⁴ R ¹⁵ and a carboxylic acid bioequivalent; R ² is selected from the group consisting of hydrogen, halogen, OR ¹⁴ , NR ¹⁴ R ¹⁵ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl and optionally substituted C ₁ -C ₆ heteroalkyl Selected; R ³ and R ⁴ are independently selected from the group consisting of hydrogen, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl and optionally substituted C ₁ -C ₆ heteroalkyl; R ⁵ is selected from the group consisting of hydrogen, halogen, OR ¹⁴ , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ haloheteroalkyl; R ⁶ is optionally substituted C ₁ -C ₁₀ alkyl, optionally substituted C ₁ -C ₁₀ haloalkyl, optionally substituted C ₁ -C ₁₀ heteroalkyl, (CH ₂ ) _m R ¹⁸ And C (O) NHR ¹⁸ ; R ⁷ is selected from the group consisting of CO ₂ R ¹⁴ , CONR ¹⁴ R ¹⁵ , SO ₃ R ¹⁴ , SO ₂ NR ¹⁴ R ¹⁵ and a carboxylic acid bioequivalent; R ⁸ and R ⁹ are hydrogen, OR ¹⁶ , NR ¹⁶ R ¹⁷ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ heteroalkyl, (CH ₂ ) each independently selected from _m R ¹⁸ and none; R ⁸ and R ⁹ together form an optionally substituted olefin; R ⁸ and R ⁹ are joined to form an optionally substituted C ₃ -C ₈ ring; R ¹⁰ is hydrogen, halogen, oxo, OR ¹⁶ , NR ¹⁶ R ¹⁷ , SR ¹⁶ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl and optionally substituted C ₁ -C ₆ hetero Selected from the group consisting of alkyl; R ¹¹ is selected from the group consisting of hydrogen, halogen, OR ¹⁴ , NR ¹⁴ R ¹⁵ and SR ¹⁴ ; R ¹¹ and R ⁴ are joined to form an optionally substituted heterocycle; R ¹² is selected from the group consisting of hydrogen, halogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ haloheteroalkyl; R ¹³ is hydrogen, halogen, CN, NO ₂ , CO ₂ R ¹⁴ , S (O) _m R ¹⁴ , C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl and C ₁ -C ₄ haloheteroalkyl; R ¹⁴ is selected from the group consisting of hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ heterohaloalkyl; R ¹⁵ is selected from the group consisting of hydrogen, SO ₂ R ¹⁹ , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ heterohaloalkyl; A group of R ¹⁶ and R ¹⁷ consisting of hydrogen, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ heteroalkyl, and (CH ₂ ) _m R ¹⁸ Each independently selected from; R ¹⁶ and R ¹⁷ If either is optionally substituted C ₂ -C ₆ alkyl, the other is none; R ¹⁶ and R ¹⁷ are joined to form an optionally substituted C ₃ -C ₈ ring; R ¹⁸ is an optionally substituted monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle; R ¹⁹ is selected from the group consisting of hydrogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl and optionally substituted aryl; D is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle; E is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle; L is NH or none; Q is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle; U is selected from the group consisting of O, NR ⁴ , CR ³ R ⁴ , CO and none; W is selected from the group consisting of O, NR ⁴ , CR ³ R ⁴ , CO and none; X is N or CR ⁵ ; Z is absent; 2 to 5 atomic spacers selected from optionally substituted C ₆ -C ₁₀ aryl and optionally substituted C ₁ -C ₈ heteroaryl, each optionally bonded with an optionally substituted non-aromatic heterocycle or carbocycle; And _{1 selected} from optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ heteroalkyl, and optionally substituted C ₁ -C ₆ haloalkyl, each optionally optionally conjugated with optionally substituted C ₆ -C ₁₀ aryl; To 5 atomic spacers; m is 0, 1 or 2; n is 0 or 1; Provided that when X is N and W is NH, then D is not phenyl; Further, provided that when X is N and W is NH in the compound of formula VI, R ⁶ , R ¹⁰ And R ¹¹ does not include carboxylic, amido, ester, or sulfurate functional groups or carboxylic acid bioisomers. The method of claim 4, wherein R ¹ is hydrogen; halogen; OR ¹⁴ ; NO ₂ ; CN; NR ¹⁴ R ¹⁵ ; Optionally substituted C ₁ -C ₆ alkyl; Optionally substituted C ₁ -C ₆ haloalkyl; Optionally substituted C ₁ -C ₆ heteroalkyl; CO ₂ R ¹⁴ ; CONR ¹⁴ R ¹⁵ ; SO ₃ R ¹⁴ ; SO ₂ NR ¹⁴ R ¹⁵ ; And tetrazole, NHSO ₂ R ¹⁹ , OC (S) NR ¹⁴ R ¹⁵ , SC (O) NR ¹⁴ R ¹⁵ and

Wherein A, B and C are each independently selected from the group consisting of O, S and N, and are selected from the group consisting of carboxylic acid bioequivalents selected from the group consisting of R ⁷ is CO ₂ R ¹⁴ ; CONR ¹⁴ R ¹⁵ ; SO ₃ R ¹⁴ ; SO ₂ NR ¹⁴ R ¹⁵ ; And tetrazole, NHSO ₂ R ¹⁹ , OC (S) NR ¹⁴ R ¹⁵ , SC (O) NR ¹⁴ R ¹⁵ and

Wherein each of A, B and C is independently selected from the group consisting of O, S, and N). Compounds of Formula I, II, III, IV, V or VI. [Formula I]

[Formula II]

[Formula III]

[Formula IV]

[Formula V] [Formula VI]

In the above formula, R ¹ is hydrogen, halogen, OR ¹⁴ , NO ₂ , CN, NR ¹⁴ R ¹⁵ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ hetero Alkyl, CO ₂ R ¹⁴ , CONR ¹⁴ R ¹⁵ , SO ₃ R ¹⁴ , SO ₂ NR ¹⁴ R ¹⁵ and a carboxylic acid bioequivalent; R ² is selected from the group consisting of hydrogen, halogen, OR ¹⁴ , NR ¹⁴ R ¹⁵ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl and optionally substituted C ₁ -C ₆ heteroalkyl Selected; R ³ and R ⁴ are independently selected from the group consisting of hydrogen, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl and optionally substituted C ₁ -C ₆ heteroalkyl; R ⁵ is selected from the group consisting of hydrogen, halogen, OR ¹⁴ , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ haloheteroalkyl; R ⁶ consists of optionally substituted C ₁ -C ₁₀ alkyl, optionally substituted C ₁ -C ₁₀ haloalkyl and optionally substituted C ₁ -C ₁₀ heteroalkyl, each optionally substituted with substituted aryl or substituted heteroaryl Is selected from the group or R ⁶ is (CH ₂ ) _m R ¹⁸ Or C (O) NHR ¹⁸ ; R ⁷ is selected from the group consisting of CO ₂ R ¹⁴ , CONR ¹⁴ R ¹⁵ , SO ₃ R ¹⁴ , SO ₂ NR ¹⁴ R ¹⁵ and a carboxylic acid bioequivalent; R ⁸ and R ⁹ are hydrogen, OR ¹⁶ , NR ¹⁶ R ¹⁷ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ heteroalkyl, (CH ₂ ) each independently selected from _m R ¹⁸ and none; R ⁸ and R ⁹ together form an optionally substituted olefin; R ⁸ and R ⁹ are joined to form an optionally substituted C ₃ -C ₈ ring; R ¹⁰ is hydrogen, halogen, oxo, OR ¹⁶ , NR ¹⁶ R ¹⁷ , SR ¹⁶ , optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl and optionally substituted C ₁ -C ₆ hetero Selected from the group consisting of alkyl; R ¹¹ is selected from the group consisting of hydrogen, halogen, OR ¹⁴ , NR ¹⁴ R ¹⁵ and SR ¹⁴ ; R ¹¹ and R ⁴ are joined to form an optionally substituted heterocycle; R ¹² is selected from the group consisting of hydrogen, halogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ haloheteroalkyl; R ¹³ is hydrogen, halogen, CN, NO ₂ , CO ₂ R ¹⁴ , S (O) _m R ¹⁴ , C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl and C ₁ -C ₄ haloheteroalkyl; R ¹⁴ is selected from the group consisting of hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ heterohaloalkyl; R ¹⁵ is selected from the group consisting of hydrogen, SO ₂ R ¹⁹ , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl and C ₁ -C ₆ heterohaloalkyl; R ¹⁶ and R ^{17 consist} of hydrogen, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ heteroalkyl, and (CH ₂ ) _m R ¹⁸ Each independently selected from the group; R ¹⁶ and R ¹⁷ If either is optionally substituted C ₂ -C ₆ alkyl, the other is none; R ¹⁶ and R ¹⁷ are joined to form an optionally substituted C ₃ -C ₈ ring; R ¹⁸ is selected from an optionally substituted monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle; R ¹⁹ is selected from the group consisting of hydrogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl and optionally substituted aryl; D is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle; E is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle; L is NH or none; Q is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally conjugated with a nonaromatic heterocycle or carbocycle; U is selected from the group consisting of O, NR ⁴ , CR ³ R ⁴ , CO and none; W is selected from the group consisting of O, NR ⁴ , CR ³ R ⁴ , CO and none; X is N or CR ⁵ ; Y is 1 to 4 atomic spacers comprising one or more groups selected from optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ heteroalkyl, optionally substituted phenyl and optionally substituted heteroaryl; Z is absent; 2 to 5 atomic spacers selected from optionally substituted C ₆ -C ₁₀ aryl and optionally substituted C ₁ -C ₈ heteroaryl, each optionally bonded with an optionally substituted non-aromatic heterocycle or carbocycle; And _{1 selected} from optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ heteroalkyl, and optionally substituted C ₁ -C ₆ haloalkyl, each optionally optionally conjugated with optionally substituted C ₆ -C ₁₀ aryl; To 5 atomic spacers; m is 0, 1 or 2; n is 0 or 1; Provided that X is N, W is NH, Y is not -N = CR ¹² -which forms dihydropyrazole, and Z or R ⁶ is not an optionally substituted non-aromatic ring bonded with an optionally substituted aromatic ring or ; X is N, W is NH, R ⁶ is alkoxy, optionally substituted alkyl, optionally substituted aryl or optionally substituted heteroaryl, and -N = CR ¹² -wherein Y forms dihydropyrazole, Unless Z is an optionally substituted non-aromatic ring bonded with an optionally substituted aromatic ring, then D is not phenyl; Provided that when X is N, W is NH and Y is -N = CR ¹² -which forms dihydropyrazole, then D is not naphthyl; Provided that U is NH; Or any one of R ¹⁰ and R ¹¹ forms D-hydroxypyrazole, X is N and W is NH; E and any of R ¹⁰ and R ¹¹ form 5-hydroxypyrazole, X is N and W is NH; E is phenyl, either R ¹⁰ or R ¹¹ is — (CH ₂ ) _0-6 OH, X is C, W is NH, R ⁶ is optionally substituted aryl or optionally substituted heteroaryl, Z is absent, optionally substituted alkyl, optionally substituted aryl or optionally substituted heteroaryl; E is phenyl, either R ¹⁰ or R ¹¹ is — (CH ₂ ) _0-6 OH, X is N, W is NH, no Z, optionally substituted alkyl, optionally substituted aryl or optionally Substituted heteroaryl, R ⁶ is C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy,-(CH ₂ ) _0-6 OR ²⁰ , optionally substituted aryl, optionally substituted heteroaryl, NR ²¹ R ²² or Represented by Formula VII

(Wherein A, B, C and V are each independently selected from the group consisting of O, S and NR ²⁰ ), a heterocyclic methylene substituent; D is phenyl, one of R ¹⁰ and R ¹¹ is — (CH ₂ ) _0-6 OH, X is C, W is NH, Z is aromatic, R ⁶ is alkoxy, optionally substituted alkyl, Optionally substituted aryl or optionally substituted heteroaryl; Y is not -N = CR ¹² -which forms dihydropyrazole; R ²⁰ is selected from the group consisting of hydrogen, substituted alkyl, substituted aryl and substituted heteroaryl; R ²¹ And R ²² is each independently selected from the group consisting of hydrogen, alkyl and aryl; R ²¹ And a 5 or 6 membered saturated ring containing up to one other heteroatom selected from oxygen and nitrogen together with N to which R ²² is attached. The compound of claim 3, wherein the compound is of formula (I). The compound of claim 3, wherein the compound is formula II. The compound of claim 3, wherein the compound is of formula III. The compound of claim 5, wherein the compound is of formula IV. The compound of claim 5, wherein the compound is Formula V. 7. The compound of claim 5, wherein the compound is Formula VI. The method of claim 1, 3 '-{[1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidenemethyl] amino} -2'-hydroxy ratio Phenyl-3-carboxylic acid (compound 101); 2,4-dihydroxybenzoic acid N '-{1- [1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] Ethyl} hydrazide (Compound 102); 3- {3-[(5-chloro-2-hydroxy-3 ', 4'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl } Benzoic acid (compound 103); 3- {3-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid (compound 104); 3 '-{[1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidenemethyl] amino} -4-fluoro-2 '-Hydroxybiphenyl-3-carboxylic acid (compound 105); 2- (3 '-{[1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindol-3-ylidenemethyl] amino} -2'- Hydroxybiphenyl-3-yl) -2-methylpropionic acid (compound 106); 3 '-{[1- (3,4-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidenemethyl] amino} -2'-hydroxy ratio Phenyl-3-carboxylic acid (compound 107); 4- {3-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid (compound 108); 3- {3-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-6-trifluoromethyl-2,3-dihydroindole- 1-yl} benzoic acid (Compound 109); 3- {3-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-6-trifluoromethyl-2,3-dihydroindole- 1-yl} benzoic acid methyl ester (Compound 110); 3- {3-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid methyl ester (Compound 111); 3- {3-[(5-fluoro-2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindole-1- Monobenzoic acid (compound 112); 3- {3- [1- (3,5-Dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylideneamino] -2-oxo-2,3 -Dihydrobenzooxazol-7-yl} benzoic acid (compound 113); 3- {3-[(2-hydroxy-5,3 ', 4'-trimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid (Compound 114); 3-hydroxybenzoic acid N '-{1- [1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] ethyl} high Drazide (Compound 115); 1- (3,5-dimethylphenyl) -3- {1- [2- (4-hydroxyphenyl) -2-oxo-ethylamino] ethylidene} -6-trifluoromethyl-1,3-di Hydroindol-2-ones (compound 116); 3- {3-[(5-fluoro-2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-6-trifluoromethyl-2,3 -Dihydroindol-1-yl} benzoic acid (compound 117); 3- {3-[(2-hydroxy-3 ', 4'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-6-trifluoromethyl-2,3-dihydroindole- 1-yl} benzoic acid (Compound 118); 3- {3-[(2-hydroxy-3 ', 4'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid (compound 119); 3- {3-[(2-hydroxy-3 ', 4'-dimethylbiphenyl-3-ylamino) methylidene] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid (compound 120); 4- {3-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-ylamino) methylidene] -2-oxo-2,3-dihydroindol-1-yl} butyric acid (compound 121); 2-chloro-3- (4-{[1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindol-3-ylidenemethyl] amino}- 3-hydroxyphenyl) acrylic acid (compound 122); 4-hydroxybenzoic acid N '-{1- [1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] ethyl} high Drazide (Compound 123); 3- {3-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -5-nitro-2-oxo-2,3-dihydroindol-1-yl } Benzoic acid (compound 124); 3- {3-[(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-ylamino) methylidene] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid (compound 125); 3- {3-[(2-hydroxy-5,3 ', 5'-trimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid (Compound 126); 4-Aminobenzoic acid N '-{1- [1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindol-3-ylidene] ethyl} hydra Zide (compound 127); 3- (7- {N '-[1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino}- 1H-indol-3-yl) propionic acid (compound 128); 4- {3- [N '-(4-methylbenzoyl) hydrazinomethylidene] -2-oxo-2,3-dihydroindol-1-yl} benzoic acid (Compound 129); 3- {2-oxo-6-trifluoromethyl-3- [4- (3-trifluoromethylphenyl) -lH-pyrrol-2-ylmethylidene] -2,3-dihydroindol-1-yl } Benzoic acid (compound 130); 3- (7- {N '-[1- (3,4-dimethylphenyl) -3-methyl-5-oxo-1,5-dihydropyrazole-4-ylidene] hydrazino} -1H- Indol-3-yl) propionic acid (compound 131); 3- (3-{[4- (3,4-dimethylphenyl) thiazol-2-ylamino] methylidene} -2-oxo-6-trifluoromethyl-2,3-dihydroindole-1- Yl) benzoic acid (compound 132); 3- (3-{[4- (4-phenyl) thiazol-2-ylamino] methylene} -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl) benzoic acid ( Compound 133); 3- {3-[(2-hydroxy-3 ', 5'-dimethyl biphenyl-3-ylamino) methylene] -2-oxo-6-trifluoromethyl-2,3-dihydroindole-1 -Yl} benzoic acid (compound 134); 3- {3-[(4- (4-methylphenyl) -2-thiazolylamino) methylene] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic acid (compound 135); 3- {3-[(3,4-Dimethylbenzoylhydrazino) methylidene] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic acid (Compound 136); 3- {3-[(4-chlorobenzoylhydrazino) methylidene] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic acid (Compound 137); 3- {3-[(4-methoxybenzoylhydrazino) methylidene] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic acid (Compound 138); 3- {3-[(3,4-dimethylbenzoylhydrazino) methylidene] -2-oxo-6-chloro-2,3-dihydroindol-1-yl} benzoic acid (Compound 139); 1- (3,4-dimethylphenyl) -3- [1- (2,4-dihydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 140); 1- (3,4-dimethylphenyl) -3- [1- (4-hydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 141); 1- (3,4-dimethylphenyl) -3-[(2,4-dihydroxybenzoylhydrazino) methylidene] -2-oxo-2,3-dihydroindole (Compound 142); 1- (3,5-dimethylphenyl) -3- [1- (2,4-dihydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 143); 1- (3,5-dimethylphenyl) -3- [1- (4-hydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 144); 1- (3,5-dimethylphenyl) -3-[(2,4-dihydroxybenzoylhydrazino) methylidene] -2-oxo-2,3-dihydroindole (Compound 145); 1- (3,5-dimethylphenyl) -3-[(4-hydroxybenzoylhydrazino) methylidene] -2-oxo-2,3-dihydroindole (Compound 146); 3- (3- [1- (3,4-Dihydroxybenzoylhydrazino) ethylidene] -2-oxo-6-chloro-2,3-dihydroindol-1-yl) benzoic acid (Compound 147) ; 1- (3,4-dimethylphenyl) -3-[(4-hydroxybenzoylhydrazino) methylidene] -2-oxo-2,3-dihydroindole (Compound 148); 1- (3,4-dimethylphenyl) -3-[(3,5-diisopropyl-2-hydroxybenzoylhydrazino) methylidene] -2-oxo-2,3-dihydroindole (Compound 149 ); 1- (3,5-dimethylphenyl) -3- [1- (3,4-dihydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 150); 1- (3,4-dimethylphenyl) -3- [1- (3,4-dihydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 151); 3- (6-chloro-3-[(2-hydroxy-3,5-diisopropylbenzoylhydrazino) methylidene] -2-oxo-2,3-dihydroindol-1-yl) benzoic acid ( Compound 152); 1- (3,4-dimethylphenyl) -3- [1- (2,5-dihydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 153); 1- (3,4-dimethylphenyl) -3- [1- (3-nitro-4-hydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 154); 1- (3,4-dimethylphenyl) -3- [1- (3-aminosulfonyl-4-chlorobenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 155) ; 1- (3,4-dimethylphenyl) -3- [1- (3-amino-4-hydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 156); 1- (3,4-dimethylphenyl) -3- [1- (4-methoxy-2-hydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 157 ); 3- {3- (1- (3,5-Dimethylphenyl) -2-oxo-2,3-dihydro-3-indoledene) methylamino-2-hydroxyphenyl} benzoic acid (Compound 158); 3- {3- (3- (3,5-Dimethylphenyl) -2-hydroxyphenyl) aminomethylidene) -2-oxo-2,3-dihydro-1-indolyl} benzoic acid (Compound 159); 3- {3- (1- (3,4-Dimethylphenyl) -2-oxo-2,3-dihydro-3-indoledene) methylamino-2-hydroxyphenyl} benzoic acid (Compound 160); 4- {1- (6-Fluoro-2-oxo-2,3-dihydro-3- (2- (3,5-dimethylphenyl) -aminocarbonylphenyl) aminomethylidene) indolyl} butanoic acid (Compound 161); 4- {1- (6-Chloro-2-oxo-2,3-dihydro-3- (2-hydroxy-3- (3,5-dimethylphenyl) -phenyl) aminomethylidene) indolyl} moiety Carbonic acid (compound 162); 3- {1- (6-Chloro-2-oxo-2,3-dihydro-3- (2-hydroxy-3- (3,5-dimethylphenyl) -phenyl) aminomethylidene) indolyl} benzoic acid (Compound 163); 4- {1- (5-Fluoro-2-oxo-2,3-dihydro-3- (2-hydroxy-3- (3,5-dimethylphenyl) -phenyl) aminomethylidene) indolyl} Butanoic acid (compound 164); 3- {3- (1- (1- (3,5-Dimethylphenyl) -6-trifluoromethyl-2-oxo-2,3-dihydro-3-indoledene) ethylamino) -2-hydro Oxyphenyl} benzoic acid (compound 165); 3- {3- (1- (1- (3,4-Dimethylphenyl) -6-trifluoromethyl-2-oxo-2,3-dihydro-3-indoledene) ethylamino) -2-hydro Oxyphenyl} benzoic acid (compound 166); 3- {1- (6-Trifluoromethyl-2-oxo-2,3-dihydro-3- (5-chloro-2-hydroxy-3-cyclohexylphenyl) hydrazono) indolyl} benzoic acid (Compound 167); 3- {1- (5-fluoro-2-oxo-2,3-dihydro-3- (1- (5-chloro-2-hydroxy-3-cyclohexylphenyl) amino) ethylidene) indolyl } Benzoic acid (compound 168); 3- {1- (5-Fluoro-2-oxo-2,3-dihydro-3- (5-chloro-2-hydroxy-3-cyclohexylphenyl) aminomethylidene) indolyl} benzoic acid (compound 169); 4- {2-hydroxy-3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolylidene) methylaminophenyl} butanoic acid ( Compound 170); 4- {2-hydroxy-3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) indolylidene) methylaminophenyl} butanoic acid ( Compound 171); 3- {3- (7- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) -3-indolylidene) methylamino) indolyl} Propanoic acid (compound 172); 3- {3- (7- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) -3-indolylidene) methylamino) indolyl} Propanoic acid (compound 173); 4- {2-hydroxy-3- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolylidene) methylaminophenyl} butanoic acid (Compound 174); 2-Chloro-3- {3-hydroxy-4- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolylidene) methylaminophenyl} propenic acid (Compound 175) ; 2-chloro-3- {3-hydroxy-4- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) indolylidene) methylaminophenyl } Propenoic acid (compound 176); 2-ethyl-3- {3-hydroxy-4- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) indolylidene) methylaminophenyl } Propenic acid (Compound 177); 2-ethyl-3- {3-hydroxy-4- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolylidene) methylaminophenyl } Propenoic acid (compound 178); 2-ethyl-3- {3-hydroxy-4- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolylidene) methylaminophenyl} propenoic acid (Compound 179) ; 4- {2-hydroxy-3- (4- (2- (3,4-dimethylphenyl) -3-oxo-3,4-dihydro-5-methyl) pyrazolidene) methylaminophenyl} butanoic acid (Compound 180); (Z) -4- {1- (2,5-dioxo-3- (3- (3,5-dimethylphenyl) -2-hydroxyphenyl) aminomethylidene) pyrrolidinyl} butanoic acid (Compound 181 ); (E) -4- {1- (2,5-dioxo-3- (3- (3,5-dimethylphenyl) -2-hydroxyphenyl) aminomethylidene) pyrrolidinyl} butanoic acid (Compound 182 ); (Z) -3- {1- (2,5-dioxo-3- (3- (3,5-dimethylphenyl) -2-hydroxyphenyl) aminomethylidene) pyrrolidinyl} benzoic acid (Compound 183) ; (E) -3- {1- (2,5-dioxo-3- (3- (3,5-dimethylphenyl) -2-hydroxyphenyl) aminomethylidene) pyrrolidinyl} benzoic acid (Compound 184) ; 4- {3- (4-oxo-2-thioxo-5- (3- (3,5-dimethylphenyl) -2-hydroxyphenyl) hydrozono)} butanoic acid (Compound 185); 3- {2- (3- (1- (3.5-Dimethylphenyl) -6-chloro-2-oxo-2,3-dihydroindoledene) methylamino) phenylamino} benzoic acid (Compound 186); 3- {2- (3- (1- (3,5-Dimethylphenyl) -6-trifluoromethyl-2-oxo-2,3-dihydroin dollydene) methylamino) phenylamino} benzoic acid (compound 187); 3- {2- (4- (2- (3,5-Dimethylphenyl) -5-methyl-3-oxo-3,4-dihydropyrazolidene) methylamino) phenylamino} benzoic acid (Compound 188); (±) -3-methyl-5- {2-hydroxy-3- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) Indolylidene) methylamino) phenyl} pentanoic acid (Compound 189); (±) -3- {1- (6-chloro-2-oxo-2,3-dihydro-3- (3- (1- (3,5-dimethylphenyl) -2-oxo-2,3- Dihydro) indolyl) aminomethylidene) indolyl} benzoic acid (Compound 190); 3- {4- (3-hydroxy-6-methyl-2- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indole Ryl) hydrazono) pyridinyl} benzoic acid (compound 191); 3- {4- (3-hydroxy-6-methyl-2- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indole Lidene) methylamino) pyridinyl} benzoic acid (compound 192); 3- {4- (3-hydroxy-2- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylamino ) Pyridinyl} benzoic acid (compound 193); 3- {4- (3-hydroxy-2- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolyl) hydrazo No) pyridinyl} benzoic acid (compound 194); 3- {5- (4-hydroxy-3- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylamino ) Pyridinyl} benzoic acid (compound 195); 3- {5- (4-hydroxy-3- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolyl) hydrazo No) pyridinyl} benzoic acid (compound 196); 3- {5- (4-hydroxy-3- (4- (3-oxo-3,4-dihydro-5-methyl-2- (3,4-dimethylphenyl) pyrazolyl) hydrazono) Pyridinyl} benzoic acid (compound 197); 4- {2- (3-Oxo-3,4-dihydro-5-methyl-4- (3- (3,4-dimethylphenyl) phenyl) hydrozono) pyrazolyl} butanoic acid (Compound 198); 3- {2-amino-5-methyl-3- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolylidene) methyl Amino) phenyl} benzoic acid (compound 199); 3- {1- (5-Fluoro-2-oxo-2,3-dihydro-3- (3- (3,4-dimethylphenyl) phenyl) aminomethylidene) indolyl} benzoic acid (Compound 200); 4- {2- (5-Methyl-2-oxo-2,3-dihydro-4- (3- (3,4-dimethylphenyl) phenyl) aminomethylidene) pyrazolyl} butanoic acid (Compound 201); (3- (5-fluoro-2-hydroxy-3- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) indolene ) Methylamino) -1-pyrazolyl) acetic acid (compound 202); (3- (5-fluoro-2-hydroxy-3- (3- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indoledene) methylamino) -1- Pyrazolyl) acetic acid (compound 203); 4- {2- (5-Methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-phenyl) ethyl) phenyl) aminomethylidene) pyrazolyl} butanoic acid ( Compound 204); 4- {2- (5-Methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-phenyl) ethyl) phenyl) hydrazono) pyrazolyl} butanoic acid ( Compound 205); 4- {2- (5-methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (4-methyl) phenyl) ethyl) phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 206); 4- (2- (5-methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3-methyl) phenyl) ethyl) phenyl) hydrazono) Pyrazolyl} butanoic acid (compound 207); 4- {2- (5-methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methyl) phenyl) ethyl) phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 208); 4- {2- (5-methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (1-naphthyl) ethyl) phenyl) hydrazono) pyrazolyl } Butanoic acid (compound 209); 3- {1- (5-Nitro-2-oxo-2,3-dihydro-3- (2-hydroxy-3- (3,5-dimethylphenyl) phenyl) aminomethylidene) indolyl} benzoic acid ( Compound 210); 3- {1- (5-Nitro-2-oxo-2,3-dihydro-3- (5-fluoro-2-hydroxy-3- (3,5-dimethylphenyl) phenyl) aminomethylidene) Indolyl} benzoic acid (compound 211); 2-hydroxy-3- {3- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolene) methylamino} benzoic acid (Compound 212); 2-hydroxy-3- {3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolene) methylamino} benzoic acid (Compound 213) ; 4- {2- (5-methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3- (3-methyl-1-butenyl) phenyl) aminomethylidene) pyrazolyl} Butanoic acid (compound 214); 4- {2- (5-Methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3-heptanylphenyl) hydrazono) pyrazolyl} butanoic acid (Compound 215); 4- {2- (5-methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3- (2- (4-methyl) phenyl) ethenylphenyl) hydrazono) pyra Jolyl} butanoic acid (compound 216); 4- {2- (5-methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3- (2- (3-methyl) phenyl) tenylphenyl) hydrazono) pyra Jolyl} butanoic acid (compound 217); 4- {1- (2-Oxo-2,3-dihydro-3- (2-hydroxy-3- (2- (2-methyl) phenyl) ethylphenyl) hydrazono) indolyl} butanoic acid ( Compound 218); 2- {1- (2-Oxo-2,3-dihydro-3- (2-hydroxy-3- (3,5-dimethylphenyl) phenyl) hydrazono) indolyl} acetic acid (Compound 219); 2- {1- (2-Oxo-2,3-dihydro-3- (2-hydroxy-3- (2- (2-methyl) phenyl) ethylphenyl) hydrazono) indolyl} acetic acid (compound 220); 4- {4- (2- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) indolylidene) methylamino) thiazolyl} Benzoic acid (compound 221); 3- {1- (5-Nitro-2-oxo-2,3-dihydro-3- (2-hydroxy-5-methyl-3- (1-adamantane) phenyl) aminomethylidene) indolyl } Benzoic acid (compound 222); 3- {1- (6-Trifluoromethyl-2-oxo-2,3-dihydro-3- (4-hydroxy-5- (3,4-dimethylphenyl) pyridinyl) hydrazono) indole Ryl} benzoic acid (compound 223); 4- {2- (5-Methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3- (2- (2-methyl) phenyl) -ethylphenyl) aminomethylidene) pyra Jolyl} butanoic acid (compound 224); 4- (2- (5-Methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3- (2- (2-fluoro) phenyl) -ethylphenyl) aminomethylidene) Pyrazolyl} butanoic acid (compound 225), or a pharmaceutically acceptable salt, ester or prodrug thereof. The method of claim 1, 4- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (1-naphthyl) -ethyl) phenyl) aminomethyl Lidene) pyrazolyl} butanoic acid (Compound 226); 4- (2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (3,5-dimethylphenyl) -ethyl) phenyl) Aminomethylidene) pyrazolyl} butanoic acid (Compound 227); 4- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-methoxyphenyl) -ethyl) phenyl) amino Methylidene) pyrazolyl} butanoic acid (Compound 228); 4- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-fluoro-3-methyl-phenyl) ethyl ) Phenyl) aminomethylidene) pyrazolyl} butanoic acid (Compound 229); 4- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-fluoro-3-methyl-phenyl) ethyl ) Phenyl) aminomethylidene) pyrazolyl} butanoic acid (compound 230); 4- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (4-phenylphenyl) -ethyl) phenyl) aminomethyl Lidene) pyrazolyl} butanoic acid (Compound 231); 4- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-cyanophenyl) -ethyl) phenyl) amino Methylidene) pyrazolyl} butanoic acid (Compound 232); 4- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-chlorophenyl) -ethyl) phenyl) aminomethyl Lidene) pyrazolyl} butanoic acid (Compound 233); 4- (2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2,6-dimethylphenyl) -ethyl) phenyl) Aminomethylidene) pyrazolyl} butanoic acid (Compound 234); 3- {2- (5-Trifluoromethyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-trifluoromethylphenyl) ethyl) Phenyl) aminomethylidene) pyrazolyl} benzoic acid (compound 235); 3- {2- (5-Trifluoromethyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-fluorophenyl) -ethyl) Phenyl) aminomethylidene) pyrazolyl} benzoic acid (compound 236); 3- {2- (5-trifluoromethyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-methyl-phenyl) ethyl) phenyl ) Aminomethylidene) pyrazolyl} benzoic acid (compound 237); 3- {2- (5-Trifluoromethyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2,5-dimethyl-phenyl) ethyl ) Phenyl) aminomethylidene) pyrazolyl} benzoic acid (compound 238); 3- {2- (5-Trifluoromethyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2,6-dimethyl-phenyl) ethyl ) Phenyl) aminomethylidene) pyrazolyl} benzoic acid (Compound 239); 3- {2- (5-phenyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2,5-dimethylphenyl) -ethyl) phenyl) Aminomethylidene) pyrazolyl} benzoic acid (compound 240); 3- {2- (5-tert-butyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2,5-dimethylphenyl) -ethyl ) Phenyl) aminomethylidene) pyrazolyl} benzoic acid (compound 241); 3- {2- (5-methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-methylphenyl) -ethyl) phenyl) aminomethylidene ) Pyrazolyl} benzoic acid (compound 242); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z)-(2-hydroxy-3- (2- (2-fluorophenyl) -ethyl) phenyl) hydro Lazono) pyrazolyl} butanoic acid (Compound 243); 4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dimethylphenyl) -ethyl) phenyl) hydrazono ) Pyrazolyl} butanoic acid (Compound 244); 4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (4-phenylphenyl) -ethyl) phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 245); 4- (2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methoxyphenyl) -ethyl) phenyl) hydrazono) Pyrazolyl} butanoic acid (Compound 246); 4- {2- (5-Methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluoro-3-methylphenyl) -ethyl) phenyl) hydro Lazono) pyrazolyl} butanoic acid (Compound 247); 4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-trifluoromethylphenyl) -ethyl) phenyl) hydrazono ) Pyrazolyl} butanoic acid (Compound 248); 4- (2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-cyanophenyl) ethyl) -phenyl) hydrazono) Pyrazolyl} butanoic acid (compound 249); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-chlorophenyl) ethyl) -phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 250); 4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dimethylphenyl) -ethyl) phenyl) hydrazono ) Pyrazolyl} butanoic acid (Compound 251); 4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-ethylphenyl) -ethyl) phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 252); 4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dichlorophenyl) -ethyl) phenyl) hydrazono ) Pyrazolyl} butanoic acid (compound 253); 4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,5-dimethylphenyl) -ethyl) phenyl) hydrazono ) Pyrazolyl} butanoic acid (Compound 254); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluoro-6-trifluoro-methylphenyl) ethyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 255); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indanyl) phenyl) -hydrazono) pyrazolyl} butanoic acid ( Compound 256); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indenyl) phenyl) -hydrazono) pyrazolyl} butanoic acid ( Compound 257); (±) -4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (1-indanylmethyl) phenyl) -hydrazono) pyra Jolyl} butanoic acid (compound 258); (±) -3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (1-indanylmethyl) phenyl) -hydrazono) pyra Jolyl} benzoic acid (compound 259); 3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methylphenyl) ethyl) -phenyl) hydrazono) pyrazolyl } Benzoic acid (compound 260); 3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluoro-3-methylphenyl) -ethyl) phenyl) hydro Lazono) pyrazolyl} benzoic acid (compound 261); 3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluorophenyl) -ethyl) phenyl) hydrazono) Pyrazolyl} benzoic acid (compound 262); 3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dimethylphenyl) -ethyl) phenyl) hydrazono ) Pyrazolyl} benzoic acid (compound 263); 3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dichlorophenyl) -ethyl) phenyl) hydrazono ) Pyrazolyl} benzoic acid (compound 264); 3- (2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methyl-6-trifluoromethylphenyl) ethyl) phenyl) Hydrazono) pyrazolyl} benzoic acid (compound 265); 3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indanyl) phenyl) -hydrazono) pyrazolyl} benzoic acid (compound 266); 3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indenyl) phenyl) -hydrazono) pyrazolyl} benzoic acid (compound 267); (E) -4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,4-difluorophenyl)-) Tenyl) phenyl) aminomethylidene) pyrazolyl} butanoic acid (Compound 268); 3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-4- (3,4-dimethylphenyl) -2-pyridyl) hydrazono) pyra Jolyl} benzoic acid (compound 269); 4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-6-methyl-4- (3,4-dimethylphenyl) -2-pyridyl) hydro Lazono) pyrazolyl} butanoic acid (Compound 270); 3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-2- (3,4-dimethylphenyl)-4-pyridyl) hydrazono) pyra Jolyl} benzoic acid (compound 271); 3- (2- (5-methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-2- (3,5-dimethylphenyl)-4-pyridyl) hydrazono) pyra Jolyl} benzoic acid (compound 272); 3- {1- (6-Trifluoromethyl-2-oxo-2,3-dihydro-3- (2-hydroxy-3- (2- (2-methylphenyl) -ethyl) phenyl) hydrazono ) Indolyl} benzoic acid (compound 273); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3-benzylphenyl) hydrazono) -pyrazolyl} butanoic acid (Compound 274); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3- (3-methylphenyl) propyl) -phenyl) hydrazono) pyrazolyl } Butanoic acid (compound 275); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3-phenylpropyl) -phenyl) hydrazono) pyrazolyl} butanoic acid ( Compound 276); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3- (2-methylphenyl) propyl) -phenyl) hydrazono) pyrazolyl } Butanoic acid (compound 277); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,4-difluorophenyl) -ethyl) phenyl) hydro Lazono) pyrazolyl} butanoic acid (Compound 278); (E) -4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-pyridyl) ethyl) -phenyl) hydro Lazono) pyrazolyl} butanoic acid (Compound 279); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z)-(2-hydroxy-3- (2- (2,6-dimethylphenyl)-(Z)- Ethenyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 280); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-benzofuranyl) phenyl) -hydrazono) pyrazolyl} butanoic acid (Compound 281); (Z) -4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-bromoethenyl) phenyl) -hydrazono) pyra Jolyl} butanoic acid (compound 282); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z)-(2-hydroxy-3- (3-methyl-1-butenyl) phenyl) -hydrazono ) Pyrazolyl} butanoic acid (compound 283); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z)-(2-hydroxy-3- (2-cyclopropylethenyl) -phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 284); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3-methylbutyl) phenyl) -hydrazono) pyrazolyl} butanoic acid ( Compound 285); 4- (2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-5-fluoro-3- (3,5-dimethylphenyl) phenyl) hydrazono) Pyrazolyl} butanoic acid (compound 286); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3,4-dimethylphenyl) phenyl) -hydrazono) pyrazolyl} part Carbonic acid (compound 287); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (5-chloro-2-hydroxy-3-cyclohexylphenyl) -hydrazono) pyrazolyl} butanoic acid ( Compound 288); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3,5-dimethylphenyl) phenyl) -hydrazono) pyrazolyl} part Carbonic acid (compound 289); 3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3,5-dimethylphenyl) phenyl) -hydrazono) pyrazolyl} benzoic acid (Compound 290); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (5-chloro-2-hydroxy-3-cyclohexylphenyl) -hydrazono) pyrazolyl} butanoic acid ( Compound 291); 3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3,4-dimethylphenyl) phenyl) -hydrazono) pyrazolyl} benzoic acid (Compound 292); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3- (2-methylphenyl) propyl) -phenyl) hydrazono) pyrazolyl } Butanoic acid (compound 293); 3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-benzofuranyl) phenyl) -hydrazono) pyrazolyl} benzoic acid ( Compound 294); 4- (2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3- (2-fluorophenyl) propyl) -phenyl) hydrazono) Pyrazolyl} butanoic acid (compound 295); 3- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (3,4-dimethylphenyl) -phenyl) aminomethylidene) pyra Jolyl} benzoic acid (compound 296); 3- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (3,5-dimethylphenyl) -phenyl) aminomethylidene) pyra Jolyl} benzoic acid (compound 297); 4- {2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z)-(2-hydroxy-3- (3,4-dimethylphenyl) -phenyl) aminomethylidene) pyra Jolyl} butanoic acid (compound 298); 3- {1- (2-Oxo-2,3-dihydro-3- (2-hydroxy-3- (3,5-dimethylphenyl) -phenyl) hydrazono) indolyl} propionic acid (Compound 299) ; 3- {1- (2-Oxo-2,3-dihydro-3- (2-hydroxy-3-benzylphenyl) hydrazono) -indolyl} benzoic acid (Compound 300); 3- {1- (2-Oxo-2,3-dihydro-3- (2-hydroxy-3- (2- (2-methylphenyl) ethyl) phenyl) -hydrazono) indolyl} propionic acid (compound 301); 3- {1- (6-Chloro-2-oxo-2,3-dihydro-3 (Z)-(2-hydroxy-3- (3- (3-methylphenyl) propyl) -phenyl) aminomethylidene ) Indolyl} benzoic acid (compound 302); (±) -3- {1- (6-chloro-2-oxo-2,3-dihydro-3 (Z)-(2-hydroxy-3- (1,2-dihydro-1-methyl- 2-indolylphenyl) aminomethylidene) indolyl} benzoic acid (Compound 303); 4- {2- (5-Methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3- (2-methylphenylcarbonyl-amino) phenyl) hydrazono) pyrazolyl} part Carbonic acid (compound 304); 4- (2- (5-methyl-3-oxo-3,4-dihydro-4- (5-chloro-2-hydroxy-3- (2-methylphenyl-carbonylamino) phenyl) hydrazono) Pyrazolyl} butanoic acid (Compound 305); 3- {2-Hydroxy-3- (2-oxo-2,3-dihydro-l- (2- (2-fluorophenyl) ethyl) indolylidene) -hydrazinophenyl} benzoic acid (Compound 306 ); 3- {2-Hydroxy-3- (2-oxo-2,3-dihydro-l- (2- (2-chlorophenyl) ethyl) indolylidene) -hydrazinophenyl} benzoic acid (Compound 307) ; 3- {3-hydroxy-2- (5-methyl-3-oxo-2,3-dihydro-2- (3,4-dimethylphenyl) -pyrazolylidene) hydrazino-4-pyridyl} Benzoic acid (compound 308); 4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl } Benzoic acid (compound 309); 3- {3-Hydroxy-2- (2-oxo-2,3-dihydro-l- (3,5-dimethylphenyl) -3-indolylidene-hydrazino) -4-pyridyl} benzoic acid (Compound 310); 3- {1- (2-Oxo-2,3-dihydro-3- (3-hydroxy-6-methyl-4- (3,4-dimethylphenyl)-2-pyridyl) hydrazono) indole Ryl} benzoic acid (compound 311); 3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-6-methyl-4- (3,4-dimethylphenyl) -2-pyridyl) hydro Lazono) pyrazolyl} benzoic acid (compound 312); 3- {3-hydroxy-4- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) -6-trifluoromethyl-3-indolylidenehydrazino)- 2-pyridyl} benzoic acid (Compound 313); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-2- (3,5-dimethylphenyl)-4-pyridyl) hydrazono) pyra Jolyl} butanoic acid (compound 314); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-5-phenyl-2-benzothienyl) -hydrazono) pyrazolyl} butanoic acid ( Compound 315); 3- {3-hydroxy-2- (5-methyl-3-oxo-2,3-dihydro-2- (3,4-dimethylphenyl) -4-pyrazolidene) hydrazino-5-benzo Thienyl} benzoic acid (compound 316); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (3- (2,3-dimethoxycarbonylphenyl) phenyl) -hydrazono) pyrazolyl} butanoic acid ( Compound 317); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z)-(2-hydroxy-3,5-diisopropylphenyl) -carbonylhydrazinomethylidene) Pyrazolyl} butanoic acid (compound 318); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z)-(2-hydroxy-3- (3,5-dimethylphenyl) phenyl) -aminomethylidene) pyra Jolyl} butanoic acid (Compound 319); (±) -4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2,3-dihydro-1-methyl-2-oxo -3-indolyl) methyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 320); 3- {1- (2-Oxo-2,3-dihydro-5-fluoro-3- (2-hydroxy-3- (2- (2-methylphenyl) ethyl) phenyl) -hydrazono) indole Ryl} propionic acid (compound 321); 3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,5-dimethylphenyl) -ethyl) phenyl) hydrazono ) Pyrazolyl} benzoic acid (compound 322); (±) -3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2,3-dihydro-1-methyl-2-oxo -3-indolyl) methyl) phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 323); 3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (l, 2-dihydro-1-methyl-2-oxo-3-indole) Lilydene) methyl) phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 324); 3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (5-fluoro-2-methylphenyl) -ethyl) phenyl) hydro Lazono) pyrazolyl} benzoic acid (compound 325); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4 (E)-(2-hydroxy-3- (2- (2,4-difluorophenyl) -ethenyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 326); 3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3-methylphenyl) hydrazono) -pyrazolyl} benzoic acid (Compound 327); 4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (1,2-dihydro-1-methyl-2-oxo-3-indole Lilydene) methyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 328); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (5-fluoro-2-methylphenyl) -ethyl) phenyl) hydro Lazono) pyrazolyl} butanoic acid (Compound 329); 4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-difluorophenyl) -ethyl) phenyl) hydro Lazono) pyrazolyl} butanoic acid (Compound 330); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (256-dimethylphenyl) -ethenyl) phenyl) hydro Lazono) pyrazolyl} butanoic acid (Compound 331); 4- {2- (5-methyl ~ 3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-methylphenyl) -ethenyl) phenyl) hydrazo No) pyrazolyl} butanoic acid (Compound 332); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (5-fluoro-2-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 333); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (Z)-(2- (5-fluoro-2-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 334); 4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (3-fluorophenyl) ethenyl) phenyl) hydro Lazono) pyrazolyl} butanoic acid (Compound 335); 4- {2- (5-methyl-3-oxo-23-dihydro-4- (2-hydroxy-3 (E)-(2- (4-fluorophenyl) ethenyl) phenyl) hydrazono ) Pyrazolyl} butanoic acid (compound 336); 4- (2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-fluorophenyl) -ethenyl) phenyl) Hydrazono) pyrazolyl} butanoic acid (compound 337); 4- {2- (5-Methyl-3-oxo-2.3-dihydro-4- (2-hydroxy-3 (E)-(2-phenylethenyl) -phenyl) hydrazono) pyrazolyl} part Carbonic acid (compound 338); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-phenylethynyl) -phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 339); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methylphenyl) ethynyl) -phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 340); 4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dimethylphenyl) -ethynyl) phenyl) hydrazo No) pyrazolyl} butanoic acid (Compound 341); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluorophenyl) ethynyl) -phenyl) hydrazono ) Pyrazolyl} butanoic acid (Compound 342); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-trifluoromethylphenyl) -ethynyl) phenyl) hydrazo No) pyrazolyl} butanoic acid (Compound 343); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-trifluoromethyl-phenyl) ethynyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 344); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (1-methyl-1-indenyl-2-) phenyl) -hydrazono ) Pyrazolyl} butanoic acid (Compound 345); 4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3,3-dimethyl-2-indenyl) phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 346); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-5-methoxy-3- (2-indenyl) -phenyl) hydrazono) pyra Jolyl} butanoic acid (Compound 347); 4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (4,7-dimethyl-2-indenyl) phenyl) hydrazono) pyra Jolyl} butanoic acid (compound 348); 4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (4,7-difluoro-2-indenyl) phenyl) hydrazono ) Pyrazolyl} butanoic acid (compound 349); 3- {2-hydroxy-3- (2-oxo-2,3-dihydro-6-trifluoromethyl-1- (2- (2-methylphenyl) -ethyl) -3 (Z) -indolily Den) methylaminophenyl} benzoic acid (compound 350); 3- {2-hydroxy-3- (2-oxo-2,3-dihydro-6-trifluoromethyl-1- (2-indenyl) -3 (Z) -indolylidene) methylaminophenyl } Benzoic acid (compound 351); (±) 4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (l, 2,3,4-tetrahydro)- Naphthyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 352); 4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro) -naphthyl) phenyl) hydrazo No) pyrazolyl} butanoic acid (compound 353); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(1-indanylidene) -methylphenyl) hydrazono) pyrazolyl } Butanoic acid (compound 354); 4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (5-fluoro-2-trifluoromethylphenyl) Ethenyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 355); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (6-fluoro-2-trifluoro-methylphenyl ) Ethenyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 356); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (6-fluoro-2-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 357); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (4-fluoro-2-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 358); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (3-fluoro-2-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 359); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,6-difluorophenyl) -ethenyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 360); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,5-difluorophenyl) -ethenyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 361); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (4-fluoro-2-trifluoro-methylphenyl ) Ethenyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 362); 4- (2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,4-difluorophenyl) -ethynyl) phenyl) Hydrazono) pyrazolyl} butanoic acid (compound 363); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(1- (l, 2,3,4-tetrahydro)- Naphthalidene) methylphenyl) hydrazono) pyrazolyl} butanoic acid (Compound 364); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-fluoro-5-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 365); 4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (3,5-dimethyl-4-isoxazolyl) Ethenyl) phenyl) hydrazono) pyrazolyl) butanoic acid (Compound 366); 4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,5-dimethyl-4-isoxazolyl) ethyl) phenyl ) Hydrazono) pyrazolyl} butanoic acid (compound 367); 3- {2-hydroxy-3- (2-oxo-2,3-dihydro-1- (2 (E)-(2-methylphenyl) ethenyl) -3 (Z) -indolylidene) methylamino Phenyl} benzoic acid (compound 368); 3- {2-hydroxy-3- (2-oxo-2,3-dihydro-1- (2 (E)-(2,4-difluorophenyl) ethenyl) -3 (Z) -indole Lilydene) methylaminophenyl} benzoic acid (compound 369); 3- {2-Hydroxy-3- (2-oxo-2,3-dihydro-l- (2-indenyl) -3 (Z) -indolylidene) methyl-aminophenyl} benzoic acid (Compound 370) ; 3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (5-fluoro-2-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 371); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3-methylphenyl) hydrazono) -pyrazolyl} butanoic acid (Compound 372); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indanylidenemethyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 373); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indanylmethyl) phenyl) hydrazono) pyrazolyl} butanoic acid ( Compound 374); 3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,4-difluorophenyl) -ethenyl ) Phenyl) hydrazono) pyrazolyl} benzoic acid (compound 375); 3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,6-difluorophenyl) -ethenyl ) Phenyl) hydrazono) pyrazolyl} benzoic acid (compound 376); 3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (4-fluoro-2-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 377); 3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-fluoro-6-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 378); 3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,3-difluorophenyl) -ethenyl ) Phenyl) hydrazono) pyrazolyl} benzoic acid (compound 379); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,3-difluorophenyl) -ethenyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 380); 4- (2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-fluoro-4-methylphenyl) ethenyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 381); 4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-chlorophenyl) -ethenyl) phenyl) hydr Lazono) pyrazolyl} butanoic acid (Compound 382); 4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,6-dichlorophenyl) -ethenyl) phenyl ) Hydrazono) pyrazolyl} butanoic acid (compound 383); 4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (3-chlorophenyl) -ethenyl) phenyl) hydr Razono) pyrazolyl} butanoic acid (compound 384); 3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,5-difluorophenyl) -ethenyl ) Phenyl) hydrazono) pyrazolyl} benzoic acid (compound 385); 4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-chloro-4-fluorophenyl) ethenyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 386); 3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-trifluoromethyl-4-fluorophenyl ) Ethenyl) phenyl) hydrazono) pyrazolyl} benzoic acid (compound 387); 4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,4-dichlorophenyl) -ethenyl) phenyl ) Hydrazono) pyrazolyl} butanoic acid (compound 388); In 3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2-chloromethyl-4-fluorophenyl) Tenyl) phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 389); 3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E)-(2- (2,4-dichloromethylphenyl) ethenyl) phenyl) Hydrazono) pyrazolyl} benzoic acid (compound 390); 3- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro) -naphthyl) phenyl) hydrazo No) pyrazolyl} benzoic acid (Compound 391); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-8-fluoro) -naphthyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 392); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-8-methyl) -naphthyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 393); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-7-methyl) -naphthyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 394); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-7-fluoro) -naphthyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 395); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-6-fluoro) -naphthyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 396); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-5-fluoro) -naphthyl ) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 397); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-8-chloro) -naphthyl) Phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 398); 3- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-7-fluoro) -naphthyl ) Phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 399), or a pharmaceutically acceptable salt, ester or prodrug thereof. The compound of any one of claims 1-20, wherein the compound is a selective TPO modulator. The compound of claim 21, wherein the compound is a TPO mimic. The compound of claim 21, wherein the compound is a selective TPO receptor agonist. The compound of claim 21, wherein the compound is a selective TPO receptor partial agonist. The compound of claim 21, wherein the compound is a selective TPO receptor antagonist. The compound of any one of claims 1-25, wherein the compound is a selective TPO receptor binding compound. The compound of claim 26, wherein the compound is a tissue-specific modulator. A method of modulating intracellular TPO activity, comprising contacting a compound according to claim 1 with a cell. 28. Identification of a compound that modulates TPO activity, comprising contacting a compound according to any one of claims 1 to 27 with a cell expressing a TPO receptor and monitoring the effect of the compound in the cell. Way. A method of treating a patient, comprising administering to the patient a compound according to any one of claims 1 to 27. The method of claim 30, wherein the patient is a thrombocytopenia patient. 32. The method of claim 31, wherein the cause of thrombocytopenia is radiation or chemotherapy. The method of claim 30, further comprising collecting cells from the patient. 32. The method of claim 30, wherein the treatment is prophylactic treatment. 31. The method of claim 30, wherein the patient is a neurological condition patient. 36. The method of claim 35, wherein the patient is a disease patient selected from the group consisting of amyotrophic lateral sclerosis, multiple sclerosis, and multiple dystrophy. 36. The method of claim 35, wherein the patient is a neurological injury patient. The method of claim 35, wherein the patient is a spinal cord injury patient. A pharmaceutical composition comprising a compound according to any one of claims 1 to 27 and a physiologically acceptable carrier, diluent or excipient. The pharmaceutical composition of claim 39, wherein the composition is selected from the group consisting of thrombocytopenia and neurological conditions.