1,2-Bis-(substituted-phenyl)-2-propen-1-ones and pharmaceutical compositions thereof

• US 20060063828A1
• Filed: 06/28/2005
• Published: 03/23/2006
• Est. Priority Date: 06/28/2004
• Status: Abandoned Application

• Current Assignee: Atherogenics, Inc.
• Original Assignee: Atherogenics, Inc.
• Inventors: Weingarten, M. David, Sikorski, James A., Hoong, Lee K., Skudlarek, Jason
• Application Number:
  US11/170,647
• Publication Number:
  US 20060063828A1
• Time in Patent Office: Days
• US Class Current: 514/438
• CPC Class Codes: C07D 207/335 Radicals substituted by nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 213/50 Ketonic radicals
• CPC Class Codes: C07D 215/14 Radicals substituted by oxygen atoms
• CPC Class Codes: C07D 333/22 Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom
• CPC Class Codes: C07D 333/56 Radicals substituted by oxygen atoms
• CPC Class Codes: C07D 409/10 linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 409/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links

Abstract

The invention relates to compounds, pharmaceutical compositions and methods of using compounds of the general formula or its pharmaceutically acceptable salt or ester, wherein the substituents are defined in the application.

Claims

1. A compound of Formula I

or its pharmaceutically acceptable salt or ester, wherein:

R<sup>2α

, R3α</sup>

, R^4α

, R^5α

, R^6α

, R^2β

, R^3β

, R^4β

, R^5β

and R^6β

are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O)₂-lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —

C(O)R², R²C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —

(O(CH₂)₂)_1-3—

O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —

OC(R¹)₂C(O)OH, —

OC(R¹)₂C(O)OR², —

OC(R¹)₂C(O)NH₂, —

OC(R¹)₂C(O)NHR², —

OC(R¹)₂C(O)N(R²)₂, —

OC(R¹)₂C(O)NR⁷R⁸, amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —

NHR², N(R²)₂, —

NR⁷R⁸, —

NHC(R¹)₂C(O)OH, —

NHC(R¹)₂C(O)OR², —

NHC(O)R², —

N(R²)C(O)R², —

NHC(O)OR², —

NHC(O)SR², —

NHSO₂NHR², —

NHSO₂R², —

NHSO₂NR⁷R⁸, —

N(C(O)NHR²)₂, —

NR²SO₂R², —

NHC(O)NHR², —

NHC(O)NR⁷R⁸, —

NHC(O)N(R²)₂, thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —

SC(R¹)₂C(O)OH, —

SC(R¹)₂C(O)OR², —

SCH₂C(O)OH, —

SCF₂C(O)OH, —

SO₂NH₂, —

SO₂NHR², —

SO₂N(R²)₂, SO₂NR⁷R⁸, —

SO₂NHC(O)R², —

SR², —

SO₂NHC(O)NHR², —

SO₂NHC(O)N(R²) 2, —

SO₂NHC(O)NR⁷R⁸, sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —

C(O)OR², —

C(O)NH₂, —

C(O)NHR², —

C(O)N(R²)₂, —

C(O)NR⁷R⁸, —

C(O)NHC(O)R², —

C(O)NHC(O)NHR², —

C(O)NHC(O)N(R²)₂, —

C(O)NHC(O)NR⁷R⁸, —

C(O)NHSO₂R², —

C(O)NHSO₂NHR², —

C(O)NHSO₂N(R²), —

C(O)NHSO₂NR⁷R⁸—

C(CH₃)₂C(O)OH, —

(CH₂)_yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —

PO₂H₂, —

PO₃H₂, —

P(R²)O₂H, and phosphate, all of which can be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R¹ is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R² is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R⁷ and R⁸ are independently selected from the group consisting of alkyl, alkenyl, heteroaryl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring;

wherein one of R^2β

, R^3β

, R^4β

, R^5β

or R^6β

, or one of R^2α

, R^3α

, R^4α

, R^5α

or R^6α

must be a carbon-carbon linked heterocyclic or heteroaryl;

or

R^2α

and R^3α

taken together or R^3α

and R^4α

taken together or R^4α

and R^5α

taken together, or R^2β

and R^3α

taken together or R^3α

and R^4α

taken together or R^4α

and R^5α

taken together form a heterocyclic or heteroaryl optionally substituted by one or more alkoxycarbonylalkyl, carboxyalkyl, hydroxyalkyl or aminoalkyl and optionally substituted where possible with one or more selected from the group consisting of hydroxy, alkyl, carboxy, hydroxyalkyl, carboxyalkyl, amino, cyano, alkoxy, alkoxycarbonyl, acyl, oxo, —

NR⁷R⁸, and halo;

or

R^2α

and R^3α

taken together or R^3α

and R^4α

taken together or R^4α

and R^5α

taken together or R^2β

and R^3β

taken together or R^3β

and R^4β

taken together or R^4β

and R^5α

taken together form a 5- or 6-membered ring containing one nitrogen, which may optionally be substituted where possible with one or more selected from the group consisting of halo, alkyl, lower alkyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

wherein all R¹, R², R⁷ and R⁸ substituents can be optionally substituted where possible with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂.

2. The compound of claim 1 or its pharmaceutically acceptable salt or ester, wherein:

R^2α

, R^3α

, R^4α

, R^5α

, R^6α

, R^2β

, R^3β

, R^4β

, R^5β

and R^6β

are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O)₂-lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —

C(O)R², R²C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alkoxy, lower alkoxy, —

(O(CH₂)₂)_1-3—

O-lower alkyl, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —

OC(R¹)₂C(O)OH, —

OC(R¹)₂C(O)OR², —

OC(R¹)₂C(O)NH₂, —

OC(R¹)₂C(O)NHR², —

OC(R¹)₂C(O)N(R²)₂, —

OC(R¹)₂C(O)NR⁷R⁸, amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —

NHR², N(R²)₂, —

NR⁷R⁸, —

NHC(R¹)₂C(O)OH, —

NHC(R¹)₂C(O)OR², —

NHC(O)R², —

N(R²)C(O)R², —

NHC(O)OR², —

NHC(O)SR², —

NHSO₂NHR², —

NHSO₂R², —

NHSO₂NR R, —

N(C(O)NHR²)₂, —

NR²SO₂R², —

NHC(O)NHR², —

NHC(O)NR⁷R², —

NHC(O)N(R²)₂, thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —

SC(R¹)₂C(O)OH, —

SC(R¹)₂C(O)OR², —

SCH₂C(O)OH, SCF₂C(O)OH, —

SO₂NH₂, —

SO₂NHR², —

SO₂N(R²)₂, SO₂NR², —

SO₂NHC(O)R², —

SR², —

SO₂NHC(O)NHR², —

SO₂NHC(O)N(R²)₂, —

SO₂NHC(O)NR⁷R⁸, sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —

C(O)OR², —

C(O)NH₂, —

C(O)NHR², —

C(O)N(R²)₂, —

C(O)NR⁷R⁸, —

C(O)NHC(O)R², —

C(O)NHC(O)NHR², —

C(O)NHC(O)N(R²)₂, —

C(O)NHC(O)NR⁷R⁸, —

C(O)NHSO₂R², —

C(O)NHSO₂NHR², —

C(O)NHSO₂N(R²), —

C(O)NHSO₂NR⁷R⁸, —

C(CH₃)₂C(O)OH, —

(CH₂)_yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —

PO₂H₂, —

PO₃H₂, —

P(R²)O₂H, and phosphate, all of which can be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R¹ is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R¹)₂;

R² is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R⁷ and R⁸ are independently selected from the group consisting of alkyl, alkenyl, heteroaryl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring;

wherein one of R^2β

, R^3β

, R^4β

, R^5β

or R^6β

, or one of R^2α

, R^3α

, R^4α

, R^5α

or R^6α

must be a carbon-carbon linked heterocyclic or heteroaryl;

wherein all R¹, R², R⁷ and R⁸ substituents can be optionally substituted where possible with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂.

3. The compound of claim 2 or its pharmaceutically acceptable salt or ester, wherein:

R^2α

, R^3α

, R^4α

, R^5α

, R^6α

, R^2β

, R^3β

, R^4β

, R^5β

and R^6β

are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, —

C(O)R², R²C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alkoxy, lower alkoxy, —

(O(CH₂)₂)_1-3—

O-lower alkyl, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —

OC(R¹)₂C(O)OH, —

OC(R¹)₂C(O)OR², —

OC(R¹)₂C(O)NH₂, —

OC(R¹)₂C(O)NHR², —

OC(R¹)₂C(O)N(R²)₂, —

OC(R¹)₂C(O)NR⁷R⁸, amino, alkyl amino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —

NHR², N(R²)₂, —

NR⁷R⁸, —

NHC(R¹)₂C(O)OH, —

NHC(R¹)₂C(O)OR₂, —

NHC(O)R², —

N(R²)C(O)R², —

NHC(O)OR², —

NHC(O)SR², —

NHSO₂NHR², —

NHSO₂R², —

NHSO₂NR⁷R⁸, —

N(C(O)NHR²)₂, —

NR²SO₂R², —

NHC(O)NHR², —

NHC(O)NR⁷R⁸, —

NHC(O)N(R²)₂, thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —

SC(R¹)₂C(O)OH, —

SC(R¹)₂C(O)OR², —

SCH₂C(O)OH, —

SCF₂C(O)OH, —

SO₂NH₂, —

SO₂NHR², —

SO₂N(R²)₂, SO₂NR⁷R⁸, —

SO₂NHC(O)R², —

SR², —

SO₂NHC(O)NHR², —

SO₂NHC(O)N(R²) 2, —

SO₂NHC(O)NR⁷R⁸, sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —

C(O)OR², —

C(O)NH₂, —

C(O)NHR², —

C(O)N(R²)₂, —

C(O)NR⁷R⁸, —

C(O)NHC(O)R², —

C(O)NHC(O)NHR², —

C(O)NHC(O)N(R²)₂, —

C(O)NHC(O)NR⁷R⁸, —

C(O)NHSO₂R², —

C(O)NHSO₂NHR², —

C(O)NHSO₂N(R²), —

C(O)NHSO₂NR⁷R⁸, —

C(CH₃)₂C(O)OH, —

(CH₂)_yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —

PO₂H₂, —

PO₃H₂, —

P(R²)O₂H, and phosphate, all of which can be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R¹ is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R² is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R⁷ and R⁸ are independently selected from the group consisting of alkyl, alkenyl, heteroaryl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring;

wherein one of R^2β

, R^3β

, R^4β

, R^5β

or R^6β

, or one of R^2α

, R^3α

, R^4α

, R^5α

or R^6α

must be a carbon-carbon linked heteroaryl;

wherein all R¹, R², R⁷ and R⁸ substituents can be optionally substituted where possible with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂.

4. The compound of claim 1 or its pharmaceutically acceptable salt or ester, wherein:

R^3α

, R^4α

, R^5α

, R^2β

, R^3β

, R^4β

, R^5β

and R^6β

are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, —

C(O)R², R²C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alkoxy, lower alkoxy, —

(O(CH₂)₂)_1-3—

O-lower alkyl, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —

OC(R¹)₂C(O)OH, —

OC(R¹)₂C(O)OR², —

OC(R¹)₂C(O)NH₂, —

OC(R¹)₂C(O)NHR², —

OC(R¹)₂C(O)N(R²)₂, —

OC(R¹)₂C(O)NR⁷R⁸, amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —

NHR², N(R²)₂, —

NR R, —

NHC(R¹)₂C(O)OH, —

NHC(R¹)₂C(O)OR², —

NHC(O)R², —

N(R²)C(O)R², —

NHC(O)OR², —

NHC(O)SR², —

NHSO₂NHR², —

NHSO₂R², —

NHSO₂NR⁷R⁸, —

N(C(O)NHR²)₂, —

NR²SO₂R², —

NHC(O)NHR², —

NHC(O)NR⁷R⁸, —

NHC(O)N(R²)₂, thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —

SC(R¹)₂C(O)OH, —

SC(R¹)₂C(O)OR², —

SCH₂C(O)OH, —

SCF₂C(O)OH, —

SO₂NH₂, —

SO₂NHR², —

SO₂N(R²)₂, SO₂NR⁷R⁸, —

SO₂NHC(O)R², —

SR², —

SO₂NHC(O)NHR², —

SO₂NHC(O)N(R²)₂, —

SO₂NHC(O)NR⁷R⁸, sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —

C(O)OR², —

C(O)NH₂, —

C(O)NHR², —

C(O)N(R²)₂, —

C(O)NR⁷R⁸, —

C(O)NHC(O)R², —

C(O)NHC(O)NHR², —

C(O)NHC(O)N(R²)₂, —

C(O)NHC(O)NR⁷R⁸, —

C(O)NHSO₂R², —

C(O)NHSO₂NHR², —

C(O)NHSO₂N(R²), —

C(O)NHSO₂NR⁷R⁸, —

C(CH₃)₂C(O)OH, —

(CH₂)_yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —

PO₂H₂, —

PO₃H₂, —

P(R²)O₂H, and phosphate, all of which can be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R^2α

and R^6α

are independently selected from the group consisting of halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, R²C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyalkyl, alkoxy, lower alkoxy, —

(O(CH₂)₂)_1-3—

O-lower alkyl, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —

OC(R¹)₂C(O)OH, —

OC(R¹)₂C(O)OR², —

OC(R¹)₂C(O)NH₂, —

OC(R¹)₂C(O)NHR², —

OC(R¹)₂C(O)N(R²)₂, —

OC(R¹)₂C(O)NR⁷R⁸, —

NHSO₂NHR², —

NHSO₂R², —

NHSO₂NR⁷R⁸, —

NR²SO₂R², alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —

SC(R¹)₂C(O)OH, —

SC(R¹)₂C(O)OR², —

SCH₂C(O)OH, —

SCF₂C(O)OH, —

SO₂NH₂, —

SO₂NHR², —

SO₂N(R²)₂, SO₂NR⁷R⁸, —

SO₂NHC(O)R², —

SR², —

SO₂NHC(O)NHR², —

SO₂NHC(O)N(R²) 2, —

SO₂NHC(O)NR⁷R⁸, sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —

C(O)OR², —

C(O)NH₂, —

C(O)NHR², —

C(O)N(R²)₂, —

C(O)NR⁷R⁸, —

C(O)NHC(O)R², —

C(O)NHC(O)NHR², —

C(O)NHC(O)N(R²)₂, —

C(O)NHC(O)NR⁷R⁸, —

C(O)NHSO₂R², —

C(O)NHSO₂NHR², —

C(O)NHSO₂N(R²), —

C(O)NHSO₂NR⁷R⁸, —

C(CH₃)₂C(O)OH, —

(CH₂)_yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —

PO₂H₂, —

PO₃H₂, —

P(R²)O₂H, and phosphate, all of which can be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R¹ is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R² is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R⁷ and R⁸ are independently selected from the group consisting of alkyl, alkenyl, heteroaryl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring;

wherein one of R^2β

, R^3β

, R^4β

, R^5β

or R^6β

, or one of R^2α

, R^3α

, R^4α

, R^5α

or R^6α

must be a carbon-carbon linked heteroaryl;

wherein all R¹, R², R⁷ and R⁸ substituents can be optionally substituted where possible with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂.

5. The compound of claim 4 or its pharmaceutically acceptable salt or ester, wherein:

R^3α

, R^4α

, R^5α

, R^2β

, R^3β

, R^4β

, R^5β

and R^6β

are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, —

C(O)R², R²C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alkoxy, lower alkoxy, —

(O(CH₂)₂)_1-3—

O-lower alkyl, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —

OC(R¹)₂C(O)OH, —

OC(R¹)₂C(O)OR², —

OC(R¹)₂C(O)NH₂, —

OC(R¹)₂C(O)NHR², —

OC(R¹)₂C(O)N(R²)₂, —

OC(R¹)₂C(O)NR⁷R⁸, amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —

NHR², N(R²)₂, —

NR⁷R⁸, —

NHC(R¹)₂C(O)OH, —

NHC(R¹)₂C(O)OR², —

NHC(O)R², —

N(R²)C(O)R², —

NHC(O)OR², —

NHC(O)SR², —

NHSO₂NHR², —

NHSO₂R², —

NHSO₂NR⁷R⁸, —

N(C(O)NHR²)₂, —

NR²SO₂R², —

NHC(O)NHR², —

NHC(O)NR⁷R⁸, —

NHC(O)N(R²)₂, thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —

SC(R¹)₂C(O)OH, —

SC(R¹)₂C(O)OR², —

SCH₂C(O)OH, —

SCF₂C(O)OH, —

SO₂NH₂, SO₂NHR², —

SO₂N(R²)₂, SO₂NR⁷R⁸, —

SO₂NHC(O)R², —

SR², —

SO₂NHC(O)NHR², —

SO₂NHC(O)N(R²)₂, —

SO₂NHC(O)NR⁷R⁸, sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —

C(O)OR², —

C(O)NH₂, —

C(O)NHR², —

C(O)N(R²)₂, —

C(O)NR⁷R⁸, —

C(O)NHC(O)R², —

C(O)NHC(O)NHR², —

C(O)NHC(O)N(R²)₂, —

C(O)NHC(O)NR⁷R⁸, —

C(O)NHSO₂R², —

C(O)NHSO₂NHR², —

C(O)NHSO₂N(R), —

C(O)NHSO₂NR⁷R⁸, —

C(CH₃)₂C(O)OH, —

(CH₂)_yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —

PO₂H₂, —

PO₃H₂, —

P(R²)O₂H, and phosphate, all of which can be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R^2α

and R^6α

are independently selected from the group consisting of halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, R²C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyalkyl, alkoxy, lower alkoxy, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —

OC(R¹)₂C(O)OH, —

OC(R¹)₂C(O)OR², —

OC(R¹)₂C(O)NH₂, —

OC(R¹)₂C(O)NHR², —

OC(R¹)₂C(O)N(R²)₂, —

OC(R¹)₂C(O)NR⁷R⁸, —

NHSO₂NHR², —

NHSO₂R, —

NHSO₂NR⁷R⁸, —

NR²SO₂R², alkylthio, cycloalkylthio, —

SC(R¹)₂C(O)OH, —

SC(R¹)₂C(O)OR², —

SCH₂C(O)OH, —

SCF₂C(O)OH, —

SO₂NHR², —

SO₂NHR², —

SO₂N(R²)₂, SO₂NR⁷R⁸, —

SO₂NHC(O)R², —

SR², —

SO₂NHC(O)NHR², —

SO₂NHC(O)N(R²) 2, —

SO₂NHC(O)NR⁷R⁸, cyano, tetrazol-5-yl, carboxy, —

C(O)OR², —

C(O)NH₂, —

C(O)NHR², —

C(O)N(R²)₂, —

C(O)NR⁷R⁸, —

C(O)NHC(O)R², —

C(O)NHC(O)NHR², —

C(O)NHC(O)N(R²)₂, —

C(O)NHC(O)NR⁷R⁸, —

C(O)NHSO₂R², —

C(O)NHSO₂NHR², —

C(O)NHSO₂N(R²), —

C(O)NHSO₂N⁷R⁸, —

C(CH₃)₂C(O)OH, —

(CH₂)_yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, all of which can be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R¹ is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R² is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R⁷ and R⁸ are independently selected from the group consisting of alkyl, alkenyl, heteroaryl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring;

wherein one of R^2α

, R^3α

, R^4α

, R^5α

or R^6α

must be a carbon-carbon linked heteroaryl;

wherein all R¹, R², R⁷ and R⁸ substituents can be optionally substituted where possible with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂.

6. The compound of claim 5 or its pharmaceutically acceptable salt or ester, wherein:

R^3α

, R^4α

, R^5α

, R^2β

, R^3β

, R^4β

, R^5β

and R^6β

are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, R²C(O)alkyl, aminoalkyl, hydroxyl, hydroxyalkyl, alkoxy, lower alkoxy, cycloalkyloxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, —

OC(R¹)₂C(O)OH, —

OC(R¹)₂C(O)OR², —

OC(R¹)₂C(O)NH₂, —

OC(R¹)₂C(O)NHR², —

OC(R¹)₂C(O)N(R²)₂, —

OC(R¹)₂C(O)NR⁷R⁸, amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, NHR², N(R²)₂, —

NR⁷R⁸, —

NHC(R¹)₂C(O)OH, —

NHC(R¹)₂C(O)OR², —

NHC(O)R², —

N(R²)C(O)R², —

NHC(O)OR², —

NHC(O)SR², —

NHSO₂NHR², —

NHSO₂R², —

NHSO₂NR⁷R⁸, —

N(C(O)NHR²)₂, —

NR²SO₂, —

NHC(O)NHR², —

NHC(O)NR⁷R⁸, —

NHC(O)N(R²)₂, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —

SC(R¹)₂C(O)OH, —

SC(R¹)₂C(O)OR², —

SCH₂C(O)OH, —

SCF₂C(O)OH, —

SO₂NH₂, —

SO₂NHR², —

SO₂N(R²)₂, SO₂NR⁷R⁸, —

SO₂NHC(O)R², —

SR², —

SO₂NHC(O)NHR², —

SO₂NHC(O)N(R²) 2, —

SO₂NHC(O)NR⁷R⁸, cyano, tetrazol-5-yl, carboxy, —

C(O)OR², —

C(O)NH₂, —

C(O)NHR², —

C(O)N(R²)₂, —

C(O)NR⁷R⁸, C(O)NHC(O)R², —

C(O)NHC(O)NHR², —

C(O)NHC(O)N(R²)₂, —

C(O)NHC(O)NR⁷R⁸, —

C(O)NHSO₂R², —

C(O)NHSO₂NHR², —

C(O)NHSO₂N(R²), —

C(O)NHSO₂NR⁷R⁸, —

C(CH₃)₂C(O)OH, all of which can be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R^2α

and R^6α

are independently selected from the group consisting of halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, R²C(O)alkyl, aminoalkyl, hydroxyalkyl, alkoxy, lower alkoxy, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —

OC(R¹)₂C(O)OH, —

OC(R¹)₂C(O)OR², —

OC(R¹)₂C(O)NH₂, —

OC(R¹)₂C(O)NHR², —

OC(R¹)₂C(O)N(R²)₂, —

OC(R¹)₂C(O)NR⁷R⁸, —

SC(R¹)₂C(O)OH, —

SC(R¹)₂C(O)OR², —

SCH₂C(O)OH, —

SCF₂C(O)OH, —

SO₂NH₂, —

SO₂NHR², —

SO₂N(R²)₂, SO₂NR⁷R⁸, —

SO₂NHC(O)R², —

SR², —

SO₂NHC(O)NHR², —

SO₂NHC(O)N(R²)₂, —

SO₂NHC(O)NR⁷R⁸, all of which can be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R¹ is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R² is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R⁷ and R⁸ are independently selected from the group consisting of alkyl, alkenyl, heteroaryl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring;

wherein one of R^2α

, R^3α

, R^4α

, R^5α

or R^6α

must be a carbon-carbon linked heteroaryl;

wherein all R¹, R², R⁷ and R⁸ substituents can be optionally substituted where possible with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂.

7. The compound of claim 6 or its pharmaceutically acceptable salt or ester, wherein:

R^3α

, R^4α

, R^5α

, R^2β

, R^3β

, R^4β

, R^5β

and R^6β

are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, R²C(O)alkyl, aminoalkyl, hydroxyl, hydroxyalkyl, alkoxy, lower alkoxy, cycloalkyloxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, —

OC(R¹)₂C(O)OH, —

OC(R¹)₂C(O)OR², —

OC(R¹)₂C(O)NH₂, —

OC(R¹)₂C(O)NHR², —

OC(R¹)₂C(O)N(R²)₂, —

OC(R¹)₂C(O)NR⁷R⁸, amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —

NHR², N(R²)₂, —

NR⁷R⁸, —

NHC(R¹)₂C(O)OH, —

NHC(R¹)₂C(O)OR², —

NHC(O)R², —

N(R²)C(O)R², —

NHC(O)OR², —

NHC(O)SR², —

NHSO₂NHR², —

NHSO₂R², —

NHSO₂NR⁷R⁸, —

N(C(O)NHR²)₂, —

NR²SO₂R², —

NHC(O)NHR², —

NHC(O)NR⁷R⁸, —

NHC(O)N(R²)₂, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —

SC(R¹)₂C(O)OH, —

SC(R¹)₂C(O)OR², —

SCH₂C(O)OH, —

SCF₂C(O)OH, —

SO₂NH₂, —

SO₂NHR², —

SO₂N(R²)₂, SO₂NR⁷R⁸, —

SO₂NHC(O)R², —

SR², —

SO₂NHC(O)NHR², —

SO₂NHC(O)N(R²)₂, —

SO₂NHC(O)NR⁷R⁸, cyano, tetrazol-5-yl, carboxy, —

C(O)OR², —

C(O)NH₂, —

C(O)NHR², —

C(O)N(R²)₂, —

C(O)NR⁷R⁸, —

C(O)NHC(O)R², —

C(O)NHC(O)NHR², —

C(O)NHC(O)N(R²)₂, —

C(O)NHC(O)NR⁷R⁸, —

C(O)NHSO₂R², —

C(O)NHSO₂NHR², —

C(O)NHSO₂N(R²), —

C(O)NHSO₂NR⁷R⁸, —

C(CH₃)₂C(O)OH, all of which can be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R^2α

and R^6α

are independently selected from the group consisting of halogen, nitro, lower alkyl, haloalkyl, aryl, heteroaryl, aminoalkyl, hydroxyalkyl, alkoxy, lower alkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, —

OC(R¹)₂C(O)OH, —

OC(R¹)₂C(O)OR², —

OC(R¹)₂C(O)NH₂, —

OC(R¹)₂C(O)NHR², —

OC(R¹)₂C(O)N(R²)₂, —

OC(R¹)₂C(O)NR⁷R⁸, —

SC(R¹)₂C(O)OH, —

SC(R¹)₂C(O)OR², —

SCH₂C(O)OH, —

SCF₂C(O)OH, —

SO₂NH₂, —

SO₂NHR², —

SO₂N(R²)₂, SO₂NR⁷R⁸, —

SO₂NHC(O)R², —

SR², —

SO₂NHC(O)NHR², —

SO₂NHC(O)N(R²)₂, —

SO₂NHC(O)NR⁷R⁸, all of which can be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R¹ is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R² is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R⁷ and R⁸ are independently selected from the group consisting of alkyl, alkenyl, heteroaryl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring;

wherein one of R^2α

, R^3α

, R^4α

, R^5α

or R^6α

must be a carbon-carbon linked heteroaryl;

wherein all R¹, R², R⁷ and R⁸ substituents can be optionally substituted where possible with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂.

8. The compound of claim 5 or its pharmaceutically acceptable salt or ester, wherein:

R^3α

, R^4α

, R^5α

, R^2β

, R^3β

, R^4β

, R^5β

and R^6β

are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heterocyclic, aminoalkyl, hydroxyl, hydroxyalkyl, alkoxy, lower alkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, —

OC(R¹)₂C(O)OH, —

OC(R¹)₂C(O)OR², amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —

NHR², N(R²)₂, —

NR⁷R⁸, —

NHC(R¹)₂C(O)OH, —

NHC(R¹)₂C(O)OR², —

NHC(O)R², —

N(R²)C(O)R²—

NHC(O)OR, —

NHC(O)SR², —

NHSO₂NHR², —

NHSO₂R², —

NHSO₂NR⁷R⁸, —

N(C(O)NHR²)₂, —

NR²SO₂R², —

NHC(O)NHR², —

NHC(O)NR⁷R⁸, —

NHC(O)N(R²)₂, —

SC(R¹)₂C(O)OH, —

SC(R¹)₂C(O)OR², —

SO₂NH₂, —

SO₂NHR², —

SO₂N(R²)₂, SO₂NR⁷R⁸, —

SO₂NHC(O)R², —

SR², —

SO₂NHC(O)NHR², —

SO₂NHC(O)N(R²) 2, —

SO₂NHC(O)NR⁷R⁸, cyano, tetrazol-5-yl, carboxy, —

C(O)OR², —

C(O)NH₂, —

C(O)NHR², —

C(O)N(R²)₂, —

C(O)NR⁷R⁸, —

C(O)NHC(O)R², —

C(O)NHC(O)NHR², —

C(O)NHC(O)N(R²)₂, —

C(O)NHC(O)NR⁷R⁸, —

C(O)NHSO₂R², —

C(O)NHSO₂NHR², —

C(O)NHSO₂N(R²), —

C(O)NHSO₂NR⁷R⁸, —

C(CH₃)₂C(O)OH, all of which can be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R^2α

and R^6α

are independently selected from the group consisting of halogen, lower alkyl, lower alkoxy, aryl, and heteroaryl;

R¹ is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R² is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R⁷ and R⁸ are independently selected from the group consisting of alkyl, alkenyl, heteroaryl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring;

wherein one of R^2α

, R^3α

, R^4α

, R^5α

or R^6α

must be a carbon-carbon linked heteroaryl;

wherein all R¹, R², R⁷ and R⁸ substituents can be optionally substituted where possible with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂.

9. The compound of claim 5 or its pharmaceutically acceptable salt or ester, wherein:

R^2β

, R^3β

, R^4β

, R^5β

and R^6β

are independently selected from the group consisting of hydrogen, halogen, nitro, lower alkyl, haloalkyl, heteroaryl, heterocyclic, hydroxyl, lower alkoxy, —

OC(R¹)₂C(O)OH, —

OC(R¹)₂C(O)OR², —

SO₂NHR², —

SO₂N(R²)₂, carboxy, and —

C(O)OR²;

R^2α

and R^6α

are independently selected from the group consisting of halogen, heteroaryl, aryl, lower alkyl, and lower alkoxy;

R¹ is independently selected from the group consisting of hydrogen and lower alkyl;

R² is lower alkyl, optionally substituted by one or more carboxy groups;

wherein one of R^2α

, R^3α

, R^4α

, R^5α

, or R^6α

must be a carbon-carbon linked heteroaryl.

10. The compound of claim 5 or its pharmaceutically acceptable salt or ester, wherein:

R^2β

, R^3β

, R^5β

and R^6β

are independently selected from the group consisting of hydrogen, nitro, lower alkyl, haloalkyl, heteroaryl, heterocyclic, hydroxyl, lower alkoxy, —

OC(R¹)₂C(O)OH, —

OC(R¹)₂C(O)OR², —

SO₂NHR², —

SO₂N(R²)₂, carboxy, and —

C(O)OR;

R^4β

is independently selected from the group consisting of hydrogen, halogen, nitro, lower alkyl, haloalkyl, heteroaryl, heterocyclic, hydroxyl, lower alkoxy, —

OC(R¹)₂C(O)OH, —

OC(R¹)₂C(O)OR², —

SO₂NHR², —

SO₂N(R²)₂, carboxy, and C(O)OR²;

R^2α

and R^6α

are independently selected from the group consisting of halogen, heteroaryl, aryl, lower alkyl, and lower alkoxy;

R¹ is independently selected from the group consisting of hydrogen and lower alkyl;

R² is lower alkyl, optionally substituted by one or more carboxy groups;

wherein one of R^2α

, R^3α

, R^4α

, R^5α

, or R^6α

must be a carbon-carbon linked heteroaryl.

11. The compound of claim 5 or its pharmaceutically acceptable salt or ester, wherein:

R^2β

, R^3β

, R^4β

, R^5β

and R^6β

are independently selected from the group consisting of hydrogen, chloro, fluoro, bromo, nitro, methyl, tert-butyl, trifluoromethyl, thienyl, benzothienyl, methoxypyridyl, pyridyl, hydroxyl, methoxy, carboxy, —

OCH₂C(O)OH, —

OC(CH₃)₂C(O)OH, and —

SO₂N(CH₃)CH₂C(O)OH;

R^2α

and R^6α

are independently selected from the group consisting of chloro, fluoro, bromo, nitro, methyl, and methoxy;

wherein one of R^2α

, R^3α

, R^4α

, R^5α

, or R^6α

must be thienyl, benzothienyl, methoxypyridyl, or pyridyl.

12. The compound of claim 1 selected from the group consisting of:

4-[1-(2,6-Dimethoxy-3-thien-2-yl-benzoyl)-vinyl]-benzoic acid;

1-(2,6-Dimethoxy-3-thien-2-yl-phenyl)-2-(2-methoxy-phenyl)-propenone;

2-(3,5-Di-tert-butyl-4-hydroxy-phenyl)-1-(2,6-dimethoxy-3-thien-2-yl-phenyl)-propenone;

2-{4-[1-(2,6-Dimethoxy-3-thien-2-yl-benzoyl)-vinyl]-phenoxy}-2-methyl-propionic acid;

1-(2,6-Dimethoxy-3-thien-2-yl-phenyl)-2-(4-trifluoromethyl-phenyl)-propenone;

1-(2,6-Dimethoxy-3-thien-2-yl-phenyl)-2-(4-nitro-phenyl)-propenone;

2-(2,6-Dichloro-phenyl)-1-(2,6-dimethoxy-3-thien-2-yl-phenyl)-propenone;

2-{3-[1-(2,6-Dimethoxy-3-thien-2-yl-benzoyl)-vinyl]-phenoxy}-2-methyl-propionic acid;

2-{3-[1-(3-Benzo[b]thien-2-yl-2,6-dimethoxy-benzoyl)-vinyl]-phenoxy}-2-methyl-propionic acid;

({4-[1-(2,6-Dimethoxy-3-thien-2-yl-benzoyl)-vinyl]-benzenesulfonyl}-methyl-amino)-acetic acid; and

1-(2,6-Dimethoxy-3-thien-2-yl-phenyl)-2-(2-fluoro-6-trifluoromethyl-phenyl)-propenone.

13. The compound of claim 4 or its pharmaceutically acceptable salt or ester, wherein:

R^3α

, R^4α

, R^5α

, R^2β

, R^3β

, R^4β

, R^5β

and R^6β

are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, —

C(O)R², R²C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alkoxy, lower alkoxy, —

(O(CH₂)₂)_1-3—

O-lower alkyl, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —

OC(R¹)₂C(O)OH, —

OC(R¹)₂C(O)OR², —

OC(R¹)₂C(O)NH₂, —

OC(R¹)₂C(O)NHR², —

OC(R¹)₂C(O)N(R²)₂, —

OC(R¹)₂C(O)NR⁷R⁸, amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —

NHR², N(R²)₂, —

NR⁷R⁸, —

NHC(R¹)₂C(O)OH, —

NHC(R¹)₂C(O)OR², —

NHC(O)R², —

N(R²)C(O)R², —

NHC(O)OR², —

NHC(O)SR², —

NHSO₂NHR², —

NHSO₂R², —

NHSO₂NR⁷R⁸, —

N(C(O)NHR²)₂, —

NR²SO₂R², —

NHC(O)NHR², —

NHC(O)NR⁷R⁸, —

NHC(O)N(R²)₂, thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —

SC(R¹)₂C(O)OH, —

SC(R¹)₂C(O)OR², —

SCH₂C(O)OH, —

SCF₂C(O)OH, —

SO₂NH₂, —

SO₂NHR², —

SO₂N(R²)₂, SO₂NR⁷R⁸, —

SO₂NHC(O)R², —

SR², —

SO₂NHC(O)NHR², —

SO₂NHC(O)N(R²)₂, —

SO₂NHC(O)NR⁷R⁸, sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —

C(O)OR², —

C(O)NH₂, —

C(O)NHR², —

C(O)N(R²)₂, —

C(O)NR⁷R⁸, —

C(O)NHC(O)R², —

C(O)NHC(O)NHR², —

C(O)NHC(O)N(R²)₂, —

C(O)NHC(O)NR⁷R⁸, —

C(O)NHSO₂R², —

C(O)NHSO₂NHR², —

C(O)NHSO₂N(R²), —

C(O)NHSO₂NR⁷R⁸, —

C(CH₃)₂C(O)OH, —

(CH₂)_yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —

PO₂H₂, —

PO₃H₂, —

P(R²)O₂H, and phosphate, all of which can be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)N⁷R⁸, and —

C(O)N(R²)₂;

R^2α

and R^6α

are independently selected from the group consisting of halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, R²C(O) alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyalkyl, alkoxy, lower alkoxy, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —

OC(R)₂C(O)OH, —

OC(R¹)₂C(O)OR², —

OC(R¹)₂C(O)NH₂, —

OC(R¹)₂C(O)NHR², —

OC(R¹)₂C(O)N(R²)₂, —

OC(R¹)₂C(O)NR⁷R⁸, —

NHSO₂NHR², —

NHSO₂R², —

NHSO₂NR⁷R⁸, —

NR²SO₂R², alkylthio, cycloalkylthio, —

SC(R¹)₂C(O)OH, —

SC(R¹)₂C(O)OR², —

SCH₂C(O)OH, —

SCF₂C(O)OH, —

SO₂NH₂, —

SO₂NHR², —

SO₂N(R²)₂, SO₂NR⁷R⁸, —

SO₂NHC(O)R², —

SR², —

SO₂NHC(O)NHR², —

SO₂NHC(O)N(R²) 2, —

SO₂NHC(O)NR⁷R⁸, cyano, tetrazol-5-yl, carboxy, —

C(O)OR², —

C(O)NH₂, —

C(O)NHR², —

C(O)N(R²)₂, —

C(O)NR⁷R⁸, C(O)NHC(O)R², —

C(O)NHC(O)NHR², —

C(O)NHC(O)N(R²)₂, —

C(O)NHC(O)NR⁷R⁸, —

C(O)NHSO₂R², —

C(O)NHSO₂NHR², —

C(O)NHSO₂N(R²), —

C(O)NHSO₂NR⁷R⁸, —

C(CH₃)₂C(O)OH, —

(CH₂)_yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, all of which can be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)N⁷R⁸, and —

C(O)N(R²)₂;

R¹ is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R² is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R⁷ and R⁸ are independently selected from the group consisting of alkyl, alkenyl, heteroaryl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring;

wherein one of R^2β

, R^3β

, R^4β

, R^5β

or R^6β

must be a carbon-carbon linked heteroaryl;

wherein all R¹, R², R⁷ and R⁸ substituents can be optionally substituted where possible with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂.

14. The compound of claim 13 or its pharmaceutically acceptable salt or ester, wherein:

R^3α

, R^4α

, R^5α

, R^2β

, R^3β

, R^4β

, R^5β

and R^6β

are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, R²C(O)alkyl, aminoalkyl, hydroxyl, hydroxyalkyl, alkoxy, lower alkoxy, cycloalkyloxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, —

OC(R¹)₂C(O)OH, —

OC(R¹)₂C(O)OR², —

OC(R¹)₂C(O)NH₂, —

OC(R¹)₂C(O)NHR², —

OC(R¹)₂C(O)N(R²)₂, —

OC(R¹)₂C(O)NR⁷R⁸, amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —

NHR², N(R²)₂, —

NR⁷R⁸, —

NHC(R¹)₂C(O)OH, —

NHC(R¹)₂C(O)OR², —

NHC(O)R², —

N(R²)C(O)R², —

NHC(O)OR², —

NHC(O)SR², —

NHSO₂NHR², —

NHSO₂R², —

NHSO₂NR⁷R⁸, —

N(C(O)NHR²)₂, —

NR²SO₂R², —

NHC(O)NHR², —

NHC(O)NR⁷R⁸, —

NHC(O)N(R²)₂, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —

SC(R¹)₂C(O)OH, —

SC(R¹)₂C(O)OR², —

SCH₂C(O)OH, —

SCF₂C(O)OH, —

SO₂NH₂, —

SO₂NHR², —

SO₂N(R²)₂, SO₂NR⁷R⁸, —

SO₂NHC(O)R², —

SR², —

SO₂NHC(O)NHR², —

SO₂NHC(O)N(R²) 2, —

SO₂NHC(O)NR⁷R⁸, cyano, tetrazol-5-yl, carboxy, —

C(O)OR², —

C(O)NH₂, —

C(O)NHR², —

C(O)N(R²)₂, —

C(O)NR⁷R⁸, —

C(O)NHC(O)R², —

C(O)NHC(O)NHR², —

C(O)NHC(O)N(R²)₂, —

C(O)NHC(O)NR⁷R⁸, —

C(O)NHSO₂R², —

C(O)NHSO₂NHR², —

C(O)NHSO₂N(R²), —

C(O)NHSO₂NR⁷R⁸, —

C(CH₃)₂C(O)OH, all of which can be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R^2α

and R^6α

are independently selected from the group consisting of halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, R²C(O)alkyl, aminoalkyl, hydroxyalkyl, alkoxy, lower alkoxy, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —

OC(R¹)₂C(O)OH, —

OC(R¹)₂C(O)OR², —

OC(R¹)₂C(O)NH₂, —

OC(R¹)₂C(O)NHR², —

OC(R¹)₂C(O)N(R²)₂, —

OC(R¹)₂C(O)NR⁷R⁸, —

SC(R)₂C(O)OH, —

SC(R¹)₂C(O)OR², —

SCH₂C(O)OH, —

SCF₂C(O)OH, —

SO₂NH₂, —

SO₂NHR², —

SO₂N(R²)₂, SO₂NR⁷R⁸, —

SO₂NHC(O)R², —

SR², —

SO₂NHC(O)NHR², —

SO₂NHC(O)N(R²) 2, —

SO₂NHC(O)NR⁷R⁸, all of which can be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R¹ is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R² is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R⁷ and R⁸ are independently selected from the group consisting of alkyl, alkenyl, heteroaryl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring;

wherein one of R^2β

, R^3β

, R^4β

, R^5β

or R^6β

must be a carbon-carbon linked heteroaryl;

wherein all R¹, R², R⁷ and R⁸ substituents can be optionally substituted where possible with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂.

15. The compound of claim 14 or its pharmaceutically acceptable salt or ester, wherein:

R^3α

, R^4α

, R^5α

, R^2β

, R^3β

, R^4β

, R^5β

and R^6β

are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, R²C(O)alkyl, aminoalkyl, hydroxyl, hydroxyalkyl, alkoxy, lower alkoxy, cycloalkyloxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, —

OC(R¹)₂C(O)OH, —

OC(R¹)₂C(O)OR², —

OC(R¹)₂C(O)NH₂, —

OC(R¹)₂C(O)NHR², —

OC(R¹)₂C(O)N(R²)₂, —

OC(R¹)₂C(O)NR⁷R⁸, amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —

NHR, N(R²)₂, —

NR⁷R⁸, —

NHC(R¹)₂C(O)OH, —

NHC(R¹)₂C(O)OR², —

NHC(O)R², —

N(R²)C(O)R², —

NHC(O)OR², —

NHC(O)SR², —

NHSO₂NHR², —

NHSO₂R², —

NHSO₂NR⁷R⁸, —

N(C(O)NHR²)₂, —

NR²SO₂R², —

NHC(O)NHR², —

NHC(O)NR⁷R⁸, —

NHC(O)N(R²)₂, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —

SC(R¹)₂C(O)OH, —

SC(R¹)₂C(O)OR², —

SCH₂C(O)OH, —

SCF₂C(O)OH, —

SO₂NH₂, —

SO₂NHR², —

SO₂N(R²)₂, SO₂NR⁷R⁸, —

SO₂NHC(O)R², —

SR², —

SO₂NHC(O)NHR², —

SO₂NHC(O)N(R²) 2, —

SO₂NHC(O)NR⁷R⁸, cyano, tetrazol-5-yl, carboxy, —

C(O)OR², —

C(O)NH₂, —

C(O)NHR², —

C(O)N(R²)₂, —

C(O)NR⁷R⁷, —

C(O)NHC(O)R², —

C(O)NHC(O)NHR², —

C(O)NHC(O)N(R²)₂, —

C(O)NHC(O)NR⁷R⁸, —

C(O)NHSO₂R², —

C(O)NHSO₂NHR², —

C(O)NHSO₂N(R²), —

C(O)NHSO₂NR⁷R⁸, —

C(CH₃)₂C(O)OH, all of which can be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R^2α

and R^6α

are independently selected from the group consisting of halogen, nitro, lower alkyl, haloalkyl, aryl, heteroaryl, aminoalkyl, hydroxyalkyl, alkoxy, lower alkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, —

OC(R¹)₂C(O)OH, —

OC(R¹)₂C(O)OR², —

OC(R¹)₂C(O)NH₂, —

OC(R¹)₂C(O)NHR², —

OC(R¹)₂C(O)N(R²)₂, —

OC(R¹)₂C(O)NR⁷R⁸, —

SC(R¹)₂C(O)OH, —

SC(R¹)₂C(O)OR², —

SCH₂C(O)OH, —

SCF₂C(O)OH, —

SO₂NH₂, —

SO₂NHR², —

SO₂N(R²)₂, SO₂NR⁷R⁸, —

SO₂NHC(O)R², —

SR², —

SO₂NHC(O)NHR², —

SO₂NHC(O)N(R²) 2, —

SO₂NHC(O)NR⁷R⁸, all of which can be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R¹ is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R² is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R⁷ and R⁸ are independently selected from the group consisting of alkyl, alkenyl, heteroaryl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring;

wherein one of R^2β

, R^3β

, R^4β

, R^5β

or R^6β

must be a carbon-carbon linked heteroaryl;

wherein all R¹, R², R⁷ and R⁸ substituents can be optionally substituted where possible with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂.

16. The compound of claim 13 or its pharmaceutically acceptable salt or ester, wherein:

R^3α

, R^4α

, R^5α

, R^2β

, R^3β

, R^4β

, R^5β

and R^6β

are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heterocyclic, aminoalkyl, hydroxyl, hydroxyalkyl, alkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, —

OC(R¹)₂C(O)OH, —

OC(R¹)₂C(O)OR², amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —

NHR², N(R²)₂, —

NR⁷R⁸, —

NHC(R¹)₂C(O)OH, —

NHC(R¹)₂C(O)OR², —

NHC(O)R², —

N(R²)C(O)R², —

NHC(O)OR², —

NHC(O)SR², —

NHSO₂NHR², —

NHSO₂R², —

NHSO₂NR⁷R⁸, —

N(C(O)NHR²)₂, —

NR²SO₂R², —

NHC(O)NHR², —

NHC(O)NR⁷R⁸, —

NHC(O)N(R²)₂, —

SC(R¹)₂C(O)OH, —

SC(R¹)₂C(O)OR², —

SO₂NH₂, —

SO₂NHR², —

SO₂N(R²)₂, SO₂NR⁷R⁸, —

SO₂NHC(O)R², —

SR², —

SO₂NHC(O)NHR², —

SO₂NHC(O)N(R²) 2, —

SO₂NHC(O)NR⁷R⁸, cyano, tetrazol-5-yl, carboxy, —

C(O)OR², —

C(O)NH₂, —

C(O)NHR², —

C(O)N(R²)₂, —

C(O)NR⁷R⁸, —

C(O)NHC(O)R², —

C(O)NHC(O)NHR², —

C(O)NHC(O)N(R²)₂, —

C(O)NHC(O)NR⁷R⁸, —

C(O)NHSO₂R², —

C(O)NHSO₂NHR², —

C(O)NHSO₂N(R²), —

C(O)NHSO₂NR⁷R⁸, —

C(CH₃)₂C(O)OH, all of which can be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R^2α

and R^6α

are independently selected from the group consisting of F, Cl, Br, —

CH₃, —

OCH₃, aryl, and heteroaryl;

R¹ is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R¹ is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R⁷ and R⁸ are independently selected from the group consisting of alkyl, alkenyl, heteroaryl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring;

wherein one of R^2β

, R^3β

, R^4β

, R^5β

or R^6β

must be a carbon-carbon linked heteroaryl;

wherein all R¹, R², R⁷ and R⁸ substituents can be optionally substituted where possible with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂.

17. The compound of claim 13 or its pharmaceutically acceptable salt or ester, wherein:

R^2β

, R^3β

, R^4β

, R^5β

and R^6β

are independently selected from the group consisting of hydrogen, halogen, lower alkyl, haloalkyl, heteroaryl, heterocyclic, lower alkoxy, —

OC(R¹)₂C(O)OH, —

OC(R¹)₂C(O)OR², —

SO₂NHR², —

SO₂N(R²)₂, carboxy, and C(O)OR²;

R^2α

and R^6α

are independently selected from the group consisting of halogen, aryl, heteroaryl, lower alkyl, and lower alkoxy;

R¹ is independently selected from the group consisting of hydrogen and lower alkyl;

R² is lower alkyl, optionally substituted by one or more carboxy groups;

wherein one of R^2β

, R^3β

, R^4β

, R^5β

or R^6β

must be a carbon-carbon linked heteroaryl.

18. The compound of claim 13 or its pharmaceutically acceptable salt or ester, wherein:

R^2β

, R^3β

, R^4β

, R^5β

and R^6β

are independently selected from the group consisting of hydrogen, lower alkyl, haloalkyl, heteroaryl, heterocyclic, lower alkoxy, OC(R¹)₂C(O)OH, —

OC(R¹)₂C(O)OR², —

SO₂NHR², —

SO₂N(R²)₂, carboxy, and —

C(O)OR²;

R^4β

is selected from the group consisting of hydrogen, halogen, lower alkyl, haloalkyl, heteroaryl, heterocyclic, lower alkoxy, —

OC(R¹)₂C(O)OH, —

OC(R¹)₂C(O)OR², —

SO₂NHR², —

SO₂N(R²)₂, carboxy, and —

C(O)OR²;

R^2β

and R^6α

are independently selected from the group consisting of halogen, aryl, heteroaryl, lower alkyl, and lower alkoxy;

R¹ is independently selected from the group consisting of hydrogen and lower alkyl;

R² is lower alkyl, optionally substituted by one or more carboxy groups;

wherein one of R^2β

, R^3β

, R^4β

, R^5β

or R^6β

must be a carbon-carbon linked heteroaryl.

19. The compound of claim 13 or its pharmaceutically acceptable salt or ester, wherein:

R^2β

, R^3β

, R^4β

, R^5β

and R^6β

are independently selected from the group consisting of hydrogen, chloro, fluoro, bromo, nitro, methyl, tert-butyl, trifluoromethyl, thienyl, benzothienyl, methoxypyridyl, pyridyl, hydroxyl, methoxy, carboxy, —

OCH₂C(O)OH, —

OC(CH₃)₂C(O)OH, and —

SO₂N(CH₃)CH₂C(O)OH;

R^2α

and R^6α

are independently selected from the group consisting of chloro, fluoro, bromo, nitro, methyl, and methoxy;

wherein one of R^2β

, R^3β

, R^4β

, R^5β

or R^6β

must be thienyl, benzothienyl, methoxypyridyl, or pyridyl.

20. The compound of claim 1 selected from the group consisting of:

1-(2,6-Dichloro-phenyl)-2-(2-methoxy-5-thien-2-yl-phenyl)-propenone;

1-(2,6-Dimethyl-phenyl)-2-(2-methoxy-5-thien-2-yl-phenyl)-propenone;

4-[1-(2-Chloro-6-methyl-benzoyl)-vinyl]-3-thien-2-yl-benzoic acid;

4-[1-(2,6-Dimethyl-benzoyl)-vinyl]-3-thien-2-yl-benzoic acid;

4-[1-(2,6-Dimethoxy-benzoyl)-vinyl]-3-thien-2-yl-benzoic acid;

2-{4-[1-(2,6-Dimethoxy-benzoyl)-vinyl]-2-thien-2-yl-phenoxy}-2-methyl-propionic acid;

1-(2,6-Dimethyl-phenyl)-2-(2-thien-2-yl-phenyl)-propenone;

1-(2,6-Dimethyl-phenyl)-2-[2-(2-methoxy-pyridin-3-yl)-phenyl]-propenone;

1-(2,6-Dimethoxy-phenyl)-2-(2-thien-2-yl-phenyl)-propenone;

1-(2,6-Dimethoxy-phenyl)-2-(2-methoxy-5-thien-2-yl-phenyl)-propenone; and

2-{2-[1-(2,6-Dimethoxy-benzoyl)-vinyl]-4-thien-2-yl-phenoxy}-2-methyl-propionic acid.

21. The compound of claim 1 or its pharmaceutically acceptable salt or ester, wherein:

R^2α

, R^3α

, R^4α

, R^5α

, R^6α

, and R^4β

are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, —

C(O)R², R²C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alkoxy, lower alkoxy, —

(O(CH₂)₂)_1-3—

O-lower alkyl, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —

OC(R¹)₂C(O)OH, —

OC(R¹)₂C(O)OR², —

OC(R¹)₂C(O)NH₂, —

OC(R¹)₂C(O)NHR², —

OC(R¹)₂C(O)N(R²)₂, —

OC(R¹)₂C(O)NR⁷R⁸, amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —

NHR², N(R²)₂, —

NR⁷R⁸, —

NHC(R¹)₂C(O)OH, —

NHC(R¹)₂C(O)OR², —

NHC(O)R², —

N(R²)C(O)R², —

NHC(O)OR², —

NHC(O)SR², —

NHSO₂NHR², —

NHSO₂R², —

NHSO₂NR⁷R⁸, —

N(C(O)NHR²)₂, —

NR²SO₂R², —

NHC(O)NHR², —

NHC(O)NR⁷R⁸, —

NHC(O)N(R²)₂, thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —

SC(R¹)₂C(O)OH, —

SC(R¹)₂C(O)OR², —

SCH₂C(O)OH, —

SCF₂C(O)OH, —

SO₂NH₂, —

SO₂NHR², —

SO₂N(R²)₂, SO₂NR⁷R⁸, —

SO₂NHC(O)R², —

SR², —

SO₂NHC(O)NHR², —

SO₂NHC(O)N(R²)₂, —

SO₂NHC(O)NR⁷R⁸, sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —

C(O)OR², —

C(O)NH₂, —

C(O)NHR², —

C(O)N(R²)₂, —

C(O)NR⁷R⁸, —

C(O)NHC(O)R², —

C(O)NHC(O)NHR², —

C(O)NHC(O)N(R²)₂, —

C(O)NHC(O)NR⁷R⁸, —

C(O)NHSO₂R², —

C(O)NHSO₂NHR², —

C(O)NHSO₂N(R²), —

C(O)NHSO₂NR⁷R⁸, —

C(CH₃)₂C(O)OH, —

(CH₂)_yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —

PO₂H₂, —

PO₃H₂, —

P(R²)O₂H, and phosphate, all of which can be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R^2β

, R^3β

, R^5β

and R^6β

are independently selected from the group consisting of hydrogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, —

C(O)R², R²C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alkoxy, lower alkoxy, —

(O(CH₂)₂)_1-3—

O-lower alkyl, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —

OC(R¹)₂C(O)OH, —

OC(R¹)₂C(O)OR², —

OC(R¹)₂C(O)NH₂, —

OC(R¹)₂C(O)NHR², —

OC(R¹)₂C(O)N(R²)₂, —

OC(R¹)₂C(O)NR⁷R⁸, amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —

NHR², N(R²)₂, —

NR⁷R⁸, —

NHC(R¹)₂C(O)OH, —

NHC(R¹)₂C(O)OR², —

NHC(O)R², —

N(R²)C(O)R², —

NHC(O)OR², —

NHC(O)SR², —

NHSO₂NHR², —

NHSO₂R², —

NHSO₂NR⁷R⁸, —

N(C(O)NHR²)₂, —

NR²SO₂R², —

NHC(O)NHR², —

NHC(O)NR⁷R⁸, —

NHC(O)N(R²)₂, thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —

SC(R¹)₂C(O)OH, —

SC(R¹)₂C(O)OR², —

SCH₂C(O)OH, —

SCF₂C(O)OH, —

SO₂NH₂, —

SO₂NHR², —

SO₂N(R²)₂, SO₂NR⁷R⁸, —

SO₂NHC(O)R², —

SR², —

SO₂NHC(O)NHR², —

SO₂NHC(O)N(R²) 2, —

SO₂NHC(O)NR⁷R⁸, sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —

C(O)OR², —

C(O)NH₂, —

C(O)NHR², —

C(O)N(R²)₂, —

C(O)NR⁷R⁸, —

C(O)NHC(O)R², —

C(O)NHC(O)NHR², —

C(O)NHC(O)N(R²)₂, —

C(O)NHC(O)NR⁷R⁸, —

C(O)NHSO₂R², —

C(O)NHSO₂NHR², —

C(O)NHSO₂N(R²), —

C(O)NHSO₂NR⁷R⁸, —

C(CH₃)₂C(O)OH, —

(CH₂)_yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —

PO₂H₂, —

PO₃H₂, —

P(R²)O₂H, and phosphate, all of which can be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R¹ is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R² is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R⁷ and R⁸ are independently selected from the group consisting of alkyl, alkenyl, heteroaryl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring;

wherein one of R^2α

, R^3α

, R^4α

, R^5α

or R^6α

must be a carbon-carbon linked heteroaryl;

wherein all R¹, R², R⁷ and R⁸ substituents can be optionally substituted where possible with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂.

22. The compound of claim 21 or its pharmaceutically acceptable salt or ester, wherein:

R^2α

, R^3α

, R^4α

, R^5α

, R^6α

and R^4β

, are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, haloalkyl, heteroaryl, heterocyclic, hydroxyl, alkoxy, haloalkoxy, heteroaryloxy, heteroarylalkoxy, heterocyclicoxy, heterocyclicalkoxy, —

OC(R¹)₂C(O)OH, —

OC(R¹)₂C(O)OR², —

OC(R¹)₂C(O)NH₂, —

OC(R¹)₂C(O)NHR², —

OC(R¹)₂C(O)N(R²)₂, —

OC(R¹)₂C(O)NR⁷R⁸, heteroarylamino, heterocyclicamino, —

NHR², N(R²)₂, —

NR⁷R⁸, —

NHC(O)R², —

N(R²)C(O)R², —

NHC(O)OR², —

NHSO₂R², —

NR²SO₂R², cyano, tetrazol-5-yl, carboxy, —

C(O)OR², —

C(O)NH₂, —

C(O)NHR², —

C(O)N(R²)₂, —

C(O)NR⁷R⁸, all of which can be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R^2β

, R^3β

, R^5β

and R^6β

are independently selected from the group consisting of hydrogen, heteroaryl, heterocyclic, alkyl, alkoxy, and lower alkoxy, all of which can be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R¹ is independently selected from the group consisting of hydrogen, and lower alkyl, optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R¹ is independently selected from the group consisting of alkyl and lower alkyl, optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R⁷ and R⁸ are independently selected from the group consisting of alkyl, alkenyl, heteroaryl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring, optionally substituted where possible with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

wherein one of R^2α

, R^3α

, R^4α

, R^5α

or R^6α

must be a carbon-carbon linked heteroaryl.

23. The compound of claim 1 selected from the group consisting of:

4-[1-(5-Benzo[b]thien-2-yl-2,4-dimethoxy-benzoyl)-vinyl]-benzoic acid methyl ester;

4-[1-(4-Methoxy-3-thien-2-yl-benzoyl)-vinyl]-benzoic acid;

4-[1-(3,4-Dimethoxy-5-thien-2-yl-benzoyl)-vinyl]-benzoic acid;

1-(5-Benzo[b]thien-2-yl-2,4-dimethoxy-phenyl)-2-(4-methoxy-phenyl)-propenone;

1-(5-Benzo[b]thien-2-yl-2,4-dimethoxy-phenyl)-2-(4-fluoro-phenyl)-propenone;

1-(2-Methoxy-5-thien-2-yl-phenyl)-2-(4-nitro-phenyl)-propenone;

4-[1-(2-Methoxy-5-thien-2-yl-benzoyl)-vinyl]-benzonitrile; and

4-[1-(2-Methoxy-5-thien-2-yl-benzoyl)-vinyl]-benzoic acid.

24. The compound of claim 1 or its pharmaceutically acceptable salt or ester, wherein:

R^2α

, R^3α

, R^4α

, R^5α

, R^6α

, and R^4β

are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, —

C(O)R², R²C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alkoxy, lower alkoxy, —

(O(CH₂)₂)_1-3—

O-lower alkyl, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —

OC(R¹)₂C(O)OH, —

OC(R¹)₂C(O)OR², —

OC(R¹)₂C(O)NH₂, —

OC(R¹)₂C(O)NHR², —

OC(R²)₂C(O)N(R²)₂, —

OC(R¹)₂C(O)NR⁷R⁸, amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —

NHR², N(R²)₂, —

NR⁷R⁸, —

NHC(R¹)₂C(O)OH, —

NHC(R¹)₂C(O)OR², —

NHC(O)R², —

N(R²)C(O)R², —

NHC(O)OR², —

NHC(O)SR², —

NHSO₂NHR², —

NHSO₂R², —

NHSO₂NR⁷R⁸, —

N(C(O)NHR²)₂, —

NR²SO₂R², —

NHC(O)NHR², —

NHC(O)NR⁷R⁸, —

NHC(O)N(R²)₂, thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —

SC(R¹)₂C(O)OH, —

SC(R¹)₂C(O)OR², —

SCH₂C(O)OH, —

SCF₂C(O)OH, —

SO₂NH₂, SO₂NHR², —

SO₂N(R²)₂, SO₂NR⁷R⁸, —

SO₂NHC(O)R², —

SR², —

SO₂NHC(O)NHR², SO₂NHC(O)N(R²) 2, —

SO₂NHC(O)NR⁷R⁸, sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —

C(O)OR², —

C(O)NHR₂, —

C(O)NHR², —

C(O)N(R²)₂, —

C(O)NR⁷R⁸, —

C(O)NHC(O)R², —

C(O)NHC(O)NHR², —

C(O)NHC(O)N(R²)₂, —

C(O)NHC(O)NR⁷R⁸, —

C(O)NHSO₂R², —

C(O)NHSO₂NHR², —

C(O)NHSO₂N(R²), —

C(O)NHSO₂NR⁷R⁸, —

C(CH₃)₂C(O)OH, —

(CH₂)_yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —

PO₂H₂, —

PO₃H₂, —

P(R²)O₂H, and phosphate, all of which can be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R^2β

, R^3β

, R^5β

and R^6β

are independently selected from the group consisting of hydrogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, —

C(O)R², R²C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alkoxy, lower alkoxy, —

(O(CH₂)₂)_1-3—

O-lower alkyl, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —

OC(R¹)₂C(O)OH, —

OC(R¹)₂C(O)OR², —

OC(R¹)₂C(O)NH₂, —

OC(R¹)₂C(O)NHR², —

OC(R¹)₂C(O)N(R²)₂, —

OC(R¹)₂C(O)NR⁷R⁸, amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —

NHR², N(R²)₂, —

NR⁷R⁸, —

NHC(R¹)₂C(O)OH, —

NHC(R¹)₂C(O)OR², —

NHC(O)R², —

N(R²)C(O)R², —

NHC(O)OR², —

NHC(O)SR², —

NHSO₂NHR², —

NHSO₂R², —

NHSO₂NR⁷R⁸, —

N(C(O)NHR²)₂, —

NR²SO₂R², —

NHC(O)NHR², —

NHC(O)NR⁷R⁸, —

NHC(O)N(R²)₂, thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —

SC(R¹)₂C(O)OH, —

SC(R¹)₂C(O)OR², —

SCH₂C(O)OH, —

SCF₂C(O)OH, —

SO₂NH₂, —

SO₂NHR², —

SO₂N(R²)₂, SO₂NR⁷R⁸, —

SO₂NHC(O)R², —

SR₂, —

SO₂NHC(O)NHR², —

SO₂NHC(O)N(R²) 2, SO₂NHC(O)NR⁷R⁸, sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —

C(O)OR², —

C(O)NH₂, —

C(O)NHR², —

C(O)N(R²)₂, —

C(O)NR⁷R⁸, —

C(O)NHC(O)R², —

C(O)NHC(O)NHR², —

C(O)NHC(O)N(R²)₂, —

C(O)NHC(O)NR⁷R⁸, —

C(O)NHSO₂R², —

C(O)NHSO₂NHR², —

C(O)NHSO₂N(R²), —

C(O)NHSO₂NR⁷R⁸, —

C(CH₃)₂C(O)OH, —

(CH₂)_yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —

PO₂H₂, —

PO₃H₂, —

P(R²)O₂H, and phosphate, all of which can be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R¹ is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R¹)₂;

R² is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R⁷ and R⁸ are independently selected from the group consisting of alkyl, alkenyl, heteroaryl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring;

wherein one of R^2β

, R^3β

, R^4β

, R^5β

or R^6β

must be a carbon-carbon linked heteroaryl;

wherein all R¹, R², R⁷ and R⁸ substituents can be optionally substituted where possible with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂.

25. The compound of claim 24 or its pharmaceutically acceptable salt or ester, wherein:

R^2α

, R^3α

, R^4α

, R^5α

, R^6α

and R^4β

, are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, haloalkyl, heteroaryl, heterocyclic, hydroxyl, alkoxy, haloalkoxy, heteroaryloxy, heteroarylalkoxy, heterocyclicoxy, heterocyclicalkoxy, —

OC(R¹)₂C(O)OH, —

OC(R¹)₂C(O)OR², —

OC(R¹)₂C(O)NH₂, —

OC(R)₂C(O)NHR², —

OC(R¹)₂C(O)N(R²)₂, —

OC(R¹)₂C(O)NR⁷R⁸, heteroarylamino, heterocyclicamino, —

NHR², N(R²)₂, —

NR⁷R⁸, —

NHC(O)R², —

N(R²)C(O)R², —

NHC(O)OR², —

NHSO₂R², —

NR²SO₂R², cyano, tetrazol-5-yl, carboxy, —

C(O)OR², —

C(O)NH₂, —

C(O)NHR², —

C(O)N(R²)₂, —

C(O)NR⁷R⁸, all of which can be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R^2β

, R^3β

, R^5β

and R^6β

are independently selected from the group consisting of hydrogen, heteroaryl, heterocyclic, alkyl, alkoxy, and lower alkoxy, all of which can be optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R¹ is independently selected from the group consisting of hydrogen, and lower alkyl, optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R² is independently selected from the group consisting of alkyl and lower alkyl, optionally substituted where possible by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

R⁷ and R⁸ are independently selected from the group consisting of alkyl, alkenyl, heteroaryl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring, optionally substituted where possible with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —

NR⁷R⁸, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —

C(O)NR⁷R⁸, and —

C(O)N(R²)₂;

wherein one of R^2β

, R^3β

, R^4β

, R^5β

or R^6β

must be a carbon-carbon linked heteroaryl.

26. The compound of claim 1 selected from the group consisting of:

4-[2-(4-Methoxy-3-thien-2-yl-phenyl)-acryloyl]-benzoic acid;

4-[2-(2-Methoxy-5-quinolin-3-yl-phenyl)-acryloyl]-benzoic acid;

2-{3-[1-(4-Carboxy-benzoyl)-vinyl]-4-methoxy-phenyl}-pyrrole-1-carboxylic acid tert-butyl ester;

4-[2-(2-Methoxy-5-pyridin-3-yl-phenyl)-acryloyl]-benzoic acid;

4-[2-(5-Benzo[b]thien-2-yl-2-methoxy-phenyl)-acryloyl]-benzoic acid;

4-[2-(2-Methoxy-5-thien-2-yl-phenyl)-acryloyl]-benzoic acid;

4-[2-(2-Methoxy-5-thien-2-yl-phenyl)-acryloyl]-benzoic acid;

4-[2-(2-Methoxy-5-thien-2-yl-phenyl)-acryloyl]-benzoic acid methyl ester;

N-(2-Hydroxy-1,1-bis-hydroxymethyl-ethyl)-4-[2-(2-methoxy-5-thien-2-yl-phenyl)-acryloyl]-benzamide;

1-[4-(4-Hydroxy-piperidine-1-carbonyl)-phenyl]-2-(2-methoxy-5-thien-2-yl-phenyl)-propenone;

1-(4-Fluoro-phenyl)-2-(2-methoxy-5-thien-2-yl-phenyl)-propenone;

2-(2-Methoxy-5-thien-2-yl-phenyl)-1-(4-pyrrolidin-1-yl-phenyl)-propenone;

1-(4-Hydroxy-phenyl)-2-(2-methoxy-5-thien-2-yl-phenyl)-propenone;

2-(2-Methoxy-5-thien-2-yl-phenyl)-1-(4-nitro-phenyl)-propenone;

N-{4-[2-(2-Methoxy-5-thien-2-yl-phenyl)-acryloyl]-phenyl}-methanesulfonamide;

N-{4-[2-(2-Methoxy-5-thien-2-yl-phenyl)-acryloyl]-phenyl}-N-methyl-methane-sulfonamide;

N-{4-[2-(2-Methoxy-5-thien-2-yl-phenyl)-acryloyl]-phenyl}-isobutyramide;

2-(2-Methoxy-5-thien-2-yl-phenyl)-1-[4-(pyrimidin-2-ylamino)-phenyl]-propenone;

2-{4-[2-(2-Methoxy-5-thien-2-yl-phenyl)-acryloyl]-phenylamino}-nicotinic acid ethyl ester;

2-{4-[2-(2-Methoxy-5-thien-2-yl-phenyl)-acryloyl]-phenylamino}-nicotinic acid;

2-(2-Methoxy-5-thien-2-yl-phenyl)-1-[4-(pyrazin-2-ylamino)-phenyl]-propenone;

3,5-Dimethyl-isoxazole-4-sulfonic acid {4-[2-(2-methoxy-5-thien-2-yl-phenyl)-acryloyl]-phenyl}-amide;

Isoxazole-5-carboxylic acid {4-[2-(2-methoxy-5-thien-2-yl-phenyl)-acryloyl]-phenyl}-amide;

1-Methyl-1H-pyrrole-2-carboxylic acid {4-[2-(2-methoxy-5-thien-2-yl-phenyl)-acryloyl]-phenyl}-amide;

4-[2-(3,4-Dimethoxy-5-thien-2-yl-phenyl)-acryloyl]-benzoic acid methyl ester;

4-[2-(3,4-Dimethoxy-5-thien-2-yl-phenyl)-acryloyl]-benzoic acid;

4-[2-(3,4-Dimethoxy-5-thien-2-yl-phenyl)-acryloyl]-N-(2-morpholin-4-yl-ethyl)-benzamide;

2-(5-Benzo[b]thien-2-yl-2,4-dimethoxy-phenyl)-1-(4-fluoro-phenyl)-propenone;

4-[2-(2,4-Dimethoxy-5-thien-2-yl-phenyl)-acryloyl]-benzoic acid;

3-[2-(2-Methoxy-5-thien-2-yl-phenyl)-acryloyl]-benzoic acid;

1-(4-tert-Butyl-phenyl)-2-(2-methoxy-5-thien-2-yl-phenyl)-propenone;

2-(2-Methoxy-5-thien-2-yl-phenyl)-1-(4-trifluoromethyl-phenyl)-propenone;

4-[2-(2-Isopropoxy-5-thien-2-yl-phenyl)-acryloyl]-benzoic acid;

4-{2-[2-(2-Oxo-2-piperidin-1-yl-ethoxy)-5-thien-2-yl-phenyl]-acryloyl}-benzoic acid;

4-{2-[2-(2-Piperidin-1-yl-ethoxy)-5-thien-2-yl-phenyl]-acryloyl}-benzoic acid hydrochloride salt; and

4-[2-(2-Methoxy-5-thien-3-yl-phenyl)-acryloyl]-benzoic acid.

27. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or 26, together with one or more pharmaceutically acceptable carrier.

28. A method for the treatment or prophylaxis of an inflammatory disorder, comprising administering an effective amount of a compound of claim 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or 26.

29. The method of claim 28, wherein the disorder is arthritis.

30. The method of claim 28, wherein the disorder is rheumatoid arthritis.

31. The method of claim 28, wherein the disorder is asthma.

32. The method of claim 28, wherein the treatment is disease modifying for the treatment of rheumatoid arthritis.

33. The method of claim 28, wherein the disorder is allergic rhinitis.

34. The method of claim 28, wherein the disorder is chronic obstructive pulmonary disease.

35. The method of claim 28, wherein the disorder is atherosclerosis.

36. The method of claim 28, wherein the disorder is restinosis.

37. A method for inhibiting the expression of VCAM-1, comprising administering an effective amount of a compound of claim 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or 26.