# US 11,077,115 B2 · Rorgamma modulators and uses thereof

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- Number: US 11,077,115 B2
- Document ID: US11077115B2
- Status: Granted
- Kind: B2
- Application number: 16/481,200
- Filed: 2018-01-29
- Published: 2020-01-02
- Granted: 2021-08-03
- Earliest claimed: 2017-01-27
- Assignees: Genfit
- Applicants: Genfit
- Inventors: Jean-Francois Delhomel; Enrico Perspicace; Zouher Majd; Peggy Parroche; Robert Walczak; Pascal Bonnet; Jade Fogha
- Web page: https://patentgrep.com/patent/US11077115B2

## CPC

- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- A61K 31/192: having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid {(cannabinoids A61K31/658)}
- A61K 31/341: not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
- A61K 31/40: having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K 31/427: not condensed and containing further heterocyclic rings
- A61K 31/428: condensed with carbocyclic rings
- A61K 31/5375: 1,4-Oxazines, e.g. morpholine
- A61K 31/54: having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K 31/541: Non-condensed thiazines containing further heterocyclic rings
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 37/02: Immunomodulators
- C07D 279/12: not condensed with other rings
- C07D 295/155: with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
- C07D 307/52: Radicals substituted by nitrogen atoms not forming part of a nitro radical
- C07D 307/54: Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D 405/12: linked by a chain containing hetero atoms as chain links
- C07D 413/04: directly linked by a ring-member-to-ring-member bond
- C07D 417/04: directly linked by a ring-member-to-ring-member bond
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The present invention provides novel compounds of formula (Ia) that are modulators of RORgamma. These compounds, and pharmaceutical compositions comprising the same, are suitable means for treating any disease wherein the modulation of RORgamma has therapeutic effects, for instance in autoimmune diseases, autoimmune-related diseases, inflammatory diseases, metabolic diseases, fibrotic diseases, or cholestatic diseases.

## Claims

### Claim 1

A compound of formula (Ia)
in which,
R1a is a hydrogen atom, a halogen atom, a nitrile group, a nitro group (NO2), a (C1-C6)alkyl group, a (C1-C6)alkyloxy group, a (C1-C6)alkylthio group, an amino group, a (C1-C6)alkylamino group, a (C1-C6)dialkylamino group, or a heterocyclic group;
R1b is a hydrogen atom, a (C1-C6)alkyloxy group, a (C1-C6)alkyl group or a heterocyclic group;
R1c is a hydrogen atom, a halogen atom, a (C1-C6)alkyl group, a (C1-C6)alkyloxy group, a (C1-C6)alkylthio group, a heterocyclic group, a cyano group, an amido group or a hydroxyl group;
R1d and R1e are, independently, a hydrogen atom, a halogen atom, a (C1-C6)alkyloxy group or a (C1-C6)alkyl group;
wherein at least one of R1a, R1b, and R1c, is a heterocyclic group;
R2 is a (C3-C6)alkyl group, a (C2-C6)alkenyl group, a (C2-C6)alkynyl group, a (C3-C14)cycloalkyl group, a (C6-C14)aryl group optionally substituted by a (C1-C6)alkyl group or a heterocyclic group optionally substituted by a (C1-C6)alkyl group or by a halogen;
R′2 is a hydrogen atom, a (C1-C6)alkyl group, a (C2-C6)alkenyl group, a (C2-C6)alkynyl group, a (C3-C14)cycloalkyl group, a (C6-C14)aryl group optionally substituted by a (C1-C6)alkyl group or a heterocyclic group, optionally substituted by a (C1-C6)alkyl group;
or R2 and R′2 can form, together with the carbon atom to which they are attached, a cycloalkyl group or a heterocycloalkyl group;
L1 is a NR7-CO—CH2, NR7-CO—, NR7-CO—C(CH3)2, CO—NH—CH2, CO—NH or CO—NH—C(CH3)2 group;
R7 represents a hydrogen atom or a (C1-C6)alkyl group;
L2 represents a bond, a (C1-C6)alkyl group, a (C3-C14)cycloalkyl group, or a CR8R′8 group;
with the proviso that when L1 is a NR7-CO— or a CO—NH group, L2 represents a (C1-C6)alkyl group, a (C3-C14)cycloalkyl group, or a CR8R′8 group;
R8 and R′8 are independently, a hydrogen atom, or a (C1-C6)alkyl group;
R8 and R′8 can form, together with the carbon atom to which they are attached, a cycloalkyl group;
X1, X2, X3, X4, X5 are, independently, a carbon, or a nitrogen atom;
X6 represents a CH group or a nitrogen atom;
X7 represents a sulfur atom, a SO2 group, or an oxygen atom; and
R4 is a hydrogen atom; an alkyl group optionally substituted by a hydroxy group or an alkoxy group; a halogen atom; an alkyloxy group or a hydroxy group.

### Claim 2 (depends on 1)

The compound according to claim 1, wherein R1a is a hydrogen atom, a halogen atom, a nitrile group, a nitro group (NO2), a (C1-C6)alkyl group optionally substituted by at least one halogen atom, a (C1-C6)alkyloxy group, a (C1-C6)alkylthio group, an amino group, a (C1-C6)alkylamino group, a (C1-C6)dialkylamino group, a piperidinyl group, a pyrrolidinyl group, a morpholinyl, an azabicyclohexanyl group, or an azepanyl group wherein said piperidinyl, pyrrolidinyl, azepanyl, or an azabicyclohexanyl group can be optionally substituted by at least one (C1-C6)alkyl groups.

### Claim 3 (depends on 1)

The compound according to claim 1, wherein:
R1a is a piperidinyl group, a morpholinyl group, an azabicyclohexanyl group or an azepanyl group, wherein said piperidinyl, pyrrolidinyl or azepanyl group can be optionally substituted by at least one (C1-C6)alkyl groups;
R1b is a hydrogen atom;
R1c is a hydrogen atom, a halogen atom, a (C1-C6)alkyl group, or a (C1-C6)alkyloxy group;
R2 is an aryl group or a heteroaryl group; and
R′2 is a hydrogen atom.

### Claim 4 (depends on 1)

The compound according to claim 1, wherein X6 is a nitrogen atom and X7 is a SO2 group or an oxygen atom.

### Claim 5 (depends on 1)

The compound according to claim 1, wherein L1 is a NR7-CO— group and L2 is a CR8R′ 8 group.

### Claim 6 (depends on 1)

The compound according to claim 1, wherein:
R1a is a halogen atom, a (C1-C6)alkyl group optionally substituted by halogen atom, a (C1-C6)dialkylamino group, a piperidinyl group, a morpholinyl group, an azabicyclohexanyl group or an azepanyl group, wherein said piperidinyl, morpholinyl, azabicyclohexanyl or azepanyl group can be optionally substituted by at least one (C1-C6)alkyl groups;
R1b is a hydrogen atom;
R1c is a hydrogen, a (C1-C6)alkyl group, or a (C1-C6)alkoxy group;
R1d and R1e are hydrogen atoms;
R2 is a phenyl group or a heterocyclic group;
L1 represents a NH—CO— group;
L2 represents a CH2 group or a group of formula (III) or of formula (IV)
R4 is a hydrogen atom, a halogen atom, a (C1-C6)alkyl group or a (C1-C6)alkoxy group;
the cycle
is a substituent of X3 (in meta or para position of the L1-L2 group); and
X6 is a nitrogen atom and X7 is a SO2 group or an oxygen atom.

### Claim 7 (depends on 1)

The compound according to claim 1, wherein:
R1a is a heterocyclic group;
R1c is a (C1-C6)alkyl group;
R2 is a heterocyclic group;
L1 represents a NH—CO— group;
L2 represents a CH2 group;
R4 is a hydrogen atom;
the cycle
is a substituent of X1, X2 or X3 (in meta or para position of the L1-L2 group); and
X6 is a nitrogen atom and X7 is a SO2 group.

### Claim 8 (depends on 1)

The compound according to claim 1, characterized in that it is selected in the group consisting of:
2-[4-(1,1-dioxo-1-thiomorpholin-4-yl)phenyl]-N-{phenyl[2-(piperidin-1-yl)phenyl]methyl}acetamide;
2-[5-(1,1-dioxo-1-thiomorpholin-4-yl)-2-methylphenyl]-N-{phenyl[2-(piperidin-1-yl)phenyl]methyl}acetamide;
2-[5-(1,1-dioxo-1-thiomorpholin-4-yl)-2-fluorophenyl]-N-{phenyl[2-(piperidin-1-yl)phenyl]methyl}acetamide;
2-[5-(1,1-dioxo-1-thiomorpholin-4-yl)-2-fluorophenyl]-N-{[4-methyl-2-(morpholin-4-yl)phenyl](phenyl)methyl}acetamide;
2-[5-(1,1-dioxo-1-thiomorpholin-4-yl)-2-methylphenyl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
2-[4-(1,1-dioxo-1-thiomorpholin-4-yl)phenyl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
2-[5-(1,1-dioxo-1-thiomorpholin-4-yl)-2-methylphenyl]-N-{[4-methyl-2-(morpholin-4-yl)phenyl](phenyl)methyl}acetamide;
2-[2-fluoro-5-(morpholin-4-yl)phenyl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](phenyl)methyl}acetamide;
2-[4-(1,1-dioxo-1-thiomorpholin-4-yl)-3-methylphenyl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
2-[4-(1,1-dioxo-1-thiomorpholin-4-yl)-3-methylphenyl]-N-{[4-methoxy-2-(4-methylpiperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
2-[4-(1,1-dioxo-1-thiomorpholin-4-yl)-3-methylphenyl]-N-({4-methoxy-2-[4-(trifluoromethyl)piperidin-1-yl]phenyl}(5-methylfuran-2-yl)methyl)acetamide;
N-[(2-{3-azabicyclo[3.1.0]hexan-3-yl}-4-methoxyphenyl)(5-methylfuran-2-yl)methyl]-2-[4-(1,1-dioxo-1-thiomorpholin-4-yl)-3-methylphenyl]acetamide;
2-[2-(1,1-dioxo-1-thiomorpholin-4-yl)pyrimidin-5-yl]-N-{[5-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
2-[4-(1,1-dioxo-1-thiomorpholin-4-yl)-2-methylphenyl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
2-[2-(1,1-dioxo-1-thiomorpholin-4-yl)pyrimidin-5-yl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
N-[(2-{3-azabicyclo[3.1.0]hexan-3-yl}-4-methylphenyl)(phenyl)methyl]-2-[4-(1,1-dioxo-1-thiomorpholin-4-yl)phenyl]acetamide;
N-[(2-{3-azabicyclo[3.1.0]hexan-3-yl}-4-methylphenyl)(phenyl)methyl]-2-[4-(1,1-dioxo-1-thiomorpholin-4-yl)-3-methylphenyl]acetamide;
N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}-2-[6-(morpholin-4-yl)pyridin-3-yl]acetamide;
N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}-2-[2-(morpholin-4-yl)pyrimidin-5-yl]acetamide;
2-[6-(1,1-dioxo-1-thiomorpholin-4-yl)pyridin-3-yl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
N-[(2-{3-azabicyclo[3.1.0]hexan-3-yl}-4-methylphenyl)(5-methylfuran-2-yl)methyl]-2-[5-(1,1-dioxo-1-thiomorpholin-4-yl)-2-methylphenyl]acetamide;
2-[4-(1,1-dioxo-1-thiomorpholin-4-yl)-3-methoxyphenyl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
2-[3-(1,1-dioxo-1-thiomorpholin-4-yl)-4-methoxyphenyl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
1-[4-(1,1-dioxo-1-thiomorpholin-4-yl)phenyl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}cyclopropane-1-carboxamide;
N-[(2-{3-azabicyclo[3.1.0]hexan-3-yl}-4-methylphenyl)(5-methylfuran-2-yl)methyl]-2-[2-(1,1-dioxo-1-thiomorpholin-4-yl)pyrimidin-5-yl]acetamide;
1-[3-bromo-4-(1,1-dioxo-1-thiomorpholin-4-yl)phenyl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}cyclopropane-1-carboxamide;
2-[2-(1,1-dioxo-1-thiomorpholin-4-yl)-4-methylpyrimidin-5-yl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
2-[3-(1,1-dioxo-1-thiomorpholin-4-yl)-4-hydroxyphenyl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
N-{[2-(azepan-1-yl)-4-methoxyphenyl](5-methylfuran-2-yl)methyl}-2-[2-(1,1-dioxo-1-thiomorpholin-4-yl)pyrimidin-5-yl]acetamide;
N-{[2-(azepan-1-yl)-4-methoxyphenyl](5-methylfuran-2-yl)methyl}-1-[4-(1,1-dioxo-1-thiomorpholin-4-yl)phenyl]cyclopropane-1-carboxamide;
2-[5-(1,1-dioxo-1-thiomorpholin-4-yl)pyridin-2-yl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
1-[4-(1,1-dioxo-1-thiomorpholin-4-yl)phenyl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}cyclobutane-1-carboxamide;
2-[4-(1,1-dioxo-1-thiomorpholin-4-yl)phenyl]-2-methyl-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}propanamide;
1-[3-(1,1-dioxo-1-thiomorpholin-4-yl)phenyl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}cyclopropane-1-carboxamide;
1-[4-(1,1-dioxo-1-thiomorpholin-4-yl)phenyl]-N-[3-methyl-1-[2-(piperidin-1-yl)phenyl]butyl]cyclopropane-1-carboxamide;
1-[4-(1,1-dioxo-1-thiomorpholin-4-yl)phenyl]-N-[(5-methylfuran-2-yl)[2-(piperidin-1-yl)phenyl]methyl]cyclopropane-1-carboxamide;
2-[4-(1,1-dioxo-1-thiomorpholin-4-yl)-3-hydroxyphenyl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
2-[3-(1,1-dioxo-1-thiomorpholin-4-yl)-4-(methoxymethyl)phenyl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
2-[3-(1,1-dioxo-1-thiomorpholin-4-yl)-4-(hydroxymethyl)phenyl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide; and
2-[5-(1,1-dioxo-1-thiomorpholin-4-yl)pyrimidin-2-yl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide.

### Claim 9 (depends on 1)

A combination product comprising:
i) a compound of formula (Ia) as defined in claim 1, or a pharmaceutically acceptable salt thereof; and
ii) another therapeutically active agent.

### Claim 10 (depends on 9)

The combination product according to claim 9, component ii) is Elafibranor, seladelpar, saroglitazar, lanifibranor, pioglitazone or a pharmaceutically acceptable salt thereof.

### Claim 11 (depends on 9)

The combination product according to claim 9, wherein the combination product is a composition comprising components i) and ii) and a pharmaceutically acceptable carrier.

### Claim 12 (depends on 9)

The combination product according to claim 9, wherein the combination product is a kit of parts comprising components i) and ii), for sequential, separate, or simultaneous use.

### Claim 13 (depends on 9)

The combination product according to claim 9, wherein components i) and ii) are formulated in an injectable suspension, a gel, an oil, a pill, a tablet, a suppository, a powder, a capsule, an aerosol, an ointment, a cream, a patch, or means of galenic forms for a prolonged and/or slow release.

### Claim 14 (depends on 1)

A method for the treatment of an autoimmune disease, an autoimmune-related disease, an inflammatory disease, a metabolic disease, a fibrotic disease, or a cholestatic disease, wherein said method comprises administering to a subject in need thereof a therapeutically effective amount of a compound according to claim 1.

### Claim 15 (depends on 9)

A method for the treatment of an autoimmune disease, an autoimmune-related disease, an inflammatory disease, a metabolic disease, a fibrotic disease, or a cholestatic disease, wherein said method comprises administering to a subject in need thereof a therapeutically effective amount of the combination product according to claim 9.

### Claim 16

A compound of formula (Ia)
in which,
R1a is a hydrogen atom, a halogen atom, a nitrile group, a nitro group (NO2), a (C1-C6)alkyl group optionally substituted by at least one halogen atom, a (C1-C6)alkyloxy group, a (C1-C6)alkylthio group, an amino group, a (C1-C6)alkylamino group, a (C1-C6)dialkylamino group, a piperidinyl group, a morpholinyl group, an azabicyclohexanyl group or an azepanyl group, wherein said piperidinyl, pyrrolidinyl or azepanyl group can be optionally substituted by at least one (C1-C6)alkyl groups;
R1b is a hydrogen atom;
R1c is a hydrogen atom, a halogen atom, a (C1-C6)alkyl group, or a (C1-C6)alkyloxy group;
R1d and R1e are, independently, a hydrogen atom, a halogen atom, a (C1-C6)alkyloxy group or a (C1-C6)alkyl group;
wherein at least one of R1a, R1b, R1c, R1d, and R1e is not a hydrogen atom;
R2 is a (C6-C14)aryl group optionally substituted by a (C1-C6)alkyl group or a heteroaryl group optionally substituted by a (C1-C6)alkyl group or by a halogen;
R′2 is a hydrogen atom;
L1 is a NR7-CO—CH2, NR7-CO—, NR7-CO—C(CH3)2, CO—NH—CH2, CO—NH or CO—NH—C(CH3)2 group;
R7 represents a hydrogen atom or a (C1-C6)alkyl group;
L2 represents a bond, a (C1-C6)alkyl group, a (C3-C14)cycloalkyl group, or a CR8R′8 group;
with the proviso that when L1 is a NR7-CO— or a CO—NH group, L2 represents a (C1-C6)alkyl group, a (C3-C14)cycloalkyl group, or a CR8R′8 group;
R8 and R′8 are independently, a hydrogen atom, or a (C1-C6)alkyl group;
R8 and R′8 can form, together with the carbon atom to which they are attached, a cycloalkyl group;
X1, X2, X3, X4, X5 are, independently, a carbon, or a nitrogen atom;
X6 represents a CH group or a nitrogen atom;
X7 represents a sulfur atom, a SO2 group, or an oxygen atom; and
R4 is a hydrogen atom; an alkyl group optionally substituted by a hydroxy group or an alkoxy group; a halogen atom; an alkyloxy group or a hydroxy group.

### Claim 17

A compound of formula (Ia)
in which,
R1a is a heterocyclic group;
R1b is a hydrogen atom, a (C1-C6)alkyloxy group, a (C1-C6)alkyl group or a heterocyclic group;
R1c is a (C1-C6)alkyl group;
R1d and R1e are, independently, a hydrogen atom, a halogen atom, a (C1-C6)alkyloxy group or a (C1-C6)alkyl group;
R2 is a heterocyclic group optionally substituted by a (C1-C6)alkyl group or by a halogen;
R′2 is a hydrogen atom, a (C1-C6)alkyl group, a (C2-C6)alkenyl group, a (C2-C6)alkynyl group, a (C3-C14)cycloalkyl group, a (C6-C14)aryl group optionally substituted by a (C1-C6)alkyl group or a heterocyclic group, optionally substituted by a (C1-C6)alkyl group;
L1 is a NH—CO— group;
L2 is a CH2 group R4 is a hydrogen atom;
X1, X2, X3, X4, X5 are, independently, a carbon, or a nitrogen atom;
the cycle
is a substituent of X1, X2 or X3; and
X6 is a nitrogen atom and X7 is a SO2 group.

### Claim 18

A compound, wherein the compound is one of the following compounds:
2-[4-(1,1-dioxo-1-thiomorpholin-4-yl)phenyl]-N-{phenyl[2-(piperidin-1-yl)phenyl]methyl}acetamide;
2-[5-(1,1-dioxo-1-thiomorpholin-4-yl)-2-methylphenyl]-N-{phenyl[2-(piperidin-1-yl)phenyl]methyl}acetamide;
2-[5-(1,1-dioxo-1-thiomorpholin-4-yl)-2-fluorophenyl]-N-{phenyl[2-(piperidin-1-yl)phenyl]methyl}acetamide;
2-[5-(1,1-dioxo-1-thiomorpholin-4-yl)-2-fluorophenyl]-N-{[4-methyl-2-(morpholin-4-yl)phenyl](phenyl)methyl}acetamide;
2-[5-(1,1-dioxo-1-thiomorpholin-4-yl)-2-methylphenyl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
2-[4-(1,1-dioxo-1-thiomorpholin-4-yl)phenyl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
2-[5-(1,1-dioxo-1-thiomorpholin-4-yl)-2-methylphenyl]-N-{[4-methyl-2-(morpholin-4-yl)phenyl](phenyl)methyl}acetamide;
2-[2-fluoro-5-(morpholin-4-yl)phenyl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](phenyl)methyl}acetamide;
N-[(2-bromo-4-methylphenyl)(phenyl)methyl]-2-[4-(1,1-dioxo-1-thiomorpholin-4-yl)phenyl]acetamide;
2-[4-(1,1-dioxo-1-thiomorpholin-4-yl)-3-methylphenyl]-N-{[4-methyl-2-(trifluoromethyl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
N-[(2-bromo-4-methylphenyl)(5-methylfuran-2-yl)methyl]-2-[4-(1,1-dioxo-1-thiomorpholin-4-yl)-3-methylphenyl]acetamide;
2-[4-(1,1-dioxo-1-thiomorpholin-4-yl)-3-methylphenyl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
2-[4-(1,1-dioxo-1-thiomorpholin-4-yl)-3-methylphenyl]-N-{[4-methoxy-2-(4-methylpiperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
2-[4-(1,1-dioxo-1-thiomorpholin-4-yl)-3-methylphenyl]-N-({4-methoxy-2-[4-(trifluoromethyl)piperidin-1-yl]phenyl}(5-methylfuran-2-yl)methyl)acetamide;
N-{[2-(dimethylamino)-4-methoxyphenyl](5-methylfuran-2-yl)methyl}-2-[4-(1,1-dioxo-1-thiomorpholin-4-yl)-3-methylphenyl]acetamide;
N-[(2-{3-azabicyclo[3.1.0]hexan-3-yl}-4-methoxyphenyl)(5-methylfuran-2-yl)methyl]-2-[4-(1,1-dioxo-1-thiomorpholin-4-yl)-3-methylphenyl]acetamide;
2-[2-(1,1-dioxo-1-thiomorpholin-4-yl)pyrimidin-5-yl]-N-{[5-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
2-[4-(1,1-dioxo-1-thiomorpholin-4-yl)-2-methylphenyl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
N-[(2,4-dimethylphenyl)(5-methylfuran-2-yl)methyl]-2-[4-(1,1-dioxo-1-thiomorpholin-4-yl)-2-methylphenyl]acetamide;
2-[2-(1,1-dioxo-1-thiomorpholin-4-yl)pyrimidin-5-yl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
N-[(2-bromo-4-methylphenyl)(5-methylfuran-2-yl)methyl]-2-[4-(1,1-dioxo-1-thiomorpholin-4-yl)-2-methylphenyl]acetamide;
N-[(2-{3-azabicyclo[3.1.0]hexan-3-yl}-4-methylphenyl)(phenyl)methyl]-2-[4-(1,1-dioxo-1-thiomorpholin-4-yl)phenyl]acetamide;
N-[(2-{3-azabicyclo[3.1.0]hexan-3-yl}-4-methylphenyl)(phenyl)methyl]-2-[4-(1,1-dioxo-1-thiomorpholin-4-yl)-3-methylphenyl]acetamide;
2-[4-(1,1-dioxo-1-thiomorpholin-4-yl)phenyl]-N-{[4-methyl-2-(trifluoromethyl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}-2-[6-(morpholin-4-yl)pyridin-3-yl]acetamide;
N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}-2-[2-(morpholin-4-yl)pyrimidin-5-yl]acetamide;
2-[6-(1,1-dioxo-1-thiomorpholin-4-yl)pyridin-3-yl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
N-[(2-{3-azabicyclo[3.1.0]hexan-3-yl}-4-methylphenyl)(5-methylfuran-2-yl)methyl]-2-[5-(1,1-dioxo-1-thiomorpholin-4-yl)-2-methylphenyl]acetamide;
2-[4-(1,1-dioxo-1-thiomorpholin-4-yl)-3-methoxyphenyl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
2-[3-(1,1-dioxo-1-thiomorpholin-4-yl)-4-methoxyphenyl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
N-[(2,4-dimethylphenyl)(5-methylfuran-2-yl)methyl]-1-[4-(1,1-dioxo-1-thiomorpholin-4-yl)phenyl]cyclopropane-1-carboxamide;
1-[4-(1,1-dioxo-1-thiomorpholin-4-yl)phenyl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}cyclopropane-1-carboxamide;
2-[2-(1,1-dioxo-1-thiomorpholin-4-yl)pyrimidin-5-yl]-N-{[4-methyl-2-(trifluoromethyl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
N-[(2-bromo-4-methylphenyl)(5-methylfuran-2-yl)methyl]-2-[2-(1,1-dioxo-1-thiomorpholin-4-yl)pyrimidin-5-yl]acetamide;
N-[(2,4-dimethylphenyl)(5-methylfuran-2-yl)methyl]-2-[2-(1,1-dioxo-1-thiomorpholin-4-yl)pyrimidin-5-yl]acetamide;
N-[(2-{3-azabicyclo[3.1.0]hexan-3-yl}-4-methylphenyl)(5-methylfuran-2-yl)methyl]-2-[2-(1,1-dioxo-1-thiomorpholin-4-yl)pyrimidin-5-yl]acetamide;
1-[3-bromo-4-(1,1-dioxo-1-thiomorpholin-4-yl)phenyl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}cyclopropane-1-carboxamide;
2-[2-(1,1-dioxo-1-thiomorpholin-4-yl)-4-methylpyrimidin-5-yl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
2-[3-(1,1-dioxo-1-thiomorpholin-4-yl)-4-hydroxyphenyl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
N-[(2,4-dimethylphenyl)(5-methylfuran-2-yl)methyl]-2-[4-(1,1-dioxo-1-thiomorpholin-4-yl)phenyl]-2-methylpropanamide;
N-[(2,4-dimethylphenyl)(5-methylfuran-2-yl)methyl]-1-[4-(1,1-dioxo-1-thiomorpholin-4-yl)phenyl]cyclobutane-1-carboxamide;
N-[(2,4-dimethylphenyl)(5-methylfuran-2-yl)methyl]-2-[2-(1,1-dioxo-1-thiomorpholin-4-yl)-4-methylpyrimidin-5-yl]acetamide;
N-[(2,4-dimethylphenyl)(5-methylfuran-2-yl)methyl]-2-[3-(1,1-dioxo-1-thiomorpholin-4-yl)-4-hydroxyphenyl]acetamide;
1-[4-(1,1-dioxo-1-thiomorpholin-4-yl)phenyl]-N-[(4-methoxy-2-methylphenyl)(5-methylfuran-2-yl)methyl]cyclopropane-1-carboxamide;
N-{[2-(azepan-1-yl)-4-methoxyphenyl](5-methylfuran-2-yl)methyl}-2-[2-(1,1-dioxo-1-thiomorpholin-4-yl)pyrimidin-5-yl]acetamide;
N-{[2-(azepan-1-yl)-4-methoxyphenyl](5-methylfuran-2-yl)methyl}-1-[4-(1,1-dioxo-1-thiomorpholin-4-yl)phenyl]cyclopropane-1-carboxamide;
2-[5-(1,1-dioxo-1-thiomorpholin-4-yl)pyridin-2-yl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
N-[(2,4-dimethylphenyl)(5-methylfuran-2-yl)methyl]-1-[2-(1,1-dioxo-1-thiomorpholin-4-yl)pyrimidin-5-yl]cyclopropane-1-carboxamide;
N-[(4-chloro-2-methylphenyl)(5-methylfuran-2-yl)methyl]-2-[2-(1,1-dioxo-1-thiomorpholin-4-yl)pyrimidin-5-yl]acetamide;
N-[(2,4-dichlorophenyl)(5-methylfuran-2-yl)methyl]-2-[2-(1,1-dioxo-1-thiomorpholin-4-yl)pyrimidin-5-yl]acetamide;
N-[(2-chloro-4-methylphenyl)(5-methylfuran-2-yl)methyl]-2-[2-(1,1-dioxo-1-thiomorpholin-4-yl)pyrimidin-5-yl]acetamide;
N-[(2-chloro-4-methylphenyl)(5-methylfuran-2-yl)methyl]-1-[2-(1,1-dioxo-1-thiomorpholin-4-yl)pyrimidin-5-yl]cyclopropane-1-carboxamide;
N-[(4-chloro-2-methylphenyl)(5-methylfuran-2-yl)methyl]-1-[2-(1,1-dioxo-1-thiomorpholin-4-yl)pyrimidin-5-yl]cyclopropane-1-carboxamide;
N-[(2,4-dichlorophenyl)(5-methylfuran-2-yl)methyl]-1-[2-(1,1-dioxo-1-thiomorpholin-4-yl)pyrimidin-5-yl]cyclopropane-1-carboxamide;
1-[4-(1,1-dioxo-1-thiomorpholin-4-yl)phenyl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}cyclobutane-1-carboxamide;
2-[4-(1,1-dioxo-1-thiomorpholin-4-yl)phenyl]-2-methyl-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}propanamide;
1-[2-(1,1-dioxo-1-thiomorpholin-4-yl)pyrimidin-5-yl]-N-[(4-methoxy-2-methylphenyl)(5-methylfuran-2-yl)methyl]cyclopropane-1-carboxamide;
1-[3-(1,1-dioxo-1-thiomorpholin-4-yl)phenyl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}cyclopropane-1-carboxamide;
1-[4-(1,1-dioxo-1-thiomorpholin-4-yl)phenyl]-N-[3-methyl-1-[2-(piperidin-1-yl)phenyl]butyl]cyclopropane-1-carboxamide;
1-[4-(1,1-dioxo-1-thiomorpholin-4-yl)phenyl]-N-[(5-methylfuran-2-yl)[2-(piperidin-1-yl)phenyl]methyl]cyclopropane-1-carboxamide;
2-[4-(1,1-dioxo-1-thiomorpholin-4-yl)-3-hydroxyphenyl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
2-[3-(1,1-dioxo-1-thiomorpholin-4-yl)-4-(methoxymethyl)phenyl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
2-[3-(1,1-dioxo-1-thiomorpholin-4-yl)-4-(hydroxymethyl)phenyl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
N-[(2,4-dimethylphenyl)(5-methylfuran-2-yl)methyl]-1-[4-(1,1-dioxo-1-thiomorpholin-4-yl)phenyl]cyclopropane-1-carboxamide;
2-[5-(1,1-dioxo-1-thiomorpholin-4-yl)pyrimidin-2-yl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;
N-[(5-chlorofuran-2-yl)(2,4-dimethylphenyl)methyl]-1-[4-(1,1-dioxo-1-thiomorpholin-4-yl)phenyl]cyclopropane-1-carboxamide;
N-[(5-chlorofuran-2-yl)(4-methylphenyl)methyl]-1-[4-(1,1-dioxo-1-thiomorpholin-4-yl)phenyl]cyclopropane-1-carboxamide;
N-[(2,4-dimethylphenyl)(5-methylfuran-2-yl)methyl]-1-[3-(1,1-dioxo-1-thiomorpholin-4-yl)phenyl]cyclopropane-1-carboxamide;
N-[(2,4-dimethylphenyl)(5-methylfuran-2-yl)methyl]-1-[3-(1,1-dioxo-1-thiomorpholin-4-yl)-4-methoxyphenyl]cyclopropane-1-carboxamide;
N-[(2,4-dimethylphenyl)(5-methylfuran-2-yl)methyl]-1-[5-(1,1-dioxo-1-thiomorpholin-4-yl)-2-methylphenyl]cyclopropane-1-carboxamide;
N-[(2,4-dimethylphenyl)(5-methylfuran-2-yl)methyl]-1-[5-(1,1-dioxo-1-thiomorpholin-4-yl)-6-methylpyridin-2-yl]cyclopropane-1-carboxamide;
N-[(2,4-dimethylphenyl)(5-methylfuran-2-yl)methyl]-1-[5-(1,1-dioxo-1-thiomorpholin-4-yl)-3-methylpyridin-2-yl]cyclopropane-1-carboxamide; and
N-[(2,4-dimethylphenyl)(5-methylfuran-2-yl)methyl]-1-[5-(1,1-dioxo-1-thiomorpholin-4-yl)pyridin-2-yl]cyclopropane-1-carboxamide.