# US 10,870,623 B2 · Trifluoromethylpropanamide derivatives as HTRA1 inhibitors

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 10,870,623 B2
- Document ID: US10870623B2
- Status: Granted
- Kind: B2
- Application number: 16/283,640
- Filed: 2019-02-22
- Published: 2019-06-20
- Granted: 2020-12-22
- Earliest claimed: 2016-08-23
- Assignees: Hoffmann-La Roche Inc.
- Applicants: Hoffmann-La Roche Inc.
- Inventors: Benoit Hornsperger; Hans Peter Maerki; Peter Mohr; Michael Reutlinger; Markus Rudolph
- Web page: https://patentgrep.com/patent/US10870623B2

## CPC

- C07D 207/12: Oxygen or sulfur atoms
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 13/12: of the kidneys
- A61P 27/00: Drugs for disorders of the senses
- A61P 27/02: Ophthalmic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 403/12: linked by a chain containing hetero atoms as chain links
- C07D 409/12: linked by a chain containing hetero atoms as chain links
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The invention provides novel compounds having the general formula (I) wherein R2, R3, R4, R5, R6, R7, R8, X, A and R11 are as described herein, compositions including the compounds and methods of using the compounds.

## Claims

### Claim 1

A compound of formula (I)
or pharmaceutically acceptable salts thereof, wherein
R2, R3, R4, R5 and R7 are each independently selected from
i) H,
ii) C1-6-alkyl, and
iii) C3-8-cycloalkyl;
X is selected from
i) —O—,
ii) —S—, and
iii) —S(O)2—;
R6 is selected from
i) aryl substituted with at least one of R12, R13 and R14,
ii) aryl-C1-6-alkyl substituted with at least one of R12, R13 and R14,
iii) heteroaryl substituted with at least one of R12, R13 and R14, and
iv) heteroaryl-C1-6-alkyl substituted with at least one of R12, R13 and R14;
A is selected from
i) —O—,
ii) —CH2—,
iii) —S(O)2NR10—, and
iv) —C(O)NR10—;
R8 is selected from
i) H, and
ii) —CH2R9;
R9 is selected from
i) H,
ii) hydroxy,
iii) amino-C1-6-alkyl substituted on the nitrogen atom by one or two substituents selected from H, C1-6-alkylcarbonyl, C1-6-alkoxycarbonyl, C1-6-alkyl, arylcarbonyl and heteroarylcarbonyl, wherein arylcarbonyl and heteroarylcarbonyl are substituted with at least one of R15, R16 and R17,
iv) aminocarbonyl substituted on the nitrogen atom by one or two substituents selected from H, C1-6-alkylcarbonyl, C1-6-alkoxycarbonyl, C1-6-alkyl, arylcarbonyl and heteroarylcarbonyl, wherein arylcarbonyl and heteroarylcarbonyl are substituted with at least one of R15, R16 and R17,
v) aminocarbonyl-C1-6-alkyl substituted on the nitrogen atom by one or two substituents selected from H, C1-6-alkylcarbonyl, C1-6-alkoxycarbonyl, C1-6-alkyl, arylcarbonyl and heteroarylcarbonyl, wherein arylcarbonyl and heteroarylcarbonyl are substituted with at least one of R15, R16 and R17,
vi) carboxy,
vii) carboxy-C1-6-alkyl,
viii) C1-6-alkoxy,
ix) C1-6-haloalkoxy,
x) C1-6-alkoxycarbonyl,
xi) C1-6-alkoxycarbonyl-C1-6-alkyl,
xii) C3-8-cycloalkyl,
xiii) aryl substituted with at least one of R15, R16 and R17,
xiv) aryl-C1-6-alkyl substituted with at least one of R15, R16 and R17,
xv) aryl-C1-6-alkoxy substituted with at least one of R15, R16 and R17,
xvi) heteroaryl substituted with at least one of R15, R16 and R17,
xvii) heteroaryl-C1-6-alkyl substituted with at least one of R15, R16 and R17, and
xviii) heteroaryl-C1-6-alkoxy substituted with at least one of R15, R16 and R17
xix) heterocycloalkyl substituted with at least one of R15, R16 and R17,
xx) heterocycloalkyl-C1-6-alkyl substituted with at least one of R15, R16 and R17,
xxi) heterocycloalkyl-C1-6-alkoxy substituted with at least one of R15, R16 and R17, and
xxii) C1-6-alkylsilyloxy;
R10 is H;
R11 is selected from
i) amino-C1-6-alkyl substituted on the nitrogen atom by at least one of R21 and R22,
ii) C3-8-cycloalkyl substituted with at least one of R18, R19 and R20,
iii) C3-8-cycloalkyl-C1-6-alkyl substituted with at least one of R18, R19 and R20,
iv) C3-8-cycloalkyl(halo)-C1-6-alkyl substituted with at least one of R18, R19 and R20,
v) aryl substituted with at least one of R18, R19 and R20,
vi) aryl-C1-6-alkyl substituted with at least one of R18, R19 and R20,
vii) aryl-C3-8-cycloalkyl substituted with at least one of R18, R19 and R20,
viii) aryl-heterocycloalkyl substituted with at least one of R18, R19 and R20
ix) aryl(halo)-C1-6-alkyl substituted with at least one of R18, R19 and R20,
x) aryl(halo)-C3-8-cycloalkyl substituted with at least one of R18, R19 and R20,
xi) aryl(halo)-heterocycloalkyl substituted with at least one of R18, R19 and R20,
xii) aryloxy-C1-6-alkyl substituted with at least one of R18, R19 and R20,
xiii) aryloxy-C3-8-cycloalkyl substituted with at least one of R18, R19 and R20,
xiv) aryloxy-heterocycloalkyl substituted with at least one of R18, R19 and R20,
xv) aryloxy(halo)-C3-8-cycloalkyl substituted with at least one of R18, R19 and R20,
xvi) aryloxy(halo)-heterocycloalkyl substituted with at least one of R18, R19 and R20
xvii) aryloxy(halo)-C1-6-alkyl,
xviii) heterocycloalkyl substituted with at least one of R18, R19 and R20,
xix) heterocycloalkyl-C1-6-alkyl substituted with at least one of R18, R19 and R20,
xx) heterocycloalkyl-C3-8-cycloalkyl substituted with at least one of R18, R19 and R20,
xxi) heterocycloalkyl(halo)-C3-8-cycloalkyl substituted with at least one of R18, R19 and R20,
i) heterocycloalkyl(halo)-C1-6-alkyl substituted with at least one of R18, R19 and R20,
ii) heteroaryl substituted with at least one of R18, R19 and R20,
iii) heteroaryl-C1-6-alkyl substituted with at least one of R18, R19 and R20,
iv) heteroaryl-C3-8-cycloalkyl substituted with at least one of R18, R19 and R20,
v) heteroaryl(halo)-C3-8-cycloalkyl substituted with at least one of R18, R19 and R20,
vi) heteroaryl(halo)-C1-6-alkyl substituted with at least one of R18, R19 and R20,
vii) heteroaryloxy-C1-6-alkyl substituted with at least one of R18, R19 and R20,
viii) heteroaryloxy-C3-8-cycloalkyl substituted with at least one of R18, R19 and R20,
ix) heteroaryloxy(halo)-C3-8-cycloalkyl substituted with at least one of R18, R19 and R20, and
x) heteroaryloxy(halo)-C1-6-alkyl substituted with at least one of R18, R19 and R20;
R12, R13, R14, R15, R16, R17, R18, R19 and R20 are each independently selected from
i) H,
ii) cyano,
iii) halogen,
iv) oxo,
v) C1-6-alkyl,
vi) amino substituted on the nitrogen atom by two substituents independently selected from H, C1-6-alkyl, C1-6-alkoxycarbonyl, arylcarbonyl and heteroarylcarbonyl,
vii) amino-C1-6-alkyl substituted on the nitrogen atom by two substituents independently selected from H, C1-6-alkyl, C1-6-alkoxycarbonyl, arylcarbonyl and heteroaryl carbonyl,
viii) C1-6-alkyl,
ix) halo-C1-6-alkyl,
x) C3-8-cycloalkyl,
xi) C1-6-alkoxycarbonyl-C1-6-alkyl,
xii) carboxy-C1-6-alkyl,
xiii) C1-6-alkoxycarbonyl-C1-6alkylaminocarbonyl-C1-6alkyl,
xiv) carboxy-C1-6-alkylaminocarbonyl-C1-6alkyl,
xv) C1-6-alkoxy,
xvi) halo-C1-6-alkoxy,
xvii) C1-6-alkoxycarbonyl-C1-6-alkoxy,
xviii) carboxy-C1-6-alkoxy,
xix) C1-6-alkoxycarbonyl-C1-6-alkylaminocarbonyl-C1-6-alkoxy,
xx) carboxy-C1-6-alkylaminocarbonyl-C1-6-alkoxy, and
xxi) heterocycloalkyl;
and
R21 and R22 are each independently selected from
i) H,
ii) C1-6-alkoxycarbonyl,
iii) carboxy-C1-6-alkyl,
iv) arylcarbonyl, and
v) heteroarylcarbonyl;
with the proviso that N-[(1S)-1-[[(1S)-1-[(2S,4R)-4-benzyloxy-2-[(1-ethyl-3,3,3-trifluoro-2-oxo-propyl)carbamoyl]pyrrolidine-1-carbonyl]-2-methyl-propyl]carbamoyl]-2-methyl-propyl]pyrazine-2-carboxamide is excluded.

### Claim 2 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein
R2 is C1-6-alkyl;
R3, R4, R5 and R7 are each H;
X is selected from
i) —O—,
ii) —S—, and
iii) —S(O)2—;
R6 is phenyl-C1-6-alkyl substituted with at least one of R12, R13 and R14;
A is selected from
i) —O—,
ii) —CH2—,
iii) —S(O)2NR10— and
iv) —C(O)NR10—;
R8 is selected from
i) H, and
ii) —CH2R9;
R9 is selected from
i) H,
ii) hydroxy,
iii) C1-6-alkoxy,
iv) phenyl substituted with at least one of R15, R16 and R17, and
v) C1-6-alkylsilyloxy;
R11 is selected from
i) phenyl substituted with at least one of R18, R19 and R20,
ii) phenyl-C3-8-cycloalkyl substituted with at least one of R18, R19 and R20,
iii) phenyl(halo)-C1-6-alkyl substituted with at least one of R18, R19 and R20, and
iv) heteroaryl substituted with at least one of R18, R19 and R20, wherein heteroaryl is selected from
a. pyrazinyl,
b. pyridinyl, and
c. thiophenyl;
R12 is selected from
i) H, and
ii) C1-6-alkoxy,
R15 is selected from
i) H,
ii) halogen, and
iii) amino-C1-6-alkyl substituted on the nitrogen atom by one H and one C1-6-alkoxycarbonyl;
R18 is selected from
i) H,
ii) halogen, and
iii) halo-C1-6-alkyl;
and
R13, R14, R16, R17, R19 and R20 are each H;
with the proviso that N-[(1S)-1-[[(1S)-1-[(2S,4R)-4-benzyloxy-2-[(1-ethyl-3,3,3-trifluoro-2-oxo-propyl)carbamoyl]pyrrolidine-1-carbonyl]-2-methyl-propyl]carbamoyl]-2-methyl-propyl]pyrazine-2-carboxamide is excluded.

### Claim 3 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R2 is C1-6-alkyl.

### Claim 4 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R3, R4, R5 and R7 are each H.

### Claim 5 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein X is selected from
i) —O—, and
ii) —S(O)2—.

### Claim 6 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein X is —O—.

### Claim 7 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R6 is phenyl-C1-6-alkyl substituted with at least one of R12, R13 and R14.

### Claim 8 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein A is selected from
i) —O—, and
ii) —CH2—.

### Claim 9 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein A is —O—.

### Claim 10 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R8 is H.

### Claim 11 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R9 is selected from
i) H,
ii) hydroxy,
iii) C1-6-alkoxy,
iv) phenyl substituted with at least one of R15, R16 and R17, and
v) C1-6-alkylsilyloxy.

### Claim 12 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R9 is phenyl substituted with at least one of R5, R16 and R17.

### Claim 13 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R11 is selected from
i) phenyl substituted with at least one of R18, R19 and R20,
ii) phenyl-C3-8-cycloalkyl substituted with at least one of R18, R19 and R20,
iii) phenyl(halo)-C1-6-alkyl substituted with at least one of R18, R19 and R20, and
iv) heteroaryl substituted with at least one of R18, R19 and R20, wherein heteroaryl is selected from
(a) pyrazinyl,
(b) pyridinyl, and
(c) thiophenyl.

### Claim 14 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R11 is phenyl substituted with at least one of R18, R19 and R20.

### Claim 15 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R12 is selected from
i) H, and
ii) C1-6-alkoxy.

### Claim 16 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R12 is H.

### Claim 17 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R15 is selected from
i) H,
ii) halogen, and
iii) amino-C1-6-alkyl substituted on the nitrogen atom by one H and one C1-6-alkoxycarbonyl.

### Claim 18 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R15 is H.

### Claim 19 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R18 is selected from
i) H,
ii) halogen, and
iii) halo-C1-6-alkyl.

### Claim 20 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R18 is halogen.

### Claim 21 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R13, R14, R16, R17, R19 and R20 are each H.

### Claim 22 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein
R2 is C1-6-alkyl;
R3, R4, R5 and R7 are each H;
X is —O—;
R6 is phenyl-C1-6-alkyl substituted with at least one of R12, R13 and R14;
A is —O—;
R8 is H;
R9 is phenyl substituted with at least one of R15, R16 and R17;
R11 is phenyl substituted with at least one of R18, R19 and R20;
R12, R13, R14, R15, R16, R17, R19 and R20 are each H; and
R18 is halogen.

### Claim 23 (depends on 1)

A compound according to claim 1, selected from the group consisting of:
N-((S)-3-(3-chlorophenyl)-1-((2S,4R)-4-((4-methoxybenzyl)sulfonyl)-2-(((S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl)carbamoyl)pyrrolidin-1-yl)-1-oxopropan-2-yl)picolinamide;
N-((S)-3-(3-chlorophenyl)-1-((2S,4R)-4-((4-methoxybenzyl)sulfonyl)-2-(((S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl)carbamoyl)pyrrolidin-1-yl)-1-oxopropan-2-yl)pyrazine-2-carboxamide;
(2S,4R)-1-[(2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]propanoyl]-4-[(4-methoxyphenyl)methyl sulfonyl]-N-[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]pyrrolidine-2-carboxamide;
(2S,4R)-1-[(2S)-2-[[2,2-difluoro-2-[2-(trifluoromethyl)phenyl]acetyl]amino]propanoyl]-4-[(4-methoxyphenyl)methyl sulfonyl]-N-[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]pyrrolidine-2-carboxamide;
(2S,4R)-1-[(2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-3-methoxypropanoyl]-4-[(4-methoxyphenyl)methyl sulfonyl]-N-[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]pyrrolidine-2-carboxamide;
(2S,4R)-1-[(2S)-2-[[2,2-difluoro-2-[2-(trifluoromethyl)phenyl]acetyl]amino]-3-methoxypropanoyl]-4-[(4-methoxyphenyl)methylsulfonyl]-N-[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]pyrrolidine-2-carboxamide;
tert-butyl N-[[4-[(2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-3-[(2S,4R)-4-[(4-methoxyphenyl)methyl sulfonyl]-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]carbamoyl]pyrrolidin-1-yl]-3-oxopropyl]phenyl]methyl]carbamate;
tert-butyl N-[[4-[(2S)-2-[(3-chlorobenzoyl)amino]-3-[(2S,4R)-4-[(4-methoxyphenyl)methyl sulfonyl]-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]carbamoyl]pyrrolidin-1-yl]-3-oxopropyl]phenyl]methyl]carbamate;
tert-butyl N-[[4-[(2S)-2-[[2,2-difluoro-2-[2-(trifluoromethyl)phenyl]acetyl]amino]-3-[(2S,4R)-4-[(4-methoxyphenyl)methylsulfonyl]-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]carbamoyl]pyrrolidin-1-yl]-3-oxopropyl]phenyl]methyl]carbamate;
tert-butyl N-[[4-[(2S)-2-[[1-(4-chlorophenyl)cyclopentanecarbonyl]amino]-3-[(2S,4R)-4-[(4-methoxyphenyl)methyl sulfonyl]-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]carbamoyl]pyrrolidin-1-yl]-3-oxopropyl]phenyl]methyl]carbamate;
(2S,4R)-1-(2-(3,5-dichlorophenoxy)acetyl)-4-((4-methoxybenzyl)sulfonyl)-N-((S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl)pyrrolidine-2-carboxamide;
(2S,4R)-1-(2-(3,5-dichlorophenoxy)acetyl)-4-((4-methoxybenzyl)thio)-N-((R)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl)pyrrolidine-2-carboxamide;
(2S,4R)-4-(benzyloxy)-1-(3-(3,4-dichlorophenyl)propanoyl)-N-((S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl)pyrrolidine-2-carboxamide;
(2S,4R)-4-(benzyloxy)-1-(2-(3,5-dichlorophenoxy)acetyl)-N-((S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl)pyrrolidine-2-carboxamide;
N-((S)-1-((2S,4R)-4-(benzyloxy)-2-(((S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl)carbamoyl)pyrrolidin-1-yl)-3-(3-chlorophenyl)-1-oxopropan-2-yl)picolinamide;
N-((S)-1-((2S,4R)-4-(benzyloxy)-2-(((S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl)carbamoyl)pyrrolidin-1-yl)-3-(3-chlorophenyl)-1-oxopropan-2-yl)pyrazine-2-carboxamide;
(2S,4R)-4-(benzyloxy)-1-((R)-2-(3,5-dichlorophenoxy)-3-phenylpropanoyl)-N-((S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl)pyrrolidine-2-carboxamide;
(2S,4R)-1-[(2S)-2-[(5-chlorothiophen-2-yl)sulfonylamino]-3-methoxypropanoyl]-4-[(4-methoxyphenyl)methyl sulfonyl]-N-[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]pyrrolidine-2-carboxamide;
(2S,4R)-1-[(2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-3-hydroxypropanoyl]-4-[(4-methoxyphenyl)methyl sulfonyl]-N-[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]pyrrolidine-2-carboxamide;
(2S,4R)-1-[(2S)-3-[4-(aminomethyl)phenyl]-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]propanoyl]-4-[(4-methoxyphenyl)methylsulfonyl]-N-[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]pyrrolidine-2-carboxamide;2,2,2-trifluoroacetic acid;
(2S,4R)-1-[(2S)-3-[4-(aminomethyl)phenyl]-2-[(3-chlorobenzoyl)amino]propanoyl]-4-[(4-methoxyphenyl)methyl sulfonyl]-N-[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]pyrrolidine-2-carboxamide;2,2,2-trifluoroacetic acid;
(2S,4R)-1-[(2S)-3-[4-(aminomethyl)phenyl]-2-[[2,2-difluoro-2-[2-(trifluoromethyl)phenyl]acetyl]amino]propanoyl]-4-[(4-methoxyphenyl)methyl sulfonyl]-N-[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]pyrrolidine-2-carboxamide;2,2,2-trifluoroacetic acid; and
(2S,4R)-1-[(2S)-3-[4-(aminomethyl)phenyl]-2-[[1-(4-chlorophenyl)cyclopentanecarbonyl]amino]propanoyl]-4-[(4-methoxyphenyl)methyl sulfonyl]-N-[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]pyrrolidine-2-carboxamide;2,2,2-trifluoroacetic acid;
or a pharmaceutically acceptable salt thereof.

### Claim 24 (depends on 1)

The compound of claim 1, selected from the group consisting of:
(2S,4R)-1-(2-(3,5-dichlorophenoxy)acetyl)-4-((4-methoxybenzyl)sulfonyl)-N-((S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl)pyrrolidine-2-carboxamide;
(2S,4R)-4-(benzyloxy)-1-(3-(3,4-dichlorophenyl)propanoyl)-N-((S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl)pyrrolidine-2-carboxamide;
(2S,4R)-4-(benzyloxy)-1-(2-(3,5-dichlorophenoxy)acetyl)-N-((S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl)pyrrolidine-2-carboxamide; and
(2S,4R)-4-(benzyloxy)-1-((R)-2-(3,5-dichlorophenoxy)-3-phenylpropanoyl)-N-((S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl)pyrrolidine-2-carboxamide;
or a pharmaceutically acceptable salt thereof.

### Claim 25 (depends on 1)

A process to prepare the compound of claim 1 comprising the reaction of a compound of formula (II) in oxidative conditions

### Claim 26 (depends on 1)

A pharmaceutical composition comprising the compound of claim 1, or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier.

### Claim 27 (depends on 1)

A method for the treatment of an HtrA1-mediated condition selected from the group consisting of wet or dry age-related macular degeneration, geographic atrophy, diabetic retinopathy, retinopathy of prematurity and polypoidal choroidal vasculopathy, which method comprises administering to a mammal in need thereof an effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt thereof.

### Claim 28 (depends on 1)

The compound of claim 1, wherein said compound is manufactured according to a process comprising the reaction of a compound of formula (II) in oxidative conditions