# US 9,751,861 B2 · N1-(3,3,3-trifluoro-2-hydroxo-2-methylpropionyl)-piperidine derivatives as inhibitors of pyruvate dehydrogenase kinase

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- Number: US 9,751,861 B2
- Document ID: US9751861B2
- Status: Granted
- Kind: B2
- Application number: 15/105,154
- Filed: 2014-11-19
- Published: 2016-10-27
- Granted: 2017-09-05
- Earliest claimed: 2013-12-17
- Assignees: Merck Patent GmbH
- Applicants: Merck Patent GmbH
- Inventors: Hans-Peter Buchstaller
- Web page: https://patentgrep.com/patent/US9751861B2

## CPC

- C07D 401/14: containing three or more hetero rings
- A61K 31/454: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
- A61K 31/4545: containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
- A61K 31/501: not condensed and containing further heterocyclic rings
- A61K 31/506: not condensed and containing further heterocyclic rings
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/06: Antihyperlipidemics
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 5/50: for increasing or potentiating the activity of insulin
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- 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 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- C07D 405/14: containing three or more hetero rings
- C07D 413/04: directly linked by a ring-member-to-ring-member bond
- C07D 413/14: containing three or more hetero rings
- C07D 417/14: containing three or more hetero rings
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- 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

## Abstract

Compounds of the formula (I) in which R, R1 and R3 have the meanings indicated in claim 1, are inhibitors of pyruvate dehydrogenase kinase (PDHK), and can be employed, inter alia, for the treatment of diseases such as cancer.

## Claims

### Claim 1

A compound,
wherein the compound is a compound of formula I or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof,
wherein formula (I) is
wherein
R denotes pyrazol-diyl, imidazol-diyl, isoxazol-diyl or triazol-diyl, each of which is unsubstituted or monosubstituted by R2,
R1 denotes (CH2)nAr, (CH2)nHet, A or Cyc,
R2 denotes A′, methoxy, hydroxy methyl, COOA′, CN, COOH, CONH2 or OH,
R3 denotes H, A′, COOA′ or CN,
Ar denotes phenyl, which is unsubstituted or mono-, di-, tri-, tetra- or pentasubstituted by Hal, A, CN, OA, [C(R5)2]pOH, [C(R5)2]pN(R5)2, NO2, [C(R5)2]pCOOR5, NR5COA, NR5SO2A, [C(R5)2]pSO2N(R5)2, S(O)nA, O[C(R5)2]mN(R5)2, NR5COOA, NR5CON(R5)2 and/or COA,
Het denotes a mono- or bicyclic saturated, unsaturated or aromatic heterocycle having 1 to 4 N, O and/or S atoms, which is unsubstituted or mono- or disubstituted by Hal, A, CN, OA, [C(R5)2]pOH, [C(R5)2]pN(R5)2, NO2, [C(R5)2]pCOOR5, NR5COA, NR5SO2A, [C(R5)2]pSO2N(R5)2, S(O)nA, O[C(R5)2]mN(R5)2, NR5COOA, NR5CON(R5)2 and/or COA,
Cyc denotes cyclic alkyl with 3, 4, 5, 6 or 7 C-atoms, which is unsubstituted or monosubstituted by OH,
A denotes unbranched or branched alkyl with 1-10 C-atoms, wherein one or two non-adjacent CH— and/or CH2-groups are optionally replaced by N—, O— and/or S-atoms and/or wherein 1-7 H-atoms are optionally replaced by R4,
R4 denotes F, Cl or OH,
R5 denotes H or A′,
A′ denotes unbranched or branched alkyl with 1-6 C-atoms, wherein 1-5H-atoms are optionally replaced by F,
Hal denotes F, Cl, Br or I,
m denotes 1, 2, 3 or 4,
n denotes 0, 1 or 2, and
p denotes 0, 1, 2, 3 or 4.

### Claim 2 (depends on 1)

The compound according to claim 1, wherein
R2 denotes A′, methoxy or hydroxymethyl.

### Claim 3 (depends on 1)

The compound according to claim 1, wherein
R3 denotes H or A′.

### Claim 4 (depends on 1)

The compound according to claim 1, wherein
Ar denotes phenyl, which is unsubstituted or mono-, di-, tri-, tetra- or pentasubstituted by Hal, A, CN and/or OA.

### Claim 5 (depends on 1)

The compound according to claim 1, wherein
Het denotes pyrimidyl, pyridyl, pyridazinyl, pyrazinyl, piperidinyl, pyrrolidinyl, pyrazolyl, thiazolyl, imidazolyl, furanyl, thiophenyl, pyrrolyl, oxazolyl, isoxazolyl, triazolyl, oxadiazolyl or thiadiazolyl, each of which is unsubstituted or mono- or disubstituted by Hal, A, CN and/or OA.

### Claim 6 (depends on 1)

The compound according to claim 1, wherein
R denotes pyrazol-diyl, imidazol-diyl, isoxazol-diyl or triazol-diyl, each of which is unsubstituted or monosubstituted by R2,
R1 denotes (CH2)nAr, (CH2)nHet, A or Cyc,
R2 denotes A′, methoxy or hydroxymethyl,
R3 denotes H or A′,
Ar denotes phenyl, which is unsubstituted or mono-, di-, tri-, tetra- or pentasubstituted by Hal, A, CN and/or OA,
Het denotes pyrimidyl, pyridyl, pyridazinyl, pyrazinyl, piperidinyl, pyrrolidinyl, pyrazolyl, thiazolyl, imidazolyl, furanyl, thiophenyl, pyrrolyl, oxazolyl, isoxazolyl, triazolyl, oxadiazolyl or thiadiazolyl, each of which is unsubstituted or mono- or disubstituted by Hal, A, CN and/or OA,
Cyc denotes cyclic alkyl with 3, 4, 5, 6 or 7 C-atoms, which is unsubstituted or monosubstituted by OH,
A denotes unbranched or branched alkyl with 1-10 C-atoms, wherein one or two non-adjacent CH— and/or CH2-groups are optionally replaced by N—, O— and/or S-atoms and/or wherein 1-7 H-atoms are optionally replaced by R4,
R4 denotes F, Cl or OH,
A′ denotes unbranched or branched alkyl with 1-6 C-atoms, wherein 1-5H-atoms are optionally replaced by F,
Hal denotes F, Cl, Br or I, and
n denotes 0, 1 or 2.

### Claim 7 (depends on 1)

The compound according to claim 1, selected from the group consisting of
No.
Name
“A1”
(R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-[4-(2-p-tolyl-2H-
pyrazol-3-yl)-piperidin-1-yl]-propan-1-one
“A2”
(R)-3,3,3-Trifluoro-2-hydroxy-1-{4-[2-(4-methoxy-phenyl)-2H-
pyrazol-3-yl]-piperidin-1-yl}-2-methyl-propan-1-one
“A3”
2-{5-[1-((R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-propionyl)-
piperidin-4-yl]-pyrazol-1-yl}-benzonitrile
“A4”
(R)-3,3,3,Trifluoro-1-{4-[2-(2-fluoro-phenyl)-2H-pyrazol-3-yl]-
piperidin-1-yl}-2-hydroxy-2-methyl-propan-1-one
“A5”
(R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-[4-(2-o-tolyl-2H-
pyrazol-3-yl)-piperidin-1-yl]-propan-1-one
“A6”
(R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-[4-(2-m-tolyl-2H-
pyrazol-3-yl)-piperidin-1-yl]-propan-1-one
“A7”
(R)-3,3,3-Trifluoro-2-hydroxy-1-{4-[2-(2-methoxy-phenyl)-2H-
pyrazol-3-yl)-piperidin-1-yl}-2-methyl-propan-1-one
“A8”
3-{5-[1-((R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-propionyl)-
piperidin-4-yl]-pyrazol-1-yl}-benzonitrile
“A9”
4-{5-[1-((R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-propionyl)-
piperidin-4-yl]-pyrazol-1-yl}-benzonitrile
“A10”
(R)-3,3,3-Trifluoro-1-{4-[2-(3-fluoro-phenyl)-2H-pyrazol-3-yl]-
piperidin-1-yl}-2-hydroxy-2-methyl-propan-1-one
“A11”
(R)-1-{4-[2-(2-Chloro-phenyl)-2H-pyrazol-3-yl]-piperidin-
1-yl}-3,3,3-trifluoro-2-hydroxy-2-methyl-propan-1-one
“A12”
(R)-1-{4-[2-(3-Chloro-phenyl)-2H-pyrazol-3-yl]-piperidin-
1-yl}-3,3,3-trifluoro-2-hydroxy-2-methyl-propan-1-one
“A13”
(R)-1-{4-[2(4-Chloro-phenyl)-2H-pyrazol-3-yl]-piperidin-1-yl}-
3,3,3-trifluoro-2-hydroxy-2-methyl-propan-1-one
“A14”
(R)-3,3,3-Trifluoro-1-{4-[2-(4-fluoro-phenyl)-2H-pyrazol-3-yl]-
piperidin-1-yl}-2-hydroxy-2-methyl-propan-1-one
“A15”
(R)-1-{4-[2-(3-Chloro-2-fluro-phenyl)-2H-pyrazol-3-yl]-
piperidin-1-yl}-3,3,3-trifluoro-2-hydroxy-
2-methyl-propan-1-one
“A16”
(R)-3,3,3-Trifluoro-1-{4-[2-(2-fluoro-4-methyl-phenyl)-2H-
pyrazol-3-yl]-piperidin-1-yl}-2-hydroxy-2-methyl-propan-1-one
“A17”
(R)-1-[4-(2-tert-Butyl-2H-pyrazol-3-yl)-piperidin-1-yl]-3,3,3-
trifluoro-2-hydroxy-2-methyl-propan-1-one
“A18”
(R)-1-{4-[2-(2-Chloro-4-trifluoromethyl-phenyl)-2H-pyrazol-3-
yl]-piperidin-1-yl}-3,3,3-trifluoro-2-hydroxy-
2-methyl-propan-1-one
“A19”
(R)-1-{4-[2-(5-Bromo-pyrimidin-2-yl)-
2H-pyrazol-3-yl]-piperidin-
1-yl]-3,3,3-trifluoro-2-hydroxy-2-methyl-propan-1-one
“A20”
(R)-3,3,3-Trifluoro-2-hydroxy-1-(4-{2-[4-(1-hydroxy-1-methyl-
ethyl)-phenyl]-2H-pyrazol-3-yl}-piperidin-1-yl)-2-methyl-
propan-1-one
“A21”
(R)-1-{4-[2-(4-tert-Butyl-phenyl)-2H-pyrazol-3-yl]-piperidin-1-
yl}-3,3,3-trifluoro-2-hydroxy-2-methyl-propan-1-one
“A22”
(R)-3,3,3-Trifluoro-2-hydroxy-1-{4-[2-(4-isopropyl-phenyl)-
2H-pyrazol-3-yl]-piperidin-1-yl}-2-methyl-propan-1-one
“A23”
(R)-1-{4-[2-(4-Chloro-2-fluoro-phenyl)-2H-pyrazol-3-yl]-
piperidin-1-yl}-3,3,3-trifluoro-2-hydroxy-
2-methyl-propan-1-one
“A24”
(R)-1-{4-[2-(4-Ethyl-phenyl)-2H-pyrazol-3-yl]-piperidin-1-yl}-
3,3,3-trifluoro-2-hydroxy-2-methyl-propan-1-one
“A25”
(R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-[4-(2-phenyl-2H-
pyrazol-3-yl)-piperidin-1-yl]-propan-1-one
“A26”
(R)-1-{4-[2-(2,4-Difluoro-phenyl)-
2H-pyrazol-3-yl]-piperidin-1-
yl}-3,3,3-trifluoro-2-hydroxy-2-methyl-propan-1-one
“A27”
(R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-{4-[2-(4-
trifluoromethyl-phenyl)-2H-pyrazol-3-yl]-
piperidin-1-yl}-propan-1-one
“A28”
(R)-3,3,3-Trifluoro-1-{4-[2-(2-fluoro-4-methoxy-phenyl)-2H-
pyrazol-3-yl]-piperidin-1-yl}-2-hydroxy-2-methyl-propan-1-one
“A29”
(R)-1-{4-[1-(5-Chloro-pyridin-2-yl)-1H-
pyrazol-3-yl]-piperidin-1-yl}-3,3,3-trifluoro-2-
hydroxy-2-methyl-propan-1-one
“A30”
rac-3,3,3-Trifluoro-1-{4-[2-(2-fluoro-4-methoxy-phenyl)-2H-
pyrazol-3-yl]-piperidin-1-yl}-2-hydroxy-2-methyl-propan-1-one
“A31”
(R)-1-{4-[2-(2,4-Difluoro-phenyl)-2H-pyrazol-3-yl]-3-methyl-
piperidin-1-yl}-3,3,3-trifluoro-2-hydroxy-
2-methyl-propan-1-one
“A32”
(R)-1-{(3R,4R)-4-[2-(2,4-difluoro-phenyl)-2H-pyrazol-3-yl]-3-
methyl-piperidin-1-yl}-3,3,3-trifluoro-2-hydroxy-2-methyl-
propan-1-one
“A33”
(R)-1-{(3S,4S)-4-[2-(2,4-difluoro-phenyl)-2H-pyrazol-3-yl]-3-
methyl-piperidin-1-yl}-3,3,3-trifluoro-2-hydroxy-2-methyl-
propan-1-one
“A34”
(R)-1-{4-[1-(4-Chloro-phenyl)-5-methyl-1H-pyrazol-3-yl]-
piperidin-1-yl}-3,3,3-trifluoro-2-hydroxy-
2-methyl-propan-1-one
“A35”
(R)-1-{4-[2-(4-Chloro-phenyl)-5-trifluoromethyl-
2H-pyrazol-3-yl]-piperidin-1-yl}-3,3,3-trifluoro-
2-hydroxy-2-methyl-propan-1-one
“A36”
(R)-1-[4-(2-isopropyl-2H-pyrazol-3-yl)-piperidin-1-yl]-3,3,3-
trifluoro-2-hydroxy-2-methyl-propan-1-one
“A37”
(R)-1-[4-(2-Cyclohexyl-2H-pyrazol-3-yl)-piperidin-1-yl]-3,3,3-
trifluoro-2-hydroxy-2-methyl-propan-1-one
“A38”
(R)-1-[4-(2-Benzyl-2H-pyrazol-3-yl)-piperidin-1-yl]-3,3,3-
trifluoro-2-hydroxy-2-methyl-propan-1-one
“A39”
(R)-1-{4-(2-(2-Chloro-4-fluoro-phenyl)-2H-pyrazol-3-yl]-
piperidin-1-yl}-3,3,3-trifluoro-2-hydroxy-
2-methyl-propan-1-one
“A40”
(R)-1-{4-[1-(4-Fluoro-phenyl)-5-methyl-1H-pyrazol-3-yl]-
piperidin-1-yl}-3,3,3-trifluoro-2-hydroxy-
2-methyl-propan-1-one
“A41”
(R)-1-{4-[2-(4-Fluoro-phenyl)-5-methyl-2H-pyrazol-3-yl]-
piperidin-1-yl}-3,3,3-trifluoro-2-hydroxy-
2-methyl-propan-1-one
“A42”
(R)-1-{4-[2-(4-Fluoro-phenyl)-5-trifluoromethyl-
2H-pyrazol-3-yl]-piperidin-1-yl}-3,3,3-trifluoro-
2-hydroxy-2-methyl-propan-1-one
“A43”
(R)-1-[4-(2-Phenyl)-5-trifluoromethyl-
2H-pyrazol-3-yl)-piperidin-
1-yl]-3,3,3-trifluoro-2-hydroxy-2-methyl-propan-1-one
“A44”
(R)-1-{4-[1-(4-Fluro-phenyl)-1H-pyrazol-3-yl]-3-methyl-
piperidin-1-yl}-3,3,3-trifluoro-2-hydroxy-
2-methyl-propan-1-one
“A45”
(R)-3,3,3-Trifluoro-1-{(3R,4R)-4-[1-(4-fluoro-phenyl)-1H-
pyrazol-3-yl]-3-methyl-piperidin-1-yl}-2-hydroxy-2-methyl-
propan-1-one
“A46”
(R)-3,3,3-Trifluoro-1-{(3S,4S)-4-[1-(4-fluoro-phenyl)-1H-
pyrazol-3-yl]-3-methyl-piperidin-1-yl}-2-hydroxy-2-methyl-
propan-1-one
“A47”
(R)-1-[4-(5-Methyl-1-phenyl-1H-pyrazol-3-yl)-piperidin-1-yl]-
3,3,3-trifluoro-2-hydroxy-2-methyl-propan-1-one
“A48”
(R)-3,3,3-Trifluoro-2-hydroxy-1-{4-[2-(3-chloro-4-methoxy-
phenyl)-2H-pyrazol-3-yl]-piperidin-1-yl}-
2-methyl-propan-1-one
“A49”
(R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-(4-{2-[4-(2,2,2-
trifluoro-ethoxy)-phenyl]-2H-pyrazol-3-yl}-piperidin-1-yl)-
propan-1-one
“A50”
(R)-1-{4-[2-(4-Chloro-phenyl)-5-methyl-2H-pyrazol-3-yl]-
piperidin-1-yl}-3,3,3-trifluoro-2-hydroxy-
2-methyl-propan-1-one
“A51”
(R)-1-{4-[2-Cyclopentyl-2H-pyrazol-3-yl)-piperidin-1-yl]-3,3,3-
trifluoro-2-hydroxy-2-methyl-propan-1-one
“A52”
(R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-[4-(2-methyl-2H-
pyrazol-3-yl)-piperidin-1-yl]-propan-1-one
“A53”
(R)-3,3,3-Trifluoro-2-hydroxy-1-
{4-[2-(6-methoxy-pyridin-3-yl)-
2H-pyrazol-3-yl]-piperidin-1-yl}-2-methyl-propan-1-one
“A54”
5-(2-Fluoro-phenyl)-4-[1-((R-3,3,3-trifluoro-2-hydroxy-2-
methyl-propionyl)-piperidin-4-yl]-2,4-dihydro-[1,2,4]triazol-3-
one
“A55”
(R)-3,3,3-Trifluoro-1-{4-[3-(2-fluoro-phenyl)-[1,2,4]triazol-
4-yl]-piperidin-1-yl]-2-hydroxy-2-methyl-propan-1-one
“A56”
(R)-1-{4-[3-(4-Chloro-phenyl)-[1,2,4]trizaol-
4-yl]-piperidin-1-yl}-3,3,3-trifluoro-
2-hydroxy-2-methyl-propan-1-one
“A57”
(R)-3,3,3-Trifluoro-2-hydroxy-1-{4-[3-(4-methoxy-phenyl)-3H-
[1,2,3]triazol-4-yl]-piperidin-1-yl}-2-methyl-propan-1-one
“A58”
(R)-1-{4-[3-(4-Chloro-phenyl)-3H-[1,2,3]trizaol-4-yl]-piperidin-
1-yl}-3,3,3-trifluoro-2-hydroxy-2-methyl-propan-1-one
“A59”
(R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-[4-(3-p-tolyl-3H-
[1,2,3]triazol-4-yl]-piperidin-1-yl]-propan-1-one
“A60”
(R)-3,3,3-Trifluoro-1-{4-[3-(2-fluoro-4-methyl-phenyl)-3H-
[1,2,3]triazol-4-yl]-piperidin-1-yl}-2-hydroxy-
2-methyl-propan-1-one
“A61”
(R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-[4-(2-phenyl-
imidazol-1-yl)-piperidin-1-yl]-propan-1-one
“A62”
(R)-1-{4-[2-(4-Chloro-phenyl)-imidazol-1-yl]-piperidin-1-yl}-
3,3,3-trifluoro-2-hydroxy-2-methyl-propan-1-one
“A63”
(2R)-3,3,3-trifluoro-2-hydroxy-2-methyl-1-[4-
(5-phenylimidazol-1-yl)-1-piperidyl]propan-1-one
“A64”
(2R)-1-[4-[5-(4-chlorophenyl)imidazol-1-yl]-1-piperidyl]-3,3,3-
trifluoro-2-hydroxy-2-methyl-propan-1-one
“A65”
(R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-[4-(3-phenyl-3H-
imidazol-4-yl)-piperidin-1-yl]-propan-1-one
“A66”
(R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-[4-(5-phenyl-
pyrazol-1-yl)-1-piperidin-1-yl]-propan-1-one
“A67”
(R)-3,3,3-Trifluoro-1-{4-[1-(4-fluoro-
phenyl)-1H-imidazol-2-yl]-
piperidin-1-yl}-2-hydroxy-2-methyl-propan-1-one
“A68”
(R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-[4-(1-p-tolyl-1H-
imidazol-2-yl)-piperidin-1-yl]-propan-1-one
“A69”
(R)-1-{4-[1-(4-Chloro-phenyl)-1H-imidazol-2-yl]-piperidin-
1-yl}-3,3,3-trifluoro-2-hydroxy-2-methyl-propan-1-one
“A70”
(R)-3,3,3-Trifluoro-2-hydroxy-1-{4-[1-(4-methoxy-phenyl)-1H-
imidazol-2-yl]-piperidin-1-yl}-2-methyl-propan-1-one
“A71”
(R)-3,3,3-Trifluoro-1-{4-[4-(4-
fluoro-phenyl)-4H-[1,2,4]triazol-3-
yl]-piperidin-1-yl}-2-hydroxy-2-methyl-propan-1-one
“A72”
(R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-[4-(4-phenyl-4H-
[1,2,4]triazol-3-yl)-piperidin-1-yl]-propan-1-one
“A73”
(R)-1-{4-[4-(4-Chloro-phenyl)-4H-[1,2,4]triazol-3-yl]-piperidin-
1-yl}-3,3,3-trifluoro-2-hydroxy-2-methyl-propan-1-one
“A74”
(R)-1-[4-(2-Cyclopropyl-2H-pyrazol-3-yl)-1-piperidyl]-3,3,3-
trifluoro-2-hydroxy-2-methyl-propan-1-one
“A75”
(R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-{4-[2-(1-methyl-
piperidin-4-yl)-2H-pyrazol-3-yl]-piperidin-1-yl}-propan-1-one
“A76”
(R)-3,3,3-Trifluoro-2-hydroxy-1-[4-(2-isobutyl-1H-
pyrazol-3-yl)-1-piperidyl]-2-methyl-propan-1-one
“A77”
(R)-3,3,3-Trifluoro-2-hydroxy-2-
methyl-1-{4-[2-(2,2,2-trifluoro-
ethyl)-2H-pyrazol-3-yl]-piperidin-1-yl}-propan-1-one
“A78”
(R)-3,3,3-Trifluoro-2-hydroxy-1-[4-[2-(2-methoxyethyl-2H-
pyrazol-3-yl]-1-piperidyl]-2-methyl-propan-1-one
“A79”
(R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-{4-[2-(6-methyl-
pyridin-3-yl)-2H-pyrazol-3-yl]-1-piperidin-1-yl}-propan-1-one
“A80”
(R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-[4-[2-[6-(trifluoro-
methyl)-3-pyridyl]-2H-pyrazol-3-yl]-1-piperidyl]propan-1-one
“A81”
5-{5-[1-((R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-propionyl)-
piperidin-4-yl]-pyrazol-1-yl}-1-piperidine-2-carbonitrile
“A82”
(R)-1-[4-[2-(3,5-Diflouro-2-pyridyl)-2H-pyrazol-3-yl]-1-
piperidyl]-3,3,3-trifluoro-2-hydroxy-2-methyl-propan-1-one
“A83”
(R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-{4-[2-(5-methyl-
pyridin-2-yl)-2H-pyrazol-3-yl]-piperidin-1-yl}-propan-1-one
“A84”
(R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-[4-[2-(5-trifluoro-
methyl-pyridin-2-yl)-2H-pyrazol-3-yl]-
piperidin-1-yl}-propan-1-one
“A85”
(R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-[4-[2-(1-
methylpyrazol-4-yl)-2H-pyrazol-3-yl]-1-
piperidyl]propan-1-one
“A86”
(R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-[4-[2-(4-
methylthiazol-2-yl)-2H-pyrazol-3-yl]-1-piperidyl]propan-1-one
“A87”
(R)-3,3,3-Trifluoro-2-hydroxy-1-{4-[2-(1H-imidazol-2-yl)-2H-
pyrazol-3-yl]-piperidin-1-yl}-2-methyl-propan-1-one
“A88”
(R)-3,3,3-Trifluoro-1-[4-[2-[2-fluoro-4-
(trifluoromethyl)phenyl]-2H-pyrazol-3-yl]-1-
piperidyl]-2-hydroxy-2-methyl-propan-1-one
“A89”
(R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-[4-[2-[2-(trifluoro-
methyl)phenyl]-2H-pyrazol-3-yl]-1-piperidyl]-propan-1-one
“A90”
(R)-3,3,3-Trifluoro-1-{4-[2-(4-fluoro-2-methoxy-phenyl)-2H-
pyrazol-3-yl]-piperidin-1-yl}-2-hydroxy-2-methyl-propan-1-one
“A91”
3-Fluoro-4-[5-[1-[(R)-3,3,3-trifluoro-2-hydroxy-2-methyl-
propanoyl]-4-piperidyl]-2H-pyrazol-1-yl]benzonitrile
“A92”
(R)-3,3,3-Trifluoro-1-[4-[2-[2-fluoro-4-(1-hydroxy-1-methyl-
ethyl)phenyl]-2H-pyrazol-3-yl]-1-piperidyl]-2-
hydroxy-2-methyl-propan-1-one
“A93”
(R)-3,3,3-Trifluoro-2-hydroxy-1-{4-[2-(6-methoxy-pyridazin-3-
yl)-2H-pyrazol-3-yl]-piperidin-1-yl}-2-methyl-propan-1-one
“A94”
(R)-3,3,3-Trifluoro-2-hydroxy-1-[4-[2-(4-hydroxycyclohexyl)-
2H-pyrazol-3-yl]-piperidyl]-2-methyl-propan-1-one
“A95”
(R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-[4-[3-[4-(trifluoro-
methoxy)-phenyl]-2H-pyrazol-3-yl]-piperidyl]-propan-1-one
“A96”
(R)-1-[4-[2-[4-(Difluoromethoxy)phenyl]-2H-pyrazol-3-yl]-1-
piperidyl]-3,3,3-trifluoro-2-hydroxy-2-methyl-propan-1-one
“A97”
(R)-1-{4-[2-(2,4-(Difluoro-phenyl)-5-methyl-2H-pyrazol-3-yl]-
piperidin-1-yl}-3,3,3-trifluoro-2-hydroxy-
2-methyl-propan-1-one
“A98”
(R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-[4-(5-methyl-2-
phenyl-2H-pyrazol-3-yl)-piperidin-1-yl]-propan-1-one
“A99”
(R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-[4-(1-methyl-1H-
pyrazol-3-yl)-piperidin-1-yl]-propan-1-one
“A100”
(R)-1-{4-[2-(4-Chloro-3-fluoro-phenyl)-2H-pyrazol-3-yl]-
piperidin-1-yl)-3,3,3-trifluoro-2-hydroxy-
2-methyl-propan-1-one
“A101”
(R)-1-{4-[2-(3,4-Dichloro-phenyl)-
2H-pyrazol-3-yl]-piperidin-1-
yl}-3,3,3-trifluoro-2-hydroxy-2-methyl-propan-1-one
“A102”
(R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-{4-[1-(5-trifluoro-
methyl-pyridin-2-yl)-1H-pyrazol-3-yl]-
piperidin-1-yl}-propan-1-one
“A103”
(R)-1-{4-[1-(5-Chloro-pyrimidin-2-yl)-1H-
pyrazol-3-yl]-piperidin-1-yl}-3,3,3-trifluoro-
2-hydroxy-2-methyl-propan-1-one
“A104”
(R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-[4-(2H-
pyrazol-3-yl)-piperidin-1-yl]-propan-1-one
“A105”
(R)-3,3,3-Trifluoro-2-hydroxy-1-{4-[1-(6-methoxy-pyridazin-3-
yl)-1H-pyrazol-3-yl]-piperidin-1-yl}-2-methyl-propan-1-one
“A106”
(R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-[(3S,4S)-3-methyl-4-
(2-phenyl-2H-pyrazol-3-yl)-piperidin-1-yl]-propan-1-one
“A107”
(R)-3,3,3-Trifluoro-1-{(3S,4S)-4-[2-(4-fluoro-phenyl)-2H-
pyrazol-3-yl]-3-methyl-piperidin-1-yl}-2-hydroxy-2-methyl-
propan-1-one
“A108”
(R)-3,3,3-Trifluoro-1-{(3R,4R)-4-[2-(4-fluoro-phenyl)-2H-
pyrazol-3-yl]-3-methyl-piperidin-1-yl}-2-hydroxy-2-methyl-
propan-1-one
“A109”
(R)-1-{4-[1-(3,5-Difluoro-pyridin-2-yl)-1H-pyrazol-3-yl]-
piperidin-1-yl}-3,3,3-trifluoro-2-
hydroxy-2-methyl-propan-1-one
“A110”
(R)-3,3,3-Trifluoro-1-{(3S,4S)-4-[2-(4-methoxy-phenyl)-2H-
pyrazol-3-yl]-3-methyl-piperidin-1-yl}-2-hydroxy-2-methyl-
propan-1-one
“A111”
4-{5-[(3S,4S)-3-Methyl-1-((R)-3,3,3-trifluoro-2-hydroxy-2-
methyl-propionyl)-piperidin-4-yl]-pyrazol-1-yl}-benzonitrile
“A112”
(2R)-1-[4-[2-(5-Fluoro-2-pyridyl)-2H-pyrazol-3-yl]-1-
piperidyl]-3,3,3-trifluoro-2-hydroxy-2-methyl-propan-1-one
“A113”
(R)-3,3,3-Trifluoro-1-{(3S,4S)-4-[2-(6-methoxy-pyridin-3-yl)-
2H-pyrazol-3-yl]-3-methyl-piperidin-1-yl}-2-hydroxy-
2-methyl-propan-1-one
“A114”
(R)-3,3,3-Trifluoro-2-hydroxy-1-[4-(1-isobutyl-1H-
pyrazol-3-yl)-piperidin-1-yl]-2-methyl-propan-1-one
“A115”
(R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-{4-[2-(5-methyl-
isoxazol-3-yl)-2H-pyrazol-3-yl]-piperidin-1-yl}-propan-1-one
“A116”
(R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-{4-[2-(tetrahydro-
pyran-4-yl)-2H-pyrazol-3-yl]-piperidin-1-yl}-propan-1-one
“A117”
(R)-1-[4-(2-Benzothiazol-2-yl-2H-pyrazol-3-yl)-piperidin-1-yl]-
3,3,3-trifluoro-2-hydroxy-2-methyl-propan-1-one
“A118”
(R)-3,3,3-Trifluoro-1-{(3S,4S)-4-[2-(5-fluoro-pyridin-2-yl)-2H-
pyrazol-3-yl]-3-methyl-piperidin-1-yl}-2-hydroxy-2-methyl-
propan-1-one
“A119”
(R)-1-{(3S,4S)-4-[2-(4-Chloro-phenyl)-2H-pyrazol-3-yl]-3-
methyl-piperidin-1-yl}-3,3,3-trifluoro-2-hydroxy-2-methyl-
propan-1-one
“A120”
(R)-3,3,3-Trifluoro-2-hydroxy-1-{(3S,4S)-4-[2-(4-hydroxy-
cyclohexyl)-2H-pyrazol-3-yl]-3-methyl-piperidin-1-yl}-
2-methyl-propan-1-one
“A121”
(R)-3,3,3-Trifluoro-2-hydroxy-1-{(3S,4S)-4-[2-(4-hydroxy-
cyclohexyl)-2H-pyrazol-3-yl]-3-methyl-piperidin-1-yl}-
2-methyl-propan-1-one
“A122”
(R)-3,3,3-Trifluoro-2-hydroxy-1-[4-(2-isoxazol-3-yl-2H-
pyrazol-3-yl)-piperidin-1-yl]-2-methyl-propan-1-one
“A123”
(R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-[4-(2-pyridazin-3-yl-
2H-pyrazol-3-yl)-piperidin-1-yl]-propan-1-one
“A124”
(R)-3,3,3-Trifluoro-1-{4-[3-(4-fluoro-phenyl)-3H-imidazol-
4-yl]-piperidin-1-yl}-2-hydroxy-2-methyl-propan-1-one
“A125”
(R)-1-{4-[3-(4-Chloro-phenyl)-3H-
imidazol-4-yl]-piperidin-1-yl}-
3,3,3-trifluoro-2-hydroxy-2-methyl-propan-1-one
“A126”
(R)-1-{4-[3-(4-Chloro-2-fluoro-phenyl)-3H-imidazol-4-yl]-
piperidin-1-yl}-3,3,3-trifluoro-2-
hydroxy-2-methyl-propan-1-one
“A127”
(R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-{4-[3-(4-trifluoro-
methyl-phenyl)-3H-imidazol-4-yl]-piperidin-1-yl}-propan-1-one
“A128”
(R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-[4-(3-phenyl-
isoxazol-4-yl)-piperidin-1-yl]-propan-1-one
“A129”
(R)-3,3,3-Trifluoro-1-{4-[3-(4-fluoro-phenyl)-isoxazol-4-yl]-
piperidin-1-yl}-2-hydroxy-2-methyl-propan-1-one
“A130”
(R)-1-{4-[3-(2,4-Difluoro-phenyl)-
3H-imidazol-4-yl]-piperidin-1-
yl}-3,3,3-trifluoro-2-hydroxy-2-methyl-propan-1-one
“A131”
(R)-3,3,3-Trifluoro-2-hydroxy-1-{4-[3-(4-methoxy-phenyl)-3H-
imidazol-4-yl]-piperidin-1-yl}-2-methyl-propan-1-one
“A132”
(R)-3,3,3-Trifluoro-1-{4-[3-(2-
fluoro-phenyl)-3H-imidazol-4-yl]-
piperidin-1-yl}-2-hydroxy-2-methyl-propan-1-one
“A133”
(R)-3,3,3-Trifluoro-2-hydroxy-
1-{4-[3-(6-methoxy-pyridin-3-yl)-
3H-imidazol-4-yl]-piperidin-1-yl}-2-methyl-propan-1-one
“A134”
(R)-3,3,3-Trifluoro-1-{4-[3-(2-fluoro-4-methoxy-phenyl)-3H-
imidazol-4-yl]-piperidin-1-yl}-2-
hydroxy-2-methyl-propan-1-one
“A135”
(2R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-[4-[2-(5-methyl-
1,2,4-oxadiazol-3-yl)pyrazol-3-yl]-1-piperidyl]propan-1-one
“A136”
(2R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-[4-[2-(2-
methylthiazol-5-yl)pyrazol-3-yl]-1-piperidyl]propan-1-one
“A137”
(2R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-[4-[2-(5-methyl-
1,3,4-thiadiazol-2-yl)pyrazol-3-yl]-1-piperidyl]propan-1-one
“A138”
(2R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-[4-[2-(5-methyl-
1,3,4-oxadiazol-2-yl)pyrazol-3-yl]-1-piperidyl]propan-1-one
“A139”
(2R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-[4-[2-(2-
methylpyrimidin-5-yl)pyrazol-3-yl]-1-piperidyl]propan-1-one
“A140”
(2R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-[4-[2-(2-
methylthiazol-4-yl)pyrazol-3-yl]-1-piperidyl]propan-1-one
“A141”
(2R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-[4-[2-(5-
methylpyrazin-2-yl)pyrazol-3-yl]-1-piperidyl]propan-1-one
“A142”
(2R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-[4-[2-(1-
methylimidazol-2-yl)pyrazol-3-yl]-1-piperidyl]propan-1-one
“A143”
(2R)-1-[4-[2-[4-(1,1-Difluoroethyl)phenyl]pyrazol-3-yl]-1-
piperidin]-3,3,3-trifluoro-2-hydroxy-2-methyl-propan-1-one
“A144”
(2R)-1-[(3S,4S)-4-[2-(3,5-Difluoro-2-pyridyl)pyrazol-3-yl]-3-
methyl-1-piperidyl]-3,3,3-trifluoro-2-hydroxy-2-methyl-propan-
1-one
“A145”
(2R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-[(3S,4S)-3-methyl-
4-[2-(1-methylpyrazol-4-yl)pyrazol-3-yl]-1-piperidyl]propan-1-
one
“A146”
(2R)-3,3,3-Trifluoro-2-hydroxy-2-
methyl-1-[4-[2-(2,2,2-trifluoro-
1,1-dimethyl-ethyl)pyrazol-3-yl]-1-piperidyl]propan-1-one
“A147”
(2R)-3,3,3-Trifluoro-2-hydroxy-2-methyl-1-[(3S,4S)-3-methyl-
4-[2-(2,2,2-trifluoro-1,1-dimethyl-ethyl)pyrazol-3-yl]-1-
piperidyl]propan-1-one
“A148”
(2R)-3,3,3-Trifluoro-2-hydroxy-1-
[(3S,4S)-4-[2-[4-(1-hydroxy-1-
methyl-ethyl)phenyl]pyrazol-3-yl]-3-methyl-1-piperidyl]-2-
methyl-propan-1-one
“A149”
(2R)-3,3,3-Trifluoro-1-[(3R,4S)-4-[3-(4-fluorophenyl)-1,2,4-
triazol-4-yl]-3-methyl-1-piperidyl]-2-hydroxy-2-methyl-propan-
1-one
“A150”
(2R)-1-[(3R,4S)-4-[3-(2,4-Difluorophenyl)-1,2,4-triazol-4-yl]-3-
methyl-1-piperidyl]-3,3,3-trifluoro-2-hydroxy-2-methyl-propan-
1-one
“A151”
(2R)-3,3,3-trifluoro-2-hydroxy-1-[4-[3-[4-(1-hydroxy-1-methyl-
ethyl)phenyl]imidazol-4-yl]-1-piperidyl]-2-methyl-propan-1-one
“A152”
(2R)-3,3,3-Trifluoro-1-[(3S,4S)-4-[3-(4-fluorophenyl)imidazol-
4-yl]-3-methyl-1-piperidyl]-2-hydroxy-2-methyl-propan-1-one
“A153”
(2R)-3,3,3-Trifluoro-1-[4-[3-(4-
fluorophenyl)-2-methyl-imidazol-
4-yl]-1-piperidyl]-2-hydroxy-2-methyl-propan-1-one
“A154”
(2R)-3,3,3-Trifluoro-1-[4-[3-(4-fluorophenyl)-2-(hydroxyl-
methyl)imidazol-4-yl]-1-piperidyl]-2-hydroxy-2-
methyl-propan-1-one
“A155”
(2R)-3,3,3-Trifluoro-1-[4-[3-(4-fluorophenyl)-2-methoxy-
imidazol-4-yl]-1-piperidyl]-2-hydroxy-2-methyl-propan-1-one
and pharmaceutically acceptable salts, tautomers and stereoisomers thereof.

### Claim 8 (depends on 1)

A process for the preparation of the compound of the formula I according to claim 1, the process comprising:
reacting a compound of formula II
in which R, R1 and R3 are as defined in formula I,
with a compound of formula III
wherein L denotes Cl, Br, I or a free or reactively functionally modified OH group, and/or
converting a base or acid of the formula I into one of its salts.

### Claim 9 (depends on 1)

A medicament, comprising:
at least one compound of the formula I according to claim 1; and
a pharmaceutically acceptable carrier, excipient or vehicle.

### Claim 10 (depends on 1)

A medicament, comprising:
at least one compound of the formula I according to claim 1, including mixtures thereof in all ratios,
at least one further medicament active ingredient which is an anticancer agent, and
a pharmaceutically acceptable carrier, excipient or vehicle.

### Claim 11 (depends on 1)

A kit, consisting of separate packs of
(a) an effective amount of the compound of the formula I according to claim 1, including mixtures thereof in all ratios, and
(b) an effective amount of a further medicament active ingredient which is an anticancer agent.

### Claim 12 (depends on 1)

A pharmaceutical composition, comprising:
the compound of claim 1, including mixtures thereof in all ratios and a pharmaceutically acceptable carrier, excipient or vehicle.

### Claim 13 (depends on 1)

A kit, comprising:
separate packs of
(a) an effective amount of the compound of the formula I according to claim 1, including mixtures thereof in all ratios, and
(b) an effective amount of a further medicament active ingredient which is an anticancer agent.