# US 9,751,842 B2 · Phthalazine derivatives

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- Number: US 9,751,842 B2
- Document ID: US9751842B2
- Status: Granted
- Kind: B2
- Application number: 14/392,145
- Filed: 2014-05-30
- Published: 2016-11-03
- Granted: 2017-09-05
- Earliest claimed: 2013-06-24
- Assignees: Marck Patent GmbH
- Applicants: Merck Patent GmbH
- Inventors: Hans-Peter Buchstaller; Dieter Dorsch; Christina Esdar; Birgitta Leuthner
- Web page: https://patentgrep.com/patent/US9751842B2

## CPC

- C07D 237/34: with nitrogen atoms directly attached to carbon atoms of the nitrogen-containing ring, e.g. hydrazine radicals
- A61K 31/502: ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- 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 R1, X and n have the meanings indicated in Claim 1, are inhibitors of Tankyrase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation.

## Claims

### Claim 1

A compound of formula I
in which
R1 is H, Hal, CH3, OCH3 or CH2OH,
X is Ar or Cyc,
Ar is phenyl, biphenyl or naphthyl, each of which is unsubstituted or mono-, di- or trisubstituted by Hal, NO2, CN, A, [C(R2)2]pOR2, S(O)mR2, [C(R2)2]pN(R2)2, [C(R2)2]pCOOR2, [C(R2)2]pCON(R2)2, [C(R2)2]pSO2N(R2)2, NR2COR2, NR2SO2R2, NR2CON(R2)2, NHCOOA, O[C(R2)2]nN(R2)2, CHO and/or COA,
R2 is H or A,
A is unbranched or branched alkyl with 1-10 C-atoms, wherein two adjacent carbon atoms optionally form a double bond and/or one or two non-adjacent CH- and/or CH2-groups are optionally replaced by N-, O- and/or S-atoms and wherein 1-7 H-atoms are optionally replaced by F, Cl and/or OH,
Cyc is cycloalkyl with 3, 4, 5, 6 or 7 C-atoms,
Hal is F, Cl, Br or I,
m is 0, 1 or 2,
n is 1, 2 or 3, and
p is 0, 1, 2, 3 or 4,
or a pharmaceutically acceptable salt, solvate, tautomer or stereoisomer thereof.

### Claim 2 (depends on 1)

The compound according to claim 1, in which
R1 is H, Hal or CH3,
or a pharmaceutically acceptable salt, solvate, tautomer or stereoisomer thereof.

### Claim 3 (depends on 1)

The compound according to claim 1, in which
Ar is phenyl, which is unsubstituted or mono-, di- or trisubstituted by Hal, NO2, CN, A and/or [C(R2)2]pOR2,
or a pharmaceutically acceptable salt, solvate, tautomer or stereoisomer thereof.

### Claim 4 (depends on 1)

The compound according to claim 1, in which
A is unbranched or branched alkyl with 1-6 C-atoms, wherein 1-5 H-atoms are optionally replaced by F,
or a pharmaceutically acceptable salt, solvate, tautomer or stereoisomer thereof.

### Claim 5 (depends on 1)

The compound according to claim 1, in which
R1 is H, Hal or CH3,
X is Ar or Cyc,
Ar is phenyl, which is unsubstituted or mono-, di- or trisubstituted by Hal, NO2, CN, A and/or [C(R2)2]pOR2,
R2 is H or A,
Cyc is cycloalkyl with 3, 4, 5, 6 or 7 C-atoms,
A is unbranched or branched alkyl with 1-6 C-atoms, wherein 1-5 H-atoms are optionally replaced by F,
Hal is F, Cl, Br or I,
p is 0, 1, 2, 3 or 4, and
n is 1, 2 or 3,
or a pharmaceutically acceptable salt, solvate, tautomer or stereoisomer thereof.

### Claim 6

A compound, which is one of the following compounds
No.
Name
“A1”
2-phenyl-N-phthalazin-1-yl-acetamide
“A2”
2-(3-methoxyphenyl)-N-phthalazin-1-yl-acetamide
“A3”
2-(4-methoxyphenyl)-N-phthalazin-1-yl-acetamide
“A4”
2-(4-ethoxyphenyl)-N-phthalazin-1-yl-acetamide
“A5”
N-phthalazin-1-yl-2-(3-trifluoromethoxyphenyl)-acetamide
“A6”
2-(3-cyanophenyl)-N-phthalazin-1-yl-acetamide
“A7”
2-(3-nitrophenyl)-N-phthalazin-1-yl-acetamide
“A8”
N-phthalazin-1-yl-2-(4-trifluoromethoxyphenyl)-acetamide
“A9”
2-(4-tert-butylphenyl)-N-phthalazin-1-yl-acetamide
“A10”
2-(2,6-dichlorophenyl)-N-phthalazin-1-yl-acetamide
“A11”
2-(4-ethoxy-phenyl)-N-(5-fluoro-phthalazin-1-yl)-acetamide
“A12”
N-(5-fluoro-phthalazin-1-yl)-2-(4-methoxy-phenyl)-acetamide
“A13”
3-cyclohexyl-N-phthalazin-1-yl-propionamide
“A14”
3-phenyl-N-phthalazin-1-yl-propionamide
“A15”
3-cyclopentyl-N-phthalazin-1-yl-propionamide
“A16”
3-(2-chloro-phenyl)-N-phthalazin-1-yl-propionamide
“A17”
3-(2,3-dichloro-phenyl)-N-phthalazin-1-yl-propionamide
“A18”
N-(8-methyl-phthalazin-1-yl)-2-phenyl-acetamide
“A19”
N-(5-methyl-phthalazin-1-yl)-2-phenyl-acetamide
“A20”
2-(4-methoxy-phenyl)-N-(8-methyl-phthalazin-1-yl)-acetamide
“A21”
2-(4-methoxy-phenyl)-N-(5-methyl-phthalazin-1-yl)-acetamide
“A22”
3-cyclohexyl-N-(8-methyl-phthalazin-1-yl)-propionamide
“A23”
3-phenyl-N-(8-methyl-phthalazin-1-yl)-propionamide
“A24”
3-cyclopentyl-N-(8-methyl-phthalazin-1-yl)-propionamide
“A25”
3-(2-chlorophenyl)-N-(8-methyl-phthalazin-1-yl)-propionamide
or
“A26”
3-(2,3-dichlorophenyl)-N-(8-methyl-phthalazin-1-yl)-
propionamide
or a pharmaceutically acceptable salt, solvate, tautomer or stereoisomer thereof.

### Claim 7 (depends on 1)

A process for preparing a compound of formula I according to claim 1 or a pharmaceutically acceptable salt thereof, comprising
reacting a compound of formula II
in which R1 has the meanings indicated for the compound of formula I, with a compound of formula III
in which X and n have the meanings indicated for the compound of formula I, and L is Cl, Br, I or a free or reactively functionally modified OH group,
and/or
converting a base or acid compound of formula I into one of its salts.

### Claim 8 (depends on 1)

A pharmaceutical composition comprising a compound of formula I according to claim 1 or a pharmaceutically acceptable salt, solvate, tautomer or stereoisomer thereof and a pharmaceutically acceptable carrier, excipient or vehicle.

### Claim 9 (depends on 8)

A pharmaceutical composition according to claim 8, and at least one further pharmaceutically active ingredient.

### Claim 10 (depends on 1)

A kit comprising separate packs of
(a) a compound of formula I according to claim 1 or a pharmaceutically acceptable salt, solvate, tautomer or stereoisomer thereof, and
(b) a further pharmaceutically active ingredient.

### Claim 11 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt thereof.

### Claim 12 (depends on 2)

The compound according to claim 2, or a pharmaceutically acceptable salt thereof.

### Claim 13 (depends on 3)

The compound according to claim 3, or a pharmaceutically acceptable salt thereof.

### Claim 14 (depends on 4)

The compound according to claim 4, or a pharmaceutically acceptable salt thereof.

### Claim 15 (depends on 5)

The compound according to claim 5, or a pharmaceutically acceptable salt thereof.

### Claim 16 (depends on 6)

The compound according to claim 6, or a pharmaceutically acceptable salt thereof.

### Claim 17 (depends on 1)

A pharmaceutical composition comprising a compound of formula I according to claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, excipient or vehicle.

### Claim 18 (depends on 6)

A pharmaceutical composition comprising a compound according to claim 6 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, excipient or vehicle.

### Claim 19 (depends on 6)

A kit comprising separate packs of
(a) a compound according to claim 6 or a pharmaceutically acceptable salt, solvate, tautomer or stereoisomer thereof, and
(b) a further pharmaceutically active ingredient.

### Claim 20 (depends on 6)

A kit comprising separate packs of
(a) a compound according to claim 6 or a pharmaceutically acceptable salt thereof, and
(b) a further pharmaceutically active ingredient.