IP Library › Granted Patent US 7,932,401
Granted Patent B2
US 7,932,401 · App. 11/659,967 · Granted Apr 26, 2011

1,5-diphenylpyrazoles

Assignee: Merck Patent GmbH
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Quick Facts
Patent No.
US 7,932,401
App. No.
11/659,967
Granted
Apr 26, 2011
Kind
B2
Abstract

Novel 1,5 diphenylpyrazole derivatives of the formula (I), in which R 1 -R 6 have the meanings indicated in Claim 1 , are HSP90 inhibitors and can be used for the preparation of a medicament for the treatment of diseases in which the inhibition, regulation and/or modulation of HSP90 plays a role.

Claims (124)

1. A compound selected from the group consisting of

5-(5-aminosulfonyl-2,4-dihydroxyphenyl)-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(N-ethyl-N′-methylaminosulfonyl)-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(N-N′-diethylaminosulfonyl)-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(piperidine-1-sulfonyl)-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(N-phenylaminosulfonyl)-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(N-phenylaminosulfonyl)-2-hydroxy-4-methoxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-{5-[N-(2-fluorophenyl)aminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole,

5-{5-[N-(3-fluorophenyl)aminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole,

5-{5-[N-(4-fluorophenyl)aminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole,

5-{5-[N-(pyridin-3-yl)aminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(3-hydroxymethylpiperidine-1-sulfonyl)-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(3-bromomethylpiperidine-1-sulfonyl)-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(N-benzyl-N′-methylaminosulfonyl)-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(N-benzyl-N′-methylaminosulfonyl)-2-methoxy-4-hydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(N-N′-dimethylaminosulfonyl)-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(N-(2-bromoethyl)-N′-methylaminosulfonyl)-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(N-cyclohexyl-N′-methylaminosulfonyl)-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(N-(2,3-dibromopropyl)-N′-methylaminosulfonyl)-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(N-butyl-N′-methylaminosulfonyl)-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(N-propyl-N′-methylaminosulfonyl)-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-{5-[N-(2-cyanoethyl)-N′-methylaminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(N-isopropyl-N′-methylaminosulfonyl)-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-{5-[N-(dimethylaminocarbonylmethyl)-N′-methylaminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(2-hydroxymethylpiperidine-1-sulfonyl)-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(morpholine-4-sulfonyl)-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole and

5-{5-[N-(2-hydroxyethyl)-N′-(2-bromoethyl)aminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole,

5-{5-[N-(2-hydroxyethyl)-N′-(2-bromoethyl)aminosulfonyl]-2-hydroxy-4-methoxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole;

5-{5-[2-(N,N′-diethylaminomethyl)piperidin-4-yl]sulfonyl}-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(1-methylpiperazin-4-yl)sulfonyl]-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(N-methylaminosulfonyl)-2,4-hydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-{5-[N-(pyridin-4-yl)aminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(N-propyl-N′-methylaminosulfonyl)-2,4-dihydroxyphenyl]-1-(2-methylphenyl)-1H-pyrazole,

5-[5-(N-propyl-N′-methylaminosulfonyl)-2,4-dihydroxyphenyl]-1-(2-fluorophenyl)-1H-pyrazole,

5-[5-(N-phenylaminosulfonyl)-2,4-dihydroxyphenyl]-1-(2-methylphenyl)-1H-pyrazole,

5-[5-(N-phenylaminosulfonyl)-2-hydroxy-4-methoxyphenyl]-1-(2-methylphenyl)-1H-pyrazole,

5-[5-(N-benzylaminosulfonyl)-2,4-dihydroxyphenyl]-1-(2-methylphenyl)-1H-pyrazole,

5-[5-(N-benzylaminosulfonyl)-2-hydroxy-4-methoxyphenyl]-1-(2-methylphenyl)-1H-pyrazole,

5-[5-(N,N′-diethylaminosulfonyl)-2,4-dihydroxyphenyl]-1-(2-methylphenyl)-1H-pyrazole,

5-[5-(N,N′-diethylaminosulfonyl)-2-hydroxy-4-methoxyphenyl]-1-(2-methylphenyl)-1H-pyrazole,

5-[5-(ethylaminosulfonyl)-2,4-dihydroxyphenyl]-1-(2-methylphenyl)-1H-pyrazole,

5-[5-(ethylaminosulfonyl)-2-hydroxy-4-methoxyphenyl]-1-(2-methylphenyl)-1H-pyrazole,

5-[5-(aminosulfonyl)-2,4-dihydroxyphenyl]-1-(2-methylphenyl)-1H-pyrazole,

5-[5-(aminosulfonyl)-2-hydroxy-4-methoxyphenyl]-1-(2-methylphenyl)-1H-pyrazole,

5-[5-iodo-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-iodo-2,4-dihydroxyphenyl]-1-(2-fluorophenyl)-1H-pyrazole,

5-[5-carboxyethyl-2,4-dihydroxyphenyl]-1-(2-fluorophenyl)-1H-pyrazole,

5-[5-methoxycarbonylethyl-2,4-dihydroxyphenyl]-1-(2-fluorophenyl)-1H-pyrazole,

5-[5-(2-phenylethyl)-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(2-phenylethyl)-2,4-dihydroxyphenyl]-1-(2-fluorophenyl)-1H-pyrazole,

5-[5-(2-phenyl-2-methoxyethyl)-2,4-dihydroxyphenyl]-1-(2-fluorophenyl)-1H-pyrazole,

5-[5-styryl-2,4-dihydroxyphenyl]-1-(2-fluorophenyl)-1H-pyrazole,

5-{5-[2-(pyridin-4-yl)ethyl]-2,4-dihydroxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole,

5-{5-[2-(pyridin-4-yl)vinyl]-2,4-dihydroxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole,

5-{5-[2-(pyridin-2-yl)ethyl]-2,4-dihydroxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole,

5-{5-[2-(4-fluorophenyl)ethyl]-2,4-dihydroxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole,

5-{5-[2-(3-fluorophenyl)ethyl]-2,4-dihydroxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole,

5-{5-[2-(2-fluorophenyl)ethyl]-2,4-dihydroxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole,

5-{5-[1-(4-fluorophenyl)ethyl]-2,4-dihydroxyphenyl}-1-phenyl-1H-pyrazole,

5-{5-[2-(3-(aminomethylcarbonylamino)phenyl)ethyl]-2,4-dihydroxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole

5-{5-[2-(3-carboxyphenyl)ethyl]-2,4-dihydroxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole,

5-{5-[2-(2-chlorophenyl)ethyl]-2,4-dihydroxyphenyl}-1-(2,3-dihydrobenzo-1,4-dioxin-6-yl)-1H-pyrazole,

5-{5-propyl-2,4-dihydroxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole

5-{5-cyclopropylmethyl-2,4-dihydroxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole,

5-{5-(2-methylbutyl)-2,4-dihydroxyphenyl}-1-(3-methylphenyl)-1H-pyrazole,

5-{5-(2-fluoropropyl)-2,4-dihydroxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole,

5-{5-[2-(4-methylphenyl)ethyl]-2,4-dihydroxyphenyl}-1-(2,3-dihydrobenzo-1,4-dioxin-6-yl)-1H-pyrazole,

5-{5-(2-phenylpropyl)-2,4-dihydroxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole,

5-{5-(2-phenylpropyl)-2,4-dihydroxyphenyl}-1-(2-aminophenyl)-1H-pyrazole,

5-[5-phenylaminomethyl-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-phenylaminomethyl-2,4-dihydroxyphenyl]-1-(2-fluorophenyl)-1H-pyrazole,

5-[5-phenoxymethyl-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-phenoxymethyl-2,4-dihydroxyphenyl]-1-(2-fluorophenyl)-1H-pyrazole,

5-[5-phenylthiomethyl-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-phenylthiomethyl-2,4-dihydroxyphenyl]-1-(2-fluorophenyl)-1H-pyrazole,

5-[5-(4-methoxyphenylthiomethyl)-2,4-dihydroxyphenyl]-1-(2-fluorophenyl)-1H-pyrazole,

5-[5-phenylsulfinylmethyl-2,4-dihydroxyphenyl]-1-(2-fluorophenyl)-1H-pyrazole,

5-[5-(4-methoxyphenylsulfinylmethyl)-2,4-dihydroxyphenyl]-1-(2-fluorophenyl)-1H-pyrazole,

5-[5-phenylsulfonylmethyl-2,4-dihydroxyphenyl]-1-(2-fluorophenyl)-1H-pyrazole,

5-[5-(4-methoxyphenylsulfonylmethyl)-2,4-dihydroxyphenyl]-1-(2-fluorophenyl)-1H-pyrazole,

5-[5-phenylsulfanyl-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-phenylsulfanyl-2-hydroxy-4-methoxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-phenylsulfonyl-2-hydroxy-4-methoxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-phenylsulfonyl-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(2-fluorobenzylamino)-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-(5-benzyloxy-2,4-dihydroxyphenyl)-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(pyridin-4-ylmethylsulfanyl)-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-(5-phenylamino-2,4-dihydroxyphenyl)-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(3-fluorophenylmethylsulfinyl)-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(pyridin-2-ylmethylamino)-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(4-fluorobenzyloxy)-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(4-fluorophenylmethylsulfonyl)-2,4-dihydroxyphenyl]-1-phenyl-1H-pyrazole,

5-[5-(3-fluorophenylsulfonyl)-2,4-dihydroxyphenyl]-1-(3-ethylphenyl)-1H-pyrazole,

5-[5-phenylsulfanyl-2,4-dihydroxyphenyl]-1-(3-methylphenyl)-1H-pyrazole,

5-[5-(2-fluorophenylsulfanyl)-2-hydroxy-4-methoxyphenyl]-1-(4-nitrophenyl)-1H-pyrazole,

5-[5-(2-fluorophenylsulfanyl)-2-hydroxy-4-methoxyphenyl]-1-(4-aminophenyl)-1H-pyrazole,

5-[5-(N,N-diethylaminocarbonyl)-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-(5-phenylaminocarbonyl-2,4-dihydroxyphenyl)-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(N-methylaminocarbonyl)-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(N,N-dimethylaminocarbonyl)-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(N-ethylaminocarbonyl)-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(N-propyl-N-methylaminocarbonyl)-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(N-cyclopentyl-N-methylaminocarbonyl)-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-{5-{N-[(benzo-1,3-dioxol-5-yl)methyl]aminocarbonyl}-2,4-dihydroxyphenyl}-1-(2-chloro-5-fluorophenyl)-1H-pyrazole,

5-[5-(N-ethyl-N-methylaminocarbonyl)-2,4-dihydroxyphenyl]-1-(2-ethylphenyl)-1H-pyrazole,

5-[5-(N-butyl-N-methylaminocarbonyl)-2,4-dihydroxyphenyl]-1-(2,3-dichlorophenyl)-1H-pyrazole,

5-[5-(N-propyl-N-methylaminocarbonyl)-2,4-dihydroxyphenyl]-1-{4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-1H-pyrazole,

5-(5-benzyl-2,4-dihydroxyphenyl)-1-(2-benzylphenyl)-1H-pyrazole,

5-(5-benzyl-2,4-dihydroxyphenyl)-1-(2-chlorophenyl)-1H-pyrazole, and

5-(5-phenyl-2,4-dihydroxyphenyl)-1-(2-chlorophenyl)-1H-pyrazole,

or a pharmaceutically usable salt, or stereoisomer thereof, including mixtures thereof in all ratios.

2. A compound selected from the group consisting of

5-[5-(N-propyl-N′-methylaminosulfonyl)-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(N-propyl-N′-methylaminosulfonyl)-2,4-dihydroxyphenyl]-1-(2-methylphenyl)-1H-pyrazole,

5-[5-(N-propyl-N′-methylaminosulfonyl)-2,4-dihydroxyphenyl]-1-(2-fluorophenyl)-1H-pyrazole,

5-[5-(N-isopropyl-N′-methylaminosulfonyl)-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-{5-[2-(2-fluorophenyl)ethyl]-2,4-dihydroxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole,

5-[5-(N-propyl-N-methylaminocarbonyl)-2,4-dihydroxyphenyl]-1-(2-chlorophenyl)-1H-pyrazole,

5-(2,4-dihydroxy-5-bromophenyl)-1-(2-chlorophenyl)-1H-pyrazole,

5-(2,4-dihydroxy-5-chlorophenyl)-1-(2-fluorophenyl)-1H-pyrazole,

5-(2,4-dihydroxy-5-bromophenyl)-1-(2-ethylphenyl)-1H-pyrazole, and

5-[5-(N-propyl-N-methylaminocarbonyl)-2,4-dihydroxyphenyl]-1-{4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-1H-pyrazole,

or a pharmaceutically usable salt, or stereoisomer thereof, including mixtures thereof in all ratios.

3. A pharmaceutical composition comprising at least one compound according to claim 1 or a pharmaceutically usable salt or stereoisomer thereof, including mixtures thereof in all ratios, and a pharmaceutically useable carrier.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 12, 2007
From: EGGENWEILER, HANS-MICHAEL; WOLF, MICHAEL
To: MERCK PATENT GMBH
Reel/Frame 018925/0259 →
Priority Claims (1)
DE 10 2004 039 280 · Aug 13, 2004 · national
Continuity (1)
Related Publication 20080085904A1 · Apr 10, 2008