Azole derivatives and pharmaceutical compositions containing them
AssigneeApplied Research Systems ARS Holding N.V.
InventorsStephen J. Arkinstall, Antonio Arulanandam, Xuliang Jiang, Sharad Magar, Roustem Nabioullin, John Yingsheng Zhang, Peter Blume-Jensen
Life of this patent
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Abstract
The invention provides substituted pyrazolidinone compounds, and methods of treatment and pharmaceutical compositions that utilize or comprise one or more such compounds. Compounds of the invention are useful for a variety of therapies, including treating or preventing various cancers, inflammation, septic shock, preterm labor, infertility, pain, and ischemia, and other diseases and disorders associated with MEK-1 and/or ERK-2 activation.
Claims37
A compound of the following Formula (I):
- wherein each of A1, A2, and A4 are carbon and A3 is nitrogen;
- each R is independently halo, nitro, optionally substituted alkyl;
- optionally substituted alkenyl;
- optionally substituted alkynyl;
- optionally substituted heteroalkyl;
- optionally substituted heteroalkenyl;
- optionally substituted heteroalkynyl;
- optionally substituted alkanol;
- optionally substituted carbocyclic aryl, optionally substituted heteroalicyclic, optionally substituted heteroaromatic, optionally substituted aralkyl;
- optionally substituted heteroarylalkyl;
- and optionally substituted heteroalicyclicalkyl;
- or two R groups on adjacent ring atoms are taken together with those ring to form a fused alicyclic, heteroalicyclic, carbocyclic aryl or heteraromatic group having from 4 to about 8 ring members;
- k is an integer;
- Y is selected from the group consisting of CH2CH, CH2CH(CH2)q, CH2CR7CH2, and a branched alkyl having the formula CH2CH(CH2)p(CH2)s, wherein R7 is H or C1-C6 alkyl, s and p are the same or different and are zero or a positive integer, and q is a positive integer;
- W and W′ are each independently a hetero atom;
- optionally substituted heteroalkyl;
- optionally substituted heteroalkenyl;
- and optionally substituted heteroalkynyl;
- Z and Z′ are each independently a chemical bond or alkanoyl;
- R1 and R2 are each independently optionally substituted carbocyclic aryl or optionally substituted heteroaromatic, wherein when R2 is a carbocyclic aryl and said carbocyclic aryl is a phenyl, said phenyl is substituted;
- or pharmaceutically acceptable salt thereof, with the exclusion of racemates of 4-methoxy-benzoic acid 1-imidazol-1-yl methyl-2-phenoxy-ethyl ester, 4-chloro benzoic acid 1-imidazol-1-yl methyl-2-phenoxy-ethyl ester, and benzoic acid 1-imidzol-1-yl methyl-2-phenoxy-ethyl ester.
A compound that is an enantiomeric excess of:
- benzoic acid 1-imidazol-1-yl methyl-2-phenoxy-ethyl ester;
- 4-methoxy-benzoic acid 1-imidazol-1-yl methyl-2-phenoxy-ethyl ester;
- 4-chloro-benzoic acid 1-imidazol-1-yl methyl-2-phenoxy-ethyl ester;
- or a pharmaceutically acceptable salt thereof.
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and one or more compounds of the following Formula (I):
- wherein each of A1, A2, and A4 is are carbon and A3 is nitrogen;
- each R is independently halo, nitro, optionally substituted alkyl;
- optionally substituted alkenyl;
- optionally substituted alkynyl;
- optionally substituted heteroalkyl;
- optionally substituted heteroalkenyl;
- optionally substituted heteroalkynyl;
- optionally substituted alkanol;
- optionally substituted carbocyclic aryl, optionally substituted heteroalicyclic, optionally substituted heteroaromatic, optionally substituted aralkyl;
- optionally substituted heteroarylalkyl;
- and optionally substituted heteroalicyclicalkyl;
- or two R groups on adjacent ring atoms are taken together with those ring to form a fused alicyclic, heteroalicyclic, carbocyclic aryl or heteraromatic group having from 4 to about 8 ring members;
- k is an integer;
- Y is selected from the group consisting of CH2CH, CH2CH(CH2)q, CH2CR7CH2, and a branched alkyl having the formula CH2CH(CH2)p(CH2)s, wherein R7 is H or C1-C6 alkyl, s and p are the same or different and are zero or a positive integer, and q is a positive integer;
- W and W′ are each independently a hetero atom;
- optionally substituted heteroalkyl;
- optionally substituted heteroalkenyl;
- and optionally substituted heteroalkynyl;
- Z and Z′ are each independently a chemical bond or alkanoyl;
- R1 and R2 are each independently optionally substituted carbocyclic aryl or optionally substituted heteroaromatic;
- or pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.