Pyrazoles
AssigneeHoffmann-La Roche Inc.
InventorsPaul Gillespie, Robert Goodnow, Qiang Zhang
Life of this patent
Estimating the term…
Abstract
Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of diseases such as, for example, type II diabetes mellitus and metabolic syndrome.
Claims22
A compound of the formula I:
- wherein:
- one of R1 or R2 is hydrogen or alkyl and the other is lower alkyl or (CH2)pY, wherein Y is a substituted or unsubstituted, saturated, partially unsaturated, or unsaturated mono-, bi- or tri-cyclic 5-10 membered cycloalkyl ring and p is 0 or 1, and wherein substituents on Y are lower alkyl, lower alkoxy, hydroxy, hydroxy-alkyl, alkyl-phenyl, phenyl-alkyl, pyridine or halogen,
- or R1 and R2, together with the N atom to which they are attached, form a substituted or unsubstituted ring Z, wherein Z is a 5- to 7-membered monocyclic or 7- to 10-membered bicyclic saturated, partially unsaturated or unsaturated substituted or unsubstituted heterocyclic ring which contains the N atom to which R1 and R2 are attached, and optionally another hetero atom which is selected from N, O and S, wherein the substituted heterocyclic ring is mono- or di-substituted with lower alkyl, hydroxy, hydroxy-alkyl, alkylphenyl, phenyl-alkyl, pyridine or halogen;
- R3 is an aromatic ring system selected from the group consisting of [2,2′]bithiophenyl, 1-methyl-indole, 2,3-dihydro-benzo[1, 4]dioxin, benzo[1,3]dioxole, benzothiophene, dibenzofuran, furane, naphthalene, phenyl, biphenyl, quinoline, thianthrene and thiophene, wherein said aromatic ring may be unsubstituted or substituted with one or more amino, cyano, formyl, halo, hydroxy, hydroxymethyl, lower-acyl, lower-acyl-amino, lower-alkoxy, lower-alkoxy-carbonyl, 2-(lower-alkoxy-carbonyl)-ethenyl, lower-alkyl, lower-alkyl-thio, nitro, trifluoromethoxy or trifluoromethyl, wherein said phenyl ring may additionally be substituted with phenoxy or benzyloxy,
- or R3 is:
- wherein Ar is a carbocyclic or heterocyclic aryl group which may be unsubstituted or substituted with one or more groups selected from the group consisting of halogen, lower alkyl, lower alkoxy, trifluoromethyl, cyano and nitro;
- and
- R4 is lower alkyl;
- and pharmaceutically acceptable salts thereof.
A pharmaceutical composition comprising a therapeutically effective amount of a compound according to formula (I):
- wherein:
- one of R1 or R2 is hydrogen or alkyl and the other is lower alkyl or (CH2)pY, wherein Y is a substituted or unsubstituted, saturated, partially unsaturated, or unsaturated mono-, bi- or tri-cyclic 5-10 membered cycloalkyl ring and p is 0 or 1, and wherein substituents on Y are lower alkyl, lower alkoxy, hydroxy, hydroxy-alkyl, alkyl-phenyl, phenyl-alkyl, pyridine or halogen,
- or R1 and R2, together with the N atom to which they are attached, form a substituted or unsubstituted ring Z, wherein Z is a 5- to 7-membered monocyclic or 7- to 10-membered bicyclic saturated, partially unsaturated or unsaturated substituted or unsubstituted heterocyclic ring which contains the N atom to which R1 and R2 are attached, and optionally another hetero atom which is selected from N, O and S, wherein the substituted heterocyclic ring is mono- or di-substituted with lower alkyl, hydroxy, hydroxy-alkyl, alkylphenyl, phenyl-alkyl, pyridine or halogen;
- R3 is an aromatic ring system selected from the group consisting of [2,2′]bithiophenyl, 1-methyl-indole, 2,3-dihydro-benzo[1, 4]dioxin, benzo[1,3]dioxole, benzothiophene, dibenzofuran, furane, naphthalene, phenyl, biphenyl, quinoline, thianthrene and thiophene, wherein said aromatic ring may be unsubstituted or substituted with one or more amino, cyano, formyl, halo, hydroxy, hydroxymethyl, lower-acyl, lower-acyl-amino, lower-alkoxy, lower-alkoxy-carbonyl, 2-(lower-alkoxy-carbonyl)-ethenyl, lower-alkyl, lower-alkyl-thio, nitro, trifluoromethoxy or trifluoromethyl, wherein said phenyl ring may additionally be substituted with phenoxy or benzyloxy,
- or R3 is:
- wherein Ar is a carbocyclic or heterocyclic aryl group which may be unsubstituted or substituted with one or more groups selected from the group consisting of halogen, lower alkyl, lower alkoxy, trifluoromethyl, cyano and nitro;
- and
- R4 is lower alkyl;
- or pharmaceutically acceptable salts thereof,
- and a pharmaceutically acceptable carrier.
A method of treating a metabolic disorder, comprising the step of administering to a patient in need thereof a therapeutically effective amount of a compound according to formula I:
- wherein:
- one of R1 or R2 is hydrogen or alkyl and the other is lower alkyl or (CH2)pY, wherein Y is a substituted or unsubstituted, saturated, partially unsaturated, or unsaturated mono-, bi- or tri-cyclic 5-10 membered cycloalkyl ring and p is 0 or 1, and wherein substituents on Y are lower alkyl, lower alkoxy, hydroxy, hydroxy-alkyl, alkyl-phenyl, phenyl-alkyl, pyridine or halogen,
- or R1 and R2, together with the N atom to which they are attached, form a substituted or unsubstituted ring Z, wherein Z is a 5- to 7-membered monocyclic or 7- to 10-membered bicyclic saturated, partially unsaturated or unsaturated substituted or unsubstituted heterocyclic ring which contains the N atom to which R1 and R2 are attached, and optionally another hetero atom which is selected from N, O and S, wherein the substituted heterocyclic ring is mono- or di-substituted with lower alkyl, hydroxy, hydroxy-alkyl, alkylphenyl, phenyl-alkyl, pyridine or halogen;
- R3 is an aromatic ring system selected from the group consisting of [2,2′]bithiophenyl, 1-methyl-indole, 2,3-dihydro-benzo[1,4]dioxin, benzo[1,3]dioxole, benzothiophene, dibenzofuran, furane, naphthalene, phenyl, biphenyl, quinoline, thianthrene and thiophene, wherein said aromatic ring may be unsubstituted or substituted with one or more amino, cyano, formyl, halo, hydroxy, hydroxymethyl, lower-acyl, lower-acyl-amino, lower-alkoxy, lower-alkoxy-carbonyl, 2-(lower-alkoxy-carbonyl)-ethenyl, lower-alkyl, lower-alkyl-thio, nitro, trifluoromethoxy or trifluoromethyl, wherein said phenyl ring may additonally be substituted with phenoxy or benzyloxy,
- or R3 is:
- wherein Ar is a carbocyclic or heterocyclic aryl group which may be unsubstituted or substituted with one or more groups selected from the group consisting of halogen, lower alkyl, lower alkoxy, trifluoromethyl, cyano and nitro;
- and
- R4 is lower alkyl;
- or a pharmaceutically acceptable salt thereof,
- and a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.