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US 6,297,261 B1Granted
Substituted phenyl derivatives, their preparation and use
AssigneeNeuroSearch A/S
InventorsPalle Christophersen, Ove Pedersen
Life of this patent
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Abstract
A compound having the formula (I) or a pharmaceutically acceptable salt thereof where the variables are defined in the specification are useful in the treatment of sickle-cell anemia.
Claims15
A compound having the formula
- or a pharmaceutically acceptable salt thereof;
- wherein one of R1, R2 and R3 is a heterocyclic acidic functional group having a pKa value below 8;
- R4, R5and a remaining two of the three substituents R1, R 2 and R3 are each independently selected from the group consisting of hydrogen;
- alkyl;
- alkoxy;
- hydroxy;
- halogen;
- trifluoromethyl;
- cyano;
- nitro;
- amino;
- alkylamino;
- —COOR7;
- —NHSO2—alkyl;
- —SO2N(R7)2;
- —SO2OR7;
- —CO—R7;
- aryl, biphenyl, phenylamino, phenoxy or heteroaryl;
- wherein the aryl, biphenyl, phenylamino, phenoxy or heteroaryl group may be substituted one or more times with substituents selected from the group consisting of alkyl, hydroxy, alkoxy, halogen, trifluoromethyl, cyano, nitro, amino and alkylamino;
- aryl and heteroaryl,
- or R3 and R4 or R4 and R5 together form a cyclic structure and a remaining three of the five substituents R1, R2, R3, R4 and R5 are as defined above;
- R7 is hydrogen, alkyl, amino or phenyl;
- Y is —CO—;
- X is —NH—, —CH2—NH—, or —SO2—NH—;
- Z is NR6, wherein R6is hydrogen, or alkyl;
- R11, R12, R13, R14 and R15 are each independently selected from the group consisting of hydrogen;
- alkyl;
- alkoxy;
- hydroxy;
- halogen;
- trifluoromethyl;
- cyano;
- nitro;
- amino;
- alkylamino;
- —COOR7;
- —NHSO2-alkyl;
- —SO2N(R7)2;
- —SO2OR7;
- —CO—R7;
- aryl, biphenyl, phenylamino, phenoxy or heteroaryl;
- wherein the aryl, biphenyl, phenylamino, phenoxy or heteroaryl group may be substituted one or more times with substituents selected from alkyl, hydroxy, alkoxy, halogen, trifluoromethyl, cyano, nitro, amino and alkylamino;
- aryl and heteroaryl;
- or one of R11 and R12, R12 and R13, R13 and R14 and R14 and R15 together form a cyclic structure, substituents R11, R12, R13, R14 and R15 is as defined above and R7is as defined above
- with the proviso that the compound is not:
- N-[3-(2,5-dihydro-5-thioxo-1H-tetrazol-1-yl)phenyl]-N′-[4-[5-[2-(hydroxymethyl)phenyl]-2-oxo-1,3,4-oxadiazol-3(2H) -yl]phenyl]-urea;
- or N-[3-2,5-dihydro-5-thioxo-1H-tetrazol -l-yl)phenyl]-N′-[4-(2-oxo-1, 3, 4-oxadiazol-3(2H)-yl)phenyl]-urea.
44 more elements
A compound according to claim 11, wherein one of R1, R2 or R3 is selected from the group consisting of:
- 3 hydroxy-4-oxo-pyranyl, 2-hydroxy-4-oxo-pyrimidyl,
- 4-hydroxy-1,2,4-triazolyl, 3,5
- dioxo-1,2,4-oxadiazolidinyl, 2,4-dioxo-imidazolidinyl,
- 2,5-dioxo-3-hydroxy-pyrrolyl, 2,5-dioxo-pyrrolidinyl,
- 2,4-dioxo-1,3-thiazolidinyl, 3-hydroxy-isoxazolyl, 5-hydroxy -isoxazolyl, 3-hydroxy-isothiazolyl,
- 3-hydroxy-1,2,5-thiadiazolyl, tetrazolyl, 3-hydroxytriazolyl,
- 3-hydroxy-pyrazolyl, 2-hydroxy-1,3,4-oxadiazolyl or
- 3-oxo-1,2-dihydro-1,2,4-triazolyl, 2-oxo-3H-1,3,4-oxadiazolyl,
- and 3-oxo-1,2dihydro-1,2,4-triazolyl.
6 more elements
A compound selected from the group consisting of:
- 3-Trifluoromethylphenyl-4-nitro-2-(5-tetrazolyl) phenyl urea;
- 3-Trifluoromethylphenyl-4-(2-naphthyl)-2-(5-tetrazolyl) phenyl urea;
- 3-Trifluoromethylphenyl-4-(3-pyridyl)-2-(5-tetrazolyl) phenyl urea;
- 3-Trifluoromethylphenyl-4-(l-naphthyl)-2-(5-tetrazolyl) phenyl urea;
- 3-Trifluoromethylphenyl-4-(4-trifluoromethyl phenyl)-2-(5-tetrazolyl) phenyl urea;
- 3-Trifluoromethylphenyl-4-(3-furyl)-2-(5-tetrazolyl) phenyl urea;
- 3-Trifluoromethylphenyl-4-(3-thienyl)-2-(5-tetrazolyl) phenyl urea;
- 3-Trifluoromethylphenyl-4-(3-nitrophenyl)-2-(5-tetrazolyl) phenyl urea;
- 3-Trifluoromethylphenyl-4-(4-ethoxycarbonylphenyl)-2-(5-tetrazolyl) phenyl urea;
- 3-Trifluoromethylphenyl-4-(4-diethylaminocarbonylphenyl)-2-(5-tetrazolyl)phenyl urea;
- 3-Trifluoromethylphenyl-4-(4-aminocarbonyl-phenyl)-2-(S-tetrazolyl) phenyl urea;
- 3-Trifluoromethylphenyl-2-(4-hydroxy-1,2,4-triazol-3-yl)phenyl urea;
- 3-Trifluoromethylphenyl-2-(3-oxo-1,2-dihydro-1,2,4-triazol-1-yl) phenyl urea;
- 3-Trifluoromethylphenyl-2-(2-oxo-3H-1,3,4-oxadiazol-5-yl) phenyl urea,
- 3-Trifluoromethylphenyl-4-biphenylyl-2-(3-oxo-1,2-dihydro-1, 2, 4-triazol-1-yl) phenyl urea;
- 3-Trifluoromethylphenyl-4-amino-2-(5-tetrazolyl) phenyl urea;
- 3-Trifluoromethylphenyl-4-acetylamino-2-(5-tetrazolyl) phenyl urea;
- 3-Trifluoromethylphenyl-4-benzoylamino-2-(5-tetrazolyl) phenyl urea;
- 3-Trifluoromethylphenyl-4-(4-carboxyphenyl)-2-(5-tetrazolyl) phenyl urea;
- 3-Trifluoromethylphenyl-4-(4-anilinocarbonylphenyl)-2-(5-tetrazolyl) phenyl urea;
- 4-Biphenylyl-2-(5-tetrazolyl) phenyl urea;
- 3-Biphenylyl-2-(5-tetrazolyl) phenyl urea;
- 5-indanyl-2-(5-tetrazolyl) phenyl urea;
- 3-Bromophenyl-4-bromo-2-(5-tetrazolyl) phenyl urea;
- 3-Acetylphenyl-2-(5-tetrazolyl) phenyl urea;
- 3-Biphenylyl-4-bromo-2-(5-tetrazolyl) phenyl urea;
- and
- 3-(3-Pyridyl) phenyl-4-bromo-2-(5-tetrazolyl) phenyl urea.
25 more elements
A compound selected from the group consisting of:
- 3-Trifluoromethylphenyl-4-bromo-2-(5-tetrazolyl) phenyl urea;
- 3-Trifluoromethylphenyl-2-(5-tetrazolyl) phenyl urea;
- 3-Trifluoromethylphenyl-4-phenyl-2-(5-tetrazolyl) phenyl urea;
- 4-Trifluoromethylphenyl-2-(5-tetrazolyl) phenyl urea;
- 3-Chlorophenyl-2-(5-tetrazolyl) phenyl urea;
- Phenyl-2-(5-tetrazolyl) phenyl urea;
- and
- 3-Trifluoromethylphenyl-4-amino-2-(5-tetrazolyl) phenyl urea.
5 more elements
Dependencies are inferred from the claim text.