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US 2010/0249069 A1Published application
S1p3 receptor inhibitors for treating pain
AssigneeAllergan, Inc.
InventorsJohn E. Donello, Richard L. Beard, Fabien J. Schweighoffer
Life of this patent
Estimating the term…
Abstract
Disclosed herein are compositions and methods for treating pain using S1P3 receptor inhibitors.
Claims8
-2. (canceled)
A method for treating pain, the method comprising the step of administering to a patient in need of such treatment a compound represented by the general formula
- wherein
- X is NR5, O, S;
- Z is O or S;
- n is 0 or an integer of from 1 to 4;
- o is 0 or an integer of from 1 to 3;
- p is 0 or an integer of from 1 to 4;
- A is (C(R5)2)m, wherein
- m is 0 or an integer of from 1 to 6;
- R5 is selected from the group consisting of hydrogen, straight or branched chain alkyl having 1 to 12 carbons, cycloalkyl having 3 to 6 carbons, alkenyl having 2 to 6 carbons and 1 or 2 double bonds, alkynyl having 2 to 6 carbons and 1 or 2 triple bonds, aryl, wherein said aryl is a carbocyclic aryl or heterocyclic aryl group wherein said carbocylic aryl comprises from 6 to 20 atoms and said heterocyclic aryl comprises from 2 to 20 carbon atoms and from 1 to 5 heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, halo, C1 to C12 haloalkyl, hydroxyl, C1 to C12 alkoxy, C1 to C12 alkylcarbonyl, formyl, oxycarbonyl, carboxy, C1 to C12 alkyl carboxylate, C1 to C12 alkyl amide, aminocarbonyl, amino, cyano, diazo, nitro, thio, sulfoxyl and sulfonyl groups;
- Y is a carbocyclic aryl or heterocyclic aryl group wherein said carbocylic aryl comprises from 6 to 20 atoms and said heterocyclic aryl comprises from 2 to 20 carbon atoms and from 1 to 5 heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, and wherein said aryl may be bonded to A at any position;
- R1, R2, R3, R4 are selected from the group consisting of hydrogen;
- straight or branched chain alkyl having 1 to 12 carbons;
- cycloalkyl having 3 to 6 carbons;
- alkenyl having 2 to 6 carbons and 1 or 2 double bonds;
- alkynyl having 2 to 6 carbons and 1 or 2 triple bonds;
- aryl wherein said aryl is a carbocyclic aryl or heterocyclic aryl group wherein said carbocylic aryl comprises from 6 to 20 atoms and said heterocyclic aryl comprises from 2 to 20 carbon atoms and from 1 to 5 heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur;
- halo;
- C1 to C12 haloalkyl;
- hydroxyl;
- C1 to C12 alkoxy;
- C3 to C20 arylalkyloxy;
- C1 to C12 alkylcarbonyl;
- formyl;
- oxycarbonyl;
- carboxy;
- C1 to C12 alkyl carboxylate;
- C1 to C12 alkyl amide;
- aminocarbonyl;
- amino;
- cyano;
- diazo;
- nitro;
- thio;
- sulfoxyl;
- sulfonyl groups;
- or a group selected from the group consisting of
- wherein R is CO2H or PO3H2, p is an integer of 1 or 2 and q is 0 or an integer of 1 to 5 and s is 0 or an integer of 1 or 2;
- provided that, if Y is phenyl, it must be substituted with at least one R4 group that is not hydrogen.
35 more elements
A method for treating pain, the method comprising the step of administering to a patient in need of such treatment a compound represented by the general formula I:
- wherein:
- R1R2, R3 and R4 are independently selected from the group consisting of hydrogen, straight or branched chain alkyl having 1 to 12 carbons, alkenyl having 2 to 6 carbons and 1 or 2 double bonds, alkynyl having 2 to 6 carbons and 1 or 2 triple bonds, carbocyclic hydrocarbon groups having from 3 to 20 carbon atoms, heterocyclic groups having up to 20 carbon atoms and at least one of oxygen, nitrogen and/or sulfur in the ring, halo, C1 to C12 haloalkyl, hydroxyl, C1 to C12 alkoxy, C3 to C20 arylalkyloxy, C1 to C12 alkylcarbonyl, formyl, oxycarbonyl, carboxy, C1 to C12 alkyl carboxylate, C1 to Cu alkyl amide, aminocarbonyl, amino, cyano, diazo, nitro, thio, sulfoxyl, and sulfonyl groups;
- X and X1 are independently selected from the group consisting of NR5, O and S;
- R5 is hydrogen, an alkyl group of 1 to 10 carbons, a cycloalkyl group of 5 to 10 carbons, phenyl or lower alkylphenyl;
- Y is a carbocyclic aryl or heterocyclic aryl group wherein said carbocylic aryl comprises from 6 to 20 atoms and said heterocyclic aryl comprises from 2 to 20 carbon atoms and from 1 to 5 heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, and wherein said aryl may be bonded to A at any position;
- Z is O or S;
- n is 0 or an integer of from 1 to 5;
- is 0 or an integer of from 1 to 3;
- p is 0 or an integer of from 1 to 3;
- q is 0 or 1;
- r is 0 or 1;
- A, A1 and A2 are independently selected from the group consisting of (CH2), wherein v is 0 or an integer of from 1 to 12, branched chain alkyl having 3 to 12 carbons, cycloalkyl having 3 to 12 carbons, alkenyl having 2 to 10 carbons and 1-3 double bonds and alkynyl having 2 to 10 carbons and 1 to 3 triple bonds;
- B is selected from the group consisting of hydrogen, OR6, COOR7, NR8R9, CONR8R9, COR10, CH═NOR11, CH═NNR12R13, wherein R6, R7, R10 and R11 are independently selected from the group consisting of hydrogen, straight or branched chain alkyl having 1 to 12 carbons, alkenyl having 2 to 6 carbons and 1 or 2 double bonds, alkynyl having 2 to 6 carbons and 1 or 2 triple bonds, a carbocyclic hydrocarbon group having from 3 to 20 carbon atoms, a heterocyclic group having up to 20 carbon atoms and at least one of oxygen, nitrogen and/or sulfur in the ring, R8, R9, R12 and R13 are independently selected from the group consisting of hydrogen, straight or branched chain alkyl having 1 to 12 carbons, alkenyl having 2 to 6 carbons and 1 or 2 double bonds, alkynyl having 2 to 6 carbons and 1 or 2 triple bonds, a carbocyclic hydrocarbon group having from 3 to 20 carbon atoms, a heterocyclic group having up to 20 carbon atoms and at least one of oxygen, nitrogen and/or sulfur in the ring, or R8 and R9 and/or R12 and R13, together, can form a divalent carbon radical of 2 to 5 carbons to form a heterocyclic R6, R7, R8, R9, R10, R11, R12 or R13 may be substituted with one or more halogen, hydroxy, alkyloxy, cyano, nitro, mercapto or thiol radical;
- provided however, when v is 0, and r is 0, B is not hydrogen;
- or B is a carbocyclic hydrocarbon group having from 3 to 20 carbon atoms, or a heterocyclic group having up to 20 carbon atoms and at least one of oxygen, nitrogen and/or sulfur in the ring, and wherein when said B is a carbocyclic or heterocyclic group B may be bonded to A2 at any position, or a pharmaceutically acceptable salt of said compound.
12 more elements
A method for treating pain, the method comprising the step of administering to a patient in need of such treatment a compound represented by the general formula
- wherein:
- A1 and A2 are independently selected from the group consisting of (CH2)m where m is 0 or an integer of from 1 to 6, lower branched chain alkyl having 2 to 6 carbons, cycloalkyl having 3 to 6 carbons, alkenyl having 2 to 6 carbons and 1 or 2 double bonds, alkynyl having 2 to 6 carbons and having 1 or 2 triple bonds, NR5, O and S;
- B is selected from the group consisting of (CH2)n, where n is 0 or an integer of from 1 to 6, lower branched chain alkyl having 2 to 6 carbons, cycloalkyl having 3 to 6 carbons, alkenyl having 2 to 6 carbons and 1 or 2 double bonds, alkynyl having 2 to 6 carbons and having 1 or 2 triple bonds, C═C(R5)2, C═O, C═S, R5C═NR5, R5C═CR5, C═NOR5, CR5OR5, C(OR5)2, CR5N(R5)2, C(N(R5)2)2, CR5SR5, C(SR5)2, SO, SO2, and heterocyclic aryl comprising from 2 to 14 carbon atoms and from 1 to 3 heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur;
- X is selected from the group consisting of (CH2)r, where r is 0 or an integer of from 1 to 6, lower branched chain alkyl having 2 to 6 carbons, cycloalkyl having 3 to 6 carbons, alkenyl having 2 to 6 carbons and 1 or 2 double bonds, alkynyl having 2 to 6 carbons and having 1 or 2 triple bonds, NR5, O and S;
- provided that when m is 0 and B is C═O then X is not NR5, O or S;
- Y is R6, or a carbocyclic aryl group comprising from 6 to 14 carbon atoms or a heterocyclic aryl group comprising from 2 to 14 carbon atoms and from 1 to 3 heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur;
- o is 0 or an integer of from 1 to 3;
- p is 0 or an integer of from 1 to 4;
- R1, R2, R3, R4 are independently selected from the group consisting of hydrogen, straight or branched chain alkyl having 1 to 12 carbons, cycloalkyl having 3 to 6 carbons, alkenyl having 2 to 6 carbons and 1 or 2 double bonds, alkynyl having 2 to 6 carbons and 1 or 2 triple bonds, aryl, halo, C1 to C12 haloalkyl, hydroxy, C1 to C12 alkoxy, C1 to C12 alkylcarbonyl, formyl, oxycarbonyl, carboxy, C1 to C12 alkyl carboxylate, C1 to C12 alkyl amide, aminocarbonyl, amino, cyano, diazo, nitro, thio, sulfoxyl, sulfonyl,
- wherein R is CO2H or PO3H2 and q is 0 or an integer of 1 to 5 and s is 0 or an integer from 1 to 3;
- R5 is selected from the group consisting of hydrogen, straight or branched chain alkyl having 1 to 12 carbons, cycloalkyl having 3 to 6 carbons, alkenyl having 2 to 6 carbons and 1 or 2 double bonds, alkynyl having 2 to 6 carbons and 1 or 2 triple bonds, aryl, halo, C1 to C12 haloalkyl, hydroxyl, C1 to C12 alkoxy, C1 to C12 alkylcarbonyl, formyl, oxycarbonyl, carboxy, C1 to C12 alkyl carboxylate, C1 to C12 alkyl amide, aminocarbonyl, amino, cyano, diazo, nitro, thio, sulfoxyl and sulfonyl;
- and
- R6 is selected from the group consisting of straight or branched chain alkyl having 1 to 12 carbons, cycloalkyl having 3 to 6 carbons, alkenyl having 2 to 6 carbons and 1 or 2 double bonds and alkynyl having 2 to 6 carbons and 1 or 2 triple bonds.
10 more elements
A method of treating pain, the method comprising the step of administering to a patient in need of such treatment a compound represented by the general formula
- wherein
- X is selected from the group consisting of CR3 and N;
- Y is selected from the group consisting of CR3 and N;
- Z is selected from the group consisting of CR3 and N;
- at least one of X, Y and Z is N;
- W is NR3 or O;
- R1 is an aryl group;
- R2 is an aryl group;
- R3 is selected from the group consisting of H and alkyl;
- and 2 of said R3 groups may together with N may form a heterocylic ring having from 2 to 6 carbon atoms;
- R4 is selected from the group consisting of H, alkyl, OR3, and N(R3)2;
- a is 0 or an integer of from 1 to 6;
- b is 0 or 1;
- c is 0 or an integer of from 1 to 6;
- d is 0 or 1;
- e is 0 or 1;
- u is 0 or 1;
- v is 0 or an integer of from 1 to 2;
- x is 0 or 1;
- y is 0 or an integer of from 1 to 3;
- z is 0 or an integer of from 1 to 3;
- provided, however, that when d is 0, e is 1, and when e is 0, d is 1.
19 more elements
(canceled)
A method for treating pain, the method comprising administering to a patient in need of such treatment a compound represented by the general formula:
- wherein R1 and R2 are each independently (CH2)n, wherein n is an integer from 1 to 4;
- A and B are each independently an aryl ring having 0, 1, 2, or 3 substituents consisting of from 0 to 8 carbon atoms, 0 to 3 oxygen atoms, 0 to 3 halogen atoms, 0 to 2 nitrogen atoms, 0 to 2 sulfur atoms, and from 0 to 24 hydrogen atoms;
- X and Y are each independently H, alkyl of 1 to 8 carbons, or hydroxyalkyl of 1 to 8 carbons;
- and
- Z is O or S.
2 more elements
(canceled)
Dependencies are inferred from the claim text.