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US 2004/0176416 A1Published application
Bridged bicyclic amine derivatives useful as CCR-3 receptor antagonists
AssigneeRoche Palo Alto LLC
InventorLeyi Gong
Life of this patent
Estimating the term…
Abstract
Compounds having the formula (I), Ar—(F)(E)-(CR3R4)—(CHR5)m-(T)-(Q)-Ar1, are useful as CCR-3 receptor antagonists, wherein T is a bridged heterocyclyl group having one N atom and a bridge of one to two bridgehead carbon atoms; Ar and Ar1 are aryl or heteroaryl; F is alkylene, alkenylene, or a bond; E is —C(═O)N(R10)—, —SO2N(R10)—, —N(R11)C(═O)N(R10O)—, —N(R11)SO2N(R10)—, —N(R11)C(═S)N(R10)—, —N(R11)C(═O)—, —N(R11)SO2—, —N(R12)C(═O)CH(R13)—, or CH(R13)C(═O)N(R12)—; Q is —C(═O)— or C1-2alkylene; and R3, R4, R5, R9, R10, R11, R12, and R13 are defined as set forth in the specification.
Claims20
A compound having the formula:
- Ar—(F)-(E)-(CR3R4)—(CHR5)m-(T)-(Q)-Ar1,
- wherein:
- T is
- 24
- where R6 is taken together with one of R7 and R8 to form a bridge of one to two bridgehead carbon atoms, and the other of R7 and R8 is selected from hydrogen and R9;
- Ar and Ar1 are, independently of each other, aryl or heteroaryl;
- F is alkylene, alkenylene, or a bond;
- E is selected from —C(═O)N(R10)—, —SO2N(R10)—, —N(R11)C(═O)N(R10)—, —N(R11)SO2N(R10)—, —N(R11)C(═S)N(R10)—, —N(R11)C(═O)—, —N(R1)SO2—, —N(R12)C(═O)CH(R13)—, and CH(R13)C(═O)N(R12)—, where:
- R10, R11, R12 , and R13 are, independently of each other, hydrogen, alkyl, acyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, aralkenyl, heteroaryl, heteroaralkyl, heterocycloalkyl, heteroalkyl, or -(alkylene)-C(═O)-Z, where Z is alkyl, haloalkyl, alkoxy, haloalkyloxy, hydroxy, amino, mono- or disubstituted amino, aryl, aralkyl, aryloxy, aralkyloxy, heteroaryl, heteroaryloxy, or heteroaralkyloxy;
- or alternatively, R12 and R13 may be taken together with the nitrogen and carbon atoms to which they are attached, respectively, to form a heterocyclyl or heteroaryl ring optionally substituted with up to two groups selected from R14;
- R3 and R4 are, independently of each other, hydrogen, alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, heterocyclylalkyl, heteroalkyl, -(alkylene)-C(═O)-Z1, or -(alkylene)-C(O)2Z1, where Z1 is alkyl, haloalkyl, alkoxy, haloalkyloxy, hydroxy, amino, mono- or disubstituted amino, aryl, aralkyl, aryloxy, aralkyloxy, heteroaryl, heteroaryloxy, or heteroaralkyloxy;
- R5 is hydrogen or alkyl;
- Q is —C(═O)— or C1-2alkylene;
- R9 is attached to any available carbon atom of ring T and is selected from lower alkyl, hydroxy, lower alkoxy, halo, cyano, trifluoromethyl, trifluoromethoxy, or a lower alkyl substituted with one of hydroxy, lower alkoxy, halo, cyano, trifluoromethyl, or trifluoromethoxy;
- R14 is selected from lower alkyl, hydroxy, lower alkoxy, halo, cyano, trifluoromethyl, trifluoromethoxy, and a lower alkyl substituted with one of hydroxy, lower alkoxy, halo, cyano, trifluoromethyl, or trifluoromethoxy;
- m is 0 or 1;
- and
- n is 0 to 4;
- and
- prodrugs, individual isomers, mixtures of isomers, and pharmaceutically acceptable salts thereof.
17 more elements
A compound having the formula (II):
- 29
- or a pharmaceutically-acceptable salt thereof, in which:
- T is
- 30
- where R6 is taken together with one of R7 and R8 to form a bridge of one to two bridgehead carbon atoms optionally substituted with one to two CH3, and the other of R7 and R8 is selected from hydrogen and lower alkyl;
- E is selected from —C(═O)N(R10)—, —N(R11)C(═O)N(R10)—, and —N(R12)C(═O)CH(R13)—, where:
- R10, R11, R12, and R13 are independently of each other hydrogen or lower alkyl, or alternatively, R12 and R13 may be taken together with the nitrogen and carbon atoms to which they are attached, respectively, to form a five-membered heterocyclyl or heteroaryl ring having up to two N atoms and optionally substituted with up to two groups selected from methyl, ethyl, hydroxy, methoxy, halo, cyano, trifluoromethyl, and trifluoromethoxy;
- is R4 is hydrogen, lower alkyl, or lower alkyl substituted with hydroxy;
- R20 and R21 are each independently selected from halo, OR22, and SO2R22, wherein R22 is lower alkyl;
- m is 0 or 1;
- p and q are independently 0, 1, 2 or 3.
8 more elements
Dependencies are inferred from the claim text.