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US 7,064,143 B1Granted
Positive modulators of nicotinic receptor agonists
AssigneeAstraZeneca AB
InventorsDavid Gurley, James Rosamond
Life of this patent
Estimating the term…
Abstract
Compounds of Formula I wherein R1, R2, R3, R4, R5, W and X as defined in the specification, enantiomers thereof, pharmaceutically-acceptable salts thereof, processes for preparing them, pharmaceutical compositions containing them and their use in therapy, especially for treatment of conditions associated with reductions in nicotinic transmission. Compounds of the invention enhance the efficacy of agonists at nicotinic receptors.
Claims6
A compound of Formula I:
- wherein:
- R1 is selected from hydrogen, C1–C4alkyl, C2–C4alkenyl or C2–C4alkynyl;
- W is selected from C(O)O or C(O)NR6;
- R2 is selected from hydrogen, C1–C4alkyl, Ar, or (CH2)pCH[(CH2)qR7](CH2)tR8;
- R3 is hydrogen;
- R5 is selected from hydrogen or C1–C4alkyl;
- X is selected from oxygen, or NH;
- R4 is selected from C1–C4alkyl;
- R6 is selected from hydrogen, C1–C4alkyl or aryl;
- R7 and R8 are independently selected from hydrogen, halogen, OR10, NR10R11, C(O)OR10, OC(O)R10, C(O)NR10R11, NR10C(O)R11, SO2NR10R11, or NR10SO2R11;
- Ar is selected from phenyl or naphthyl;
- Ar is optionally substituted with one or more substituents independently selected from:
- hydrogen, halogen, C1–C4alkyl, C2–C4alkenyl, C2–C4alkynyl, (CH2)naryl, CN, NO2, CF3, OR12, NR12R13 and COOR12;
- R10, R11, R12 and R13 are independently at each occurrence selected from hydrogen, C1–C4alkyl or aryl;
- j is 2–4;
- n, p, q and t are independently 0–2;
- R14 is selected from hydrogen, C1–C4alkyl, aryl or heteroaryl;
- or an enantiomer thereof, or a pharmaceutically-acceptable salt thereof.
15 more elements
A compound selected from:
- ethyl 4-hydroxy-1-methyl-1H-indole-2-carboxylate;
- 4-hydroxy-1-methyl-1H-indole-2-carboxylic acid;
- N-phenethyl 4-hydroxy-1-methyl-1H-indole-2-carboxamide;
- N-methyl-N-phenethyl 4-hydroxy-1-methyl-1H-indole-2-carboxamide;
- N-(4-dimethylaminobenzyl) 4-hydroxy-1-methyl-1H-indole-2-carboxamide;
- N-(4-chlorobenzyl) 4-hydroxy-1-methyl-1H-indole-2-carboxamide;
- N-benzyl 4-hydroxy-1-methyl-1H-indole-2-carboxamide;
- N-(4-phenylbutyl) 4-hydroxy-1-methyl-1H-indole-2-carboxamide;
- N-(3-phenylpropyl) 4-hydroxy-1-methyl-1H-indole-2-carboxamide;
- N-phenyl 4-hydroxy-1-methyl-1H-indole-2-carboxamide;
- N-(4-chlorophenyl) 4-hydroxy-1-methyl-1H-indole-2-carboxamide;
- N-(3-biphenyl) 4-hydroxy-1-methyl-1H-indole-2-carboxamide;
- N-ethyl 4-hydroxy-1-methyl-1H-indole-2-carboxamide;
- 4-hydroxy-1-methyl-2-(pyrrolidin-1-ylcarbonyl)-1H-indole;
- N-(1-fluoromethyl-2-phenylethyl) 4-hydroxy-1-methyl-1H-indole-2-carboxamide;
- (R)-N-(2-hydroxy-1-phenylethyl) 4-hydroxy-1-methyl-] H-indole-2-carboxamide;
- (S)-N-(2-azido-1-benzylethyl) 4-hydroxy-1-methyl-1H-indole-2-carboxamide;
- N-(2-fluoroethyl) 4-hydroxy-1-methyl-1H-indole-2-carboxamide, or
- (R)-N-(2-fluoro-3-phenylpropyl) 4-hydroxy-1-methyl-1H-indole-2-carboxamide;
- or an enantiomer thereof, or a pharmaceutically-acceptable salt thereof.
17 more elements
Dependencies are inferred from the claim text.