Positive modulators of nicotinic acetylcholine receptors
OwnerChristopher Becker, Jeanne Comstock +5inventors
InventorsChristopher Becker, Jeanne Comstock, William Michne, Megan Murphy, Eifion Phillips, James Rosamond, Thomas Simpson
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Abstract
Compounds of Formula I or Formula II wherein R1, X and Ar are as described in the specification, 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.
Claims10
A method of treatment or prophylaxis of psychotic disorders, intellectual impairment disorders or diseases or conditions in which modulation of the α7 nicotinic receptor is beneficial, which method comprises administering a therapeutically-effective amount of a compound of Formula I or formula II:
- wherein:
- R1 is —OH, —N(R2)2, —NR2—SO2—R2, —SO2—N(R2)2, —CON(R2)2, or —NR2COR2 where R2 at each occurrence is independently selected from hydrogen, C1-4alkyl, halogenatedC1-4alkyl, aryl or heteroaryl where any alkyl, halogenated-alkyl, aryl or heteroaryl moiety is substituted with 0, 1, 2 or 3 R3 moieties;
- X is O, S or CH2;
- Ar is a moiety selected from furyl, pyridyl, thienyl, phenyl or naphthyl, said moiety having 0, 1, 2, 3 or more R3 substituents where R3 is at each occurrence independently selected from hydrogen, halogen, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, OC1-4alkyl, NH2, CO2H, CO2C1-4alklyl, CN, NO2, and CF3;
- or a diastereoisomer, enantiomer or pharmnaceutically-acceptable salt thereof.
A pharmaceutical composition comprising a compound according to Formula I or Formula II
- wherein:
- R1 is —OH, —N(R2)2, —NR2—SO2—R2, —SO2—N(R2)2, —CON(R2)2, or —NR2COR2 where R2 at each occurrence is independently selected from hydrogen, C1-4alkyl, halogenatedC1-4alkyl, aryl or heteroaryl where any alkyl, halogenated-alkyl, aryl or heteroaryl moiety is substituted with 0, 1, 2 or 3 R3 moieties;
- X is O, S or CH2;
- Ar is a moiety selected from furyl, pyridyl, thienyl, phenyl or naphthyl, said moiety having 0, 1, 2, 3 or more R3 substituents where R3 is at each occurrence independently selected from hydrogen, halogen, C1-4akyl, C2-4alkenyl, C2-4alkynyl, OC1-4alkyl, NH2, CO2H, CO2C1-4alkyl, CN, NO2, and CF3;
- or a diastereoisomer, enantiomner or pharmaceutically-acceptable salt thereof, together with at least one pharmaceutically-acceptable diluent or carrier.
(canceled)
A compound of Formula I or Formula II:
- wherein:
- R1 is NR2—SO2—R2 or —SO2—N(R2)2 where R2 at each occurrence is independently selected from hydrogen, C1-4alkyl, halogenatedC1-4alkyl, aryl or heteroaryl where any alkyl, halogenated-alkyl, aryl or heteroaryl moiety is substituted with 0, 1, 2 or 3 R3 moieties;
- X is O, S or CH2;
- Ar is a moiety selected from furyl, pyridyl, thienyl, phenyl or naphthyl, said moiety having 0, 1, 2, 3 or more R3 substituents where R3 is at each occunence independently selected from hydrogen, halogen, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, OC1-4alkyl, NH2, CO2H, CO2C1-4aklkyl, CN, NO2, and CF3;
- or a diastereoisomer, enantiomer or pharmaceutically-acceptable salt thereof.
A method of making a compound according to Formula I or Formula II
- wherein:
- R1 is NR2—SO2—R2 or —SO2—N(R2)2 where R2 at each occurrence is independently selected from hydrogen, C1-4alkyl, halogenatedC1-4alkyl, aryl or heteroaryl where any alkyl, halogenated-alkyl, aryl or heteroaryl moiety is substituted with 0, 1, 2 or 3 R3 moieties;
- X is O, S or CH2;
- Ar is a moiety selected from furyl, pyridyl, thienyl, phenyl or naphthyl, said moiety having 0, 1, 2, 3 or more R3 substituents where R3 is at each occurrence independently selected from hydrogen, halogen, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, OC1-4alkyl, NH2, CO2H, CO2C1-4alkyl, CN, NO2, and CF3;
- comprising:
- adding indium chloride to a solution of an arylaldehyde of formula Ar—CHO.
- a 4-aminobenzenesulfonamide of the following formula
- and cyclopentadiene or a compound of the following formula
- in acetonitrile and stirring overnight;
- neutralizing, extracting, concentrating and purifying to afford a quinoline of Formula I or Formula II.
Dependencies are inferred from the claim text.