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US 2008/0176843 A1Published application
Modulators of muscarinic receptors
AssigneeVertex Pharmaceuticals Incorporated
InventorsLewis R. Makings, Dennis J. Hurley, Gabriel Raffai
Life of this patent
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Abstract
The present invention relates to modulators of muscarinic receptors. The present invention also provides compositions comprising such modulators, and methods therewith for treating muscarinic receptor mediated diseases.
Claims81
A method of modulating activity of a muscarinic receptor, comprising the step of contacting said receptor with a compound of formula I:
- or a pharmaceutically acceptable salt thereof, wherein:
- X is —NR50— or —O—, wherein R50 is independently hydrogen or an optionally substituted C1-6 aliphatic;
- R1 is an optionally substituted aliphatic, an optionally substituted cycloaliphatic, or an optionally substituted heterocycloaliphatic;
- R2 is —ZBR5, wherein each ZB is independently a bond or an optionally substituted branched or straight C1-6 aliphatic chain wherein up to two carbon units of ZB are optionally and independently replaced by —CO—, —CS—, —CONRB, —CONRBNRB—, —CO2—, —OCO—, —NRBCO2—, —O—, —NRBCONRB—, —OCONRB—, —NRBNRB—, —NRBCO—, —S—, —SO—, —SO2—, —NRB—, —SO2NRB—, —NRBSO2—, or —NRBSO2NRB—;
- Each R5 is independently RB, halo, —OH, —NH2, —NO2, —CN, or —OCF3;
- and
- Each RB is independently hydrogen, optionally substituted C1-4 aliphatic, optionally substituted cycloaliphatic, optionally substituted heterocycloaliphatic, optionally substituted aryl, or optionally substituted heteroaryl;
- Each R3 is independently hydrogen, halo, nitro, cyano, hydroxy, optionally substituted aliphatic, optionally substituted (aliphatic)oxy, optionally substituted cycloaliphatic, optionally substituted heterocycloaliphatic, optionally substituted aryl, or optionally substituted heteroaryl;
- and
- n is 0-4.
7 more elements
A method of modulating activity of a muscarinic receptor, comprising the step of contacting said receptor with a compound selected from:
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A compound of formula Ia
- or a pharmaceutically acceptable salt thereof, wherein
- X is —NR50— or —O—,
- R50 is independently hydrogen or optionally substituted C1-6 aliphatic;
- R1a is optionally substituted aliphatic, optionally substituted cycloaliphatic, or optionally substituted heterocycloaliphatic;
- R2 is —ZBR5, wherein each ZB is independently a bond or an optionally substituted branched or straight C1-6 aliphatic chain wherein up to two carbon units of ZB are optionally and independently replaced by —CO—, —CS—, —CONRB—, —CONRBNRB—, —CO2—, —OCO—, —NRBCO2—, —O—, —NRBCONRB—, —OCONRB—, —NRBNRB—, —NRBCO—, —S—, —SO—, —SO2—, —NRB—, —SO2NRB—, —NRBSO2—, or —NRBSO2NRB—;
- Each R5 is independently RB, halo, —OH, —NH2, —NO2, —CN, or —OCF3;
- and
- Each RB is independently hydrogen, optionally substituted C1-4 aliphatic, optionally substituted cycloaliphatic, optionally substituted heterocycloaliphatic, optionally substituted aryl, or an optionally substituted heteroaryl;
- Each R3 is independently hydrogen, halo, optionally substituted aliphatic, optionally substituted (aliphatic)oxy, optionally substituted cycloaliphatic, optionally substituted heterocycloaliphatic, optionally substituted aryl, or optionally substituted heteroaryl;
- and
- n is 0-4,
- Provided that
- when R1a is substituted aliphatic, R1a is substituted with 1-3 of halo, cyano, nitro, hydroxy, —NH2, optionally substituted alkoxy, optionally substituted cycloaliphatic, or optionally substituted heterocycloaliphatic;
- when R1a is aliphatic substituted with a monocyclic heterocycloaliphatic, the monocyclic heterocycloaliphatic is not substituted with aryl;
- and
- when R1a is optionally substituted cycloaliphatic, R1a is not substituted with a substituted monocyclic heterocycloaliphic.
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A compound selected from:
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105 more elements
Dependencies are inferred from the claim text.