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US 6,649,603 B2Granted
Cyclylamine sulfonamides as β3-adrenergic receptor agonists
AssigneeWyeth
InventorFuk-Wah Sum
Life of this patent
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Abstract
This invention provides compounds of Formula I having the structure wherein R1, R2, R3, W, X, and Z are as defined hereinbefore or a pharmaceutically acceptable salt thereof, which are useful in treating metabolic disorders related to insulin resistance or hyperglycemia.
Claims17
A compound of formula I having the structure
- wherein:
- W is (CH2)m;
- X is (CH2)n;
- Y is OCH2, SCH2, or a bond;
- Z is SO2, CO, or P(O)OR;
- R is alkyl or aryl;
- R1 is phenyl substituted with R4 and R5, or Het substituted with R4 and R5;
- R2 is hydrogen, trifluoromethyl, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms or cycloalkyl of 4-8 carbon atoms;
- R3 is alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, cycloalkyl of 4-8 carbon atoms, aryl substituted with R4 and R5, Het substituted with R4 and R5, aryloxy, —NHCOR7, —NR8R8, arylamino, Het-amino, arylalkylamino having 1-6 carbon atoms in the alkyl chain, Het-alkylamino having 1-6 carbon atoms in the alkyl chain, alkoxycarbonylalkyl of 3-13 carbon atoms, carboxyalkyl of 2-7 carbon atoms, alkylcarbonylalkyl of 3-13 carbon atoms, arylcarbonylalkyl having 1-6 carbon atoms in the alkyl chain, Het-carbonylalkyl having 1-6 carbon atoms in the alkyl chain, aminocarbonylalkyl of 2-7 carbon atoms, alkylaminocarbonylalkyl of 3-13 carbon atoms, arylaminocarbonylalkyl having 1-6 carbon atoms in the alkyl chain, Het-aminocarbonylalkyl having 1-6 carbon atoms in the alkyl chain, aminosulfonylalkyl of 1-6 carbon atoms, alkylsulfonylalkyl of 2-12 carbon atoms, arylsulfonylalkyl having 1-6 carbon atoms in the alkyl chain, alkylaminosulfonylalkyl of 2-12 carbon atoms, arylaminosulfonylalkyl having 1-6 carbon atoms in the alkyl chain, Het-aminosulfonylalkyl having 1-6 carbon atoms in the alkyl chain, phosphonylalkyl of 1-6 carbon atoms, or phosphorylalkyl of 1-6 carbon atoms;
- R4, and R5, are each, independently, hydrogen, trifluoromethyl, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, cycloalkyl of 4-8 carbon atoms, aryl, Het, arylalkyl having 1-6 carbon atoms in the alkyl chain, Het-alkyl having 1-6 carbon atoms in the alkyl chain, halogen, cyano, nitro, hydroxy, alkoxy of 1-6 carbon atoms, aryloxy, arylalkyloxy having 1-6 carbon atoms in the alkyl chain, alkylthio having 1-6 carbon atoms, arylthio, arylamino, Het-amino, arylalkylamino of 1-6 carbons in the alkyl chain, Het-alkylamino having 1-6 carbon atoms in the alkyl chain, hydroxyamino, —OSO2phenylbutoxy, —NHCOR7, —NHSO2R7, —NHP(O)(R7)2, —COR8, —SO2R8, —NR8R8, carboxy, alkylcarbonyl of 2-7 carbon atoms, phosphoryl, alkoxycarbonylalkyl of 3-13 carbon atoms, carboxyalkyl of 2-7 carbon atoms, alkylcarbonylalkyl of 2-13 carbon atoms, arylcarbonylalkyl having 1-6 carbon atoms in the alkyl chain, Het-carbonylalkyl having 1-6 carbon atoms in the alkyl chain, aminocarbonylalkyl of 2-7 carbon atoms, alkylaminocarbonylalkyl of 3-13 carbon atoms, arylaminocarbonylalkyl having 1-6 carbon atoms in the alkyl chain, Het-aminocarbonylalkyl having 1-6 carbon atoms in the alkyl chain, aminosulfonylalkyl of 1-6 carbon atoms, alkylsulfonylalkyl of 2-12 carbon atoms, arylsulfonylalkyl having 1-6 carbon atoms in the alkyl chain, alkylaminosulfonylalkyl of 2-12 carbon atoms, arylaminosulfonylalkyl of 1-6 carbon atoms, Het-aminosulfonylalkyl of 1-6 carbon atoms, phosphonylalkyl of 1-6 carbon atoms, or phosphorylalkyl of 1-6 carbon atoms;
- R7 is hydrogen, trifluoromethyl, alkyl of 1-6 carbon atoms, cycloalkyl of 4-8 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, aryl, alkoxy of 1-6 carbon atoms, —NR8R9, or —NR9(CH2)p—R8;
- R8 is hydrogen, alkoxy of 1-6 carbon atoms, alkyl of 1-6 carbon atoms, hydroxy, —(CH2)p—COR9, or —(CH2)p—R9;
- R9 is hydrogen, hydroxy, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, or —NR10R10;
- R10 is hydrogen, alkyl of 1-6 carbon atoms, aryl, or Het;
- Het is a monocyclic or bicyclic heterocycle of 5-10 ring atoms, having 1 to 4 heteroatoms selected from oxygen, nitrogen, or sulfur;
- wherein the heterocycle may be saturated, unsaturated, or partially unsaturated;
- and may be optionally fused to a phenyl ring;
- m is 1,2, or 3;
- n is 1,2, or 3;
- m+n is 2 or 3;
- p is 0 to 6;
- or a pharmaceutically acceptable salt thereof.
19 more elements
A pharmaceutical composition comprising
- a) at least one compound of formula I having the structure
- wherein:
- W is (CH2)m;
- X is (CH2)n;
- Y is OCH2, SCH2, or a bond;
- Z is SO2, CO, or P(O)OR;
- R is alkyl or aryl;
- R1 is phenyl substituted with R4 and R5, or Het substituted with R4 and R5;
- R2 is hydrogen, trifluoromethyl, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms or cycloalkyl of 4-8 carbon atoms;
- R3 is alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, cycloalkyl of 4-8 carbon atoms, aryl substituted with R4 and R5, Het substituted with R4 and R5, aryloxy, —NHCOR7, —NR8R8, arylamino, Het-amino, arylalkylamino having 1-6 carbon atoms in the alkyl chain, Het-alkylamino having 1-6 carbon atoms in the alkyl chain, alkoxycarbonylalkyl of 3-13 carbon atoms, carboxyalkyl of 2-7 carbon atoms, alkylcarbonylalkyl of 3-13 carbon atoms, arylcarbonylalkyl having 1-6 carbon atoms in the alkyl chain, Het-carbonylalkyl having 1-6 carbon atoms in the alkyl chain, aminocarbonylalkyl of 2-7 carbon atoms, alkylaminocarbonylalkyl of 3-13 carbon atoms, arylaminocarbonylalkyl having 1-6 carbon atoms in the alkyl chain, Het-aminocarbonylalkyl having 1-6 carbon atoms in the alkyl chain, aminosulfonylalkyl of 1-6 carbon atoms, alkylsulfonylalkyl of 2-12 carbon atoms, arylsulfonylalkyl having 1-6 carbon atoms in the alkyl chain, alkylaminosulfonylalkyl of 2-12 carbon atoms, arylaminosulfonylalkyl having 1-6 carbon atoms in the alkyl chain, Het-aminosulfonylalkyl having 1-6 carbon atoms in the alkyl chain, phosphonylalkyl of 1-6 carbon atoms, or phosphorylalkyl of 1-6 carbon atoms;
- R4, and R5, are each, independently, hydrogen, trifluoromethyl, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, cycloalkyl of 4-8 carbon atoms, aryl, Het, arylalkyl having 1-6 carbon atoms in the alkyl chain, Het-alkyl having 1-6 carbon atoms in the alkyl chain, halogen, cyano, nitro, hydroxy, alkoxy of 1-6 carbon atoms, aryloxy, arylalkyloxy having 1-6 carbon atoms in the alkyl chain, alkylthio 1-6 carbon atoms, arylthio, arylamino, Het-amino, arylalkylamino of 1-6 carbons in the alkyl chain, Het-alkylamino having 1-6 carbon atoms in the alkyl chain, hydroxyamino, —OSO2phenylbutoxy, —NHCOR7, —NHSO2R7, —NHP(O)(R7)2, —COR8, —SO2R8, —NR8R8, carboxy, alkylcarbonyl of 2-7 carbon atoms, phosphoryl, alkoxycarbonylalkyl of 3-13 carbon atoms, carboxyalkyl of 2-7 carbon atoms, alkylcarbonylalkyl of 2-13 carbon atoms, arylcarbonylalkyl having 1-6 carbon atoms in the alkyl chain, Het-carbonylalkyl having 1-6 carbon atoms in the alkyl chain, aminocarbonylalkyl of 2-7 carbon atoms, alkylaminocarbonylalkyl of 3-13 carbon atoms, arylaminocarbonylalkyl having 1-6 carbon atoms in the alkyl chain, Het-aminocarbonylalkyl having 1-6 carbon atoms in the alkyl chain, aminosulfonylalkyl of 1-6 carbon atoms, alkylsulfonylalkyl of 2-12 carbon atoms, arylsulfonylalkyl having 1-6 carbon atoms in the alkyl chain, alkylaminosulfonylalkyl of 2-12 carbon atoms, arylaminosulfonylalkyl of 1-6 carbon atoms, Het-aminosulfonylalkyl of 1-6 carbon atoms, phosphonylalkyl of 1-6 carbon atoms, or phosphorylalkyl of 1-6 carbon atoms
- R7 is hydrogen, trifluoromethyl, alkyl of 1-6 carbon atoms, cycloalkyl of 4-8 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, aryl, alkoxy of 1-6 carbon atoms, —NR8R9, or —NR9(CH2)p—R8
- R8 is hydrogen, alkoxy of 1-6 carbon atoms, alkyl of 1-6 carbon atoms, hydroxy, —(CH2)p—COR9, or —(CH2)p—R9;
- R9 is hydrogen, hydroxy, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, or —NR10R10;
- R10 is hydrogen, alkyl of 1-6 carbon atoms, aryl, or Het;
- Het is a monocyclic or bicyclic heterocycle of 5-10 ring atoms, having 1-4 heteroatoms selected from oxygen, nitrogen, and sulfur;
- wherein the heterocycle may be saturated, unsaturated, or partially unsaturated;
- and may be optionally fused to a phenyl ring;
- m is 1, 2 or 3,
- n is 1,2 or 3;
- m+n is 2 or 3;
- p is 0-6;
- or a pharmaceutically acceptable salt thereof;
- and
- b) at least one pharmaceutical carrier.
22 more elements
Dependencies are inferred from the claim text.