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US 6,413,947 B1Granted
Anilide derivative, production and use thereof
AssigneeTakeda Chemical Industries, Ltd.
InventorsMitsuru Shiraishi, Takahito Kitayoshi, Yoshio Aramaki, Susumu Honda, Tsuneo Oda
Life of this patent
Estimating the term…
Abstract
This invention is to provide a compound of the formula: wherein R1 is an optionally substituted 5- to 6-membered ring; W is a divalent group of the formula: wherein the ring A is an optionally substituted 5- to 6-membered aromatic ring, X is an optionally substituted C, N or O atom, and the ring B is an optionally substituted 5- to 7-membered ring; Z is a chemical bond or a divalent group; R2 is (1) an, optionally substituted amino group in which a nitrogen atom may form a quaternary ammonium, etc., or a salt thereof, which is useful for antagonizing MCP-1 receptor.
Claims18
A compound of the formula:
- wherein
- R1 is phenyl, furyl, thiophenyl, pyridyl, cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl or tetrahydropyranyl, each of which may be substituted,
- W is a divalent group of the formula:
- wherein the ring A is an optionally substituted 5- to 6-membered aromatic ring, X is an optionally substituted carbon atom, an optionally substituted nitrogen atom, sulfur atom or oxygen atom,
- Z is a chemical bond or a divalent group,
- R2 is (1) an optionally substituted amino group in which a nitrogen atom may form a quaternary ammonium, (2) an optionally substituted nitrogen-containing heterocyclic ring group which may contain a sulfur atom or an oxygen atom as ring constituting atoms and wherein a nitrogen atom may form a quaternary ammonium, (3) a group binding through a sulfur atom or (4) a group of the formula:
- wherein k is 0 or 1, and when k is 0, a phosphorus atom may form a phosphonium;
- and R5 and R6 are independently an optionally substituted hydrocarbon group or an optionally substituted amino group, or R5 and R6 may bind to each other to form a cyclic group together with the adjacent phosphorus atom,
- or a pharmaceutically acceptable salt thereof.
6 more elements
A compound of the formula:
- wherein
- R1 is an optionally substituted 5- to 6-membered ring,
- W is a divalent group of the formula:
- wherein the ring A is an optionally substituted 5- to 6-membered aromatic ring, X is an optionally substituted carbon atom, an optionally substituted nitrogen atom, sulfur atom or oxygen atom,
- Z is an optionally substituted C1-3 alkylene,
- R2 is (1) an optionally substituted amino group in which a nitrogen atom may form a quaternary ammonium, (2) an optionally substituted nitrogen-containing heterocyclic ring group which may contain a sulfur atom or an oxygen atom as ring constituting atoms and wherein a nitrogen atom may form a quaternary ammonium, (3) a group binding through a sulfur atom or (4) a group of the formula:
- wherein k is 0 or 1, and when k is 0, a phosphorus atom may form a phosphonium;
- and R5 and R6 are independently an optionally substituted hydrocarbon group or an optionally substituted amino group, or R5 and R6 may bind to each other to form a cyclic group together with the adjacent phosphorus atom,
- or a pharmaceutically acceptable salt thereof.
6 more elements
A method for producing a compound of the formula:
- wherein
- R1 is an optionally substituted 5- to 6-membered ring,
- W is a divalent group of the formula:
- wherein the ring A is an optionally substituted 5- to 6-membered aromatic ring, X is an optionally substituted carbon atom, an optionally substituted nitrogen atom, sulfur atom or oxygen atom,
- Z is a chemical bond or a divalent group,
- R2 is (1) an optionally substituted amino group in which a nitrogen atom may form a quaternary ammonium, (2) an optionally substituted nitrogen-containing heterocyclic ring group which may contain a sulfur atom or an oxygen atom as ring constituting atoms and wherein a nitrogen atom may form a quaternary ammonium, (3) a group binding through a sulfur atom or (4) a group of the formula:
- wherein k is 0 or 1, and when k is 0, a phosphorus atom may form a phosphonium;
- and R5 and R6 are independently an optionally substituted hydrocarbon group or an optionally substituted amino group, or R5 and R6 may bind to each other to form a cyclic group together with the adjacent phosphorus atom, or a pharmaceutically acceptable salt thereof, which comprises subjectinga compound of the formula:
- R1—W—COOH
- wherein R1 and W are defined above, a salt or a reactive derivative thereof to a condensation reaction with a compound of the formula:
- wherein Z is defined above and
- R2′ is (1) an optionally substituted amino group in which a nitrogen atom may form a quaternary ammonium, (2) an optionally substituted nitrogen-containing heterocyclic ring group which may contain a sulfur atom or an oxygen atom as ring constituting atoms and wherein a nitrogen atom may form a quaternary ammonium, (3) a group binding through a sulfur atom or (4) a group of the formula:
- wherein k is 0 or 1, and when k is 0, a phosphorus atom may form a phosphonium;
- and R5 and R6 are independently an optionally substituted hydrocarbon group or an optionally substituted amino group, or R5 and R6 may bind to each other to form a cyclic group together with the adjacent phosphorus atom, the above groups (1)-(4) being optionally protected, or a salt thereof, and, optionally, subjecting the obtained product to deprotection, oxidation, reduction and/or ammoniumation.
11 more elements
A pharmaceutical composition for antagonizing MCP-1 receptor, which comprises a compound of the formula:
- wherein
- R1 is an optionally substituted 5- to 6-membered ring,
- W is a divalent group of the formula:
- wherein the ring A is an optionally substituted 5- to 6-membered aromatic ring, X is an optionally substituted carbon atom, an optionally substituted nitrogen atom, sulfur atom or oxygen atom,
- Z is a chemical bond or a divalent group,
- R2 is (1) an optionally substituted amino group in which a nitrogen atom may form a quaternary ammonium, (2) an optionally substituted nitrogen-containing heterocyclic ring group which may contain a sulfur atom or an oxygen atom as ring constituting atoms and wherein a nitrogen atom may form a quaternary ammonium, (3) a group binding through a sulfur atom or (4) a group of the formula:
- wherein k is 0 or 1, and when k is 0, a phosphorus atom may form a phosphonium;
- and R5′ and R6′ are independently an optionally substituted hydrocarbon group, an optionally substituted hydroxy group or an optionally substituted amino group, or R5′ and R6′ may bind to each other to form a cyclic group together with the adjacent phosphorus atom,
- or a pharmaceutically acceptable salt thereof,
- together with a pharmaceutically acceptable carrier.
7 more elements
A method for antagonizing MCP-1 receptor which comprises administering to a mammal in need thereof an effective amount of a compound of the formula:
- wherein R1 is an optionally substituted 5- to 6-membered ring;
- W is a divalent group of the formula:
- wherein the ring A is an optionally substituted 5- to 6-membered aromatic ring, X is an optionally substituted carbon atom, an optionally substituted nitrogen atom, sulfur atom or oxygen atom,
- Z is a chemical bond or adivalent group;
- R2 is (1) an optionally substituted amino group in which a nitrogen atom may form a quaternary ammonium, (2) an optionally substituted nitrogen-containing heterocyclic ring group which may contain a sulfur atom or an oxygen atom as ring constituting atoms and wherein a nitrogen atom may form a quaternary ammonium, (3) a group binding through a sulfur atom or (4) a group of the formula:
- wherein k is 0 or 1, and when k is 0, a phosphorus atom may form a phosphonium;
- and R5′ and R6′ are independently an optionally substituted hydrocarbon group, an optionally substituted hydroxy group or an optionally substituted amino group, or R5′ and R6′ may bind to each other to form a cyclic group together with the adjacent phosphorus atom,
- or a pharmaceutically acceptable salt thereof.
5 more elements
A method for antagonizing MCP-1 receptor, which comprises administering to a mammal in need thereof an effective amount of a compound of the formula:
- wherein
- R1 is an optionally substituted 5- to 6-membered ring,
- W is a divalent group of the formula:
- wherein the ring A is an optionally substituted 5- to 6-membered aromatic ring, X is an optionally substituted carbon atom, an optionally substituted nitrogen atom, sulfur atom or oxygen atom,
- Z is a chemical bond or a divalent group,
- R2 is (1) an optionally substituted amino group in which a nitrogen atom may form a quaternary ammonium, (2) an optionally substituted nitrogen-containing heterocyclic ring group which may contain a sulfur atom or an oxygen atom as ring constituting atoms and wherein a nitrogen atom may form a quaternary ammonium, (3) a group binding through a sulfur atom or (4) a group of the formula:
- wherein k is 0 or 1, and when k is 0, a phosphorus atom may form a phosphonium;
- and R5 and R6 are independently an optionally substituted hydrocarbon group or an optionally substituted amino groups or R5 and R6 may bind to each other to form a cyclic group together with the adjacent phosphorus atom,
- or a pharmaceutically acceptable salt thereof.
6 more elements
A method for making a pharmaceutical composition for antagonizing MCP-1 receptor, comprising mixing a compound of the formula:
- wherein
- R1 is an optionally substituted 5- to 6-membered ring;
- W is a divalent group of the formula:
- wherein the ring A is an optionally substituted 5- to 6-membered aromatic ring, X is an optionally substituted carbon atom, an optionally substituted nitrogen atom, sulfur atom or oxygen atom,
- Z is a chemical bond or a divalent group,
- R2 is (1) an optionally substituted amino group in which a nitrogen atom may form a quaternary ammonium, (2) an optionally substituted nitrogen-containing heterocyclic ring group which may contain a sulfur atom or an oxygen atom as ring constituting atoms and wherein a nitrogen atom may form a quaternary ammonium, (3) a group binding through a sulfur atom or (4) a group of the formula:
- wherein k is 0 or 1, and when k is 0, a phosphorus atom may form a phosphonium;
- and R5′ and R6′ are independently an optionally substituted hydrocarbon group, an optionally substituted hydroxy group or an optionally substituted amino group, or R5′ and R6′ may bind to each other to form a cyclic group together with the adjacent phosphorus atom,
- or a pharmaceutically acceptable salt thereof,
- together with a pharmaceutically acceptable carrier.
7 more elements
Dependencies are inferred from the claim text.