US RE44,874 E1Granted

Phenethanolamine derivatives for treatment of respiratory diseases

AssigneeGlaxo Group Limited

InventorsPhilip Charles Box, Diane Mary Coe, Brian Edgar Looker, Panayiotis Alexandrou Procopiou

Life of this patent

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Abstract

The present invention relates to novel compounds of formula (I), to a process for their manufacture, to pharmaceutical compositions containing them, and to their use in therapy, in particular their use in the prophylaxis and treatment of respiratory diseases

Claims30

Dependent claims

A compound of formula (I)

or a salt, solvate, or physiologically functional derivative thereof, wherein:
m is an integer of from 2 to 8;
n is an integer of from 2 to 5;
with the proviso that m+n is 4 to 10;
R1 is selected from hydrogen, C1-6alkyl, hydroxy, halo, C1-6haloalkyl, —XC(O)NR9R10, —XNR8C(O)R9, —XNR8C(O)NR9R10, —XNR8SO2R9, —XSO2NR11R12, XNR8SO2R9R10, —XNR9R10, XN+R8R9R10, —XNR8C(O)OR9, —XCO2R9, —XNR8C(O)NR8C(O)NR9R10, —XSR9, XSOR9, and —XSO2R9;
or R1 is selected from —X-aryl, —X-hetaryl, and —X-(aryloxy), each optionally substituted by 1 or 2 groups independently selected from hydroxy, C1-6alkoxy, halo, C1-6alkyl, C1-6haloalkyl, —NHC(O)(C1-6alkyl), —SO2(C1-6alkyl), —SO2(aryl), —SO2NH2, —SO2NH(C1-6alkyl), —SO2NH(C3-7cycloalkyl), —CO2H, —CO2(C1-6alkyl), —SO2NH(C3-7cycloalkylC1-6alkyl), —NH2, —NH(C1-6alkyl), or hetaryl optionally substituted by 1 or 2 groups independently selected from hydroxy, C1-6alkoxy, halo, C1-6alkyl, or C1-6haloalkyl;
X is —(CH2)p— or C2-6 alkenylene;
p is an integer from 0 to 6,
R8 and R9 are independently selected from hydrogen, C1-6alkyl, C3-7cycloalkyl, aryl, hetaryl, hetaryl(C1-6alkyl)- and aryl(C1-6alkyl)- and R8 and R9 are each independently optionally substituted by 1 or 2 groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, —NHC(O)(C1-6alkyl), —SO2(C1-6alkyl), —SO2(aryl), —CO2H, —CO2(C1-4alkyl), —NH2, —NH(C1-6alkyl), aryl(C1-6alkyl)-, aryl(C2-6alkenyl)-, aryl(C2-6alkynyl)-, hetaryl(C1-6alkyl)-, —NHSO2aryl, —NH(hetarylC1-6alkyl), —NHSO2hetaryl, —NHSO2(C1-6alkyl), —NHC(O)aryl, or —NHC(O)hetaryl:
R10 is selected from hydrogen, C1-6alkyl and C3-7cycloalkyl;
R11 and R12 are independently selected from hydrogen, C1-6alkyl, C3-7cycloalkyl, aryl, hetaryl, hetaryl(C1-6alkyl)- and aryl(C1-6alkyl)-, or R11 and R12,together with the nitrogen to which they are bonded, form a 5-, 6-, or 7-membered nitrogen containing ring;
and R11 and R12 are each optionally substituted by one or two groups independently selected from halo, C1-6alkyl, and C1-6haloalkyl;
where R1 is —XNR8C(O)NR9R10, R8 and R9 may, together with the —NC(O)N— portion of the group R1 to which they are bonded, form a 5-, 6- or 7-membered saturated or unsaturated ring;
where R1 is —XNR8C(O)OR9, R8 and R9 may, together with the —NC(O)O— portion of the group R1 to which they are bonded, form a 5-, 6- or 7-membered saturated or unsaturated ring;
where R1 is —XC(O)NR9R10 or —XNR8C(O)NR9R10, R9 and R10 may, together with the nitrogen to which they are bonded, form a 5-, 6-, or 7-membered nitrogen containing ring;
R2 is selected from hydrogen, hydroxy, C1-6alkyl, C1-6alkoxy, halo, aryl, aryl(C1-6alkyl)-, C1-6haloalkoxy, and C1-6 haloalkyl;
R3 is selected from hydrogen, hydroxy, C1-6alkyl, C1-6alkoxy, halo, aryl, aryl(C1-6alkyl)-, C1-6haloalkoxy, and C1-6haloalkyl;
R4 and R5 are independently selected from hydrogen and C1-4 alkyl with the proviso that the total number of carbon atoms in R4 and R5 is not more than 4;
and,
R6 and R7 are independently selected from hydrogen and C1-4alkyl with the proviso that the total number of carbon atoms in R4 and R5is R6 and R7 is not more than 4.

17 more elements

A compound of formula (I)

or a salt, solvate, or physiologically functional derivative thereof, wherein:
m is an integer of from 2 to 8;
n is an integer of from 2 to 5;
with the proviso that m+n is 4 to 10;
R1 is selected from hydrogen, C1-6alkyl, hydroxy, halo, C1-6haloalkyl, —XC(O)NR9R10, —XNR8C(O)R9, —XNR8C(O)NR9R10, —XNR8SO2R9, —XSO2NR11R12;, —XNR9R10, —XNR8C(O)OR9,
or R1 is selected from —X-aryl, —X-hetaryl, or —X-(aryloxy), each optionally substituted by 1 or 2 groups independently selected from hydroxy, C1-6alkoxy, halo, C1-6alkyl, C1-6haloalkyl, —NHC(O)(C1-6alkyl), —SO2(C1-6alkyl), —SO2(aryl), —SO2NH2, —SO2NH(C1-6alkyl), —SO2NH(C3-7cycloalkyl), —CO2H, —CO2(C1-6alkyl), —SO2NH(C3-7cycloalkylC1-6alkyl), —NH2, —NH(C1-6alkyl), or hetaryl optionally substituted by 1 or 2 groups independently selected from hydroxy, C1-6alkoxy, halo, C1-6alkyl, or C1-6haloalkyl;
X is —(CH2)p— or C2-6 alkenylene;
p is an integer from 0 to 6,;
R8 and R9 are independently selected from hydrogen, C1-6alkyl, C3-7cycloalkyl, aryl, hetaryl, hetaryl(C1-6alkyl)- and aryl(C1-6alkyl)- and R8 and R9 are each independently optionally substituted by 1 or 2 groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, —NHC(O)(C1-6alkyl), —SO2(C1-6alkyl), —SO2(aryl), —CO2H, and —CO2(C1-4alkyl), —NH2, —NH(C1-6alkyl), aryl(C1-6alkyl)-, aryl(C2-6alkenyl)-, aryl(C2-6alkynyl)-, hetaryl(C1-6alkyl)-, —NHSO2aryl, —NH(hetarylC1-6alkyl), —NHSO2hetaryl, —NHSO2(C1-6alkyl), —NHC(O)aryl, or —NHC(O)hetaryl:
R10 is selected from hydrogen, C1-6alkyl and C3-7cycloalkyl;
R11 and R12 are independently selected from hydrogen, C1-6alkyl, C3-7cycloalkyl, aryl, hetaryl, hetaryl(C1-6alkyl)- and aryl(C1-6alkyl)-, or R11 and R12, together with the nitrogen to which they are bonded, form a 5-, 6-, or 7-membered nitrogen containing ring;
and R11 and R12 are each optionally substituted by one or two groups independently selected from halo, C1-6alkyl, and C1-6haloalkyl;
where R1 is —XNR8C(O)NR9R10, R8 and R9 may, together with the portion —NC(O)N— of the group R1 to which they are bonded, form a 5-, 6-, or 7-membered saturated or unsaturated ring;
where R1 is —XNR8C(O)OR9, R8 and R9 may, together with the portion —NC(O)O— of the group R1 to which they are bonded, form a 5-, 6-, or 7-membered saturated or unsaturated ring;
where R1 is —XC(O)NR9R10 or —XNR8C(O)NR9R10, R9 and R10 may, together with the nitrogen to which they are bonded, form a 5-, 6-, or 7-membered nitrogen containing ring;
R2 is selected from hydrogen, hydroxy, C1-6alkyl, C1-6alkoxy, halo, aryl, aryl(C1-6alkyl)-, C1-6haloalkoxy, and C1-6 haloalkyl;
R3 is selected from hydrogen, hydroxy, C1-6alkyl, C1-6alkoxy, halo, aryl, aryl(C1-6alkyl)-, C1-6haloalkoxy, and C1-6haloalkyl;
R4 and R5 are independently selected from hydrogen and C1-4 alkyl with the proviso that the total number of carbon atoms in R4 and R5 is not more than 4;
and,
R6 and R7 are independently selected from hydrogen and C1-4alkyl with the proviso that the total number of carbon atoms in R4 and R5 is not more than 4.

17 more elements

Dependencies are inferred from the claim text.

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US RE44,874 E1Granted

Phenethanolamine derivatives for treatment of respiratory diseases

AssigneeGlaxo Group Limited

InventorsPhilip Charles Box, Diane Mary Coe, Brian Edgar Looker, Panayiotis Alexandrou Procopiou

Life of this patent

Estimating the term…

Abstract

Claims30

Dependent claims

A compound of formula (I)

or a salt, solvate, or physiologically functional derivative thereof, wherein:
m is an integer of from 2 to 8;
n is an integer of from 2 to 5;
with the proviso that m+n is 4 to 10;
R1 is selected from hydrogen, C1-6alkyl, hydroxy, halo, C1-6haloalkyl, —XC(O)NR9R10, —XNR8C(O)R9, —XNR8C(O)NR9R10, —XNR8SO2R9, —XSO2NR11R12, XNR8SO2R9R10, —XNR9R10, XN+R8R9R10, —XNR8C(O)OR9, —XCO2R9, —XNR8C(O)NR8C(O)NR9R10, —XSR9, XSOR9, and —XSO2R9;
or R1 is selected from —X-aryl, —X-hetaryl, and —X-(aryloxy), each optionally substituted by 1 or 2 groups independently selected from hydroxy, C1-6alkoxy, halo, C1-6alkyl, C1-6haloalkyl, —NHC(O)(C1-6alkyl), —SO2(C1-6alkyl), —SO2(aryl), —SO2NH2, —SO2NH(C1-6alkyl), —SO2NH(C3-7cycloalkyl), —CO2H, —CO2(C1-6alkyl), —SO2NH(C3-7cycloalkylC1-6alkyl), —NH2, —NH(C1-6alkyl), or hetaryl optionally substituted by 1 or 2 groups independently selected from hydroxy, C1-6alkoxy, halo, C1-6alkyl, or C1-6haloalkyl;
X is —(CH2)p— or C2-6 alkenylene;
p is an integer from 0 to 6,
R8 and R9 are independently selected from hydrogen, C1-6alkyl, C3-7cycloalkyl, aryl, hetaryl, hetaryl(C1-6alkyl)- and aryl(C1-6alkyl)- and R8 and R9 are each independently optionally substituted by 1 or 2 groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, —NHC(O)(C1-6alkyl), —SO2(C1-6alkyl), —SO2(aryl), —CO2H, —CO2(C1-4alkyl), —NH2, —NH(C1-6alkyl), aryl(C1-6alkyl)-, aryl(C2-6alkenyl)-, aryl(C2-6alkynyl)-, hetaryl(C1-6alkyl)-, —NHSO2aryl, —NH(hetarylC1-6alkyl), —NHSO2hetaryl, —NHSO2(C1-6alkyl), —NHC(O)aryl, or —NHC(O)hetaryl:
R10 is selected from hydrogen, C1-6alkyl and C3-7cycloalkyl;
R11 and R12 are independently selected from hydrogen, C1-6alkyl, C3-7cycloalkyl, aryl, hetaryl, hetaryl(C1-6alkyl)- and aryl(C1-6alkyl)-, or R11 and R12,together with the nitrogen to which they are bonded, form a 5-, 6-, or 7-membered nitrogen containing ring;
and R11 and R12 are each optionally substituted by one or two groups independently selected from halo, C1-6alkyl, and C1-6haloalkyl;
where R1 is —XNR8C(O)NR9R10, R8 and R9 may, together with the —NC(O)N— portion of the group R1 to which they are bonded, form a 5-, 6- or 7-membered saturated or unsaturated ring;
where R1 is —XNR8C(O)OR9, R8 and R9 may, together with the —NC(O)O— portion of the group R1 to which they are bonded, form a 5-, 6- or 7-membered saturated or unsaturated ring;
where R1 is —XC(O)NR9R10 or —XNR8C(O)NR9R10, R9 and R10 may, together with the nitrogen to which they are bonded, form a 5-, 6-, or 7-membered nitrogen containing ring;
R2 is selected from hydrogen, hydroxy, C1-6alkyl, C1-6alkoxy, halo, aryl, aryl(C1-6alkyl)-, C1-6haloalkoxy, and C1-6 haloalkyl;
R3 is selected from hydrogen, hydroxy, C1-6alkyl, C1-6alkoxy, halo, aryl, aryl(C1-6alkyl)-, C1-6haloalkoxy, and C1-6haloalkyl;
R4 and R5 are independently selected from hydrogen and C1-4 alkyl with the proviso that the total number of carbon atoms in R4 and R5 is not more than 4;
and,
R6 and R7 are independently selected from hydrogen and C1-4alkyl with the proviso that the total number of carbon atoms in R4 and R5is R6 and R7 is not more than 4.

17 more elements

A compound of formula (I)

or a salt, solvate, or physiologically functional derivative thereof, wherein:
m is an integer of from 2 to 8;
n is an integer of from 2 to 5;
with the proviso that m+n is 4 to 10;
R1 is selected from hydrogen, C1-6alkyl, hydroxy, halo, C1-6haloalkyl, —XC(O)NR9R10, —XNR8C(O)R9, —XNR8C(O)NR9R10, —XNR8SO2R9, —XSO2NR11R12;, —XNR9R10, —XNR8C(O)OR9,
or R1 is selected from —X-aryl, —X-hetaryl, or —X-(aryloxy), each optionally substituted by 1 or 2 groups independently selected from hydroxy, C1-6alkoxy, halo, C1-6alkyl, C1-6haloalkyl, —NHC(O)(C1-6alkyl), —SO2(C1-6alkyl), —SO2(aryl), —SO2NH2, —SO2NH(C1-6alkyl), —SO2NH(C3-7cycloalkyl), —CO2H, —CO2(C1-6alkyl), —SO2NH(C3-7cycloalkylC1-6alkyl), —NH2, —NH(C1-6alkyl), or hetaryl optionally substituted by 1 or 2 groups independently selected from hydroxy, C1-6alkoxy, halo, C1-6alkyl, or C1-6haloalkyl;
X is —(CH2)p— or C2-6 alkenylene;
p is an integer from 0 to 6,;
R8 and R9 are independently selected from hydrogen, C1-6alkyl, C3-7cycloalkyl, aryl, hetaryl, hetaryl(C1-6alkyl)- and aryl(C1-6alkyl)- and R8 and R9 are each independently optionally substituted by 1 or 2 groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, —NHC(O)(C1-6alkyl), —SO2(C1-6alkyl), —SO2(aryl), —CO2H, and —CO2(C1-4alkyl), —NH2, —NH(C1-6alkyl), aryl(C1-6alkyl)-, aryl(C2-6alkenyl)-, aryl(C2-6alkynyl)-, hetaryl(C1-6alkyl)-, —NHSO2aryl, —NH(hetarylC1-6alkyl), —NHSO2hetaryl, —NHSO2(C1-6alkyl), —NHC(O)aryl, or —NHC(O)hetaryl:
R10 is selected from hydrogen, C1-6alkyl and C3-7cycloalkyl;
R11 and R12 are independently selected from hydrogen, C1-6alkyl, C3-7cycloalkyl, aryl, hetaryl, hetaryl(C1-6alkyl)- and aryl(C1-6alkyl)-, or R11 and R12, together with the nitrogen to which they are bonded, form a 5-, 6-, or 7-membered nitrogen containing ring;
and R11 and R12 are each optionally substituted by one or two groups independently selected from halo, C1-6alkyl, and C1-6haloalkyl;
where R1 is —XNR8C(O)NR9R10, R8 and R9 may, together with the portion —NC(O)N— of the group R1 to which they are bonded, form a 5-, 6-, or 7-membered saturated or unsaturated ring;
where R1 is —XNR8C(O)OR9, R8 and R9 may, together with the portion —NC(O)O— of the group R1 to which they are bonded, form a 5-, 6-, or 7-membered saturated or unsaturated ring;
where R1 is —XC(O)NR9R10 or —XNR8C(O)NR9R10, R9 and R10 may, together with the nitrogen to which they are bonded, form a 5-, 6-, or 7-membered nitrogen containing ring;
R2 is selected from hydrogen, hydroxy, C1-6alkyl, C1-6alkoxy, halo, aryl, aryl(C1-6alkyl)-, C1-6haloalkoxy, and C1-6 haloalkyl;
R3 is selected from hydrogen, hydroxy, C1-6alkyl, C1-6alkoxy, halo, aryl, aryl(C1-6alkyl)-, C1-6haloalkoxy, and C1-6haloalkyl;
R4 and R5 are independently selected from hydrogen and C1-4 alkyl with the proviso that the total number of carbon atoms in R4 and R5 is not more than 4;
and,
R6 and R7 are independently selected from hydrogen and C1-4alkyl with the proviso that the total number of carbon atoms in R4 and R5 is not more than 4.

17 more elements

Dependencies are inferred from the claim text.