US 8,618,144 B2Granted

Pyrrolidine-derived beta 3 adrenergic receptor agonists

AssigneeMerck Sharp & Dohme Corp.

InventorsPeter Lin, Lehua Chang, Scott D. Edmondson

Life of this patent

Estimating the term…

Abstract

The present invention provides compounds of Formula (I), pharmaceutical compositions thereof, and method of using the same in the treatment or prevention of diseases mediated by the activation of β3-adrenoceptor.

Claims15

Dependent claims

A compound of Formula I, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt of the stereoisomer thereof:

wherein
m is 0, 1, 2, 3, or 4;
n is 0, 1, 2, 3, 4, or 5;
p is 0, 1, or 2;
q is 0, 1, 2, 3, or 4;
X is —CO— or —SO2—;
Y is selected from the group consisting of:
(1) C1-C3 alkylene, optionally substituted with —NR2R2 or hydroxy,
(2) —N(R6)—,
(3) —O—,
(4) a bond, and
(5) phenylene, optionally substituted with 1 to 3 groups independently selected from R1;
Z is selected from the group consisting of:
(4) a 5- or 6-membered heterocyclic ring with from 1 to 4 heteroatoms selected from oxygen, sulfur and nitrogen,
R1 is selected from the group consisting of:
(1) C1-C10 alkyl, optionally substituted with 1 to 5 groups selected from the group consisting of:
(a) hydroxy,
(b) halogen,
(c) cyano,
(d) QR2,
(e) C3-C8 cycloalkyl,
(f) Q′COR3,
(g) —S(O)p—NR2R2,
(h) —N(R2)SO2R3, and
(i) Q′CO2R2,
(2) C3-C8 cycloalkyl,
(3) oxo,
(4) halogen,
(5) cyano,
(6) QR2,
(7) —S(O)p—NR2R2,
(8) Q′COR3,
(9) —N(R2)SO2R3,
(10) Q′CO2R2, and
(11) Z, optionally substituted with 1 to 5 groups selected from the group consisting of:
(a) R2,
(b) QR2,
(e) halogen, and
(d) oxo;
R2 is selected from the group consisting of
(1) hydrogen,
(2) C1-C10 alkyl, optionally substituted with 1 to 5 groups selected from the group consisting of:
(a) hydroxy,
(b) halogen,
(c) —CO2R4,
(d) —S(O)p—C1-C10 alkyl,
(e) C3-C8 cycloalkyl,
(f) C1-C10 alkoxy, optionally substituted with 1 to 5 halogens, and
(g) Z, optionally substituted with 1 to 5 groups selected from the group consisting of halogen, trifluoromethyl, trifluoromethoxy, C1-C10 alkyl and C1-C10 alkoxy;
(3) C3-C8 cycloalkyl,
(4) Z, optionally substituted with 1 to 5 groups selected from the group consisting of:
(a) halogen,
(b) nitro,
(c) oxo,
(d) —NR4R4,
(e) C1-C10 alkoxy, optionally substituted with 1 to 5 halogens,
(f) —S(O)p—C1-C10 alkyl, and
(g) C1-C10 alkyl, optionally substituted with 1 to 5 groups selected from hydroxy, halogen, trifluoromethyl, cyano, —CO2R4, C3-C8 cycloalkyl, and QR5;
R3 is selected from the group consisting of:
(1) oxo,
(2) halogen,
(3) R2, and
(4) —NR2R2;
R4 is selected from the group consisting of:
(1) hydrogen, and
(2) C1-C10 alkyl;
R5 is selected from the group consisting of:
(1) Z, optionally substituted with 1 to 5 groups selected from the group consisting of halogen, trifluoromethyl, cyano, C1-C10 alkyl, and C1-C10 alkoxy, and
(2) C1-C10 alkyl;
R6 is selected from the group consisting of:
(1) hydrogen, and
(2) C1-C10 alkyl;
Q is selected from the group consisting of:
(1) —N(R2)—,
(2) —O—, and
(3) —S(O)p—;
and
Q′ is selected from the group consisting of:
(1) —N(R2)—,
(2) —O—, and
(3) a bond.

78 more elements

Dependencies are inferred from the claim text.

Facts

Application: 13/319,250Filed 28 Apr 2010 · us provisional application
Priority: 8 May 2009
Published: US 2012/0053181 A11 Mar 2012
Granted: 31 Dec 2013
Term ends: Not estimatedThe source records don’t support an estimate.

Classification7 codes

C07D 403/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
A61P 13/00
Drugs for disorders of the urinary system
A61P 13/10
Drugs for disorders of the urinary system: of the bladder
C07D 207/09
With hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms: radicals substituted by nitrogen atoms, not forming part of…

Family

Application61/176,654Us provisional application · filed 8 May 2009
US 2012/0053181 A1Pre-grant publication · published 1 Mar 2012
US 8,618,144 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound of Formula I, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt of the stereoisomer thereof:

wherein
m is 0, 1, 2, 3, or 4;
n is 0, 1, 2, 3, 4, or 5;
p is 0, 1, or 2;
q is 0, 1, 2, 3, or 4;
X is —CO— or —SO2—;
Y is selected from the group consisting of:
(1) C1-C3 alkylene, optionally substituted with —NR2R2 or hydroxy,
(2) —N(R6)—,
(3) —O—,
(4) a bond, and
(5) phenylene, optionally substituted with 1 to 3 groups independently selected from R1;
Z is selected from the group consisting of:
(4) a 5- or 6-membered heterocyclic ring with from 1 to 4 heteroatoms selected from oxygen, sulfur and nitrogen,
R1 is selected from the group consisting of:
(1) C1-C10 alkyl, optionally substituted with 1 to 5 groups selected from the group consisting of:
(a) hydroxy,
(b) halogen,
(c) cyano,
(d) QR2,
(e) C3-C8 cycloalkyl,
(f) Q′COR3,
(g) —S(O)p—NR2R2,
(h) —N(R2)SO2R3, and
(i) Q′CO2R2,
(2) C3-C8 cycloalkyl,
(3) oxo,
(4) halogen,
(5) cyano,
(6) QR2,
(7) —S(O)p—NR2R2,
(8) Q′COR3,
(9) —N(R2)SO2R3,
(10) Q′CO2R2, and
(11) Z, optionally substituted with 1 to 5 groups selected from the group consisting of:
(a) R2,
(b) QR2,
(e) halogen, and
(d) oxo;
R2 is selected from the group consisting of
(1) hydrogen,
(2) C1-C10 alkyl, optionally substituted with 1 to 5 groups selected from the group consisting of:
(a) hydroxy,
(b) halogen,
(c) —CO2R4,
(d) —S(O)p—C1-C10 alkyl,
(e) C3-C8 cycloalkyl,
(f) C1-C10 alkoxy, optionally substituted with 1 to 5 halogens, and
(g) Z, optionally substituted with 1 to 5 groups selected from the group consisting of halogen, trifluoromethyl, trifluoromethoxy, C1-C10 alkyl and C1-C10 alkoxy;
(3) C3-C8 cycloalkyl,
(4) Z, optionally substituted with 1 to 5 groups selected from the group consisting of:
(a) halogen,
(b) nitro,
(c) oxo,
(d) —NR4R4,
(e) C1-C10 alkoxy, optionally substituted with 1 to 5 halogens,
(f) —S(O)p—C1-C10 alkyl, and
(g) C1-C10 alkyl, optionally substituted with 1 to 5 groups selected from hydroxy, halogen, trifluoromethyl, cyano, —CO2R4, C3-C8 cycloalkyl, and QR5;
R3 is selected from the group consisting of:
(1) oxo,
(2) halogen,
(3) R2, and
(4) —NR2R2;
R4 is selected from the group consisting of:
(1) hydrogen, and
(2) C1-C10 alkyl;
R5 is selected from the group consisting of:
(1) Z, optionally substituted with 1 to 5 groups selected from the group consisting of halogen, trifluoromethyl, cyano, C1-C10 alkyl, and C1-C10 alkoxy, and
(2) C1-C10 alkyl;
R6 is selected from the group consisting of:
(1) hydrogen, and
(2) C1-C10 alkyl;
Q is selected from the group consisting of:
(1) —N(R2)—,
(2) —O—, and
(3) —S(O)p—;
and
Q′ is selected from the group consisting of:
(1) —N(R2)—,
(2) —O—, and
(3) a bond.

78 more elements

Facts

Application

13/319,250Filed 28 Apr 2010 · us provisional application

Priority

8 May 2009

Published

US 2012/0053181 A11 Mar 2012

Granted

31 Dec 2013

Term ends

Not estimatedThe source records don’t support an estimate.

Classification7 codes

C07D 403/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
A61P 13/00
Drugs for disorders of the urinary system
A61P 13/10
Drugs for disorders of the urinary system: of the bladder
C07D 207/09
With hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms: radicals substituted by nitrogen atoms, not forming part of…