US 2009/0023774 A1 · Pyridine analogs as C5A antagonists

Abstract

The present invention provides novel compounds of Formula I which are antagonists of the C5a receptor. Compounds of the present invention are useful for the treatment of various C5a-mediated diseases and disorders; accordingly the present invention provides a method for the treatment of C5a-mediated diseases using the novel compounds described herein, as well as pharmaceutical compositions containing them.

Claims12

Dependent claims

-26. (canceled)

A compound of Formula I

or a pharmaceutically acceptable salts thereof;
k is 0, 1, 2 or 3;
R2 and R3 are each hydrogen;
R1 is selected from the group consisting of
(1) hydrogen,
(2) —C1-6alkyl,
(3) —OC1-6alkyl,
(4) —SC1-6alkyl,
(5) —C2-6alkenyl,
(6) —C3-6cycloalkyl,
(7) aryl,
(8) heteroaryl,
(9) heterocyclic,
(10) —C1-6alkylaryl,
(11) —C1-6alkylheteroaryl
(12) —C1-6alkylheterocyclic,
(13) —O-aryl,
(14) —O-heteroaryl,
(15) —O-heterocyclic,
(16) —OC1-6alkylaryl,
(17) —OC1-6alkylheteroaryl
(18) —OC1-6alkylheterocyclic,
(19) halo,
(20) —CN,
(21) —NO2,
(22) —C(O)—C1-6alkyl,
(23) —C(O)-aryl,
(24) —C(O)-heteroaryl,
(25) —C(O)-heterocyclic,
(26) —C(O)—C1-6alkyl,
(27) —NH—C1-6alkyl,
(28) —N(C1-6alkyl)(C1-6alkyl)
(29) —C(O)—NH2,
(30) —C(O)—NH—C1-6alkyl,
(31) —C(O)—N(C1-6alkyl)(C1-6alkyl), and
(32) S(O)n-C1-6alkyl,
wherein definitions (1) to (18) and (22) to (32) are optionally substituted with 1, 2 or 3 substituents selected from the group consisting of halo, hydroxyl, —CN, —NO2, NH2,
R4 and R5 are each independently selected from the group consisting of
(1) hydrogen,
(2) —C1-6alkyl,
(3) —OC1-6alkyl,
(4) —SC1-6alkyl,
(5) —C2-6alkenyl,
(6) —C3-6cycloalkyl,
(7) aryl,
(8) heteroaryl,
(9) heterocyclic,
(10) —C1-6alkylaryl,
(11) —C1-6alkylheteroaryl
(12) —C1-6alkylheterocyclic,
(13) —O-aryl,
(14) —O-heteroaryl,
(15) —O-heterocyclic,
(16) —OC1-6alkylaryl,
(17) —OC1-6alkylheteroaryl,
(18) —OC1-6alkylheterocyclic,
(19) halo,
(20) —CN,
(21) —NO2,
(22) —C(O)—C1-6alkyl,
(23) —C(O)-aryl,
(24) —C(O)-heteroaryl,
(25) —C(O)-heterocyclic,
(26) —C(O)—C1-6alkyl,
(27) NH2,
(28) —NH—C1-6alkyl,
(29) —N(C1-6alkyl)(C1-6alkyl)
(30) —C(O)—NH2,
(31) —C(O)—NH—C1-6alkyl,
(32) —C(O)—N(C1-6alkyl)(C1-6alkyl),
(33) —SH, and
(34) S(O)n-C1-6alkyl, wherein n is 1 or 2;
wherein definitions (1) to (18) and (22) to (32) and (34) are optionally substituted with 1, 2 or 3 substituents selected from the group consisting of halo, hydroxyl, —CN, —NO2, NH2;
R6 is hydrogen or C1-3alkyl, optionally substituted with 1, 2 or 3 substituents selected from
R6 is hydrogen or C1-3alkyl, optionally substituted with 1, 2 or 3 substituents selected from
(1) -halo,
(2) —NR7R8,
(3) aryl,
(4) —OC1-3alkyl,
(5) —SC1-3alkyl, and
(6) —S(O)2C1-3alkyl,
(7) hydroxyl;
each R7 and each R8 are each independently hydrogen or C1-3alkyl, optionally substituted with 1, 2 or 3 substituents selected from
(1) -halo,
(2) C1-3alkyl,
(3) —OC1-6alkyl,
(4) —SC1-6alkyl,
(5) —S(O)2C1-6alkyl,
Ar is aryl or heteroaryl, optionally substituted with 1, 2 or 3 substitutents selected from
(1) -halo,
(2) C1-6alkyl, optionally substituted with 1, 2, 3 or 4 halo groups,
(3) —NR7R8,
(4) aryl,
(5) —OC1-6alkyl, optionally substituted with 1, 2, 3 or 4 halo groups,
(6) —SC1-6alkyl,
(7) —S(O)2C1-6alkyl;
Ar1 is aryl or heteroaryl or C3-6cycloalkyl, optionally substituted with 1, 2 or 3 substitutents selected from
(1) -halo,
(2) C1-6alkyl, optionally substituted with 1, 2, 3 or 4 halo groups,
(3) —NR7R8,
(4) aryl,
(5) —OC1-6alkyl, optionally substituted with 1, 2, 3 or 4 halo groups,
(6) —SC1-6alkyl, and
(7) —S(O)2C1-6alkyl.

101 more elements

Dependencies are inferred from the claim text.

Facts

Application

12/284,122Filed 18 Sep 2008

Priority

10 Jun 2004

Published

22 Jan 2009

Term ends

Not estimatedThe source records don’t support an estimate.

Classification19 codes

C07D 221/04
Condensed with carbocyclic rings or ring systems: ortho- or peri-condensed ring systems
A61P 1/00
Drugs for disorders of the alimentary tract or the digestive system
A61P 9/10
Drugs for disorders of the cardiovascular system: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary…
A61P 11/06
Drugs for disorders of the respiratory system: antiasthmatics

Family

Application60/578,500Us provisional application · filed 10 Jun 2004

Application11/053,623Continuation · filed 8 Feb 2005

Application12/284,122Continuation

US 2005/0277644 A1Published application

US 7,429,666 B2Related patent

US 2009/0023774 A1This patent

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

Abstract

Claims12

Dependent claims

-26. (canceled)

A compound of Formula I

or a pharmaceutically acceptable salts thereof;
k is 0, 1, 2 or 3;
R2 and R3 are each hydrogen;
R1 is selected from the group consisting of
(1) hydrogen,
(2) —C1-6alkyl,
(3) —OC1-6alkyl,
(4) —SC1-6alkyl,
(5) —C2-6alkenyl,
(6) —C3-6cycloalkyl,
(7) aryl,
(8) heteroaryl,
(9) heterocyclic,
(10) —C1-6alkylaryl,
(11) —C1-6alkylheteroaryl
(12) —C1-6alkylheterocyclic,
(13) —O-aryl,
(14) —O-heteroaryl,
(15) —O-heterocyclic,
(16) —OC1-6alkylaryl,
(17) —OC1-6alkylheteroaryl
(18) —OC1-6alkylheterocyclic,
(19) halo,
(20) —CN,
(21) —NO2,
(22) —C(O)—C1-6alkyl,
(23) —C(O)-aryl,
(24) —C(O)-heteroaryl,
(25) —C(O)-heterocyclic,
(26) —C(O)—C1-6alkyl,
(27) —NH—C1-6alkyl,
(28) —N(C1-6alkyl)(C1-6alkyl)
(29) —C(O)—NH2,
(30) —C(O)—NH—C1-6alkyl,
(31) —C(O)—N(C1-6alkyl)(C1-6alkyl), and
(32) S(O)n-C1-6alkyl,
wherein definitions (1) to (18) and (22) to (32) are optionally substituted with 1, 2 or 3 substituents selected from the group consisting of halo, hydroxyl, —CN, —NO2, NH2,
R4 and R5 are each independently selected from the group consisting of
(1) hydrogen,
(2) —C1-6alkyl,
(3) —OC1-6alkyl,
(4) —SC1-6alkyl,
(5) —C2-6alkenyl,
(6) —C3-6cycloalkyl,
(7) aryl,
(8) heteroaryl,
(9) heterocyclic,
(10) —C1-6alkylaryl,
(11) —C1-6alkylheteroaryl
(12) —C1-6alkylheterocyclic,
(13) —O-aryl,
(14) —O-heteroaryl,
(15) —O-heterocyclic,
(16) —OC1-6alkylaryl,
(17) —OC1-6alkylheteroaryl,
(18) —OC1-6alkylheterocyclic,
(19) halo,
(20) —CN,
(21) —NO2,
(22) —C(O)—C1-6alkyl,
(23) —C(O)-aryl,
(24) —C(O)-heteroaryl,
(25) —C(O)-heterocyclic,
(26) —C(O)—C1-6alkyl,
(27) NH2,
(28) —NH—C1-6alkyl,
(29) —N(C1-6alkyl)(C1-6alkyl)
(30) —C(O)—NH2,
(31) —C(O)—NH—C1-6alkyl,
(32) —C(O)—N(C1-6alkyl)(C1-6alkyl),
(33) —SH, and
(34) S(O)n-C1-6alkyl, wherein n is 1 or 2;
wherein definitions (1) to (18) and (22) to (32) and (34) are optionally substituted with 1, 2 or 3 substituents selected from the group consisting of halo, hydroxyl, —CN, —NO2, NH2;
R6 is hydrogen or C1-3alkyl, optionally substituted with 1, 2 or 3 substituents selected from
R6 is hydrogen or C1-3alkyl, optionally substituted with 1, 2 or 3 substituents selected from
(1) -halo,
(2) —NR7R8,
(3) aryl,
(4) —OC1-3alkyl,
(5) —SC1-3alkyl, and
(6) —S(O)2C1-3alkyl,
(7) hydroxyl;
each R7 and each R8 are each independently hydrogen or C1-3alkyl, optionally substituted with 1, 2 or 3 substituents selected from
(1) -halo,
(2) C1-3alkyl,
(3) —OC1-6alkyl,
(4) —SC1-6alkyl,
(5) —S(O)2C1-6alkyl,
Ar is aryl or heteroaryl, optionally substituted with 1, 2 or 3 substitutents selected from
(1) -halo,
(2) C1-6alkyl, optionally substituted with 1, 2, 3 or 4 halo groups,
(3) —NR7R8,
(4) aryl,
(5) —OC1-6alkyl, optionally substituted with 1, 2, 3 or 4 halo groups,
(6) —SC1-6alkyl,
(7) —S(O)2C1-6alkyl;
Ar1 is aryl or heteroaryl or C3-6cycloalkyl, optionally substituted with 1, 2 or 3 substitutents selected from
(1) -halo,
(2) C1-6alkyl, optionally substituted with 1, 2, 3 or 4 halo groups,
(3) —NR7R8,
(4) aryl,
(5) —OC1-6alkyl, optionally substituted with 1, 2, 3 or 4 halo groups,
(6) —SC1-6alkyl, and
(7) —S(O)2C1-6alkyl.

101 more elements

Dependencies are inferred from the claim text.

Pyridine analogs as C5A antagonists

Life of this patent

Abstract

Claims12

Pyridine analogs as C5A antagonists

Life of this patent

Abstract

Claims12