US 2011/0034514 A1 · 5-Lipoxygenase-Activating Protein (FLAP) Inhibitors

Abstract

Described herein are compounds and pharmaceutical compositions containing such compounds, which modulate the activity of 5-lipoxygenase-activating protein (FLAP). Also described herein are methods of using such FLAP modulators, alone and in combination with other compounds, for treating respiratory, cardiovascular, and other leukotriene-dependent or leukotriene mediated conditions or diseases.

Claims26

Dependent claims

1-45. (canceled)

A compound having the structure of Formula (H):

wherein,
Z is selected from C(R1)2[C(R2)2]n, [C(R2)2]nC(R1)2O, OC(R1)2[C(R2)2]n, [C(R2)2]nO[C(R1)2]n, [C(R1)2]nO[C(R2)2]n, wherein each R1 is independently H, CF3, or an optionally substituted lower alkyl or two R1 on the same carbon may join to form a oxo (═O);
and each R2 is independently H, OH, OMe, CF3, or an optionally substituted lower alkyl or two R2 on the same carbon may join to form a oxo (═O);
m is 0, 1 or 2;
each n is independently 0, 1, 2, or 3;
Y is —CO2H, —CONH2, —C(═O)N(R4b)2, CO2R4b, —OR3b, —C(═O)(C1-C5 fluoroalkyl), —C(═NOH)R4b, C(═NOR3b)R4b, -L1-(substituted or unsubstituted alkyl), -L1-(substituted or unsubstituted alkenyl), -L1-(substituted or unsubstituted alkynyl), -L1-(substituted or unsubstituted cycloalkyl), -L1-(substituted or unsubstituted phenyl), -L1-(substituted or unsubstituted heteroaryl), or -L1-(substituted or unsubstituted heteroalicyclic group);
where L1 is —C(═O), CR8OH, CR8OMe, C(═NOH), C(═NOR4b), C(═O)NH, C(═O)NR4b, —NHC(═O), NR4bC(═O), S, S(═O), S(═O)2, —NHC(═O)NH, or NR4bC(═O)NR4b;
where each substituent on Y or Z is (LsRs)j, wherein each Ls is independently selected from a bond, —NH, —O—, —C(═O)—, —S—, —S(═O)—, —S(═O)2—, —NHC(O)—, —C(O)NH—, S(═O)2NH—, —NHS(═O)2, —OC(O)NH—, —NHC(O)O—, —OC(O)O—, —NHC(O)NH—, —C(O)O—, —OC(O)—, C1-C6 alkyl, C2-C6 alkenyl, —C1-C6 fluoroalkyl, phenyl;
and each Rs is independently selected from H, halogen, —N(R4)2, —CN, —NO2, N3, —S(═O)2NH2, lower alkyl, lower cycloalkyl, —C1-C6 fluoroalkyl, heteroaryl, or heteroalkyl;
where j is 0, 1, 2, 3, or 4;
each R3b is independently selected from substituted or unsubstituted lower alkyl, substituted or unsubstituted lower cycloalkyl, phenyl or benzyl;
each R4 is independently selected from H, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower cycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted benzyl;
each R4b is independently selected from H, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower cycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted benzyl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted heteroalicyclic group;
R6 is H, L2-(substituted or unsubstituted alkyl), L2-(substituted or unsubstituted cycloalkyl), L2-(substituted or unsubstituted alkenyl), L2-(substituted or unsubstituted cycloalkenyl), L2-(substituted or unsubstituted heteroalicyclic group), L2-(substituted or unsubstituted heteroaryl), or L2-(substituted or unsubstituted aryl), where L2 is a bond, O, S, —S(═O), —S(═O), —S(═O)2, C(O), —CH(OH), -(substituted or unsubstituted C1-C6 alkyl), or -(substituted or unsubstituted C2-C6 alkenyl);
R7 is L3-X-L4-G1, wherein,
L3 is a bond, or substituted or unsubstituted alkyl;
X is a bond, O, —C(═O), —CR9(OR9), S, —S(═O), —S(═O)2, —NR9, —NR9C(O), —C(O)NR9, —S(═O)2NR9, —NR9S(═O)2, —OC(O)NR9—, —NR9C(O)O—, —CH═NO—, —ON═CH—, —NR9C(O)NR9—, heteroaryl, aryl, —NR9C(═NR10)NR9—, —NR9C(═NR10)—, —C(═NR10)NR9—, —OC(═NR10)—, or —C(═NR10)O—;
L4 is a bond or substituted or unsubstituted alkyl;
G1 is H, tetrazolyl, —NHS(═O)2R8, S(═O)2N(R9)2, —OR9, —C(═O)CF3, —C(O)NHS(═O)2R8, —S(═O)2NHC(O)R9, CN, N(R9)2, —N(R9)C(O)R9, —C(═NR10)N(R9)2, —NR9C(═NR10)N(R9)2, —NR9C(═CR10)N(R9)2, —C(O)NR9C(═NR10)N(R9)2, —C(O)NR9C(═CR10)N(R9)2, —CO2R9, —C(O)R9, —CON(R9)2, —SR8, —S(═O)R8, —S(═O)2R8, -L5-(substituted or unsubstituted alkyl), -L5-(substituted or unsubstituted alkenyl), -L5-(substituted or unsubstituted heteroaryl), or -L5-(substituted or unsubstituted aryl), wherein L5 is —OC(O)O—, —NHC(O)NH—, —NHC(O)O, —O(O)CNH—, —NHC(O), —C(O)NH, —C(O)O, or —OC(O);
each R8 is independently selected from substituted or unsubstituted lower alkyl, substituted or unsubstituted lower cycloalkyl, substituted or unsubstituted phenyl or substituted or unsubstituted benzyl;
each R9 is independently selected from H, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower cycloalkyl, substituted or unsubstituted phenyl or substituted or unsubstituted benzyl;
or two R9 groups can together form a 5-, 6-, 7-, or 8-membered heterocyclic ring;
or R8 and R9 can together form a 5-, 6-, 7-, or 8-membered heterocyclic ring and
each R10 is independently selected from H, —S(═O)2R8, —S(═O)2NH2—C(O)R8, —CN, —NO2, heteroaryl, or heteroalkyl;
R5 is H, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted O—C1-C6 alkyl;
R11 is L7-L10-G6;
wherein L7 is a bond;
L10 is a bond, (substituted or unsubstituted alkyl), (substituted or unsubstituted cycloalkyl), (substituted or unsubstituted cycloalkenyl), (substituted or unsubstituted heteroaryl), (substituted or unsubstituted aryl), or (substituted or unsubstituted heteroalicyclic group);
G6 is H, CN, SCN, N3, NO2, halogen, OR9, —C(═O)CF3, —C(═O)R9, —SR8, —S(═O)R8, —S(═O)2R8, N(R9)2, tetrazolyl, —NHS(═O)2R8, —S(═O)2N(R9)2, —C(O)NHS(═O)2R8, —S(═O)2NHC(O)R9, —C(═NR10)N(R9)2, —NR9C(═NR10)N(R9)2, —NR9C(═CR10)N(R9)2, -L5-(substituted or unsubstituted alkyl), -L5-(substituted or unsubstituted alkenyl), -L5-(substituted or unsubstituted heteroaryl), or -L5-(substituted or unsubstituted aryl), wherein L5 is —NHC(O)O, —NHC(O)NH—, —OC(O)O—, —OC(O)NH—, —NHC(O), —C(O)NH, —C(O)O, or —OC(O);
or G6 is W-G7, wherein W is (substituted or unsubstituted cycloalkyl), (substituted or unsubstituted cycloalkenyl), (substituted or unsubstituted aryl), (substituted or unsubstituted heteroalicyclic group) or a (substituted or unsubstituted heteroaryl) and G7 is H, halogen, CN, NO2, N3, CF3, OCF3, C1-C6 alkyl, C3-C6 cycloalkyl, —C1-C6 fluoroalkyl, tetrazolyl, —NHS(═O)2R8, S(═O)2N(R9)2, OH, —OR8, —C(═O)CF3, —C(O)NHS(═O)2R8, —S(═O)2NHC(O)R9, CN, N(R9)2, —N(R9)C(O)R9, —C(═NR10)N(R9)2, —NR9C(═NR10)N(R9)2, —NR9C(═CR10)N(R9)2, —C(O)NR9C(═NR10)N(R9)2, —C(O)NR9C(═CR10)N(R9)2, —CO2R9, —C(O)R9, —CON(R9)2, —SR8, —S(═O)R8, or —S(═O)2R8, -L5-(substituted or unsubstituted alkyl), -L5-(substituted or unsubstituted alkenyl), -L5-(substituted or unsubstituted heteroalkyl), -L5-(substituted or unsubstituted heteroaryl), -L5-(substituted or unsubstituted heteroalicyclic group), or -L5-(substituted or unsubstituted aryl), wherein L5 is a bond, —O—, C(═O), S, S(═O), S(═O)2, —NH, —NHC(O)O, —NHC(O)NH—, —OC(O)O—, —OC(O)NH—, —NHC(O), —C(O)NH, —C(O)O, or —OC(O);
R12 is H;
or a pharmaceutically acceptable salt thereof.

29 more elements

A compound selected from among:

3-[3-tert-butylsulfanyl-5-carbamoylmethoxy-1-(4-chloro-benzyl)-1H-indol-2-yl]-2,2-dimethyl-propionic acid;
3-[5-((S)-2-tert-butoxycarbonylamino-2-phenyl-ethoxy)-3-tert-butylsulfanyl-1-(4-chloro-benzyl)-1H-indol-2-yl]-2,2-dimethyl-propionic acid;
3-[5-((R)-2-tert-butoxycarbonylamino-2-phenyl-ethoxy)-3-tert-butylsulfanyl-1-(4-chloro-benzyl)-1H-indol-2-yl]-2,2-dimethyl-propionic acid;
3-[5-((R)-2-amino-2-phenyl-ethoxy)-3-tert-butylsulfanyl-1-(4-chloro-benzyl)-1H-indol-2-yl]-2,2-dimethyl-propionic acid;
3-[5-((S)-2-amino-2-phenyl-ethoxy)-3-tert-butylsulfanyl-1-(4-chloro-benzyl)-1H-indol-2-yl]-2,2-dimethyl-propionic acid;
3-[5-((R)-2-acetylamino-2-phenyl-ethoxy)-3-tert-butylsulfanyl-1-(4-chloro-benzyl)-1H-indol-2-yl]-2,2-dimethyl-propionic acid;
3-[5-((S)-2-acetylamino-2-phenyl-ethoxy)-3-tert-butylsulfanyl-1-(4-chloro-benzyl)-1H-indol-2-yl]-2,2-dimethyl-propionic acid;
3-[5-[(3-tert-butoxycarbonylamino-propylcarbamoyl)-methoxy]-3-tert-butylsulfanyl-1-(4-chloro-benzyl)-1H-indol-2-yl]-2,2-dimethyl-propionic acid;
3-[5-[(3-amino-propylcarbamoyl)-methoxy]-3-tert-butylsulfanyl-1-(4-chloro-benzyl)-1H-indol-2-yl]-2,2-dimethyl-propionic acid;
3-{3-tert-butylsulfanyl-1-(4-chloro-benzyl)-5-[2-(4-fluoro-phenyl)-2-oxo-ethoxy]-1H-indol-2-yl}-2,2-dimethyl-propionic acid;
3-{3-tert-butylsulfanyl-1-(4-chloro-benzyl)-5-[2-(4-fluoro-phenyl)-2-hydroxy-ethoxy]-1H-indol-2-yl}-2,2-dimethyl-propionic acid;
3-(3-tert-butylsulfanyl-1-(4-chloro-benzyl)-5-{2-(4-fluoro-phenyl)-2-[(Z)-hydroxyimino]-ethoxy}-1H-indol-2-yl)-2,2-dimethyl-propionic acid;
3-(3-tert-butylsulfanyl-1-(4-chloro-benzyl)-5-{2-(4-fluoro-phenyl)-2-[(Z)-methoxyimino]-ethoxy}-1H-indol-2-yl)-2,2-dimethyl-propionic acid;
3-[3-tert-butylsulfanyl-5-carbamoylmethoxy-1-(4-chloro-benzyl)-1H-indol-2-yl]-2,2-dimethyl-propionic acid ethyl ester;
3-[3-tert-butylsulfanyl-1-(4-chloro-benzyl)-5-cyanomethoxy-1H-indol-2-yl]-2,2-dimethyl-propionic acid ethyl ester;
3-[5-(benzylcarbamoyl-methoxy)-1-(4-bromo-benzyl)-3-tert-butylsulfanyl-1H-indol-2-yl]-2,2-dimethyl-propionic acid ethyl ester;
3-[3-tert-butylsulfanyl-5-carboxymethoxy-1-(4-thiazol-2-yl-benzyl)-1H-indol-2-yl]-2,2-dimethyl-propionic acid;
3-[3-tert-butylsulfanyl-5-(2-hydroxy-propoxy)-1-(4-thiazol-2-yl-benzyl)-1H-indol-2-yl]-2,2-dimethyl-propionic acid;
3-[3-tert-butylsulfanyl-5-carbamoylmethoxy-1-(4-thiazol-2-yl-benzyl)-1H-indol-2-yl]-2,2-dimethyl-propionic acid;
3-[3-tert-butylsulfanyl-5-(1-carbamoyl-1-methyl-ethoxy)-1-(4-thiazol-2-yl-benzyl)-1H-indol-2-yl]-2,2-dimethyl-propionic acid;
3-[3-tert-butylsulfanyl-5-(1-carboxy-1-methyl-ethoxy)-1-(4-thiazol-2-yl-benzyl)-1H-indol-2-yl]-2,2-dimethyl-propionic acid;
3-{3-tert-butylsulfanyl-5-(2-methoxy-propoxy)-1-[4-(6-methoxy-pyridin-3-yl)-benzyl]-1H-indol-2-yl}-2,2-dimethyl-propionic acid;
3-{3-tert-butylsulfanyl-5-(2-hydroxy-propoxy)-1-[4-(6-methoxy-pyridin-3-yl)-benzyl]-1H-indol-2-yl}-2,2-dimethyl-propionic acid;
3-{3-tert-butylsulfanyl-5-(2-hydroxy-2-methyl-propoxy)-1-[4-(6-methoxy-pyridin-3-yl)-benzyl]-1H-indol-2-yl}-2,2-dimethyl-propionic acid;
3-{3-tert-butylsulfanyl-5-(2-hydroxy-3,3-dimethyl-butoxy)-1-[4-(6-methoxy-pyridin-3-yl)-benzyl]-1H-indol-2-yl}-2,2-dimethyl-propionic acid;
3-{3-tert-butylsulfanyl-5-[2-(4-fluoro-phenyl)-2-hydroxy-ethoxy]-1-[4-(6-methoxy-pyridin-3-yl)-benzyl]-1H-indol-2-yl}-2,2-dimethyl-propionic acid;
3-[3-tert-butylsulfanyl-5-carbamoylmethoxy-1-(4-thiazol-2-yl-benzyl)-1H-indol-2-yl]-2,2-dimethyl-propionic acid ethyl ester;
2-[3-tert-butylsulfanyl-1-(4-chloro-benzyl)-2-(2-hydroxy-2-methyl-propyl)-1H-indol-5-yloxy]-acetamide;
2-[3-tert-butylsulfanyl-2-(2-hydroxy-2-methyl-propyl)-1-pyridin-4-ylmethyl-1H-indol-5-yloxy]-acetamide;
2-[3-tert-Butylsulfanyl-1-(4-cyano-benzyl)-2-(2-hydroxy-2-methyl-propyl)-1H-indol-5-yloxy]-acetamide;
2-[3-tert-butylsulfanyl-2-(2-hydroxy-2-methyl-propyl)-1-(4-iodo-benzyl)-1H-indol-5-yloxy]-acetamide;
2-[3-tert-butylsulfanyl-1-cyclopropylmethyl-2-(2-hydroxy-2-methyl-propyl)-1H-indol-5-yloxy]-acetamide;
2-[3-tert-butylsulfanyl-1-(4-chloro-benzyl)-2-(2-hydroxy-2-methyl-propyl)-1H-indol-5-yloxy]-N,N-diethyl-acetamide;
2-[3-tert-butylsulfanyl-2-(2-hydroxy-2-methyl-propyl)-1-pyridin-4-ylmethyl-1H-indol-5-yloxy]-N-(4-fluoro-phenyl)-acetamide;
2-[3-tert-butylsulfanyl-1-(4-chloro-benzyl)-2-(2-hydroxy-2-methyl-propyl)-1H-indol-5-yloxy]-N-(4-chloro-benzyl)-N-pyridin-3-yl-acetamide;
2-[3-tert-butylsulfanyl-2-(2-hydroxy-2-methyl-propyl)-1-pyridin-4-ylmethyl-1H-indol-5-yloxy]-N-cyclopropyl-acetamide;
2-[3-tert-butylsulfanyl-2-(2-hydroxy-2-methyl-propyl)-1-(4-iodo-benzyl)-1H-indol-5-yloxy]-N-(4-iodo-benzyl)-acetamide;
2-[3-tert-butylsulfanyl-2-(2-hydroxy-2-methyl-propyl)-1-(4-pyridin-3-yl-benzyl)-1H-indol-5-yloxy]-acetamide;
[3-tert-butylsulfanyl-1-(4-chloro-benzyl)-2-(2-hydroxy-2-methyl-propyl)-1H-indol-5-yloxy]-acetic acid;
[3-tert-butylsulfanyl-1-(4-chloro-benzyl)-2-(2-hydroxy-2-methyl-propyl)-1H-indol-5-yloxy]-acetic acid ethyl ester;
1-[3-tert-butylsulfanyl-1-(4-chloro-benzyl)-5-(2-hydroxy-2-methyl-propoxy)-1H-indol-2-yl]-2-methyl-propan-2-ol;
1-[3-tert-butylsulfanyl-1-(4-chloro-benzyl)-5-(2-hydroxy-propoxy)-1H-indol-2-yl]-2-methyl-propan-2-ol;
1-[3-tert-butylsulfanyl-1-(4-chloro-benzyl)-2-(2-hydroxy-2-methyl-propyl)-1H-indol-5-yloxy]-propan-2-one.

40 more elements

Dependencies are inferred from the claim text.

Facts

Application

12/906,325Filed 18 Oct 2010

Priority

4 Nov 2005

Published

10 Feb 2011

Term ends

Not estimatedThe source records don’t support an estimate.

Classification52 codes

C07D 401/10
Containing two hetero rings: linked by a carbon chain containing aromatic rings
A61P 1/00
Drugs for disorders of the alimentary tract or the digestive system
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…
A61P 1/06
Drugs for disorders of the alimentary tract or the digestive system: anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia

Family

Application60/734,030Us provisional application · filed 4 Nov 2005

Application60/747,174Us provisional application · filed 12 May 2006

Application60/823,344Us provisional application · filed 23 Aug 2006

Application11/925,841Continuation · filed 27 Oct 2007

Application12/906,325Continuation

US 2009/0018170 A1Published application

US 7,834,037 B2Related patent

US 2011/0034514 A1This patent

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

Abstract

Claims26

Dependent claims

1-45. (canceled)

A compound having the structure of Formula (H):

wherein,
Z is selected from C(R1)2[C(R2)2]n, [C(R2)2]nC(R1)2O, OC(R1)2[C(R2)2]n, [C(R2)2]nO[C(R1)2]n, [C(R1)2]nO[C(R2)2]n, wherein each R1 is independently H, CF3, or an optionally substituted lower alkyl or two R1 on the same carbon may join to form a oxo (═O);
and each R2 is independently H, OH, OMe, CF3, or an optionally substituted lower alkyl or two R2 on the same carbon may join to form a oxo (═O);
m is 0, 1 or 2;
each n is independently 0, 1, 2, or 3;
Y is —CO2H, —CONH2, —C(═O)N(R4b)2, CO2R4b, —OR3b, —C(═O)(C1-C5 fluoroalkyl), —C(═NOH)R4b, C(═NOR3b)R4b, -L1-(substituted or unsubstituted alkyl), -L1-(substituted or unsubstituted alkenyl), -L1-(substituted or unsubstituted alkynyl), -L1-(substituted or unsubstituted cycloalkyl), -L1-(substituted or unsubstituted phenyl), -L1-(substituted or unsubstituted heteroaryl), or -L1-(substituted or unsubstituted heteroalicyclic group);
where L1 is —C(═O), CR8OH, CR8OMe, C(═NOH), C(═NOR4b), C(═O)NH, C(═O)NR4b, —NHC(═O), NR4bC(═O), S, S(═O), S(═O)2, —NHC(═O)NH, or NR4bC(═O)NR4b;
where each substituent on Y or Z is (LsRs)j, wherein each Ls is independently selected from a bond, —NH, —O—, —C(═O)—, —S—, —S(═O)—, —S(═O)2—, —NHC(O)—, —C(O)NH—, S(═O)2NH—, —NHS(═O)2, —OC(O)NH—, —NHC(O)O—, —OC(O)O—, —NHC(O)NH—, —C(O)O—, —OC(O)—, C1-C6 alkyl, C2-C6 alkenyl, —C1-C6 fluoroalkyl, phenyl;
and each Rs is independently selected from H, halogen, —N(R4)2, —CN, —NO2, N3, —S(═O)2NH2, lower alkyl, lower cycloalkyl, —C1-C6 fluoroalkyl, heteroaryl, or heteroalkyl;
where j is 0, 1, 2, 3, or 4;
each R3b is independently selected from substituted or unsubstituted lower alkyl, substituted or unsubstituted lower cycloalkyl, phenyl or benzyl;
each R4 is independently selected from H, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower cycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted benzyl;
each R4b is independently selected from H, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower cycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted benzyl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted heteroalicyclic group;
R6 is H, L2-(substituted or unsubstituted alkyl), L2-(substituted or unsubstituted cycloalkyl), L2-(substituted or unsubstituted alkenyl), L2-(substituted or unsubstituted cycloalkenyl), L2-(substituted or unsubstituted heteroalicyclic group), L2-(substituted or unsubstituted heteroaryl), or L2-(substituted or unsubstituted aryl), where L2 is a bond, O, S, —S(═O), —S(═O), —S(═O)2, C(O), —CH(OH), -(substituted or unsubstituted C1-C6 alkyl), or -(substituted or unsubstituted C2-C6 alkenyl);
R7 is L3-X-L4-G1, wherein,
L3 is a bond, or substituted or unsubstituted alkyl;
X is a bond, O, —C(═O), —CR9(OR9), S, —S(═O), —S(═O)2, —NR9, —NR9C(O), —C(O)NR9, —S(═O)2NR9, —NR9S(═O)2, —OC(O)NR9—, —NR9C(O)O—, —CH═NO—, —ON═CH—, —NR9C(O)NR9—, heteroaryl, aryl, —NR9C(═NR10)NR9—, —NR9C(═NR10)—, —C(═NR10)NR9—, —OC(═NR10)—, or —C(═NR10)O—;
L4 is a bond or substituted or unsubstituted alkyl;
G1 is H, tetrazolyl, —NHS(═O)2R8, S(═O)2N(R9)2, —OR9, —C(═O)CF3, —C(O)NHS(═O)2R8, —S(═O)2NHC(O)R9, CN, N(R9)2, —N(R9)C(O)R9, —C(═NR10)N(R9)2, —NR9C(═NR10)N(R9)2, —NR9C(═CR10)N(R9)2, —C(O)NR9C(═NR10)N(R9)2, —C(O)NR9C(═CR10)N(R9)2, —CO2R9, —C(O)R9, —CON(R9)2, —SR8, —S(═O)R8, —S(═O)2R8, -L5-(substituted or unsubstituted alkyl), -L5-(substituted or unsubstituted alkenyl), -L5-(substituted or unsubstituted heteroaryl), or -L5-(substituted or unsubstituted aryl), wherein L5 is —OC(O)O—, —NHC(O)NH—, —NHC(O)O, —O(O)CNH—, —NHC(O), —C(O)NH, —C(O)O, or —OC(O);
each R8 is independently selected from substituted or unsubstituted lower alkyl, substituted or unsubstituted lower cycloalkyl, substituted or unsubstituted phenyl or substituted or unsubstituted benzyl;
each R9 is independently selected from H, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower cycloalkyl, substituted or unsubstituted phenyl or substituted or unsubstituted benzyl;
or two R9 groups can together form a 5-, 6-, 7-, or 8-membered heterocyclic ring;
or R8 and R9 can together form a 5-, 6-, 7-, or 8-membered heterocyclic ring and
each R10 is independently selected from H, —S(═O)2R8, —S(═O)2NH2—C(O)R8, —CN, —NO2, heteroaryl, or heteroalkyl;
R5 is H, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted O—C1-C6 alkyl;
R11 is L7-L10-G6;
wherein L7 is a bond;
L10 is a bond, (substituted or unsubstituted alkyl), (substituted or unsubstituted cycloalkyl), (substituted or unsubstituted cycloalkenyl), (substituted or unsubstituted heteroaryl), (substituted or unsubstituted aryl), or (substituted or unsubstituted heteroalicyclic group);
G6 is H, CN, SCN, N3, NO2, halogen, OR9, —C(═O)CF3, —C(═O)R9, —SR8, —S(═O)R8, —S(═O)2R8, N(R9)2, tetrazolyl, —NHS(═O)2R8, —S(═O)2N(R9)2, —C(O)NHS(═O)2R8, —S(═O)2NHC(O)R9, —C(═NR10)N(R9)2, —NR9C(═NR10)N(R9)2, —NR9C(═CR10)N(R9)2, -L5-(substituted or unsubstituted alkyl), -L5-(substituted or unsubstituted alkenyl), -L5-(substituted or unsubstituted heteroaryl), or -L5-(substituted or unsubstituted aryl), wherein L5 is —NHC(O)O, —NHC(O)NH—, —OC(O)O—, —OC(O)NH—, —NHC(O), —C(O)NH, —C(O)O, or —OC(O);
or G6 is W-G7, wherein W is (substituted or unsubstituted cycloalkyl), (substituted or unsubstituted cycloalkenyl), (substituted or unsubstituted aryl), (substituted or unsubstituted heteroalicyclic group) or a (substituted or unsubstituted heteroaryl) and G7 is H, halogen, CN, NO2, N3, CF3, OCF3, C1-C6 alkyl, C3-C6 cycloalkyl, —C1-C6 fluoroalkyl, tetrazolyl, —NHS(═O)2R8, S(═O)2N(R9)2, OH, —OR8, —C(═O)CF3, —C(O)NHS(═O)2R8, —S(═O)2NHC(O)R9, CN, N(R9)2, —N(R9)C(O)R9, —C(═NR10)N(R9)2, —NR9C(═NR10)N(R9)2, —NR9C(═CR10)N(R9)2, —C(O)NR9C(═NR10)N(R9)2, —C(O)NR9C(═CR10)N(R9)2, —CO2R9, —C(O)R9, —CON(R9)2, —SR8, —S(═O)R8, or —S(═O)2R8, -L5-(substituted or unsubstituted alkyl), -L5-(substituted or unsubstituted alkenyl), -L5-(substituted or unsubstituted heteroalkyl), -L5-(substituted or unsubstituted heteroaryl), -L5-(substituted or unsubstituted heteroalicyclic group), or -L5-(substituted or unsubstituted aryl), wherein L5 is a bond, —O—, C(═O), S, S(═O), S(═O)2, —NH, —NHC(O)O, —NHC(O)NH—, —OC(O)O—, —OC(O)NH—, —NHC(O), —C(O)NH, —C(O)O, or —OC(O);
R12 is H;
or a pharmaceutically acceptable salt thereof.

29 more elements

A compound selected from among:

3-[3-tert-butylsulfanyl-5-carbamoylmethoxy-1-(4-chloro-benzyl)-1H-indol-2-yl]-2,2-dimethyl-propionic acid;
3-[5-((S)-2-tert-butoxycarbonylamino-2-phenyl-ethoxy)-3-tert-butylsulfanyl-1-(4-chloro-benzyl)-1H-indol-2-yl]-2,2-dimethyl-propionic acid;
3-[5-((R)-2-tert-butoxycarbonylamino-2-phenyl-ethoxy)-3-tert-butylsulfanyl-1-(4-chloro-benzyl)-1H-indol-2-yl]-2,2-dimethyl-propionic acid;
3-[5-((R)-2-amino-2-phenyl-ethoxy)-3-tert-butylsulfanyl-1-(4-chloro-benzyl)-1H-indol-2-yl]-2,2-dimethyl-propionic acid;
3-[5-((S)-2-amino-2-phenyl-ethoxy)-3-tert-butylsulfanyl-1-(4-chloro-benzyl)-1H-indol-2-yl]-2,2-dimethyl-propionic acid;
3-[5-((R)-2-acetylamino-2-phenyl-ethoxy)-3-tert-butylsulfanyl-1-(4-chloro-benzyl)-1H-indol-2-yl]-2,2-dimethyl-propionic acid;
3-[5-((S)-2-acetylamino-2-phenyl-ethoxy)-3-tert-butylsulfanyl-1-(4-chloro-benzyl)-1H-indol-2-yl]-2,2-dimethyl-propionic acid;
3-[5-[(3-tert-butoxycarbonylamino-propylcarbamoyl)-methoxy]-3-tert-butylsulfanyl-1-(4-chloro-benzyl)-1H-indol-2-yl]-2,2-dimethyl-propionic acid;
3-[5-[(3-amino-propylcarbamoyl)-methoxy]-3-tert-butylsulfanyl-1-(4-chloro-benzyl)-1H-indol-2-yl]-2,2-dimethyl-propionic acid;
3-{3-tert-butylsulfanyl-1-(4-chloro-benzyl)-5-[2-(4-fluoro-phenyl)-2-oxo-ethoxy]-1H-indol-2-yl}-2,2-dimethyl-propionic acid;
3-{3-tert-butylsulfanyl-1-(4-chloro-benzyl)-5-[2-(4-fluoro-phenyl)-2-hydroxy-ethoxy]-1H-indol-2-yl}-2,2-dimethyl-propionic acid;
3-(3-tert-butylsulfanyl-1-(4-chloro-benzyl)-5-{2-(4-fluoro-phenyl)-2-[(Z)-hydroxyimino]-ethoxy}-1H-indol-2-yl)-2,2-dimethyl-propionic acid;
3-(3-tert-butylsulfanyl-1-(4-chloro-benzyl)-5-{2-(4-fluoro-phenyl)-2-[(Z)-methoxyimino]-ethoxy}-1H-indol-2-yl)-2,2-dimethyl-propionic acid;
3-[3-tert-butylsulfanyl-5-carbamoylmethoxy-1-(4-chloro-benzyl)-1H-indol-2-yl]-2,2-dimethyl-propionic acid ethyl ester;
3-[3-tert-butylsulfanyl-1-(4-chloro-benzyl)-5-cyanomethoxy-1H-indol-2-yl]-2,2-dimethyl-propionic acid ethyl ester;
3-[5-(benzylcarbamoyl-methoxy)-1-(4-bromo-benzyl)-3-tert-butylsulfanyl-1H-indol-2-yl]-2,2-dimethyl-propionic acid ethyl ester;
3-[3-tert-butylsulfanyl-5-carboxymethoxy-1-(4-thiazol-2-yl-benzyl)-1H-indol-2-yl]-2,2-dimethyl-propionic acid;
3-[3-tert-butylsulfanyl-5-(2-hydroxy-propoxy)-1-(4-thiazol-2-yl-benzyl)-1H-indol-2-yl]-2,2-dimethyl-propionic acid;
3-[3-tert-butylsulfanyl-5-carbamoylmethoxy-1-(4-thiazol-2-yl-benzyl)-1H-indol-2-yl]-2,2-dimethyl-propionic acid;
3-[3-tert-butylsulfanyl-5-(1-carbamoyl-1-methyl-ethoxy)-1-(4-thiazol-2-yl-benzyl)-1H-indol-2-yl]-2,2-dimethyl-propionic acid;
3-[3-tert-butylsulfanyl-5-(1-carboxy-1-methyl-ethoxy)-1-(4-thiazol-2-yl-benzyl)-1H-indol-2-yl]-2,2-dimethyl-propionic acid;
3-{3-tert-butylsulfanyl-5-(2-methoxy-propoxy)-1-[4-(6-methoxy-pyridin-3-yl)-benzyl]-1H-indol-2-yl}-2,2-dimethyl-propionic acid;
3-{3-tert-butylsulfanyl-5-(2-hydroxy-propoxy)-1-[4-(6-methoxy-pyridin-3-yl)-benzyl]-1H-indol-2-yl}-2,2-dimethyl-propionic acid;
3-{3-tert-butylsulfanyl-5-(2-hydroxy-2-methyl-propoxy)-1-[4-(6-methoxy-pyridin-3-yl)-benzyl]-1H-indol-2-yl}-2,2-dimethyl-propionic acid;
3-{3-tert-butylsulfanyl-5-(2-hydroxy-3,3-dimethyl-butoxy)-1-[4-(6-methoxy-pyridin-3-yl)-benzyl]-1H-indol-2-yl}-2,2-dimethyl-propionic acid;
3-{3-tert-butylsulfanyl-5-[2-(4-fluoro-phenyl)-2-hydroxy-ethoxy]-1-[4-(6-methoxy-pyridin-3-yl)-benzyl]-1H-indol-2-yl}-2,2-dimethyl-propionic acid;
3-[3-tert-butylsulfanyl-5-carbamoylmethoxy-1-(4-thiazol-2-yl-benzyl)-1H-indol-2-yl]-2,2-dimethyl-propionic acid ethyl ester;
2-[3-tert-butylsulfanyl-1-(4-chloro-benzyl)-2-(2-hydroxy-2-methyl-propyl)-1H-indol-5-yloxy]-acetamide;
2-[3-tert-butylsulfanyl-2-(2-hydroxy-2-methyl-propyl)-1-pyridin-4-ylmethyl-1H-indol-5-yloxy]-acetamide;
2-[3-tert-Butylsulfanyl-1-(4-cyano-benzyl)-2-(2-hydroxy-2-methyl-propyl)-1H-indol-5-yloxy]-acetamide;
2-[3-tert-butylsulfanyl-2-(2-hydroxy-2-methyl-propyl)-1-(4-iodo-benzyl)-1H-indol-5-yloxy]-acetamide;
2-[3-tert-butylsulfanyl-1-cyclopropylmethyl-2-(2-hydroxy-2-methyl-propyl)-1H-indol-5-yloxy]-acetamide;
2-[3-tert-butylsulfanyl-1-(4-chloro-benzyl)-2-(2-hydroxy-2-methyl-propyl)-1H-indol-5-yloxy]-N,N-diethyl-acetamide;
2-[3-tert-butylsulfanyl-2-(2-hydroxy-2-methyl-propyl)-1-pyridin-4-ylmethyl-1H-indol-5-yloxy]-N-(4-fluoro-phenyl)-acetamide;
2-[3-tert-butylsulfanyl-1-(4-chloro-benzyl)-2-(2-hydroxy-2-methyl-propyl)-1H-indol-5-yloxy]-N-(4-chloro-benzyl)-N-pyridin-3-yl-acetamide;
2-[3-tert-butylsulfanyl-2-(2-hydroxy-2-methyl-propyl)-1-pyridin-4-ylmethyl-1H-indol-5-yloxy]-N-cyclopropyl-acetamide;
2-[3-tert-butylsulfanyl-2-(2-hydroxy-2-methyl-propyl)-1-(4-iodo-benzyl)-1H-indol-5-yloxy]-N-(4-iodo-benzyl)-acetamide;
2-[3-tert-butylsulfanyl-2-(2-hydroxy-2-methyl-propyl)-1-(4-pyridin-3-yl-benzyl)-1H-indol-5-yloxy]-acetamide;
[3-tert-butylsulfanyl-1-(4-chloro-benzyl)-2-(2-hydroxy-2-methyl-propyl)-1H-indol-5-yloxy]-acetic acid;
[3-tert-butylsulfanyl-1-(4-chloro-benzyl)-2-(2-hydroxy-2-methyl-propyl)-1H-indol-5-yloxy]-acetic acid ethyl ester;
1-[3-tert-butylsulfanyl-1-(4-chloro-benzyl)-5-(2-hydroxy-2-methyl-propoxy)-1H-indol-2-yl]-2-methyl-propan-2-ol;
1-[3-tert-butylsulfanyl-1-(4-chloro-benzyl)-5-(2-hydroxy-propoxy)-1H-indol-2-yl]-2-methyl-propan-2-ol;
1-[3-tert-butylsulfanyl-1-(4-chloro-benzyl)-2-(2-hydroxy-2-methyl-propyl)-1H-indol-5-yloxy]-propan-2-one.

40 more elements

Dependencies are inferred from the claim text.

5-Lipoxygenase-Activating Protein (FLAP) Inhibitors

Life of this patent

Abstract

Claims26

5-Lipoxygenase-Activating Protein (FLAP) Inhibitors

Life of this patent

Abstract

Claims26