USRE49893EActiveUtility

[1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds

Assignee: BRISTOL MYERS SQUIBB COPriority: Jun 29, 2016Filed: Jan 25, 2022Granted: Apr 2, 2024
Est. expiryJun 29, 2036(~9.9 yrs left)· nominal 20-yr term from priority
A61K 31/4196A61K 31/437A61K 31/4427A61K 45/06C07D 249/00C07D 471/04A61P 19/02A61P 25/00A61P 29/00A61P 35/00A61P 37/00A61P 37/02A61P 43/00
91
PatentIndex Score
1
Cited by
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References
17
Claims

Abstract

Disclosed are compounds of Formula (I) or a salt thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , m, n, and p are defined herein. Also disclosed are methods of using such compounds as inhibitors of signaling through Toll-like receptor 7, or 8, or 9, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating inflammatory and autoimmune diseases.

Claims

exact text as granted — not AI-modified
The invention claimed is: 
     
       1. A compound of Formula (I) 
       
         
           
           
               
               
           
         
         or a salt thereof, wherein: 
         R 1  is H, Cl, —CN, C 1-4  alkyl, C 1-3  fluoroalkyl, C 1-3  hydroxy-fluoroalkyl, —CR z ═CH 2 , C 3-6  cycloalkyl, —CH 2 (C 3-6  cycloalkyl), —C(O)O(C 1-3  alkyl), or tetrahydropyranyl; 
         each R 2  is independently halo, —CN, —OH, —NO 2   + , C 1-3  alkyl, C 1-2  fluoroalkyl, C 1-2  cyanoalkyl, C 1-3  hydroxyalkyl, C 1-3  aminoalkyl, —O(CH 2 ) 1-2 OH, —(CH 2 ) 0-4 O(C 1-4  alkyl), C 1-3  fluoroalkoxy, —(CH 2 ) 1-4 O(C 1-3  alkyl), —O(CH 2 ) 1-2 OC(O)(C 1-3  alkyl), —O(CH 2 ) 1-2 NR x R x , —C(O)O(C 1-3  alkyl), —C(O)NR y R y , —NR y R y , —NR y (C 1-3  fluoroalkyl), —NR y (C 1-4  hydroxyalkyl), —NR x CH 2 (phenyl), —NR x S(O) 2 (C 3-6  cycloalkyl), —NR x C(O)(C 1-3  alkyl), —NR x (CH 2 -cyclopropyl), C 3-6  cycloalkyl, morpholinyl, dioxothiomorpholinyl, methylpiperidinyl, methylpiperazinyl, amino-oxadiazolyl, imidazolyl, triazolyl, or —C(O)(thiazolyl); 
         R 3  is -L 1 -A; 
         L 1  is bond; 
         A is 2-oxa-6-azaspiro[3,3]heptanyl, 4-oxaspiro[2.5]octanyl, 7-azaspiro[3.5]nonanyl, 8-azabicyclo[3.2.1]octanyl, 8-oxa-3-azabicyclo[3.2.1]octanyl, 9-azabicyclo[3.3.1]nonanyl, adamantanyl, azepanyl, azetidinyl, C 3-6  cycloalkyl, diazepanyl, dihydroinonyl, dihydropyrimidinonyl, dioxanyl, dioxidothiadiazinanyl, dioxidothiazolidinyl, dioxidothiomorpholinyl, dioxoisothiazolidinyl, dioxidothiazinanyl, dioxotetrahydrothiophenyl, dioxotetrahydrothiopyranyl, dioxothiomorpholinyl, furanyl, imidazolyl, imidazolidinonyl, indolyl, isoquinolinyl, isoxazolyl, morpholinyl, morpholinonyl, naphthalenyl, octahydrocyclopenta[b]pyranyl, octahydropyrrolo[3,4-b]pyridinyl, oxazolidinonyl, oxadiazolyl, oxazolyl, oxetanyl, phenyl, piperidinyl, piperidinonyl, piperazinyl, piperazinonyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridazinonyl, pyridinonyl, pyridinyl, pyrimidinyl, pyrrolidinonyl, pyrrolidinyl, pyrrolyl, quinolinyl, quinolizinonyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrazolyl, thiadiazolyl, thiazolyl, triazolonyl, or triazolyl, each substituted with -L 2 -R a  and zero to 4 R b ; 
         L 2  is a bond or —CR x R x —; 
         R a  is:
 (a) H, F, Cl, —CN, —OH, C 1-6  alkyl, C 1-3  fluoroalkyl, C 1-5  hydroxyalkyl, —(CH 2 ) 0-4 O(C 1-3  alkyl), —(CR x R x ) 1-3 S(C 1-3  alkyl), —NHC(O)OC(CH 3 ) 3 , —(CR x R x ) 1-3 NHC(O)O(C 1-4  alkyl), —(CR x R x ) 1-3 NR y R y , —(CR x R x ) 1-3 C(O)NR y R y , —O(C 1-3  fluoroalkyl), —S(O) 2 NR x R x , —O(CR x R x ) 1-3 NR x R x , —NHS(O) 2 (C 1-3  alkyl), —NR x R x , —NR x (C 1-4  alkyl), —NR x C(O)(C 1-4  alkyl), —(CR x R x ) 0-3 C(O)OH, —C(O)(C 1-5  alkyl), —C(O)(C 1-3  fluoroalkyl), —C(O)O(C 1-4  alkyl), —C(O)NH(C 1-3  cyanoalkyl), —C(O)NR y R y , —C(O)NR x CH 2 C(O)NR x R x , or —C(O)NR x CH 2 CH 2 NHC(O)(C 1-3  alkyl); 
 (b) C 3-6  cycloalkyl or —C(O)NH(C 3-6  cycloalkyl), wherein each cycloalkyl is substituted with zero to 2 substituents independently selected from —OH, C 1-3  alkyl, C 1-3  hydroxyalkyl, C 1-3  fluoroalkyl, and —C(O)O(C 1-3  alkyl); or 
 (c) A 1 , —CH 2 A 1 , —C(O)A 1 , —NR x A 1 , or —C(O)NR x A 1 , wherein A 1  is furanyl, imidazolyl, indolyl, isoxazolyl, morpholinyl, octahydropyrrolo[3,4-c]pyrrolyl, oxazolyl, oxetanyl, phenyl, piperazinonyl, piperazinyl, piperidinyl, pyrazinyl, pyrazolyl, pyridinyl, pyrimidinyl, pyrrolidinonyl, pyrrolidinyl, pyrrolyl, tetrahydrofuranyl, tetrahydropyranyl, thiadiazolyl, thiazolyl, thiophenyl, or triazolyl, each substituted with zero to three substituents independently selected from —OH, C 1-3  alkyl, C 1-3  hydroxyalkyl, —C(O)(C 1-2  alkyl), —C(O)O(C 1-3  alkyl), —NR x R x , phenyl, trifluoromethyl-phenyl, —CH 2 (bromophenyl), and —CH 2 CH 2 (pyrrolidinyl); 
 
         each R b  is independently F, —OH, —CH 3 , —CF 3 , or —OCH 3 ; 
         each R x  is independently H or —CH 3 ; 
         each R y  is independently H or C 1-6  alkyl; 
         R z  is H, C 1-2  alkyl, or C 1-2  fluoroalkyl; 
         each R 4  is independently F, —OH, C 1-2  alkyl, or —OCH 3 ; or two R 4  attached to the same carbon atom form ═O; or wherein when m is at least 2, two R 4 , each attached to a different carbon atom adjacent to the nitrogen atom in the piperidinyl ring, can form a —CH 2 CH 2 — bridge; 
         each R 5  is independently F, Cl, —CN, C 1-2  alkyl, C 1-2  fluoroalkyl, or —OCH 3 ; 
         m is zero, 1, 2, 3, or 4; 
         n is zero, 1, or 2; and 
         p is zero, 1, 2, 3, or 4. 
       
     
     
       2. The compound according to  claim 1  or salt thereof, wherein:
 R 1  is H, Cl, —CN, C 1-4  alkyl, or C 1-2  fluoroalkyl; 
 each R 2  is independently F, Cl, —CN, —OH, C 1-3  alkyl, C 1-2  fluoroalkyl, C 1-2  cyanoalkyl, C 1-3  hydroxyalkyl, C 1-3  aminoalkyl, —O(CH 2 ) 1-2 OH, —O(C 1-4  alkyl), C 1-2  fluoroalkoxy, —(CH 2 ) 1-4 O(C 1-3  alkyl), —O(CH 2 ) 1-2 OC(O)(C 1-3  alkyl), —O(CH 2 ) 1-2 NR x R x , —C(O)O(C 1-3  alkyl), —C(O)NR y R y , —NR y R y , —NR y (C 1-3  fluoroalkyl), —NR y (C 1-4  hydroxyalkyl), —NR x CH 2 (phenyl), —NR x S(O) 2 (C 3-6  cycloalkyl), —NR x C(O)(C 1-3  alkyl), —NR x (CH 2 -cyclopropyl), C 3-6  cycloalkyl, morpholinyl, dioxothiomorpholinyl, methylpiperidinyl, methylpiperazinyl, amino-oxadiazolyl, imidazolyl, triazolyl, or —C(O)(thiazolyl); 
 A is azetidinyl, C 3-6  cycloalkyl, dioxotetrahydrothiopyranyl, dioxidothiadiazinanyl, dioxidothiomorpholinyl, furanyl, imidazolyl, isoquinolinyl, morpholinyl, oxazolyl, 2-oxa-6-azaspiro[3.3]heptanyl, octahydropyrrolo[3,4-b]pyridinyl, oxetanyl, phenyl, piperazinonyl, piperazinyl, piperidinyl, pyrazinyl, pyrazolyl, pyridinyl, pyrrolidinonyl, pyrrolidinyl, pyrrolyl, quinolinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrazolyl, thiadiazolyl, thiazolyl, or triazolyl, each substituted with -L 2 -R a  and zero to 4 R b ; 
 R a  is:
 (a) H, F, —CN, —OH, C 1-3  alkyl, C 1-2  fluoroalkyl, C 1-3  hydroxyalkyl, —(CH 2 ) 0-2 O(C 1-3  alkyl), —NHC(O)OC(CH 3 ) 3 , —(CR x R x ) 1-3 NHC(O)O(C 1-4  alkyl), —(CR x R x ) 1-3 NH 2 , —(CR x R x ) 1-3 NR x (C 1-4  alkyl), —O(C 1-2  fluoroalkyl), —S(O) 2 NR x R x , —NHS(O) 2 (C 1-3  alkyl), —NR x R x , —NR x (C 1-4  alkyl), —(CR x R x ) 1-2 C(O)OH, —C(O)OH, —C(O)(C 1-3  alkyl), —C(O)O(C 1-4  alkyl), —C(O)NR x (C 1-2  alkyl), —C(O)N(C 1-3  alkyl) 2 , —C(O)NR x CH 2 C(O)NR x R x , or —C(O)NR x CH 2 CH 2 NHC(O)(C 1-3  alkyl); 
 (b) C 3-6  cycloalkyl or —C(O)NH(C 3-6  cycloalkyl), wherein each cycloalkyl is substituted with zero to 2 substituents independently selected from —OH, C 1-3  alkyl, C 1-3  hydroxyalkyl, C 1-3  fluoroalkyl, and —C(O)O(C 1-3  alkyl); or 
 (c) A 1 , —CH 2 A 1 , —C(O)A 1 , or —C(O)NHA 1 , wherein A 1  is furanyl, imidazolyl, indolyl, isoxazolyl, octahydropyrrolo[3,4-c]pyrrolyl, oxazolyl, oxetanyl, phenyl, piperazinyl, piperidinyl, pyrazinyl, pyrazolyl, pyridinyl, pyrimidinyl, pyrrolidinyl, pyrrolyl, tetrahydrofuranyl, tetrahydropyranyl, thiadiazolyl, thiazolyl, thiophenyl, or triazolyl, each substituted with zero to three substituents independently selected from —OH, C 1-3  alkyl, C 1-3  hydroxyalkyl, —C(O)(C 1-2  alkyl), —C(O)O(C 1-3  alkyl), —NR x R x , phenyl, trifluoromethylphenyl, —CH 2 (bromophenyl), and —CH 2 CH 2 (pyrrolidinyl); 
 
 each R 4  is independently F, —OH, C 1-2  alkyl, or —OCH 3 ; or two R 4  attached to the same carbon atom form ═O; 
 R 5  is F, Cl, —CN, —CH 3 , —CF 3 , or —OCH 3 ; 
 each R b  is independently —OH, —CH 3 , or —CF 3 ; 
 each R x  is independently H or —CH 3 ; 
 each R y  is independently H or C 1-5  alkyl; 
 m is zero, 1, or 2; 
 n is zero or 1; and 
 p is zero, 1, or 2. 
 
     
     
       3. The compound according to  claim 1  or salt thereof, wherein:
 R 1  is —CH 2 CH 3 , —CH(CH 3 ) 2 , or —CH 2 CHF 2 ; 
 each R 2  is independently F, Cl, —CN, —CH 3 , —CD 3 , —CH 2 CH 3 , —CH(CH 3 ) 2 , —CF 3 , —CH 2 CN, —CH 2 OH, —CH 2 CH 2 OH, —CH(CH 3 )OH, —C(CH 3 ) 2 OH, —OCH 2 CH 2 OH, —OCH 3 , —OCH 2 CH 3 , —CH 2 OCH 3 , —OCH 2 CH 2 OC(O)CH 3 , —NH(CH 2 CF 3 ), —NHS(O) 2 (cyclopropyl), cyclopropyl, morpholinyl, dioxothiomorpholinyl, or methylpiperazinyl; 
 A is C 4-6  cycloalkyl, dioxanyl, dioxotetrahydrothiophenyl, dioxotetrahydrothiopyranyl, oxetanyl, pyridinyl, pyrimidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiopyranyl, or triazolyl, each substituted with -L 2 -R a  and zero to 1 R b ; 
 L 2  is a bond; 
 R a  is —CN, —OH, —CH 3 , —NHC(O)OC(CH 3 ) 3 , or —C(O)OCH 2 CH 3 ; 
 R b  is —CH 3 ; 
 m is zero; 
 n is zero; and 
 p is zero, 1 or 2. 
 
     
     
       4. The compound according to  claim 1  or salt thereof, wherein:
 R 1  is —CH 2 CH 3 , —CH(CH 3 ) 2 , or —CH 2 CHF 2 ; 
 A is oxetanyl, tetrahydrofuranyl, or tetrahydropyranyl, each substituted with -L 2 -R a  and zero to 2 R b ; 
 L 2  is a bond; 
 m is zero or 1; 
 n is zero; and 
 p is zero, 1 or 2. 
 
     
     
       5. The compound according to  claim 1  or salt thereof, wherein:
 R 1  is —CH 2 CH 3 , —CH(CH 3 ) 2 , or —CH 2 CHF 2 ; 
 A is cyclobutyl, cyclopentyl, or dioxotetrahydrothiopyranyl, each substituted with -L 2 -R a  and zero to 2 R b ; 
 L 2  is a bond; 
 m is zero or 1; 
 n is zero; and 
 p is zero, 1 or 2. 
 
     
     
       6. The compound according to  claim 1  or a salt thereof, wherein said compound is:
 4-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)tetrahydro-2H-thiopyran 1,1-dioxide (20); 
 6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (26); 
 6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (35); 
 4-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)tetrahydro-2H-thiopyran 1,1-dioxide (37); 
 6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (38); 
 6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (40); 
 6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (44); 
 6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (45); 
 3-(4-(2-(8-(hydroxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)oxetane-3-carbonitrile (235); 
 6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine (351); 
 6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine (352); 
 6-(3-isopropyl-5-(1-((1-methyl-1H-1,2,4-triazol-3-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine (353); 
 6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine (354); 
 6-(3-isopropyl-5-(1-(tetrahydrofuran-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine (355); 
 6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-(trideuteromethyl)-[1,2,4]triazolo[1,5-a]pyridine (357); 
 6-(3-isopropyl-5-(1-(tetrahydrofuran-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (393); 
 6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (394); 
 3-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)tetrahydrothiophene 1,1-dioxide (395); 
 4-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)cyclohexan-1-ol (403); 
 2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-1-methylcyclopentane-1-carbonitrile (416-417); 
 6-(3-isopropyl-5-(1-(tetrahydro-2H-thiopyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (425); 
 6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine (441); 
 6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine (443); 
 3-(4-(3-isopropyl-2-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)tetrahydrothiophene 1,1-dioxide (460); 
 8-fluoro-6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine (469); 
 6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridine (473); 
 6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (487); 
 6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (488); 
 4-(4-(2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)tetrahydro-2H-thiopyran 1,1-dioxide (489); 
 2-(6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)propan-2-ol (492); 
 2-(6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)propan-2-ol (493); 
 4-(4-(2-(8-(2-hydroxypropan-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)tetrahydro-2H-thiopyran 1,1-dioxide (496); 
 6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-(methoxymethyl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine (499); 
 6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine-8-carbonitrile (500); 
 6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine-8-carbonitrile (501); 
 1-(6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)ethan-1-ol (503); 
 (6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-8-yl)methanol (504); 
 2-(6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)acetonitrile (506); 
 8-fluoro-6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine (507); 
 (6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)methanol (508); 
 (6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)methanol (510); 
 4-(4-(2-(8-(hydroxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)tetrahydro-2H-thiopyran 1,1-dioxide (514); 
 (6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)methanol (521); 
 2-(6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)ethan-1-ol (525); 
 2-((6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)oxy)ethyl acetate (528); 
 2-((6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)oxy)ethan-1-ol (529-530); 
 6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-2-methyl-[1,2,4]triazolo[1,5-a]pyridine (534); 
 6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-2-methyl-[1,2,4]triazolo[1,5-a]pyridine (535); 
 tert-butyl (3-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)cyclobutyl)carbamate (538); 
 ethyl 3-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)cyclobutane-1-carboxylate (539); 
 6-(3-isopropyl-5-(1-(tetrahydrofuran-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (540-541); 
 6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (542); 
 6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (543); 
 4-(4-(2-(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)tetrahydro-2H-thiopyran 1,1-dioxide (545); 
 6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-2,7-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (546); 
 6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-2,7-dimethyl-[1,2,4]triazolo [1,5-a]pyridine (547); 
 4-(4-(2-(2,7-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)tetrahydro-2H-thiopyran 1,1-dioxide (548); 
 6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine (549); 
 4-(4-(3-isopropyl-2-(8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)tetrahydro-2H-thiopyran 1,1-ioxide (550); 
 6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine (552); 
 6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine (554); 
 4-(4-(3-isopropyl-2-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)tetrahydro-2H-thiopyran 1,1-dioxide (455); 
 6-(3-isopropyl-5-(1-(tetrahydrofuran-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine (556-557); 
 6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-2,5-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (558); 
 4-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)tetrahydro-2H-thiopyran 1,1-dioxide (561); 
 6-(5-(1-(2,2-dimethyltetrahydro-2H-pyran-4-yl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (562-564); 
 3-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)cyclobutane-1-carbonitrile (567); 
 6-(3-isopropyl-5-(1-(tetrahydrofuran-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (568-569); 
 8-ethoxy-6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine (571); 
 8-ethoxy-6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine (572); 
 4-(4-(2-(8-ethoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)tetrahydro-2H-thiopyran 1,1-dioxide (573); 
 6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-2-methyl-[1,2,4]triazolo[1,5-a]pyridine (574); 
 6-(3-isopropyl-5-(1-(tetrahydrofuran-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-2-methyl-[1,2,4]triazolo[1,5-a]pyridine (575-576); 
 8-ethyl-6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-2-methyl-[1,2,4]triazolo[1,5-a]pyridine (577); 
 8-ethyl-6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-2-methyl-[1,2,4]triazolo[1,5-a]pyridine (578); 
 8-chloro-6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine (579); 
 8-chloro-6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine (580); 
 4-(6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)morpholine (581); 
 8-ethyl-6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine (583); 
 8-isopropyl-6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine (585); 
 6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-N-(2,2,2-trifluoroethyl)-[1,2,4]triazolo[1,5-a]pyridin-8-amine (586); 
 8-ethyl-6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine (587); 
 6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridine (588); 
 N-(6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)cyclopropanesulfonamide (590); 
 4-(6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)thiomorpholine 1,1-dioxide (591); 
 6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-(4-methylpiperazin-1-yl)-[1,2,4]triazolo[1,5-a]pyridine (592); 
 8-cyclopropyl-6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine (593); 
 8-cyclopropyl-6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-2-methyl-[1,2,4]triazolo[1,5-a]pyridine (594); 
 8-cyclopropyl-6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine (595); 
 6-(3-ethyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (596); 
 6-(3-(2,2-difluoroethyl)-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (597); 
 6-(3-(2,2-difluoroethyl)-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (598); 
 6-(3-ethyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (600); 
 6-(3-isopropyl-5-(1-(pyridin-2-yl)piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (986); 
 6-(3-isopropyl-5-(1-(pyrimidin-2-yl)piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (989); or 
 6-(5-(1-(2,2-dimethyl-1,3-dioxan-5-yl)piperidin-4-yl)-4-fluoro-3-isopropyl-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (993). 
 
     
     
       7. The compound according to  claim 1  or a salt thereof, wherein said compound is: 
       
         
           
           
               
               
           
         
       
     
     
       8. The compound according to  claim 1  or a salt thereof, wherein said compound is: 
       
         
           
           
               
               
           
         
       
     
     
       9. The compound according to  claim 1  or a salt thereof, wherein said compound is: 
       
         
           
           
               
               
           
         
       
     
     
       10. A pharmaceutical composition comprising a compound according to  claim 1  or a pharmaceutically-acceptable salt thereof; and a pharmaceutically acceptable carrier. 
     
     
       11. A pharmaceutical composition comprising a compound according to  claim 7  or a pharmaceutically-acceptable salt thereof; and a pharmaceutically acceptable carrier. 
     
     
       12. A pharmaceutical composition comprising a compound according to  claim 8  or a pharmaceutically-acceptable salt thereof; and a pharmaceutically acceptable carrier. 
     
     
       13. A pharmaceutical composition comprising a compound according to  claim 9  or a pharmaceutically-acceptable salt thereof; and a pharmaceutically acceptable carrier. 
     
     
       14. A method of treating an autoimmune disease or a chronic inflammatory disease, comprising administering to a mammalian patent patient a compound according to  claim 1  or a pharmaceutically acceptable salt thereof, wherein said autoimmune disease or chronic inflammatory disease is systemic lupus erythematosus. 
     
     
       15. A method of treating an autoimmune disease or a chronic inflammatory disease, comprising administering to a mammalian patent patient a compound according to  claim 7  or a pharmaceutically acceptable salt thereof, wherein said autoimmune disease or chronic inflammatory disease is systemic lupus erythematosus. 
     
     
       16. A method of treating an autoimmune disease or a chronic inflammatory disease, comprising administering to a mammalian patent patient a compound according to  claim 8  or a pharmaceutically acceptable salt thereof, wherein said autoimmune disease or chronic inflammatory disease is systemic lupus erythematosus. 
     
     
       17. A method of treating an autoimmune disease or a chronic inflammatory disease, comprising administering to a mammalian patent patient a compound according to  claim 9  or a pharmaceutically acceptable salt thereof, wherein said autoimmune disease or chronic inflammatory disease is systemic lupus erythematosus.

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