Haloallylamine indole and azaindole derivative inhibitors of lysyl oxidases and uses thereof

1. A method of treating a condition associated with LOX, LOXL1, LOXL2, LOXL3 and LOXL4 protein, wherein the condition is selected from the group consisting of a liver disorder, a kidney disorder, a cardiovascular disease, fibrosis, a cancer and angiogenesis, the method comprising administering to a subject in need thereof a therapeutically effective amount of compound according to Formula I:

or a stereoisomer, pharmaceutically acceptable salt, or tautomer thereof; wherein:

a is N or CR 3 ;

b is N or CR 4 ;

c is N or CR 5 ;

d is N or CR 6 ;

and from 0 to 2 of a, b, c and d are N;

R 1 is selected from the group consisting of hydrogen, halogen, C 1-6 alkyl, C 3-7 cycloalkyl, —O—C 1-6 alkyl, —O—C 3-7 cycloalkyl, —C(O)OR 8 , —C(O)NR 9 R 10 and —NR 9 C(O)R 11 ; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —SH, —C 1-3 alkyl, —O—C 1-3 alkyl, —CF 3 , —CH 2 CF 3 , and —O—CF 3 ;

R 2 is aryl or heteroaryl; wherein each R 2 is optionally substituted by one or more R 12 ;

R 3 , R 4 , R 5 and R 6 are each independently selected from the group consisting of hydrogen, halogen, hydroxyl, C 1-6 alkyl, C 3-7 cycloalkyl, —O—C 1-6 alkyl, —O—C 3-7 cycloalkyl, —CN, —NO 2 , —NR 9 R 10 , —C(O)OR 8 , —C(O)NR 9 R 10 , —NR 9 C(O)R 11 , —S(O 2 )NR 9 R 10 , —NR 9 S(O 2 )R 11 , —S(O)R 11 , —S(O 2 )R 11 , tetrazole and oxadiazole; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —SH, —C 1-3 alkyl, —CF 3 , —CH 2 CF 3 , and —O—CF 3 ;

R 8 is selected from the group consisting of hydrogen, C 1-6 alkyl, and C 3-7 cycloalkyl; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —SH, —C 1-3 alkyl, —O—C 1-3 alkyl, —CF 3 , —CH 2 CF 3 , and —O—CF 3 ;

R 9 and R 10 are independently selected from the group consisting of hydrogen, C 1-6 alkyl and C 3-7 cycloalkyl; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —SH, —C 1-3 alkyl, —O—C 1-3 alkyl, —CF 3 , —CH 2 CF 3 , and —O—CF 3 ; or

R 9 and R 10 when attached to the same nitrogen atom are combined to form a 3- to 7-membered ring having from 0 to 2 additional heteroatoms as ring members;

R 11 is selected from the group consisting of C 1-6 alkyl and C 3-7 cycloalkyl; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —SH, —C 1-3 alkyl, —O—C 1-3 alkyl, —CF 3 , —CH 2 CF 3 , and —O—CF 3 ; and

R 12 is selected from the group consisting of halogen, C 1-6 alkyl, —O—C 1-6 alkyl, —S—C 1-6 alkyl C 3-7 cycloalkyl, —O—C 3-7 cycloalkyl, —C(O)OR 8 , —C(O)NR 9 R 10 , —NR 9 C(O)R 11 , —S(O 2 )NR 9 R 10 , —NR 9 S(O 2 )R 11 , —S(O)R 11 and —S(O 2 )R 11 ; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —C 1-3 alkyl, —O—C 1-3 alkyl, —CF 3 , —CH 2 CF 3 , and —O—CF 3 or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 , wherein the condition is a liver disorder selected from the group consisting of biliary atresia, cholestatic liver disease, chronic liver disease, nonalcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), fatty liver disease associated with disorders such as hepatitis or metabolic syndrome; hepatitis C infection, alcoholic liver disease, primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), liver damage due to progressive fibrosis, liver fibrosis and liver cirrhosis.

3. The method of claim 1 , wherein the condition is a kidney disorder selected from the group consisting of kidney fibrosis, renal fibrosis, acute kidney injury, chronic kidney disease, diabetic nephropathy, glomerulosclerosis, vesicoureteral reflux, tubulointerstitial renal fibrosis and glomerulonephritis.

4. The method of claim 1 , wherein the condition is a cardiovascular disease selected from the group consisting of atherosclerosis, arteriosclerosis, hypercholesteremia, and hyperlipidemia.

5. The method of claim 1 , wherein the condition is fibrosis selected from the group consisting of liver fibrosis, lung fibrosis, kidney fibrosis, cardiac fibrosis, cystic fibrosis, idiopathic pulmonary fibrosis, radiation-induced fibrosis, ocular fibrosis, Peyronie's disease and scleroderma or is associated with respiratory disease, abnormal wound healing and repair, post-surgical operations, cardiac arrest and all conditions where excess or aberrant deposition of fibrous material is associated with disease, including Crohn's disease and inflammatory bowel disease.

6. The method of claim 1 , wherein the condition is a cancer selected from the group consisting of lung cancer; breast cancer; colorectal cancer; anal cancer; pancreatic cancer; prostate cancer; ovarian carcinoma; liver and bile duct carcinoma; esophageal carcinoma; non-Hodgkin's lymphoma; bladder carcinoma; carcinoma of the uterus; glioma, glioblastoma, medulloblastoma, and other tumors of the brain; myelofibrosis, kidney cancer; cancer of the head and neck; cancer of the stomach; multiple myeloma; testicular cancer; germ cell tumor; neuroendocrine tumor; cervical cancer; oral cancer, carcinoids of the gastrointestinal tract, breast, and other organs; signet ring cell carcinoma; mesenchymal tumors including sarcomas, fibrosarcomas, haemangioma, angiomatosis, hemangiopericytoma, pseudoangiomatous stromal hyperplasia, myofibroblastoma, fibromatosis, inflammatory myofibroblastic tumour, lipoma, angiolipoma, granular cell tumour, neurofibroma, schwannoma, angiosarcoma, liposarcoma, rhabdomyosarcoma, osteosarcoma, leiomyoma or a leiomyosarcoma.

7. The method of claim 1 , wherein the condition is angiogenesis.

8. The method according to claim 1 , further comprising administering a second therapeutic agent.

9. The method according to claim 8 , wherein the second therapeutic agent is selected from the group consisting of an anti-cancer agent, anti-inflammatory agent, anti-hypertensive agent, an anti-fibrotic agent, an anti-angiogenic agent and an immunosuppressive agent.

10. The method according to claim 1 , comprising administering to a subject in need thereof a therapeutically effective amount of compound according to Formula Ia:

or a pharmaceutically acceptable salt thereof; wherein:

R 1 is selected from the group consisting of hydrogen, halogen, C 1-6 alkyl, C 3-7 cycloalkyl, —O—C 1-6 alkyl, —O—C 3-7 cycloalkyl, —C(O)OR 8 , —C(O)NR 9 R 10 and —NR 9 C(O)R 11 ; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —SH, —C 1-3 alkyl, —O—C 1-3 alkyl, —CF 3 , —CH 2 CF 3 , and —O—CF 3 ;

R 2 is aryl or heteroaryl; wherein each R 2 is optionally substituted by one or more R 12 ;

R 3 , R 4 , R 5 and R 6 are each independently selected from the group consisting of hydrogen, halogen, hydroxyl, C 1-6 alkyl, C 3-7 cycloalkyl, —O—C 1-6 alkyl, —O—C 3-7 cycloalkyl, —CN, —NO 2 , —NR 9 R 10 , —C(O)OR 8 , —C(O)NR 9 R 10 , —NR 9 C(O)R 11 , —S(O 2 )NR 9 R 10 , —NR 9 S(O 2 )R 11 , —S(O)R 11 , —S(O 2 )R 11 , tetrazole and oxadiazole; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —SH, —C 1-3 alkyl, —O—C 1-3 alkyl, —CF 3 , —CH 2 CF 3 , and —O—CF 3 ;

R 8 is selected from the group consisting of hydrogen, C 1-6 alkyl, and C 3-7 cycloalkyl; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —SH, —C 1-3 alkyl, —O—C 1-3 alkyl, —CF 3 , —CH 2 CF 3 , and —O—CF 3 ;

R 9 and R 10 are independently selected from the group consisting of hydrogen, C 1-6 alkyl and C 3-7 cycloalkyl; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —SH, —C 1-3 alkyl, —O—C 1-3 alkyl, —CF 3 , —CH 2 CF 3 , and —O—CF 3 ; or

R 9 and R 10 when attached to the same nitrogen atom are combined to form a 3- to 7-membered ring having from 0 to 2 additional heteroatoms as ring members;

R 11 is selected from the group consisting of C 1-6 alkyl and C 3-7 cycloalkyl; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —SH, —C 1-3 alkyl, —O—C 1-3 alkyl, —CF 3 , —CH 2 CF 3 , and —O—CF 3 ; and

R 12 is selected from the group consisting of halogen, C 1-6 alkyl, —O—C 1-6 alkyl, —S—C 1-6 alkyl, C 3-7 cycloalkyl, —O—C 3-7 cycloalkyl, —C(O)OR 8 , —C(O)NR 9 R 10 , —NR 9 C(O)R 11 , —S(O 2 )NR 9 R 10 , —NR 9 S(O 2 )R 11 , —S(O)R 11 and —S(O 2 )R 11 ; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —C 1-3 alkyl, —O—C 1-3 alkyl, —CF 3 , —CH 2 CF 3 , and —O—CF 3 .

11. The method according to claim 1 , comprising administering to a subject in need thereof a therapeutically effective amount of compound according to Formula Ib:

or a pharmaceutically acceptable salt thereof; wherein:

R 1 is selected from the group consisting of hydrogen, halogen, C 1-6 alkyl, C 3-7 cycloalkyl, —O—C 1-6 alkyl, —O—C 3-7 cycloalkyl, —C(O)OR 8 , —C(O)NR 9 R 10 and —NR 9 C(O)R 11 ; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —SH, —CF 3 , —CH 2 CF 3 , and —O—CF 3 ;

R 2 is aryl or heteroaryl; wherein each R 2 is optionally substituted by one or more R 12 ;

R 3 , R 4 and R 5 are each independently selected from the group consisting of hydrogen, halogen, hydroxyl, C 1-6 alkyl, C 3-7 cycloalkyl, —O—C 3-7 cycloalkyl, —CN, —NO 2 , —NR 9 R 10 , —C(O)OR 8 , —C(O)NR 9 R 10 , —NR 9 C(O)R 11 , —S(O 2 )NR 9 R 10 , —NR 9 S(O 2 )R 11 , —S(O)R 11 , —S(O 2 )R 11 , tetrazole and oxadiazole; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —SH, —CF 3 , —CH 2 CF 3 , and —O—CF 3 ;

R 8 is selected from the group consisting of hydrogen, C 1-6 alkyl, and C 3-7 cycloalkyl; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —SH, —CF 3 , —CH 2 CF 3 , and —O—CF 3 ;

R 9 and R 10 are independently selected from the group consisting of hydrogen, C 1-6 alkyl and C 3-7 cycloalkyl; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —SH, —C 1-3 alkyl, —O—C 1-3 alkyl, —CF 3 , —CH 2 CF 3 , and —O—CF 3 ; or

R 9 and R 10 when attached to the same nitrogen atom are combined to form a 3- to 7-membered ring having from 0 to 2 additional heteroatoms as ring members;

R 11 is selected from the group consisting of C 1-6 alkyl and C 3-7 cycloalkyl; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —SH, —C 1-3 alkyl, —O—C 1-3 alkyl, —CF 3 , —CH 2 CF 3 , and —O—CF 3 ; and

R 12 is selected from the group consisting of halogen, C 1-6 alkyl, —O—C 1-6 alkyl, —S—C 1-6 alkyl, C 3-7 cycloalkyl, —O—C 3-7 cycloalkyl, —C(O)OR 8 , —C(O)NR 9 R 10 , —NR 9 C(O)R 11 , —S(O 2 )NR 9 R 10 , —NR 9 S(O 2 )R 11 , —S(O)R 11 and —S(O 2 )R 11 ; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —C 1-3 alkyl, —O—C 1-3 alkyl, —CF 3 , —CH 2 CF 3 , and —O—CF 3 .

12. The method according to claim 1 , comprising administering to a subject in need thereof a therapeutically effective amount of compound according to Formula Ic:

or a pharmaceutically acceptable salt thereof; wherein:

R 1 is selected from the group consisting of hydrogen, halogen, C 1-6 alkyl, C 3-7 cycloalkyl, —O—C 1-6 alkyl, —O—C 3-7 cycloalkyl, —C(O)OR 8 , —C(O)NR 9 R 10 and —NR 9 C(O)R 11 ; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —SH, —C 1-3 alkyl, —O—C 1-3 alkyl, —CF 3 , —CH 2 CF 3 , and —O—CF 3 ;

R 2 is aryl or heteroaryl; wherein each R 2 is optionally substituted by one or more R 12 ;

R 3 , R 4 and R 6 are each independently selected from the group consisting of hydrogen, halogen, hydroxyl, C 1-6 alkyl, C 3-7 cycloalkyl, —O—C 1-6 alkyl, —O—C 3-7 cycloalkyl, —CN, —NO 2 , —NR 9 R 10 , —C(O)OR 8 , —C(O)NR 9 R 10 , —NR 9 C(O)R 11 , —S(O 2 )NR 9 R 10 , —NR 9 S(O 2 )R 11 , —S(O)R 11 , —S(O 2 )R 11 , tetrazole and oxadiazole; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —SH, —C 1-3 alkyl, —O—C 1-3 alkyl, —CF 3 , —CH 2 CF 3 , and —O—CF 3 ;

R 8 is selected from the group consisting of hydrogen, C 1-6 alkyl, and C 3-7 cycloalkyl; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —SH, —C 1-3 alkyl, —O—C 1-3 alkyl, —CF 3 , —CH 2 CF 3 , and —O—CF 3 ;

R 9 and R 10 are independently selected from the group consisting of hydrogen, C 1-6 alkyl and C 3-7 cycloalkyl; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —SH, —C 1-3 alkyl, —O—C 1-3 alkyl, —CF 3 , —CH 2 CF 3 , and —O—CF 3 ; or

R 9 and R 10 when attached to the same nitrogen atom are combined to form a 3- to 7-membered ring having from 0 to 2 additional heteroatoms as ring members;

R 11 is selected from the group consisting of C 1-6 alkyl and C 3-7 cycloalkyl; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —SH, —C 1-3 alkyl, —O—C 1-3 alkyl, —CF 3 , —CH 2 CF 3 , and —O—CF 3 ; and

R 12 is selected from the group consisting of halogen, C 1-6 alkyl, —O—C 1-6 alkyl, —S—C 1-6 alkyl, C 3-7 cycloalkyl, —O—C 3-7 cycloalkyl, —C(O)OR 8 , —C(O)NR 9 R 10 , —NR 9 C(O)R 11 , —S(O 2 )NR 9 R 10 , —NR 9 S(O 2 )R 11 , —S(O)R 11 and —S(O 2 )R 11 ; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —C 1-3 alkyl, —O—C 1-3 alkyl, —CF 3 , —CH 2 CF 3 , and —O—CF 3 .

13. The method according to claim 1 , comprising administering to a subject in need thereof a therapeutically effective amount of compound according to Formula Id:

or a pharmaceutically acceptable salt thereof; wherein:

R 1 is selected from the group consisting of hydrogen, halogen, C 1-6 alkyl, C 3-7 cycloalkyl, —O—C 1-6 alkyl, —O—C 3-7 cycloalkyl, —C(O)OR 8 , —C(O)NR 9 R 10 and —NR 9 C(O)R 11 ; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —SH, —C 1-3 alkyl, —O—C 1-3 alkyl, —CF 3 , —CH 2 CF 3 , and —O—CF 3 ;

R 2 is aryl or heteroaryl; wherein each R 2 is optionally substituted by one or more R 12 ;

R 3 , R 5 and R 6 are each independently selected from the group consisting of hydrogen, halogen, hydroxyl, C 1-6 alkyl, C 3-7 cycloalkyl, —O—C 1-6 alkyl, —O—C 3-7 cycloalkyl, —CN, —NO 2 , —NR 9 R 10 , —C(O)OR 8 , —C(O)NR 9 R 10 , —NR 9 C(O)R 11 , —S(O 2 )NR 9 R 10 , —NR 9 S(O 2 )R 11 , —S(O)R 11 , —S(O 2 )R 11 , tetrazole and oxadiazole; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —SH, —C 1-3 alkyl, —O—C 1-3 alkyl, —CF 3 , —CH 2 CF 3 , and —O—CF 3 ;

R 8 is selected from the group consisting of hydrogen, C 1-6 alkyl, and C 3-7 cycloalkyl; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —SH, —C 1-3 alkyl, —O—C 1-3 alkyl, —CF 3 , —CH 2 CF 3 , and —O—CF 3 ;

R 9 and R 10 are independently selected from the group consisting of hydrogen, C 1-6 alkyl and C 3-7 cycloalkyl; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —SH, —C 1-3 alkyl, —O—C 1-3 alkyl, —CF 3 , —CH 2 CF 3 , and —O—CF 3 ; or

R 9 and R 10 when attached to the same nitrogen atom are combined to form a 3- to 7-membered ring having from 0 to 2 additional heteroatoms as ring members;

R 11 is selected from the group consisting of C 1-6 alkyl and C 3-7 cycloalkyl; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —SH, —C 1-3 alkyl, —O—C 1-3 alkyl, —CF 3 , —CH 2 CF 3 , and —O—CF 3 ; and

R 12 is selected from the group consisting of halogen, C 1-6 alkyl, —O—C 1-6 alkyl, —S—C 1-6 alkyl, C 3-7 cycloalkyl, —O—C 3-7 cycloalkyl, —C(O)OR 8 , —C(O)NR 9 R 10 , —NR 9 C(O)R 11 , —S(O 2 )NR 9 R 10 , —NR 9 S(O 2 )R 11 , —S(O)R 11 and —S(O 2 )R 11 ; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —C 1-3 alkyl, —O—C 1-3 alkyl, —CF 3 , —CH 2 CF 3 , and —O—CF 3 .

14. The method according to claim 1 , comprising administering to a subject in need thereof a therapeutically effective amount of compound according to Formula Ie:

or a pharmaceutically acceptable salt thereof; wherein:

R 1 is selected from the group consisting of hydrogen, halogen, C 1-6 alkyl, C 3-7 cycloalkyl, —O—C 1-6 alkyl, —O—C 3-7 cycloalkyl, —C(O)OR 8 , —C(O)NR 9 R 10 and —NR 9 C(O)R 11 ; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —SH, —C 1-3 alkyl, —O—C 1-3 alkyl, —CF 3 , —CH 2 CF 3 , and —O—CF 3 ;

R 2 is aryl or heteroaryl; wherein each R 2 is optionally substituted by one or more R 12 ;

R 4 , R 5 and R 6 are each independently selected from the group consisting of hydrogen, halogen, hydroxyl, C 1-6 alkyl, C 3-7 cycloalkyl, —O—C 1-6 alkyl, —O—C 3-7 cycloalkyl, —CN, —NO 2 , —NR 9 R 10 , —C(O)OR 8 , —C(O)NR 9 R 10 , —NR 9 C(O)R 11 , —S(O 2 )NR 9 R 10 , —NR 9 S(O 2 )R 11 , —S(O)R 11 , —S(O 2 )R 11 , tetrazole and oxadiazole; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —SH, —C 1-3 alkyl, —O—C 1-3 alkyl, —CF 3 , —CH 2 CF 3 , and —O—CF 3 ;

R 8 is selected from the group consisting of hydrogen, C 1-6 alkyl, and C 3-7 cycloalkyl; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —SH, —C 1-3 alkyl, —O—C 1-3 alkyl, —CF 3 , —CH 2 CF 3 , and —O—CF 3 ;

R 9 and R 10 are independently selected from the group consisting of hydrogen, C 1-6 alkyl and C 3-7 cycloalkyl; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —SH, —C 1-3 alkyl, —O—C 1-3 alkyl, —CF 3 , —CH 2 CF 3 , and —O—CF 3 ; or

R 9 and R 10 when attached to the same nitrogen atom are combined to form a 3- to 7-membered ring having from 0 to 2 additional heteroatoms as ring members;

R 11 is selected from the group consisting of C 1-6 alkyl and C 3-7 cycloalkyl; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —SH, —C 1-3 alkyl, —O—C 1-3 alkyl, —CF 3 , —CH 2 CF 3 , and —O—CF 3 ; and

R 12 is selected from the group consisting of halogen, C 1-6 alkyl, —O—C 1-6 alkyl, —S—C 1-6 alkyl, C 3-7 cycloalkyl, —O—C 3-7 cycloalkyl, —C(O)OR 8 , —C(O)NR 9 R 10 , —NR 9 C(O)R 11 , —S(O 2 )NR 9 R 10 , —NR 9 S(O 2 )R 11 , —S(O)R 11 and —S(O 2 )R 11 ; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl and C 3-7 cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH, —C 1-3 alkyl, —O—C 1-3 alkyl, —CF 3 , —CH 2 CF 3 , and —O—CF 3 .

15. The method according to claim 1 , comprising administering to a subject in need thereof a therapeutically effective amount of compound Formula Ib:

or a pharmaceutically acceptable salt thereof; wherein:

R 1 is selected from the group consisting of hydrogen and C 1-6 alkyl; wherein each C 1-6 alkyl is a straight or branched chain alkyl;

R 2 is phenyl substituted by one or more R 12 ;

R 3 is hydrogen;

R 4 is selected from the group consisting of hydrogen and halogen;

R 5 is selected from the group consisting of hydrogen, halogen, hydroxyl, C 1-6 alkyl, —O—C 1-6 alkyl, —NR 9 R 10 , —C(O)OR 8 , and —C(O)NR 9 R 10 ; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and wherein each C 1-6 alkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, —OH and O—C 1-3 alkyl;

R 8 is selected from the group consisting of hydrogen and, C 1-6 alkyl;

R 9 and R 10 are independently selected from the group consisting of hydrogen and C 1-6 alkyl; wherein each C 1-6 alkyl is a straight or branched chain alkyl;

R 11 is C 1-6 alkyl; wherein each C 1-6 alkyl is a straight or branched chain alkyl; and

R 12 is selected from the group consisting of —S(O 2 )NR 9 R 10 and —S(O 2 )R 11 .

16. The method according to claim 15 , wherein:

R 1 is selected from the group consisting of hydrogen, methyl and isopropyl;

R 2 is phenyl substituted by one or more R 12 ;

R 3 is hydrogen;

R 4 is selected from the group consisting of hydrogen, fluorine and chlorine;

R 5 is selected from the group consisting of hydrogen, fluorine, hydroxyl, —CH 3 , —CH 2 F, —CHF 2 , —CF 3 , —CF 2 CH 3 , —C(CH 3 ) 2 OH, —CH 2 OCH 3 , —OCH 3 , —C(O)OH, —N(CH 3 ) 2 , —C(O)OEt, —C(O)N(CH 3 ) 2 , —C(O)NHCH 3 and —C(O)NH i Pr; and

R 12 is selected from the group consisting of —S(O 2 )N(CH 3 ) 2 , —S(O 2 )NH 2 , —S(O 2 )CH 3 , —S(O 2 )Et and —S(O 2 ) i Pr.

17. The method according to claim 1 , comprising administering to a subject in need thereof a therapeutically effective amount of compound selected from the group consisting of:

2

(Z)-3-(1-(4-amino-2-fluorobut-2-en-1- yl)-2-methyl-1H-indol-3-yl)-N,N- dimethylbenzenesulfonamide

4

(Z)-3-(1-(4-amino-2-fluorobut-2-en-1- yl)-2-methyl-1H-pyrrolo[2,3- b]pyridin-3-yl dimethylbenzenesulfonamide

5

(Z)-methyl 1-(4-amino-2-fluorobut-2- en-1-yl)-3-(3-(N,N- dimethylsulfamoyl)phenyl)-2-methyl- 1H-indole-5-carboxylate

6

(Z)-1-(4-amino-2-fluorobut-2-en-1- yl)-3-(3-(N,N- dimethylsulfamoyl)phenyl)-N,N,2- trimethyl-1H-indole-5-carboxamide

7

(Z)-methyl 1-(4-amino-2-fluorobut-2- en-1-yl)-3-(3-(N,N- dimethylsulfamoyl)phenyl)-2-methyl- 1H-indole-6-carboxylate

8

(Z)-1-(4-amino-2-fluorobut-2-en-1 - yl)-3-(3-(N,N- dimethylsulfamoyl)phenyl)-2-methyl- 1H-indole-5-caiboxylic acid

10

(Z)-1-(4-amino-2-fluorobut-2-en-1 - yl)-3-(3-(N,N- dimethylsulfamoyl)phenyl)-N,N,2- trimethyl-1H-indole-6-carboxamide

11

(Z)-1-(4-aniino-2-fluorobut-2-en-1- yl)-3-(3-(N,N- dimethylsulfamoyl)phenyl)-2-methyl- 1H-indole-6-carboxamide

12

(Z)-ethyl 1-(4-amino-2-fluorobut-2- en-1-yl)-3-(3-(N,N- dimethylsulfamoyl)phenyl)-2-methyl- 1H-indole-5-carboxylate

13

(Z)-1-(4-amino-2-fluorobut-2-en-1- yl)-3-(3-(N,N-dimethylsulfamoyl)-2- methylphenyl)-2-methyl-1H-indole-5- carboxylic acid

14

(Z)-1-(4-amino-2-fluorobut-2-en-1- yl)-2-methyl-3-(3- (methylsulfonyl)phenyl)-1H-indole-5- carboxylic acid

15

(Z)-ethyl 1-(4-amino-2-fluorobut-2- en-1-yl)-3-(3- (dimethylcarbamoyl)phenyl)-2- methyl-1H-indole-5-carboxylate

16

(Z)-1-(4-amino-2-fluorobut-2-en-1- yl)-3-(3-(dimethylcarbamoyl)phenyl)- 2-methyl-1H-indole-5-carboxylic acid

17

(Z)-ethyl 1-(4-amino-2-fluorobut-2- en-1-yl)-2-methyl-3-(3- (rnethylsulfonyl)phenyl)-1H-indole-5- carboxylate

18

(Z)-1-(4-amino-2-fluorobut-2-en-1- yl)-2-methyl-3-(3-(N- methylsulfamoyl)phenyl)-1H-indole- 5-carboxylic acid

19

(Z)-ethyl 1-(4-amino-2-fluorobut-2- en-1-yl)-3-(5-(N,N- dimethylsulfamoyl)-2-methylphenyl)- 2-methyl-1H-indole-5-carboxylate

20

(Z)-1-(4-amino-2-fluorobut-2-en-1- yl)-3-(5-(N,N-dimethylsulfamoyl)-2- methylphenyl)-2-methyl-1H-indole-5- carboxylic acid

21

(Z)-1-(4-amino-2-fluorobut-2-en-1- yl)-3-(3-(N,N- dimethylsulfamoyl)phenyl)-6-fluoro- 2-methyl-1H-indole-5-carboxylic acid

22

(Z)-ethyl 1-(4-amino-2-fluorobut-2- en-1-yl)-3-(3-(N,N- dimethylsulfamoyl)phenyl)-6-fluoro- 2-methyl-1H-indole-5-carboxylate

25

(Z)-3-(1-(4-amino-2-fluorobut-2-en-1- yl)-2-methyl-1H-pyrrolo[3,2- b]pyridin-3-yl)-N,N- dimethylbenzenesulfonamide

26

(Z)-3-(1-(4-amino-2-fluorobut-2-en-1- yl)-2-methyl-1H-pyrrolo[3,2- c]pyridin-3-yl)-N,N- dimethylbenzenesulfonamide

29

(Z)-3-(1-(4-amino-2-fluorobut-2-en-1- yl)-2-methyl-5-(2H-tetrazol-5-yl)-1H- indol-3-yl)-N,N- dimethylbenzenesulfonamide

32

(Z)-3-(1-(4-amino-2-fluorobut-2-en-1- yl)-2-methyl-1H-pyrrolo[2,3- c]pyridin-3-yl)-N,N- dimethylbenzenesulfonamide

35

(Z)-1-(4-amino-2-fluorobut-2-en-1- yl)-3-(3-(N,N- dimethylsulfamoyl)phenyl)-N- isopropyl-2-methyl-2H-indole-5- carboxamide

36

(Z)-1-(4-amino-2-fluorobut-2-en-1- yl)-3-(3-(N,N- dimethylsulfamoyl)phenyl)-N- isopropyl-N,2-dimethyl-1H-indole-5- carboxamide

37

(Z)-3-(1-(4-amino-2-fluorobut-2-en-1- yl)-5-hydroxy-2-methyl-1H-indol-3- yl)-N,N-dimethylbenzenesulfonamide

38

(Z)-1-(4-amino-2-fluorobut-2-en-1- yl)-2-methyl-3-(3-(N- methylmethylsulfonamido)phenyl)- 1H-indole-5-carboxylic acid

39

(Z)-1-(4-amino-2-fluorobut-2-en-1- yl)-N,N,2-trimethyl-3-(3-(N- methylmethylsulfonamido)phenyl)- 1H-indole-5-carboxamide

40

(Z)-1-(4-amino-2-fluorobut-2-en-1- yl)-3-(5-(N,N- dimethylsulfamoyl)pyridin-3-yl)-2- methyl-1H-indole-5-carboxylic acid

41

(Z)-1-(4-amino-2-fluorobut-2-en-1- yl)-3-(5-(N,N- dimethylsulfamoyl)pyridin-3-yl)- N,N,2-trimethyl-1H-indole-5- carboxamide

42

(Z)-ethyl 1-(4-amino-2-fluorobut-2- en-1-yl)-3-(5-(N,N- dimethylsulfamoyl)phenyl)-2-methyl- 1H-pyrrolo[3,2-b]pyridine-5- carboxylate

43

(Z)-1-(4-amino-2-fluorobut-2-en-1- yl)-3-(3-(N,N- dimethylsulfamoyl)phenyl)-2-methyl- 1H-pyrrolo[3,2-b]pyridine-5- carboxylic acid

44

(Z)-1-(4-amino-2-fluorobut-2-en-1- yl)-3-(3-(N,N- dimethylsulfamoyl)phenyl)-N,N,2- trimethyl-1H-pyrrolo[3,2-b]pyridine- 5-carboxamide

45

(Z)-1-(4-amino-2-fluorobut-2-en-1- yl)-3-(3-(N,N- dimethylsulfamoyl)phenyl)-N- isopropyl-2-methyl-1H-pyrrolo[3,2- b]pyridine-5-carboxamide

46

(Z)-1-(4-amino-2-fluorobut-2-en-1- yl)-3-(3-(N,N- dimethylsulfamoyl)phenyl)-N,2- dimethyl-1H-pyrrolo[3,2-b]pyridine- 5-carboxamide

49

(Z)-3-(1-(4-amino-2-fluorobut-2-en-1- yl)-5-methoxy-2-methyl-1H-indol-3- yl)-N,N-dimethylbenzenesulfonamide

50

(Z)-1-(4-amino-2-fluorobut-2-en-1- yl)-N,N,2-trimethyl-3-(3- (methylsulfonyl)phenyl)-1H-indole-5- carboxamide

51

(Z)-3-(1-(4-amino-2-fluorobut-2-en-1- yl)-5-cyano-2-methyl-1H-indol-3-yl)- N,N-dimethylbenzenesulfonamide

52

(Z)-1-(4-amino-2-fluorobut-2-en-1- yl)-3-(3-(N,N- dimethylsulfamoyl)phenyl)-N,N,2- trimethyl-1H-indole-5-carboxamide

53

(Z)-1-(4-amino-2-fluorobut-2-en-1- yl)-3-(3-(N,N- dimethylsulfamoyl)phenyl)-N,N,2- trimethyl-1H-pyrrolo[3,2-b]pyridine- 5-carboxamide

54

(Z)-1-(4-amino-2-fluorobut-2-en-1- yl)-N,N,2-trimethyl-3-(3- sulfamoylphenyl)-1H-indole-5- carboxamide

55

(Z)-3-(1-(4-amino-2-fluorobut-2-en-1- yl)-2-methyl-5-(1,2,4-oxadiazol-3-yl)- 1H-indol-3-yl)-N,N- dimethylbenzenesulfonamide

57

(Z)-1-(4-amino-2-fluorobut-2-en-1- yl)-N,N,2-trimethyl-3-(3- ((trifluoromethyl)sulfonyl)phenyl)- 1H-indole-5-carboxamide

58

(Z)-1-(4-amino-2-fluorobut-2-en-1- yl)-3-(3-(N,N- dimethylsulfamoyl)phenyl)-N,N,2- trimethyl-1H-indole-5-sulfonamide

59

(Z)-3-(1-(4-amino-2-fluorobut-2-en-1- yl)-5-(difluoromethyl)-2-methyl-1H- indol-3-yl)-N,N-dimethylbenzene- sulfonamide

60

(Z)-3-(1-(4-amino-2-fluorobut-2-en-1- yl)-5-hydroxy-2-methyl-1H- pyrrolo[3,2-b]pyridin-3-yl)-N,N- dimethylbenzene-sulfonamide

61

(Z)-3-(1-(4-amino-2-fluorobut-2-en-1- yl)-5-methoxy-2-methyl-1H- pyrrolo[3,2-b]pyridin-3-yl)-N,N- dimethylbenzene-sulfonamide

62

(Z)-3-(1-(4-amino-2-fluorobut-2-en-1- yl)-5-chloro-2-methyl-1H-indol-3-yl)- N,N-dimethylbenzenesulfonamide

63

(Z)-5-(1-(4-amino-2-fluorobut-2-en-1- yl)-2-methyl-1H-indol-3-yl)-N,N- dimethylpyridine-3-sulfonamide

64

(Z)-5-(1-(4-amino-2-fluorobut-2-en-1- yl)-5-chloro-2-methyl-1H-indol-3-yl)- N,N-dimethylpyridine-3-sulfonamide

65

(Z)-4-(5-chloro-2-melhyl-3-(5- (methylsulfonyl)pyridin-3-yl)-1H- indol-1-yl)-3-fluorobut-2-en-1-amine

66

(Z)-5-(1-(4-amino-2-fluorobut-2-en- yl)-5-chloro-1H-indol-3-yl)-N,N- dimethylpyridine-3-sulfonamide

67

(Z)-5-(1-(4-amino-2-fluorobut-2-en-1- yl)-6-chloro-2-methyl-1H-indol-3-yl)- N,N-dimethylpyridine-3-sulfonamide

69

(Z)-3-fluoro-4-(5-methoxy-2-methyl- 3-(3-(methylsulfonyl)phenyl)-1H- pyrrolo[3,2-b]pyridin-1-yl)but-2-en- amine

70

(Z)-5-(1-(4-amino-2-fluorobut-2-en-1- yl)-5-chloro-2-methyl-1H-indol-3-yl)- N-methylpyridine-3-sulfonamide

71

(Z)-5-(1-(4-amino-2-fluorobut-2-en-1- yl)-5-fluoro-2-methyl-1H-indol-3-yl)- N,N-dimethylpyridine-3-sulfonamide

72

(Z)-5-(1-(4-amino-2-fluorobut-2-en-1- yl)-6-chloro-2-methyl-1H- pyrrolo[3,2-b]pyridin-3-yl)-N,N- dimethylpyridine-3-sulfonamide

73

(Z)-5-(1-(4-amino-2-fluorobut-2-en-1- yl)-5-chloro-2-methyl-1H- pyrrolo[2,3-b]pyridin-3-yl)-N,N- dimethylpyridine-3-sulfonamide

75

(Z)-5-(1-(4-amino-2-fluorobut-2-en-1- yl)-4-chloro-2-methyl-1H-indol-3-yl)- N,N-dimethylpyridine-3-sulfonamide

76

(Z)-4-(5-chloro-2-methyl-3-(pyridin- 4-yl)-1H-indol-1-yl)-3-fluorobut-2- en-1-amine

77

(Z)-4-(5-chloro-2-methyl-3-(pyridin- 3-yl)-1H-indol-1-yl)-3-fluorobut-2- en-1-amine

78

(Z)-6-(1-(4-amino-2-fluorobut-2-en-1- yl)-5-chloro-2-methyl-1H-indol-3-yl)- N,N-dimethylpyridine-2-sulfonamide

79

(Z)-5-(1-(4-amino-2-fluorobut-2-en-1- yl)-5-cyclopropyl-2-methyl-1H-indol- 3-yl)-N,N-dimethylpyridine-3- sulfonamide

80

(Z)-4-(5-chloro-2-methyl-3- (pyrimidin-5-yl)-1H-indol-1-yl)-3- fluorobut-2-en-1-amine

81

(Z)-1-(4-amino-2-fluorobut-2-en-1- yl)-N,N,2-trimethyl-3-(pyridin-4-yl)- 1H-indole-5-sulfonamide

83

(Z)-5-(1-(4-amino-2-fluorobut-2-en-1- yl)-5-chloro-2-methyl-1H-indol-3- yl)pyridine-3-sulfonamide

84

(Z)-1-(4-amino-2-fluorobut-2-en-1- yl)-2-methyl-3-(pyridin-4-yl)-1H- indole-5-sulfonamide

85

(Z)-5-(1-(4-amino-2-fluorobut-2-en-1- yl)-2-methyl-5-(trifluoromethoxy)- 1H-indol-3-yl)-N,N-dimethylpyridine- 3-sulfonamide

86

(Z)-1-(4-amino-2-fluorobut-2-en-1- yl)-N,N,2-trimethyl-3-phenyl-1H- indole-5-sulfonamide

87

(Z)-3-fluoro-4-(2-methyl-5- (methylsulfonyl)-3-phenyl-1H-indol- 1-yl)but-2-en-1-amine

88

(Z)-3-fluoro-4-(2-rnethyl-5- (methylsulfonyl)-3-(pyridin-4-yl)-1H- indol-1-yl)but-2-en-1-amine

92

(Z)-4-(3-(benzo[d][1,3]dioxol-5-yl)-2- methyl-5-(methylsulfonyl)-1H-indol- 1-yl)-3-fluorobut-2-en-1-amine

93

(Z)-3-fluoro-4-(3-(4-fluorophenyl)-2- methyl-5-(methylsulfonyl)-1H-indol- 1-yl)but-2-en-1-amine

94

(Z)-3-fluoro-4-(2-methyl-3-(2- methylpyridin-4-yl)-5- (methylsulfonyl)-1H-indol-1-yl)but-2- en-1-amine

95

(Z)-1-(4-amino-2-fluorobut-2-en-1- yl)-3-(4-fluorophenyl)-2-methyl-1H- indole-5-sulfonamide

96

(Z)-5-(1-(4-amino-2-fiuorobut-2-en-1- yl)-2-chloro-1H-indol-3-yl)-N,N- dimethylpyridine-3-sulfonamide

97

(Z)-3-(1-(4-amino-2-fluorobut-2-en-1- yl)-2-methyl-5-(methylsulfonyl)-1H- indol-3-yl)-N,N- dimethylbenzenesulfonamide

98

(Z)-3-fluoro-4-(3-(2-methoxypyridin- 4-yl)-2-methyl-5-(methylsulfonyl)- 1H-indol-1-yl)but-2-en-1-amine

99

(Z)-3-(1-(4-amino-2-fluorobut-2-en-1- yl)-2-chloro-1H-pyrrolo[3,2- b]pyridin-3-yl)-N,N- dimethylbenzenesulfonamide

100

(Z)-3-(1-(4-amino-2-fluorobut-2-en-1- yl)-2-chloro-5-(methylsulfonyl)-1H- indol-3-yl)-N,N- dimethylbenzenesulfonamide

101

(Z)-4-(3-(2,6-dimethylpyridin-4-yl)-2- methyl-5-nitro-1H-indol-1-yl)-3- fluorobut-2-en-1-amine

102

(Z)-N-(1-(4-amino-2-fluorobut-2-en- 1-yl)-3-(2,6-dimethylpyridin-4-yl)-2- methyl-1H-indol-5- yl)methanesulfonamide

103

(Z)-3-(1-(4-amino-2-fluorobut-2-en-1- yl)-5-(methoxymethyl)-2-methyl-1H- pyrrolo[3,2-b]pyridin-3-yl)-N,N- dimethylbenzenesulfonamide

104

(Z)-3-(1-(4-amino-2-fluorobut-2-en-1- yl)-2-methyl-5-(methylsulfonamido)- 1H-indol-3-yl)-N,N- dimethylbenzenesulfonamide

105

(Z)-3-(1-(4-amino-2-fluorobut-2-en-1- yl)-5-(dimethylamino)-2-methyl-1H- pyrrolo[3,2-b]pyridin-3-yl)-N,N- dimethylbenzenesulfonamide

106

(Z)-3-(1-(4-amino-2-fluorobut-2-en-1- yl)-5-(isopropylsulfonyl)-2-methyl- 1H-indol-3-yl)-N,N- dimethylbenzenesulfonamide

107

(Z)-3-(1-(4-amino-2-fluorobut-2-en-1- yl)-2,5-dimethyl-1H-pyrrolo[3,2- b]pyridin-3-yl)-N,N- dimethylbenzenesulfonamide

108

(Z)-3-(1-(4-amino-2-fluorobut-2-en-1- yl)-6-fluoro-2-methyl-1H-pyrrolo[3,2- b]pyridin-3-yl)-N,N- dimethylbenzenesulfonamide

109

(Z)-3-(1-(4-amino-2-fluorobut-2-en-1- yl)-5-fluoro-2-methyl-1H-pyrrolo[3,2- b]pyridin-3-yl)-N,N- dimethylbenzenesulfonamide

110

(Z)-3-(1-(4-amino-2-fluorobut-2-en-1- yl)-2-methyl-5-(trifluoromethyl)-1H- pyrrolo[3,2-b]pyridin-3-yl)-N,N- dimethylbenzenesulfonamide

111

(Z)-3-(1-(4-amino-2-fluorobut-2-en-1- yl)-5-(1,1-difluoroethyl)-2-methyl- 1H-pyrrolo[3,2-b]pyridin-3-yl)-N,N- dimethylbenzenesulfonamide

112

(Z)-4-(2,5-dimethyl-3-(3- (methylsulfonyl)phenyl)-1H- pyrrolo[3,2-b]pyridin-1-yl)-3- fluorobut-2-en-1-amine

113

(Z)-4-(3-(3-(ethylsulfonyl)phenyl)-2- isopropyl-5-methyl-1H-pyrrolo[3,2- b]pyridin-1-yl)-3-fluorobut-2-en-1- amine

114

(Z)-4-(3-(3-(ethylsulfonyl)phenyl) 2,5-dimethyl-1H-pyrrolo[3,2- b]pyridin-1-yl)-3-fluorobut-2-en-1- amine

115

(Z)-3-fluoro-4-(5-(fluoromethyl)-2- methyl-3-(3-(methylsulfonyl)phenyl)- 1H-pyrrolo[3,2-b]pyridin-1-yl)but-2- en-1-amine

116

(Z)-2-(1-(4-amino-2-fluorobut-2-en-1- yl)-2-methyl-3-(3- (methylsulfonyl)phenyl)-1H- pyrrolo[3,2-b]pyridin-5-yl)propan-2- ol

117

(Z)-2-(1-(4-amino-2-fluorobut-2-en-1- yl)-3-(3-(isopropylsulfonyl)phenyl)-2- methyl-1H-pyrrolo[3,2-b]pyridin-5- yl)propan-2-ol

18. The method according to claim 1 , comprising administering to a subject in need thereof a therapeutically effective amount of a compound which is

or a pharmaceutically acceptable salt thereof.

19. The method according to claim 1 , comprising administering to a subject in need thereof a therapeutically effective amount of a compound which is

or a pharmaceutically acceptable salt thereof.

20. The method according to claim 1 , comprising administering to a subject in need thereof a therapeutically effective amount of a compound which is

or a pharmaceutically acceptable salt thereof.