Colony-stimulating factor-1 receptor (CSF-1R) inhibitors

JP7652867B2Active Publication Date: 2025-03-27GENZYME CORP

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Patent Information

Application Number: JP2023205068
Authority / Receiving Office: JP · JP
Patent Type: Patents
Current Assignee / Owner
Priority Date: 2015-07-20
Filing Date: 2023-12-05
Publication Date: 2025-03-27
Estimated Expiration: 2036-07-19

Application Information

Patent Timeline

20 Jul 2015

Priority

05 Dec 2023

Application

JP2023205068

27 Mar 2025

Publication

JP7652867B2

IPC: C07D213/81; A61K31/444; C07D487/04; A61K31/5025; A61K31/519; A61P25/00; A61P21/02; A61P25/14; A61P13/12; A61P19/02

CPC: C07D405/06; C07D471/04; C07D487/04; C07D519/00; C07D405/04; A61P37/06; A61P25/00; A61K31/437

Inventors: ジョン·エル·ケイン·ジュニア; クロード·バーベリス

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Abstract

To provide compounds for preparing pharmaceuticals for treating diseases or disorders selected from Multiple Sclerosis, ALS, Huntington's disease, lupus, lupus nephritis, and rheumatoid arthritis.SOLUTION: The present invention provides specific compounds having pyridine rings. Examples of these compounds include 3-((5-ethoxy-6-((6-methylpyridine-3-yl)methoxy)pyridine-3-yl)methyl)pyrazolo[1,5-a]pyrimidine and 3-((5-ethoxy-6-((6-(trifluoromethyl)pyridine-3-yl)methoxy)pyridine-3-yl)methyl)-N,N-dimethyl imidazo[1,2-b]pyridazine-7-carboxamide.SELECTED DRAWING: None

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Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 62 / 194,619, filed July 20, 2015, the disclosure of which is incorporated herein in its entirety.

[0002] The present invention relates to colony-stimulating factor-1 receptor inhibitors ("CSF-1R inhibitors"). The CSF-1R inhibitors of the present invention are small molecules that can cross the blood-brain barrier and reach the central nervous system (CNS). The present invention also relates to pharmaceutical preparations containing the CSF-1R inhibitors, as well as the use of the CSF-1R inhibitors and pharmaceutical compositions containing the CSF-1R inhibitors for treating diseases. The present invention further relates to the use of the CSF-1R inhibitors and pharmaceutical compositions containing the CSF-1R inhibitors for treating immune-mediated diseases (including, but not limited to, multiple sclerosis, lupus nephritis, and rheumatoid arthritis) and neurological diseases (including, but not limited to, amyotrophic lateral sclerosis (ALS) and Huntington's disease). The CSF-1R inhibitors of the present invention can be used to inhibit c-FMS, the cellular receptor for colony-stimulating factor-1 (CSF-1). Summary of the Invention [Means for solving the problem]

[0003] The present invention relates to a compound of formula (I): [ka] [In the formula, n is 0, 1, 2, 3, 4 or 5; m is 1, 2, 3 or 4; X 1 is C, N or CR 7 and X 2 , X 3 , X 4 , X 5 , X 6 and X7 are each independently N, NR 7 or CR 7 is selected from Here, each R 7 are independently H, (C1~C 10 ) Alkyl, (C3-C 10 ) Cycloal alkyl, (C2-C9)heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heptane Roaryls (C2-C 10 ) Alkyl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) 2 amine, (C2-C 10 ) Alkynylamine, C(O)-, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl-, COOH-(C3-C 10 ) cycloalkyl-, (C1-C 10 ) alkoxy-, R 8 -(C1~C 10 ) alkyl-, R 8 -(C3~C 10 ) cycloalkyl, R 8 -(C2-C9)heterocycloalkyl, R 8 -(C6~C 14 ) aryl, R 8 -(C2-C9) heteroaryl, R 8 -(C2~C 10 ) Alkyl , R 8 -(C1~C 10 ) alkylamine, R 8 -((C1~C 10 ) alkyl) 2 amine, R 8 - (C2~C 10 ) alkynylamine, R 8 -C(O)-, R 8 -(C1~C 10 ) alkyl-C(O)O-, R 8 -(C1~C 10 )Alkoxy-, (C3-C 10 ) cycloalkyl-O-, ( C2-C9)heterocycloalkyl-O-, (C6-C 14 ) Aryl-O-, (C2-C9) Heteroaryl-O-, R 8 -(C3~C 10 ) Cycloalkyl-O-, R 8 -(C2~C9) Heterocycloalkyl-O-, R 8 -(C6~C 14 ) Aryl-O-, R 8 -(C2~C9) Heteroaryl-O-, HO-, halo, cyano, H2N-, (CH3)HN-, (CH3)2N-, R 8 R 9 N-, R 8 R 9 N(O)C-, R 8 (R 9 C(O))N-, R 8 R 9 NC(O)O-, R 8 C(O)-, R 8 R 9 NC(O)R 8 N-, (C1~C 10 )Alkyl-OC(O)R 8 N-, (C3~C 10 )Cycloalkyl-OC(O)R 8 N-, (C2-C9)heterocycloalkyl-OC(O)R 8 N-, (C6~C 14 )Aryl-OC(O)R 8 N-, (C2~C9 )Heteroaryl-OC(O)R 8 N-, F3C-, F2HC-, CH3F2C-, FH2C-, CH3FHC-, (CH3)2FC-;NC-, (C1~C 10 ) alkyl(O)P-, (C1-C 10 ) Alkyl-S-, (C1-C 10 )Alkyl-S-(C1-C 10 ) alkyl-, ( C3~C 10 )Cycloalkyl-S-, (C6-C 14)aryl-S-, (C2-C9)heteroalkyl-S-, (C2-C9)heterocycloalkyl-S-, (C2-C9)heteroaryl-S-, (C1-C 10 ) alkyl-S(O)-, (C3-C 10 ) Cycloalkyl-S(O)-, (C6-C 14 )aryl-S(O)-, (C2-C9)heterocycloalkyl-S( O)-, (C2-C9)heteroaryl-S(O)-, (C3-C 10 ) alkyl-S(O)2-, (C3-C 10 )Cycloalkyl-S(O)2-, (C6-C 14 )aryl-S(O)2-, (C2-C9)heterocycloalkyl-S(O)2-, (C2-C9)heteroaryl-S (O)2-, R 8 R 9 NS(O)2-, (C1-C 10 )Alkyl-S(O)R 8 N-, (C3~C 10 )Cycloalkyl-S(O)R 8 N-, (C6~C 14 )Aryl-S(O)R 8 N- , (C2-C9)heterocycloalkyl-SO2R 8 N- and (C2-C9)heteroaryl-S(O)2R 8 N-; where R 8 and R 9 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) Alkyl-C(O)O-, COOH -(C1~C 10 ) alkyl, COOH-(C3-C 10) cycloalkyl, (C1-C 10 )a Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) Shik (C2-C9)heterocycloalkyl-O-, (C6-C 14 ) Aryl selected from the group consisting of —O—, (C2-C9)heteroaryl-O—, HO—, halo, (CH3)2N—, and H2N—; or R 8 and R 9 taken together form a 3- to 10-membered cycloalkyl, heterocycloalkyl, aryl, or heteroaryl ring; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 ) cycloalkyl or (C2-C9) heterocycloalkyl is ( C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl-O-, (C6-C 14 )aryl-O-, (C2-C9)heteroaryl-O-, HO- , halo, or H2N-, ;

[0004] X 8 and X 9 are each independently selected from N or C; T 1 , T 2 and T 3 are each independently N or CR 10 is selected from Here, each R 10 are independently H, (C1~C 10 ) Alkyl, (C3-C 10 ) Cycloal alkyl, (C2-C9)heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heptane Roaryls (C2-C 10 ) Alkyl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) 2 amine, (C2-C 10 ) Alkynylamine, C(O)-, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl-, COOH-(C3-C 10 ) cycloalkyl-, (C1-C 10 ) alkoxy-, R 10A -(C1~C 10 ) alkyl-, R 10A -(C3~C 10 ) cycloalkyl, R 10A -(C2-C9)heterocycloalkyl, R 10A -(C6~C 14 ) aryl, R 10A -(C2-C9) heteroaryl, R 10A -(C2~C 10 ) alkylnyl, R 10A -(C1~C 10 ) alkylamine, R 10A -((C1~C 10 ) alkyl) 2 amine, R 10A -(C2~C10 ) alkynylamine, R 10A -C(O)-, R 10A -(C1~C 10 ) alkyl-C(O)O-, R 10A -(C1~C 10 )Alkoxy-, (C3-C 10 ) Cycloalkyl-O-, (C2-C9)heterocycloalkyl-O-, (C6-C 14 ) Ant (C2-C9)heteroaryl-O-, R 10A -(C3~C 10 ) Cycloalkyl-O-, R 10A -(C2-C9)heterocycloalkyl-O-, R 10A -(C6~C 14 ) Ant Rool-O-, R 10A -(C2-C9)heteroaryl-O-, HO-, halo, cyano, H2N-, (CH3)HN-, (CH3)2N-, R 10A R 11 N-, R 10A R 11 N(O)C-, R 10A (R 11 C(O))N-, R 10A R 11 NC(O)O-, R 10A C(O)-, R 10A R 11 NC( O)R 10A N-, (C1~C 10 )Alkyl-OC(O)R 10A N-, (C3~C 10 )Cycloalkyl-OC(O)R 10A N-, (C2-C9)heterocycloalkyl-OC(O)R 10A N-, (C6~C 14 )Aryl-OC(O)R 10A N-, (C2-C9)heteroaryl-OC(O)R 10A N-, F3C-, F2HC-, CH3F2C-, FH2C-, CH3FHC-, ( CH3)2FC-;NC-, (C1~C 10 ) alkyl(O)P-, (C1-C 10) Alkyl-S-, (C1-C 10 )Alkyl-S-(C1-C 10 ) Alkyl-, (C3-C 10 ) Cycloa Rukill-S-, (C6~C 14 ) aryl-S-, (C2-C9) heteroalkyl-S-, ( (C2-C9)heterocycloalkyl-S-, (C2-C9)heteroaryl-S-, (C1- C 10 ) alkyl-S(O)-, (C3-C 10 ) Cycloalkyl-S(O)-, (C6-C 14 )aryl-S(O)-, (C2-C9)heterocycloalkyl-S(O)-, (C2-C9)heteroaryl-S(O)-, (C3-C 10 ) alkyl-S(O)2-, (C3-C 10 ) Cycloalkyl-S(O)2-, (C6-C 14 )Aryl-S(O)2-, (C2-C9) Heterocycloalkyl-S(O)2-, (C2-C9)heteroaryl-S(O)2-, R 10A R 11 NS(O)2-, (C1-C 10 )Alkyl-S(O)R 10A N-, (C3~C 10 ) Shik alkyl-S(O)R 10A N-, (C6~C 14 )Aryl-S(O)R 10A N-, (C2-C9)heterocycloalkyl-SO2R 10A N- and (C2-C9)heteroaryl- S(O)2R 10A N-; where R 10A and R 11 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C10 ) Alkylamines, ((C1-C 10 )Alkyl)2 Amines, (C1-C3) alkynylamines, (C1-C 10 )Alkyl-C(O)O-, CO OH-(C1~C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) Cycloalkyl-O-, (C2-C9)heterocycloalkyl-O-, (C6-C 14 ) Ant selected from the group consisting of heteroaryl-O—, (C2-C9)heteroaryl-O—, HO—, halo, (CH3)2N—, and H2N—; or R 10A and R 11 are taken together to form a 3- to 10-membered cycloalkyl, heterocyclo forming an alkyl, aryl or heteroaryl ring, Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 ) cycloalkyl or (C2-C9) heterocycloalkyl is ( C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10)Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl-O-, (C6-C 14 )aryl-O-, (C2-C9)heteroaryl-O-, HO- , halo, or H2N-, ;

[0005] Y 1 O, S, NR 12 or CR 12 R 13 and where R 12 is absent or R 12 and R 13 are each independently H, (C1~ C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6~C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 )a alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 )Cycloalkyl-O-, (C2-C9)heterocycloalkyl -O-, (C6~C 14 )aryl-O-, (C2-C9)heteroaryl-O-, HO-, selected from the group consisting of halo, and H2N-; R 1combines with the carbon to which it is attached to form a carbonyl, and R 2 is absent or R 1 and R 2 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl-O-, (C6-C 14 ) Aryl-O-, (C2-C9) heteroaryl -O-, HO-, halo, and HN-, or R 1 and R 2 teeth , together with the carbon to which they are attached, form a 3- to 10-membered ring; R 4 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heptane Cycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) alkyl-, (C3~C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl-O-, (C6-C 14)aryl-O—, (C2-C9)heteroaryl-O—, HO—, halo, and HN—, or R 4 and R 5 are identical to the carbon to which they are attached. Together they form 3- to 10-membered rings; R 5 is absent or H, (C1 to C 10 ) Alkyl, (C3-C 10 )Cycloalkyl , (C2-C9)heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl Reel, (C1~C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 )Cycloalkyl-O-, (C2-C9)heterocycloa Rukyru-O-, (C6~C 14 )aryl-O-, (C2-C9)heteroaryl-O-, H selected from the group consisting of O-, halo, and HN-;

[0006] R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heptane Cycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C2-C 10 ) Alkyl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) 2 amine, (C2~C 10 ) Alkynylamine, C(O)-, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl-, COOH-(C3-C 10) cycloalkyl-, (C1-C 10 ) alkoxy-, R 14 -(C1~C 10 ) alkyl-, R 14 -(C3~C 10 ) Cyclo Alkyl, R 14 -(C2-C9)heterocycloalkyl, R 14 -(C6~C 14 ) aryl, R 14 -(C2-C9) heteroaryl, R 14 -(C2~C 10 ) alkylnyl, R 14 -(C1~C 10 ) alkylamine, R 14 -((C1~C 10 ) alkyl) 2 amine, R 14 -(C2~C 10 ) alkynylamine, R 14 -C(O)-, R 14 -(C1~C 10 )Alkyl-C(O)O- , R 14 -(C1~C 10 )Alkoxy-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl-O-, (C6-C 14 ) Aryl-O-, (C2-C9) Heteroaryl Reel-O-, R 14 -(C3~C 10 ) Cycloalkyl-O-, R 14 -(C2~C9) Hetero Cycloalkyl-O-, R 14 -(C6~C 14 ) Aryl-O-, R 14 -(C2~C9) Haitai Aryl-O-, HO-, halo, cyano, H2N-, (CH3)HN-, (CH3)2N-, R 14 R 15 N-, R 14 R 15 N(O)C-, R 14 (R 15 C(O))N-, R 14 R15 NC(O)O-, R 14 C(O)-, R 14 R 15 NC(O)R 14 N-, (C1~C 10 ) Alkyl-OC (O)R 14 N-, (C3~C 10 )Cycloalkyl-OC(O)R 14 N-, (C2~C9) Tetracycloalkyl-OC(O)R 14 N-, (C6~C 14 )Aryl-OC(O)R 14 N -, (C2-C9)heteroaryl-OC(O)R 14 N-, F3C-, F2HC-, CH3F2C-, FH2C-, CH3FHC-, (CH3)2FC-;NC-, (C1~C 10 ) alkyl (O)P-, (C1~C 10 ) Alkyl-S-, (C1-C 10 )Alkyl-S-(C1-C 10 ) Alkyl-, (C3-C 10 )Cycloalkyl-S-, (C6-C 14 )aryl-S-, (C2-C9)heteroalkyl-S-, (C2-C9)heterocycloalkyl-S-, (C2- C9) heteroaryl-S-, (C1-C 10 ) alkyl-S(O)-, (C3-C 10 ) Shik alkyl-S(O)-, (C6-C 14 ) Aryl-S(O)-, (C2-C9) heterocyclic Chloroalkyl-S(O)-, (C2-C9)heteroaryl-S(O)-, (C3-C 10 ) Alkyl-S(O)2-, (C3-C 10 )Cycloalkyl-S(O)2-, (C6-C 14 ) aryl-S(O)2-, (C2-C9) heterocycloalkyl-S(O)2-, (C2-C9) heteroaryl-S(O)2-, R 14 R 15NS(O)2-, (C1-C 10 ) alkyl-S( O)2R 14 N-, (C3~C 10 )Cycloalkyl-S(O)R 14 N-, (C6~C 14 )Aryl-S(O)R 14 N-, (C2-C9)heterocycloalkyl-SO2R 14 N- and (C2-C9)heteroaryl-S(O)2R 14 N-; where R 14 and R 15 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 )Alkyl-C(O)O-, COO H-(C1~C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 ) Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) Shi cycloalkyl-O-, (C2-C9)heterocycloalkyl-O-, (C6-C 14 ) Ally selected from the group consisting of aryl-O-, (C2-C9)heteroaryl-O-, HO-, F2HC-O-, halo, (CH3)2N-, H2N-, F3C-C(O)-, F3C-, and F2HC- be; or R 14 and R 15 taken together form a 3- to 10-membered cycloalkyl, heterocycloalkyl, aryl, or heteroaryl ring; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 ) cycloalkyl or (C2-C9) heterocycloalkyl is ( C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl-O-, (C6-C 14 )aryl-O-, (C2-C9)heteroaryl-O-, HO- , halo, or H2N-, ;

[0007] R 3 is N or CR 16 and where R 16 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2 C9) heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) 2 amine, (C1-C3) alkyl Nylamine, (C1-C 10) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2 ~C9)heterocycloalkyl-O-, (C6~C 14 )aryl-O—, (C2-C9)heteroaryl-O—, HO—, halo, and H2N—; or When m is 1, R 16 and R 4 together with the carbon to which they are attached form the formula ( II): [ka] {In the formula, The dotted line represents an optional double bond; p is 0, 1, 2, 3, 4 or 5; Z 1 are each independently H, halo, (C1 to C 10 ) alkyl, (C2-C9) heteroalkyl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) 2 amine, (C2-C 10 ) Alkynylamine, (C1-C 10 ) alkoxy-, or HN-; Y 2 O, S, NR 17 or CR 17 R 18 and where R 17 is absent or R 17 and R 18 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) Alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl Ru-O-, (C6~C 14 )aryl-O-, (C2-C9)heteroaryl-O-, HO- , halo, or H2N-} to form a compound by or a pharmaceutically acceptable salt thereof.

[0008] The present invention also relates to a compound of formula (XIII): [ka] [In the formula, V 101 is C, N, O or S, r is 0, 1, 2, 3, 4 or 5; where V 101 is C, r is 0, 1, 2, 3, 4 or 5, where V 101 When is N, r is 1 and R 102 is absent; where V 101 When is O, r is 1 and R 101 and R 102 is absent; where V 101 When is S, r is 1 and R 101 and 102 is absent; s is 1, 2, 3 or 4;

[0009] X 101 , X 102 , X 103 , X 104 and X 105 are each independently N, NR 107 or CR 107 is selected from Here, each R 107 are independently H, (C1~C 10 ) Alkyl, (C3-C 10 ) Cycloa alkyl, (C2-C9)heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C2-C 10 ) Alkyl, (C1-C 10 ) alkylamines, ((C1 C 10 ) alkyl) 2 amine, (C2-C 10 ) Alkynylamine, C(O)-, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl-, COOH-(C3-C 10 ) cycloalkyl-, (C1-C 10 ) alkoxy-, R 108 -(C1~C 10 ) Alkyl- , R 108 -(C3~C 10 ) cycloalkyl, R 108 -(C2-C9)heterocycloalkyl, R 108 -(C6~C 14 ) aryl, R 108 -(C2-C9) heteroaryl, R 108 -(C2~ C 10 ) alkylnyl, R 108 -(C1~C 10 ) alkylamine, R 108 -((C1~C 10 ) alkyl) 2 amine, R108 -(C2~C 10 ) alkynylamine, R 108 -C(O)-, R 108 -(C1~C 10 ) alkyl-C(O)O-, R 108 -(C1~C 10 )Alkoxy-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl-O-, (C6-C 14 )aryl-O-, (C2-C9)heteroaryl-O-, R 108 -(C3~C 10 ) Cycloalkyl-O-, R 108 -(C2-C9)heterocycloalkyl-O-, R 108 -(C6~C 14 ) Aryl-O-, R 108 -(C2-C9)heteroaryl-O-, HO-, halo, cyano , H2N-, (CH3)HN-, (CH3)2N-, R 108 R 109 N-, R 108 R 109 N(O)C-, R 108 (R 109 C(O))N-, R 108 R 109 NC(O)O-, R 108 C(O)-, R 108 R 109 NC(O)R 108 N-, (C1~C 10 )Alkyl-OC(O)R 108 N-, (C3~C 10 )Cycloalkyl-OC(O)R 108 N-, (C2-C9)heterocycloalkyl-OC(O)R 108 N-, (C6~C 14 )Aryl-OC(O)R 108 N-, (C2-C9) heteroaromatic Reel-OC(O)R 108 N-, F3C-, F2HC-, CH3F2C-, FH2C-, CH3 FHC-, (CH3)2FC-;NC-, (C1-C10 ) alkyl(O)P-, (C1-C 10 ) Alkyl-S-, (C1-C 10 )Alkyl-S-(C1-C 10 ) Alkyl-, (C3-C 10 )Cycloalkyl-S-, (C6-C 14 )aryl-S-, (C2-C9)heteroalkyl-S-, (C2-C9)heterocycloalkyl-S-, (C2-C9)heteroaryl-S-, (C1-C 10 ) alkyl-S(O)-, (C3-C 10 ) Cycloalkyl-S(O)-, (C6-C 14 ) aryl-S(O)-, (C2-C9) heterocycloalkyl-S(O)-, (C2-C9)heteroaryl-S(O)-, (C3-C 10 ) alkyl-S(O)2-, (C3-C 10 )Cycloalkyl-S(O)2-, (C6-C 14 ) aryl-S(O)2-, (C2 ~C9)heterocycloalkyl-S(O)2-, (C2-C9)heteroaryl-S(O)2 -, R 108 R 109 NS(O)2-, (C1-C 10 )Alkyl-S(O)R 108 N-, (C3~ C 10 )Cycloalkyl-S(O)R 108 N-, (C6~C 14 )Aryl-S(O)R 108 N-, (C2-C9)heterocycloalkyl-SO2R 108 N- and (C2-C9)heteroaryl-S(O)2R 108 N-; where R 108 and R 109 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, ( C2-C9)heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) Cycloalkyl-O-, (C2-C9)heterocycloalkyl-O-, (C6-C 14 ) Ant selected from the group consisting of heteroaryl-O—, (C2-C9)heteroaryl-O—, HO—, halo, (CH3)2N—, and H2N—; or R 108 and R 109 taken together form a 3- to 10-membered cycloalkyl, heterocycloalkyl, aryl, or heteroaryl ring; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 ) cycloalkyl or (C2-C9) heterocycloalkyl is (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkenyl Kill-O-, (C6~C 14 )aryl-O-, (C2-C9)heteroaryl-O-, HO Optionally further substituted with 1 to 4 groups selected from -, halo, or H2N- Re;

[0010] T 101 , T 102 and T 103 are each independently N or CR 110 is selected from Here, each R 110 are independently H, (C1~C 10 ) Alkyl, (C3-C 10 ) Cycloa alkyl, (C2-C9)heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C2-C 10 ) Alkyl, (C1-C 10 ) alkylamines, ((C1 C 10 ) alkyl) 2 amine, (C2-C 10 ) Alkynylamine, C(O)-, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl-, COOH-(C3-C 10 ) cycloalkyl-, (C1-C 10 ) alkoxy-, R 110A -(C1~C 10 ) alkyl-, R 110A -(C3~C 10 ) cycloalkyl, R 110A -(C2-C9)heterocycloalkyl , R 110A -(C6~C 14 ) aryl, R 110A -(C2-C9) heteroaryl, R 110A -( C2~C 10) alkylnyl, R 110A -(C1~C 10 ) alkylamine, R 110A -((C1~ C 10 ) alkyl) 2 amine, R 110A -(C2~C 10 ) alkynylamine, R 110A -C(O)-, R 110A -(C1~C 10 ) alkyl-C(O)O-, R 110A -(C1~C 10 )Alkoxy-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl-O-, (C6~C 14 )aryl-O-, (C2-C9)heteroaryl-O-, R 110A -(C3~C 10 ) Cycloalkyl-O-, R 110A -(C2-C9)heterocycloalkyl-O-, R 110A -(C6~C 14 ) Aryl-O-, R 110A -(C2-C9)heteroaryl-O-, HO- , halo, cyano, H2N-, (CH3)HN-, (CH3)2N-, R 110A R 111 N-, R 110A R 111 N(O)C-, R 110A (R 111 C(O))N-, R 110A R 111 NC(O)O-, R 110A C(O)-, R 110A R 111 NC(O)R 110A N-, (C1~C 10 )Alkyl-OC(O)R 110A N-, (C3~C 10 )Cycloalkyl-OC(O)R 110A N-, (C2~C9) Haitai Cycloalkyl-OC(O)R 110A N-, (C6~C 14 )Aryl-OC(O)R 110A N-, (C2-C9)heteroaryl-OC(O)R 110A N-, F3C-, F2HC-, CH 3F2C-, FH2C-, CH3FHC-, (CH3)2FC-;NC-, (C1~C 10 )Al Kill (O) P-, (C1~C 10 ) Alkyl-S-, (C1-C 10 )Alkyl-S-(C1~ C 10 ) Alkyl-, (C3-C 10 )Cycloalkyl-S-, (C6-C 14 )aryl-S-, (C2-C9)heteroalkyl-S-, (C2-C9)heterocycloalkyl-S-, (C2-C9)heteroaryl-S-, (C1-C 10 ) alkyl-S(O)-, (C3-C 10 ) Cycloalkyl-S(O)-, (C6-C 14 ) Aryl-S(O)-, (C2-C9) Hetero Cycloalkyl-S(O)-, (C2-C9)heteroaryl-S(O)-, (C3-C 10 ) alkyl-S(O)2-, (C3-C 10 )Cycloalkyl-S(O)2-, (C6-C 14 ) aryl-S(O)2-, (C2-C9) heterocycloalkyl-S(O)2-, (C2-C9) heteroaryl-S(O)2-, R 110A R 111 NS(O)2-, (C1-C 10 )Alkyl-S(O)R 110A N-, (C3~C 10 )Cycloalkyl-S(O)R 110A N-, (C6~C 14 )Aryl-S(O)R 110A N-, (C2-C9)heterocycloalkyl-SO2R 110A N- and (C2-C9)heteroaryl-S(O)2R 110A N- Re; where R 110A and R 111 are each independently H, (C1 to C10 ) alkyl, (C3~ C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl-O-, (C6-C 14 ) Ant selected from the group consisting of heteroaryl-O—, (C2-C9)heteroaryl-O—, HO—, halo, (CH3)2N—, and H2N—; or R 110A and R 111 are taken together to form a 3- to 10-membered cycloalkyl, heterocyclo forming an alkyl, aryl or heteroaryl ring; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 ) cycloalkyl or (C2-C9) heterocycloalkyl is (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkenyl Kill-O-, (C6~C 14 )aryl-O-, (C2-C9)heteroaryl-O-, HO Optionally further substituted with 1 to 4 groups selected from -, halo, or H2N- R

[0011] Y 101 O, S, NR 112 or CR 112 R 113 and where R 112 is absent or R 112 and R 113 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl , (C6~C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) Alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl Ru-O-, (C6~C 14 )aryl-O-, (C2-C9)heteroaryl-O-, HO- selected from the group consisting of halo, and H2N-; R 101 combines with the carbon to which it is attached to form a carbonyl, and R 102 is absent or R 101 and R 102 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2 ~C9)heterocycloalkyl-O-, (C6~C 14 )aryl-O—, (C2-C9)heteroaryl-O—, HO—, halo, and HN—, or R 101 and R 102 form a 3- to 10-membered ring together with the carbon to which they are attached; R 104 is H, (C1~C 10 ) Alkyl, (C3-C 10 )Cycloalkyl, (C2-C9) Tetracycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl- , (C3~C 10) cycloalkyl-O-, (C2-C9) heterocycloalkyl-O-, ( C6~C 14 )aryl-O-, (C2-C9)heteroaryl-O-, HO-, halo, and and H2N-, or R 104 and R 105 are combined Together with carbon, they form 3- to 10-membered rings; R 105 is absent or H, (C1 to C 10 ) Alkyl, (C3-C 10 ) Cycloalkane (C2-C9)heterocycloalkyl, (C6-C 14 ) Aryl, (C2-C9) Hetero Aryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 )Cycloalkyl-O-, (C2-C9)heterocyclo Alkyl-O-, (C6-C 14 )aryl-O-, (C2-C9)heteroaryl-O-, selected from the group consisting of HO-, halo, and HN-;

[0012] R 106 is H, (C1~C 10 ) Alkyl, (C3-C 10 )Cycloalkyl, (C2-C9) Tetracycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C2-C 10 ) Alkyl, (C1-C 10 ) Alkylamines, ((C1-C 10 )Alkyl)2amine , (C2~C 10 ) Alkynylamine, C(O)-, (C1-C10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl-, COOH-(C3-C 10 ) cycloalkyl-, (C1-C 10 ) alkoxy-, R 114 -(C1~C 10 ) alkyl-, R 114 -(C3~C 10 ) Shi Chloroalkyl, R 114 -(C2-C9)heterocycloalkyl, R 114 -(C6~C 14 ) Ant Ruhr, R 114 -(C2-C9) heteroaryl, R 114 -(C2~C 10 ) alkylnyl, R 114 -(C1~C 10 ) alkylamine, R 114 -((C1~C 10 ) alkyl) 2 amine, R 114 - (C2~C 10 ) alkynylamine, R 114 -C(O)-, R 114 -(C1~C 10 ) alkyl-C(O)O-, R 114 -(C1~C 10 )Alkoxy-, (C3-C 10 )Cycloalkyl-O -, (C2-C9)heterocycloalkyl-O-, (C6-C 14 )aryl-O-, (C2-C9)heteroaryl-O-, R 114 -(C3~C 10 ) Cycloalkyl-O-, R 114 -(C2-C9)heterocycloalkyl-O-, R 114 -(C6~C 14 ) Aryl-O-, R 114 - (C2-C9) heteroaryl-O-, HO-, halo, cyano, H2N-, (CH3)HN-, (CH3)2N-, R 114 R 115 N-, R 114 R 115 N(O)C-, R114 (R 115 C(O))N-, R 114 R 115 NC(O)O-, R 114 C(O)-, R 114 R 115 NC(O)R 114 N-, (C1~C 10 )Alkyl-OC(O)R 114 N-, (C3~C 10 )Cycloalkyl-OC( O)R 114 N-, (C2-C9)heterocycloalkyl-OC(O)R 114 N-, (C6~C 14 )Aryl-OC(O)R 114 N-, (C2-C9)heteroaryl-OC(O)R 114 N -, F3C-, F2HC-, CH3F2C-, FH2C-, CH3FHC-, (CH3)2FC-;NC-, (C1~C 10 ) alkyl(O)P-, (C1-C 10 ) Alkyl-S-, (C1~ C 10 )Alkyl-S-(C1-C 10 ) Alkyl-, (C3-C 10 )Cycloalkyl-S-, (C6-C 14 ) aryl-S-, (C2-C9) heteroalkyl-S-, (C2-C9) hetero (C1-C9)heterocycloalkyl-S-, (C2-C9)heteroaryl-S-, (C1-C 10 ) alkyl -S(O)-, (C3~C 10 ) Cycloalkyl-S(O)-, (C6-C 14 )aryl-S(O)-, (C2-C9)heterocycloalkyl-S(O)-, (C2-C9)heteroaryl-S(O)-, (C3-C 10 ) alkyl-S(O)2-, (C3-C 10 )Cycloalkyl -S(O)2-, (C6~C 14 )Aryl-S(O)2-, (C2-C9)heterocycloar alkyl-S(O)2-, (C2-C9)heteroaryl-S(O)2-, R114 R 115 NS(O)2-, (C1-C 10 )Alkyl-S(O)R 114 N-, (C3~C 10 )Cycloalkyl-S (O)2R 114 N-, (C6~C 14 )Aryl-S(O)R 114 N-, (C2~C9) hetero Cycloalkyl-SO2R 114 N- and (C2-C9)heteroaryl-S(O)2R 114 N-; where R 114 and R 115 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, ( C2-C9)heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) Cycloalkyl-O-, (C2-C9)heterocycloalkyl-O-, (C6-C 14 ) Ant C2-C9 heteroaryl-O-, HO-, F2HC-O-, halo, (C H3)2N-, H2N-, F3C-C(O)-, F3C-, and F2HC-; or R 114 and R 115taken together form a 3- to 10-membered cycloalkyl, heterocycloalkyl, aryl, or heteroaryl ring; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 ) cycloalkyl or (C2-C9) heterocycloalkyl is ( C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl-O-, (C6-C 14 )aryl-O-, (C2-C9)heteroaryl-O-, HO- , halo, or H2N-, ;

[0013] R 103 is N or CR 116 and where R 116 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10) alkyl) 2 amine, (C1-C3) alkane Quinylamine, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl-O-, (C6-C 14 )aryl-O—, (C2-C9)heteroaryl-O—, HO—, halo, and H2N—; or When s is 1, R 116 and R 104 together with the carbon to which they are attached to form the formula (XIV): [ka] {In the formula, The dotted line represents an optional double bond; t is 0, 1, 2, 3, 4 or 5; Z 101 are each independently H, halo, (C1 to C 10 ) alkyl, (C2-C9) heteroalkyl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) 2 amine, (C2-C 10 ) Alkynylamine, (C1-C 10 ) alkoxy-, or HN-; Y 102 O, S, NR 117 or CR 117 R 118 and where R 117 is absent or R 117 and R 118 are each independently H, (C1~C 10 ) Alkyl, (C3-C 10) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkenyl Kill-O-, (C6~C 14 )aryl-O-, (C2-C9)heteroaryl-O-, HO -, halo, or H2N-} to form a compound by The present invention also relates to compounds comprising the structure:

[0014] The present invention further comprises X 1 is N;X 2 is N;X 3 is CR 7 and X 4 is CR 7 and X 5 is CR 7 and X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is C or X 3 is CH;X 4 is CR 7 and X 5 is CH;X 7 is CH The present invention also relates to a compound according to formula (I) or formula (II), wherein:

[0015] The present invention further comprises X 1is N;X 2 is CR 7 and X 3 is CR 7 and X 4 is CR 7 and X 5 is CR 7 and X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is C; or X 2 is CH;X 3 is CH;X 4 is CR 7 and X 5 is C H;X 7 is CH.

[0016] The present invention further comprises X 1 is N;X 2 is CR 7 and X 3 is N;X 4 is CR 7 and X 5 is CR 7 and X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is C or X 2 is CH;X 4 is CR 7 and X 5 is CH;X 7 is CH The present invention also relates to a compound according to formula (I) or formula (II), wherein:

[0017] The present invention further comprises X 1 is N;X 2 is CR 7 and X 3 is CR 7 and X 4 is N;X 5is CR 7 and X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is C The present invention also relates to a compound according to formula (I) or formula (II), wherein:

[0018] The present invention further comprises X 1 is N;X 2 is CR 7 and X 3 is CR 7 and X 4 is CR 7 and X 5 is N;X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is C or X 2 is CH;X 3 is CH;X 4 is CR 7 and X 7 is CH The present invention also relates to a compound according to formula (I) or formula (II), wherein:

[0019] The present invention further comprises X 1 is N;X 2 is N;X 3 is N;X 4 is CR 7 Yes Ri;X 5 is CR 7 and X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is C or X 4 is CR 7 and X 5 is CH;X 7 is CR 7 Formula (I) or a compound according to formula (II).

[0020] The present invention further comprises X 1 is N;X 2 is N;X 3 is CR 7 and X 4 is N Ri;X 5 is CR 7 and X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is C The present invention also relates to certain compounds according to formula (I) or formula (II).

[0021] The present invention further comprises X 1 is N;X 2 is N;X 3 is CR 7 and X 4 is CR 7 and X 5 is N;X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is C; or X 3 is CH;X 4 is CR 7 and X 7 is CH.

[0022] The present invention further comprises X 1 is N;X 2 is N;X 3 is N;X 4 is CR 7 Yes Ri;X 5 is N;X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is C; or X 4is CR 7 and X 7 is CH, It also relates to compounds.

[0023] The present invention further comprises X 1 is N;X 2 is N;X 3 is CR 7 and X 4 is N Ri;X 5 is N;X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is C.

[0024] The present invention further comprises X 1 is C;X 2 is N;X 3 is CR 7 and X 4 is CR 7 and X 5 is CR 7 and X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is C or X 3 is CH;X 4 is CR 7 and X 5 is CH;X 7 is CH The present invention also relates to a compound according to formula (I) or formula (II), wherein:

[0025] The present invention further comprises X 1 is C;X 2 is CR 7 and X 3 is CR 7 and X 4 is CR 7 and X 5 is CR7 and X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is C; or X 2 is CH;X 3 is CH;X 4 is CR 7 and X 5 is C H;X 7 is CH.

[0026] The present invention further comprises X 1 is C;X 2 is CR 7 and X 3 is N;X 4 is CR 7 and X 5 is CR 7 and X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is C or X 2 is CH;X 4 is CR 7 and X 5 is CH;X 7 is CH The present invention also relates to a compound according to formula (I) or formula (II), wherein:

[0027] The present invention further comprises X 1 is C;X 2 is CR 7 and X 3 is CR 7 and X 4 is N;X 5 is CR 7 and X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is C The present invention also relates to a compound according to formula (I) or formula (II), wherein:

[0028] The present invention further comprises X 1 is C;X 2 is CR 7 and X 3 is CR 7 and X 4 is CR 7 and X 5 is N;X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is C or X 2 is CH;X 3 is CH;X 4 is CR 7 and X 7 is CH The present invention also relates to a compound according to formula (I) or formula (II), wherein:

[0029] The present invention further comprises X 1 is C;X 2 is N;X 3 is N;X 4 is CR 7 Yes Ri;X 5 is CR 7 and X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is C or X 4 is CR 7 and X 5 is CH;X 7 is CR 7 Formula (I) or a compound according to formula (II).

[0030] The present invention further comprises X 1 is C;X 2 is N;X 3 is CR7 and X 4 is N Ri;X 5 is CR 7 and X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is C The present invention also relates to certain compounds according to formula (I) or formula (II).

[0031] The present invention further comprises X 1 is C;X 2 is N;X 3 is CR 7 and X 4 is CR 7 and X 5 is N;X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is C; or X 3 is CH;X 4 is CR 7 and X 5 is N;X 7 is CH It also relates to compounds according to formula (I) or formula (II).

[0032] The present invention further comprises X 1 is C;X 2 is N;X 3 is N;X 4 is CR 7 Yes Ri;X 5 is N;X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is C; or X 4 is CR 7 and X 7 is CH, It also relates to compounds.

[0033] The present invention further comprises X 1 is C;X 2 is N;X 3 is CR 7 and X 4 is N Ri;X 5 is N;X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is C.

[0034] The present invention further comprises X 1 is C;X 2 is N;X 3 is CR 7 and X 4 is CR 7 and X 5 is CR 7 and X 6 is N;X 7 is CR 7 and X 8 is N;X 9 is C or X 3 is CH;X 4 is CR 7 and X 5 is CH;X 7 is CH The present invention also relates to a compound according to formula (I) or formula (II), wherein:

[0035] The present invention further comprises X 1 is C;X 2 is CR 7 and X 3 is CR 7 and X 4 is CR 7 and X 5 is CR 7 and X 6 is N;X 7 is CR 7 and X 8 is N;X9 is C; or X 2 is CH;X 3 is CH;X 4 is CR 7 and X 5 is C H;X 7 is CH.

[0036] The present invention further comprises X 1 is C;X 2 is CR 7 and X 3 is N;X 4 is CR 7 and X 5 is CR 7 and X 6 is N;X 7 is CR 7 and X 8 is N;X 9 is C or X 2 is CH;X 4 is CR 7 and X 5 is CH;X 7 is CH The present invention also relates to a compound according to formula (I) or formula (II), wherein:

[0037] The present invention further comprises X 1 is C;X 2 is CR 7 and X 3 is CR 7 and X 4 is N;X 5 is CR 7 and X 6 is N;X 7 is CR 7 and X 8 is N;X 9 is C The present invention also relates to a compound according to formula (I) or formula (II), wherein:

[0038] The present invention further comprises X 1is C;X 2 is N;X 3 is N;X 4 is CR 7 Yes Ri;X 5 is CR 7 and X 6 is N;X 7 is CR 7 and X 8 is N;X 9 is C or X 4 is CR 7 and X 5 is CH;X 7 is CR 7 Formula (I) or a compound according to formula (II).

[0039] The present invention further comprises X 1 is C;X 2 is N;X 3 is CR 7 and X 4 is N Ri;X 5 is CR 7 and X 6 is N;X 7 is CR 7 and X 8 is N;X 9 is C The present invention also relates to certain compounds according to formula (I) or formula (II).

[0040] The present invention further comprises X 1 is C;X 2 is N;X 3 is CR 7 and X 4 is CR 7 and X 5 is CR 7 and X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is N or X 3is CH;X 4 is CR 7 and X 5 is CH;X 7 is CH The present invention also relates to a compound according to formula (I) or formula (II), wherein:

[0041] The present invention further comprises X 1 is C;X 2 is CR 7 and X 3 is CR 7 and X 4 is CR 7 and X 5 is CR 7 and X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is N; or X 2 is CH;X 3 is CH;X 4 is CR 7 and X 5 is C H;X 7 is CH.

[0042] The present invention further comprises X 1 is C;X 2 is CR 7 and X 3 is N;X 4 is CR 7 and X 5 is CR 7 and X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is N or X 2 is CH;X 4 is CR 7 and X 5 is CH;X 7 is CH The present invention also relates to a compound according to formula (I) or formula (II), wherein:

[0043] X 1 is C;X 2 is CR 7 and X 3 is CR 7 and X 4 is N;X 5 is CR 7 and X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is N, or a compound according to formula (II).

[0044] The present invention further comprises X 1 is C;X 2 is CR 7 and X 3 is CR 7 and X 4 is CR 7 and X 5 is N;X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is N or X 2 is CH;X 3 is CH;X 4 is CR 7 and X 7 is CH The present invention also relates to a compound according to formula (I) or formula (II), wherein:

[0045] The present invention further comprises X 1 is C;X 2 is N;X 3 is CR 7 and X 4 is N Ri;X 5 is CR 7 and X 6 is N;X 7 is CR7 and X 8 is C;X 9 is N The present invention also relates to certain compounds according to formula (I) or formula (II).

[0046] The present invention further comprises X 1 is C;X 2 is N;X 3 is CR 7 and X 4 is CR 7 and X 5 is N;X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is N; or X 3 is CH;X 4 is CR 7 and X 7 is CH.

[0047] The present invention further comprises X 1 is C;X 2 is N;X 3 is CR 7 and X 4 is N Ri;X 5 is N;X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is N.

[0048] The present invention further comprises X 1 is C;X 2 is CR 7 and X 3 is N;X 4 is N Ri;X 5 is CR 7 and X 6 is N;X 7 is CR 7and X 8 is C;X 9 is N The present invention also relates to certain compounds according to formula (I) or formula (II).

[0049] The present invention further comprises X 1 is C;X 2 is CR 7 and X 3 is N;X 4 is CR 7 and X 5 is N;X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is N; or X 2 is CH;X 4 is CR 7 and X 7 is CH.

[0050] The present invention further comprises X 1 is C;X 2 is CR 7 and X 3 is CR 7 and X 4 is N;X 5 is N;X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is N.

[0051] The present invention further comprises X 1 is N;X 2 is CR 7 and X 3 is N;X 4 is N Ri;X 5 is CR 7 and X 6 is N;X 7 is CR 7 and X8 is C;X 9 is C The present invention also relates to certain compounds according to formula (I) or formula (II).

[0052] The present invention further comprises X 1 is N;X 2 is CR 7 and X 3 is N;X 4 is CR 7 and X 5 is N;X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is C; or X 2 is CH;X 4 is CR 7 and X 7 is CH.

[0053] The present invention further comprises X 1 is N;X 2 is CR 7 and X 3 is CR 7 and X 4 is N;X 5 is N;X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is C.

[0054] The present invention further comprises X 1 is C;X 2 is CR 7 and X 3 is N;X 4 is N Ri;X 5 is CR 7 and X 6 is N;X 7 is CR 7 and X 8is C;X 9 is C The present invention also relates to certain compounds according to formula (I) or formula (II).

[0055] The present invention further comprises X 1 is C;X 2 is CR 7 and X 3 is N;X 4 is CR 7 and X 5 is N;X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is C; or X 2 is CH;X 4 is CR 7 and X 7 is CH.

[0056] The present invention further comprises X 1 is C;X 2 is CR 7 and X 3 is CR 7 and X 4 is N;X 5 is N;X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is C.

[0057] The present invention further comprises X 1 is C;X 2 is CR 7 and X 3 is N;X 4 is N Ri;X 5 is CR 7 and X 6 is N;X 7 is CR 7 and X 8 is N;X9 is C The present invention also relates to certain compounds according to formula (I) or formula (II).

[0058] The present invention further comprises X 1 is N;X 2 is N;X 3 is CR 7 and X 4 is CR 7 and X 5 is CR 7 and X 6 is N;X 7 is N;X 8 is C;X 9 is C; or X 3 is CH;X 4 is CR 7 and X 5 is CH.

[0059] The present invention further comprises X 1 is N;X 2 is CR 7 and X 3 is CR 7 and X 4 is CR 7 and X 5 is CR 7 and X 6 is N;X 7 is N;X 8 is C;X 9 is C or X 2 is CH;X 3 is CH;X 4 is CR 7 and X 5 is CH The present invention also relates to a compound according to formula (I) or formula (II), wherein:

[0060] The present invention further comprises X 1 is N;X 2 is CR 7 and X 3 is N;X 4is CR 7 and X 5 is CR 7 and X 6 is N;X 7 is N;X 8 is C;X 9 is C; or X 1 is CH;X 2 is CH;X 4 is CR 7 and X 5 is CH The present invention also relates to compounds according to formula (I) or formula (II),

[0061] The present invention further comprises X 1 is N;X 2 is CR 7 and X 3 is CR 7 and X 4 is N;X 5 is CR 7 and X 6 is N;X 7 is N;X 8 is C;X 9 is C.

[0062] The present invention further comprises X 1 is N;X 2 is CR 7 and X 3 is CR 7 and X 4 is CR 7 and X 5 is N;X 6 is N;X 7 is N;X 8 is C;X 9 is C; or X 2 is CH;X 3 is CH;X 4 is CR 7 The present invention also relates to a compound according to formula (I) or formula (II), wherein:

[0063] The present invention further comprises X1 is N;X 2 is N;X 3 is N;X 4 is CR 7 Yes Ri;X 5 is CR 7 and X 6 is N;X 7 is N;X 8 is C;X 9 is C; or X 4 is CR 7 and X 5 is CH, It also relates to compounds.

[0064] The present invention further comprises X 1 is N;X 2 is N;X 3 is CR 7 and X 4 is N Ri;X 5 is CR 7 and X 6 is N;X 7 is N;X 8 is C;X 9 is C.

[0065] The present invention further comprises X 1 is N;X 2 is N;X 3 is CR 7 and X 4 is CR 7 and X 5 is N;X 6 is N;X 7 is N;X 8 is C;X 9 is C or X 3 is CH;X 4 is CR 7 a compound according to formula (I) or (II) It also relates to compounds.

[0066] The present invention further comprises X 1 is N;X 2 is N;X 3 is N;X 4 is CR 7 Yes Ri;X 5 is N;X 6 is N;X 7 is N;X 8 is C;X 9 is C, It also relates to compounds according to formula (I) or formula (II).

[0067] The present invention further comprises X 1 is N;X 2 is N;X 3 is CR 7 and X 4 is N Ri;X 5 is N;X 6 is N;X 7 is N;X 8 is C;X 9 is C, It also relates to compounds according to formula (I) or formula (II).

[0068] The present invention further comprises X 1 is N;X 2 is CR 7 and X 3 is N;X 4 is N Ri;X 5 is CR 7 and X 6 is N;X 7 is N;X 8 is C;X 9 is C.

[0069] The present invention further comprises X 1 is N;X 2 is CR 7 and X 3 is N;X 4 is CR 7and X 5 is N;X 6 is N;X 7 is N;X 8 is C;X 9 is C or X 2 is CH;X 4 is CR 7 a compound according to formula (I) or (II) It also relates to compounds.

[0070] The present invention further comprises X 1 is N;X 2 is CR 7 and X 3 is CR 7 and X 4 is N;X 5 is N;X 6 is N;X 7 is N;X 8 is C;X 9 is C It also relates to compounds according to formula (I) or formula (II).

[0071] The present invention further comprises X 1 is C;X 2 is N;X 3 is CR 7 and X 4 is CR 7 and X 5 is CR 7 and X 6 is N;X 7 is N;X 8 is C;X 9 is C; or X 3 is CH;X 4 is CR 7 and X 5 is CH.

[0072] The present invention further comprises X 1 is C;X 2 is CR 7 and X 3 is CR7 and X 4 is CR 7 and X 5 is CR 7 and X 6 is N;X 7 is N;X 8 is C;X 9 is C or X 2 is CH;X 3 is CH;X 4 is CR 7 and X 5 is CH The present invention also relates to a compound according to formula (I) or formula (II), wherein:

[0073] The present invention further comprises X 1 is C;X 2 is CR 7 and X 3 is N;X 4 is CR 7 and X 5 is CR 7 and X 6 is N;X 7 is N;X 8 is C;X 9 is C; or X 2 is CH;X 4 is CR 7 and X 5 is CH.

[0074] The present invention further comprises X 1 is C;X 2 is CR 7 and X 3 is CR 7 and X 4 is N;X 5 is CR 7 and X 6 is N;X 7 is N;X 8 is C;X 9 is C.

[0075] The present invention further comprises X 1 is C;X 2 is CR 7 and X 3 is CR 7 and X 4 is CR 7 and X 5 is N;X 6 is N;X 7 is N;X 8 is C;X 9 is C; or X 2 is CH;X 3 is CH;X 4 is CR 7 The present invention also relates to a compound according to formula (I) or formula (II), wherein:

[0076] The present invention further comprises X 1 is C;X 2 is N;X 3 is N;X 4 is CR 7 Yes Ri;X 5 is CR 7 and X 6 is N;X 7 is N;X 8 is C;X 9 is C; or X 4 is CR 7 and X 5 is CH, It also relates to compounds.

[0077] The present invention further comprises X 1 is C;X 2 is N;X 3 is CR 7 and X 4 is N Ri;X 5 is CR 7 and X 6 is N;X 7 is N;X 8 is C;X 9is C.

[0078] The present invention further comprises X 1 is C;X 2 is N;X 3 is CR 7 and X 4 is CR 7 and X 5 is N;X 6 is N;X 7 is N;X 8 is C;X 9 is C or X 3 is CH;X 4 is CR 7 a compound according to formula (I) or (II) It also relates to compounds.

[0079] The present invention further comprises X 1 is C;X 2 is N;X 3 is N;X 4 is CR 7 Yes Ri;X 5 is N;X 6 is N;X 7 is N;X 8 is C;X 9 is C, It also relates to compounds according to formula (I) or formula (II).

[0080] The present invention further comprises X 1 is C;X 2 is N;X 3 is CR 7 and X 4 is N Ri;X 5 is N;X 6 is N;X 7 is N;X 8 is C;X 9 is C, It also relates to compounds according to formula (I) or formula (II).

[0081] The present invention further comprises X 1 is C;X 2 is CR 7 and X 3 is N;X 4 is N Ri;X 5 is CR 7 and X 6 is N;X 7 is N;X 8 is C;X 9 is C.

[0082] The present invention further comprises X 1 is C;X 2 is CR 7 and X 3 is N;X 4 is CR 7 and X 5 is N;X 6 is N;X 7 is N;X 8 is C;X 9 is C or X 2 is CH;X 4 is CR 7 a compound according to formula (I) or (II) It also relates to compounds.

[0083] The present invention further comprises X 1 is C;X 2 is CR 7 and X 3 is CR 7 and X 4 is N;X 5 is N;X 6 is N;X 7 is N;X 8 is C;X 9 is C It also relates to compounds according to formula (I) or formula (II).

[0084] The present invention further provides a compound comprising R 7are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C2-C 10 ) Alkyl, (C1-C 10 ) alkylamines, ((C1~C 10 ) alkyl) 2 amine, (C2-C 10 ) Alkynylamine, C(O)-, ( C1~C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl-, COOH-(C3-C 10 ) cycloalkyl-, (C1-C 10 ) alkoxy-, R 8 (C1~C 10 ) alkyl-, R 8 (C3~C 10 ) cycloalkyl, R 8 (C2-C9) heterocycloalkyl, R 8 (C6~C 14 ) aryl, R 8 (C2-C9) heteroaryl, R 8 (C2~C 10 ) alkylnyl, R 8 (C1~C 10 ) alkylamine, R 8 ((C1~C 10 ) alkyl) 2 amine, R 8 (C2 ~C 10 ) alkynylamine, R 8 C(O)-, R 8 (C1~C 10 )Alkyl-C(O)O- , R 8 (C1~C 10 )Alkoxy-, (C3-C 10 ) Cycloalkyl-O-, (C2-C9) Heterocycloalkyl-O-, (C6-C 14 )Aryl-O-, (C2-C9)heteroaryl Rool-O-, R8 (C3~C 10 ) Cycloalkyl-O-, R 8 (C2-C9) heterocycloa Rukill-O-, R 8 (C6~C 14 ) Aryl-O-, R 8 (C2-C9) Heteroaryl-O -, HO-, halo, cyano, H2N-, (CH3)HN-, (CH3)2N-, R 8 R 9 N-, R 9 R 9 selected from N(O)C-, F3C-, F2HC-, CH3F2C-, FH2C-, CH3FHC-, or (CH3)2FC-; where R 8 and R 9 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) Alkyl-C(O)O-, COOH -(C1~C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )a Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) Shik (C2-C9)heterocycloalkyl-O-, (C6-C 14 ) Aryl selected from the group consisting of —O—, (C2-C9)heteroaryl-O—, HO—, halo, (CH3)2N—, and H2N—; or 8 and R 9taken together form a 3- to 10-membered cycloalkyl, heterocycloalkyl, aryl, or heteroaryl ring; and Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 ) cycloalkyl or (C2-C9) heterocycloalkyl is (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) 2 amine, (C2-C 10 ) Alkynylamine, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1~ C 10 ) Alkyl-, (C3-C 10 )Cycloalkyl-O-, (C2-C9)heterocycloa Rukyru-O-, (C6~C 14 )aryl-O-, (C2-C9)heteroaryl-O-, H O-, halo, H2N-, (CH3)HN-, (CH3)2N-, F3C-, F2HC-, CH3 1 to 4 selected from F2C-, FH2C-, CH3FHC-, or (CH3)2FC- The present invention also relates to compounds according to formula (I) or formula (II), optionally further substituted by a group of:

[0085] The present invention further provides a compound comprising R 7 are each independently H, (C2-C9)heteroaryl, (C2-C 10 ) Alkynylamine, (C1-C 10 )Alkoxy-, (C1-C10 )Alkyl-(C2 ~C9)heterocycloalkyl, (C2~C9)heterocycloalkyl-(C1~C 10 )Alkoxy-, (C1-C 10 )alkoxy-(C2-C9)heterocycloalkyl-, (C2-C9)heteroalkyl-C(O)—, or F2HC—, wherein each (C1-C 10 ) alkyl, (C2-C9) heteroaryl or (C2-C9) heterocycloalkyl , (C1~C 10 ) alkyl, optionally further substituted with 1 to 4 groups selected from The present invention also relates to compounds according to formula (I) or formula (II) in which

[0086] The present invention further provides a compound comprising R 7 is H. do.

[0087] The present invention further relates to compounds according to formula (I) or formula (II), wherein n is 1, 2 or 3.

[0088] The present invention further relates to compounds according to formula (I) or formula (II), wherein n is 1.

[0089] The present invention further provides a compound comprising R 1 and R 2 are each independently H, (C1 to C 10 ) alkyl, ( C1~C 10 ) Alkylamines, (C1-C 10 ) alkoxy- or NH2; It also relates to compounds according to formula (I) or formula (II).

[0090] The present invention further provides a compound comprising R 1 is H. do.

[0091] The present invention further provides a compound comprising R2 is H. do.

[0092] The present invention further provides a compound comprising R 1 and R 2 and R are each H.

[0093] The present invention further provides T 1 is CR 10 And;T 2 is CR 10 And;T 3 is CR 10 and;R 3 is CR 16 The present invention also relates to compounds according to formula (I) wherein:

[0094] The present invention further provides T 1 is CR 10 And;T 2 is CR 10 And;T 3 is CR 10 and;R 3 is N.

[0095] The present invention further provides T 1 is N;T 2 is CR 10 And;T 3 is CR 10 and;R 3 is CR 16 The present invention also relates to compounds according to formula (I) wherein:

[0096] The present invention further provides T 1 is N;T 2 is N;T 3 is CR 10 and;R 3 is CR 16 The present invention also relates to compounds according to formula (I) wherein:

[0097] The present invention further provides T 1 is N;T 2 is CR10 And;T 3 is N;R 3 is CR 16 The present invention also relates to compounds according to formula (I) wherein:

[0098] The present invention further provides T 1 is CR 10 And;T 2 is N;T 3 is CR 10 and;R 3 is N.

[0099] The present invention further provides T 1 is CR 10 And;T 2 is CR 10 And;T 3 is N;R 3 is N.

[0100] The present invention further provides T 1 is CR 10 And;T 2 is N;T 3 is N;R 3 is N.

[0101] The present invention further provides T 1 is N;T 2 is N;T 3 is N;R 3 is CR 16 The present invention also relates to compounds according to formula (I) wherein:

[0102] The present invention further provides a compound comprising R 10 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) Cycloalkane (C1~C 10 ) a compound according to formula (I) selected from the group consisting of alkoxy and halo; It also relates to compounds.

[0103] The present invention further provides a compound comprising R10 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C1-C 10 ) a compound according to formula (I) selected from the group consisting of alkoxy and halo; It also relates to compounds.

[0104] The present invention further provides a compound comprising R 16 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C1-C 10 ) a compound according to formula (I) selected from the group consisting of alkoxy and halo; It also relates to compounds.

[0105] The present invention further provides a compound comprising R 16 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C1-C 10 ) a compound according to formula (I) selected from the group consisting of alkoxy and halo; It also relates to compounds.

[0106] The present invention further provides a compound comprising R 10 and R 16 are each independently H, (C1 to C 10 ) alkyl, (C3~C 10 ) cycloalkyl, (C1-C 10 The present invention also relates to compounds according to formula (I) wherein R is selected from the group consisting of alkoxy and halo.

[0107] The present invention further provides T 1 is CR 10 and R 10 is H, (C1~C 10 ) alkyl or (C3-C 10 ) cycloalkyl; T 2 is CR 10 and R 10 is (C1~C 10 )a Rukill, (C3~C 10) cycloalkyl, (C1-C 10 ) alkoxy and halo; T 3 is CH;R 3 It also relates to compounds according to formula (I), wherein is CH.

[0108] The present invention further provides T 1 is CH;T 2 is CR 10 and R 10 is (C1~C 10 )a alkoxy);T 3 is CH, and R 3 It also relates to compounds according to formula (I), wherein is CH.

[0109] The present invention further provides T 1 is CR 10 and R 10 is H, (C1~C 10 ) alkyl or (C3-C 10 ) cycloalkyl; T 2 is CR 10 and R 10 is (C1~C 10 )Archi (C1~C 10 ) cycloalkyl, (C1-C 10 ) alkoxy and halo; T 3 teeth CH, and R 3 is N.

[0110] The present invention further provides T 1 is CH;T 2 is CR 10 and R 10 is (C1~C 10 )a alkoxy;T 3 is CH, and R 3 is N.

[0111] The present invention further provides a method for producing a compound comprising: 1 O, NR 18or CR 18 R 19 A compound according to formula (I) Also relates to.

[0112] The present invention further provides a method for producing a compound comprising: 1 is O.

[0113] The present invention further provides a method for producing a compound comprising: 1 is CR 18 R 19 The present invention also relates to compounds according to formula (I) wherein:

[0114] The present invention further provides a compound comprising R 18 and R 19 and R are each H.

[0115] The present invention further provides a method for producing a compound comprising: 1 is NR 18 The present invention also relates to compounds according to formula (I) wherein:

[0116] The present invention further relates to compounds according to formula (I), wherein m is 0, 1 or 2.

[0117] The present invention further relates to compounds according to formula (I), wherein m is 1.

[0118] The present invention further provides a compound comprising R 4 and R 5 are each independently H, (C1 to C 10 ) Alkyl, hydroxy The present invention also relates to compounds according to formula (I) wherein the hydroxyl group is selected from the group consisting of hydroxy, halo and amino.

[0119] The present invention further provides a compound comprising R 4 is H.

[0120] The present invention further provides a compound comprising R 5 is H.

[0121] The present invention further provides a compound comprising R4 and R 5 and R are each H.

[0122] The present invention further provides a compound comprising R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) Cycloalkane (C2-C9)heterocycloalkyl, (C6-C 14 ) Aryl, (C2-C9) Hetero Aryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amine, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl-, COOH-(C3-C 10 ) cycloalkyl-, (C1-C 10 ) alkoxy-, R 14 -(C1~C 10 ) alkyl-, R 14 -(C3~C 10 ) cycloalkyl, R 14 -(C2-C9)heterocycloalkyl, R 14 -(C6~C 14 ) aryl, R 14 -(C2-C9) heteroaryl, R 14 -(C2~C 10 ) alkylnyl, R 14 -(C1~C 10 ) alkylamine, R 14 -((C1~C 10 ) alkyl) amine, and R 14 -C(O)-; where R 14 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C-, and F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 ) cycloalkyl or (C2-C9) heterocycloalkyl is ( C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl-O-, (C6-C 14 )aryl-O-, (C2-C9)heteroaryl-O-, HO- , halo, or H2N-, The present invention also relates to compounds according to formula (I)

[0123] The present invention further provides a compound comprising R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) Cycloalkane (C2-C9) heteroaryl, R 14 -(C6~C 14 ) aryl, R 14 -(C2~C9) Heteroaryl and R 14 -(C1~C10 ) alkylamines, where R 14 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C-, and F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 ) cycloalkyl or (C2-C9) heterocycloalkyl is ( C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 )aryl, (C2-C9)heteroaryl, HO-, halo or H2N- The present invention also relates to compounds according to formula (I) optionally further substituted with 1 to 4 groups selected from:

[0124] The present invention further provides a compound comprising R 16 and R 4 together with the carbon to which they are attached form the formula ( II): [ka] The present invention also relates to a compound according to formula (I), which forms a compound of the formula:

[0125] The present invention further provides T 1 is CR 10 And;T 2 is CR 10 And;T 3 is CR 10 is the formula It also relates to compounds according to (II).

[0126] The present invention further provides a compound comprising R 10 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C1-C 10 ) selected from the group consisting of alkoxy and halo, according to formula (II) It also relates to compounds.

[0127] The present invention further provides T 1 is CR 10 and CR 10 is H, (C1~C 10 ) alkyl or (C3-C 10 ) cycloalkyl; T 2 is CR 10 and R 10 is (C1~C 10 )a Rukill, (C3~C 10 ) cycloalkyl, (C1-C 10 ) alkoxy and halo; T 3 It also relates to compounds according to formula (II), wherein is CH.

[0128] The present invention further provides T 1 is CH;T 2 is CR 10 and R 10 (C1~C 10 )a alkoxy;T 3 It also relates to compounds according to formula (II), wherein is CH.

[0129] The present invention further provides T 1 is CH;T 2 is CR 10 and R 10 is a halo;T 3 It also relates to compounds according to formula (II), wherein is CH.

[0130] The present invention further provides a method for producing a compound comprising: 1 and Y 2are each independently O, S, or NR 18 or CR 18 R 19 The present invention also relates to a compound according to formula (II) selected from:

[0131] The present invention further provides a method for producing a compound comprising: 1 is O.

[0132] The present invention further provides a method for producing a compound comprising: 2 is O.

[0133] The present invention further provides a method for producing a compound comprising: 1 is CR 18 R 19 The present invention also relates to a compound according to formula (II)

[0134] The present invention further provides a compound comprising R 18 and R 19 and R are each H.

[0135] The present invention further provides a method for producing a compound comprising: 2 is CR 18 R 19 The present invention also relates to a compound according to formula (II)

[0136] The present invention further provides a compound comprising R 18 and R 19 and R are each H.

[0137] The present invention further provides a method for producing a compound comprising: 1 is S.

[0138] The present invention further provides a method for producing a compound comprising: 2 is S.

[0139] The present invention further provides a method for producing a compound comprising: 1 is NR 18 and R 18 is H or (C1~C 10) alkyl.

[0140] The present invention further provides a method for producing a compound comprising: 2 is NR 18 and R 18 is H or (C1~C 10 ) alkyl.

[0141] The present invention is 1 is O;Y 2 O, S, NR 18 or CR 18 R 19 The present invention also relates to a compound according to formula (II)

[0142] The present invention further provides a method for producing a compound comprising: 2 is O.

[0143] The present invention further relates to compounds according to formula (II), wherein p is 0, 1 or 2.

[0144] The present invention further relates to compounds according to formula (II), wherein p is 1.

[0145] The present invention further provides Z 1 are each independently H, halo, or (C1-C 10 ) alkyl.

[0146] The present invention further provides a compound comprising R 5 is H, (C1~C 10 ) Alkyl, HO-, Halo and H2N- The present invention also relates to a compound according to formula (II) selected from the group consisting of:

[0147] The present invention further provides a compound comprising R 5 is H or (C1~C 10 ) alkyl.

[0148] The present invention further provides a compound comprising R5 is H.

[0149] The present invention further provides a compound comprising R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) Cycloalkane (C2-C9)heterocycloalkyl, (C6-C 14 ) Aryl, (C2-C9) Hetero Aryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amine, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl-, COOH-(C3-C 10 ) cycloalkyl-, (C1-C 10 ) alkoxy-, R 14 -(C1~C 10 ) alkyl-, R 14 -(C3~C 10 ) cycloalkyl, R 14 -(C2-C9)heterocycloalkyl, R 14 -(C6~C 14 ) aryl, R 14 -(C2-C9) heteroaryl, R 14 -(C2~C 10 ) alkylnyl, R 14 -(C1~C 10 ) alkylamine, R 14 -((C1~C 10 ) alkyl) amine, and R 14 -C(O)-; where R 14 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C-, and F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl Reel, (C3~C 10 ) cycloalkyl or (C2-C9) heterocycloalkyl is ( C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl-O-, (C6-C 14 )aryl-O-, (C2-C9)heteroaryl-O-, HO- , halo, or H2N-, The present invention also relates to compounds according to formula (II)

[0150] The present invention further provides a compound comprising R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) Cycloalkane (C2-C9) heteroaryl, R 14 -(C6~C 14 ) aryl, R 14 -(C2~C9) heteroaryl, and R 14-(C1~C 10 ) alkylamines; where R 14 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C-, and F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 ) cycloalkyl or (C2-C9) heterocycloalkyl is ( C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 The present invention also relates to compounds according to formula (II) optionally further substituted with 1 to 4 groups selected from (C2-C9)aryl, (C2-C9)heteroaryl, HO—, halo, or H2N—.

[0151] The present invention further provides a compound comprising R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) Cycloalkane (C2-C9)heterocycloalkyl, (C6-C 14 ) Aryl, (C2-C9) Hetero Aryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amine, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl-, COOH-(C3-C 10 ) cycloalkyl-, (C1-C 10 ) alkoxy-, R14 -(C1~C 10 ) alkyl-, R 14 -(C3~C 10 ) cycloalkyl, R 14 -(C2-C9)heterocycloalkyl, R 14 -(C6~C 14 ) aryl, R 14 -(C2-C9) heteroaryl, R 14 -(C2~C 10 ) alkylnyl, R 14 -(C1~C 10 ) alkylamine, R 14 -((C1~C 10 ) alkyl) amine, and R 14 -C(O)-; where R 14 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C-, and F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 ) cycloalkyl or (C2-C9) heterocycloalkyl is ( C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl-O-, (C6-C 14 )aryl-O-, (C2-C9)heteroaryl-O-, HO- , halo, or H2N-, The present invention also relates to compounds according to formula (II)

[0152] The present invention further provides a compound comprising R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) Cycloalkane (C2-C9) heteroaryl, R 14 -(C6~C 14 ) aryl, R 14 -(C2~C9) Heteroaryl and R 14 -(C1~C 10 ) alkylamines; where R 14 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C-, and F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 ) cycloalkyl or (C2-C9) heterocycloalkyl is ( C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 The present invention also relates to compounds according to formula (II) optionally further substituted with 1 to 4 groups selected from (C2-C9)aryl, (C2-C9)heteroaryl, HO—, halo, or H2N—.

[0153] The present invention further provides a compound of formula (III): [ka] [In the formula, n is 1, 2 or 3; m is 0, 1 or 2; R 1 and R 2 are each independently H, (C1 to C 10 ) alkyl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from alkoxy- or NH2; T 1 is CR 10 And;T 2 is CR 10 And;T 3 is CR 10 and;R 3 is CR 16 or N; Y 1 , O, NR 18 or CR 18 R 19 and; R 4 and R 5 are each independently H, (C1 to C 10 ) alkyl, hydroxy, halo and selected from the group consisting of amino; R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heptane Cycloalkyl, (C6-C 14) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amine, (C1-C 10 ) alkyl-C( O)O-, COOH-(C1-C 10 ) alkyl-, COOH-(C3-C 10 ) cycloalkyl-, (C1-C 10 ) alkoxy-, R 14 -(C1~C 10 ) alkyl-, R 14 -(C3~C 10 ) cycloalkyl, R 14 -(C2-C9)heterocycloalkyl, R 14 -(C6~C 14 ) aryl, R 14 -(C2-C9) heteroaryl, R 14 -(C2~C 10 ) alkylnyl, R 14 -(C1~C 10 ) alkylamine, R 14 -((C1~C 10 ) alkyl) amine, and R 14 -C(O)-; where R 14 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10 )Alkoxy-, HO-, F selected from the group consisting of 2HC—O—, F3C—C(O)—, F3C—, and F2HC—; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 ) cycloalkyl or (C2-C9) heterocycloalkyl is ( C1~C10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl-O-, (C6-C 14 )aryl-O-, (C2-C9)heteroaryl-O-, HO- , halo, or H2N-, [I'm] The present invention also relates to compounds according to the present invention.

[0154] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is CR 7 and X 5 is CR 7 The present invention also relates to compounds according to formula (III),

[0155] The present invention further comprises X 2 is CR 7 and X 3 is CR 7 and X 4 is CR 7 and X 5 teeth CR 7 The present invention also relates to compounds according to formula (III),

[0156] The present invention further comprises X2 is CR 7 and X 3 is N;X 4 is CR 7 and X 5 is CR 7 The present invention also relates to compounds according to formula (III),

[0157] The present invention further comprises X 1 is N;X 2 is CR 7 and X 3 is CR 7 and X 4 is N;X 5 is CR 7 The present invention also relates to compounds according to formula (III),

[0158] The present invention further comprises X 2 is CR 7 and X 3 is CR 7 and X 4 is CR 7 and X 5 teeth It also relates to compounds according to formula (III) wherein N.

[0159] The present invention further comprises X 2 is N;X 3 is N;X 4 is CR 7 and X 5 is CR 7 The present invention also relates to compounds according to formula (III),

[0160] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is N;X 5 is CR 7 The present invention also relates to compounds according to formula (III),

[0161] The present invention further comprises X 2 is N;X 3 is CR 7 and X4 is CR 7 and X 5 is N.

[0162] The present invention further comprises X 2 is N;X 3 is N;X 4 is CR 7 and X 5 is N The present invention also relates to compounds according to formula (III):

[0163] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is N;X 5 is N The present invention also relates to compounds according to formula (III):

[0164] The present invention further comprises X 2 is CR 7 and X 3 is N;X 4 is N;X 5 is CR 7 The present invention also relates to compounds according to formula (III),

[0165] The present invention further comprises X 2 is CR 7 and X 3 is N;X 4 is CR 7 and X 5 is N.

[0166] The present invention further comprises X 2 is CR 7 and X 3 is CR 7 and X 4 is N;X 5 is N.

[0167] The present invention further relates to compounds according to formula (III), wherein n is 1.

[0168] The present invention further provides a compound comprising R 1 and R 2 and R are each H.

[0169] The present invention further provides a compound comprising R 10 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C1-C 10 ) alkoxy and halo, The present invention also relates to compounds which

[0170] The present invention further provides T 1 is CR 10 and R 10 is H, (C1~C 10 ) alkyl or (C3-C 10 ) cycloalkyl; T 2 is CR 10 and R 10 is (C1~C 10 )Al Kill, (C3~C 10 ) cycloalkyl, (C1-C 10 ) alkoxy and halo; T 3 is CH;R 3 It also relates to compounds according to formula (III) wherein is CH or N.

[0171] The present invention further provides a method for producing a compound comprising: 1 is O.

[0172] The present invention further relates to compounds according to formula (III), wherein m is 1.

[0173] The present invention further provides a compound comprising R 4 and R 5 and R are each H.

[0174] The present invention further provides a compound comprising R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) Cycloalkane (C2-C9) heteroaryl, R 14 -(C6~C 14 ) aryl, R 14 -(C2~C9) Heteroaryl and R 14 -(C1~C 10 ) alkylamines; where R 14 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C-, and F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 ) cycloalkyl or (C2-C9) heterocycloalkyl is ( C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 The present invention also relates to compounds according to formula (III) optionally further substituted with 1 to 4 groups selected from (C2-C9)aryl, (C2-C9)heteroaryl, HO—, halo, or H2N—.

[0175] The present invention further provides a method for producing a compound according to the present invention, wherein n is 1; m is 1; 1 and R 2 are H and T 1 is CR 10 (In the formula, R 10 is H, (C1~C10 ) alkyl or (C3-C 10 ) Cycloa It is a good ol' killer. 2 is CR 10 (In the formula, R 10 is (C1~C 10 ) alkyl, (C3 ~C 10 ) cycloalkyl, (C1-C 10 ) alkoxy or halo); T 3 is CH;R 3 is CH or N; Y 1 is O;R 4 and R 5 are H; R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heptane Roarile, R 14 -(C6~C 14 ) aryl, R 14 -(C2-C9) heteroaryl and R 14 -(C1~C 10 ) alkylamines; where R 14 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C- and F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 ) cycloalkyl or (C2-C9) heterocycloalkyl is ( C1~C 10 ) Alkyl, (C3-C10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 The present invention also relates to compounds according to formula (III) optionally further substituted with 1 to 4 groups selected from (C2-C9)aryl, (C2-C9)heteroaryl, HO—, halo, or H2N—.

[0176] The present invention further provides a compound of formula (IV): [ka] [In the formula, n is 1, 2 or 3; m is 0, 1 or 2; R 1 and R 2 are each independently H, (C1 to C 10 ) alkyl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from alkoxy- or NH2; T 1 is CR 10 And;T 2 is CR 10 And;T 3 is CR 10 and;R 3 is CR 16 or N; Y 1 , O, NR 18 or CR 18 R 19 and; R 4 and R 5 are each independently H, (C1 to C 10 ) alkyl, hydroxy, halo and selected from the group consisting of amino; R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heptane Cycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10) Alkylamines, ((C1-C 10 ) alkyl) amine, (C1-C 10 ) alkyl-C( O)O-, COOH-(C1-C 10 ) alkyl-, COOH-(C3-C 10 ) cycloalkyl-, (C1-C 10 ) alkoxy-, R 14 -(C1~C 10 ) alkyl-, R 14 -(C3~C 10 ) cycloalkyl, R 14 -(C2-C9)heterocycloalkyl, R 14 -(C6~C 14 ) aryl, R 14 -(C2-C9) heteroaryl, R 14 -(C2~C 10 ) alkylnyl, R 14 -(C1~C 10 ) alkylamine, R 14 -((C1~C 10 ) alkyl) amine, and R 14 -C(O)-; where R 14 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C-, and F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 ) cycloalkyl or (C2-C9) heterocycloalkyl is ( C1~C 10 ) Alkyl, (C3-C 10) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C1 0) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl-O-, (C6-C 14 )aryl-O-, (C2-C9)heteroaryl-O-, HO- , halo, or H2N-, [I'm] The present invention also relates to compounds according to the present invention.

[0177] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is CR 7 and X 5 is CR 7 The present invention also relates to a compound according to formula (IV), wherein

[0178] The present invention further comprises X 2 is CR 7 and X 3 is CR 7 and X 4 is CR 7 and X 5 teeth CR 7 The present invention also relates to a compound according to formula (IV), wherein

[0179] The present invention further comprises X 2 is CR 7 and X3 is N;X 4 is CR 7 and X 5 is CR 7 The present invention also relates to a compound according to formula (IV), wherein

[0180] The present invention further comprises X 2 is CR 7 and X 3 is CR 7 and X 4 is N;X 5 is CR 7 The present invention also relates to a compound according to formula (IV), wherein

[0181] The present invention further comprises X 2 is CR 7 and X 3 is CR 7 and X 4 is CR 7 and X 5 teeth It also relates to compounds according to formula (IV) wherein N.

[0182] The present invention further comprises X 2 is N;X 3 is N;X 4 is CR 7 and X 5 is CR 7 The present invention also relates to a compound according to formula (IV), wherein

[0183] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is N;X 5 is CR 7 The present invention also relates to a compound according to formula (IV), wherein

[0184] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is CR 7 and X 5is N.

[0185] The present invention further comprises X 2 is N;X 3 is N;X 4 is CR 7 and X 5 is N The present invention also relates to a compound according to formula (IV):

[0186] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is N;X 5 is N The present invention also relates to a compound according to formula (IV):

[0187] The present invention further comprises X 2 is CR 7 and X 3 is N;X 4 is N;X 5 is CR 7 The present invention also relates to a compound according to formula (IV), wherein

[0188] The present invention further comprises X 2 is CR 7 and X 3 is N;X 4 is CR 7 and X 5 is N.

[0189] The present invention further comprises X 2 is CR 7 and X 3 is CR 7 and X 4 is N;X 5 is N.

[0190] The present invention further relates to compounds according to formula (IV), wherein n is 1.

[0191] The present invention further provides a compound comprising R 1 and R 2 and each are H.

[0192] The present invention further provides a compound comprising R 10 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C1-C 10 ) selected from the group consisting of alkoxy and halo, according to formula (IV) It also relates to compounds.

[0193] The present invention further provides T 1 is CR 10 and R 10 is H, (C1~C 10 ) alkyl or (C3-C 10 ) cycloalkyl; T 2 is CR 10 and R 10 is (C1~C 10 )Al Kill, (C3~C 10 ) cycloalkyl, (C1-C 10 ) alkoxy or halo; T 3 is CH;R 3 is CH or N.

[0194] The present invention further provides a method for producing a compound comprising: 1 is O.

[0195] The present invention further relates to compounds according to formula (IV), wherein m is 1.

[0196] The present invention further provides a compound comprising R 4 and R 5 and R are each H.

[0197] The present invention further provides a compound comprising R 6 is H, (C1~C 10 ) Alkyl, (C3-C10 ) Cycloalkane (C2-C9) heteroaryl, R 14 -(C6~C 14 ) aryl, R 14 -(C2~C9) Heteroaryl and R 14 -(C1~C 10 ) alkylamines; where R 14 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C-, and F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 )cycloalkyl or (C2-C9)heterocycloalkyl is (C1-C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl , (C6~C 14 The present invention also relates to compounds according to formula (IV) optionally further substituted by 1 to 4 groups selected from (C2-C9)aryl, (C2-C9)heteroaryl, HO—, halo, or H2N—.

[0198] The present invention further provides a method for producing a compound according to the present invention, wherein n is 1; m is 1; 1 and R 2 are H and T 1 is CR 10 (In the formula, R 10 is H, (C1~C 10 ) alkyl or (C3-C 10 ) Cycloa It is a good ol' killer. 2is CR 10 (In the formula, R 10 is (C1~C 10 ) alkyl, (C3 ~C 10 ) cycloalkyl, (C1-C 10 ) alkoxy or halo); T 3 is CH;R 3 is CH or N; Y 1 is O;R 4 and R 5 are H; R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heptane Roarile, R 14 -(C6~C 14 ) aryl, R 14 -(C2-C9) heteroaryl and R 14 -(C1~C 10 ) alkylamines; where R 14 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C- and F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 )cycloalkyl or (C2-C9)heterocycloalkyl is (C1-C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl , (C6~C 14The present invention also relates to compounds according to formula (IV) optionally further substituted by 1 to 4 groups selected from (C2-C9)aryl, (C2-C9)heteroaryl, HO—, halo, or H2N—.

[0199] The present invention further provides a compound of formula (V): [ka] [In the formula, n is 1, 2 or 3; m is 0, 1 or 2; R 1 and R 2 are each independently H, (C1 to C 10 ) alkyl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from alkoxy- or NH2; T 1 is CR 10 And;T 2 is CR 10 And;T 3 is CR 10 and;R 3 is CR 16 or N; Y 1 , O, NR 18 or CR 18 R 19 and; R 4 and R 5 are each independently H, (C1 to C 10 ) alkyl, hydroxy, halo and selected from the group consisting of amino; R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heptane Cycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amine, (C1-C 10 ) alkyl-C( O)O-, COOH-(C1-C 10 ) alkyl-, COOH-(C3-C 10 ) cycloalkyl-, (C1-C 10 ) alkoxy-, R 14 -(C1~C 10 ) alkyl-, R 14 -(C3~C 10 ) cycloalkyl, R 14 -(C2-C9)heterocycloalkyl, R 14 -(C6~C 14 ) aryl, R 14 -(C2-C9) heteroaryl, R 14 -(C2~C 10 ) alkylnyl, R 14 -(C1~C 10 ) alkylamine, R 14 -((C1~C 10 ) alkyl) amine, and R 14 -C(O)-; where R 14 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C-, and F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 )cycloalkyl or (C2-C9)heterocycloalkyl is (C1-C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl , (C6~C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) Alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl Ru-O-, (C6~C 14 )aryl-O-, (C2-C9)heteroaryl-O-, HO- , halo, or H2N-, [I'm] The present invention also relates to compounds according to the present invention.

[0200] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is CR 7 and X 5 is CR 7 The present invention also relates to compounds according to formula (V),

[0201] The present invention further comprises X 2 is CR 7 and X 3 is CR 7 and X 4 is CR 7 and X 5 teeth CR 7 The present invention also relates to compounds according to formula (V),

[0202] The present invention further comprises X 2 is CR 7 and X 3 is N;X 4 is CR 7 and X5 is CR 7 The present invention also relates to compounds according to formula (V),

[0203] The present invention further comprises X 2 is CR 7 and X 3 is CR 7 and X 4 is N;X 5 is CR 7 The present invention also relates to compounds according to formula (V),

[0204] The present invention further comprises X 2 is N;X 3 is N;X 4 is CR 7 and X 5 is CR 7 The present invention also relates to compounds according to formula (V),

[0205] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is N;X 5 is CR 7 The present invention also relates to compounds according to formula (V),

[0206] The present invention further comprises X 2 is CR 7 and X 3 is N;X 4 is N;X 5 is CR 7 The present invention also relates to compounds according to formula (V),

[0207] The present invention further relates to compounds according to formula (V), wherein n is 1.

[0208] The present invention further provides a compound comprising R 1 and R 2 and R are each H.

[0209] The present invention further provides a compound comprising R 10 is H, (C1~C10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C1-C 10 ) a compound according to formula (V) selected from the group consisting of alkoxy and halo; It also relates to compounds.

[0210] The present invention further provides T 1 is CR 10 and R 10 is H, (C1~C 10 ) alkyl or (C3-C 10 ) cycloalkyl; T 2 is CR 10 and R 10 is (C1~C 10 )Al Kill, (C3~C 10 ) cycloalkyl, (C1-C 10 ) alkoxy or halo; T 3 is CH;R 3 is CH or N.

[0211] The present invention further provides a method for producing a compound comprising: 1 is O.

[0212] The present invention further relates to compounds according to formula (V), wherein m is 1.

[0213] The present invention further provides a compound comprising R 4 and R 5 and R are each H.

[0214] The present invention further provides a compound comprising R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) Cycloalkane (C2-C9) heteroaryl, R 14 -(C6~C 14 ) aryl, R 14 -(C2~C9) Heteroaryl and R 14-(C1~C 10 ) alkylamines; where R 14 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C-, and F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 )cycloalkyl or (C2-C9)heterocycloalkyl is (C1-C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl , (C6~C 14 The present invention also relates to compounds according to formula (V) optionally further substituted with 1 to 4 groups selected from (C2-C9)aryl, (C2-C9)heteroaryl, HO—, halo, or H2N—.

[0215] The present invention further provides a method for producing a compound according to the present invention, wherein n is 1; m is 1; 1 and R 2 are H and T 1 is CR 10 (In the formula, R 10 is H, (C1~C 10 ) alkyl or (C3-C 10 ) Cycloa It is a good ol' killer. 2 is CR 10 (In the formula, R 10 is (C1~C 10 ) alkyl, (C3 ~C 10 ) cycloalkyl, (C1-C 10 ) alkoxy or halo); T3 is CH;R 3 is CH or N; Y 1 is O;R 4 and R 5 are H; R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heptane Roarile, R 14 -(C6~C 14 ) aryl, R 14 -(C2-C9) heteroaryl and R 14 -(C1~C 10 ) alkylamines; where R 14 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C- and F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 )cycloalkyl or (C2-C9)heterocycloalkyl is (C1-C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl , (C6~C 14 The present invention also relates to compounds according to formula (V) optionally further substituted with 1 to 4 groups selected from (C2-C9)aryl, (C2-C9)heteroaryl, HO—, halo, or H2N—.

[0216] The present invention further provides a compound of formula (VI) [ka] [In the formula, n is 1, 2 or 3; m is 0, 1 or 2; R 1 and R 2 are each independently H, (C1 to C 10 ) alkyl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from alkoxy- or NH2; T 1 is CR 10 And;T 2 is CR 10 And;T 3 is CR 10 and;R 3 is CR 16 or N; Y 1 , O, NR 18 or CR 18 R 19 and; R 4 and R 5 are each independently H, (C1 to C 10 ) alkyl, hydroxy, halo and selected from the group consisting of amino; R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heptane Cycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amine, (C1-C 10 ) alkyl-C( O)O-, COOH-(C1-C 10 ) alkyl-, COOH-(C3-C 10 ) cycloalkyl-, (C1-C 10 ) alkoxy-, R 14 -(C1~C 10 ) alkyl-, R 14 -(C3~C10 ) cycloalkyl, R 14 -(C2-C9)heterocycloalkyl, R 14 -(C6~C 14 ) aryl, R 14 -(C2-C9) heteroaryl, R 14 -(C2~C 10 ) alkylnyl, R 14 -(C1~C 10 ) alkylamine, R 14 -((C1~C 10 ) alkyl) amine, and R 14 -C(O)-; where R 14 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C-, and F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 )cycloalkyl or (C2-C9)heterocycloalkyl is (C1-C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl , (C6~C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) Alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl Ru-O-, (C6~C 14 )aryl-O-, (C2-C9)heteroaryl-O-, HO- , halo, or H2N-, [I'm] The present invention also relates to compounds according to the present invention.

[0217] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is CR 7 and X 5 is CR 7 The present invention also relates to compounds according to formula (VI), wherein:

[0218] The present invention further comprises X 2 is CR 7 and X 3 is CR 7 and X 4 is CR 7 and X 5 teeth CR 7 The present invention also relates to compounds according to formula (VI), wherein:

[0219] The present invention further comprises X 2 is CR 7 and X 3 is N;X 4 is CR 7 and X 5 is CR 7 The present invention also relates to compounds according to formula (VI),

[0220] The present invention further comprises X 2 is CR 7 and X 3 is CR 7 and X4 is N;X 5 is CR 7 The present invention also relates to compounds according to formula (VI),

[0221] The present invention further comprises X 2 is CR 7 and X 3 is CR 7 and X 4 is CR 7 and X 5 teeth It also relates to compounds according to formula (VI) wherein N.

[0222] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is N;X 5 is CR 7 The present invention also relates to compounds according to formula (VI),

[0223] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is CR 7 and X 5 is N.

[0224] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is N;X 5 is N The present invention also relates to compounds according to formula (VI):

[0225] The present invention further comprises X 2 is CR 7 and X 3 is N;X 4 is N;X 5 is CR 7 The present invention also relates to compounds according to formula (VI),

[0226] The present invention further comprises X 2 is CR 7 and X 3 is N;X 4 is CR 7 and X 5 is N.

[0227] The present invention further comprises X 2 is CR 7 and X 3 is CR 7 and X 4 is N;X 5 is N.

[0228] The present invention further relates to compounds according to formula (VI), wherein n is 1.

[0229] The present invention further provides a compound comprising R 1 and R 2 and R are each H.

[0230] The present invention further provides a compound comprising R 10 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C1-C 10 ) alkoxy and halo, according to formula (VI) It also relates to compounds.

[0231] The present invention further provides T 1 is CR 10 and R 10 is H, (C1~C 10 ) alkyl or (C3-C 10 ) cycloalkyl; T 2 is CR 10 and R 10 is (C1~C 10 )Al Kill, (C3~C 10 ) cycloalkyl, (C1-C 10 ) alkoxy or halo; T 3 is CH;R 3 is CH or N.

[0232] The present invention further provides a method for producing a compound comprising: 1 is O.

[0233] The present invention further relates to compounds according to formula (VI), wherein m is 1.

[0234] The present invention further provides a compound comprising R 4 and R 5 and R are each H.

[0235] The present invention further provides a compound comprising R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) Cycloalkane (C2-C9) heteroaryl, R 14 -(C6~C 14 ) aryl, R 14 -(C2~C9) Heteroaryl and R 14 -(C1~C 10 ) alkylamines; where R 14 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C-, and F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10)cycloalkyl or (C2-C9)heterocycloalkyl is (C1-C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl , (C6~C 14 The present invention also relates to compounds according to formula (VI) optionally further substituted with 1 to 4 groups selected from (C2-C9)aryl, (C2-C9)heteroaryl, HO—, halo, or H2N—.

[0236] The present invention further provides a method for producing a compound according to the present invention, wherein n is 1; m is 1; 1 and R 2 are H and T 1 is CR 10 (In the formula, R 10 is H, (C1~C 10 ) alkyl or (C3-C 10 ) Cycloa It is a good ol' killer. 2 is CR 10 (In the formula, R 10 is (C1~C 10 ) alkyl, (C3 ~C 10 ) cycloalkyl, (C1-C 10 ) alkoxy or halo); T 3 is CH;R 3 is CH or N; Y 1 is O;R 4 and R 5 are H; R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heptane Roarile, R 14 -(C6~C 14 ) aryl, R 14 -(C2-C9) heteroaryl and R 14 -(C1~C 10 ) alkylamines; where R 14 are each independently H, (C1 to C 10) Alkyl, (C3-C 10 ) Cycloa alkyl, (C2-C9)heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C- and F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 )cycloalkyl or (C2-C9)heterocycloalkyl is (C1-C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl , (C6~C 14 The present invention also relates to compounds according to formula (VI) optionally further substituted with 1 to 4 groups selected from (C2-C9)aryl, (C2-C9)heteroaryl, HO—, halo, or H2N—.

[0237] The present invention further provides a compound of formula (VII) [ka] [In the formula, n is 1, 2 or 3; p is 0, 1 or 2; R 1 and R 2 are each independently H, (C1 to C 10 ) alkyl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from alkoxy- or NH2; T 1 is CR 10 And;T 2 is CR 10 And;T 3 is CR 10 and; Y 1 and Y2 are each independently O, S, or NR 18 or CR 18 R 19 Selected from; Z 1 are each independently H, halo, or (C1-C 10 ) alkyl; R 5 is H, (C1~C 10 ) selected from the group consisting of alkyl, HO-, halo, and HN- Re; R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heptane Cycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amine, (C1-C 10 ) alkyl-C( O)O-, COOH-(C1-C 10 ) alkyl-, COOH-(C3-C 10 ) cycloalkyl-, (C1-C 10 ) alkoxy-, R 14 -(C1~C 10 ) alkyl-, R 14 -(C3~C 10 ) cycloalkyl, R 14 -(C2-C9)heterocycloalkyl, R 14 -(C6~C 14 ) aryl, R 14 -(C2-C9) heteroaryl, R 14 -(C2~C 10 ) alkylnyl, R 14 -(C1~C 10 ) alkylamine, R 14 -((C1~C 10 ) alkyl) amine, and R 14 -C(O)-; where R 14 are each independently H, (C1 to C10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C-, and F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 ) cycloalkyl or (C2-C9) heterocycloalkyl is ( C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl (C6~C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl-O-, (C6-C 14 )aryl-O-, (C2-C9)heteroaryl-O-, HO- , halo, or H2N-, [I'm] The present invention also relates to compounds according to the present invention.

[0238] The present invention further comprises X 2 is N;X3 is CR 7 and X 4 is CR 7 and X 5 is CR 7 The present invention also relates to compounds according to formula (VII),

[0239] The present invention further comprises X 2 is CR 7 and X 3 is CR 7 and X 4 is CR 7 and X 5 teeth CR 7 The present invention also relates to compounds according to formula (VII),

[0240] The present invention further comprises X 2 is CR 7 and X 3 is N;X 4 is CR 7 and X 5 is CR 7 The present invention also relates to compounds according to formula (VII),

[0241] The present invention further comprises X 1 is N;X 2 is CR 7 and X 3 is CR 7 and X 4 is N;X 5 is CR 7 The present invention also relates to compounds according to formula (VII),

[0242] The present invention further comprises X 2 is CR 7 and X 3 is CR 7 and X 4 is CR 7 and X 5 teeth It also relates to compounds according to formula (VII) wherein N.

[0243] The present invention further comprises X 2 is N;X3 is N;X 4 is CR 7 and X 5 is CR 7 The present invention also relates to compounds according to formula (VII),

[0244] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is N;X 5 is CR 7 The present invention also relates to compounds according to formula (VII),

[0245] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is CR 7 and X 5 is N.

[0246] The present invention further comprises X 2 is N;X 3 is N;X 4 is CR 7 and X 5 is N The present invention also relates to a compound according to formula (VII):

[0247] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is N;X 5 is N The present invention also relates to a compound according to formula (VII):

[0248] The present invention further comprises X 2 is CR 7 and X 3 is N;X 4 is N;X 5 is CR 7 The present invention also relates to compounds according to formula (VII),

[0249] The present invention further comprises X 2 is CR 7 and X 3 is N;X 4 is CR 7 and X 5 is N.

[0250] The present invention further comprises X 2 is CR 7 and X 3 is CR 7 and X 4 is N;X 5 is N.

[0251] The present invention further relates to compounds according to formula (VII), wherein n is 1.

[0252] The present invention further provides a compound comprising R 1 and R 2 and each are H.

[0253] The present invention further provides that each R 10 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C1-C 10 ) selected from the group consisting of alkoxy and halo, The present invention also relates to compounds according to the present invention.

[0254] The present invention further provides that each R 10 is H.

[0255] The present invention further provides a method for producing a compound comprising: 1 is O;Y 2 O, S, NR 18 or CR 18 R 19 The present invention also relates to compounds according to formula (VII),

[0256] The present invention further provides a method for producing a compound comprising: 2is O.

[0257] The present invention further relates to compounds according to formula (VII), wherein p is 1.

[0258] The present invention further provides a compound comprising R 5 is H or (C1~C 10 ) alkyl.

[0259] The present invention further provides a compound comprising R 5 is H.

[0260] The present invention further provides a compound comprising R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) Cycloalkane (C2-C9) heteroaryl, R 14 -(C6~C 14 ) aryl, R 14 -(C2~C9) Heteroaryl and R 14 -(C1~C 10 ) alkylamines; where R 14 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C-, and F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 ) cycloalkyl or (C2-C9) heterocycloalkyl is ( C1~C 10) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 The present invention also relates to compounds according to formula (VII) optionally further substituted by 1 to 4 groups selected from (C2-C9)aryl, (C2-C9)heteroaryl, HO—, halo, or H2N—.

[0261] The present invention further provides a method for producing a compound according to the present invention, wherein n is 1; p is 1; 1 and R 2 are H; R 10 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C1-C 10 )Al Y is selected from the group consisting of koxy and halo; 1 is O;Y 2 O, S, NR 18 or CR 18 R 19 and;R 5 is H or (C1~C 10 ) alkyl; R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heteroaryl, R 14 -(C6~C 14 ) aryl, R 14 -(C2-C9) heteroaryl and R 14 -(C1~C 10 ) alkylamines; where R 14 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C-, and F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 ) cycloalkyl or (C2-C9) heterocycloalkyl is ( C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl (C6~C 14 The present invention also relates to compounds according to formula (VII) optionally further substituted by 1 to 4 groups selected from (C2-C9)aryl, (C2-C9)heteroaryl, HO—, halo, or H2N—.

[0262] The present invention further provides a compound comprising R 5 is H and Y 2 is O.

[0263] The present invention further provides a compound of formula (VIII): [ka] [In the formula, n is 1, 2 or 3; p is 0, 1 or 2; R 1 and R 2 are each independently H, (C1 to C 10 ) alkyl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from alkoxy- or NH2; T 1 is CR 10 And;T 2 is CR 10 And;T 3 is CR 10 and; Y 1 and Y 2 are each independently O, S, or NR 18 or CR 18 R 19 Selected from; Z1 are each independently H, halo, or (C1-C 10 ) alkyl; R 5 is H, (C1~C 10 ) selected from the group consisting of alkyl, HO-, halo, and HN- Re; R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heptane Cycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amine, (C1-C 10 ) alkyl-C( O)O-, COOH-(C1-C 10 ) alkyl-, COOH-(C3-C 10 ) cycloalkyl-, (C1-C 10 ) alkoxy-, R 14 -(C1~C 10 ) alkyl-, R 14 -(C3~C 10 ) cycloalkyl, R 14 -(C2-C9)heterocycloalkyl, R 14 -(C6~C 14 ) aryl, R 14 -(C2-C9) heteroaryl, R 14 -(C2~C 10 ) alkylnyl, R 14 -(C1~C 10 ) alkylamine, R 14 -((C1~C 10 ) alkyl) amine, and R 14 -C(O)-; where R 14 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C-, and F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 )cycloalkyl or (C2-C9)heterocycloalkyl is (C1-C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl , (C6~C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) Alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl Ru-O-, (C6~C 14 )aryl-O-, (C2-C9)heteroaryl-O-, HO- , halo, or H2N-, [I'm] The present invention also relates to compounds according to the present invention.

[0264] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is CR 7 and X 5 is CR7 The present invention also relates to compounds according to formula (VIII),

[0265] The present invention further comprises X 2 is CR 7 and X 3 is CR 7 and X 4 is CR 7 and X 5 teeth CR 7 The present invention also relates to compounds according to formula (VIII),

[0266] The present invention further comprises X 2 is CR 7 and X 3 is N;X 4 is CR 7 and X 5 is CR 7 The present invention also relates to compounds according to formula (VIII),

[0267] The present invention further comprises X 2 is CR 7 and X 3 is CR 7 and X 4 is N;X 5 is CR 7 The present invention also relates to compounds according to formula (VIII),

[0268] The present invention further comprises X 2 is CR 7 and X 3 is CR 7 and X 4 is CR 7 and X 5 teeth It also relates to compounds according to formula (VIII) wherein N.

[0269] The present invention further comprises X 2 is N;X 3 is N;X 4 is CR 7 and X 5 is CR 7The present invention also relates to compounds according to formula (VIII),

[0270] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is N;X 5 is CR 7 The present invention also relates to compounds according to formula (VIII),

[0271] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is CR 7 and X 5 is N.

[0272] The present invention further comprises X 2 is N;X 3 is N;X 4 is CR 7 and X 5 is N The present invention also relates to compounds according to formula (VIII):

[0273] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is N;X 5 is N The present invention also relates to compounds according to formula (VIII):

[0274] The present invention further comprises X 2 is CR 7 and X 3 is N;X 4 is N;X 5 is CR 7 The present invention also relates to compounds according to formula (VIII),

[0275] The present invention further comprises X 2 is CR 7 and X 3 is N;X4 is CR 7 and X 5 is N.

[0276] The present invention further comprises X 2 is CR 7 and X 3 is CR 7 and X 4 is N;X 5 is N.

[0277] The present invention further relates to compounds according to formula (VIII), wherein n is 1.

[0278] The present invention further provides a compound comprising R 1 and R 2 and each are H.

[0279] The present invention further provides that each R 10 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C1-C 10 ) selected from the group consisting of alkoxy and halo, formula (VIII) The present invention also relates to compounds according to the present invention.

[0280] The present invention further provides that each R 10 is H.

[0281] The present invention further provides a method for producing a compound comprising: 1 is O;Y 2 O, S, NR 18 or CR 18 R 19 The present invention also relates to compounds according to formula (VIII),

[0282] The present invention further provides a method for producing a compound comprising: 2 is O.

[0283] The present invention further relates to compounds according to formula (VIII), wherein p is 1.

[0284] The present invention further provides a compound comprising R 5 is H or (C1~C 10 ) alkyl.

[0285] The present invention further provides a compound comprising R 5 is H.

[0286] The present invention further provides a compound comprising R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) Cycloalkane (C2-C9) heteroaryl, R 14 -(C6~C 14 ) aryl, R 14 -(C2~C9) Heteroaryl and R 14 -(C1~C 10 ) alkylamines; where R 14 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C-, and F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 )cycloalkyl or (C2-C9)heterocycloalkyl is (C1-C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl , (C6~C14 The present invention also relates to compounds according to formula (VIII) optionally further substituted by 1 to 4 groups selected from (C2-C9)aryl, (C2-C9)heteroaryl, HO—, halo, or H2N—.

[0287] The present invention further provides a method for producing a compound according to the present invention, wherein n is 1; p is 1; 1 and R 2 are H; R 10 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C1-C 10 )Al Y is selected from the group consisting of koxy and halo; 1 is O;Y 2 O, S, NR 18 or CR 18 R 19 and;R 5 is H or (C1~C 10 ) alkyl; R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heteroaryl, R 14 -(C6~C 14 ) aryl, R 14 -(C2-C9) heteroaryl and R 14 -(C1~C 10 ) alkylamines; where R 14 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C-, and F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 )cycloalkyl or (C2-C9)heterocycloalkyl is (C1-C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl , (C6~C 14 The present invention also relates to compounds according to formula (VIII) optionally further substituted by 1 to 4 groups selected from (C2-C9)aryl, (C2-C9)heteroaryl, HO—, halo, or H2N—.

[0288] The present invention further provides a compound comprising R 5 is H and Y 2 is O.

[0289] The present invention further provides a compound of formula (IX): [ka] [In the formula, n is 1, 2 or 3; p is 0, 1 or 2; R 1 and R 2 are each independently H, (C1 to C 10 ) alkyl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from alkoxy- or NH2; T 1 is CR 10 And;T 2 is CR 10 And;T 3 is CR 10 and; Y 1 and Y 2 are each independently O, S, or NR 18 or CR 18 R 19 Selected from; Z 1 are each independently H, halo, or (C1-C 10 ) alkyl; R 5 is H, (C1~C 10 ) selected from the group consisting of alkyl, HO-, halo, and HN- Re; R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heptane Cycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amine, (C1-C 10 ) alkyl-C( O)O-, COOH-(C1-C 10 ) alkyl-, COOH-(C3-C 10 ) cycloalkyl-, (C1-C 10 ) alkoxy-, R 14 -(C1~C 10 ) alkyl-, R 14 -(C3~C 10 ) cycloalkyl, R 14 -(C2-C9)heterocycloalkyl, R 14 -(C6~C 14 ) aryl, R 14 -(C2-C9) heteroaryl, R 14 -(C2~C 10 ) alkylnyl, R 14 -(C1~C 10 ) alkylamine, R 14 -((C1~C 10 ) alkyl) amine, and R 14 -C(O)-; where R 14 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C-, and F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 )cycloalkyl or (C2-C9)heterocycloalkyl is (C1-C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl , (C6~C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) Alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl Ru-O-, (C6~C 14 )aryl-O-, (C2-C9)heteroaryl-O-, HO- , halo, or H2N-, [I'm] The present invention also relates to compounds according to the present invention.

[0290] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is CR 7 and X 5 is CR 7 The present invention also relates to a compound according to formula (IX), wherein

[0291] The present invention further comprises X 2 is CR 7 and X 3 is CR 7 and X 4 is CR 7 and X 5 teeth CR 7 The present invention also relates to a compound according to formula (IX), wherein

[0292] The present invention further comprises X 2 is CR 7 and X 3 is N;X 4 is CR 7 and X 5 is CR 7 The present invention also relates to a compound according to formula (IX), wherein

[0293] The present invention further comprises X 2 is CR 7 and X 3 is CR 7 and X 4 is N;X 5 is CR 7 The present invention also relates to a compound according to formula (IX), wherein

[0294] The present invention further comprises X 2 is N;X 3 is N;X 4 is CR 7 and X 5 is CR 7 The present invention also relates to a compound according to formula (IX), wherein

[0295] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is N;X 5 is CR 7 The present invention also relates to a compound according to formula (IX), wherein

[0296] The present invention further comprises X 2 is CR 7 and X 3is N;X 4 is N;X 5 is CR 7 The present invention also relates to a compound according to formula (IX), wherein

[0297] The present invention further relates to compounds according to formula (IX), wherein n is 1.

[0298] The present invention further provides a compound comprising R 1 and R 2 and each are H.

[0299] The present invention further provides that each R 10 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C1-C 10 ) alkoxy and halo, The present invention also relates to compounds which

[0300] The present invention further provides that each R 10 is H.

[0301] The present invention further provides a method for producing a compound comprising: 1 is O;Y 2 O, S, NR 18 or CR 18 R 19 The present invention also relates to a compound according to formula (IX), wherein

[0302] The present invention further provides a method for producing a compound comprising: 2 is O.

[0303] The present invention further relates to compounds according to formula (IX), wherein p is 1.

[0304] The present invention further provides a compound comprising R 5 is H or (C1~C 10 ) alkyl.

[0305] The present invention further provides a compound comprising R 5 is H.

[0306] The present invention further provides a compound comprising R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) Cycloalkane (C2-C9) heteroaryl, R 14 -(C6~C 14 ) aryl, R 14 -(C2~C9) Heteroaryl and R 14 -(C1~C 10 ) alkylamines; where R 14 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) Cycloa alkyl, (C2-C9)heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C-, and F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 )cycloalkyl or (C2-C9)heterocycloalkyl is (C1-C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl , (C6~C 14 The present invention also relates to compounds according to formula (IX) optionally further substituted by 1 to 4 groups selected from (C2-C9)aryl, (C2-C9)heteroaryl, HO—, halo, or H2N—.

[0307] The present invention further provides a method for producing a compound according to the present invention, wherein n is 1; p is 1; 1 and R2 are H; R 10 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C1-C 10 )Al Y is selected from the group consisting of koxy and halo; 1 is O;Y 2 O, S, NR 18 or CR 18 R 19 and;R 5 is H or (C1~C 10 ) alkyl; R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heteroaryl, R 14 -(C6~C 14 ) aryl, R 14 -(C2-C9) heteroaryl and R 14 -(C1~C 10 ) alkylamines; where R 14 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C-, and F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 )cycloalkyl or (C2-C9)heterocycloalkyl is (C1-C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl , (C6~C 14The present invention also relates to compounds according to formula (IX) optionally further substituted by 1 to 4 groups selected from (C2-C9)aryl, (C2-C9)heteroaryl, HO—, halo, or H2N—.

[0308] The present invention further provides a compound comprising R 5 is H and Y 2 is O.

[0309] The present invention further provides a compound of formula (X) [ka] [In the formula, n is 1, 2 or 3; p is 0, 1 or 2; R 1 and R 2 are each independently H, (C1 to C 10 ) alkyl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from alkoxy- or NH2; T 1 is CR 10 And;T 2 is CR 10 And;T 3 is CR 10 and; Y 1 and Y 2 are each independently O, S, or NR 18 or CR 18 R 19 Selected from; Z 1 are each independently H, halo, or (C1-C 10 ) alkyl; R 5 is H, (C1~C 10 ) selected from the group consisting of alkyl, HO-, halo, and HN- Re; R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heptane Cycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amine, (C1-C 10 ) alkyl-C( O)O-, COOH-(C1-C 10 ) alkyl-, COOH-(C3-C 10 ) cycloalkyl-, (C1-C 10 ) alkoxy-, R 14 -(C1~C 10 ) alkyl-, R 14 -(C3~C 10 ) cycloalkyl, R 14 -(C2-C9)heterocycloalkyl, R 14 -(C6~C 14 ) aryl, R 14 -(C2-C9) heteroaryl, R 14 -(C2~C 10 ) alkylnyl, R 14 -(C1~C 10 ) alkylamine, R 14 -((C1~C 10 ) alkyl) amine, and R 14 -C(O)-; where R 14 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C-, and F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10)cycloalkyl or (C2-C9)heterocycloalkyl is (C1-C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl , (C6~C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) Alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl Ru-O-, (C6~C 14 )aryl-O-, (C2-C9)heteroaryl-O-, HO- , halo, or H2N-, [I'm] The present invention also relates to compounds according to the present invention.

[0310] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is CR 7 and X 5 is CR 7 The present invention also relates to compounds according to formula (X), wherein:

[0311] The present invention further comprises X 2 is CR 7 and X 3 is CR 7 and X 4 is CR 7 and X 5 teeth CR7 The present invention also relates to compounds according to formula (X), wherein:

[0312] The present invention further comprises X 2 is CR 7 and X 3 is N;X 4 is CR 7 and X 5 is CR 7 The present invention also relates to compounds according to formula (X), wherein:

[0313] The present invention further comprises X 2 is CR 7 and X 3 is CR 7 and X 4 is N;X 5 is CR 7 The present invention also relates to compounds according to formula (X), wherein:

[0314] The present invention further comprises X 2 is CR 7 and X 3 is CR 7 and X 4 is CR 7 and X 5 teeth It also relates to compounds according to formula (X) wherein N.

[0315] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is N;X 5 is CR 7 The present invention also relates to compounds according to formula (X), wherein:

[0316] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is CR 7 and X 5 is N The present invention also relates to certain compounds according to formula (X):

[0317] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is N;X 5 is N The present invention also relates to compounds according to formula (X):

[0318] The present invention further comprises X 2 is CR 7 and X 3 is N;X 4 is N;X 5 is CR 7 The present invention also relates to compounds according to formula (X), wherein:

[0319] The present invention further comprises X 2 is CR 7 and X 3 is N;X 4 is CR 7 and X 5 is N.

[0320] The present invention further comprises X 2 is CR 7 and X 3 is CR 7 and X 4 is N;X 5 is N.

[0321] The present invention further relates to compounds according to formula (X), wherein n is 1.

[0322] The present invention further provides a compound comprising R 1 and R 2 and R are each H.

[0323] The present invention further provides that each R 10 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C1-C 10 ) alkoxy and halo, according to formula (X) It also relates to compounds.

[0324] The present invention further provides that each R 10 is H.

[0325] The present invention further provides a method for producing a compound comprising: 1 is O;Y 2 O, S, NR 18 or CR 18 R 19 The present invention also relates to compounds according to formula (X), wherein:

[0326] The present invention further provides a method for producing a compound comprising: 2 is O.

[0327] The present invention further relates to compounds according to formula (X), wherein p is 1.

[0328] The present invention further provides a compound comprising R 5 is H or (C1~C 10 ) alkyl.

[0329] The present invention further provides a compound comprising R 5 is H.

[0330] The present invention further provides a compound comprising R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) Cycloalkane (C2-C9) heteroaryl, R 14 -(C6~C 14 ) aryl, R 14 -(C2~C9) Heteroaryl and R 14 -(C1~C 10 ) alkylamines; where R 14 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C-, and F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 )cycloalkyl or (C2-C9)heterocycloalkyl is (C1-C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl , (C6~C 14 The present invention also relates to compounds according to formula (X) optionally further substituted with 1 to 4 groups selected from (C2-C9)aryl, (C2-C9)heteroaryl, HO—, halo, or H2N—.

[0331] The present invention further provides a method for producing a compound according to the present invention, wherein n is 1; p is 1; 1 and R 2 are H; R 10 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C1-C 10 )Al Y is selected from the group consisting of koxy and halo; 1 is O;Y 2 O, S, NR 18 or CR 18 R 19 and;R 5 is H or (C1~C 10 ) alkyl; R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heteroaryl, R 14 -(C6~C 14 ) aryl, R 14 -(C2-C9) heteroaryl and R 14-(C1~C 10 ) alkylamines; where R 14 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C-, and F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 )cycloalkyl or (C2-C9)heterocycloalkyl is (C1-C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl , (C6~C 14 The present invention also relates to compounds according to formula (X) optionally further substituted with 1 to 4 groups selected from (C2-C9)aryl, (C2-C9)heteroaryl, HO—, halo, or H2N—.

[0332] The present invention further provides a compound comprising R 5 is H and Y 2 is O.

[0333] The present invention further provides a compound of formula (XI) [ka] [In the formula, n is 1, 2 or 3; p is 0, 1 or 2; R 1 and R 2 are each independently H, (C1 to C 10 ) alkyl, (C1-C 10) Alkylamines, (C1-C 10 ) selected from alkoxy- or NH2; T 1 is CR 10 And;T 2 is CR 10 And;T 3 is CR 10 and; Y 1 and Y 2 are each independently O, S, or NR 18 or CR 18 R 19 Selected from; Z 1 are each independently H, halo, or (C1-C 10 ) alkyl; R 5 is H, (C1~C 10 ) selected from the group consisting of alkyl, HO-, halo, and HN- Re; R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heptane Cycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amine, (C1-C 10 ) alkyl-C( O)O-, COOH-(C1-C 10 ) alkyl-, COOH-(C3-C 10 ) cycloalkyl-, (C1-C 10 ) alkoxy-, R 14 -(C1~C 10 ) alkyl-, R 14 -(C3~C 10 ) cycloalkyl, R 14 -(C2-C9)heterocycloalkyl, R 14 -(C6~C 14 ) aryl, R 14 -(C2-C9) heteroaryl, R 14 -(C2~C 10) alkylnyl, R 14 -(C1~C 10 ) alkylamine, R 14 -((C1~C 10 ) alkyl) amine, and R 14 -C(O)-; where R 14 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C-, and F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 )cycloalkyl or (C2-C9)heterocycloalkyl is (C1-C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl , (C6~C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) Alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl Ru-O-, (C6~C14 )aryl-O-, (C2-C9)heteroaryl-O-, HO- , halo, or H2N-, [I'm] The present invention also relates to compounds according to the present invention.

[0334] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is CR 7 and X 5 is CR 7 The present invention also relates to compounds according to formula (XI), wherein:

[0335] The present invention further comprises X 2 is CR 7 and X 3 is CR 7 and X 4 is CR 7 and X 5 teeth CR 7 The present invention also relates to compounds according to formula (XI), wherein:

[0336] The present invention further comprises X 2 is CR 7 and X 3 is N;X 4 is CR 7 and X 5 is CR 7 The present invention also relates to compounds according to formula (XI), wherein:

[0337] The present invention further comprises X 2 is CR 7 and X 3 is CR 7 and X 4 is N;X 5 is CR 7 The present invention also relates to compounds according to formula (XI), wherein:

[0338] The present invention further comprises X 2 is CR 7 and X3 is CR 7 and X 4 is CR 7 and X 5 teeth It also relates to compounds according to formula (XI) wherein N.

[0339] The present invention further comprises X 2 is N;X 3 is N;X 4 is CR 7 and X 5 is CR 7 The present invention also relates to compounds according to formula (XI), wherein:

[0340] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is N;X 5 is CR 7 The present invention also relates to compounds according to formula (XI), wherein:

[0341] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is CR 7 and X 5 is N.

[0342] The present invention further comprises X 2 is N;X 3 is N;X 4 is CR 7 and X 5 is N The present invention also relates to compounds according to formula (XI):

[0343] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is N;X 5 is N The present invention also relates to compounds according to formula (XI):

[0344] The present invention further comprises X 2 is CR 7 and X 3 is N;X 4 is N;X 5 is CR 7 The present invention also relates to compounds according to formula (XI), wherein:

[0345] The present invention further comprises X 2 is CR 7 and X 3 is N;X 4 is CR 7 and X 5 is N.

[0346] The present invention further comprises X 2 is CR 7 and X 3 is CR 7 and X 4 is N;X 5 is N.

[0347] The present invention further relates to compounds according to formula (XI), wherein n is 1.

[0348] The present invention further provides a compound comprising R 1 and R 2 and R are each H.

[0349] The present invention further provides that each R 10 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C1-C 10 ) alkoxy and halo, The present invention also relates to compounds which

[0350] The present invention further provides that each R 10 is H.

[0351] The present invention further provides a method for producing a compound comprising: 1 is O;Y 2 O, S, NR 18 or CR 18 R 19 The present invention also relates to compounds according to formula (XI), wherein:

[0352] The present invention further provides a method for producing a compound comprising: 2 is O.

[0353] The present invention further relates to compounds according to formula (XI), wherein p is 1.

[0354] The present invention further provides a compound comprising R 5 is H or (C1~C 10 ) alkyl.

[0355] The present invention further provides a compound comprising R 5 is H.

[0356] The present invention further provides a compound comprising R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) Cycloalkane (C2-C9) heteroaryl, R 14 -(C6~C 14 ) aryl, R 14 -(C2~C9) Heteroaryl and R 14 -(C1~C 10 ) alkylamines; where R 14 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C-, and F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 ) cycloalkyl or (C2-C9) heterocycloalkyl is ( C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 The present invention also relates to compounds according to formula (XI) optionally further substituted by 1 to 4 groups selected from (C2-C9)aryl, (C2-C9)heteroaryl, HO—, halo, or H2N—.

[0357] The present invention further provides a method for producing a compound according to the present invention, wherein n is 1; p is 1; 1 and R 2 are H; R 10 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C1-C 10 )Al Y is selected from the group consisting of koxy and halo; 1 is O;Y 2 O, S, NR 18 or CR 18 R 19 and;R 5 is H or (C1~C 10 ) alkyl; R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heteroaryl, R 14 -(C6~C 14 ) aryl, R 14 -(C2-C9) heteroaryl and R 14 -(C1~C 10 ) alkylamines; where R 14are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C-, and F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 ) cycloalkyl or (C2-C9) heterocycloalkyl is ( C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 The present invention also relates to compounds according to formula (XI) optionally further substituted by 1 to 4 groups selected from (C2-C9)aryl, (C2-C9)heteroaryl, HO—, halo, or H2N—.

[0358] The present invention further provides a compound comprising R 5 is H and Y 2 is O.

[0359] The present invention further provides a compound of formula (XII) [ka] [In the formula, n is 1, 2 or 3; p is 0, 1 or 2; R 1 and R 2 are each independently H, (C1 to C 10 ) alkyl, (C1-C 10 ) Alkylamines, (C1-C 10 ) alkoxy- or NH2-; T 1is CR 10 And;T 2 is CR 10 And;T 3 is CR 10 and; Y 1 and Y 2 are each independently O, S, or NR 18 or CR 18 R 19 Selected from; Z 1 are each independently H, halo, or (C1-C 10 ) alkyl; R 5 is H, (C1~C 10 ) selected from the group consisting of alkyl, HO-, halo, and HN- Re; R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heptane Cycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amine, (C1-C 10 ) alkyl-C( O)O-, COOH-(C1-C 10 ) alkyl-, COOH-(C3-C 10 ) cycloalkyl-, (C1-C 10 ) alkoxy-, R 14 -(C1~C 10 ) alkyl-, R 14 -(C3~C 10 ) cycloalkyl, R 14 -(C2-C9)heterocycloalkyl, R 14 -(C6~C 14 )a Lille, R 14 -(C2-C9) heteroaryl, R 14 -(C2~C 10 ) alkylnyl, R 14 -(C1~C 10 ) alkylamine, R14 -((C1~C 10 ) alkyl) 2 amine, R 14 -C (O)-; where R 14 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C-, F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 ) cycloalkyl or (C2-C9) heterocycloalkyl is ( C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl-O-, (C6-C 14 )aryl-O-, (C2-C9)heteroaryl-O-, HO- , halo, H2N-, and optionally further substituted with 1 to 4 groups selected from ] The present invention also relates to compounds according to the present invention.

[0360] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is CR 7 and X 5 is CR 7 The present invention also relates to a compound according to formula (XII),

[0361] The present invention further comprises X 2 is CR 7 and X 3 is CR 7 and X 4 is CR 7 and X 5 teeth CR 7 The present invention also relates to a compound according to formula (XII),

[0362] The present invention further comprises X 2 is CR 7 and X 3 is N;X 4 is CR 7 and X 5 is CR 7 The present invention also relates to a compound according to formula (XII),

[0363] The present invention further comprises X 2 is CR 7 and X 3 is CR 7 and X 4 is N;X 5 is CR 7 The present invention also relates to a compound according to formula (XII),

[0364] The present invention further comprises X 2 is CR 7 and X 3 is CR 7 and X 4 is CR7 and X 5 teeth It also relates to compounds according to formula (XII) wherein N.

[0365] The present invention further comprises X 2 is N;X 3 is N;X 4 is CR 7 and X 5 is CR 7 The present invention also relates to a compound according to formula (XII),

[0366] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is N;X 5 is CR 7 The present invention also relates to a compound according to formula (XII),

[0367] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is CR 7 and X 5 is N.

[0368] The present invention further comprises X 2 is N;X 3 is N;X 4 is CR 7 and X 5 is N The present invention also relates to a compound according to formula (XII):

[0369] The present invention further comprises X 2 is N;X 3 is CR 7 and X 4 is N;X 5 is N The present invention also relates to a compound according to formula (XII):

[0370] The present invention further comprises X 2 is CR7 and X 3 is N;X 4 is N;X 5 is CR 7 The present invention also relates to a compound according to formula (XII),

[0371] The present invention further comprises X 2 is CR 7 and X 3 is N;X 4 is CR 7 and X 5 is N.

[0372] The present invention further comprises X 2 is CR 7 and X 3 is CR 7 and X 4 is N;X 5 is N.

[0373] The present invention further relates to compounds according to formula (XII), wherein n is 1.

[0374] The present invention further provides a compound comprising R 1 and R 2 and each are H.

[0375] The present invention further provides that each R 10 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C1-C 10 ) selected from the group consisting of alkoxy and halo, The present invention also relates to compounds according to the present invention.

[0376] The present invention further provides that each R 10 is H.

[0377] The present invention further provides a method for producing a compound comprising: 1 is O;Y 2O, S, NR 18 or CR 18 R 19 The present invention also relates to a compound according to formula (XII),

[0378] The present invention further provides a method for producing a compound comprising: 2 is O.

[0379] The present invention further relates to compounds according to formula (XII), wherein p is 1.

[0380] The present invention further provides a compound comprising R 5 is H or (C1~C 10 ) alkyl.

[0381] The present invention further provides a compound comprising R 5 is H.

[0382] The present invention further provides a compound comprising R 6 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) Cycloalkane (C2-C9) heteroaryl, R 14 -(C6~C 14 ) aryl, R 14 -(C2~C9) Heteroaryl and R 14 -(C1~C 10 ) alkylamines; where R 14 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C-, F2HC-; Here, each (C1 to C10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 ) cycloalkyl or (C2-C9) heterocycloalkyl is ( C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 The present invention also relates to compounds according to formula (XII) optionally further substituted with 1 to 4 groups selected from: (C2-C9)aryl, (C2-C9)heteroaryl, HO—, halo, H2N—.

[0383] The present invention further provides a method for producing a compound according to the present invention, wherein n is 1; p is 1; 1 and R 2 are H; R 10 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C1-C 10 )Al Y is selected from the group consisting of koxy and halo; 1 is O;Y 2 O, S, NR 18 or CR 18 R 19 and;R 5 is H or (C1~C 10 ) alkyl; R 6 is H, (C1 ~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heteroaryl, R 14 -(C6~C 14 ) aryl, R 14 -(C2-C9) heteroaryl R 14 -(C1~C 10 ) alkylamines; where R 14 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C14 )Aryl, (C2-C9) Tetraaryl, (C1-C 10 ) Alkylamines, (C1-C 10 ) selected from the group consisting of alkoxy-, HO-, F2HC-O-, F3C-C(O)-, F3C-, F2HC-; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 ) cycloalkyl or (C2-C9) heterocycloalkyl is ( C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 The present invention also relates to compounds according to formula (XII) optionally further substituted with 1 to 4 groups selected from: (C2-C9)aryl, (C2-C9)heteroaryl, HO—, halo, H2N—.

[0384] The present invention further provides a compound comprising R 5 is H and Y 2 is O.

[0385] The present invention further provides the following: 3-(3-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-6-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridine, (S)-4-(3-((2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridin-6-yl)-2-methylbut-3-yn-2-amine, 6-methoxy-3-((8-methoxy-2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine, (S)-6-methoxy-3-((8-methoxy-2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine, (R)-6-methoxy-3-((8-methoxy-2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine, 3-((8-methoxy-2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-6-((1-methylazetidin-3-yl)oxy)-3H-imidazo[4,5-b]pyridine, 6-(difluoromethyl)-3-((8-methoxy-2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine, (S)-6-(difluoromethyl)-3-((8-methoxy-2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine, (R)-6-(difluoromethyl)-3-((8-methoxy-2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine, 3-((8-methoxy-2-(6-methoxypyridin-3-yl)-3-methyl-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine, 3-(((2R,3S)-8-methoxy-2-(6-methoxypyridin-3-yl)-3-methyl-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine, 3-(((2S,3R)-8-methoxy-2-(6-methoxypyridin-3-yl)-3-methyl-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine, 3-(((2S,3S)-8-methoxy-2-(6-methoxypyridin-3-yl)-3-methyl-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine, 3-(((2R,3R)-8-methoxy-2-(6-methoxypyridin-3-yl)-3-methyl-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine, 3-((2-(6-(1,1-difluoroethyl)pyridin-3-yl)-8-methoxy-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine, (R)-3-((2-(6-(1,1-difluoroethyl)pyridin-3-yl)-8-methoxy-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine, (S)-3-((2-(6-(1,1-difluoroethyl)pyridin-3-yl)-8-methoxy-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine, 3-((8-methoxy-2-(6-(trifluoromethyl)pyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine, (S)-3-((8-methoxy-2-(6-(trifluoromethyl)pyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine, (R)-3-((8-methoxy-2-(6-(trifluoromethyl)pyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine, Azetidin-1-yl(3-((8-methoxy-2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridin-6-yl)methanone, (S)-Azetidin-1-yl(3-((8-methoxy-2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridin-6-yl)methanone, (S)-Azetidin-1-yl(3-((8-methoxy-2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridin-6-yl)methanone, 3-((2-(6-cyclopropylpyridin-3-yl)-8-methoxy-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine, (S)-3-((2-(6-cyclopropylpyridin-3-yl)-8-methoxy-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine, (R)-3-((2-(6-cyclopropylpyridin-3-yl)-8-methoxy-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine, 3-((8-fluoro-2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-6-(2-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridine, 3-((8-methoxy-2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-6-(3-methoxyazetidine -1-yl)-3H-imidazo[4,5-b]pyridine 4-(3-((2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridin-6-yl)-2-methylbut-3-yn-2-amine (R)-4-(3-((2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridin-6-yl)-2-methylbut-3-yn-2-amine (R)-3-((8-methoxy-2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-6-((1-methylazetidin-3-yl)oxy)-3H-imidazo[4,5-b]pyridine (S)-3-((8-methoxy-2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-6-((1-methylazetidin-3-yl)oxy)-3H-imidazo[4,5-b]pyridine (R)-Azetidin-1-yl(3-((8-methoxy-2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridin-6-yl)methanone 3-((2-(6-(2-fluoropropan-2-yl)pyridin-3-yl)-8-methoxy-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine, (S)-3-((2-(6-(2-fluoropropan-2-yl)pyridin-3-yl)-8-methoxy-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine, and (R)-3-((2-(6-(2-fluoropropan-2-yl)pyridin-3-yl)-8-methoxy-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine The present invention also relates to a compound according to formula (I) or formula (II) selected from:

[0386] The present invention further provides a compound of formula (XIII): [ka] [In the formula, V 101 is C, N, O or S, r is 0, 1, 2, 3, 4 or 5; where V 101 is C, r is 0, 1, 2, 3, 4 or 5, where V 101 When is N, r is 1 and R 102 is absent; where V 101 When is O, r is 1 and R 101 and R 102 is absent; where V 101 When is S, r is 1 and R 101 and 102 is absent; s is 1, 2, 3 or 4;

[0387] X 101 , X 102 , X 103 , X 104 and X 105 are each independently N, NR 107 or CR 107 is selected from Here, each R 107 are independently H, (C1~C 10 ) Alkyl, (C3-C 10 ) Cycloal alkyl, (C2-C9)heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heptane Roaryls (C2-C 10 ) Alkyl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) 2 amine, (C2-C 10 ) Alkynylamine, C(O)-, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl-, COOH-(C3-C 10 ) cycloalkyl-, (C1-C 10 ) alkoxy-, R 108-(C1~C 10 ) alkyl-, R 108 -(C3~C 10 ) cycloalkyl, R 108 -(C2-C9)heterocycloalkyl, R 108 -(C6~C 14 ) aryl, R 108 -(C2-C9) heteroaryl, R 108 -(C2~C 10 ) alkylnyl, R 108 -(C1~C 10 ) alkylamine, R 108 -((C1~C 10 ) alkyl) 2 amine, R 108 -(C2~C 10 ) alkynylamine, R 108 -C(O)-, R 108 -(C1~C 10 ) alkyl-C(O)O-, R 108 -(C1~C 10 )Alkoxy-, (C3-C 10 ) Cycloalkyl-O-, (C2-C9)heterocycloalkyl-O-, (C6-C 14 ) Ant (C2-C9)heteroaryl-O-, R 108 -(C3~C 10 ) Cycloalkyl-O-, R 108 -(C2-C9)heterocycloalkyl-O-, R 108 -(C6~C 14 ) Ant Rool-O-, R 108 -(C2-C9)heteroaryl-O-, HO-, halo, cyano, H2N-, (CH3)HN-, (CH3)2N-, R 108 R 109 N-, R 108 R 109 N(O)C-, R 108 (R 109 C(O))N-, R 108 R 109 NC(O)O-, R 108 C(O)-, R 108 R 109 NC(O)R 108 N-, (C1~C10 )Alkyl-OC(O)R 108 N-, (C3~C 10 )Cycloalkyl-OC(O)R 108 N-, (C2-C9)heterocycloalkyl-OC(O)R 108 N-, (C6~C 14 )Aryl-OC(O)R 108 N-, (C2-C9)heteroaryl-OC(O)R 108 N-, F3C-, F2HC-, CH3F2C-, FH2C-, CH3FHC- , (CH3)2FC-;NC-, (C1~C 10 ) alkyl(O)P-, (C1-C 10 ) Alkyl-S-, (C1-C 10 )Alkyl-S-(C1-C 10 ) Alkyl-, (C3-C 10 ) Shik alkyl-S-, (C6-C 14 )aryl-S-, (C2-C9)heteroalkyl-S- , (C2-C9)heterocycloalkyl-S-, (C2-C9)heteroaryl-S-, (C1-C 10 ) alkyl-S(O)-, (C3-C 10 ) Cycloalkyl-S(O)-, (C6 C 14 )aryl-S(O)-, (C2-C9)heterocycloalkyl-S(O)-, (C2 ~C9)heteroaryl-S(O)-, (C3-C 10 ) alkyl-S(O)2-, (C3-C 10 )Cycloalkyl-S(O)2-, (C6-C 14 ) Aryl-S(O)2-, (C2-C9 ) heterocycloalkyl-S(O)2-, (C2-C9) heteroaryl-S(O)2-, R 108 R 109 NS(O)2-, (C1-C 10 )Alkyl-S(O)R 108 N-, (C3~C 10 ) Cycloalkyl-S(O)R 108 N-, (C6~C 14)Aryl-S(O)R 108 N-, (C2-C9)heterocycloalkyl-SO2R 108 N- and (C2-C9)heteroaryl-S(O)2R 108 N-; where R 108 and R 109 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, ( C2-C9)heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) Cycloalkyl-O-, (C2-C9)heterocycloalkyl-O-, (C6-C 14 ) Ant selected from the group consisting of heteroaryl-O—, (C2-C9)heteroaryl-O—, HO—, halo, (CH3)2N—, and H2N—; or R 108 and R 109 taken together form a 3- to 10-membered cycloalkyl, heterocycloalkyl, aryl, or heteroaryl ring; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 ) cycloalkyl or (C2-C9) heterocycloalkyl is ( C1~C 10 ) Alkyl, (C3-C10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl-O-, (C6-C 14 )aryl-O-, (C2-C9)heteroaryl-O-, HO- , halo, or H2N-, ;

[0388] T 101 , T 102 and T 103 are each independently N or CR 110 is selected from Here, each R 110 are independently H, (C1~C 10 ) Alkyl, (C3-C 10 ) Cycloa alkyl, (C2-C9)heterocycloalkyl, (C6-C 14 )Aryl, (C2-C9) Tetraaryl, (C2-C 10 ) Alkyl, (C1-C 10 ) alkylamines, ((C1 C 10 ) alkyl) 2 amine, (C2-C 10 ) Alkynylamine, C(O)-, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10) alkyl-, COOH-(C3-C 10 ) cycloalkyl-, (C1-C 10 ) alkoxy-, R 110A -(C1~C 10 ) alkyl-, R 110A -(C3~C 10 ) cycloalkyl, R 110A -(C2-C9)heterocycloalkyl , R 110A -(C6~C 14 ) aryl, R 110A -(C2-C9) heteroaryl, R 110A -( C2~C 10 ) alkylnyl, R 110A -(C1~C 10 ) alkylamine, R 110A -((C1~ C 10 ) alkyl) 2 amine, R 110A -(C2~C 10 ) alkynylamine, R 110A -C(O)-, R 110A -(C1~C 10 ) alkyl-C(O)O-, R 110A -(C1~C 10 )Alkoxy-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl-O-, (C6~C 14 )aryl-O-, (C2-C9)heteroaryl-O-, R 110A -(C3~C 10 ) Cycloalkyl-O-, R 110A -(C2-C9)heterocycloalkyl-O-, R 110A -(C6~C 14 ) Aryl-O-, R 110A -(C2-C9)heteroaryl-O-, HO- , halo, cyano, H2N-, (CH3)HN-, (CH3)2N-, R 110A R 111 N-, R 110A R 111 N(O)C-, R 110A (R 111 C(O))N-, R 110A R111 NC(O)O-, R 110A C(O)-, R 110A R 111 NC(O)R 110A N-, (C1~C 10 )Alkyl-OC(O)R 110A N-, (C3~C 10 )Cycloalkyl-OC(O)R 110A N-, (C2~C9) Haitai Cycloalkyl-OC(O)R 110A N-, (C6~C 14 )Aryl-OC(O)R 110A N-, (C2-C9)heteroaryl-OC(O)R 110A N-, F3C-, F2HC-, CH3F2C-, FH2C-, CH3FHC-, (CH3)2FC-;NC-, (C1~C 10 )Al Kill (O) P-, (C1~C 10 ) Alkyl-S-, (C1-C 10 )Alkyl-S-(C1~ C 10 ) Alkyl-, (C3-C 10 )Cycloalkyl-S-, (C6-C 14 )aryl-S-, (C2-C9)heteroalkyl-S-, (C2-C9)heterocycloalkyl-S-, (C2-C9)heteroaryl-S-, (C1-C 10 ) alkyl-S(O)-, (C3-C 10 ) Cycloalkyl-S(O)-, (C6-C 14 ) Aryl-S(O)-, (C2-C9) Hetero Cycloalkyl-S(O)-, (C2-C9)heteroaryl-S(O)-, (C3-C 10 ) alkyl-S(O)2-, (C3-C 10 )Cycloalkyl-S(O)2-, (C6-C 14 ) aryl-S(O)2-, (C2-C9) heterocycloalkyl-S(O)2-, (C2-C9) heteroaryl-S(O)2-, R 110A R 111 NS(O)2-, (C1-C 10 )Alkyl-S(O)R110A N-, (C3~C 10 )Cycloalkyl-S(O)R 110A N-, (C6~C 14 )Aryl-S(O)R 110A N-, (C2-C9)heterocycloalkyl-SO2R 110A N- or (C2-C9)heteroaryl-S(O)2R 110A N- Re; where R 110A and R 111 are each independently H, (C1 to C 10 ) alkyl, (C3~ C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl-O-, (C6-C 14 ) Ant Heteroaryl-O-, (C2-C9)heteroaryl-O-, HO-, halo, (CH3)2N-, H2 N-; or R 110A and R 111 are taken together to form a 3- to 10-membered cycloalkyl, heterocyclo forming an alkyl, aryl or heteroaryl ring; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C10 ) cycloalkyl or (C2-C9) heterocycloalkyl is ( C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl-O-, (C6-C 14 )aryl-O-, (C2-C9)heteroaryl-O-, HO- , halo, H2N-,

[0389] Y 101 O, S, NR 112 or CR 112 R 113 and where R 112 is absent or R 112 and R 113 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl , (C6~C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) Alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl Ru-O-, (C6~C 14 )aryl-O-, (C2-C9)heteroaryl-O-, HO- selected from the group consisting of halo, and H2N-; R 101 combines with the carbon to which it is attached to form a carbonyl, and R 102 is absent or R 101 and R 102 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2 ~C9)heterocycloalkyl-O-, (C6~C 14 )aryl-O—, (C2-C9)heteroaryl-O—, HO—, halo, and HN—, or R 101 and R 102 form a 3- to 10-membered ring together with the carbon to which they are attached; R 104 is H, (C1~C 10 ) Alkyl, (C3-C 10)Cycloalkyl, (C2-C9) Tetracycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl- , (C3~C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl-O-, ( C6~C 14 )aryl-O-, (C2-C9)heteroaryl-O-, HO-, halo, and and H2N-, or R 104 and R 105 are combined Together with carbon, they form 3- to 10-membered rings; R 105 is absent or H, (C1 to C 10 ) Alkyl, (C3-C 10 ) Cycloalkane (C2-C9)heterocycloalkyl, (C6-C 14 ) Aryl, (C2-C9) Hetero Aryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 )Cycloalkyl-O-, (C2-C9)heterocyclo Alkyl-O-, (C6-C 14 )aryl-O-, (C2-C9)heteroaryl-O-, selected from the group consisting of HO-, halo, and HN-;

[0390] R 106is H, (C1~C 10 ) Alkyl, (C3-C 10 )Cycloalkyl, (C2-C9) Tetracycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C2-C 10 ) Alkyl, (C1-C 10 ) Alkylamines, ((C1-C 10 )Alkyl)2amine , (C2~C 10 ) Alkynylamine, C(O)-, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl-, COOH-(C3-C 10 ) cycloalkyl-, (C1-C 10 ) alkoxy-, R 114 -(C1~C 10 ) alkyl-, R 114 -(C3~C 10 ) Shi Chloroalkyl, R 114 -(C2-C9)heterocycloalkyl, R 114 -(C6~C 14 ) Ant Ruhr, R 114 -(C2-C9) heteroaryl, R 114 -(C2~C 10 ) alkylnyl, R 114 -(C1~C 10 ) alkylamine, R 114 -((C1~C 10 ) alkyl) 2 amine, R 114 - (C2~C 10 ) alkynylamine, R 114 -C(O)-, R 114 -(C1~C 10 ) alkyl-C(O)O-, R 114 -(C1~C 10 )Alkoxy-, (C3-C 10 )Cycloalkyl-O -, (C2-C9)heterocycloalkyl-O-, (C6-C 14 )aryl-O-, (C2-C9)heteroaryl-O-, R 114-(C3~C 10 ) Cycloalkyl-O-, R 114 -(C2-C9)heterocycloalkyl-O-, R 114 -(C6~C 14 ) Aryl-O-, R 114 - (C2-C9) heteroaryl-O-, HO-, halo, cyano, H2N-, (CH3)HN-, (CH3)2N-, R 114 R 115 N-, R 114 R 115 N(O)C-, R 114 (R 115 C(O))N-, R 114 R 115 NC(O)O-, R 114 C(O)-, R 114 R 115 NC(O)R 114 N-, (C1~C 10 )Alkyl-OC(O)R 114 N-, (C3~C 10 )Cycloalkyl-OC( O)R 114 N-, (C2-C9)heterocycloalkyl-OC(O)R 114 N-, (C6~C 14 )Aryl-OC(O)R 114 N-, (C2-C9)heteroaryl-OC(O)R 114 N -, F3C-, F2HC-, CH3F2C-, FH2C-, CH3FHC-, (CH3)2FC-;NC-, (C1~C 10 ) alkyl(O)P-, (C1-C 10 ) Alkyl-S-, (C1~ C 10 )Alkyl-S-(C1-C 10 ) Alkyl-, (C3-C 10 )Cycloalkyl-S-, (C6-C 14 ) aryl-S-, (C2-C9) heteroalkyl-S-, (C2-C9) hetero (C1-C9)heterocycloalkyl-S-, (C2-C9)heteroaryl-S-, (C1-C 10 ) alkyl -S(O)-, (C3~C 10) Cycloalkyl-S(O)-, (C6-C 14 )aryl-S(O)-, (C2-C9)heterocycloalkyl-S(O)-, (C2-C9)heteroaryl-S(O)-, (C3-C 10 ) alkyl-S(O)2-, (C3-C 10 )Cycloalkyl -S(O)2-, (C6~C 14 )Aryl-S(O)2-, (C2-C9)heterocycloar alkyl-S(O)2-, (C2-C9)heteroaryl-S(O)2-, R 114 R 115 NS(O)2-, (C1-C 10 )Alkyl-S(O)R 114 N-, (C3~C 10 )Cycloalkyl-S (O)2R 114 N-, (C6~C 14 )Aryl-S(O)R 114 N-, (C2~C9) hetero Cycloalkyl-SO2R 114 N- and (C2-C9)heteroaryl-S(O)2R 114 N-; where R 114 and R 115 are each independently H, (C1 to C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, ( C2-C9)heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10) Cycloalkyl-O-, (C2-C9)heterocycloalkyl-O-, (C6-C 14 ) Ant C2-C9 heteroaryl-O-, HO-, F2HC-O-, halo, (C H3)2N-, H2N-, F3C-C(O)-, F3C-, and F2HC-; or R 114 and R 115 taken together form a 3- to 10-membered cycloalkyl, heterocycloalkyl, aryl, or heteroaryl ring; Here, each (C1 to C 10 ) Alkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C3-C 10 ) cycloalkyl or (C2-C9) heterocycloalkyl is ( C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl-O-, (C6-C 14 )aryl-O-, (C2-C9)heteroaryl-O-, HO- , halo, or H2N-, ;

[0391] R103 is N or CR 116 and where R 116 is H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) 2 amine, (C1-C3) alkane Quinylamine, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkyl-O-, (C6-C 14 )aryl-O—, (C2-C9)heteroaryl-O—, HO—, halo, and H2N—; or When s is 1, R 116 and R 104 together with the carbon to which they are attached to form the formula (XIV): [ka] {In the formula, The dotted line represents an optional double bond; t is 0, 1, 2, 3, 4 or 5; Z 101 are each independently H, halo, (C1 to C 10 ) alkyl, (C2-C9) heteroalkyl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) 2 amine, (C2-C 10 ) Alkynylamine, (C1-C 10 ) alkoxy- or H2N-; Y102 O, S, NR 117 or CR 117 R 118 and where R 117 is absent or R 117 and R 118 are each independently H, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, (C1-C 10 ) Alkylamines, ((C1-C 10 ) alkyl) amines, (C1-C3) alkynylamines, (C1-C 10 ) alkyl-C(O)O-, COOH-(C1-C 10 ) alkyl, COOH-(C3-C 10 ) cycloalkyl, (C1-C 10 )Alkoxy-, (C1-C 10 )Alkoxy-(C1-C 10 ) Alkyl-, (C3-C 10 ) cycloalkyl-O-, (C2-C9) heterocycloalkenyl Kill-O-, (C6~C 14 )aryl-O-, (C2-C9)heteroaryl-O-, HO -, halo, or H2N-} to form a compound by The present invention also relates to compounds according to the present invention.

[0392] The present invention further comprises X 1 is N;X 2 is N;X 3 is CR 7 and X 4 is CR 7 and X 5 is CR 7 and X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is C and / or X 3 is CH;X 4 is CR 7 and X 5 is CH;X 7 It also relates to compounds according to formula (XIII) or formula (XIV), wherein is CH.

[0393] The present invention further comprises X 1 is N;X 2 is CR 7 and X 3 is CR 7 and X 4 is CR 7 and X 5 is CR 7 and X 6 is N;X 7 is CR 7 and X 8 is C;X 9 is C; and / or X 2 is CH;X 3 is CH;X 4 is CR 7 and X 5 is CH;X 7 It also relates to compounds according to formula (XIII) or formula (XIV), wherein is CH.

[0394] A method of treating a disease or disorder mediated by colony-stimulating factor-1 receptor (CSF-1R), or a disease or disorder in which CSF-1R is implicated, in a subject in need of such treatment, comprising administering to the subject an effective amount of a compound according to Formula (I) or Formula (II).

[0395] A method for treating a disease or disorder comprising administering to a subject an effective amount of a compound according to Formula (I) or Formula (II), wherein the disease or disorder is a neurological or immune-mediated disease, including multiple sclerosis, ALS, Huntington's disease, lupus, lupus nephritis, and rheumatoid arthritis, in a subject in need of such treatment.

[0396] A pharmaceutical composition comprising a compound according to formula (I) or formula (II). DETAILED DESCRIPTION OF THE INVENTION

[0397] The present invention relates to colony-stimulating factor-1 receptor inhibitors ("CSF-1R inhibitors"). The CSF-1R inhibitors of the present invention are small molecules that can cross the blood-brain barrier and reach the central nervous system (CNS). The present invention also relates to pharmaceutical preparations containing the CSF-1R inhibitors, as well as the use of the CSF-1R inhibitors and pharmaceutical compositions containing the CSF-1R inhibitors for treating diseases. The present invention further relates to the use of the CSF-1R inhibitors and pharmaceutical compositions containing the CSF-1R inhibitors for treating immune-mediated diseases (including, but not limited to, multiple sclerosis, lupus nephritis, and rheumatoid arthritis) and neurological diseases (including, but not limited to, amyotrophic lateral sclerosis (ALS) and Huntington's disease). The CSF-1R inhibitors of the present invention can be used to inhibit c-FMS, the cellular receptor for colony-stimulating factor-1 (CSF-1).

[0398] Multiple sclerosis is a chronic, inflammatory, demyelinating disease of the CNS that causes intermittent relapses and progressive neurological deterioration. Activated microglial cells and macrophages contribute to CNS damage and play a key role in disease progression and neurodegeneration in multiple sclerosis. These activated innate immune cells are involved in antigen presentation and may produce inflammatory and neurotoxic mediators that are harmful to neurons and oligodendrocytes. CSF-1R is a receptor tyrosine kinase expressed in macrophages, monocytes, and microglial cells and is a promising target for therapeutic modulation of effector function.

[0399] The CSF-1R inhibitors of the present invention are particularly useful for the treatment of multiple sclerosis, and in in vitro and in vivo preclinical studies have demonstrated reduced production of inflammatory cytokines / chemokines and nitric oxide, inhibited macrophage / microglial cell proliferation and activation, preserved the phagocytic activity of macrophages and microglial cells, inhibited CNS infiltration in multiple in vivo disease models, protected against demyelination in rat brain slice cultures, and demonstrated therapeutic benefit in mouse disease models. These data suggest that inhibiting CNS macrophage / microglial effector function through CSF-1R antagonism provides neuroprotection in multiple sclerosis by reducing inflammation, demyelination, and axonal loss.

[0400] In one embodiment, the present invention relates to a pharmaceutical composition comprising a CSF-1R inhibitor according to formula (I) and formula (II). In another embodiment of the present invention, the pharmaceutical composition comprising a CSF-1R inhibitor according to formula (I) and formula (II) is administered in an effective amount to achieve the desired therapeutic effect. Those skilled in the art can determine the effective amount of the pharmaceutical composition comprising a CSF-1R inhibitor according to formula (I) and formula (II) depending on the individual and symptoms to be treated.

[0401] In one embodiment of the present invention, the CSF-1R inhibitor and the pharmaceutical composition comprising the CSF-1R inhibitor can be used in the treatment of immune-mediated diseases. In another embodiment of the present invention, the CSF-1R inhibitor and the pharmaceutical composition comprising the CSF-1R inhibitor can be used in the treatment of multiple sclerosis. In yet another embodiment of the present invention, the CSF-1R inhibitor and the pharmaceutical composition comprising the CSF-1R inhibitor can be used in the treatment of lupus nephritis.

[0402] In one embodiment of the present invention, the CSF-1R inhibitor and the pharmaceutical composition comprising the CSF-1R inhibitor can be used in the treatment of neurological diseases.In another embodiment of the present invention, the CSF-1R inhibitor and the pharmaceutical composition comprising the CSF-1R inhibitor can be used in the treatment of ALS.

[0403] In one embodiment of the present invention, the CSF-1R inhibitors and pharmaceutical compositions comprising the CSF-1R inhibitors may be for use in inhibiting c-FMS, the cellular receptor for colony-stimulating factor-1 (CSF-1).

[0404] The CSF-1R inhibitors of the present invention can be administered alone or in a pharmaceutical composition containing one or more CSF-1R inhibitors. Suitable pharmaceutical compositions can include a CSF-1R inhibitor and one or more pharmaceutically acceptable excipients. The form in which the CSF-1R inhibitor is administered, such as a powder, tablet, capsule, liquid, suspension, or emulsion, depends in part on the route by which it is administered. The CSF-1R inhibitor can be administered, for example, orally or by injection. Suitable excipients include, but are not limited to, inorganic or organic materials such as gelatin, albumin, lactose, starch, stabilizers, melting agents, emulsifiers, salts, and buffers. Suitable pharmaceutically acceptable excipients for intra-articular formulations, such as solutions or suspensions, include, but are not limited to, commercially available inert gels or liquids.

[0405] The CSF-1R inhibitor and the pharmaceutical composition comprising the CSF-1R inhibitor can be administered alone or in combination with one or more additional drugs.The additional drugs administered in combination with the CSF-1R inhibitor and the pharmaceutical composition comprising the CSF-1R inhibitor of the present invention include therapies for the treatment of immune-mediated diseases and neurological diseases, including multiple sclerosis, lupus nephritis and ALS.The additional drugs can be administered simultaneously with the CSF-1R inhibitor and the pharmaceutical composition comprising the CSF-1R inhibitor.The additional drugs can also be administered in series with the CSF-1R inhibitor and the pharmaceutical composition comprising the CSF-1R inhibitor.

[0406] The in vitro and in vivo effects of CSF-1R inhibitors, as well as methods for preparing preferred CSF-1R inhibitors of the present invention, are described in the Examples.

[0407] While specific embodiments of the present disclosure will now be described with reference to preparations and schemes, it is to be understood that such embodiments are merely illustrative and merely illustrating a few of the many possible specific embodiments which can represent applications of the principles of the present disclosure. Various changes and modifications will become apparent to those skilled in the art having the benefit of this disclosure and will become apparent to those skilled in the art as set forth in the appended claims. are deemed to be within the spirit and scope of the present disclosure as further defined by the scope of

[0408] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Certain preferred methods are described herein in connection with the following preparations and schemes, although other compounds or methods may be used in practice or testing.

[0409] Scheme 1: Preparation Method A [ka]

[0410] In reaction 1 of Preparation Method A, T 1 , T2 and T 3 is as defined above; G 1 is -CN, -CO2Me, -CONH2 or -CH2NHBOC, and G 2 is -F, -I, or -OBn; or G 1 is Br and B 2 is -Br or -OPMB Compound A-1, 6 (CO)CH(Br)(Z 1 ) in the presence of a base such as cesium carbonate in a polar aprotic solvent such as acetonitrile at room temperature for 1 to 24 hours.

[0411] In reaction 2 of Preparation Method A, G 1 is -CN or -CONH2, and G 2 -F or -I; or G 1 is -Br and G 2 converts compound A-2, which is -Br or -OPMB, to compound A-3 by reducing the ketone of A-2 with a reducing agent such as sodium borohydride in a suitable solvent or solvent mixture such as methanol or methanol / tetrahydrofuran at 0° C. for 1 hour.

[0412] In reaction 3 of Preparation Method A, G 1 is -CN and G 2 Compound A-3, where G is -F, is converted to compound A-5 by cyclization of A-3 in the presence of a base such as potassium carbonate in a polar aprotic solvent such as dimethylformamide at 80° C. for 24 hours. Alternatively, in reaction 3 of Preparation A, G 1 is -Br and G 2Compound A-3, where G is -Br, is converted to compound A-5 by cyclization of A-3 in the presence of a catalyst such as copper(I) iodide, a base such as cesium carbonate, and a diamine ligand such as N,N-dimethylethylenediamine in a polar aprotic solvent such as dimethylformamide at reflux for 48 hours. Alternatively, in reaction 3 of Preparation A, G 1 is -CONH2, and G 2 is -I Compound A-3 is converted to compound A-5 by cyclization of A-3 in the presence of a catalyst such as copper(I) iodide and a base such as sodium hydride in a polar aprotic solvent such as dimethylformamide at 80° C. for 2 hours.

[0413] In reaction 4 of Preparation Method A, G 1 converts compound A-5, which is -CN or -CONH2, to compound A-6 by reducing A-4 in the presence of a reducing agent such as borane-tetrahydrofuran complex in an ethereal solvent such as tetrahydrofuran at reflux for 1-16 hours, or by reducing A-5 in the presence of a reducing agent such as lithium aluminum hydride in an ethereal solvent such as tetrahydrofuran starting at 0°C and warming to room temperature over 1-5 hours. Alternatively, in reaction 4 of Preparation A, G 1 Compound A-5, where G is —CHNHBOC, is converted to compound A-6 by deprotecting A-5 in the presence of an acid such as trifluoroacetic acid in a halogenated solvent such as dichloromethane at room temperature for 1 hour. Alternatively, in reaction 4 of Preparation A, G 1Compound A-5, which is -COMe, is converted to compound A-6 by first, reducing A-4 in the presence of a reducing agent such as lithium aluminum hydride in an ethereal solvent such as tetrahydrofuran starting at 0°C for 1 hour, second, converting it to the azide by reaction with a phosphoryl azide such as diphenylphosphoryl azide and a base such as 1,8-diazabicycloundec-7-ene in an ethereal solvent such as tetrahydrofuran at room temperature to reflux for 1-16 hours, or third, reducing it with a phosphine such as resin-bound triphenylphosphine in an aqueous solvent mixture such as a tetrahydrofuran / water mixture at reflux for 1-3 hours.

[0414] In reaction 5 of Preparation Method A, G 1 is -CO2Me or -CH2NHBOC, and G 2 Compound A-2, where G is -OBn, is converted to compound A-4 by first deprotection under hydrogenation conditions with a solid supported catalyst such as palladium on carbon in the presence of hydrogen in an ethereal solvent such as tetrahydrofuran at room temperature for 1-5 hours, and second reduction with a reducing agent such as sodium borohydride in a solvent mixture such as a tetrahydrofuran / methanol mixture at 0°C for 30 minutes. Alternatively, in reaction 5 of Preparation A, G 1 is -Br and G 2 Compound A-2, which is -OPMB, is converted to compound A-4 by first, deprotection with an acid such as trifluoroacetic acid in a halogenated solvent such as dichloromethane at room temperature for 1-5 hours, and second, reduction with a reducing agent such as sodium borohydride in a solvent mixture such as a tetrahydrofuran / methanol mixture at 0° C. for 30 minutes.

[0415] In reaction 6 of Preparation A, compound A-4 is converted to compound A-5 by reacting with a resin-bound phosphine, such as triphenylphosphine, a carbon tetrahalide, such as carbon tetrachloride, and a base, such as triethylamine, in a polar aprotic solvent, such as acetonitrile, at reflux for 1 to 15 hours. Alternatively, in reaction 6 of Preparation A, compound A-4 is converted to compound A-5 by reacting with a phosphine, such as triphenylphosphine, and an azodicarboxylate, such as bis(2-methoxyethyl) azodicarboxylate, in an ethereal solvent, such as tetrahydrofuran, at room temperature to reflux for 3 to 20 hours.

[0416] In reaction 7 of Preparation Method A, T 1 , T 2 and T 3 is as defined above, and G 1 is -CO2Me, and G 2 Compound A-1, which is -OBn, is converted to compound A-7 by reacting A-1 with an alkylating agent such as p-methoxy-benzyl chloride in the presence of a base such as potassium carbonate in a polar aprotic solvent such as acetonitrile at reflux for 20 hours.

[0417] In reaction 8 of preparation method A, compound A-7 is converted to compound A-8 by first reacting A-7 with a base such as lithium hydroxide in an aqueous solvent mixture such as a tetrahydrofuran / water mixture at room temperature for 45 minutes, second reacting A-7 with an amine or amine salt, for example, ammonium chloride, an amide coupling reagent such as 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate, and a base such as triethylamine in a polar aprotic solvent such as dimethylformamide at 50° C. for 20 hours, and third reducing A-7 in the presence of a reducing agent such as lithium aluminum hydride in an ethereal solvent such as tetrahydrofuran starting at 0° C. and refluxing for 20 hours.

[0418] In reaction 9 of Preparation Method A, G 1converts compound A-5, which is -Br, to compound A-9 This is achieved by reacting A-5 with an organoboron compound such as 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) in the presence of a catalyst such as (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) chloride and a base such as potassium acetate at reflux in an ethereal solvent such as 1,4-dioxane for 2 hours.

[0419] In reaction 10 of preparation method A, compound A-9 is converted to compound A-10 by reacting A-9 with an oxidizing agent, such as sodium periodate, in an acidic aqueous solvent mixture, such as a tetrahydrofuran / water / hydrochloric acid mixture, at room temperature for 16 hours.

[0420] In reaction 11 of Preparation Method A, G 1 converts compound A-5, an ester such as -COMe, to compound A-11 by hydrolyzing A-5 with a base such as lithium hydroxide in an aqueous alcohol mixture such as a methanol / water mixture at room temperature for 16 hours.

[0421] In reaction 12 of preparation method A, compound A-11 is converted to compound A-12 by first reacting A-11 with a chlorinating reagent such as oxalyl chloride in the presence of a catalyst such as dimethylformamide in a halogenated solvent such as dichloromethane at room temperature for 1.5 hours, second reacting A-11 with a diazoalkane such as (trimethylsilyl)diazomethane in an aprotic solvent or solvent mixture such as tetrahydrofuran / acetonitrile at 0° C. to room temperature for 19 hours, and third reacting A-11 with an acid such as 48% aqueous hydrobromic acid in an aprotic solvent or solvent mixture such as tetrahydrofuran / acetonitrile at 0° C. for 10 minutes.

[0422] In reaction 13 of Preparation Method A, G 1 is Br and G 2 Compound A-1 is NH2 A-1 is converted to compound A-13 by the addition of R6 CO2H(R 6 is as defined above.

[0044] The reaction is carried out by reacting the compound with a carboxylic acid such as 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate, an amide coupling reagent such as 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate, and a base such as triethylamine in a polar aprotic solvent such as dimethylformamide at room temperature for 3 hours.

[0423] In reaction 14 of Preparation Method A, compound A-13 is converted to compound A-14 by reacting A-13 with an azodicarboxylate, such as diethyl azodicarboxylate, and a phosphine, such as triphenylphosphine, in an aprotic solvent, such as tetrahydrofuran, at room temperature for 16 hours.

[0424] In reaction 15 of preparation method A, compound A-14 is converted to compound A-15 by reacting A-14 with a cyanide salt such as zinc(II) cyanide, a catalyst such as tris(dibenzylideneacetone)dipalladium, and a ligand such as 1,1'-bis(diphenylphosphino)ferrocene in a polar aprotic solvent such as dimethyl sulfoxide at 100°C for 3 hours.

[0425] In reaction 16 of Preparation Method A, compound A-15 is converted to compound A-16 by reacting A-15 with a reducing agent such as Raney nickel in the presence of ammonia and hydrogen in an alcohol such as methanol at room temperature for 2 hours.

[0426] Scheme 2: Preparation Method B [ka]

[0427] In reaction 1 of Preparation Method B, T 1 , T 2 and T 3 is as defined above, and G 3converts compound B-1, which is -CH3, to the corresponding compound B-2, which is Dehyde R 6 (CHO)(R 6 is as defined above) in the presence of a base such as potassium hydride in an aqueous alcohol mixture such as an ethanol / water mixture at room temperature for 16 hours.

[0428] In reaction 2 of preparation method B, compound B-2 is converted to compound B-3 by cyclization of compound B-2 in the presence of a base such as sodium acetate in an aqueous alcohol mixture such as an ethanol / water mixture at reflux for 17 hours.

[0429] In reaction 3 of Preparation Method B, Compound B-3 is converted to Compound B-4 by converting the ketone of Compound B-3 with an organosilane such as triethylsilane in an acid such as trifluoroacetic acid. By reacting at 65°C for 20 hours.

[0430] In reaction 4 of preparation method B, compound B-4 is converted to compound B-7 by, first, reacting with an organoborane such as potassium vinyltrifluoroboronate, a catalyst such as palladium(II) chloride, a phosphine such as triphenylphosphine, and a base such as cesium carbonate in an aqueous ethereal solvent mixture such as a tetrahydrofuran / water mixture at reflux; second, reacting with an oxidizing reagent system such as osmium tetraoxide and sodium periodate in an aqueous ethereal solvent mixture such as a tetrahydrofuran / water mixture at room temperature for 1 hour; third, reacting with an amine or amine salt, for example, hydroxylamine hydrochloride, and a base such as sodium acetate in an alcoholic solvent such as methanol at reflux for 2 hours; and fourth, reacting with a reducing agent such as zinc dust in an acid such as acetic acid at 40° C. for 2 hours. Alternatively, in reaction 4 of preparation method B, compound B-4 is converted to compound B-7 by first reacting with a cyanating reagent such as potassium hexacyanoferulate(II) trihydrate, a catalyst such as palladium(II) acetate, a base such as cesium carbonate, and a polar solvent or solvent mixture, for example, N-methyl-2-pyrrolidone / isopropanol mixture, from room temperature to 140° C. for 16 hours, and secondly, reducing with a solid supported catalyst such as palladium on carbon (10%) in the presence of hydrogen in an acidic aqueous alcohol mixture such as methanol and concentrated HCl at room temperature for 20 hours.

[0431] In reaction 5 of Preparation Method B, T 1 , T 2 and T 3 and Z 1 is as defined above, and G 3 is —H to the corresponding compound B-5, which converts B-1 into Ketone R 6 (CO)CH3(R 6 are described above), and By reacting in an alcohol such as ethanol at reflux for 3 hours in the presence of a base such as 10 N sodium hydroxide.

[0432] In reaction 6 of preparation method B, compound B-5 is converted to compound B-6 by first reacting B-5 with a reducing reagent system such as zinc chloride and ammonium chloride in an aqueous ethereal solvent mixture such as a tetrahydrofuran / water mixture at room temperature for 10 minutes, and second reducing the carbonyl moiety with a reducing agent such as sodium borohydride in an alcohol such as methanol at 0° C. for 15 minutes. Alternatively, in reaction 6 of preparation method B, compound B-5 is converted to compound B-6 by reacting B-5 with a reducing reagent system such as cobalt(II) chloride and sodium borohydride in an ethereal solvent such as tetrahydrofuran at 0° C. to room temperature for 2 hours.

[0433] In reaction 7 of preparation B, compound B-6 is converted to compound B-7 by cyclizing B-6 with an acid such as glacial acetic acid at 110° C. for 45 minutes. Alternatively, in reaction 7 of preparation B, compound B-6 is converted to compound B-7 by cyclizing B-6 with a phosphine, such as triphenylphosphine, and an azodicarboxylate, such as bis(2-methoxyethyl) azodicarboxylate, in an ethereal solvent, such as tetrahydrofuran, at room temperature to reflux for 3 to 20 hours.

[0434] In reaction 8 of preparation method B, compound B-4 is converted to compound B-8 by reacting B-4 with an organoborane compound such as (CHCH)BFK in the presence of a catalyst such as palladium(II) chloride, a phosphine such as triphenylphosphine, and a base such as cesium carbonate in an aqueous ethereal solvent mixture such as a tetrahydrofuran / water mixture at reflux for 16 hours.

[0435] In reaction 9 of Preparation Method B, compound B-8 is converted to compound B-9 by oxidizing B-8 with an oxidizing reagent system such as osmium tetraoxide and sodium periodate in an aqueous ethereal solvent mixture such as a tetrahydrofuran / water mixture at room temperature for 1 hour. According to.

[0436] In reaction 10 of preparation method B, compound B-9 is converted to compound B-10 by reacting B-9 with a reducing agent such as sodium borohydride in an alcohol such as methanol at 0° C. for 1 hour.

[0437] In reaction 11 of preparation method B, compound B-10 is converted to compound B-11 by reacting B-10 with a carbon tetrahalide, such as carbon tetrabromide, in the presence of a phosphine, such as resin-bound triphenylphosphine, in an ethereal solvent, such as tetrahydrofuran, at reflux for 2 hours.

[0438] In reaction 12 of preparation method B, compound B-4 is converted to compound B-12 by reacting B-4 with an organolithium reagent, such as n-butyllithium, and an organoborate, such as tri-isopropoxyborate, in an ethereal solvent, such as tetrahydrofuran, at −78° C. to room temperature for 30 minutes.

[0439] In reaction 13 of preparation method B, compound B-4 is converted to compound B-13 by reacting B-4 with an organoborane compound such as 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-oxaborane) in the presence of a catalyst such as (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) chloride and a base such as potassium acetate in an ethereal solvent such as 1,4-dioxane at reflux for 2 hours.

[0440] In reaction 14 of preparation method B, compound B-13 is converted to compound B-12 by reacting B-13 with an oxidizing reagent, such as sodium periodate, in an aqueous ethereal solvent mixture, such as a tetrahydrofuran / water mixture, at room temperature for 16 hours.

[0441] Scheme 3: Preparation Method C [ka]

[0442] In reaction 1 of Preparation Method C, T1 , T 2 and T 3 is a compound C as defined above C-1 was converted to the corresponding compound C-2, which was prepared by reacting C-1 with the bromo ester CHO(C O)CH(Br)(R 6 )(R 6 is as defined above) in the presence of a base such as potassium carbonate in an aprotic solvent such as acetone at reflux for 16 hours.

[0443] In reaction 2 of Preparation Method C, compound C-2 is converted to compound C-3 (R 17 is as defined above which is obtained by converting C-2 to methyl iodide (e.g., R 17 is methyl) in the presence of a base such as potassium hydroxide in an aprotic solvent such as acetone at reflux for 45 minutes.

[0444] In reaction 3 of Preparation C, compound C-3 is converted to compound C-4 by reacting C-3 with a reducing agent such as borane-methyl sulfide complex in an ethereal solvent such as tetrahydrofuran at 50° C. for 16 hours.

[0445] In reaction 4 of preparation method C, compound C-4 is converted to compound C-5 by reacting C-4 with a cyanide salt, such as zinc(II) cyanide, and tetrakis(triphenylphosphine)palladium(0) in a polar aprotic solvent, such as diphenylformamide, at 80° C. for 16 hours.

[0446] In reaction 5 of preparation method C, compound C-5 is converted to compound C-6 by reacting C-5 with a reducing agent system such as nickel(II) chloride hexahydrate, sodium borohydride, and di-t-butyl dicarbonate in an alcohol such as methanol at 0° C. to room temperature for 4 hours.

[0447] In reaction 6 of preparation method C, compound C-6 is converted to compound C-7 by reacting C-6 with an acid such as 4N hydrogen chloride in 1,4-dioxane in a halogenated solvent such as dichloromethane at room temperature for 1 hour.

[0448] Scheme 4: Preparation Method D [ka]

[0449] In reaction 1 of Preparation Method C, T 1 , T 3 , R 3 and -R 10 is as defined above and , e.g. -R 10 is -H, halo, cyano or (C1-C 10 ) alkoxy- D-1 is converted to compound D-2, which is prepared by reacting D-1 with an alkyl chloride (R 4 )(R 5 )(R 6 )CCl(R 4 , R 5 and R 6 is defined above) and a base such as potassium carbonate In the presence of acetonitrile, the reaction is carried out at reflux for 23 hours.

[0450] In reaction 2 of preparation method C, compound D-2 is converted to compound D-3 by deprotecting D-2 with an acid such as trifluoroacetic acid in a halogenated solvent such as dichloromethane at room temperature for 30 minutes.

[0451] Scheme 5: Preparation Method E [ka]

[0452] In reaction 1 of preparation method E, T 1 and T 2is as defined above, compound E-1, R 10 is as defined above, for example, (C1~C 10 ) Compound E which is alkoxy- -2, which converts E-1 into (C1~C 10 ) alkyl iodide and potassium carbonate, etc. By reacting in the presence of a base in a polar aprotic solvent such as acetonitrile at reflux for 16 hours.

[0453] In reaction 2 of Preparation Method E, R 10 is as defined above, e.g., —H, halo, cyano or (C1-C 10 ) alkoxy- to compound E-3, which is E-2 is reacted with an alcohol (R 4 )(R 5 )(R 6 )COH(R 4 , R 5 and R 6 is as defined above) in the presence of a base such as sodium hydride in a polar aprotic solvent such as dimethyl sulfoxide at room temperature for 2 hours.

[0454] In reaction 3 of preparation method E, compound E-3 is converted to compound E-4 by first reacting E-3 with an organoboron compound such as potassium trifluoroborate (N-Boc-aminoethyl), a catalyst such as 2nd Gen XPhos precatalyst, and a base such as cesium carbonate at reflux in a biphasic solvent system such as a toluene / water mixture for 20 hours, and secondly deprotecting E-3 with an acid such as trifluoroacetic acid in a halogenated solvent such as dichloromethane at room temperature for 30 minutes.

[0455] In reaction 4 of preparation method E, compound E-3 is converted to compound E-5 by reacting E-3 with an organoboron compound, such as potassium vinyltrifluoroborate, in the presence of a catalyst, such as palladium(II) chloride, a phosphine, such as triphenylphosphine, and a base, such as cesium carbonate, in an aqueous ethereal solvent mixture, such as a tetrahydrofuran / water mixture, at reflux for 16 hours.

[0456] In reaction 5 of preparation method E, compound E-5 is converted to compound E-6 by reacting E-5 with an oxidizing agent system such as osmium tetraoxide and sodium periodate in an aqueous ethereal solvent mixture such as a tetrahydrofuran / water mixture at room temperature for 1 hour.

[0457] In reaction 6 of preparation method E, compound E-6 is converted to compound E-7 by reacting E-6 with a reducing agent such as sodium borohydride in an alcohol such as methanol at 0° C. for 1 hour.

[0458] In reaction 7 of preparation method E, compound E-7 is converted to compound E-8 by reacting E-7 with a carbon tetrahalide, such as carbon tetrabromide, in the presence of a phosphine, such as resin-bound triphenylphosphine, in an ethereal solvent, such as tetrahydrofuran, at reflux for 2 hours.

[0459] In reaction 8 of preparation method E, compound E-3 is converted to compound E-9 by reacting E-3 with an organolithium reagent, such as n-butyllithium, and an organoborate, such as tri-isopropoxyborate, in an ethereal solvent, such as tetrahydrofuran, at −78° C. to room temperature for 30 minutes.

[0460] In reaction 9 of preparation method E, compound E-3 is converted to compound E-10 by reacting E-3 with an organoboron compound such as 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) in the presence of a catalyst such as (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) chloride and a base such as potassium acetate in an ethereal solvent such as 1,4-dioxane at reflux for 2 hours.

[0461] In reaction 10 of preparation method E, compound E-10 is converted to compound E-9 by reacting E-10 with an oxidizing agent, such as sodium periodate, in an aqueous ethereal solvent mixture, such as a tetrahydrofuran / water mixture, at room temperature for 16 hours.

[0462] Scheme 6: Preparation Method F [ka]

[0463] In reaction 1 of preparation method F, T 1 , T 2 and T 3 is a compound F as defined above F-1 is converted to compound F-2, which is prepared by converting F-1 into bromoketone R 6 (CO)CH2Br(R 6 is as defined above) and a base such as potassium carbonate In the presence of dimethylformamide or another polar aprotic solvent, the reaction is carried out at a temperature between 0° C. and room temperature for 1.5 hours.

[0464] In reaction 2 of preparation method F, compound F-2 is converted to compound F-3 by reacting F-2 with a reducing agent such as sodium borohydride in an alcohol such as methanol at 0° C. for 1 hour.

[0465] In reaction 3 of Preparation Method F, compound F-3 is converted to compound F-4, which is by reacting the compound with a cyanide salt such as zinc(II) cyanide in the presence of a catalyst such as tetrakis(triphenylphosphine)palladium(0) in a polar aprotic solvent such as dimethylformamide at 90°C for 4 hours.

[0466] In reaction 4 of preparation method F, compound F-4 is converted to compound F-5 by cyclization of F-4 in the presence of a base such as potassium carbonate in a polar aprotic solvent such as dimethylformamide at 80° C. for 24 hours.

[0467] In reaction 5 of preparation method F, compound F-5 is converted to compound F-6 by reacting F-5 with a reducing agent such as lithium aluminum hydride in an ethereal solvent such as tetrahydrofuran at 0° C. for 1 hour.

[0468] In reaction 6 of preparation method F, compound F-6 is converted to compound F-7 by reacting F-6 with a reducing agent such as sodium borohydride in an alcohol such as methanol at 0° C. for 1 hour.

[0469] In reaction 7 of preparation method F, compound F-7 is converted to compound F-8 by reacting F-7 with a carbon tetrahalide, such as carbon tetrabromide, in the presence of a phosphine, such as resin-bound triphenylphosphine, in an ethereal solvent, such as tetrahydrofuran, at reflux for 2 hours.

[0470] Scheme 7: Preparation Method G [ka]

[0471] In reaction 1 of preparation method G, T 1 , T 2 , T 3 , R 6 and Z 1 is as defined above. Ri, G 1 Compound A-5, which is —CO2Me, is converted to compound G-1 by reacting A-5 with a reducing agent such as lithium aluminum hydride in an ethereal solvent such as tetrahydrofuran at 0° C. for 1 hour.

[0472] In reaction 2 of preparation method G, compound G-1 is converted to G-2 by reacting G-1 with a carbon tetrahalide, such as carbon tetrabromide, in the presence of a phosphine, such as resin-bound triphenylphosphine, in an ethereal solvent, such as tetrahydrofuran, at reflux for 2 hours.

[0473] In reaction 3 of Preparation Method G, T 1 , T 2 , T 3 , R 6 and Z 1 is as defined above. and G 1 converts compound A-5, which is Br, to G-3, which converts A-5 to n- By reaction with an organolithium reagent such as butyllithium followed by dimethylformamide in an ethereal solvent such as tetrahydrofuran at -78°C to room temperature over 1 hour.

[0474] In reaction 4 of preparation method G, compound G-1 is converted to compound G-3 by reacting G-1 with an oxidizing reagent such as a Dess-Martin hypervalent iodine compound in a halogenated solvent such as dichloromethane at room temperature for 30 minutes, or by reacting G-1 with an oxidizing reagent such as manganese(IV) oxide in a halogenated solvent such as dichloromethane at room temperature for 22 hours.

[0475] Scheme 8: Preparation Method H [ka]

[0476] In reaction 1 of Preparation Method H, X 2 , X 3 , X 4 and X 5 is as defined above; LG represents a leaving group such as -F or -Cl to convert compound H-1 to compound H-2, which is obtained by converting H-1 to an amine R *1 NH2(R *1 NH2 represents, for example, compound A-6, A-8, B-7, C-7, D-3 or E-4 as defined above) in the presence of a base such as diisopropylethylamine in acetonitrile at reflux for 2 to 16 hours.

[0477] In reaction 2 of preparation method H, compound H-2 is converted to compound H-3 by reacting H-2 with a reducing agent system such as zinc chloride and ammonium chloride in an aqueous ethereal / alcoholic mixture such as a tetrahydrofuran / methanol / water mixture at room temperature for 1 hour, or by reacting H-2 with a reducing agent such as iron in an acid such as acetic acid at 100° C. for 30 minutes.

[0478] In reaction 3 of Preparation H, compound H-3 is converted to compound H-4 by reacting H-3 with an orthoester such as triethyl orthoformate (EtO)3CR. 7 (R 7 is defined above as The reaction is carried out by reacting the compound (which is a carboxylic acid) with an alcohol such as ethanol in the presence of an acid such as p-toluenesulfonic acid at reflux for 1 to 4 hours.

[0479] In reaction 4 of preparation method H, compound H-3 is converted to compound H-5 by reacting H-3 with sodium nitrite in the presence of an acid such as acetic acid at room temperature for 2 hours.

[0480] Scheme 9: Preparation Method I [ka]

[0481] In reaction 1 of Preparation Method I, X 3 , X 4 and X 5 is as defined above, compound I -1, X 3 , X 4 , X 5 , T 1 , T 2 and T 3 is converted to compound I-2, which is as defined above, by reacting I-1 with an amine compound A-8 (R 1 and R 2 each independently represents H, G 2 is -OBn) and diisopropylethylamine, etc. The reaction is carried out in the presence of a base in a polar aprotic solvent such as acetonitrile at reflux for 2 to 16 hours.

[0482] In reaction 2 of preparation method I, compound I-2 is converted to compound I-3 by reacting I-2 with a reducing agent system, such as zinc chloride and ammonium chloride, in an aqueous ethereal / alcoholic mixture, such as a tetrahydrofuran / methanol / water mixture, at room temperature for 1 hour.

[0483] In reaction 3 of Preparation I, compound I-3 is converted to compound I-4, which can be prepared by reacting I-3 with an orthoester such as triethyl orthoformate (EtO)3CR. 7 (R 7 is defined above as The reaction is carried out by reacting the compound (which is a carboxylic acid) with an alcohol such as ethanol in the presence of an acid such as p-toluenesulfonic acid at reflux for 1 to 4 hours.

[0484] In reaction 4 of Preparation I, compound I-4 is converted to compound I-5 by reacting I-4 with an acid such as glacial acetic acid at 110° C. for 20 hours.

[0485] In reaction 5 of Preparation I, compound I-5 is converted to compound I-6, which is prepared by reacting I-5 with a bromoketone R 6 (CO)CH(Br)(Z 1 ) in the presence of a base such as cesium carbonate in a polar aprotic solvent such as acetonitrile at room temperature for 1 to 24 hours.

[0486] In reaction 6 of Preparation I, compound I-6 is converted to compound I-7 by first, deprotection under hydrogenation conditions over a solid supported catalyst such as palladium on carbon in the presence of hydrogen in an ethereal solvent such as tetrahydrofuran at room temperature for 1-5 hours, second, reduction with a reducing agent such as sodium borohydride in a solvent mixture such as a tetrahydrofuran / methanol mixture at 0°C for 30 minutes, and third, reaction with a phosphine such as resin-bound triphenylphosphine, a carbon tetrahalide such as carbon tetrachloride, or a base such as triethylamine in acetonitrile at reflux for 1-15 hours.

[0487] Scheme 10: Preparation Method J [ka]

[0488] In reaction 1 of Preparation Method J, X 3 , X 4 , X 5 , X 7 and X 8 is as defined above. For example, X 2 and X 8 are independently C or N, and X 9 Compound J-1 is C is converted to compound J-2 by reacting J-1 with a formylating reagent such as phosphorus oxychloride in dimethylformamide at 0° C. to room temperature for 16 hours.

[0489] In reaction 2 of preparation method J, compound J-2 is converted to compound J-3 by reacting J-2 with a sulfonyl hydrazide, such as p-toluenesulfonyl hydrazide, in an ethereal solvent, such as 1,4-dioxane, at 100° C. for 2 hours.

[0490] In reaction 3 of Preparation Method J, compound J-3 is converted to compound J-4, which is prepared by reacting J-3 with a boronic acid compound R *2 B(OH)2(R *2B(OH)2 represents, for example, compound A-10, B-12 or E-9 as defined above) in the presence of a base such as potassium carbonate in an ethereal solvent such as 1,4-dioxane at 100°C for 16 hours.

[0491] Scheme 11: Preparation Method K [ka]

[0492] In reaction 1 of Preparation Method K, X 2 , X 3 , X 4 , X 5 , X 7 and X 8 is as defined above, for example, X 2 and X 8 are independently C or N, and X 9 is C compound K -1 to compound K-2, which is prepared by converting K-1 to a bromide compound R *3 Br[R *3 Br can be, for example, the compound A-5 (G 1 is Br), B-4, C-4, E-2 or represents E-3] in the presence of a base such as n-butyllithium in tetrahydrofuran at −78° C. for 30 minutes.

[0493] In reaction 2 of preparation method K, compound K-2 is converted to compound K-3 by reacting K-2 with an organosilane such as triethylsilane in an acid such as trifluoroacetic acid at room temperature for 30 minutes.

[0494] Scheme 12: Preparation Method L [ka]

[0495] In reaction 1 of preparation method L, X 2 , X 3 , X 4 , X5 and X 7 is as defined above. For example, X 2 and X 8 are independently C and X 9 is C or N, or For example, X 2 and X 8 are independently C or N, and X 9 C is compound L-1 Compound L-2 is converted by reacting L-1 with a brominating reagent such as N-bromosuccinimide in a polar aprotic solvent such as dimethylformamide at 0° C. for 1.5 hours.

[0496] In reaction 2 of preparation method L, compound L-2 is converted to compound L-3 by first reacting L-2 with an organometallic reagent such as ethyl magnesium bromide in an ethereal solvent such as tetrahydrofuran at room temperature for 30 minutes, and secondly, reacting L-2 with an aldehyde compound R *4 CHO(R *4 CHO represents, for example, compound B-9, E-6, F-6 or G-3 as defined above) at room temperature for 0.5 to 3 hours.

[0497] In reaction 3 of preparation method L, compound L-3 is converted to compound L-4 by reacting L-3 with an organosilane, such as triethylsilane, in an acid, such as trifluoroacetic acid, at room temperature for 30 minutes.

[0498] Scheme 13: Preparation Method M [ka]

[0499] In reaction 1 of preparation method M, amine compound R *1 NH2(R *1 NH2 represents, for example, compound A-6, A-8, B-7, C-7, D-3 or E-4 as defined above) into compound M-1, which is obtained by firstly reacting R *1NH2 to 1,1-bis(methylthio)-2-nitro by reacting with ethylene in an alcohol such as ethanol at reflux for 19 hours, and secondly by reacting with hydrazine, such as hydrazine hydrate, in an alcohol such as ethanol at reflux for 2.5 hours.

[0500] In reaction 2 of preparation method M, compound M-1 is reacted with each R 10 is independently converted to compound M-2, as defined above, by reacting M-1 with a 1,2-dicarbonyl compound, such as dioxal, in the presence of a base, such as sodium carbonate, in an aqueous ethereal alcohol mixture, such as a tetrahydrofuran / ethanol / water mixture, at room temperature for 19 hours.

[0501] In reaction 3 of Preparation M, compound M-2 is converted to compound M-3 by first reacting M-1 with a reducing agent such as iron in an acid such as glacial acetic acid at 125° C. for 10 minutes, and secondly, reacting M-1 with an orthoester such as triethyl orthoformate (EtO)3CR. 7 (R 7 is as defined above ) in the presence of an acid such as p-toluenesulfonic acid in an alcohol such as ethanol at reflux for 1 hour.

[0502] Scheme 14: Preparation Method N [ka]

[0503] In reaction 1 of preparation method N, X 2 , X 3 and X 5 is the compound N as defined above N-1 is converted to compound N-2, which is obtained by converting N-1 into the alpha-bromoketone compound BrCH(CO)R *5 (BrCH2(CO)R *5 represents, for example, compound A-12 as defined above) in a polar aprotic solvent such as acetonitrile at reflux for 48 hours.

[0504] In reaction 2 of preparation method N, compound N-2 is converted to compound N-3 by first reacting N-2 with a reducing agent such as sodium borohydride in an alcohol such as methanol at room temperature for 30 minutes, and second reacting N-2 with an organosilane such as triethylsilane in an acid such as trifluoroacetic acid at room temperature for 2 hours.

[0505] Scheme 15: Preparation Method O [ka]

[0506] In reaction 1 of Preparation Method O, X 2 , X 3 , X 4 , X 5 and X 7 is as defined above. Compound O-1 is converted to compound O-2, which is obtained by reacting O-1 with an azodicarboxylate such as bis(2-methoxyethyl) azodicarboxylate, a phosphine such as triphenylphosphine, and an alcohol compound HOCH2R *6 (HOCH2R *6 represents, for example, the compound B-10, E-7, F-7 or G-1 defined above) in an ethereal solvent such as tetrahydrofuran at room temperature for 3 hours, or by reacting O-1 with (tributylphosphoranylidene)acetonitrile and the alcohol compound HOCH2R *6 (HOCH2R *6 represents, for example, compound B-10, E-7, F-7 or G-1 as defined above) in an aromatic solvent such as toluene at 100° C. for 1 hour.

[0507] Scheme 16: Preparation Method P [ka]

[0508] In reaction 1 of preparation method P, compound P-1 (wherein X 101 , X102 , X 103 , X 104 and X 105 is as defined above, for example, in the formula, X 102 , X 103 or X 104 are independently N; where Hal represents a halogen) to P-2 or P-3, which can be achieved by reacting P-1 with a catalyst such as a 2nd Gen XPhos palladium precatalyst, a base such as potassium phosphate, and (4,4,5,5-tetramethyl-1,3,2-dioxaborolyl)-R *7 [Wherein, (4,4,5,5-tetramethyl-1,3,2-dioxaborolyl)-R *7 represents, for example, compound A-9, B-13 or E-10 as defined above] in an aqueous ethereal solvent mixture such as a tetrahydrofuran / water mixture at 80° C. for 15 hours to give P-2, or P-1 can be converted to P-3 by reacting P-3 with a catalyst such as 2nd Gen XPhos palladium precatalyst, a base such as potassium phosphate, and a boronic acid compound (HO)BR *8 [In the formula, (HO)2BR *8 represent, for example, compounds A-10, B-12 or E-9, respectively, as defined above, in an aqueous ethereal solvent mixture such as a tetrahydrofuran / water mixture at 80° C. for 15 hours to give P-3.

[0509] Scheme 17: Preparation Method Q [ka]

[0510] In reaction 1 of preparation method Q, X 2 , X 3 , X 4 and X 7 converts a compound Q-1, which is as defined above, to a compound Q-2, which can be obtained by reacting Q-1 with a catalyst such as palladium(II) acetate, a phosphine such as tricyclohexylphosphine, a base such as potassium phosphate, and a bromine compound BrCHR *9 (BrCH2R *9represents for example compound B-11, E-8, F-8 or G-2 as defined above) in a biphasic solvent mixture such as a toluene / water mixture at reflux for 18 hours.

[0511] In reaction 2 of preparation method Q, compound Q-2 is converted to compound Q-3 by reacting Q-2 with an acid such as trifluoroacetic acid in a halogenated solvent such as dichloromethane at room temperature for 30 minutes.

[0512] Scheme 18: Preparation Method R [ka]

[0513] In reaction 1 of preparation method R, X 3 , X 4 and X 7 is a compound R as defined above R-1 is converted to compound R-2 by first reacting R-1 with an organometallic reagent such as ethyl magnesium bromide in an ethereal solvent such as tetrahydrofuran at room temperature for 30 minutes, and secondly, by reacting the aldehyde compound R *4 CHO(R *4 CHO represents, for example, the compound B-9, E-6, F-6 or G-3 defined above) at room temperature for 0.5 to 3 hours.

[0514] In reaction 2 of preparation method R, compound R-2 is converted to compound R-3 by reacting R-2 with an organosilane, such as triethylsilane, in an acid, such as trifluoroacetic acid, at room temperature for 30 minutes.

[0515] Scheme 19: Preparation Method S [ka]

[0516] In reaction 1 of preparation method S, X 103 , X 104 , X 105 , X 106, X 107 and X 108 is as defined above, for example, X 103 is N and X 108 is NR 117 For example, R 117 Compound S-1, where R is H, is converted to compound S-2 by first reacting S-1 with a first molar equivalent of an organometallic reagent, such as n-butyllithium, in an ethereal solvent, such as tetrahydrofuran, at −78° C. for 30 minutes, second reacting S-1 with a second molar equivalent of an organometallic reagent, such as t-butyllithium, in an ethereal solvent, such as tetrahydrofuran, at −78° C. for 15 minutes, and third reacting S-1 with an aldehyde compound R *4 CHO(R *4 CHO represents, for example, compound B-9, E-6, F-6 or G-3 as defined above) at -78°C to room temperature for 40 minutes.

[0517] In reaction 2 of preparation method S, compound S-2 is converted to compound S-3 by reacting S-2 with an organosilane, such as triethylsilane, in an acid, such as trifluoroacetic acid, at room temperature for 30 minutes.

[0518] Scheme 20: Preparation Method T [ka]

[0519] In reaction 1 of Preparation Method T, aldehyde compound R *4 CHO(R *4 CHO represents, for example, compound B-9, E-6, F-6 or G-3 as defined above) into compound T-1, which is *4 By reacting CHO with 3-(phenylamino)propanenitrile in the presence of a base such as sodium methoxide in a polar aprotic solvent such as dimethyl sulfoxide at 95° C. for 1 hour.

[0520] In reaction 2 of preparation method T, compound T-1 is converted to compound T-2 by reacting T-2 with guanidine hydrochloride in the presence of a base such as potassium t-butoxide in an alcohol such as ethanol at 70° C. for 48 hours.

[0521] Scheme 21: Preparation Method U [ka]

[0522] In reaction 1 of Preparation Method U, an organoborate compound, such as (4,4,5,5-tetramethyl-1,3,2-dioxaborolyl)-R *7 [Wherein, (4,4,5,5-tetramethyl-1,3,2-dioxaborolyl)-R *7 represents, for example, compound A-9, B-13 or E-10 as defined above] in the presence of an alcohol compound U-1 (R *7 -OH), which is converted to (4,4,5,5-tetramethyl-1,3,2-dioxaborolyl)-R *7 by reacting with sodium borate monohydrate in a tetrahydrofuran / water mixture at room temperature for 16 hours.

[0523] In reaction 2 of Preparation Method U, alcohol compound U-1 (R *7 -OH) to X 101 , X 104 and X 105 is converted to compound U-2, which is as defined above, which is *7 - OH) with methyl 4-chloropicolinate in the presence of sodium hydride in dimethyl sulfoxide at room temperature to 100°C for 5 hours.

[0524] In reaction 3 of preparation method U, compound U-2 is converted to compound U-3 by reacting U-2 with an amine, such as methylamine, in the presence of sodium cyanide in ethanol at 125° C. for 30 minutes.

[0525] Scheme 22: Preparation Method V [ka]

[0526] Sonogashira Coupling: In reaction 1 of Preparation Method V, X 1 , X 2 , X 3 , X 5 , X 6 , X 7 , X 8 , X 9 , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , T 1 , T 2 , T 3 , Y 1 , n and m are defined above Compound V-1, in which Hal is I, Br or Cl, is prepared by reacting R 7 is defined above (C2~C 10 ) alkynyl, (C2-C 10 ) alkynylamine, R 8 -(C2~C 10 ) alkylnyl or R 8 -(C2~C 10 ) to the alkylnylamine, compound V-2, by reacting V-1 with an alkyne, a catalyst system such as copper(I) iodide and bis(triphenylphosphine)palladium(II) chloride, and an amine such as piperidine at 100 °C for 30 min in a microwave reactor.

[0527] Suzuki Coupling: In reaction 2 of Preparation Method V, X 1 , X 2 , X 3 , X 5 , X 6 , X 7 , X 8 , X 9 , R 1 , R 2 , R3 , R 4 , R 5 , R 6 , T 1 , T 2 , T 3 , Y 1 , n and m are defined above Compound V-1, in which Hal is I, Br or Cl, is prepared by reacting R 7 is defined above Defined, (C1~C 10 ) Alkyl, (C3-C 10 ) cycloalkyl, (C2-C9) heterocycloalkyl, (C6-C 14 ) aryl, (C2-C9) heteroaryl, R 8 -(C1~C 10 ) alkyl-, R 8 -(C3~C 10 ) cycloalkyl, R 8 -(C2-C9)heterocycloalkyl, R 8 -(C6~C 14 ) aryl or R 8 -(C2-C9) heteroaryl V-1 is converted to compound V-3 by the reaction of V-1 with an organoboron compound, a catalyst such as palladium(II) acetate, a ligand such as tricyclohexylphosphine, and a carboxylic acid such as potassium phosphate tribasic. By reacting with a base in a biphasic solvent mixture such as a toluene / water mixture at reflux for 1-18 hours.

[0528] Amination coupling reaction: In reaction 3 of Preparation Method V, X 1 , X 2 , X 3 , X 5 , X 6 , X 7 , X 8 , X 9 , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , T 1 , T 2 , T 3 , Y1 , n and m are Compound V-1, wherein Hal is as defined above and is I, Br or Cl, can be prepared by reacting R 7 teeth , as defined above, H2N-, (CH3)HN- or (CH3)2N- or R 8 R 9 V-1 is converted to compound V-4, which is N-, by reacting V-1 with a primary or secondary amine, a catalyst such as a third generation BrettPhos precatalyst, a ligand such as RuPhos, and a base such as sodium t-butoxide in an ethereal solvent such as 1,4-dioxane at 100°C for 1-16 hours; or V-1 is converted to V-4 by reacting V-1 with a primary or secondary amine, a catalyst such as copper(I) iodide, a ligand such as L-proline, and a base such as potassium carbonate in a polar aprotic solvent such as dimethyl sulfoxide at 150°C for 1-6 hours; or V-1 is converted to V-4 by reacting V-1 with an aromatic heterocycle such as 1-H-imidazole, a catalyst such as copper(I) iodide, a diamine ligand such as N,N'-dimethyl-1,2-cyclohexanediamine, and a base such as potassium carbonate in a polar aprotic solvent such as dimethylformamide at 135°C for 3-16 hours.

[0529] Etherification coupling reaction: In reaction 4 of Preparation Method V, X 1 , X 2 , X 3 , X 5 , X 6 , X 7 , X 8 , X 9 , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , T 1 , T 2 , T 3 , Y 1 , n and m are , as defined above, and Hal is I, Br or Cl, 7 is defined above as (C1~C 10 ) alkoxy-, R 8 -(C1~C 10 ) alkoxy-, ( C2-C9)heterocycloalkyl-O-, (C6-C 14 ) Aryl-O-, (C2-C9) Heteroaryl-O-, R 8 -(C3~C 10 ) Heterocycloalkyl-O-, R 8 -(C2-C9)heterocycloalkyl-O-, R 8 -(C6~C 14 ) Aryl-O- or R 8 V-1 is converted to compound V-5, which is -(C2-C9)heteroaryl-O-, by reacting V-1 with an alcohol, a catalyst such as copper(I) iodide, a ligand such as 1,10-phenanthroline, and a base such as cesium carbonate in a polar solvent such as alcohol or dimethyl sulfoxide at 110°C for 1-20 hours, or V-1 is converted to V-5 by reacting V-1 with an alcohol, a catalyst such as third generation RockPhos, and a base such as cesium carbonate in a non-polar solvent such as toluene at 100°C for 5-20 hours.

[0530] Cyanation reaction: In reaction 5 of Preparation Method V, X 1 , X 2 , X 3 , X 5 , X 6 , X 7 , X 8 , X 9 , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , T 1 , T 2 , T 3 , Y 1Compound V-1, where n and m are as defined above and Hal is I, Br or Cl, is converted to compound V-6 by reacting V-1 with a cyanide salt such as zinc(II) cyanide, a catalyst such as tetrakis(triphenylphosphine)palladium(0) in a polar aprotic solvent such as dimethylformamide at 100° C. for 3 hours.

[0531] Scheme 23: Preparation Method W [ka]

[0532] In reaction 1 of preparation method W, X 1 , X 2 , X 3 , X 5 , X 6 , X 7 , X 8 , X 9 , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , T 1 , T 2 , T 3 , Y 1 Compound W-1, wherein n and m are as defined above, is converted to compound W-2 by reacting W-1 with a base such as lithium hydroxide monohydrate in an aqueous ethereal alcohol mixture such as a water / tetrahydrofuran / methanol mixture at room temperature for 1 hour.

[0533] In reaction 2 of preparation method W, compound W-2 is reacted with R 7 is the R defined above. 8 R 9 N(O)C -, which is compound W-3, which is obtained by converting W-2 into an amine, O-(benzotriazole) by reaction with an amide coupling reagent such as (-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate and a base such as diisopropylethylamine in a halogenated solvent such as dichloromethane at room temperature for 30 minutes.

[0534] In reaction 3 of preparation method W, compound W-1 is converted to compound W-4 by reacting W-1 with a reducing agent such as lithium aluminum hydride in an ethereal solvent such as tetrahydrofuran at room temperature for 30 minutes.

[0535] In reaction 4 of preparation method W, compound W-4 is converted to compound W-5 by reacting W-4 with an oxidizing reagent such as manganese(IV) oxide in a halogenated solvent such as dichloromethane at room temperature for 22 hours.

[0536] In reaction 5 of preparation method W, compound W-5 is reacted with R 7 is the (C2-C9) heterocyclic group defined above. Aryl or R 8 -(C2-C9) heteroaryl compound W-6, which is , by reacting W-5 with a 1,2-dicarbonyl compound such as glyoxal and an amine salt such as ammonium acetate in a polar aprotic solvent such as N-methyl-2-pyrrolidone at 120° C. for 16 hours.

[0537] As used herein, the term "amino" refers to a functional group having one nitrogen atom and one to two hydrogen atoms. Amino is generally used herein to describe primary, secondary, or tertiary amines, and one of ordinary skill in the art can easily identify the context in which the term is used in this disclosure. The term "amine" or "amine group" or "ammonia group" refers to a group derived from ammonia (NH3). It refers to a functional group containing a nitrogen atom. The amine group is preferably a primary amine, which means that the nitrogen is bonded to two hydrogen atoms and one substituent, including a substituted or unsubstituted alkyl or aryl group, or an aliphatic or aromatic group. The amine group may be a secondary amine, which means that the nitrogen is bonded to one hydrogen atom and two substituents, including a substituted or unsubstituted alkyl or aryl group, or an aliphatic or aromatic group, as defined below. The amine group may be a tertiary amine, which means that the nitrogen is bonded to three substituents, including a substituted or unsubstituted alkyl or aryl group, or an aliphatic or aromatic group. The amine group may also be a quaternary amine, which means that the designated amine group may be bonded to a fourth group, resulting in a positively charged ammonium group.

[0538] Any or all of the amines in the present invention may be in the free amine form (i.e., as —NH for primary amines) or may be substituted with a pharmaceutically acceptable amine. Protonated form with anion [i.e., -NH3 for primary amines] - Y - (Y - is a pharmaceutically acceptable anion).

[0539] As used herein, the term "amide group" refers to a functional group containing a carbonyl group attached to a nitrogen atom. "Carbonyl group" refers to a functional group containing a carbon atom double-bonded to an oxygen atom, represented as (C=O).

[0540] The term "alkane" means a saturated hydrocarbon connected by a single bond. Alkanes can be straight-chain or branched. "Cycloalkane" means a saturated hydrocarbon ring connected by a single bond.

[0541] As used herein, the term "(C1-C 10)Alkyl is a group of 1 to 10 carbon atoms. means a saturated, straight-chain, branched-chain or cyclic hydrocarbon consisting essentially of 1 to 10 carbon atoms and the corresponding number of hydrogen atoms. Typically, a straight-chain or branched-chain group contains 1 to 10 carbon atoms. carbon, or more typically 1 to 5 carbons. 10 ) Alkyl groups include methyl (represented by -CH3), ethyl (represented by -CH2-CH3) , n-propyl, isopropyl, n-butyl, isobutyl, etc. C 10 ) alkyl groups will be readily apparent to those of ordinary skill in the art given the benefit of this disclosure.

[0542] As used herein, the term "(C2-C9)heteroalkyl" means a saturated, straight-chain, branched, or cyclic hydrocarbon group consisting essentially of 2 to 10 atoms, wherein 2 to 9 of the atoms are carbon, and the remaining atoms are selected from the group consisting of nitrogen, sulfur, and oxygen. Illustrative (C2-C9)heteroalkyl groups will be readily apparent to those of ordinary skill in the art given the benefit of this disclosure.

[0543] As used herein, the term "(C3-C 10 )Cycloalkyl" is a group consisting of 3 to 10 It means a non-aromatic saturated hydrocarbon group consisting essentially of carbon atoms and a corresponding number of hydrogen atoms forming at least one ring. (C3-C 10 ) Cycloalkyl is a monocyclic The individual rings of a polycyclic cycloalkyl group can have different connectivity, for example, fused, bridged, spiro-bonded, etc., in addition to covalent bond substitution. Exemplary (C3-C 10 ) Cycloalkyl includes cyclopropyl, cyclobutyl cyclopentyl, cyclohexyl, norbornanyl, bicyclooctanyl, octahydropentalenyl, spiro-decanyl, cyclopropyl substituted with cyclobutyl, cyclobutyl substituted with cyclopentyl, cyclohexyl substituted with cyclopropyl, etc. 10 ) Cycloalkyl groups are useful in the present disclosure. This will be readily apparent to those skilled in the art.

[0544] As used herein, the term "(C2-C9)heterocycloalkyl" refers to a non-aromatic group having 3 to 10 atoms forming at least one ring, wherein 2 to 9 of the ring atoms are carbon, and the remaining ring atoms are selected from the group consisting of nitrogen, sulfur, and oxygen. A (C2-C9)heterocycloalkyl group can be monocyclic or polycyclic. The individual rings of such polycyclic heterocycloalkyl groups can have different connectivity, for example, fused, bridged, spiro-bonded, etc., in addition to covalent bond substitution. Exemplary (C2-C9)heterocycloalkyl groups include pyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydropyranyl, pyranyl, thiopyranyl, aziridinyl, azetidinyl, oxiranyl, methylenedioxyl, chromenyl, barbituryl, isoxazolidinyl, 1,3-oxazolidin-3-yl, isothiazolidinyl, 1,3-thiazolidin-3-yl, 1,2-pyrazolidin-2-yl, 1,3-pyrazolidin-1-yl, piperidinyl, thiomorpholinyl, 1,2-tetrahydrothiazin-2-yl, 1,3-tetrahydrothiazin-3-yl, tetrahydrothiadiazinyl, morpholinyl, 1,2-tetrahydrodiazin-2-yl, 1,3-tetrahydrodiazin-1-yl, tetrahydroazepinyl, piperazinyl, piperidinyl, thiazolid ... 2-Azabicyclo[3.2.1]octanyl, 3-Azabicyclo[3.2.1]octanyl, 3,8-Diazabicyclo[3.2.1]octanyl, 2,5-Diazabicyclo[2.2.1]heptanyl, 2,5-Diazabicyclo[2.2.1]heptanyl, 2,5-Diazabicyclo[2.2.1]heptanyl, 2,5-Diazabicyclo[2.2.1]octan ... Examples include azabicyclo[2.2.2]octanyl, octahydro-2H-pyrido[1,2-a]pyrazinyl, 3-azabicyclo[4.1.0]heptanyl, 3-azabicyclo[3.1.0]hexanyl, 2-azaspiro[4.4]nonanyl, 7-oxa-1-aza-spiro[4.4]nonanyl, 7-azabicyclo[2.2.2]heptanyl, octahydro-1H-indolyl, etc. (C2-C9) heterocycloalkyl groups are typically attached to the main structure through a carbon atom or a nitrogen atom.Other (C2-C9)heterocycloalkyl groups will be readily apparent to those of ordinary skill in the art given the benefit of this disclosure.

[0545] The terms "aliphatic group" or "aliphatic" refer to a non-aromatic group composed of carbon and hydrogen, which may optionally contain one or more double and / or triple bonds. In other words, an aliphatic group is any group composed of carbon and hydrogen that does not contain aromatic functionality. Aliphatic groups may be straight-chained, branched-chained, or cyclic and typically contain between about 1 and about 24 carbon atoms.

[0546] The term "aryl group" can be used interchangeably with "aryl," "aryl ring," "aromatic," "aromatic group," and "aromatic ring." Aryl groups include carbocyclic aromatic groups typically having from 6 to 14 ring carbon atoms. Aryl groups also include heteroaryl groups typically having from 5 to 14 ring carbon atoms and having one or more heteroatoms selected from nitrogen, oxygen, and sulfur.

[0547] As used herein, the term "(C6-C 14 ) aryl" means a group having at least one ring means an aromatic functional group having 6 to 14 carbon atoms that forms the following formula:

[0548] As used herein, the term "(C2-C9)heteroaryl" refers to an aromatic functional group having 5 to 10 atoms forming at least one ring, where 2 to 9 of the ring atoms are carbon and the remaining ring atoms are selected from the group consisting of nitrogen, sulfur, and oxygen. (C2-C9)heteroaryl groups can be monocyclic or polycyclic. The individual rings of such polycyclic heteroaryl groups can have different connectivity, such as fused bonds in addition to covalent bond substitution. Exemplary (C2-C9)heteroaryl groups include furyl, thienyl, thiazolyl, pyrazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyrrolyl, triazolyl, tetrazolyl, imidazolyl, 1,3,5-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,3-oxadiazolyl, 1,3,5-thiadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, 1,2,4-thiazinyl, 1,2,3-thiazinyl, 1,3,5-thiazinyl, pyrazolo[3,4-b]pi Examples include lysinyl, cinnolinyl, pteridinyl, purinyl, 6,7-dihydro-5H-[1]pyrindinyl, benzo[b]thiophenyl, 5,6,7,8-tetrahydroquinolin-3-yl, benzoxazolyl, benzothiazolyl, benzisothiazolyl, benzisoxazolyl, benzimidazolyl, thianaphthenyl, isothianaphthenyl, benzofuranyl, isobenzofuranyl, isoindolyl, indolizinyl, indazolyl, isoquinolyl, quinolyl, phthalazinyl, quinoxalinyl, quinazolinyl, and benzoxazinyl. (C2-C9)Heteroaryl is typically attached to the main structure via a carbon atom; however, those skilled in the art will recognize when certain other atoms, such as heterocyclic atoms, can be attached to the main structure. Other (C2-C9)heteroaryl groups will be readily apparent to those skilled in the art given the benefit of this disclosure.

[0549] The term "alkynyl" refers to an alkynyl group (C-C 10 ) alkynyl-, which contains a triple bond carbon atom It means a functional group having

[0550] As used herein, the term "alkylamine" refers to an amine selected from the group consisting of alkylamines (C1-C 10 )Alkylamine and ((C1~C 10 ) alkyl) amine, which contains a primary, secondary or tertiary amine group in place of one hydrogen atom (C1-C 10 ) alkyl.

[0551] The term "alkynylamine" refers to an alkynylamine (C2-C 10 ) alkylamine, represented by triple bond carbon and one amine group (C2-C 10 ) group.

[0552] The term "alkoxy" refers to an alkyl group (C1-C 10 ) alkyl, (C1-C 10 ) alkyl-O- or (C1-C 10 The term "alkoxy" is used. "Alkyl" is another (C1-C 10 ) bonded to alkyl, bonded to oxygen (C1-C 10 ) alkyl, (C1-C 10 )Alkyl-O-(C1-C 10 ) alkyl or (C1 ~C 10 )Alkoxy-(C1-C 10 ) alkyl-.

[0553] The term "alkyl ester" refers to an alkyl group containing an ester group in place of one hydrogen atom (C1 ~C 10 ) alkyl, -O(O)C-(C1-C 10 ) alkyl.

[0554] The term "alkyl acid" refers to an alkyl group containing a carboxylic acid group (C1-C 10 ) alkyl, (C1-C 10 ) alkyl-COOH.

[0555] The term "aliphatic acid" means an acid of a non-aromatic hydrocarbon, (C1-C 10 )Alkyl-CO OH and (C3-C 10 ) cycloalkyl-COOH.

[0556] The term "dicarbonyl" refers to an organic molecule containing two or more adjacent carbonyl groups. The carbonyl group, represented by C=O, can be, for example, an aldehyde, a ketone, or other group having an oxygen atom double-bonded to a carbon atom. Examples include, but are not limited to, glyoxal, methylglyoxal, dimethylglyoxal, and 3-deoxyglucosone.

[0557] The term "halo" or "Hal" refers to the ions fluorine (F), chlorine (Cl), bromine (Br), iodine (I), or astatine (At).

[0558] The term "methoxy" refers to a (C1) alkyl containing an oxygen atom in place of one hydrogen atom. It has the taste and is represented by -(O)CH3.

[0559] The term "polyol" means an alcohol containing multiple hydroxyl (-OH) groups.

[0560] "Substituted" means the replacement of a carbon in an alkyl, heterocyclic, or aryl group with one or more non-carbon substituents selected from nitrogen, oxygen, and sulfur.

[0561] "Unsubstituted" means that the group consists only of hydrogen and carbon.

[0562] A 3- to 10-membered ring means a closed ring; the 3- to 10-membered ring can be acyclic, aromatic or heterocyclic.

[0563] The term "pharmaceutically acceptable anion" means an anion that is suitable for pharmaceutical use. Pharmaceutically acceptable anions include, but are not limited to, halides, carbonates, bicarbonates, sulfates, bisulfates, hydroxides, nitrates, persulfates, phosphates, sulfites, acetates, ascorbates, benzoates, citrates, dihydrogen citrates, hydrogen citrates, oxalates, succinates, tartrates, taurocholates, glycocholates, and cholates.

[0564] All pharmaceutically acceptable salts, prodrugs, tautomers, hydrates and solvates of the compounds disclosed herein are also within the scope of the present disclosure.

[0565] The compounds disclosed herein that are basic in nature are generally capable of forming a wide variety of different salts with various inorganic and / or organic acids. Although the compounds are pharmaceutically acceptable for administration to humans, it is often desirable in practice to initially isolate the compound from the reaction mixture as a pharmaceutically unacceptable salt, then simply convert the latter back to the free base compound by treatment with an alkaline reagent, followed by conversion of the free base to a pharmaceutically acceptable acid addition salt. Acid addition salts of basic compounds can be readily prepared using conventional techniques, for example, by treating the basic compound with an approximately equal amount of a selected inorganic or organic acid in an aqueous solvent medium or in a suitable organic solvent, such as methanol or ethanol. Upon careful evaporation of the solvent, the desired solid salt is obtained.

[0566] Acids that can be used to prepare pharmaceutically acceptable acid addition salts of base compounds are those capable of forming non-toxic acid addition salts, i.e., salts containing pharmacologically acceptable anions, such as chloride, bromide, iodide, nitrate, sulfate or bisulfate, phosphoric acid or acid phosphate, acetic acid, lactic acid, citric acid or acid citric acid, tartaric acid or bitartaric acid, succinic acid, maleic acid, fumaric acid, gluconate, sugar acid, benzoic acid, methanesulfonic acid, and pamoic acid [i.e., 1,1'-methylene-bis-(2-hydroxy-3-naphthoate)] salts.

[0567] The compounds disclosed herein that are acidic in nature, for example, containing a COOH or tetrazole moiety, can generally form a wide variety of salts with various inorganic and / or organic bases. While these salts are generally pharmaceutically acceptable for administration to animals and humans, it is often desirable in practice to initially isolate the compound from the reaction mixture as a pharmaceutically unacceptable salt, then simply convert the latter back to the free acid compound by treatment with an alkaline reagent, followed by conversion of the free acid to a pharmaceutically acceptable base addition salt. These base addition salts can be readily prepared using conventional techniques, for example, by treating the corresponding acidic compound with an aqueous solution containing the desired pharmacologically acceptable cation, and then evaporating the resulting solution to dryness, preferably under reduced pressure. Alternatively, they can also be prepared by mixing a low-alcohol solution of the acidic compound with the desired alkali metal alkoxide, and then evaporating the resulting solution to dryness in the same manner as before. In either case, stoichiometric amounts of reagents are preferably used to ensure complete reaction and maximum product yield of the desired solid salt.

[0568] Bases that can be used to prepare pharmaceutically acceptable base addition salts of basic compounds are those capable of forming non-toxic base addition salts, i.e., salts containing pharmacologically acceptable cations, such as alkali metal cations (e.g., potassium and sodium), alkaline earth metal cations (e.g., calcium and magnesium), ammonium or other water-soluble amine addition salts, such as N-methylglucamine (meglumine), lower alkanolammonium and other such bases of organic amines.

[0569] Isotopically labeled compounds are also within the scope of the present disclosure.As used herein, "isotopically labeled compounds" refers to compounds disclosed in the present invention, including pharmaceutically acceptable salts thereof and prodrugs thereof, each of which is described herein, wherein one or more atoms are replaced with atoms having atomic masses or atomic mass numbers different from those usually found in nature.Examples of isotopes that can be incorporated into compounds disclosed in the present invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphate, fluorine and chlorine, for example, respectively. 2 H, 3 H, 13 C. 14 C. 15 N, 18 O. 17 O. 31 P, 32 P, 35 S, 18 F and 36 Examples include Cl.

[0570] By isotopically labeling the compounds disclosed herein, the compounds may be useful in drug and / or substrate tissue distribution assays. 3 H) and carbon- 14( 14 C) labeled compounds are particularly preferred due to their ease of preparation and detectability. Furthermore, deuterium ( 2 Substitution with heavier isotopes, such as 1H, may confer certain therapeutic advantages. This can result in greater metabolic stability, e.g., increased in vivo half-life, or reduced dosage requirements, and is therefore preferred in some situations. The isotopically labeled compounds disclosed herein, including pharmaceutical salts thereof and prodrugs thereof, are prepared by any means known in the art.

[0571] All stereoisomers (e.g., cis and trans isomers) and optical isomers (e.g., R and S enantiomers) of the compounds disclosed herein, as well as racemic, diastereomeric, and other mixtures of such isomers, are within the scope of this disclosure.

[0572] The compounds, salts, prodrugs, hydrates and solvates disclosed in the present invention can exist in several tautomeric forms, including enol and imine forms, and keto and enamine forms, as well as geometric isomers, and mixtures thereof. Tautomers exist as a mixture of tautomeric sets in solution. In solid form, one tautomer usually predominates. Even if one tautomer is described, all tautomers are within the scope of this disclosure.

[0573] Atropisomers are also within the scope of this disclosure. Atropisomers refer to compounds that can be separated into isomers with restricted rotation.

[0574] The present disclosure also provides pharmaceutical compositions, comprising at least one compound disclosed in the present invention and at least one pharmaceutically acceptable carrier.Pharmaceutically acceptable carriers can be any such carriers known in the art, including, for example, those described in Remington's Pharmaceutical Sciences, Mack Publishing Co., (AR Gennaro editor., 1985).The pharmaceutical compositions of the compounds disclosed in the present invention can be prepared by conventional means known in the art, for example, by mixing at least one compound disclosed in the present invention with a pharmaceutically acceptable carrier.

[0575] The pharmaceutical compositions disclosed herein can be used in animals or humans, and thus the compounds disclosed herein are formulated as pharmaceutical compositions in a form suitable for oral, buccal, parenteral (e.g., intravenous, intramuscular, or subcutaneous), topical, rectal, or intranasal administration, or for administration by inhalation or insufflation.

[0576] The compounds disclosed herein can also be formulated for sustained delivery by methods well known to those skilled in the art. Examples of such formulations can be found in U.S. Patent Nos. 3,119,742, 3,492,397, 3,538,214, 4,060,598, and 4,173,626.

[0577] For oral administration, the pharmaceutical compositions can take the form of, for example, tablets or capsules, which are manufactured by conventional means with pharmaceutically acceptable excipients, such as binders (e.g., pregelatinized corn starch, polyvinylpyrrolidone, or hydroxypropylmethylcellulose); fillers (e.g., lactose, microcrystalline cellulose, or calcium phosphate); lubricants (e.g., magnesium stearate, talc, or silica); disintegrants (e.g., potato starch or sodium starch glycolate); and / or wetting agents (e.g., sodium lauryl sulfate). Tablets are coated by methods well known in the art. Liquid preparations for oral administration may take the form of, for example, solutions, syrups, or suspensions, or they may be presented as a dry product for reconstitution with water or other suitable vehicle before use. Such liquid preparations may be added to suspending agents (e.g., sorbitol syrup, methylcellulose, or hydrogenated edible fats). ); emulsifying agents (e.g., lecithin or acacia); non-aqueous vehicles (e.g., almond oil, oily esters, or ethyl alcohol); and / or preservatives (e.g., methyl or propyl p-hydroxybenzoate or sorbic acid) prepared by conventional means.

[0578] For buccal administration, the compositions may take the form of tablets or lozenges formulated in conventional manner.

[0579] The compounds disclosed in the present invention are formulated for parenteral administration by injection, including the use of conventional catheter insertion techniques or infusion. Injectable formulations are presented in unit dosage form, for example, in ampoules or in multi-dose containers, with added preservatives. The compositions may take the form of suspensions, solutions, or emulsions in oily or aqueous vehicles, and may contain formulating agents, such as suspending agents, stabilizers, and / or dispersing agents, recognized by those skilled in the art. Alternatively, the active ingredient may be in the form of a powder for reconstitution before use in a suitable vehicle, for example, sterile, pyrogen-free, distilled water.

[0580] For topical administration, the compounds disclosed herein are formulated as ointments or creams.

[0581] The compounds of the present disclosure may also be formulated in rectal compositions such as suppositories or retention enemas, eg, containing conventional suppository bases such as cocoa butter or other glycerides.

[0582] For intranasal administration or inhalation administration, the compounds disclosed herein are conveniently delivered in the form of a solution or suspension from a pump spray container, which is squeezed or pumped by the patient, or from a pressurized container or nebulizer as an aerosol spray presentation, using a suitable propellant, such as dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide, or other suitable gas.In the case of pressurized aerosol, the dosage unit is determined by providing a valve that delivers a metered amount.The pressurized container or nebulizer may contain a solution or suspension of the compounds disclosed herein.Capsules and cartridges (e.g., made of gelatin) for use in inhalers or insufflators are formulated to contain a powder mix of the compounds disclosed herein and a suitable powder base, such as lactose or starch.

[0583] The suggested dose of the compounds disclosed herein for oral, parenteral, or buccal administration to an average adult for the treatment or prevention of CSF-1R-related disease states is about 0.1 mg to about 2000 mg. In certain embodiments, the suggested dose is about 0.1 mg to about 200 mg of active ingredient per unit dose. Regardless of the suggested dose, the compound can be administered, for example, one to four times per day.

[0584] Aerosol formulations for the treatment or prevention of the above-listed conditions are preferably formulated so that each metered dose or "puff" of the aerosol contains about 20 mg to about 10,000 mg, preferably about 20 mg to about 1,000 mg, of a compound disclosed herein for an average adult. The total daily dose of the aerosol will be in the range of about 100 mg to about 100 mg. In certain embodiments, the total daily dose of the aerosol will generally be in the range of about 100 mg to about 10 mg. Administration may be several times daily, for example, two, three, four, or eight times daily, with, for example, one, two, or three doses given each time.

[0585] Aerosol formulations for the treatment or prevention of the above-listed conditions are preferably adjusted so that each metered dose or "puff" of the aerosol contains from about 0.01 mg to about 1000 mg of a formulation comprising a compound disclosed herein for an average adult. In certain embodiments, each metered dose or "puff" of the aerosol contains from about 0.01 mg to about 1000 mg of a formulation comprising a compound disclosed herein. g of a formulation comprising a compound disclosed herein. In certain embodiments, each metered dose or "puff" of aerosol contains about 1 mg to about 10 mg of a formulation comprising a compound disclosed herein. Administration can be several times daily, for example, 2, 3, 4, or 8 times, giving, for example, 1, 2, or 3 doses each time.

[0586] Pharmaceutical compositions and methods of treatment or prevention that include administering a prodrug of at least one of the presently disclosed compounds are also within the scope of this disclosure.

[0587] Non-limiting examples of suitable CSF-1R inhibitors according to Formula (I) and Formula (II) are provided in the following examples. It is understood that any or all of the amines in the structures provided in the inhibitors according to Formula (I) and Formula (II) provided in the following examples may be in free amine form or in protonated form with a pharmaceutically acceptable anion. Preferred pharmaceutically acceptable anions include, but are not limited to, halides, carbonates, bicarbonates, sulfates, bisulfates, hydroxides, nitrates, persulfates, phosphates, sulfites, acetates, ascorbates, benzoates, citrates, dihydrogen citrates, hydrogen citrates, oxalates, succinates, tartrates, taurocholates, glycocholates, and cholates. Most preferred pharmaceutically acceptable anions include hydrochlorides, carbonates, and bicarbonates. It is understood that any or all of the CSF-1R inhibitors according to formula (I) and formula (II) may also be racemic, or an enantiomer of a racemate. [Example]

[0588] Synthesis method Certain embodiments of the present disclosure will now be described with reference to the preparations and schemes set forth below; it is to be understood that such embodiments are by way of example only and are merely illustrative of but a few of the many possible specific embodiments which can illustrate application of the principles of the present disclosure. Various changes and modifications to the preparations, schemes and examples will be apparent to those skilled in the art given the benefit of this disclosure.

[0589] [ka]

[0590] [ka]

[0591] The following examples illustrate compounds of formula (I) and formula (XIII) synthesized according to the above schemes.

[0592] Example 1-1: Synthesis of 4-(1-((2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-1H-benzo[d]imidazol-5-yl)-2-methylbut-3-yn-2-amine Example 1-1-1: Preparation of 4-iodo-3-(2-(4-methoxyphenyl)-2-oxoethoxy)benzamide To a stirred solution of 3-hydroxy-4-iodobenzamide (1.90 g, 7.23 mmol) in N,N-dimethylformamide (20 mL) was added 2-bromo-1-(4-methoxyphenyl)ethan-1-one (1.80 g, 7.86 mmol) and potassium carbonate (2.00 g, 14.47 mmol). The mixture was stirred at room temperature. After 1 h, the mixture was diluted with brine (50 mL) and extracted with ethyl acetate (2 × 50 mL). The combined organic phases were dried over magnesium sulfate, filtered, and concentrated. The crude product was purified chromatographically (silica gel, eluting with 5% methanol in dichloromethane) to give 1.60 g (55%) of 4-iodo-3-(2-(4-methoxyphenyl)-2-oxoethoxy)benzamide as a yellow solid.

[0593] Example 1-1-2: Preparation of 3-(2-hydroxy-2-(4-methoxyphenyl)ethoxy)-4-iodobenzamide To a stirred solution of 4-iodo-3-(2-(4-methoxyphenyl)-2-oxoethoxy)benzamide (1.60 g, 3.89 mmol) in methanol (25 mL) at 0° C. was slowly added sodium borohydride (0.158 g, 4.18 mmol). The resulting mixture was stirred at 0° C. After 1 h, the mixture was diluted with brine (50 mL) and extracted with ethyl acetate (2×50 mL). The combined organic phases were dried over magnesium sulfate, filtered, and concentrated. The crude product was purified chromatographically (silica gel, eluting with 5% methanol in dichloromethane) to give 1.50 g (94%) of 3-(2-hydroxy-2-(4-methoxyphenyl)ethoxy)-4-iodobenzamide as a yellow solid.

[0594] Example 1-1-3: Preparation of 2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamide To a stirred solution of 3-(2-hydroxy-2-(4-methoxyphenyl)ethoxy)-4-iodobenzamide (0.78 g, 1.88 mmol) in N,N-dimethylformamide (15 mL) was added sodium hydride (60% dispersion in mineral oil, 0.23 g, 5.75 mmol) and copper(I) iodide (0.36 g, 1.88 mmol). The resulting mixture was heated to 80 °C. After 2 h, the mixture was cooled to room temperature and filtered through Celite. The filtrate was concentrated. The crude product was purified chromatographically (silica gel, eluting with 1–2% methanol in dichloromethane) to give 0.41 g (76%) of 2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamide as a white solid.

[0595] Example 1-1-4: Preparation of (2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methanamine To a stirred solution of 2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-carboxamide (0.43 g, 1.51 mmol) in tetrahydrofuran (10 mL) was added 1.0 M borane-tetrahydrofuran complex (30 mL, 30 mmol). The resulting mixture was heated to reflux. After 16 h, the mixture was cooled to room temperature and quenched by the slow addition of methanol (20 mL). The mixture was stirred at room temperature. After 2 h, the mixture was concentrated. The crude product was purified chromatographically (silica gel, eluting with 10% methanol in dichloromethane) to afford 0.32 g (75%) of (2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methanamine as a yellow solid.

[0596] Example 1-1-5: Preparation of 4-iodo-N-((2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-2-nitroaniline To a stirred solution of (2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methanamine (0.25 g, 0.92 mmol) in acetonitrile (25 mL) was added 2-fluoro-4-iodo-1-nitrobenzene (0.27 g, 1.01 mmol) and potassium carbonate (0.26 mg, 1.85 mmol). The resulting mixture was heated to reflux. After 1 h, the mixture was cooled to room temperature and filtered. The filtrate was concentrated. The crude product was purified chromatographically (silica gel, eluting with 10% methanol in dichloromethane) to give 0.24 g (50%) of 4-iodo-N-((2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-2-nitroaniline as a yellow solid.

[0597] Example 1-1-6: 4-Iodo-N 1 -((2-(4-methoxyphenyl)-2,3-di Preparation of hydrobenzo[b][1,4]dioxin-6-yl)methyl)benzene-1,2-diamine 4-Iodo-N-((2-(4-methoxyphenyl)-2,3-dihydrobenzo[b] To a stirred suspension of [1,4]dioxin-6-yl)methyl)-2-nitroaniline (0.26 g, 0.51 mmol) in ethanol (20 mL) and water (5 mL) was added iron powder (0.14 g, 2.52 mmol) and ammonium chloride (0.13 g, 2.52 mmol). The resulting mixture was heated to reflux. After 1 h, the mixture was cooled to room temperature and filtered. The filtrate was concentrated. The crude product was purified chromatographically (neutral alumina, eluting with 5% methanol in dichloromethane) to give 4-iodo-N 1 -((2-(4-methoxyphenyl) 0.23 g (91%) of 2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)benzene-1,2-diamine was obtained as a yellow solid.

[0598] Example 1-1-7: Preparation of 5-iodo-1-((2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-1H-benzo[d]imidazole 4-Iodo-N 1 -((2-(4-methoxyphenyl)-2,3-dihydrobenzo[b To a stirred solution of 5-iodo-1-((2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)benzene-1,2-diamine (0.22 g, 0.42 mmol) in N,N-dimethylformamide (30 mL) was added triethyl orthoformate (0.46 g, 3.09 mmol) and p-toluenesulfonic acid monohydrate (0.038 g, 0.22 mmol). The mixture was stirred at room temperature. After 1 h, the mixture was diluted with water (150 mL), and the resulting precipitate was collected by filtration. The crude product was purified chromatographically (neutral alumina, eluting with 2% methanol in dichloromethane) to give 0.20 g (93%) of 5-iodo-1-((2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-1H-benzo[d]imidazole as a yellow solid.

[0599] Example 1-1-8: Preparation of 4-(1-((2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-1H-benzo[d]imidazol-5-yl)-2-methylbut-3-yn-2-amine To a stirred solution of 5-iodo-1-((2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-1H-benzo[d]imidazole (0.17 g, 0.34 mmol) in tetrahydrofuran (3 mL) was added 2-methylbut-3-yn-2-amine (0.057 g, 0.68 mmol), copper(I) iodide (0.026 g, 0.14 mmol), piperidine (0.15 g, 1.70 mmol), and bis(triphenylphosphine)palladium(II) dichloride (0.048 g, 0.068 mmol). The mixture was heated to 60° C. in a microwave reactor. After 30 min, the mixture was cooled to room temperature and filtered. The crude product was purified chromatographically (preparative HPLC) to give 0.029 g (19%) of 4-(1-((2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-1H-benzo[d]imidazol-5-yl)-2-methylbut-3-yn-2-amine as a yellow solid: 1 H NMR (500 MHz, CDCl3) δ 7.96 (s, 1H), 7.88 (s, 1H), 7.35 - 7.30 (m, 3H), 7.25 (d, J = 8.5 Hz, 1H), 6.97 - 6.93 (m, 3H), 6.77 (d, J = 2.0 Hz, 1H), 6.73 (dd, J = 8.5, 2.0 Hz, 1H), 5.26 (s, 2H), 5.07 - 5.05 (m, 1H), 4.32 - 4.30 (m, 1H), 4.03 - 3.99 (m, 1H), 3.84 (s, 3H), 1.54 (s, 6H) ppm; (M+1) = 454.

[0600] Example 1-2: Synthesis of 4-(3-((2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridin-6-yl)-2-methylbut-3-yn-2-amine Example 1-2-1: Preparation of 5-iodo-N-((2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3-nitropyridin-2-amine (2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methanamine (0.51 g, 1.87 mmol, Example 1-1-4) To a stirred solution of acetonitrile (10 mL) was added 2-chloro-5-iodo-3-nitropyridine (0.64 g, 2.25 mmol) and diisopropylethylamine (0.60 g, 4.68 mmol). The resulting bright yellow mixture was heated to reflux. After 5 h, the mixture was cooled to room temperature and diluted with water (40 mL). The mixture was extracted with ethyl acetate (3 × 25 mL). The combined organic extracts were washed with brine (30 mL), dried over magnesium sulfate, filtered, and concentrated. The crude product was purified chromatographically (CombiFlash, 40 g silica gel column, 0–33% ethyl acetate / hexane elution) to afford 0.81 g (84%) of 5-iodo-N-((2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3-nitropyridin-2-amine as a yellow solid.

[0601] Example 1-2-2: 5-Iodo-N 2 -((2-(4-methoxyphenyl)-2,3-di Preparation of hydrobenzo[b][1,4]dioxin-6-yl)methyl)pyridine-2,3-diamine To a stirred solution of 5-iodo-N-((2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3-nitropyridin-2-amine (0.81 g, 1.57 mmol) in acetic acid (15 mL) was added iron powder (0.61 g, 10.96 mmol). The mixture was heated to 100° C., and the initial bright yellow color gradually darkened to gray-brown as the mixture warmed. After 45 minutes, the gray-brown suspension was cooled to room temperature and diluted with ethyl acetate (50 mL). The resulting suspension was filtered through Celite with additional ethyl acetate (30 mL). The filtrate was washed with brine (1×25 mL) and 1 N sodium hydroxide solution (3×25 mL). The organic phase was dried over magnesium sulfate, filtered, and concentrated to give 5-iodo-N 2 -((2-(4-methoxyphenyl)-2,3-dihydrobenzo[b]phenyl] ... Obtained 0.77 g (100%) of zo[b][1,4]dioxin-6-yl)methyl)pyridine-2,3-diamine as a brown solid.

[0602] Example 1-2-3: Preparation of 6-iodo-3-((2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine 5-Iodo-N 2 -((2-(4-methoxyphenyl)-2,3-dihydrobenzo[b To a stirred suspension of [1,4]dioxin-6-yl)methyl)pyridine-2,3-diamine (0.77 mg, 1.57 mmol) in ethanol (15 mL) was added triethyl orthoformate (0.70 g, 4.70 mmol) and p-toluenesulfonic acid monohydrate (0.014 g, 0.078 mmol). The mixture was heated to reflux. After 30 min, the brown solution was cooled to room temperature. The mixture was diluted with water (40 mL) and extracted with dichloromethane (2 × 30 mL). The combined organic phase was washed with brine (30 mL), dried over magnesium sulfate, filtered, and concentrated. The crude product was purified chromatographically (CombiFlash, 40 g silica gel column, 1-5% 2 M ammonia in methanol / dichloromethane eluent) to give 0.54 g (70%) of 6-iodo-3-((2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine as a tan solid.

[0603] Example 1-2-4: Preparation of 4-(3-((2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridin-6-yl)-2-methylbut-3-yn-2-amine To a stirred solution of 6-iodo-3-((2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine (0.10 g, 0.20 mmol) in piperidine (3.5 mL) was added 2-methylbut-3-yn-2-amine (0.021 g, 0.24 mmol), copper(I) iodide (0.008 g, 0.040 mmol), and bis(triphenylphosphine)palladium. (II) chloride (0.014 g, 0.020 mmol) was added. The mixture was heated to 100 °C in a microwave reactor. After 30 min, the reaction mixture was diluted with 5 N ammonium hydroxide solution (30 mL) and extracted with dichloromethane (3 × 25 mL). The combined organic phases were dried over magnesium sulfate, filtered, and concentrated. The crude product was purified chromatographically (CombiFlash, 40 g silica gel column, 1-5% 2 M ammonia in methanol / dichloromethane eluent) to give 0.060 g (66%) of 4-(3-((2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridin-6-yl)-2-methylbut-3-yn-2-amine as an off-white solid: 1 H NMR (400 MHz, CDCl3) δ 8.46 (d, J = 1.8 Hz, 1H), 8.07 (d, J = 1.8 Hz, 1H), 8.02 (s, 1H), 7.34 - 7.30 (m, 2H), 6.96 - 6.92 (m, 3H), 6.89 (d, J = 2.0 Hz, 1H), 6.83 (dd, J = 8.3, 2.1 Hz, 1H), 5.36 (s, 2H), 5.04 (dd, J = 8.9, 2.3 Hz, 1H), 4.29 (dd, J = 11.5, 2.4 Hz, 1H), 3.99 (dd, J = 11.5, 9.0 Hz, 1H), 3.82 (s, 3H), 1.77 (br s, 2H), 1.53 (s, 6H) ppm; (M+1) = 455.

[0604] Example 1-2-5: Chiral separation of 4-(3-((2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridin-6-yl)-2-methylbut-3-yn-2-amine Racemic 4-(3-((2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridin-6-yl)-2-methylbut-3-yn-2-amine was subjected to preparative SFC purification (21.2 × 250 mm LUX-3 column, 50% methanol / 0.2% diethylamine modifier, flow rate 45 g / min, 100 bar pressure, sample concentration 20 mg / mL) to give the individual enantiomers (absolute configuration not assigned).

[0605] Example 1-3: Synthesis of 3-((2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-6-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridine To a stirred solution of 6-iodo-3-((2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine (0.19 g, 0.38 mmol, Example 1-2-3) in dimethyl sulfoxide (3.5 mL) was added 1-methylpiperazine (0.046 g, 0.46 mmol), L-proline (0.011 g, 0.091 mmol), potassium carbonate (0.18 g, 1.33 mmol), and copper(I) iodide (0.009 g, 0.047 mmol). The resulting pale yellow suspension was heated to 150 °C. After 16 h, the mixture was cooled to room temperature and diluted with 3N ammonium hydroxide solution (15 mL). The mixture was extracted with dichloromethane (3 × 20 mL). The combined organic phases were washed with water (2 × 15 mL) and brine (20 mL), dried over magnesium sulfate, filtered, and concentrated. The crude product was purified chromatographically (CombiFlash, 12 g silica gel column, 1–10% methanol / dichloromethane eluent) to afford 0.048 g (27%) of 3-((2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-6-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridine as an off-white solid: 1H NMR (400 MHz, CDCl3) δ 8.26 (d, J = 2.5 Hz, 1H), 7.95 (s, 1H), 7.63 (d, J = 2.5 Hz, 1H), 7.33 - 7.29 (m, 2H), 6.79 - 7.00 (m, 5H), 5.33 (s, 2H), 5.03 (dd, J = 9.0, 2.4 Hz, 1H), 4.29 (dd, J = 11.5, 2.4 Hz, 1H), 3.99 (dd, J = 11.5, 9.0 Hz, 1H), 3.82 (s, 3H), 3.19 - 3.33 (m, 4H), 2.57 - 2.70 (m, 4H), 2.38 (s, 3H) ppm (M+1) = 472.

[0606] Example 1-4: Synthesis of 3-((2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-6-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine To a stirred solution of 6-iodo-3-((2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine (0.15 g, 0.30 mmol) in 1,2-dimethoxyethane (3 mL) and water (0.3 mL) was added 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.076 g, 0.36 mmol), cesium carbonate (0.30 g, 0.91 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.035 g, 0.030 mmol). The resulting mixture was heated to 100 °C. After 7 h, the mixture was cooled to room temperature and diluted with ethyl acetate. The mixture was filtered through Celite, and the filtrate was concentrated. The crude product was purified chromatographically (CombiFlash, silica gel column, 90% ethyl acetate / heptane eluent) to give a beige oil that crystallized on standing. The beige solid was treated with acetonitrile and water, and the resulting precipitate was collected by filtration to give 0.050 g (37%) of 3-((2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-6-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine as a white solid: 1 H NMR (400 MHz, DMSO-d6) δ 8.65 (d, J = 1.9 Hz, 1H), 8.56 (s, 1H), 8.29 - 8.19 (m, 2H), 7.97 (d, J = 0.9 Hz, 1H), 7.41 - 7.30 (m, 2H), 7.02 - 6.93 (m, 3H), 6.90 (d, J = 1.2 Hz, 2H), 5.39 (s, 2H), 5.12 (dd, J = 8.5, 2.4 Hz, 1H), 4.33 (dd, J = 11.6, 2.5 Hz, 1H), 4.04 (dd, J = 11.6, 8.5 Hz, 1H), 3.88 (s, 3H), 3.75 (s, 3H).

[0607] Example 1-5: Synthesis of 4-(3-((2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridin-6-yl)-2-methylbut-3-yn-2-amine Example 1-5-1: Preparation of 4-iodo-3-(2-(6-methoxypyridin-3-yl)-2-oxoethoxy)benzamide To a stirred solution of 3-hydroxy-4-iodobenzamide (1.36 g, 5.16 mmol) in N,N-dimethylformamide (20 mL) was added potassium carbonate (1.95 g, 14.08 mmol) and 2-bromo-1-(6-methoxypyridin-3-yl)ethanone (1.08 g, 4.69 mmol). The resulting reaction mixture was heated to 80 °C. After 2 h, the mixture was cooled to room temperature and diluted with water (100 mL). The mixture was extracted with dichloromethane (2 × 40 mL). The combined organic extracts were washed with water (40 mL) and brine (40 mL), dried over magnesium sulfate, filtered, and concentrated. The crude product was purified chromatographically (CombiFlash, silica gel column, 0-100% ethyl acetate / heptane eluent) to give 0.89 g (46%) of 4-iodo-3-(2-(6-methoxypyridin-3-yl)-2-oxoethoxy)benzamide as a tan solid.

[0608] Example 1-5-2: Preparation of 3-(2-hydroxy-2-(6-methoxypyridin-3-yl)ethoxy)-4-iodobenzamide To a stirred solution of 4-iodo-3-(2-(6-methoxypyridin-3-yl)-2-oxoethoxy)benzamide (0.89 g, 2.15 mmol) in tetrahydrofuran (20 mL) and water (5 mL) was added sodium borohydride (0.16 g, 4.30 mmol). The resulting mixture was stirred at room temperature. After 16 h, the mixture was quenched with saturated ammonium chloride solution (30 mL). The mixture was extracted with ethyl acetate (3×25 mL). The combined organic phases were washed with brine (30 mL), dried over magnesium sulfate, filtered, and concentrated to give 0.89 g (100%) of 3-(2-hydroxy-2-(6-methoxypyridin-3-yl)ethoxy)-4-iodobenzamide as an off-white solid.

[0609] Example 1-5-3: Preparation of 2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamide To a stirred solution of 3-(2-hydroxy-2-(6-methoxypyridin-3-yl)ethoxy)-4-iodobenzamide (0.93 g, 2.24 mmol) in N,N-dimethylformamide (15 mL) was added sodium hydride (60% dispersion, 0.27 g, 6.71 mmol). The reaction was stirred at room temperature for 15 minutes, then copper(I) iodide (0.43 g, 2.24 mmol) was added. The mixture was heated to 80° C. After 3 hours, the mixture was cooled to room temperature and diluted with water (75 mL). The mixture was extracted with dichloromethane (3×25 mL). The combined organic phase was washed with brine (50 mL), dried over magnesium sulfate, filtered, and concentrated. The crude product was purified chromatographically (CombiFlash, 40 g silica gel column, 1–10% methanol / dichloromethane eluent) to give 0.40 g (63%) of 2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamide as a tan solid.

[0610] Example 1-5-4: Preparation of (2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methanamine To a stirred solution of 2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamide (0.40 g, 1.40 mmol) in tetrahydrofuran (10 mL) was added 1.0 M borane-tetrahydrofuran complex (5.6 mL, 5.60 mmol). The mixture was heated to reflux. After 2 hours, the mixture was cooled to 0°C. The reaction was quenched by the slow addition of methanol (5 mL), and the resulting mixture was heated to reflux. After 1 hour, the mixture was cooled to room temperature and concentrated. The residue was dissolved in tetrahydrofuran (20 mL) and 1 N hydrochloric acid solution (10 mL). The resulting mixture was heated to reflux. After 2 hours, the mixture was cooled to room temperature, and the pH of the mixture was adjusted to approximately 7 by adding 1 N sodium hydroxide solution. The neutral mixture was extracted with dichloromethane (3 × 25 mL). The combined organic phases were washed with brine (40 mL), dried over magnesium sulfate, filtered, and concentrated to give 0.38 g (100%) of (2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methanamine as an oil.

[0611] Example 1-5-5: Preparation of 5-iodo-N-((2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3-nitropyridin-2-amine To a stirred solution of (2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methanamine (0.38 g, 1.40 mmol) in acetonitrile (10 mL) was added 2-chloro-5-iodo-3-nitropyridine (0.48 g, 1.67 mmol) and diisopropylethylamine (0.54 g, 4.19 mmol). The resulting yellow mixture was heated to reflux. After 4 h, the mixture was cooled to room temperature and diluted with water (40 mL). The mixture was extracted with ethyl acetate (3 × 25 mL). The combined organic phases were washed with brine (40 mL), dried over magnesium sulfate, filtered, and concentrated. The crude product was purified chromatographically (CombiFlash, 40 g silica gel column, 0–33% ethyl acetate / hexane eluent) to give 0.35 g (48%) of 5-iodo-N-((2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3-nitropyridin-2-amine as a yellow solid.

[0612] Example 1-5-6: 5-Iodo-N 2 -((2-(6-methoxypyridin-3-yl)- Preparation of 2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)pyridine-2,3-diamine To a stirred suspension of 5-iodo-N-((2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3-nitropyridin-2-amine (0.35 g, 0.67 mmol) in acetic acid (8 mL) was added iron powder (0.26 g, 4.71 mmol) was added. The mixture was heated to 100°C, and the initial bright yellow color gradually darkened to gray-brown as the mixture warmed. After 45 minutes, the gray-brown suspension was cooled to room temperature and diluted with ethyl acetate (50 mL). The resulting suspension was added with additional ethyl acetate (25 mL) and filtered through Celite. The filtrate was washed with brine (1 x 25 mL) and 1N sodium hydroxide solution (3 x 25 mL). The organic phase was dried over magnesium sulfate, filtered, and concentrated to give 5-iodo-N 2 -((2-(6-methoxypyridin-3-yl)-2, Obtained 0.30 g (91%) of 3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)pyridine-2,3-diamine as an orange solid.

[0613] Example 1-5-7: Preparation of 6-iodo-3-((2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine 5-Iodo-N 2 -((2-(6-methoxypyridin-3-yl)-2,3-dihydro To a stirred suspension of benzo[b][1,4]dioxin-6-yl)methyl)pyridine-2,3-diamine (0.300 g, 0.61 mmol) in ethanol (10 mL) was added triethyl orthoformate (0.27 g, 1.84 mmol) and p-toluenesulfonic acid monohydrate (0.006 g, 0.031 mmol). The resulting mixture was heated to reflux. After 30 min, the brown solution was cooled to room temperature and diluted with water (40 mL). The mixture was extracted with dichloromethane (3 × 25 mL). The combined organic extracts were washed with brine (30 mL), dried over magnesium sulfate, filtered, and concentrated. The crude product was purified chromatographically (CombiFlash, 40 g silica gel column, 1-5% 2 M ammonia in methanol / dichloromethane eluent) to give 0.30 g (98%) of 6-iodo-3-((2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine as a tan solid.

[0614] Example 1-5-8: Preparation of 4-(3-((2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridin-6-yl)-2-methylbut-3-yn-2-amine To a stirred solution of 6-iodo-3-((2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine (0.22 g, 0.45 mmol) in piperidine (3.5 mL) was added 2-methylbut-3-yn-2-amine (0.047 g, 0.53 mmol), copper(I) iodide (0.017 mg, 0.089 mmol), and bis(triphenylphosphine)palladium(II) chloride (0.031 mg, 0.044 mmol). The mixture was heated to 100 °C in a microwave reactor. After 30 min, the reaction mixture was diluted with 5 N ammonium hydroxide solution (30 mL) and extracted with dichloromethane (3 × 25 mL). The combined organic phases were dried over magnesium sulfate, filtered, and concentrated. The crude product was purified chromatographically (CombiFlash, 12 g silica gel column, 1-5% 2 M ammonia in methanol / dichloromethane eluent) to give 0.16 g (79%) of 4-(3-((2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridin-6-yl)-2-methylbut-3-yn-2-amine, also known as GENZ-882706 and RA03546849, as an off-white solid: 1 H NMR (400 MHz, CDCl3) δ 8.46 (d, J = 1.8 Hz, 1H), 8.19 (d, J = 2.4 Hz, 1H), 8.07 (d, J = 1.8 Hz, 1H), 8.03 (s, 1H), 7.59 (dd, J = 8.6, 2.5 Hz, 1H), 6.87 - 6.96 (m, 2H), 6.84 (dd, J = 8.3, 2.1 Hz, 1H), 6.79 (d, J = 8.6 Hz, 1H), 5.36 (s, 2H), 5.07 (dd, J = 8.7, 2.3 Hz, 1H), 4.30 (dd, J = 11.6, 2.3 Hz, 1H), 4.02 (dd, J = 11.6, 8.7 Hz, 1H), 3.95 (s, 3H), 1.80 (br s, 2H), 1.53 (s, 6H) ppm; (M+1) = 456.

[0615] Example 1-5-9: 4-(3-((2-(6-methoxypyridin-3-yl)-2,3- Chiral separation of dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridin-6-yl)-2-methylbut-3-yn-2-amine Racemic 4-(3-((2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridin-6-yl)-2-methylbut-3-yn-2-amine was subjected to preparative SFC purification (21.2 × 250 mm Chiralcel OJ column, 25% ethanol / 0.2% diethylamine modifier, flow rate 75 g / min) to give the individual enantiomers.

[0616] Example 1-6: Synthesis of 3-((2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-6-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridine The title compound was prepared from 3-((2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-6-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridine (Example 1-5-7) and 1-methylpiperazine as described in Example 1-3: 1H NMR (400 MHz, CDCl3) δ 8.26 (d, J = 2.5 Hz, 1H), 8.19 (d, J = 2.4 Hz, 1H), 7.95 (s, 1H), 7.63 (d, J = 2.4 Hz, 1H), 7.59 (dd, J = 8.6, 2.5 Hz, 1H), 6.87 - 6.95 (m, 2H), 6.84 (dd, J = 8.3, 2.1 Hz, 1H), 6.79 (d, J = 8.6 Hz, 1H), 5.33 (s, 2H), 5.07 (dd, J = 8.8, 2.3 Hz, 1H), 4.29 (dd, J = 11.6, 2.3 Hz, 1H), 4.02 (dd, J = 11.6, 8.8 Hz, 1H), 3.95 (s, 3H), 3.14 - 3.30 (m, 4H), 2.60 - 2.70 (m, 4H), 2.38 (s, 3H) ppm; (M+1) = 473.

[0617] Example 1-7: Synthesis of 3-((2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine-6-carbonitrile A solution of 6-iodo-3-((2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine (0.10 g, 0.20 mmol, Example 1-5-7) in N,N-dimethylformamide (3 mL) was degassed with nitrogen. The mixture was treated with tetrakis(triphenylphosphine)palladium(0) (0.023 g, 0.019 mmol) and zinc cyanide (0.014 g, 0.12 mmol) and heated to 100 °C in a sealed vessel. After 3 hours, the mixture was cooled to room temperature. The mixture was diluted with ethyl acetate and water, and the phases were separated. The aqueous phase was extracted with ethyl acetate. The combined organic phase was washed with brine and concentrated. Chromatographic purification of the crude product (CombiFlash, silica gel column, 70% ethyl acetate / hexane eluent) followed by trituration of the isolated material with acetone / hexane afforded 0.054 g (68%) of 3-((2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine-6-carbonitrile as a white solid: 1 H NMR (400 MHz, DMSO-d6) δ 8.91 - 8.76 (m, 2H), 8.71 (d, J = 1.8 Hz, 1H), 8.24 (d, J = 2.3 Hz, 1H), 7.76 (dd, J = 8.6, 2.5 Hz, 1H), 7.00 (t, J = 1.2 Hz, 1H), 6.96 - 6.78 (m, 3H), 5.44 (s, 2H), 5.21 (dd, J = 8.4, 2.4 Hz, 1H), 4.37 (dd, J = 11.6, 2.5 Hz, 1H), 4.14 (dd, J = 11.6, 8.4 Hz, 1H), 3.84 (s, 3H).

[0618] Example 1-8: Synthesis of 6-(azetidin-1-yl)-3-((2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine To a stirred solution of 6-iodo-3-((2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine (0.11 g, 0.22 mmol, Example 1-5-7) in 1,2-dimethoxyethane (3 mL) was added palladium(II) acetate (0.003 mg, 0.013 mmol) and (R)-1-[(S P )-2-(dicyclohexylphosphino)ferro To the resulting yellow solution was added [azetidine] (0.025 g, 0.44 mmol) and solid sodium t-butoxide (0.042 g, 0.44 mmol). The mixture was heated to 100 °C in a sealed vessel. After 20 h, the mixture was cooled to room temperature and concentrated. The crude product was purified chromatographically (CombiFlash, silica gel column, 0-5% methanol / dichloromethane eluent) to give 0.043 g (46%) of 6-(azetidin-1-yl)-3-((2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine as a white solid: 1 H NMR (400 MHz, DMSO-d6) δ 8.39 (s, 1H), 8.24 (d, J = 2.5 Hz, 1H), 7.75 (dd, J = 8.6, 2.5 Hz, 1H), 7.68 (d, J = 2.5 Hz, 1H), 7.06 (d, J = 2.5 Hz, 1H), 7.00 - 6.76 (m, 4H), 5.30 (s, 2H), 5.20 (dd, J = 8.4, 2.5 Hz, 1H), 4.36 (dd, J = 11.5, 2.5 Hz, 1H), 4.13 (dd, J = 11.5, 8.4 Hz, 1H), 3.92 - 3.74 (m, 4H), 3.32 (s, 3H), 2.37 - 2.27 (m, 2H) ppm; (M+1) = 430.

[0619] Example 1-9: Synthesis of 6-cyclopropyl-3-((2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine To a mixture of 6-iodo-3-((2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine (0.11 g, 0.21 mmol, Example 1-5-7), [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) chloride (0.016 g, 0.021 mmol), cesium carbonate (0.21 g, 0.66 mmol), and cyclopropylboronic acid (0.028 g, 0.33 mmol), 1,2-dimethoxyethane (3 mL) and water (0.3 mL) were added. The resulting mixture was heated to 100 °C in a sealed vessel. After 4 h, additional amounts of catalyst and boronic acid were added, and the mixture was stirred. After a total of 7 h, the mixture was cooled to room temperature and diluted with ethyl acetate. The mixture was filtered through a short pad of silica gel and Celite, and the residue was concentrated. The crude product was purified chromatographically (CombiFlash, silica gel column, 0-5% methanol / dichloromethane eluent) followed by preparative HPLC (10-90% acetonitrile / 0.1% trifluoroacetic acid in water) to give 0.012 g (10%) of 6-cyclopropyl-3-((2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine (trifluoroacetate) as a white solid: 1H NMR (400 MHz, DMSO-d6) δ 8.80 (s, 1H), 8.33 (d, J = 2.0 Hz, 1H), 8.24 (d, J = 2.4 Hz, 1H), 7.76 (dd, J = 8.5, 2.4 Hz, 2H), 7.00 - 6.98 (m, 1H), 6.92 - 6.90 (m, 2H), 6.86 (d, J = 8.5 Hz, 1H), 5.41 (s, 2H), 5.21 (dd, J = 8.3, 2.5 Hz, 1H), 4.37 (dd, J = 11.6, 2.5 Hz, 1H), 4.14 (dd, J = 11.6, 8.3 Hz, 1H), 3.85 (s, 3H), 2.16 - 2.06 (m, 1H), 1.05 - 0.96 (m, 2H), 0.83 - 0.75 (m, 2H) ppm; (M+1) = 415.

[0620] Example 1-10: Synthesis of 4-(3-((2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridin-6-yl)morpholine To a stirred solution of 6-iodo-3-((2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine (0.23 g, 0.45 mmol, Example 1-5-7) in 1,4-dioxane (3 mL) was added morpholine (0.062 g, 0.70 mmol), [(2-di-cyclohexylphosphino-3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl)-2-(2'-amino-1,1'-biphenyl)]palladium(II) methanesulfonate (0.012 g, 0.013 mmol), 2-di ...)- Xylphosphino-2',6'-di-i-propoxy-1,1'-biphenyl (0.006 g, 0.013 mmol) and sodium t-butoxide (62.38 mg, 629.64 μmol) were added. The vessel was sealed, and the contents were degassed under vacuum and refilled with nitrogen (three times). The mixture was then heated to 110 °C. After 16 h, the mixture was cooled to room temperature and diluted with water (50 mL). The mixture was extracted with ethyl acetate (3 × 30 mL). The combined organic phases were washed with brine (25 mL), dried over magnesium sulfate, filtered, and concentrated. The crude product was purified chromatographically (CombiFlash, 24 g silica gel gold column, 0-5% methanol / dichloromethane eluent) to give 0.066 g (32%) of 4-(3-((2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridin-6-yl)morpholine as a white solid: 1 H NMR (400 MHz, CDCl3) δ 8.24 (d, J = 2.5 Hz, 1H), 8.21 - 8.17 (m, 1H), 7.96 (s, 1H), 7.61 (d, J = 2.5 Hz, 1H), 7.59 (dd, J = 8.6, 2.5 Hz, 1H), 6.93 - 6.82 (m, 3H), 6.79 (d, J = 8.6 Hz, 1H), 5.34 (s, 2H), 5.07 (dd, J = 8.8, 2.5 Hz, 1H), 4.30 (dd, J = 11.6, 2.5 Hz, 1H), 4.02 (dd, J = 11.6, 8.8 Hz, 1H), 3.95 (s, 3H), 3.93 - 3.90 (m, 4H), 3.20 - 3.14 (m, 4H) ppm; (M+1) = 460.

[0621] Example 1-11: Synthesis of 6-methoxy-3-((2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine To a stirred solution of 6-iodo-3-((2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine (0.26 g, 0.52 mmol, Example 1-5-7) in methanol (3.0 mL) was added copper(I) iodide (0.010 g, 0.052 mmol), 1,10-phenanthroline (0.019 g, 0.10 mmol), and cesium carbonate (0.34 g, 1.05 mmol). The mixture was heated to 110 °C in a sealed vessel. After 20 h, the mixture was cooled to room temperature and diluted with 5N ammonium hydroxide solution (50 mL) and dichloromethane (50 mL). The phases were separated, and the aqueous phase was extracted with dichloromethane (2 × 30 mL). The combined organic phases were dried over magnesium sulfate, filtered, and concentrated. Chromatographic purification of the crude product (CombiFlash, 24 g silica gel gold column, 0–5% methanol / dichloromethane elution) afforded 0.17 g of a white solid (impregnated with 1,10-phenanthroline). The material was dissolved in dichloromethane (30 mL) and washed with 1 N hydrochloric acid solution (2 × 30 mL). The combined aqueous phases were made basic with 1 N sodium hydroxide solution (approximately 60 mL), and the resulting milky mixture was extracted with diethyl ether (3 × 15 mL). The combined organic phases were dried over magnesium sulfate, filtered, and concentrated to afford a colorless oil. The material was redissolved in diethyl ether (15 mL) and sonicated to afford a precipitate. The solid was collected by filtration and dried to give 0.090 g (43%) of 6-methoxy-3-((2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine as a white solid: 1H NMR (400 MHz, CDCl3) δ 8.21 (d, J = 2.6 Hz, 1H), 8.19 (d, J = 2.4 Hz, 1H), 7.97 (s, 1H), 7.61 - 7.58 (m, 2H), 6.93 - 6.88 (m, 2H), 6.84 (dd, J = 8.3, 2.2 Hz, 1H), 6.79 (d, J = 8.6 Hz, 1H), 5.35 (s, 2H), 5.07 (dd, J = 8.8, 2.5 Hz, 1H), 4.30 (dd, J = 11.6, 2.5 Hz, 1H), 4.02 (dd, J = 11.6, 8.8 Hz, 1H), 3.95 (s, 3H), 3.90 (s, 3H) ppm: (M+1) = 405.

[0622] Example 1-12: Synthesis of 4-(3-((2-(4-methoxyphenyl)-3-methyl-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridin-6-yl)-2-methylbut-3-yn-2-amine Example 1-12-1: Preparation of t-butyl (4-(benzyloxy)-3-hydroxybenzyl)carbamate A stirred solution of 3-hydroxy-4-benzyloxybenzaldehyde (4.05 g, 16.86 mmol) and t-butyl carbamate (3.02 g, 25.29 mmol) in acetonitrile (100 mL) was cooled to 0 °C while triethylsilane (5.94 g, 50.57 mmol) and trifluoroacetic acid (3.88 g, 33.71 mmol) were added. The resulting yellow solution was stirred at 0 °C for 15 minutes, and then the mixture was allowed to warm to room temperature. After 3 hours, an additional amount of t-butyl carbamate (1.00 g), triethylsilane (5.94 g), and trifluoroacetic acid (3.88 g) was added, and the mixture was stirred at room temperature. After 20 hours, the mixture was concentrated, and the residue was diluted with saturated sodium bicarbonate solution (150 mL). The mixture was extracted with diethyl ether (3 × 75 mL). The combined organic phases were washed with 1N sodium hydroxide solution (2 x 50 mL), 1N hydrochloric acid solution (2 x 50 mL), and brine (50 mL). The organic phase was dried over magnesium sulfate, filtered, and concentrated. The crude product was purified chromatographically (CombiFlash, 120 g silica gel gold column, 0-10% ethyl acetate / dichloromethane eluent) to give a white solid. This material was triturated with heptane to give 2.25 g (41%) of t-butyl 4-(benzyloxy)-3-hydroxybenzylcarbamate as a white solid.

[0623] Example 1-12-2: Preparation of t-butyl (4-(benzyloxy)-3-((1-(4-methoxyphenyl)-1-oxopropan-2-yl)oxy)benzyl)carbamate To a stirred solution of t-butyl 4-(benzyloxy)-3-hydroxybenzylcarbamate (1.25 g, 3.79 mmol) in acetonitrile (40 mL) was added cesium carbonate (1.86 g, 5.69 mmol) and 2-bromo-1-(4-methoxyphenyl)propan-1-one (0.97 g, 3.79 mmol). After 2 h, the mixture was diluted with water (100 mL) and extracted with ethyl acetate (3 × 50 mL). The combined organic phases were dried over magnesium sulfate, filtered, and concentrated. The crude product was purified chromatographically (CombiFlash, 40 g silica gel column, 10–30% ethyl acetate / heptane eluent) to afford 1.35 g (72%) of t-butyl 4-(benzyloxy)-3-((1-(4-methoxyphenyl)-1-oxopropan-2-yl)oxy)benzylcarbamate as a white solid.

[0624] Example 1-12-3: Preparation of t-butyl (4-hydroxy-3-((1-hydroxy-1-(4-methoxyphenyl)propan-2-yl)oxy)benzyl)carbamate To a stirred solution of t-butyl 4-(benzyloxy)-3-((1-(4-methoxyphenyl)-1-oxopropan-2-yl)oxy)benzylcarbamate (1.35 g, 2.75 mmol) in tetrahydrofuran (30 mL) was added 10% palladium on carbon (aqueous) (0.89 g, 0.84 mmol). The mixture was degassed under vacuum and refilled with nitrogen (three times). After the final evacuation, the atmosphere was replaced with hydrogen via a balloon. The reaction mixture was stirred at room temperature. After 1 h, the vessel was evacuated and the atmosphere replaced with nitrogen. Tetrahydrofuran (50 mL) was added and the mixture filtered through Celite. The filtrate was diluted with methanol (10 mL), and the yellow solution was treated with sodium borohydride (0.13 g, 3.43 mmol) (gas evolution and a mild exotherm were observed). After 90 min, the mixture was treated with water (2 mL) and concentrated. The residue was dissolved in ethyl acetate (75 mL) and washed with saturated sodium bicarbonate solution (75 mL). The organic phase was dried over magnesium sulfate, filtered, and concentrated to give 1.18 g (>100%) of tert-butyl 4-hydroxy-3-((1-hydroxy-1-(4-methoxyphenyl)propan-2-yl)oxy)benzylcarbamate as a colorless oil.

[0625] Example 1-12-4: Preparation of t-butyl ((2-(4-methoxyphenyl)-3-methyl-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)carbamate t-Butyl 4-hydroxy-3-((1-hydroxy-1-(4-methoxyphenyl) To a stirred solution of (propan-2-yl)oxy)benzylcarbamate (1.11 g, 2.75 mmol) and triphenylphosphine (0.98 g, 3.71 mmol) in tetrahydrofuran (30 mL) was added a solution of bis(2-methoxyethyl)azodicarboxylate (0.90 g, 3.71 mmol) in tetrahydrofuran (10 mL) over 3 minutes. The resulting yellow solution was heated to reflux. After 3 hours, the mixture was cooled to room temperature and diluted with ethyl acetate (75 mL). The organic phase was washed with water (2 × 50 mL), 1N hydrochloric acid solution (50 mL), 1N sodium hydroxide solution (50 mL), and brine (50 mL). The organic phase was dried over magnesium sulfate, filtered, and concentrated. The crude product was purified chromatographically (CombiFlash, 40 g silica gel gold column, 10–25% ethyl acetate / heptane eluent) to give 0.50 g (47%) of tert-butyl ((2-(4-methoxyphenyl)-3-methyl-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)carbamate as a white solid.

[0626] Example 1-12-5: Preparation of (2-(4-methoxyphenyl)-3-methyl-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methanamine To a stirred solution of t-butyl ((2-(4-methoxyphenyl)-3-methyl-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)carbamate (0.50 g, 1.30 mmol) in dichloromethane (10 mL) was added trifluoroacetic acid (5.0 mL, 64.64 mmol). After 30 minutes, the solution was concentrated, and the residue was dissolved in 5N ammonium hydroxide solution (20 mL). The basic mixture was extracted with dichloromethane (2 × 30 mL). The combined organic phases were dried over magnesium sulfate, filtered, and concentrated to give 0.36 g (97%) of (2-(4-methoxyphenyl)-3-methyl-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methanamine as a colorless oil.

[0627] Example 1-12-6: Preparation of 4-(3-((2-(4-methoxyphenyl)-3-methyl-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridin-6-yl)-2-methylbut-3-yn-2-amine The title compound was prepared in four steps from (2-(4-methoxyphenyl)-3-methyl-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methanamine as described in Examples 1-5-5 to 1-5-8: 1 H NMR (400 MHz, chloroform-d) δ 8.46 (d, J = 1.9 Hz, 1H), 8.07 (d, J = 1.9 Hz, 1H), 8.02 (s, 1H), 7.29 - 7.24 (m, 2H), 6.96 - 6.80 (m, 5H), 5.36 (s, 2H), 4.57 (d, J = 8.0 Hz, 1H), 4.08 (dq, J = 8.0, 6.4 Hz, 1H), 3.82 (s, 3H), 1.53 (s, 6H), 1.14 (d, J = 6.4 Hz, 3H) ppm: (M+1) = 469.

[0628] Example 1-13: Synthesis of 6-methoxy-3-((2-(6-methoxypyridin-3-yl)-3-methyl-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine Example 1-13-1: Preparation of (2-(6-methoxypyridin-3-yl)-3-methyl-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methanamine The title compound was prepared in four steps from 2-bromo-1-(6-methoxypyridin-3-yl)propan-1-one as described in Example 1-12-2 to Example 1-12-5.

[0629] Example 1-13-2: Preparation of 6-iodo-3-((2-(6-methoxypyridin-3-yl)-3-methyl-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine As described in Examples 1-5-5 to 1-5-7, (2-(6-methoxypyridin-3-yl)-3-methyl-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methanamine and 2-chloro-5-iodo-3-nitropyridine were synthesized in three steps. The title compound was prepared by

[0630] Example 1-13-3: Preparation of 6-methoxy-3-((2-(6-methoxypyridin-3-yl)-3-methyl-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine The title compound was prepared from 6-iodo-3-((2-(6-methoxypyridin-3-yl)-3-methyl-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine and methanol as described in Examples 1-11: (approximately 55:45 trans / cis) 1 H NMR (400 MHz, chloroform-d) δ 8.23 - 8.20 (m, 1H), 8.16 - 8.12 (m, 1H), 8.00 - 7.96 (m, 1H), 7.60 - 7.57 (m, 1H), 7.57 - 7.53 (m, 1H), 6.93 - 6.72 (m, 4H), 5.35 (s, 2H), 5.12 (d, J = 2.6 Hz, 1H, cis isomer), 4.60 (d, J = 8.0 Hz, 1H, trans isomer), 4.51 - 4.43 (m, 1H, cis isomer), 4.13 - 4.04 (m, 1H, trans isomer), 3.99 - 3.88 (m, 9H), 1.17 (d, J = 6.3 Hz, 3H, trans isomer), 1.12 (d, J = 6.6 Hz, 3H, cis isomer) ppm; (M+1) = 419.

[0631] Example 1-14: Synthesis of 4-(3-((2-(2,4-dichlorophenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridin-6-yl)-2-methylbut-3-yn-2-amine Example 1-14-1: Preparation of 3-(2-(2,4-dichlorophenyl)-2-oxoethoxy)-4-fluorobenzonitrile To a stirred and cooled (0°C) suspension of 4-fluoro-3-hydroxybenzonitrile (5.00 g, 36.47 mmol) and potassium carbonate (10.08 g, 72.93 mmol) in N,N-dimethylformamide (80 mL) was added dropwise over 3 minutes a solution of 2-bromo-1-(2,4-dichlorophenyl)ethanone (9.77 g, 36.47 mmol) in N,N-dimethylformamide (10 mL). After 15 minutes, the cooling bath was removed and the mixture was allowed to warm to room temperature. After 90 minutes, the mixture was recooled to 0°C while water was added to give a precipitate. The solid was collected by filtration, washed with water followed by hexane, and dried to give 11.80 g (97%) of 3-(2-(2,4-dichlorophenyl)-2-oxoethoxy)-4-fluorobenzonitrile as a beige solid.

[0632] Example 1-14-2: Preparation of 3-(2-(2,4-dichlorophenyl)-2-hydroxyethoxy)-4-fluorobenzonitrile Methanol (80 mL) was cooled to 0° C. while sodium borohydride (2.45 g, 64.76 mmol) was slowly added. After the addition was complete, the mixture was stirred at 0° C. for 15 minutes, after which 3-(2-(2,4-dichlorophenyl)-2-oxoethoxy)-4-fluorobenzonitrile (7.00 g, 21.60 mmol) was slowly added. A precipitate formed near the end of the addition, so an additional amount of methanol (70 mL) was added. The resulting suspension was allowed to warm to room temperature. After 1 hour, the mixture was recooled to 0° C., after which 0.1 N hydrochloric acid solution (20 mL) was added. The mixture was extracted with dichloromethane, and the combined organic phases were concentrated. The crude solid was triturated with dichloromethane, filtered, and washed with hexanes. A second trituration with dichloromethane / washing with hexanes gave 5.90 g (84%) of 3-(2-(2,4-dichlorophenyl)-2-hydroxyethoxy)-4-fluorobenzonitrile as an off-white solid.

[0633] Example 1-14-3: Preparation of 2-(2,4-dichlorophenyl)-2,3-dihydrobenzo[b][1,4]dioxine-6-carbonitrile A stirred suspension of potassium carbonate (6.25 g, 45.22 mmol) and 3-(2-(2,4-dichlorophenyl)-2-hydroxyethoxy)-4-fluorobenzonitrile (5.90 g, 18.09 mmol) in N,N-dimethylformamide (60 mL) was heated to 80° C. After 24 h, the mixture was cooled to room temperature while water and ethyl acetate were added. The phases were separated, and the aqueous phase was extracted with ethyl acetate. The combined organic phases were washed with brine, dried over magnesium sulfate, filtered, and concentrated. The crude material was triturated with methanol and filtered to give 2.75 g of a white solid. The filtrate was concentrated, and the residue was purified (CombiFlash, silica gel column, 10-20% ethyl acetate / heptane eluent) to give an additional 0.73 g of a white solid. A total of 3.48 g (63%) of 2-(2,4-dichlorophenyl)-2,3-dihydrobenzo[b][1,4]dioxine-6-carbonitrile was obtained.

[0634] Example 1-14-4: Preparation of (2-(2,4-dichlorophenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methanamine To a stirred and cooled (0 °C) solution of 2-(2,4-dichlorophenyl)-2,3-dihydrobenzo[b][1,4]dioxine-6-carbonitrile (3.48 g, 11.37 mmol) in tetrahydrofuran (60 mL) was added 2.4 M lithium aluminum hydride solution in ether (9.5 mL, 22.80 mmol) via syringe. The mixture was stirred at 0 °C. After 30 min, the cooling bath was removed and the mixture was allowed to warm to room temperature. After 4 h, the mixture was recooled to 0 °C and diluted with EtO. Water (0.87 mL), 1 N sodium hydroxide solution ( The mixture was quenched by the slow addition of 0.87 mL of HCl (HCl 3 HCl) and water (2.6 mL). The mixture was stirred at 0° C. for 1 hour. The resulting white suspension was filtered through Celite, and the filter cake was washed with ethyl acetate. The filtrate was concentrated to give 3.53 g (93%) of (2-(2,4-dichlorophenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methanamine as a colorless oil that crystallized on standing.

[0635] Example 1-14-5: Preparation of 4-(3-((2-(2,4-dichlorophenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridin-6-yl)-2-methylbut-3-yn-2-amine The title compound was prepared in four steps from (2-(2,4-dichlorophenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methanamine, 2-chloro-5-iodo-3-nitropyridine, and 2-methylbut-3-yn-2-amine as described in Examples 1-5-5 to 1-5-8: 1H NMR (400 MHz, DMSO-d6) δ 8.72 (s, 1H), 8.58 (s, 2H), 8.48 (d, J = 1.8 Hz, 1H), 8.20 (d, J = 1.9 Hz, 1H), 7.73 (d, J = 1.6 Hz, 1H), 7.53 (d, J = 2.0 Hz, 2H), 7.10 - 6.81 (m, 3H), 5.42 (q, J = 2.6 Hz, 3H), 4.44 (dd, J = 11.7, 2.4 Hz, 1H), 4.01 (dd, J = 11.7, 8.2 Hz, 1H), 3.61 - 3.31 (m, 1H), 1.65 (s, 4H) ppm; (M+1) = 493.

[0636] Example 1-15: Synthesis of 2,2,2-trifluoro-N-((6-((6-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)-2,3-dihydrobenzo[b][1,4]dioxin-2-yl)methyl)acetamide Example 1-15-1: Preparation of 6-(hydroxymethyl)-2,3-dihydrobenzo[b][1,4]dioxine-2-carbonitrile The title compound was prepared from 6-formyl-2,3-dihydrobenzo[b][1,4]dioxine-2-carbonitrile as described in Example 1-14-2.

[0637] Example 1-15-2: Preparation of 6-((6-bromo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)-2,3-dihydrobenzo[b][1,4]dioxine-2-carbonitrile To a stirred solution of 6-(hydroxymethyl)-2,3-dihydrobenzo[b][1,4]dioxine-2-carbonitrile (1.16 g, 6.06 mmol) in toluene (17 mL) was added 2-(tributylphosphoranylidene)acetonitrile (1.46 g, 6.06 mmol). The mixture was stirred at room temperature. After 10 minutes, 6-bromo-3H-imidazo[4,5-b]pyridine (1.00 g, 5.05 mmol) was added to the mixture, and the resulting mixture was The mixture was heated to 90°C. After 6 hours, the mixture was cooled to room temperature and concentrated. The crude product was purified by chromatography (CombiFlash, silica gel column, 80% ethyl acetate / hexane eluent) to give 0.82 g (44%) of 6-((6-bromo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)-2,3-dihydrobenzo[b][1,4]dioxine-2-carbonitrile as an off-white foam.

[0638] Example 1-15-3: Preparation of 6-((6-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)-2,3-dihydrobenzo[b][1,4]dioxine-2-carbonitrile The title compound was prepared from 6-((6-bromo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)-2,3-dihydrobenzo[b][1,4]dioxine-2-carbonitrile and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole as described in Examples 1-4.

[0639] Example 1-15-4: (6-((6-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)-2,3-dihydrobenzo[b][1,4]dioxin-2-yl)methanamine The title compound was prepared from 6-((6-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)-2,3-dihydrobenzo[b][1,4]dioxine-2-carbonitrile as described in Example 1-14-4.

[0640] Example 1-15-5: Preparation of 2,2,2-trifluoro-N-((6-((6-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)-2,3-dihydrobenzo[b][1,4]dioxin-2-yl)methyl)acetamide To a stirred and cooled (0° C.) solution of (6-((6-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)-2,3-dihydrobenzo[b][1,4]dioxin-2-yl)methanamine (0.030 g, 0.079 mmol) in dichloromethane (2 mL) was added triethylamine (0.022 mL, 0.15 mmol), followed by trifluoroacetic anhydride (0.007 mL, 0.079 mmol). The mixture was stirred at 0° C. After 15 minutes, the cooling bath was removed and the mixture was allowed to warm to room temperature. After 1 hour, the mixture was diluted with dichloromethane (10 mL) and saturated sodium bicarbonate solution. The phases were separated and the aqueous phase was extracted with dichloromethane. The combined organic phases were dried over magnesium sulfate, filtered, and concentrated. The crude product was purified chromatographically (CombiFlash, silica gel column, 5% methanol / dichloromethane eluent) to give 0.038 g (8%) of 2,2,2-trifluoro-N-((6-((6-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)-2,3-dihydrobenzo[b][1,4]dioxin-2-yl)methyl)acetamide as a white solid: 1 H NMR (400 MHz, DMSO-d6) δ 9.67 (s, 1H), 8.63 (d, J = 1.9 Hz, 1H), 8.53 (s, 1H), 8.30 - 8.17 (m, 2H), 7.96 (s, 1H), 7.00 - 6.77 (m, (M+1) = 473.

[0641] Example 1-16: Synthesis of 6-(3-methoxyazetidin-1-yl)-3-((2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine As described in Example 1-10, 6-iodo-3-((2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridine (Example 1-5-7) and 3-methoxybenzo[b]pyridine were reacted with 2- ... The title compound was prepared from zetidine hydrochloride: 1 H NMR (400 MHz, CDCl3) δ 8.19 (d, J = 2.5 Hz, 1H), 7.91 (s, 1H), 7.78 (d, J = 2.5 Hz, 1H), 7.59 (dd, J = 8.6, 2.5 Hz, 1H), 7.15 (d, J = 2.5 Hz, 1H), 6.95 - 6.76 (m, 4H), 5.31 (s, 2H), 5.07 (dd, J = 8.8, 2.5 Hz, 1H), 4.43 - 4.35 (m, 1H), 4.29 (dd, J = 11.6, 2.5 Hz, 1H), 4.22 - 4.15 (m, 2H), 4.02 (dd, J = 11.6, 8.8 Hz, 1H), 3.95 (s, 3H), 3.79 - 3.73 (m, 2H), 3.36 (s, 3H) ppm; (M+1) = 460.

[0642] Example 1-17: Synthesis of 2-methyl-4-(3-((2-(1-methyl-1H-pyrazol-4-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3H-imidazo[4,5-b]pyridin-6-yl)but-3-yn-2-amine The title compound was prepared in eight steps from 3-hydroxy-4-iodobenzamide, 2-bromo-1-(1-methyl-1H-pyrazol-4-yl)ethan-1-one, 2-chloro-5-iodo-3-nitropyridine, and 2-methylbut-3-yn-2-amine as described in Example 1-5-1 to Example 1-5-8: 1 H NMR (400 MHz, chloroform-d) δ 8.45 (d, J = 1.8 Hz, 1H), 8.07 (d, J = 1.8 Hz, 1H), 8.01 (s, 1H), 7.52 (d, J = 0.8 Hz, 1H), 7.44 (s, 1H), 6.90 - 6.78 (m, 3H), 5.35 (s, 2H), 5.14 (dd, J = (M+H) = 429.

[0643] Example 1-18: Synthesis of 4-(3-(1-(2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)ethyl)-3H-imidazo[4,5-b]pyridin-6-yl)-2-methylbut-3-yn-2-amine Example 1-18-1: Preparation of methyl 4-(benzyloxy)-3-(2-(6-methoxypyridin-3-yl)-2-oxoethoxy)benzoate To a stirred solution of methyl 4-(benzyloxy)-3-hydroxybenzoate (3.37 g, 13.05 mmol) in N,N-dimethylformamide (20 mL) was added potassium carbonate (2.71 g, 19.57 mmol) and 2-bromo-1-(6-methoxypyridin-3-yl)ethanone (3.00 g, 13.05 mmol). The reaction was stirred at room temperature. After 16 hours, the mixture was diluted with ethyl acetate and water. The phases were separated, and the aqueous phase was extracted with ethyl acetate. The combined organic phase was washed with water and brine, dried over magnesium sulfate, filtered, and concentrated. The crude product was purified chromatographically (CombiFlash, silica gel column, 0-50% ethyl acetate / heptane eluent) to give 3.81 g (72%) of methyl 4-(benzyloxy)-3-(2-(6-methoxypyridin-3-yl)-2-oxoethoxy)benzoate as a white solid.

[0644] Example 1-18-2: Preparation of methyl 4-(benzyloxy)-3-(2-hydroxy-2-(6-methoxypyridin-3-yl)ethoxy)benzoate The title compound was prepared from methyl 4-(benzyloxy)-3-(2-(6-methoxypyridin-3-yl)-2-oxoethoxy)benzoate as described in Example 1-14-2.

[0645] Example 1-18-3: Preparation of methyl 4-hydroxy-3-(2-hydroxy-2-(6-methoxypyridin-3-yl)ethoxy)benzoate To a stirred solution of methyl 4-(benzyloxy)-3-(2-hydroxy-2-(6-methoxypyridin-3-yl)ethoxy)benzoate (3.53 g, 8.62 mmol) was added 10% palladium on carbon (0.92 g, 0.86 mmol). The mixture was degassed under vacuum / backfilled with nitrogen (three times). After the final evacuation, the atmosphere was replaced with hydrogen via a balloon. The reaction mixture was heated to 65° C. After 16 h, the mixture was cooled to room temperature, the vessel was evacuated, and the atmosphere was replaced with nitrogen. The mixture was filtered through Celite, and the filtrate was concentrated to give methyl 4-hydroxy-3-(2-hydroxy-2-(6-methoxypyridin-3-yl)ethoxy)benzoate. 2.39 g (87%) of the benzoate was obtained as a white solid.

[0646] Example 1-18-4: Preparation of methyl 2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxine-6-carboxylate The title compound was prepared from methyl 4-hydroxy-3-(2-hydroxy-2-(6-methoxypyridin-3-yl)ethoxy)benzoate as described in Example 1-12-4.

[0647] Example 1-18-5: Preparation of 2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxine-6-carboxylic acid To a stirred solution of methyl 2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxine-6-carboxylate (1.69 g, 5.61 mmol) in 1:4 water / methanol (25 mL) was added lithium hydroxide (1.41 g, 56.10 mmol). The reaction was stirred at room temperature. After 16 h, the mixture was concentrated and the residue was dissolved in water. The pH was adjusted to approximately 5 with concentrated hydrochloric acid solution, resulting in the formation of a precipitate. The mixture was filtered, and the filter cake was washed with water and dried to give 1.56 g (97%) of 2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxine-6-carboxylic acid as a white solid.

[0648] Example 1-18-6: Preparation of N-methoxy-2-(6-methoxypyridin-3-yl)-N-methyl-2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamide To a stirred solution of 2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxine-6-carboxylic acid (1.56 g, 5.43 mmol) in N,N-dimethylformamide (15 mL) was added 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (4.26 g, 10.86 mmol), N,O-dimethylhydroxylamine hydrochloride (1.08 g, 10.86 mmol), and N,N-diisopropylethylamine (3.86 mL, 21.70 mmol). The mixture was stirred at room temperature. After 5 minutes, the mixture was diluted with ethyl acetate and water. The phases were separated, and the aqueous phase was extracted with ethyl acetate (3 × 50 mL). The combined organic phases were washed with water (3 × 40 mL) and brine, dried over magnesium sulfate, filtered, and concentrated to give 1.51 g (84%) of the desired material, N-methoxy-2-(6-methoxypyridin-3-yl)-N-methyl-2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamide, as a colorless semi-solid.

[0649] Example 1-18-7: Preparation of 1-(2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)ethan-1-one To a stirred and cooled (0 °C) solution of N-methoxy-2-(6-methoxypyridin-3-yl)-N-methyl-2,3-dihydrobenzo[b][1,4]dioxin-6-carboxamide (1.51 g, 4.57 mmol) in tetrahydrofuran (40 mL) was added 3.0 M methylmagnesium bromide solution in ether (3.0 mL, 9.00 mmol). The mixture was stirred at 0 °C. After 30 minutes, the mixture was quenched with water and diluted with ethyl acetate. The phases were separated, and the organic phase was washed with brine, dried over magnesium sulfate, filtered, and concentrated to give 1.16 g (87%) of 1-(2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)ethan-1-one as a white solid.

[0650] Example 1-18-8: Preparation of (E / Z)-1-(2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)ethan-1-one oxime 1-(2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1 To a stirred solution of (E / Z)-1-(2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)ethanone (1.16 g, 4.07 mmol) in methanol (10 mL) was added sodium acetate (1.67 g, 20.33 mmol) and hydroxylamine hydrochloride (0.30 g, 4.97 mmol). The mixture was heated to 60° C. After 2 h, the solution was cooled to room temperature and concentrated. The residue was diluted with water, resulting in the formation of a precipitate. The solid was collected by filtration, and the filter cake was dried to give 1.16 g (95%) of (E / Z)-1-(2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)ethan-1-one oxime as a white solid.

[0651] Example 1-18-9: Preparation of 1-(2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)ethan-1-amine To a stirred solution of (E / Z)-1-(2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)ethanone oxime (1.16 g, 3.86 mmol) in glacial acetic acid (20 mL) was added zinc dust (3.03 g, 46.4 mmol). The reaction was heated to 40 °C. After 2 h, the mixture was cooled to room temperature and diluted with ethyl acetate and water. The phases were separated (the organic phase was discarded), and the aqueous phase was neutralized with 1 N sodium hydroxide solution. The neutral aqueous phase was extracted with ethyl acetate (2 × 50 mL). The combined organic phases were dried over magnesium sulfate, filtered, and concentrated to give 0.29 g (26%) of 1-(2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)ethan-1-amine as a brown oil.

[0652] Example 1-18-10: Preparation of 4-(3-(1-(2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)ethyl)-3H-imidazo[4,5-b]pyridin-6-yl)-2-methylbut-3-yn-2-amine The title compound was prepared in four steps from 1-(2-(6-methoxypyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)ethan-1-amine, 2-chloro-5-iodo-3-nitropyridine, and 2-methylbut-3-yn-2-amine as described in Example 1-...

Claims

1. A compound selected from: 3-((5-ethoxy-6-((6-methylpyridin-3-yl)methoxy)pyridin-3-yl)methyl)pyrazolo[1,5-a]pyrimidine; 3-((5-ethoxy-6-((6-(trifluoromethyl)pyridin-3-yl)methoxy)pyridin-3-yl)methyl)-N,N-dimethylimidazo[1,2-b]pyridazine-7-carboxamide; 4-((6-((6-cyclopropylpyridin-3-yl)methoxy)-5-ethoxypyridin-3-yl)methyl)-N-methylpicolinamide; 4-((6-((6-cyclopropylpyridin-3-yl)methoxy)-5-ethoxypyridin-3-yl)oxy)-N-methylpicolinamide; and 4-((6-((6-cyclopropylpyridin-3-yl)methoxy)-5-fluoropyridin-3-yl)oxy)-N-methylpicolinamide, and / or the stereoisomers, optical isomers, racemic and diastereomeric mixtures, and / or pharma- ceutically acceptable salts thereof.

2. 10. A pharmaceutical composition comprising a compound according to claim 1 and / or a pharma- ceutically acceptable salt, and a pharma- ceutically acceptable excipient.

3. 13. Use of a compound according to claim 1 for the preparation of a medicament.

4. 13. Use of a compound according to claim 1 for the preparation of a medicament for treating a disease or disorder selected from multiple sclerosis, ALS, Huntington's disease, lupus, lupus nephritis, and rheumatoid arthritis.

Citation Information

Patent Citations

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Novel 3,5-disubstituted-3H-imidazo[4,5-B]pyridine compounds and 3,5-disubstituted-3H-[1,2,3]triazolo[4,5-B]pyridine compounds as protein kinase regulators
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Novel 3,5-disubstituted-3H-imidazo[4,5-B]pyridine compounds and 3,5-disubstituted-3H-[1,2,3]triazolo[4,5-B]pyridine compounds as C-MET protein kinase modifiers
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Patent Information

Abstract

Description

Patent Citations

2-arylquinoline and its production

Crystal of n-((quinolin-2-yl)phenyl)sulfonamides and its production

Novel 3,5-disubstituted-3H-imidazo[4,5-B]pyridine compounds and 3,5-disubstituted-3H-[1,2,3]triazolo[4,5-B]pyridine compounds as protein kinase regulators

Novel 3,5-disubstituted-3H-imidazo[4,5-B]pyridine compounds and 3,5-disubstituted-3H-[1,2,3]triazolo[4,5-B]pyridine compounds as C-MET protein kinase modifiers

Chromanderivatives as angiotensin ii antagonists