Parp7 inhibitors
Patent Information
- Application Number
- HK62026126233
- Authority / Receiving Office
- HK · HK
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-07-26
- Filing Date
- 2026-07-16
- Publication Date
- 2026-10-09
- Estimated Expiration
- 2044-07-24
Abstract
Description
(19) State Intellectual Property Office (12) Invention Patent Application (10) Publication Number (43) Publication Date (21) Application Number 202480048729.8 (22) Application Date 2024.07.25 (30) Priority Data 63 / 515,755 2023.07.26 US (85) PCT International Application Entering National Phase Date 2026.01.22 (86) PCT International Application Application Data PCT / US2024 / 039549 2024.07.25 (87) PCT International Application Publication Data WO2025 / 024663 EN 2025.01.30 (71) Applicant: Gilead Sciences, Inc. Address: California, USA (72) Inventors: J.J. Zhang, J. Chandrasekar, K.S. Curry, S.D. Holmbo, J.M. Jacobson, D.L. Kukla, S.H. Lee, Y. Moyazami, L.B. Patel, T.J. Paul, S. Perot, P.J. Salvo, J.A. Treiberg, H.A. Weaver (74) Patent Agency: Beijing Liu Shen Law Firm, 11105 Patent Attorney: Qin Jian (51) Int.Cl. C07D 401 / 14 (2006.01) C07D 403 / 14 (2006.01) C07D 405 / 14 (2006.01) C07D 417 / 14 (2006.01) C07D 471 / 04 (2006.01) C07D 491 / 04(2006.01) C07D 498 / 04(2006.01) A61P 35 / 00(2006.01) A61K 31 / 501(2006.01) (54) Invention Title: PARP7 Inhibitor (57) Abstract: This document provides a compound of formula (I) or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers or deuterated analogue thereof, a pharmaceutical composition comprising the compound of the present disclosure and a pharmaceutically acceptable excipient thereof, and a method of treating cancer therewith. (I) Claims: 23 pages Description: 240 pages CN 121568935 A 2026.02.24 CN 1 21 56 89 35 A
Claims
1. A compound of formula (I): (I)， Or its pharmaceutically acceptable salts, stereoisomers, mixtures of stereoisomers, or deuterated analogs. Where J is: or , X 1 It is N, CR 4 or CR 4 R 4 ; X 2 It is CR 5 ; X 3 It is CR 5 ; X 4 Is it N or CR? 5 ; X 5 It is CR 5 ; X 6 It is CR 5 ; A is O or NH; R 1 Selected from H, C1-6 alkyl and C 3-12 cycloalkyl, wherein the C1-6 alkyl group is optionally surrounded by one or more R 6 replace; R 2 Selected from H, halogen, C1-6 alkyl, -OH, -O(C 1-6 alkyl) and cyclopropyl; R 3a and R 3b Each is independently selected from H, halogen, -OH, C1-6 alkyl, and -O(C 1-6 Alkyl groups), wherein each C1-6 alkyl group is independently and optionally bounded by one or more R groups. 6 replace; Z is selected from one or more R. 7 Substituted 5-12 heteroaryl groups; optionally substituted with one or more R 7 Replacement C 6-10 aryl; optionally constituting one or more R 7 Replacement C 3-12 cycloalkyl; and optionally by one or more R 7 Substituted 4-12-membered heterocyclic groups; wherein the 5-12-membered heteroaryl group or C 6-10 The aryl group is monocyclic or bicyclic; and the C 3-12 The cycloalkyl or 4-12 membered heterocyclic group can be monocyclic, bicyclic, fused bicyclic, spirocyclic, or bridged; Each R 4 Independently selected from H, halogen, C 1-6 Alkyl, C 3-12 cycloalkyl and -O(C) 1-6 alkyl); Each R 5 Independently selected from H, halogen, C 1-6 Alkyl, C 4-10 Cycloalkyl, -OH and -O(C 1-6 alkyl); Each R 6 Independently selected from H, halogen groups, -OH, -O(C) 1-6 (halogenated alkyl) and -O(C) 1-6 alkyl); Each R 7 Independently selected from halogen groups, C 1-6 Alkyl, -NH2, -SO2(C 1-6 alkyl), -O(C) 1-6 alkyl) and C 3-12 cycloalkyl, wherein each C 1-6 The alkyl group is optionally substituted with one or more halogen groups or -OH or CN; and The compound in question is not: 2-[4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]-6-[5-(trifluoromethyl)pyridin-2-yl]isoquinoline-1-one; 2-[(4R)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]-6-[5-(trifluoromethyl)pyridin-2-yl]isoquinoline-1-one; 2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]-6-[5-(trifluoromethyl)pyridin-2-yl]isoquinoline-1-one; 2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]-6-[5-(trifluoromethyl)pyrimidin-2-yl]isoquinoline-1-one; 5-Fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]-6-[5-(trifluoromethyl)pyrimidin-2-yl]isoquinoline-1-one; 8-Fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]-6-[5-(trifluoromethyl)pyrimidin-2-yl]isoquinoline-1-one; 7-Fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]-6-[5-(trifluoromethyl)pyrimidin-2-yl]isoquinoline-1-one; 7-Fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]-6-[5-(trifluoromethyl)pyridin-2-yl]isoquinoline-1-one; 5-Fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]-6-[5-(trifluoromethyl)pyridin-2-yl]isoquinoline-1-one; 8-Fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]-6-[5-(trifluoromethyl)pyridin-2-yl]isoquinoline-1-one; 6-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]-2-[5-(trifluoromethyl)pyridin-2-yl]-1,6-naphthidin-5-one; 6-[5-(difluoromethoxy)pyridin-2-yl]-8-fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 8-Fluoro-6-(5-Fluoropyridin-2-yl)-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 7,8-Difluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]-6-[5-(trifluoromethyl)pyrimidin-2-yl]isoquinoline-1-one; 7-Fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]-6-[5-(trifluoromethyl)pyrazin-2-yl]isoquinoline-1-one; 7-Fluoro-6-(5-methoxypyrimidin-2-yl)-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 6-(2,3-dihydro-1-benzofuran-7-yl)-7-fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinolin-1-one; 6-(2,3-dihydro-1,4-benzodioxin-5-yl)-7-fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinolin-1-one; 6-(2,3-dihydro-1,4-benzodioxin-6-yl)-7-fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 6-Fluoro-3-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]-7-[5-(trifluoromethyl)pyrimidin-2-yl]quinazolin-4-one; 7-Fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]-6-pyridin-2-ylisoquinoline-1-one; 7-Fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]-6-[5-(trifluoromethoxy)pyridin-2-yl]isoquinoline-1-one; 6-[5-(difluoromethyl)pyridin-2-yl]-7-fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 7-Fluoro-6-(5-Fluoropyrimidin-2-yl)-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 7-Fluoro-6-(5-Fluoropyridin-2-yl)-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 2-[(4R)-4-cyclopropyl-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]butyl]-7-fluoro-6-[5-(trifluoromethyl)pyrimidin-2-yl]isoquinoline-1-one; 7-Fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]hexyl]-6-[5-(trifluoromethyl)pyrimidin-2-yl]isoquinoline-1-one; 8-Fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]-6-[5-(2,2,2-trifluoroethyl)pyridin-2-yl]isoquinoline-1-one; 6-[5-(difluoromethoxy)pyrimidin-2-yl]-7-fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 6-[5-(difluoromethoxy)pyridin-2-yl]-7-fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 7-Chloro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]-6-[5-(trifluoromethyl)pyrimidin-2-yl]isoquinolin-1-one; 4-Methyl-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]-6-[5-(trifluoromethyl)pyrimidin-2-yl]isoquinoline-1-one; 6-[4-amino-5-(trifluoromethyl)pyridin-2-yl]-7-fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 6-[5-(difluoromethyl)pyridin-2-yl]-7,8-difluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 7,8-Difluoro-6-(5-fluoropyridin-2-yl)-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 6-[5-(difluoromethyl)pyrimidin-2-yl]-7,8-difluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinolin-1-one; 7,8-Difluoro-6-(5-fluoropyrimidin-2-yl)-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 7,8-Difluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]-6-[5-(trifluoromethyl)pyridin-2-yl]isoquinoline-1-one; 6-[5-(difluoromethoxy)pyrimidin-2-yl]-7,8-difluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 6-[5-(difluoromethoxy)pyridin-2-yl]-7,8-difluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 6-Fluoro-3-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]-7-[5-(trifluoromethyl)pyridin-2-yl]quinazolin-4-one; 6-Fluoro-7-(5-Fluoropyridin-2-yl)-3-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]quinazolin-4-one; 6-Fluoro-7-(5-Fluoropyrimidin-2-yl)-3-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]quinazolin-4-one; 6-Fluoro-3-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]-7-(7H-pyrrolo[2,3-d]pyrimidin-2-yl)quinazolin-4-one; 6-Fluoro-7-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-3-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]quinazolin-4-one; 6-Fluoro-7-(5-Fluoro-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-3-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]quinazolin-4-one; 7-(4-amino-5-cyclopropylpyrimidin-2-yl)-6-fluoro-3-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]quinazolin-4-one; 7-(4-amino-5-methoxypyrimidin-2-yl)-6-fluoro-3-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]quinazolin-4-one; 7-(4-amino-5-fluoropyrimidin-2-yl)-6-fluoro-3-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]quinazolin-4-one; 6-[4-amino-5-(trifluoromethyl)pyrimidin-2-yl]-7-fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]hexyl]isoquinolin-1-one; 7-Fluoro-2-[(4R)-5-hydroxy-5-methyl-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]hexyl]-6-[5-(trifluoromethyl)pyrimidin-2-yl]isoquinoline-1-one; 7-Fluoro-6-[5-(2-hydroxypropyl-2-yl)pyrimidin-2-yl]-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 6-[5-(1,1-difluoro-2-hydroxyethyl)pyridin-2-yl]-7-fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 6-[5-(difluoromethyl)pyrimidin-2-yl]-7-fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 6-(4-amino-5-methylpyrimidin-2-yl)-7,8-difluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinolin-1-one; 7-(4-amino-5-methylpyrimidin-2-yl)-6-fluoro-3-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]quinazolin-4-one; 7-(2-amino-5-methylpyrimidin-4-yl)-6-fluoro-3-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]quinazolin-4-one; 6-(2-amino-5-methylpyrimidin-4-yl)-7,8-difluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinolin-1-one; 6-[4-amino-5-(trifluoromethyl)pyrimidin-2-yl]-7,8-difluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 7-[5-(difluoromethyl)pyrimidin-2-yl]-6-fluoro-3-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]quinazolin-4-one; 7-(5-Cyclopropylpyrimidin-2-yl)-6-fluoro-3-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]quinazolin-4-one; 7-Fluoro-6-(5-methylsulfonylpyrimidin-2-yl)-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 7,8-Difluoro-2-[4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]butyl]-6-[5-(trifluoromethyl)pyrimidin-2-yl]isoquinoline-1-one; 2-[(4R)-4-deuterated-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]-7,8-difluoro-6-[5-(trifluoromethyl)pyrimidin-2-yl]isoquinoline-1-one; 2-[(4S)-4-deuterated-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]-7,8-difluoro-6-[5-(trifluoromethyl)pyrimidin-2-yl]isoquinoline-1-one; 7-Fluoro-2-[(4R)-5-hydroxy-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]-6-[5-(trifluoromethyl)pyrimidin-2-yl]isoquinoline-1-one; (S)-2-(2,2-difluoro-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7-fluoro-6-(5-(trifluoromethyl)pyrimidin-2-yl)isoquinoline-1(2H)-one; 6-(6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-7-fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 6-Fluoro-7-(5-methylpyrimidin-2-yl)-3-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]quinazolin-4-one; 6-(5-amino-4-fluoropyridin-2-yl)-7-fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 6-[5-amino-4-(trifluoromethyl)pyridin-2-yl]-7-fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 6-(5-chloropyrimidin-2-yl)-7-fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 6-[4-amino-5-(trifluoromethyl)pyrimidin-2-yl]-7-fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 6-(4-amino-5-methoxypyrimidin-2-yl)-7-fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 6-(4-amino-5-fluoropyrimidin-2-yl)-7-fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 6-[4-amino-5-(difluoromethyl)pyrimidin-2-yl]-7-fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 6-[2-amino-5-(difluoromethyl)pyrimidin-4-yl]-7-fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 6-(4-amino-5-cyclopropylpyrimidin-2-yl)-7-fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 7-[4-amino-5-(difluoromethyl)pyrimidin-2-yl]-6-fluoro-3-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]quinazolin-4-one; 6-(4-amino-5-methoxypyrimidin-2-yl)-7,8-difluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinolin-1-one; 6-(5,5-dimethyl-6,7-dihydropyrrolo[2,3-d]pyrimidin-2-yl)-7-fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinolin-1-one; 6-[4-amino-5-(difluoromethyl)pyrimidin-2-yl]-7,8-difluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 6-[2-amino-5-(difluoromethyl)pyrimidin-4-yl]-7,8-difluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 6-(7,8-dihydro-6H-pyrimidino[5,4-b][1,4]oxazin-2-yl)-7-fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinolin-1-one; 6-Fluoro-7-(5-methylsulfonylpyrimidin-2-yl)-3-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]quinazolin-4-one; 6-Fluoro-7-[5-(2-hydroxyethoxy)pyrimidin-2-yl]-3-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]quinazolin-4-one; 7-[4-amino-5-(trifluoromethyl)pyrimidin-2-yl]-6-fluoro-3-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]quinazolin-4-one; 7-Fluoro-6-[5-(2-hydroxyethoxy)pyrimidin-2-yl]-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 7-Fluoro-2-[(4R)-5-methoxy-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]-6-[5-(trifluoromethyl)pyrimidin-2-yl]isoquinoline-1-one; 7-Fluoro-2-[4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]oxy]pentyl]-6-[5-(trifluoromethyl)pyrimidin-2-yl]isoquinoline-1-one; 6-[4-amino-5-(trifluoromethyl)pyrimidin-2-yl]-2-[(4R)-4-cyclopropyl-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]butyl]-7-fluoroisoquinoline-1-one; 6-(4-amino-5-methoxypyrimidin-2-yl)-2-[(4R)-4-cyclopropyl-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]butyl]-7-fluoroisoquinoline-1-one; 6-[4-amino-5-(difluoromethyl)pyrimidin-2-yl]-2-[(4R)-4-cyclopropyl-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]butyl]-7-fluoroisoquinoline-1-one; 6-Fluoro-3-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]hexyl]-7-[5-(trifluoromethyl)pyrimidin-2-yl]quinazolin-4-one; 7-[5-(difluoromethyl)pyrimidin-2-yl]-6-fluoro-3-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]hexyl]quinazolin-4-one; 7-(5-chloropyrimidin-2-yl)-6-fluoro-3-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]hexyl]quinazolin-4-one; 7,8-Difluoro-2-[(4R)-5-hydroxy-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]-6-[5-(trifluoromethyl)pyrimidin-2-yl]isoquinoline-1-one; 6-Fluoro-3-[(4R)-5-hydroxy-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]-7-[5-(trifluoromethyl)pyrimidin-2-yl]quinazolin-4-one; 6-[5-(difluoromethyl)pyrimidin-2-yl]-7-fluoro-2-[(4R)-5-hydroxy-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 6-(5-chloropyrimidin-2-yl)-7-fluoro-2-[(4R)-5-hydroxy-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 6-[6-amino-5-(trifluoromethyl)pyridin-2-yl]-7-fluoro-2-[(4R)-5-hydroxy-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; 2-[(4R)-5-(difluoromethoxy)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]-7-fluoro-6-[5-(trifluoromethyl)pyrimidin-2-yl]isoquinoline-1-one; 2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]-6-[4-(trifluoromethyl)pyrazol-1-yl]isoquinoline-1-one; 2-[(4R)-5-ethoxy-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]-7-fluoro-6-[5-(trifluoromethyl)pyrimidin-2-yl]isoquinoline-1-one; 7-Fluoro-2-[(4R)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]-5-(trideuteromethoxy)pentyl]-6-[5-(trifluoromethyl)pyrimidin-2-yl]isoquinoline-1-one; (S)-6-(4-amino-5-ethoxypyrimidin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-6-(6-amino-5-ethoxypyridin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-6-(4-amino-5-(difluoromethoxy)pyrimidin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-6-(6-amino-5-methoxypyridin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; 6-[4-amino-5-(trideuterated methoxy)pyrimidin-2-yl]-7-fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinoline-1-one; (S)-6-(4-(difluoromethyl)pyrimidin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-6-(4-aminopyrimidin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-6-(5-aminopyrimidin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-7-(5-chloropyrimidin-2-yl)-6-fluoro-3-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)quinazolin-4(3H)-one; (S)-6-(4-amino-5-chloropyrimidin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-6-(4-(difluoromethyl)pyrimidin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-6-(4-aminopyrimidin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-7-(5-chloropyrimidin-2-yl)-6-fluoro-3-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)quinazolin-4(3H)-one; (S)-6-fluoro-7-(4-morpholino-5-(trifluoromethyl)pyrimidin-2-yl)-3-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)quinazoline-4(3H)-one; (S)-6-(6-amino-5-(difluoromethyl)pyridin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-6-(thieno[2,3-d]pyrimidin-2-yl)isoquinoline-1(2H)-one; (S)-6-(6-amino-5-chloropyridin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-7-(6-amino-5-chloropyridin-2-yl)-6-fluoro-3-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)quinazolin-4(3H)-one; (S)-6-(4-amino-5-(difluoromethyl)pyrimidin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)hexyl)isoquinoline-1(2H)-one; (S)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-6-(1H-pyrazolo[3,4-d]pyrimidin-6-yl)isoquinoline-1(2H)-one; (S)-7-fluoro-6-(1-methyl-5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-6-(4-(difluoromethyl)thiazo-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-6-(4-amino-5-chloropyrimidin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)hexyl)isoquinoline-1(2H)-one; (S)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-6-(pyrazolo[1,5-a]pyridin-2-yl)isoquinoline-1(2H)-one; (S)-7-fluoro-6-(imidazo[1,2-a]pyridin-2-yl)-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-6-([1,2,4]triazolo[1,5-a]pyridin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-6-(benzo[d]oxazol-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-6-(benzo[d]thiazo-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-6-(5-(trifluoromethyl)thiazo-2-yl)isoquinoline-1(2H)-one; (S)-6-(4-amino-6-methylpyrimidin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-6-(6-amino-5-(trifluoromethyl)pyrazin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-6-(4-amino-5-chloro-6-methylpyrimidin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-7-(4-amino-5-(difluoromethyl)pyrimidin-2-yl)-6-fluoro-3-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)hexyl)quinazolin-4(3H)-one; (S)-7-(4-amino-5-(trifluoromethyl)pyrimidin-2-yl)-6-fluoro-3-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)hexyl)quinazolin-4(3H)-one; (S)-7-fluoro-6-(6-fluoroquinazolin-2-yl)-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinolin-1(2H)-one; (S)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-6-(4-(trifluoromethyl)oxazol-2-yl)isoquinoline-1(2H)-one; (S)-6-(6-amino-5-(difluoromethyl)pyrazin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-6-(4-amino-5-isopropylpyrimidin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-6-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-6-(4-amino-6-methyl-5-(trifluoromethyl)pyrimidin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-6-(3-amino-5-(trifluoromethyl)pyridin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-6-(5-(difluoromethyl)pyrazin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-6-(6-(difluoromethyl)-5-fluoropyridin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-7-fluoro-6-(4-methoxy-5-(trifluoromethyl)pyridin-2-yl)-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-6-(8-aminoimidazo[1,2-a]pyrazin-6-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-6-(thiazo[5,4-b]pyridin-5-yl)isoquinoline-1(2H)-one; (S)-6-([1,2,4]triazolo[1,5-a]pyrazin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-7-fluoro-6-(7-fluoro-[1,2,4]triazolo[1,5-a]pyridin-2-yl)-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-7-(6-amino-5-(trifluoromethyl)pyrazin-2-yl)-6-fluoro-3-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)quinazolin-4(3H)-one; (S)-7-(5-(difluoromethyl)pyridin-2-yl)-6-fluoro-3-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)hexyl)quinazolin-4(3H)-one; (S)-6-(6-amino-5-(trifluoromethyl)pyrazin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)hexyl)isoquinoline-1(2H)-one; (S)-7-(5-(difluoromethoxy)pyridin-2-yl)-6-fluoro-3-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)hexyl)quinazolin-4(3H)-one; (S)-6-(4-amino-5-chloropyrimidin-2-yl)-7,8-difluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-7-(4-amino-5-chloropyrimidin-2-yl)-6-fluoro-3-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)hexyl)quinazolin-4(3H)-one; (S)-6-(4-amino-5-methoxypyrimidin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)hexyl)isoquinoline-1(2H)-one; (S)-6-(5-(difluoromethyl)pyrimidin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)hexyl)isoquinoline-1(2H)-one; (S)-7-(5-(difluoromethyl)pyrazin-2-yl)-6-fluoro-3-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)hexyl)quinazolin-4(3H)-one; (S)-7-(6-amino-5-(trifluoromethyl)pyrazin-2-yl)-6-fluoro-3-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)hexyl)quinazolin-4(3H)-one; (S)-6-(4-amino-5-(trifluoromethyl)pyrimidin-2-yl)-7,8-difluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)hexyl)isoquinoline-1(2H)-one; (S)-6-(6-amino-5-(trifluoromethyl)pyrazin-2-yl)-7,8-difluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-6-(4-amino-5-methoxypyrimidin-2-yl)-7,8-difluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)hexyl)isoquinoline-1(2H)-one; (S)-6-(6-amino-5-chloropyrazin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-7-(6-amino-5-chloropyrazin-2-yl)-6-fluoro-3-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)quinazolin-4(3H)-one; (S)-7,8-difluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)hexyl)-6-(5-(trifluoromethyl)pyrimidin-2-yl)isoquinoline-1(2H)-one; (S)-4-amino-6'-fluoro-3'-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-[2,7'-diquinazoline]-4'(3'H)-one; (S)-6-(5-(difluoromethyl)pyrimidin-2-yl)-7,8-difluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)hexyl)isoquinoline-1(2H)-one; (S)-6-(4-amino-5-(difluoromethyl)pyrimidin-2-yl)-7,8-difluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)hexyl)isoquinoline-1(2H)-one; (S)-6-(4-amino-5,7-dihydrofurano[3,4-d]pyrimidin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-6-(4-amino-7,7-dimethyl-5,7-dihydrofurano[3,4-d]pyrimidin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-6-(4-amino-5-chloropyrimidin-2-yl)-7,8-difluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)hexyl)isoquinoline-1(2H)-one; (S)-6-(4-amino-5-(difluoromethoxy)pyrimidin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)hexyl)isoquinoline-1(2H)-one; (S)-6-(4-amino-5-(difluoromethoxy)pyrimidin-2-yl)-7,8-difluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)hexyl)isoquinoline-1(2H)-one; (S)-6-(6-amino-5-(trifluoromethyl)pyrazin-2-yl)-7,8-difluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)hexyl)isoquinoline-1(2H)-one; (S)-6-(4-aminoquinazoline-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-7-(4-amino-5-(difluoromethoxy)pyrimidin-2-yl)-6-fluoro-3-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)hexyl)quinazolin-4(3H)-one; (S)-6-(4-amino-1,3,5-triazin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-6-(4-amino-6-methyl-1,3,5-triazin-2-yl)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one; (S)-7-(4-amino-5-(difluoromethoxy)pyrimidin-2-yl)-6-fluoro-3-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)quinazolin-4(3H)-one; (R)-6-(6-amino-5-(difluoromethyl)pyridin-2-yl)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7-fluoroisoquinoline-1(2H)-one; (R)-6-(4-amino-5-(difluoromethoxy)pyrimidin-2-yl)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7-fluoroisoquinoline-1(2H)-one; (R)-6-(4-amino-5-methoxypyrimidin-2-yl)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7-fluoroisoquinoline-1(2H)-one; (R)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-6-(5-(difluoromethoxy)pyrazin-2-yl)-7-fluoroisoquinoline-1(2H)-one; (R)-3-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7-(5-(difluoromethyl)pyrazin-2-yl)-6-fluoroquinazoline-4(3H)-one; (R)-3-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7-(5-(difluoromethoxy)pyrazin-2-yl)-6-fluoroquinazoline-4(3H)-one; (R)-7-(4-amino-5-(difluoromethoxy)pyrimidin-2-yl)-3-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-6-fluoroquinazoline-4(3H)-one; (R)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7,8-difluoro-6-(5-(trifluoromethyl)pyrimidin-2-yl)isoquinoline-1(2H)-one; (R)-6-(4-amino-5-(difluoromethyl)pyrimidin-2-yl)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7-fluoroisoquinoline-1(2H)-one; (R)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-6-(5-(difluoromethyl)pyrimidin-2-yl)-7-fluoroisoquinoline-1(2H)-one; (R)-6-(4-amino-5-chloropyrimidin-2-yl)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7-fluoroisoquinoline-1(2H)-one; (R)-6-(4-amino-5-(trifluoromethyl)pyrimidin-2-yl)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7-fluoroisoquinoline-1(2H)-one; (R)-6-(6-amino-5-(trifluoromethyl)pyridin-2-yl)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7-fluoroisoquinoline-1(2H)-one; (R)-6-(5-chloropyrimidin-2-yl)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7-fluoroisoquinoline-1(2H)-one; (R)-3-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-6-fluoro-7-(5-(trifluoromethyl)pyrimidin-2-yl)quinazolin-4(3H)-one; (R)-7-(4-amino-5-(difluoromethyl)pyrimidin-2-yl)-3-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-6-fluoroquinazoline-4(3H)-one; (R)-3-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7-(5-(difluoromethyl)pyrimidin-2-yl)-6-fluoroquinazoline-4(3H)-one; (R)-7-(4-amino-5-(trifluoromethyl)pyrimidin-2-yl)-3-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-6-fluoroquinazoline-4(3H)-one; (R)-6-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-2-(5-(trifluoromethyl)pyridin-2-yl)-1,6-naphthidium-5(6H)-one; (R)-6-(4-amino-5-(difluoromethyl)pyrimidin-2-yl)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7,8-difluoroisoquinoline-1(2H)-one; (R)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-6-(5-(difluoromethyl)pyrimidin-2-yl)-7,8-difluoroisoquinoline-1(2H)-one; (R)-6-(4-amino-5-(trifluoromethyl)pyrimidin-2-yl)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7,8-difluoroisoquinoline-1(2H)-one; (R)-7-(6-amino-5-(trifluoromethyl)pyridin-2-yl)-3-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-6-fluoroquinazoline-4(3H)-one; (R)-6-(4-amino-5-chloropyrimidin-2-yl)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7,8-difluoroisoquinoline-1(2H)-one; (R)-6-(5-chloropyrimidin-2-yl)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7,8-difluoroisoquinoline-1(2H)-one; (R)-7-(4-amino-5-methoxypyrimidin-2-yl)-3-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-6-fluoroquinazoline-4(3H)-one; (R)-7-(5-chloropyrimidin-2-yl)-3-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-6-fluoroquinazoline-4(3H)-one; (R)-7-(6-amino-5-(difluoromethyl)pyridin-2-yl)-3-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-6-fluoroquinazoline-4(3H)-one; (R)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7-fluoro-6-(5-(trifluoromethyl)thiazo-2-yl)isoquinoline-1(2H)-one; (R)-6-(4-amino-5-(difluoromethoxy)pyrimidin-2-yl)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7,8-difluoroisoquinoline-1(2H)-one; (R)-3-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7-(3,4-dihydro-2H-pyran-6-yl)-6-fluoroquinazoline-4(3H)-one; (R)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7-fluoro-6-(5-(trifluoromethyl)pyridin-2-yl)isoquinoline-1(2H)-one; (R)-6-(5-amino-6-(trifluoromethyl)pyridin-3-yl)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7-fluoroisoquinoline-1(2H)-one; (R)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-6-(5-(difluoromethyl)pyridin-2-yl)-7-fluoroisoquinoline-1(2H)-one; (R)-3-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7-(5-(difluoromethyl)pyridin-2-yl)-6-fluoroquinazoline-4(3H)-one; (R)-3-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-6-fluoro-7-(5-(trifluoromethyl)pyridin-2-yl)quinazolin-4(3H)-one; (R)-3-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7-(5-(trifluoromethyl)pyridin-2-yl)pyridino[2,3-d]pyrimidin-4(3H)-one; (R)-2-(6-amino-5-(trifluoromethyl)pyridin-2-yl)-6-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-1,6-naphthidium-5(6H)-one; (R)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-6-(5-(difluoromethyl)pyridin-2-yl)-7,8-difluoroisoquinoline-1(2H)-one; (R)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7,8-difluoro-6-(5-(trifluoromethyl)pyridin-2-yl)isoquinoline-1(2H)-one; (R)-6-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-2-(5-(difluoromethyl)pyridin-2-yl)-1,6-naphthidium-5(6H)-one; (R)-6-(6-amino-5-fluoropyridin-2-yl)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7-fluoroisoquinoline-1(2H)-one; (R)-6-(6-amino-5-chloropyridin-2-yl)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7-fluoroisoquinoline-1(2H)-one; (R)-6-(6-amino-5-methylpyridin-2-yl)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7-fluoroisoquinoline-1(2H)-one; (R)-7-(5-cyclopropylpyrazin-2-yl)-3-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-6-fluoroquinazoline-4(3H)-one; (R)-7-(4-amino-5-chloro-6-cyclopropylpyrimidin-2-yl)-3-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-6-fluoroquinazoline-4(3H)-one; (R)-6-(6-amino-5-methoxypyrazin-2-yl)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7-fluoroisoquinoline-1(2H)-one; (R)-6-(6-amino-5-(trifluoromethyl)pyrazin-2-yl)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7-fluoroisoquinoline-1(2H)-one; (R)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7-fluoro-6-(5-(trifluoromethyl)pyrazin-2-yl)isoquinoline-1(2H)-one; (R)-6-(6-amino-5-(trifluoromethyl)pyrazin-2-yl)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7,8-difluoroisoquinoline-1(2H)-one; (R)-7-(6-amino-5-(trifluoromethyl)pyrazin-2-yl)-3-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-6-fluoroquinazoline-4(3H)-one; (R)-3-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-6-fluoro-7-(5-(trifluoromethyl)pyrazin-2-yl)quinazolin-4(3H)-one; (R)-6-(5-amino-1H-1,2,4-triazol-3-yl)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7-fluoroisoquinoline-1(2H)-one; (R)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-6-(5-(difluoromethyl)pyrazin-2-yl)-7-fluoroisoquinoline-1(2H)-one; (R)-3-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7-(3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-6-fluoroquinazolin-4(3H)-one; (R)-7-(4-amino-5-chloropyrimidin-2-yl)-3-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-6-fluoroquinazoline-4(3H)-one; 6-[4-amino-5-(trifluoromethyl)pyrimidin-2-yl]-7-fluoro-2-[(4R)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]-5-(trideuteratedmethoxy)pentyl]isoquinoline-1-one; 6-[5-(difluoromethyl)pyrimidin-2-yl]-7-fluoro-2-[(4R)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]-5-(trideuteromethoxy)pentyl]isoquinoline-1-one; 6-[4-amino-5-(difluoromethyl)pyrimidin-2-yl]-7-fluoro-2-[(4R)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]-5-(trideuteromethoxy)pentyl]isoquinoline-1-one; 6-Fluoro-3-[(4R)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]-5-(trideuteromethoxy)pentyl]-7-[5-(trifluoromethyl)pyrimidin-2-yl]quinazolin-4-one; 7-[5-(difluoromethyl)pyrimidin-2-yl]-6-fluoro-3-[(4R)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]-5-(trideuteromethoxy)pentyl]quinazolin-4-one; 7-[4-amino-5-(trifluoromethyl)pyrimidin-2-yl]-6-fluoro-3-[(4R)-4-[[6-oxo-5-(trifluoromethyl)-1-(2-trimethylsilylethoxymethyl)pyridazin-4-yl]amino]-5-(trideuteroxy)pentyl]quinazolin-4-one; 7-[4-amino-5-(difluoromethyl)pyrimidin-2-yl]-6-fluoro-3-[(4R)-4-[[6-oxo-5-(trifluoromethyl)-1-(2-trimethylsilylethoxymethyl)pyridazin-4-yl]amino]-5-(trideuteroxy)pentyl]quinazolin-4-one; 7-Fluoro-2-[(4R)-4-[[6-oxo-5-(trifluoromethyl)-1-(2-trimethylsilylethoxymethyl)pyridazin-4-yl]amino]-5-(trideuteroxy)pentyl]-6-[5-(trifluoromethyl)-2-pyridyl]isoquinoline-1-one; (R)-7-fluoro-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)-5-(trifluoromethoxy)pentyl)-6-(5-(trifluoromethyl)pyrimidin-2-yl)isoquinoline-1(2H)-one; (R)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7-fluoro-6-(5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)isoquinoline-1(2H)-one; 7-Fluoro-2-((3S,4S)-3-hydroxy-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-6-(5-(trifluoromethyl)pyrimidin-2-yl)isoquinoline-1(2H)-one; 7-Fluoro-2-((3R,4S)-3-hydroxy-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-6-(5-(trifluoromethyl)pyrimidin-2-yl)isoquinoline-1(2H)-one; (R)-7-fluoro-2-(6,6,6-trifluoro-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)hexyl)-6-(5-(trifluoromethyl)pyrimidin-2-yl)isoquinoline-1(2H)-one; (R)-7-(6-amino-5-(trifluoromethyl)pyrazin-2-yl)-3-(4-cyclopropyl-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)butyl)-6-fluoroquinazoline-4(3H)-one; (R)-7-(4-amino-5-chloropyrimidin-2-yl)-3-(4-cyclopropyl-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)butyl)-6-fluoroquinazoline-4(3H)-one; (R)-7-(4-amino-5-(difluoromethyl)pyrimidin-2-yl)-3-(4-cyclopropyl-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)butyl)-6-fluoroquinazoline-4(3H)-one; (R)-2-(6-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)hexyl)-7-fluoro-6-(5-(trifluoromethyl)pyrimidin-2-yl)isoquinoline-1(2H)-one; (R)-6-(4-amino-5-(trifluoromethyl)pyrimidin-2-yl)-2-(6-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)hexyl)-7-fluoroisoquinoline-1(2H)-one; (R)-3-(4-cyclopropyl-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)butyl)-7-(5-(difluoromethyl)pyrimidin-2-yl)-6-fluoroquinazoline-4(3H)-one; (R)-7-(4-amino-5-(trifluoromethyl)pyrimidin-2-yl)-3-(4-cyclopropyl-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)butyl)-6-fluoroquinazoline-4(3H)-one; (R)-7-(5-chloropyrimidin-2-yl)-3-(4-cyclopropyl-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)butyl)-6-fluoroquinazoline-4(3H)-one; (R)-3-(4-cyclopropyl-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)butyl)-6-fluoro-7-(5-(trifluoromethyl)pyrimidin-2-yl)quinazolin-4(3H)-one; (R)-7-(4-amino-5-(difluoromethoxy)pyrimidin-2-yl)-3-(4-cyclopropyl-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)butyl)-6-fluoroquinazoline-4(3H)-one; 7-Fluoro-2-((4S)-2-hydroxy-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-6-(5-(trifluoromethyl)pyrimidin-2-yl)isoquinoline-1(2H)-one; 7-Fluoro-2-((2S,4S)-2-hydroxy-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-6-(5-(trifluoromethyl)pyrimidin-2-yl)isoquinoline-1(2H)-one; 7-Fluoro-2-((2R,4S)-2-hydroxy-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-6-(5-(trifluoromethyl)pyrimidin-2-yl)isoquinoline-1(2H)-one; (R)-6-([1,2,4]triazolo[1,5-a]pyridin-2-yl)-2-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-7-fluoroisoquinoline-1(2H)-one; (R)-7-([1,2,4]triazolo[1,5-a]pyridin-2-yl)-3-(5-(difluoromethoxy)-4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)-6-fluoroquinazoline-4(3H)-one; 6-Fluoro-7-(5-methoxypyrimidin-2-yl)-3-[[(1R,3S)-3-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]cyclohexyl]methyl]quinazolin-4-one; or (S)-7-fluoro-6-(5-methyl-6-(trifluoromethyl)pyridin-2-yl)-2-(4-((6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl)amino)pentyl)isoquinoline-1(2H)-one.
2. The compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein R 1 It is methyl, ethyl, -CH2OCF2H, -CH2OCH3, -CF3 or -CH2OH.
3. The compound according to claim 1 or claim 2, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein R 2 It is H, halogen, C 1-6 Alkyl, -OH or -O (C 1-6 alkyl).
4. The compound according to any one of claims 1 to 3, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein R 3a and R 3b Each can be independently H, F, -OH, -OCH3, or methyl.
5. The compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein J is: 。 6. The compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein Z is reacted with one or more R 7 Substituted 5-12 heteroaryl groups.
7. The compound according to any one of claims 1 to 6, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein Z is: or , Where w is zero to three, inclusive; and t is zero to four, inclusive; and where R 7 Combined to any replaceable position on Z.
8. The compound according to any one of claims 1 to 6, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein Z is: , , , , , , , , , , , , , , , , , , , , or .
9. The compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein R 3a It is H, and R 3b It is F.
10. The compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein R 3a It is H, and R 3b It is -OH or methyl.
11. The compound according to any one of claims 1 to 10, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein A is NH.
12. The compound according to any one of claims 1 to 10, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein A is O.
13. The compound of claim 4, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein J is selected from the group consisting of: and .
14. The compound according to claim 4, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein J is: or .
15. The compound according to claim 4, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein J is: or .
16. The compound according to claim 4, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein J is: or .
17. The compound according to any one of claims 13 to 16, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein R 1 It is a methyl group.
18. The compound according to any one of claims 13 to 17, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein Z is: , , , , , , , , , , , , , , , , , , , , or .
19. The compound according to any one of claims 13 to 18, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein A is NH.
20. The compound according to any one of claims 13 to 18, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein A is O.
21. The compound according to any one of claims 13 to 20, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein R 2 It is H.
22. The compound according to any one of claims 13 to 20, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein R 2 It is -OH.
23. The compound according to any one of claims 13 to 22, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein R 3a It is H, and R 3b It is F.
24. The compound according to any one of claims 13 to 22, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein R 3a It is H, and R 3b It is -OH or methyl.
25. The compound according to claim 4, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein J is: or .
26. The compound according to claim 4, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein J is: or .
27. The compound according to claim 25 or claim 26, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein R 1 It is ethyl or -CH2(OCHF2).
28. The compound according to any one of claims 25 to 27, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein Z is: , , , , , , , , , , , , , , , , , , , , or .
29. The compound according to any one of claims 25 to 28, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein A is NH.
30. The compound according to any one of claims 25 to 28, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein A is O.
31. The compound according to any one of claims 25 to 30, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein R 2 It is H.
32. The compound according to any one of claims 25 to 30, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein R 2 It is -OH.
33. The compound according to any one of claims 25 to 32, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein R 3a It is H, and R 3b It is F.
34. The compound according to any one of claims 25 to 32, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein R 3a It is H, and R 3b It is -OH or methyl.
35. The compound according to any one of claims 25 to 32, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, wherein R 3a and R 3b It is H.
36. The compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, selected from: 。 37. A compound, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analogue thereof, selected from Table 1 or Table 2.
38. A pharmaceutical composition comprising a compound according to any one of claims 1 to 37, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers or deuterated analog thereof, and a pharmaceutically acceptable excipient.
39. A method of treating cancer, the method comprising administering to a patient in need an effective amount of a compound according to any one of claims 1 to 37, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers or deuterated analogue thereof, or a pharmaceutical composition according to claim 38.