US 12,071,441 B2
10-(di(phenyl)methyl)-4-hydroxy-8,9,9A,10-tetrahydro-7H-pyrrolo[1′,2′:4,5]pyrazino[1,2-b]pyridazine-3,5-dione derivatives and related compounds as inhibitors of the orthomyxovirus replication for treating influenza
Maxime Dauphinais, Emeryville, CA (US); Rama Jain, Emeryville, CA (US); Dennis Christofer Koester, Emeryville, CA (US); James R. Manning, Emeryville, CA (US); Vanessa Marx, Emeryville, CA (US); Daniel Poon, Emeryville, CA (US); Lifeng Wan, Emeryville, CA (US); Xiaojing Michael Wang, Livermore, CA (US); Aregahegn Yifru, Benicia, CA (US); and Qian Zhao, Louisville, CO (US)
Assigned to Novartis AG, Basel (CH)
Filed by Novartis AG, Basel (CH)
Filed on Feb. 27, 2023, as Appl. No. 18/114,336.
Application 18/114,336 is a continuation of application No. 16/975,784, granted, now 11,629,149, previously published as PCT/IB2019/051549, filed on Feb. 26, 2019.
Claims priority of provisional application 62/636,378, filed on Feb. 28, 2018.
Prior Publication US 2023/0322793 A1, Oct. 12, 2023
Int. Cl. C07D 487/14 (2006.01); C07D 498/14 (2006.01)
CPC C07D 487/14 (2013.01) [C07D 498/14 (2013.01)] 4 Claims
 
1. A compound, or a pharmaceutically acceptable salt thereof, selected from:
 
43
 

OG Complex Work Unit Chemistry
 (9aR,10S)-10- ((R)-(2,3- difluorophenyl) (phenyl)methyl)-4- ((5-methyl-2-oxo- 1,3-dioxol-4- yl)methoxy)-8,9,9a, 10-tetrahydro- 7H-pyrrolo [1′,2′:4,5] pyrazino[1,2-b] pyridazine- 3,5-dione;
 
65
 

OG Complex Work Unit Chemistry
 (9aR,10S)-10- ((R)-(2,3- difluorophenyl) (phenyl)methyl)-3,5- dioxo-3,5,8,9,9a, 10-hexahydro-7H- pyrrolo[1′,2′:4,5] pyrazino[1,2-b] pyridazin-4-yl [1,4′-bipiperidine]- 1′-carboxylate;
 
73
 

OG Complex Work Unit Chemistry
 (9aR,10S)-10- ((R)-(2,3- difluorophenyl) (phenyl)methyl)-3,5- dioxo-3,5,8,9,9a, 10-hexahydro-7H- pyrrolo[1′,2′:4,5] pyrazino[1,2-b] pyridazin-4-yl 2-(tetrahydro-2H- pyran-4-yl)acetate;
 
79
 

OG Complex Work Unit Chemistry
 (((9aR,10S)-10- ((R)-(2,3- difluorophenyl) (phenyl)methyl)-3,5- dioxo-3,5,8,9,9a, 10-hexahydro-7H- pyrrolo[1′,2′:4,5] pyrazino[1,2-b] pyridazin-4-yl) oxy)methyl [1,4′- bipiperidine]- 1′-carboxylate;
 
80
 

OG Complex Work Unit Chemistry
 (9aR,10S)-10- ((R)-(2,3- difluorophenyl)(4- fluorophenyl) methyl)-4-((5-methyl- 2-oxo-1,3-dioxol-4-yl) methoxy)- 8,9,9a,10-tetrahydro- 7H-pyrrolo[1′,2′:4,5] pyrazino[1,2-b] pyridazine-3,5-dione;
 
102
 

OG Complex Work Unit Chemistry
 (9aR,10S)-10-((R)- (2,3-difluorophenyl) (3-fluorophenyl) methyl)-3,5-dioxo- 3,5,8,9,9a,10-hexahydro- 7H-pyrrolo[1′,2′:4,5] pyrazino[1,2-b] pyridazin-4-yl [1,4′-bipiperidine]- 1′-carboxylate;
 
116
 

OG Complex Work Unit Chemistry
 (9aR,10S)-10-((R)- (2,3-difluorophenyl)(3- fluorophenyl)methyl)- 4-((5-methyl- 2-oxo-1,3-dioxol-4-yl) methoxy)- 8,9,9a,10-tetrahydro- 7H-pyrrolo[1′,2′:4,5] pyrazino[1,2-b] pyridazine-3,5-dione.