US 12,071,412 B2
Caspase inhibitors and methods of use thereof
Alfred P. Spada, Carlsbad, CA (US); Robert J. Temansky, San Diego, CA (US); and Michael Mueller, San Diego, CA (US)
Assigned to NOBO Medicine Inc., Seoul (KR)
Filed by NOBO Medicine Inc., Seoul (KR)
Filed on Feb. 1, 2023, as Appl. No. 18/104,691.
Application 18/104,691 is a continuation of application No. 16/812,063, filed on Mar. 6, 2020, granted, now 11,597,703.
Claims priority of provisional application 62/815,270, filed on Mar. 7, 2019.
Prior Publication US 2023/0250067 A1, Aug. 10, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 239/42 (2006.01); A61P 29/00 (2006.01); C07C 233/56 (2006.01); C07D 213/75 (2006.01); C07D 215/38 (2006.01); C07D 215/40 (2006.01); C07D 217/24 (2006.01); C07D 239/34 (2006.01); C07D 257/04 (2006.01)
CPC C07D 239/42 (2013.01) [A61P 29/00 (2018.01); C07C 233/56 (2013.01); C07D 213/75 (2013.01); C07D 215/38 (2013.01); C07D 215/40 (2013.01); C07D 217/24 (2013.01); C07D 239/34 (2013.01); C07D 257/04 (2013.01)] 3 Claims
 
1. A compound selected from
N1—((S)-1-(((S)-5-(Benzyloxy)-2-oxo-1-(2,3,5,6-tetrafluorophenoxy)pentan-3-yl)amino)-1-oxopropan-2-yl)-N2-(2,6-difluorophenyl)oxalamide;
N1-(2,6-Difluorophenyl)-N2—((S)-1-(((S)-5-hydroxy-2-oxo-1-(2,3,5,6-tetrafluorophenoxy)pentan-3-yl)amino)-1-oxopropan-2-yl)oxalamide;
N1—((S)-1-(((S)-5-((4-Chlorobenzyl)oxy)-2-oxo-1-(2,3,5,6-tetrafluorophenoxy)pentan-3-yl)amino)-1-oxopropan-2-yl)-N2-(2,6-difluorophenyl)oxalamide;
N1-(2,6-difluorophenyl)-N2—((S)-1-oxo-1-(((S)-2-oxo-1-(2,3,5,6-tetrafluorophenoxy)-5-(thiophen-3-ylmethoxy)pentan-3-yl)amino)propan-2-yl)oxalamide;
N1-(2,6-Difluorophenyl)-N2—((S)-1-(((S)-5-methoxy-2-oxo-1-(2,3,5,6-tetrafluorophenoxy)pentan-3-yl)amino)-1-oxopropan-2-yl)oxalamide;
(S)-4-((S)-2-(2-((2,6-Difluorophenyl)amino)-2-oxoacetamido)propanamido)-5-oxo-6-(2,3,5,6-tetrafluorophenoxy)hexanoic acid;
(S)-3-((S)-2-(2-((2,6-Difluorophenyl)amino)-2-oxoacetamido)propanamido)-4-oxo-5-(2,3,5,6-tetrafluorophenoxy)pentyl phenyl carbonate;
(S)-3-((S)-2-(2-((2,6-Difluorophenyl)amino)-2-oxoacetamido)propanamido)-4-oxo-5-(2,3,5,6-tetrafluorophenoxy)pentyl benzoate;
(S)-4-(2-(2-((2,6-difluorophenyl)amino)-2-oxoacetamido)acetamido)-5-oxo-6-(2,3,5,6-tetrafluorophenoxy)hexanoic acid;
(S)-6-(3,5-bis(trifluoromethyl)phenoxy)-4-((S)-2-(2-((2,6-difluorophenyl)amino)-2-oxoacetamido)propanamido)-5-oxohexanoic acid;
(S)-4-((S)-2-(2-((2-(tert-Butyl)phenyl)amino)-2-oxoacetamido)propanamido)-5-oxo-6-(2,3,5,6-tetrafluorophenoxy)hexanoic acid;
(S)-4-(2-(2-((2,6-Difluorophenyl)amino)-2-oxoacetamido)-2-methylpropanamido)-5-oxo-6-(2,3,5,6-tetrafluorophenoxy)hexanoic acid;
(S)-5-((S)-2-(2-((2,6-Difluorophenyl)amino)-2-oxoacetamido)propanamido)-6-oxo-7-(2,3,5,6-tetrafluorophenoxy)heptanoic acid;
(S)-4-(1-(2-((2,6-Difluorophenyl)amino)-2-oxoacetamido)cyclopentane-1-carboxamido)-5-oxo-6-(2,3,5,6-tetrafluorophenoxy)hexanoic acid;
(S)-4-((S)-2-(2-((2,6-Difluorophenyl)amino)-2-oxoacetamido)propanamido)-5-oxo-6-((2-(trifluoromethyl)pyrimidin-4-yl)oxy)hexanoic acid;
(S)-4-(2-(7-Chloro-1-oxoisoquinolin-2(1H)-yl)acetamido)-5-oxo-6-(2,3,5,6-tetrafluorophenoxy)hexanoic acid;
(S)-4-((S)-2-(2-((4-fluorophenyl)amino)-2-oxoacetamido)propanamido)-5-oxo-6-(2,3,5,6-tetrafluorophenoxy)hexanoic acid;
(S)-4-((S)-2-(2-((3-fluorophenyl)amino)-2-oxoacetamido)propanamido)-5-oxo-6-(2,3,5,6-tetrafluorophenoxy)hexanoic acid;
(S)-4-((S)-2-(2-((4-methylphenyl)amino)-2-oxoacetamido)propanamido)-5-oxo-6-(2,3,5,6-tetrafluorophenoxy)hexanoic acid;
(S)-4-((S)-2-(2-((3-methylphenyl)amino)-2-oxoacetamido)propanamido)-5-oxo-6-(2,3,5,6-tetrafluorophenoxy)hexanoic acid;
(S)-4-((S)-2-(2-((2-methylphenyl)amino)-2-oxoacetamido)propanamido)-5-oxo-6-(2,3,5,6-tetrafluorophenoxy)hexanoic acid;
(S)-4-((S)-2-(2-((2-methyoxyphenyl)amino)-2-oxoacetamido)propanamido)-5-oxo-6-(2,3,5,6-tetrafluorophenoxy)hexanoic acid;
(S)-4-((S)-2-(2-((3-methyoxyphenyl)amino)-2-oxoacetamido)propanamido)-5-oxo-6-(2,3,5,6-tetrafluorophenoxy)hexanoic acid;
(S)-4-((S)-2-(2-((4-methyoxyphenyl)amino)-2-oxoacetamido)propanamido)-5-oxo-6-(2,3,5,6-tetrafluorophenoxy)hexanoic acid;
(S)-4-((S)-2-(2-((5-methylpyridin-2-yl)amino)-2-oxoacetamido)propanamido)-5-oxo-6-(2,3,5,6-tetrafluorophenoxy)hexanoic acid;
(S)-5-oxo-4-((S)-2-(2-oxo-2-((3-(trifluoromethyl)phenyl)amino)acetamido)propanamido)-6-(2,3,5,6-tetrafluorophenoxy)hexanoic acid;
(S)-5-oxo-4-((S)-2-(2-oxo-2-((4-(trifluoromethyl)phenyl)amino)acetamido)propanamido)-6-(2,3,5,6-tetrafluorophenoxy)hexanoic acid;
benzyl (S)-4-((S)-2-(2-((2,6-difluorophenyl)amino)-2-oxoacetamido)propanamido)-5-oxo-6-(2,3,5,6-tetrafluorophenoxy)hexanoate;
(S)-4-((S)-2-(2-((5-chloropyridin-2-yl)amino)-2-oxoacetamido)propanamido)-5-oxo-6-(2,3,5,6-tetrafluorophenoxy)hexanoic acid;
(S)-4-((S)-2-(2-((4-acetylphenyl)amino)-2-oxoacetamido)propanamido)-5-oxo-6-(2,3,5,6-tetrafluorophenoxy)hexanoic acid;
(S)-4-((S)-2-(2-((3-(1H-tetrazol-5-yl)phenyl)amino)-2-oxoacetamido)propanamido)-5-oxo-6-(2,3,5,6-tetrafluorophenoxy)hexanoic acid;
(S)-4-((S)-2-(2-((2-cyanophenyl)amino)-2-oxoacetamido)propanamido)-5-oxo-6-(2,3,5,6-tetrafluorophenoxy)hexanoic acid;
(S)-6-((2,6-bis(trifluoromethyl)pyrimidin-4-yl)oxy)-4-((S)-2-(2-((2,6-difluorophenyl)amino)-2-oxoacetamido)propanamido)-5-oxohexanoic acid;
(S)-5-oxo-4-((S)-2-(2-oxo-2-((4-(trifluoromethoxy)phenyl)amino)acetamido)propanamido)-6-(2,3,5,6-tetrafluorophenoxy)hexanoic acid;
(S)-5-oxo-4-((S)-2-(2-oxo-2-(quinolin-3-ylamino)acetamido)propanamido)-6-(2,3,5,6-tetrafluorophenoxy)hexanoic acid;
(S)-4-((S)-2-(2-(naphthalen-1-ylamino)-2-oxoacetamido)propanamido)-5-oxo-6-(2,3,5,6-tetrafluorophenoxy)hexanoic acid;
(S)-5-oxo-4-((S)-2-(2-oxo-2-(quinolin-8-ylamino)acetamido)propanamido)-6-(2,3,5,6-tetrafluorophenoxy)hexanoic acid;
(S)-5-oxo-4-((S)-2-(2-oxo-2-(pyridin-4-ylamino)acetamido)propanamido)-6-(2,3,5,6-tetrafluorophenoxy)hexanoic acid;
(R)-4-((S)-2-(2-((2,6-difluorophenyl)amino)-2-oxoacetamido)propanamido)-5-oxo-6-(2,3,5,6-tetrafluorophenoxy)hexanoic acid;
(S)-5-oxo-4-((S)-2-(2-oxo-2-(pyridin-2-ylamino)acetamido)propanamido)-6-(2,3,5,6-tetrafluorophenoxy)hexanoic acid;
(S)-5-oxo-4-((S)-2-(2-oxo-2-(pyridin-3-ylamino)acetamido)propanamido)-6-(2,3,5,6-tetrafluorophenoxy)hexanoic acid;
(S)-4-((S)-2-(2-((4,6-dimethylpyrimidin-2-yl)amino)-2-oxoacetamido)propanamido)-5-oxo-6-(2,3,5,6-tetrafluorophenoxy)hexanoic acid;
(S)-5-oxo-4-((S)-2-(2-oxo-2-(pyrimidin-2-ylamino)acetamido)propanamido)-6-(2,3,5,6-tetrafluorophenoxy)hexanoic acid; and
N1-(2,6-difluorophenyl)-N2—((S)-1-(((S)-6-(hydroxyamino)-2,6-dioxo-1-(2,3,5,6-tetrafluorophenoxy)hexan-3-yl)amino)-1-oxopropan-2-yl)oxalamide.