US 11,834,450 B2
Compounds having ((3-nitrophenyl)sulfonyl)acetamide as BCL-2 inhibitors
Volodymyr Kysil, San Diego, CA (US); Vladislav Zenonovich Parchinsky, Moscow (RU); Alexei Pushechnikov, San Diego, CA (US); Alexandre Vasilievich Ivachtchenko, Hallandale Beach, FL (US); Ruben Abagyan, La Jolla, CA (US); Andrew Orry, San Diego, CA (US); Polo Chun-Hung Lam, San Diego, CA (US); and Nikolay Savchuk, San Diego, CA (US)
Assigned to EIL THERAPEUTICS, INC., San Diego, CA (US)
Filed by Eil Therapeutics, Inc., San Diego, CA (US)
Filed on Mar. 18, 2022, as Appl. No. 17/698,956.
Claims priority of provisional application 63/163,326, filed on Mar. 19, 2021.
Prior Publication US 2022/0306625 A1, Sep. 29, 2022
Int. Cl. C07D 471/04 (2006.01); C07D 405/14 (2006.01); A61K 45/06 (2006.01); C07D 519/00 (2006.01); C07D 405/12 (2006.01)
CPC C07D 471/04 (2013.01) [A61K 45/06 (2013.01); C07D 405/12 (2013.01); C07D 405/14 (2013.01); C07D 519/00 (2013.01)] 9 Claims
 
1. A compound selected from:
 
Com-
 
 
pound
 
 
No Structure Name
 
 1
 

OG Complex Work Unit Chemistry
 4-[4-[[1-(4-chlorophenyl)-3-oxo- 2-azaspiro[3.4]octan-2-yl]methyl]- 1-piperidyl]-N-[3-nitro-4- (tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-2- (1H-pyrrolo[2,3-b]pyridin-5- yloxy)benzamide
 
 2
 

OG Complex Work Unit Chemistry
 N-[3-nitro-4-(tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-4- [4-[(3-oxo-1-phenyl-2- azaspiro[3.4]octan-2-yl)methyl]-1- piperidyl]-2-(1H-pyrrolo[2,3- b]pyridin-5-yloxy)benzamide
 
 3
 

OG Complex Work Unit Chemistry
 4-[4-[[1-(4-chloro-2-methyl- phenyl)-3-oxo-2- azaspiro[3.4]octan-2-yl]methyl]-1- piperidyl]-N-[3-nitro-4- (tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-2- (1H-pyrrolo[2,3-b]pyridin-5- yloxy)benzamide
 
 5
 

OG Complex Work Unit Chemistry
 4-[4-[[(3S)-2- (cyclopropanecarbonyl)-3,4- dihydro-1H-isoquinolin-3- yl]methyl]piperazin-1-yl]-N-[3- nitro-4-(tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-2- (1H-pyrrolo[2,3-b]pyridin-5- yloxy)benzamide
 
 6
 

OG Complex Work Unit Chemistry
 N-[3-nitro-4-(tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-2- (1H-pyrrolo[2,3-b]pyridin-5- yloxy)-4-[4-[[2-(thiophene-2- carbonyl)-3,4-dihydro-1H- isoquinolin-3-yl]methyl]piperazin- 1-yl]benzamide
 
 8
 

OG Complex Work Unit Chemistry
 4-[4-[[2-(2-methylpropanoyl)-3,4- dihydro-1H-isoquinolin-3- yl]methyl]piperazin-1-yl]-N-[3- nitro-4-(tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-2- (1H-pyrrolo[2,3-b]pyridin-5- yloxy)benzamide
 
 9
 

OG Complex Work Unit Chemistry
 4-[4-[[1-(5-chloro-3-pyridyl)-3- oxo-2-azaspiro[3.4]octan-2- yl]methyl]-1-piperidyl]-N-[3- nitro-4-(tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-2- (1H-pyrrolo[2,3-b]pyridin-5- yloxy)benzamide
 
10
 

OG Complex Work Unit Chemistry
 4-[4-[[1-(4-chlorophenyl)-3-oxo- 2-azaspiro[3.4]octan-2-yl]methyl]- 1-piperidyl]-2-(1H-indol-5-yloxy)- N-[3-nitro-4-(tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl- benzamide
 
20
 

OG Complex Work Unit Chemistry
 4-[4-[[7-chloro-2- (cyclopropanecarbonyl)-3,4- dihydro-1H-isoquinolin-3- yl]methyl]piperazin-1-yl]-N-[3- nitro-4-(tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-2- (1H-pyrrolo[2,3-b]pyridin-5- yloxy)benzamide
 
21
 

OG Complex Work Unit Chemistry
 4-[4-[[7-chloro-2-(pyrrolidine-3- carbonyl)-3,4-dihydro-1H- isoquinolin-3-yl]methyl]piperazin- 1-yl]-N-[3-nitro-4- (tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-2- (1H-pyrrolo[2,3-b]pyridin-5- yloxy)benzamide
 
22
 

OG Complex Work Unit Chemistry
 4-[4-[[6-chloro-2- (cyclopropanecarbonyl)-3,4- dihydro-1H-isoquinolin-3- yl]methyl]piperazin-1-yl]-N-[3- nitro-4-(tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-2- (1H-pyrrolo[2,3-b]pyridin-5- yloxy)benzamide
 
23
 

OG Complex Work Unit Chemistry
 4-[4-[[2-(azetidine-3-carbonyl)-7- chloro-3,4-dihydro-1H- isoquinolin-3-yl]methyl]piperazin- 1-yl]-N-[3-nitro-4- (tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-2- (1H-pyrrolo[2,3-b]pyridin-5- yloxy)benzamide
 
24
 

OG Complex Work Unit Chemistry
 4-[4-[[6-(cyclopropanecarbonyl)- 7,8-dihydro-5H-[1,3]dioxolo[4,5- g]isoquinolin-7- yl]methyl]piperazin-1-yl]-N-[3- nitro-4-(tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-2- (1H-pyrrolo[2,3-b]pyridin-5- yloxy)benzamide
 
25
 

OG Complex Work Unit Chemistry
 4-[4-[[7-chloro-2-(oxetane-3- carbonyl)-3,4-dihydro-1H- isoquinolin-3-yl]methyl]piperazin- 1-yl]-N-[3-nitro-4- (tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-2- (1H-pyrrolo[2,3-b]pyridin-5- yloxy)benazmide
 
26
 

OG Complex Work Unit Chemistry
 4-[4-[[1-(3-[[1-(3- benzyloxyphenyl)-3-oxo-2- azaspiro[3.4]octan-2-yl]methyl]-1- piperidyl]-N-[4-(3-chloro-4- methyl-anilino)-3-nitro- phenyl]sulfonyl-2-(1H-indol-5- yloxy)benzamide
 
27
 

OG Complex Work Unit Chemistry
 N-[3-nitro-4-(tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-4- [4-[(3-phenyl-2- azaspiro[3.4]octan-2-yl)methyl]-1- piperidyl]-2-(1H-pyrrolo[2,3- b]pyridin-5-yloxy)benzamide
 
33
 

OG Complex Work Unit Chemistry
 4-[4-[[(3R)-2- (cyclopropanecarbonyl)-3,4- dihydro-1H-isoquinolin-3- yl]methyl]piperazin-1-yl]-N-[3- nitro-4-(tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-2- (1H-pyrrolo[2,3-b]pyridin-5- yloxy)benzamide
 
34
 

OG Complex Work Unit Chemistry
 N-[3-nitro-4-(tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-2- (1H-pyrrolo[2,3-b]pyridin-5- yloxy)-4-[4-[[(3R)-2-(thiophene-2- carbonyl)-3,4-dihydro-1H- isoquinolin-3-yl]methyl]piperazin- 1-yl]benzamide
 
35
 

OG Complex Work Unit Chemistry
 4-[4-[[(3S)-2-(5-chlorothiophene- 2-carbonyl)-3,4-dihydro-1H- isoquinolin-3-yl]methyl]piperazin- 1-yl]-N-[3-nitro-4- (tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-2- (1H-pyrrolo[2,3-b]pyridin-5- yloxy)benzamide
 
36
 

OG Complex Work Unit Chemistry
 N-[3-nitro-4-(tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-2- (1H-pyrrolo[2,3-b]pyridin-5- yloxy)-4-[4-[[(3S)-2-(thiophene-3- carbonyl)-3,4-dihydro-1H- isoquinolin-3-yl]methyl]piperazin- 1-yl]benzamide
 
37
 

OG Complex Work Unit Chemistry
 4-[4-[[(3R)-2-(2- methylpropanoyl)-3,4-dihydro- 1H-isoquinolin-3- yl]methyl]piperazin-1-yl]-N-[3- nitro-4-(tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-2- (1H-pyrrolo[2,3-b]pyridin-5- yloxy)benzamide
 
38
 

OG Complex Work Unit Chemistry
 4-[4-[(3,3-dimethyl-1,4- dihydroisoquinolin-2-yl)methyl]- 1-piperidyl]-N-[3-nitro-4- (tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-2- (1H-pyrrolo[2,3-b]pyridin-5- yloxy)benzamide
 
39
 

OG Complex Work Unit Chemistry
 4-[4-[(4,4-dimethyl-1,3- dihydroisoquinolin-2-yl)methyl]- 1-piperidyl]-N-[3-nitro-4- (tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-2- (1H-pyrrolo[2,3-b]pyridin-5- yloxy)benzamide
 
40
 

OG Complex Work Unit Chemistry
 4-[4-[[(3S)-6-chloro-2-(2- methylpropanoyl)-3,4-dihydro- 1H-isoquinolin-3- yl]methyl]piperazin-1-yl]-N-[3- nitro-4-(tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-2- (1H-pyrrolo[2,3-b]pyridin-5- yloxy)benzamide
 
41
 

OG Complex Work Unit Chemistry
 N-[3-nitro-4-(tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-4- [4-[(3-phenyl-3,4-dihydro-1H- isoquinolin-2-yl)methyl]-1- piperidyl]-2-(1H-pyrrolo[2,3- b]pyridin-5-yloxy)benzamide
 
42
 

OG Complex Work Unit Chemistry
 4-[4-[[(3S)-6-chloro-2- (cyclopropanecarbonyl)-3,4- dihydro-1H-isoquinolin-3- yl]methyl]piperazin-1-yl]-N-[3- nitro-4-(tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-2- (1H-pyrrolo[2,3-b]pyridin-5- yloxy)benzamide
 
45
 

OG Complex Work Unit Chemistry
 4-[4-[[(3S)-6-fluoro-2-(2- methylpropanoyl)-3,4-dihydro- 1H-isoquinolin-3- yl]methyl]piperazin-1-yl]-N-[3- nitro-4-(tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-2- (1H-pyrrolo[2,3-b]pyridin-5- yloxy)benzamide
 
46
 

OG Complex Work Unit Chemistry
 N-[3-nitro-4-(tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-2- (1H-pyrrolo[2,3-b]pyridin-5- yloxy)-4-[4-(spiro[1,3- dihydroisoquinoline-4,1′- cyclobutane]-2-ylmethyl)-1- piperidyl]benzamide
 
48
 

OG Complex Work Unit Chemistry
 4-[4-[[(3S)-7-fluoro-2-(2- methylpropanoyl)-3,4-dihydro- 1H-isoquinolin-3- yl]methyl]piperazin-1-yl]-N-[3- nitro-4-(tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-2- (1H-pyrrolo[2,3-b]pyridin-5- yloxy)benzamide
 
49
 

OG Complex Work Unit Chemistry
 4-[4-[[(3S)-2- (cyclopropanecarbonyl)-6-fluoro- 3,4-dihydro-1H-isoquinolin-3- yl]methyl]piperazin-1-yl]-N-[3- nitro-4-(tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-2- (1H-pyrrolo[2,3-b]pyridin-5- yloxy)benzamide
 
50
 

OG Complex Work Unit Chemistry
 4-[4-[[(3S)-2- (cyclopropanecarbonyl)-7-fluoro- 3,4-dihydro-1H-isoquinolin-3- yl]methyl]piperazin-1-yl]-N-[3- nitro-4-(tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-2- (1H-pyrrolo[2,3-b]pyridin-5- yloxy)benzamide
 
55
 

OG Complex Work Unit Chemistry
 4-[4-[[(1R,4R,5R)-4-(4- chlorophenyl)-6-methyl-3- azabicyclo[3.3.1]non-6-en-3- yl]methyl]-1-piperidyl]-N-[3- nitro-4-(tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-2- (1H-pyrrolo[2,3-b]pyridin-5- yloxy)benzamide
 
56
 

OG Complex Work Unit Chemistry
 4-[4-[[1-(4-chlorophenyl)-3-oxo- 2,7-diazaspiro[3.5]nonan-2- yl]methyl]-1-piperidyl]-N-[3- nitro-4-(tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-2- (1H-pyrrolo[2,3-b]pyridin-5- yloxy)benzamide
 
57
 

OG Complex Work Unit Chemistry
 4-[4-[[(3S)-7-chloro-2-(2- methylpropanoyl)-3,4-dihydro- 1H-isoquinolin-3- yl]methyl]piperazin-1-yl]-N-[3- nitro-4-(tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-2- (1H-pyrrolo[2,3-b]pyridin-5- yloxy)benzamide
 
59
 

OG Complex Work Unit Chemistry
 N-[3-nitro-4-(tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-2- (1H-pyrrolo[2,3-b]pyridin-5- yloxy)-4-[4-[[(3R)-2-(thiophene-3- carbonyl)-3,4-dihydro-1H- isoquinolin-3-yl]methyl]piperazin- 1-yl]benzamide
 
74
 

OG Complex Work Unit Chemistry
 4-[4-[[(1S,2S,4S)-2-(4- chlorophenyl)-4-hydroxy-4- methyl- cyclohexyl]methyl]piperazin-1- yl]-N-[3-nitro-4-(tetrahydropyran- 4-ylmethylamino)phenyl]sulfonyl- 2-(1H-pyrrolo[2,3-b]pyridin-5- yloxy)benzamide
 
75
 

OG Complex Work Unit Chemistry
 4-[4-[[(1S,6S)-6-(4-chlorophenyl)- 3,4-dimethyl-cyclohex-3-en-1- yl]methyl]piperazin-1-yl]-N-[3- nitro-4-(tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-2- (1H-pyrrolo[2,3-b]pyridin-5- yloxy)benzamide
 
78
 

OG Complex Work Unit Chemistry
 N-[3-nitro-4-(tetrahydropyran-4- ylmethylamino)phenyl]sulfonyl-4- [4-[[(3S)-2-(pyrrolidine-3- carbonyl)-3,4-dihydro-1H- isoquinolin-3-yl]methyl]piperazin- 1-yl]-2-(1H-pyrrolo[2,3-b]pyridin- 5-yloxy)benzamide
 
or a pharmaceutically acceptable salt, isomer, solvate, prodrug, or tautomer thereof.